All Mrcp Theory Notes for Dr Abeer in One PDF

C

V

S

Coronary Artery Diseases Risk Factors  Traditional -↑ LDL, HTN, smoking. - ↓HDL, obesity, DM, - age >45♂, >55♀, - FH of premature CHD < 55 ♂, < 65 ♀, - others; hyperuricemia, CRF. Stress, personality.  Non traditional; Lp(a) , homocysteine , PAI-1, fibrinogen, cytokines, CRP, apo B , small dense LDL, visceral obesity , fasting hyperinsulinemia, microalbuminuria. NB; Effect of smoking; - ↑ Bl viscosity, ↑ carboxyHb, & Hct. - ↑ plat adh/agg, - ↓HDL. Leading to  ischemic stroke, SA Hge, CAD, HTN, AA, thromboembolism.

Protective factors; 1- ↓cholesterol in diet. 2- ↑HDL by; estrogen, exercise, alcohol. Effect of Estrogen. 1. ↑HDL, ↓LDL, ↓Lpa. 2. ↓LDL coronary uptake 3. ↓coagulation factors. 4. ↑insulin sensitivity. Beneficial effect of small amount of alcohol; ↑HDL, ↑ insulin sensitivity, anti-thrombotic (↑TPA), anti-plat (↑PC/ tx), anti-oxidant (flavinoids & polyphenolin red wine).

Normal adult 12-lead ECG

1)Hyperacute T

2)Raised ST

4)Q wave, inverted T

3)Q wave, T inversion

5)Q wave

Cardiac enzymes; Enzyme CPK-MB Troponin LDH

Onset (hs) 4 3 10

peak 18 24 24

Return(day) 2 10 14

 CPK-MB ratio>2.5% of total CPK,  new rise infarction extension.  Troponin; - most sensitive, more specific than CPK. - indicator of severity. - n=<0.4 ng/ml. - false +verenal, PE, myocarditis baseline & 12 hs after.

definitions  Angina pectoris; -

transient attacks of chest pain caused by myocardial ischemia. It is a symptom of CAD. Ccc by burning,or boring substernal pressure or heaviness. Precipitated by exertion, stress, cold. Releived by rest, nitroglycerine. ECG; subendocardial ischemia= *transient ST depression in ant, inf or all leads ) during the attack. *sometimes T wave inversion.

 Prinzmetal angina; - non infarction ischemia due to coronary artery spasm leading to transient transmural ischemia. - Atypical angina due to; ST elevation not depression, occur at rest or at night. - Rt coronary. - ¾ patients coronary atherosclerosis. - ECG; transient ST elevation, without Q or t wave inversion.

 Subendocardial infarction; - ECG; non Q wave infarction= NSTEMI= persistent ST depression &/or T wave inversion. 

Transmural infarction - ECG; STEMI = Q wave infarction = 1) Hypercute T, 2) ST elevation & reciprocal ST depression 3) Q wave, 4) T wave inversion.

NB; - ECG may be normal in acute MI especially early infarction. - it is better to say Q or non-Q infarction. Diagnosis of recent MI - ↑enzymes + (sympt.

or ST)

or – postmortum pathological finding.

Diagnosis of Full thickness MI = + akinetic area or scar on ECHO .

Acute anterior myocardial infarction ST elevation in the anterior leads V1 - 6, I and aVL reciprocal ST depression in the inferior leads

Old anterior MI

Q wave infarction transmural infarction Hypercute T, ST elevation, Q wave, T wave inversion.

Non-infarction transmural ischemia. (Prinzmetal angina) transient ST elevation

Myocardial ischemia Non-infarction subendocardial ischemia (classic angina) Transient ST depression

non Q wave infarction subendocardial infarction persistent ST depression &/or T wave inversion without path Q

DD of ST changes  Raised ST; - transmural infarction (>2 □ in chest leads, >1 □ in limb leads), with evolutional changes & reciprocal depression. - prinzmetal angina; transient without evolutional changes or reciprocal depression. - early repolarization pattern; young, stable ST elevation without evolutional changes or reciprocal depression. - pericarditis; special pattern, in all leads. - LBBB; with characteristic QS pattern in V1,2 & notched R in V5,6. - Depressed ST; - angina. - LVH with strain. - non-Q MI=NSTEMI= subendocardial infarction. - reciprocal depression in transmural infarction. - digitalis; scooping of ST-T. - Post. Wall infarction.

DD of T wave inversion Normally in avR, V1. Ischemia. Ventricular strain pattern. Pericarditis. Subarachnoid Hge (deep, wide + prolonged QT, U wave), may be due autonomic dysf. BBB. Ventricular Pacemaker.

Stable angina; - signs (+/- S4, MR). - Management.; - ECG during the attack, transient ST depression &/or T wave inversion. - TTT During the attacknitroglycerine tab, 0.4 mg not more than 3 tab. - Exercise Stress test, if normal ECG in between the attacks; *The test is stopped if the patient develop angina, fatigue, diagnostic ST changes, *+ve results = failed ↑or ↓BP, ischemic ECG changes. * if early + ve results angio. If achieve 9 min medical ttt (BB, CCB, aspirin 150mg, exercise). - Thallium stress, to increase the diagnostic accuracy of Exercise Stress test, - coronary angio, indication; - unsettled diagnosis. - refractory to medical ttt. - suspect Lt main stem or 3 vessels dis. - pt > 40 yrs before valve replacement. *if proximal stenosis  dilatation by PTCA (may need repeated procedure). *CABG is done if - restenosis after PTCA. - severe 3 vs - severe Lt main stem. - DM + 2 vs.

Unstable angina.  angina is said to be unstable if; - accelerated (severe, frequent, longer). - at rest. - post MI, PTCA, CABG.  TTT ; 1. Medical; Aspirin (or clopidogril), Heparin (or

LMWH),GP IIb IIIa(absiximab, tirofiban), nitroglycerin (PO or IV), BB.( during the attack), . 2. early percutaneous coronary intervention (PCI), with or without stenting, is recommended in all except low risk patients. 3. In low risk patients discharge with outpatient stress testing within 72 hours. 4. After dischargeBB, Aspirin, nitrates, lipid lowering, ACEI.

NSTEMI= Non Q wave infarction= subendocardial infarction ; - ECG; persistent ST depression &/or T wave inversion. - evidence indicates that subendocardial infarction may have as bad long term prognosis as transmural infarction with higher 1 yr mortality. - should be investigated early & aggressively. - TTT; GP IIb IIIa. - no benefit from thrombolysis.

 -

Syndrome X; Middle aged female presented with atypical chest pain. May be related to estrogen deficiency. Due to small vessel disease or Lt ventricular dysfunction. ↓ST on exercise test. Normal angio. TTT; medical ttt, Laser percutaneous transmyocardial revascularization; = Laser holes in the epicardium to form channels connected to vent cavities, benefit in distal dis e.g. DM.

coronaries  Rt coronary supplies the inferior (diaphragmatic) portion of the HT.  LAD supplies septum & most LT ventricle.  LT circumflex supplies the lateral wall of Lt ventricle.  Frequency of occlusion; LAD, RCA, Lt circumflex.

Transmural Myocardial infarction Definition; ischemia & necrosis of a portion of the entire thickness of the LT ventricular wall. ECG changes; - Acute phase; Hypercute T, ST elevation + reciprocal depression. - Evolving phase; Q wave,T wave inversion.

Localization of infarction; Anterior wall infarction; - anteroseptal; in V1,2. - Strictly ant= in v3,4. - Anterolateral; in V5,6.

Acute anterior myocardial infarction ST elevation in the anterior leads V1 - 6, I and aVL reciprocal ST depression in the inferior leads

 Complications of anterior wall Infarction; 1 - septal perforation & VSD.---- lt vent failure. 2- cardiac rupture (tamponade). 3- vent aneurysm; - double apex, - persistent ↑ ST without reciprocal depression. - complication; 1.VT-  syncope , 2.thromboembolism, 3. rupture . - TTT: warfarin for 3-6 ms, surgery if significant dec in COP.

4- thromboembolism in 1/3 cases. 5- dressler $= post cardiotomy $ ↑ESR, fever, anemia, pericardial eff, anticardiac ms ab ttt=NSAIDs, steroids.

Mobitz II. 7- BBB. 6-

inf. Infarction  inferior (diaphragmatic) portion of the LT ventricle.  Changes in lead II, III, AVF.  Due to occlusion of RT coronary & less commonly Lt circum.

Complications of inf. Infarction; - Papillary ms dysfunction (rupture is rare). - conduction abn; CHB, Mobitz I (SAN is supplied by RCA in 60%). - RT vent infarction.  fluid & thrombolysis. - Posterior wall inf.

Acute inferior myocardial infarction ST elevation in the inferior leads II, III and aVF reciprocal ST depression in the anterior leads

 Papillary ms dysfunction ( with Inf. MI); - in 0.1% of MI. - 80% the post. Papillary ms (supplied by RT coronary, so more common with Inf. MI. - several days after MI. - TTT; emergency MVR. - Prognosis; 24 hs survival = 25% with medical ttt, 50% with emergency MVR.

Posterior wall infarction Posterior wall of the LT ventricle.  ECG; tall R, ST depression & tall +ve T in V1,2. May extend to the lateral or inferior wall (postero-inferior). Due to occlusion of RT coronary.

Acute posterior myocardial infarction (hyperacute) the mirror image of acute injury in leads V1 - 3 (fully evolved) tall R wave, tall upright T wave in leads V1 -3 usually associated with inferior and/or lateral wall MI

RV infarction; - in 1/3 of inferior infarction. - ↓BP, congested neck, clear lung bases. - diag.; ECG ↑ ST in V1, V3R, V4R,V5R. - confirmed; ECHO, coronary angio, thallium scan. - TTT= monitor by PCWP, IV fluid, thrombolysis but never nitroprusside or VD.

inf-post-lat

NB; * Cause of Post-MI VT; - scar EPS & ablation. - ischemia angio & thallium. if associated with LVEF < 40%ICD. * Indications for temporary pacing post MI (for 2 wks ) - ant wall & CHB or new BBB. - inf wall & CHB if HD unstable. - if no sinus rhythm within 2 wks permanent pacing.

Shock after MI; 1 - RV infarctionfluids. 2- VSD Vs. papillary ms rupture (severe MR)  ECHO & IABP. 3- LV extensive infarction or re-infarction (loss of > 40% of LV) IABP. 4- free wall rupture (fatal) & tamponade.

 PCWP = Lt atrial pressure = LVDP. Post MI LVF MR VSD Tamponade RVI

CVP ↑ N N ↑ ↑

PCWP ↑ ↑↑ ↑↑ ↑ ↓

Management of transmural infarction 1) Thrombolysis Indication ( pain & ECG) - pain < 12 hs + ↑ ST in 2 leads. - pain + new BBB. Most benefit; - early 1 hr. - poor LVF or syst BP < 100. - high ↑ ST. - large ant. infarction.

Thrombolysis  1)

2)



Contraindications; Absolute; - active internal, uncontrolled ext. bleeding. - suspected Aortic dissection. - uncontrolled BP > 200/100. - head trauma < 2w, stroke< 2 m. - cranial or abd neoplasm. - pregnancy. Relative; - CPR > ½ hr probable IC thrombus e.g. (AF+MS)

Complications - reperfusion arrhythmia within 2 hs.

-Hge. NB; - 1ry angioplasty is better than thrombolysis, preferred if HD unstable

2) Drugs which decrease mortality in MI; 1) Aspirin (not dypyridamol). 2) thrombolytics/ angioplasty. 3) BB (FU with PR < 0.24, HR >45, SBP > 100)3 doses of 5 mg metoprolol 4) ACEI esp. CHF, EF< 40%, cardiomegaly. 5) Statin ( ↓ mortality & recurrence) even with

average cholesterol prior to discharge. - LV function is the prognosticator post MI. NB: - nitrate ↓ morbidity not mortality. - DHP CCBs inc.CVS risk after MI. - In type II DM, must be kept on insulin infusion for 24 hs then SC for 3 months  ↓ mortality.

3) PTCA  Indication; - discrete lesion. - proximal. - non calcified . - non-occluded - short history of angina.  Complication; 1) acute occlusion. 2) restenosis. * for stent restenosis (for high risk patients as DM).  drug eluting stents + GP IIbIIIa + aspirin + clopidogril for 1 m .  GP IIbIIIa

used in;

- high risk PTCA - NSTMI

- stents - unstable angina

4) CABG  Indication; - symptomatic LT main stem dis. - symptomatic proximal 3 vs dis. - 2 vs including LAD.  Most benefit; moderately impaired LVF.  Complication; 1) mortality: < 2% , 10% for 2ry procedure. 2)periop. Graft occlusion; 10% esp venous grafts. ( art. Grafts have higher patency). 3) post cardiotomy $ up to 6 m after.

5) Laser percutaneous transmyocardial revascularization; = Laser holes in the epicardium to form channels connected to vent cavities, benefit in distal dis e.g. DM. 6) Elective balloon pump insertion; - cardiogenic shock - VSD - papillary ms rupture.

Post MI rehabilitation 1 month abstinence from sex & driving. 2 months off work. Abstinence from driving after revascularisation - 1 m for ordinary driver - 3 m for vocational drivers. - Loss of license after ICD.

perioperative cardiac complication  cardiac complication are the most common cause of perioperative mortality & morbidity esp. after vascular surgery. Investigations;  So if high risk of ischemia (history of CAD)coronary angio.  If intermediate risk ( DM, PVD) dipyridamol thalium scan or dopamine stress ECHO ( both are equivalent, NPP > 95%.  if low risk exercise stress test. TTT;  Perioperative BB ↓risk of morbidity by 50% & recommended for high & intermediate risk.  Temporary pacing for trifascicular block.

Myocardial diseases

Myocarditis Infective

Non- Infective

*Viral Coxsakie, ECHO, mumps, measles, influenza, EBV, HIV, adeno, rubella, robeola. *Bacterial TB, brucella, Hemophilus.

-Rheumatic -CT dis; SLE, Rheumatoid, myocarditis recurrent refractory VT. -Drugs; adriamycin, chloroquine, phenothiazine, lithium, sulfa, paracetamol. -irradiation

* spirochital;leptospirosis, borellia burgdorferi *Fungal (aspergillus, histoplasmosis) *parasitic; trypanosomes cruzi, trichinosis, toxoplasma, amoeba, malaria

History

Myocarditis

DCM

-Young -Acute onset -Prodrome (fever, flu like,arthralgia)

-Older - chronic

Investigation -Neutrophilia -↑viral Ab titre e.g. cox B titre1:160. -CXR; Slight cardiomegaly. -ECG; episodic VT, HB, ST/T.

ttt

Avoid BB, digitalis

-ve -ve - CXR; Huge cardiomegaly

Cardiomyopathies These are conditions that;  1ry affect Ht muscle.  Of unknown etiology.  Characterised by myocardial dysfunction  After exclusion of - volume & pressure overload. - IsHD - pericardial disease. NB; ischemic CM= IsHD that has no other manifestations as angina or MI but only present with Ht failure.

Hypertrophic cardiomyopathy (HCM)  AD in 50%.  Mutation of ß myosin gene on chr 1, 11, 14, 15.  Bimodal 1st peak 2nd decade. 2nd peak 4-6 decade.  LV outlet obstruction occur in late systole.  Associations; - Friedreich ataxia. - WPW. - pheochromocytoma  Symptoms; - exertional dyspnea - chest pain. - palpitation. - syncope. - sudden death VT (dt acc. Path- associated AF) massive infarction outflow obst

(HCM) Signs;  general, - prominent a wave in neck veins  Local, palpdouble apical impulse (S4), LS thrill. auscmurmur; late or pansystolic over LSE or apex more than A1, not over carotid dt outflow obst & MR. ↑ by obst e.g. digitalis, inotropics, ↓volume e.g. standing, valsalva, diuretics, VD as nitrates. ↓ by squatting, hand grip.

(HCM) Invest;  ECHO- Asymetrical septal hypertrophy 60% concentric 30%, apical 10% - septum/post wall>1.5. - >30% LV outflow gradient - obliteration of LV cavity. - systolic ant. Motion of mitral valve leaflet.  Catheterbanana or spade like LV.  Poor prognostic features; - young age < 30 yrs. - FH of sudden death. - syncopal sympt. - LVH > 3 cm. - VT on Holter ECG. - hypotension on peak exercise test. NB; no correlation with outflow tract obst gradient.

(HCM)  1. 2. 3.

4. 5.

Management; Avoid volume depletion avoid intense physical exertion and competitive sport. Treatment of dyspnea and chest pain generally begins with medical therapy.  negative inotropic agent; - verapamil or - beta blocker, +/- disopyramide, - cautious addition of a diuretic, If medical therapy fails  non-pharmacologic therapy; surgical myectomy or alcohol septal ablation. Prophylaxis for endocarditis.

Dilated cardiomyopathies (DCM) ♂, Causes;  Alcohol.  Nutritional; thiamine, selenium, ↓Ca, ↓P.  Endocrinal; hypo &, DM, acromegaly.  Metabolic; glycogen storage diseases.  Infiltrative; hemochromatosis.  Toxic; cocaine, adriamycin.  Peripartum.  Viral, cox, HIV.  autoimmune,; SLE, Sclero. C/P; biventricular failure. ECG biventricular ++ ; LBBB , poor R prog., +/- AF. Catheter; ↓CO, ↑EDP in both vent. TTT; antifailure= ACEI, digoxin. anticoag= AF, mural thrombosis. antiarrhyth=

Restrictive CM  Causes; - myocardial= idiopathic, amyloidosis, sarcoidosis, scleroderma, hemochromatosis, glycogen storage, Gaucher. - Endomyocardial =fibrosis, hyperesinophilic S, carcinoid, malignancy, irradiation, toxin-related.  Sympt; SVC, PVC, low COP, AF.  Signs; steep x, y. pulsus paradoxus, AF.  TTT; antifailure + anticoag + ttt of etiology.

Pericardial diseases

Pericarditis Infective

Non- Infective ( T U M O R)

*Viral Coxsakie. *Bacterial Strept, staph, TB.

-TB, trauma. -Uremia -Malignancy, medication (those causing SLE as hydralazine, procainamide, INH), MI -Other infections, viral , bacterial . -Rheumatic fever, rheumatoid &Other CT, radiation, recurrent

Types 1- acute dry= fibrinous. 2- associated with pericardial effusion; serous CT. serofibrinous  T U M O R hgic TB, tumors, trauma 3- constrictive.

Pericarditis

Constrictive pericarditis

(TB)

  -

Causes = T U M O R without ( medications, MI, RF). Symptoms; Rt vent failure (cachexia, ascites, hepatomegaly, oedema, ↑JVP) + dyspnea, AF due to atrial enlargement.

 -

Signs; X, y descent deep . Kaussmaul sign (inspiratory filling of neck v). Impalpable apex. Pericardial knock. AF. Ascites precox.

• • • •

CXR; pericardial calcification. ECHO; thick bright pericardium, biatrial enlargement, normal systolic function, poor diastolic function, ↓peak systolic & diastolic values during inspiration. ECG; ↓PR (early & specific), ↑ST, inverted T. CT scan , pericardial rim of calcification.

pericardial effusion  Types; 1) serous; transudateoedematous states. Exudate hypothyroid, CT, viral, TB, malignancy. 2) hgic; TB, tumors, trauma, CRF + heparin on HD. 3) bloody; ruptured aneurysm, dissecting AA, MI. 4) chylous; lymphedema .

• • • • •

Signs; ↑JVP, pulsus paradoxus, loss of y descent dt atrial compression, Ewart sign= bronchial breathing at Lt lung base dt compression of lingual lobe. CXR; globular cardiomegaly( flask shaped). ECG; electrical alternans, electromechanical dissociation in tamponade. TTT; drainage or pericardial window in chronic cases.

Restrictive CM Neck veins

Constrictive P Common; ↑JVP, Deep X & Y

P.effusion/tampon Y obliterated

palpation

Systolic bulge

Systolic retraction

Impalpable apex

auscultatio n

S3 gallop, TR +/-MR (cardiomyopathy as Ht failure)

Pericardial knock (as S3 due to catching effect of pericardium on the relaxing ventricle)

Distant Ht sounds

liver CXR

Common; congested non pulsating Ht failure without cardiomegaly

ECG Catheter

Flask shaped cardiomegaly

Common; AF - Difference bet 2 ventricle LT VEDP > RT -Difference of pressure in the chamber during cardiac cycle

ECHO Confirmed by

pericardial calcification

-Less

-Less

Common; normal systolic function biopsy

CT, MRI

ECHO

Endocardial diseases

Rheumatic Fever  Diagnosis; evidence of recent strept infection (↑ASOT >250 adult or 333 children, scarlet fever, +ve throat swap, other antistrep Ab) + 2 Major or 1M & 2m criteria. Major

minor

1-carditis

fever

2- arthritis

arthralgia

3- chorea

CRP, ESR

4-erythema marginatum

↑PR

5- SC nodules (non tender, on knee, elbow, spine)

Previous RF

 Prophylaxis from recurrence; 1- TTT of strep infection with penicillin. 2-long term long lasting penicillin (Benzathine penicillin 1.2 million unit IM/month (erythromycin/12 hr if penicillin allergy) till - 25 yrs or - 30 yrs if RHD or - 5 yrs after the last attack.

 Treatment; 1. Benzathine penicillin 1.2 million unit/wk IM for 3 wks or oral penicillin 500 mg/6 hrs for 10 days. 2. Salicylates (5-6 g/d) for 6 wks e.g. indomethazin, diclofenac. or steroids 50 mg/d for 4 wks if intolerance to salicylates.  FU with ESR.

Endocarditis  Causes of endocarditis Infective

Non- Infective

*Bacterial -Strept viridans (subacute), fecalis (=enterococci after urinary cath) bovis (colorectal cancer) -Staph aureus (skin, drug abuse, acute), albus (cardiac surgery), epidermidis ( valve replacement) -Pseudomonus. -Hemophillus (HACEK, ceftrioxone very effective) * Ricketsia, coxsiella (=Q fever) *Chlamydia *Fungal (candida, aspergillus)

-Rheumatic -Lebmansac endocarditis -Carcinoid -Marantic

IEC  IEC; 40% no valve lesion. 10%IV drug, cong, prothetic 50% strept viridans  Signs of IEC; - toxic manifestation + clubbing, subconj Hge, - spleen, soft small palpable ( -ve in renal, old, debilitated, HT failure), - cardiac( varying murmur, new murmur, conduction defect, dt abscess formation, Ht failure, infarction dt emboli0. - Thromboembolic ; *acute septic emboli pyemia, mycotic aneurysm in the brain subarachnoid Hge *SBE infarctions e.g. CNS, mesenteric, - renal, infarction, CRAO ,UL, LL. Immunological Kidney focal proliferative , MPGN. - skin, osler nodes ( tender, cutaneous), splinter He,, Janway spots. - eye; Roth spots,,.

 Poor prognostic factors. - staph, - culture neg. , - proth.valve, - low complement.  Indications for surgery - relapses, - septic emboli, - septal abscess, - fungal, - large vegetations, - extensive valve incompetence.  FU by CRP (ESR fall slowly).

Medical ttt till culture results. Pen G 2-4 mill U/4h + gentamycin 1 mg/kg/8h + nafcillin or oxacillin 1.5 g IV/4h Medical ttt after C& S; Strep benzyl pen (or vanco) + low dose genta. Staph. Flucloxacillin (or vanco) Rickettsia -> Rifampicin + doxycyclin. Pseudomonus carbinicillin 10 g/d + genta 240mg Medical ttt in special situations; Penicillin hypersensitivity vancomycin 15 mg/kg/12hr. Prothetic valve- vancomycin 15 mg/kg/12hr. - gentamycin 1 mg/kg/8h for 2 wks. - Rifampicin 300 mg/8 hrs. Rt sided; - 50% staph, 15% pseudom, - diagnosed with transthoracic ECHO, - flucloxacillin (vanco or teicoplanin) + gentamycin for 2 wks. - no valve replacement if pulm septic emboli. 2-6 months Post operative (staph, 85% MRSA)  vancomycin.

Antibiotic prophylaxis   

NICE guidelines 2008 recommended that Antibiotic prophylaxis is no longer offered routinely for defined inteventional procedure. Antibiotic prophylaxis has not been proven to be effective & there is no clear association between episodes of IEC & interventional procedures. Benefits of antibiotic prophylaxis must be weighed against the adverse effects for the patients & the risk of developing antibiotic resistance.



People at risk are;

1. 2. 3.

Acquired valvular HD with stenosis or regurge. Valve replacement. structural congenital HD except isolated ASD, fully repaired VSD or PDA, closure devices that are judged to be endothelialised. HCM Previous IEC.

4. 5.

 -

Advice people at risk about; Good oral hygiene. Symptoms of IEC. Risks of invasive procedures Why ab prophylaxis is no longer indicated.

•

Do not offer ab prophylaxis for; - All dental procedure. except…. - Upper & lower GIT, respiratory, genitourinary. - Do not offer chlorhexidine mouth wash before dental procedures. - Investigate & treat any episode of infection. - Offer ab that cover organisms causing IEC for those pts undergoing procedures at a site where there is a suspected infection.

Antibiotic prophylaxis *

not indicated for; - cardiac cath - diagnostic upper GI endoscopy. - large secondum ASD. - MVP without regurge. - after 6 month of valve repair. - TEE.

•

indicated for; -- all surgery. - rigid bronchoscopy. - therapeutic upper GI endoscopy.

regimen

Upper (e.g. dental) BeforeAmox 2 g oral or 1 g IV 1 hr After genta 1.5 mg/kg IV + 500 mg oral amox 6 hr if general anathesia. Lower (colonoscopy and biopsy) Amox 1 g IV + genta 1.5 mg/kg IV + Amox 1g oral 6 hrs

Cardiac tumors

 50% -Myxomas * 2ries from breast & lung  But tumor that most commonly metastasis to the heart= melanoma.  Atrial myxoma; - interatrial septum, LT atrium. - ♀. - sympt.constitutional (IL-6fever, clubbing) systemic embolism. postural syncope. - signsMS , early diastolic plop (murmur). PHT, sinus rhythm. - invest; ↑ WCC., ↑ESR in 60%, ↑IG (hypergammaglobulinemia) . - diag.=TEE, avoid catheter. - TTT= surgical resection without delay ( rapidly growing, & embolize)

Valvular Diseases MS Normal valve area Causes

MR

average =4.5 cm, MS<2cm, tight MS<1cm. 1-

organic;

-Rh, -cong 2- functional; - Austin flint (with AR). Cary comb(Rh carditis - MR, VSD, PDA. - tumors

AR

AS

2.5 cm, AS<0.7 cm, severe AS<0.5 1-organic; 1- organic; -Rh chronic -Cong marfan -Rh -syphilis, RA, -Cong e.g. Ank. Sp. Marfan, MVP -Acute; IEC, -Ischemic dissecting aneurysm Acute (infarction, IEC, post valvotomy)

functional; -LVF -HCM

1- organic; -Rh -Cong valv; bicuspid suprav; wiliam, coarct subv; HCM calcific; 2- functional; Hemic HTN AR

MS

MR

AR

AS

Symptoms

1- PVC 2-Low COP 3-SVC

1-palpitation 2- PVC 3- Low COP

1-palpitation 1-Angina 2- angina 2-syncope(Low 3-PVC dt LVF COP) 3-dyspnea(PVC)

Signs 1- general

- Malar flush

2-local

-Palpable S1 -Loud S1,OS, -Loud S2 -Mid-diastolic rumbling murmur.

Peripheral signs e.g. corrigan, DeMussey, waterhummer pulse, Duroziez, Hill’s

Soft S1 Early soft Soft blowing blowing diast murmur pansystolic murmur

Soft S2 Harsh ejection systolic murmur at A1

MS

MR

AR

AS

Signs of severity

-OS near S2 -long murmur -PH, loud S2, PR, RV heave, TR - ECHO; M area <1cm -Cath; PCWP>25. pr gr>15. COP<2.5L/min/m2.

-PH,

-LVF -Peripheral signs - S3. -Long murmur -Funct MS (austin flint)

-Syncope, LVF

Indication for surgical interventi on

Severe symptoms Severe MS Thromboembolism despite adequate anticoag inr=2.5-3.5)

Severe symp Severe MR ECHO; EF<60%,

symptoms Severe AR -ECHO; EF<50%, AV root>50mm, LVESD>50mm

symptoms Severe AS

-Thrill -LV++ -S3 -Func MS

-Pulsus T&P -Low pulse pr, low BP -Thrill -Single soft A2, reversed splitting -S3,S4 -Long murmur -ECHO; V area<0.5 SP gr>60

MS

MR

AR

AS

TTT

1- Prophylaxis from IEC. 2- diuretics 3- ttt of AF 4-+/-surgery

1- Prophylaxis from IEC. 2-ttt of AF 3-VD 4-+/-surgery

-If asymtomatic FU with ECHO. -surgery

-surgery - No role for medical ttt

NB;

Silent MS; 1-lutembacher (+ASD) 2-PH 3-RVF Calcified 1-soft S! 2-no OS NB; huge Lt atrum in MR, AF in MS

Predominant MI in Double M; 1-soft S1 2-S3 3-displaced hypertrophied apex S1+ MR; 1-MS 2-post. Leaflet

without surgery, sudden death 73%. in Asympt. Adult, sudden death3-5%. child, sudden death in 6-9%. Complications (S Death, CHB, calcific emboli, CAD in 50% of severe AS)

Bicuspid AV - Most common cong HT - Sporadic, familial in 10%. - calcify with age AS. - Surgery is likely to be required. Aortic sclerosis - Only localized murmur - No LVH - Normal pulse volume Cause of AS according to the age; <60yrs Rh, cong >60yrs + calcified valve.

TR  Causes; - organic; Rh, cong (Ebstein anomaly), IEC, carcinoid. - Functional; RVF.

Symptoms; palp, SVC, low COP.  Signs; general cyanoecterous, prominent V, absent X, ascites precox. local  pansystolic murmur to the Lt of the sternum, carvello sign(↑murmur by inspiration). PS  Causes - organic cong (fallot).. - Functional; ASD, hemic , PHT.

Prothetic valve  Types 1. Mechanical valve; adv; durable. disadv; lifelong anticoagulation. NB; INR target for AV= 2-3, for MV=2.5-3.5. 2. Tissue valve (porcine, homograft) indications; old age. adv; no anticoagulation. disadv; calcify with restenosis, replaced after 5-10 yrs.  Indications; 1. Severe AS, AI, MI. 2. MS in the following conditions; - MV score >8 (according to mobility, thickness, calc., subvalvular apparatus. - associated MR 2/4. - Lt atrial thrombus.  Signs; MV prothesis; metalic S1, metalic OS+ systolic murm+/-diastolic murmur. AV prothesis; metalic S2, metalic E click + systolic murmur only. NB; any early diastolic mrmur at AV area malfunctioning V. tissue valves does not produce metalic sounds.

 Complications; - infection; mortality 60%. early ½-1 y staph epidermidis. later fungal. if↑ PR septal abcess. - dehescencesurgery. - hemolysis. - thromboembolism.  Anticoagulation + surgery; - stop warfarin & give heparin/6h, 3 days before. - stop heparin 6 h before till 24 h after major surgery or to 6 h after minor surgery.  Anticoagulation + pregnancy; - 1st tri.heparin, 2nd warfarin, 3rdheparin, lactationwarfarin. - warfarinfetal hge teratogenic 5-30% acc. To dose; mental R, optic A, nasal hypoplasia, chondrodysplasia.

MVP  Associations; - WPW, ASD, PDA, LA myxoma. -CT disorders. pseudoxanthoma, osteogenesis imperfecta, Marfan, - Symptoms; palpitation, pain due to stress ischemia of papillae.  Signs; - midsystolic click ↑by squating, - midsystolic murmur ↑by standing .  Complications; - long QT, arrhysthmias, death. - rupture of chordae. - embolism. - neurosis.  ECG;depressed ST, T inversion in inferior leads, long QT,  ECHO; systolic posterior motion of 1 or2 leaflet, mainly post. Leaflet).  Treatment; - BB for palpitation, pain. - anticoag for embolic manifest. - prophylaxis of IEC if audible murmur or thick leaflets. - valve repair (not for the click only).

Pulmonary hypertension  Mean P pressure =20mmHg,  Mean P pressure=pulm. Diastolic pressure+1/3 pulm puls pressure  PH = mean PP> 30 mmHg  C/P; inspection; Pulm. pulsation. palpation; palpable P2, auscultation, 2 sounds= P2, S4; 2 murmur = PS, PR (graham steel), 1 click= ejection systolic at Pulm.area.

Causes; A) 2ry PH - Passive; MVD, const p, restrictive CM, Lt atrial myx. - Hyperkinetic; ASD, VSD - reactive=VC e.g. high altitude, COPD. - obliterative= sclerosis, fibrosis (EAO e.g. B). - obstructive = embolic ,vasculitis , Bilarz.  TTT of PH; 1-Digoxin (even in sinus rhythm) 2-diuretic in RVF 3-Ttt of the cause,

B) 1ry PH (<1% of all cases) - Def; mean PAP>25 at rest without any cause. - Female /male = 2:1. - 1/10 may be familial, other possible causes; CT dis, vasculitis, HIV, drugs as appetite suppressor (fenfluramine). - CXR; dilated proximal artery & pruned (very small diameter) peripheral. - Median survival if untreated = 3 yrs. - Management; 1-Do 1st PFTs, ECHO, immunologic markers, V/Q scan, Rt catheter & VD test with adenosine or inhaled NO if dec. in PAP without ↓COP CaCB if no  SC pump of epoprostenol 2-avoid pregnancy, exercise. 3-Digoxin (even in sinus rhythm) 4-diuretic in RVF 5-O2 6-Anticoag 7- surgery; - HL transplant if; RVF, PASP>60 mmhg, expected 2 yr survival <50%. - atrial septostomy in no resting hypoxia.

Congenital heart diseases without shunt

+ shunt

Acyanotic

-AS -coarctation - dextrocardia

(potentially cyanotic) Mixed blood -ASD, VSD, PDA -Coarctation of Aorta

cyanotic

-P atresia -Severe PS -Hypoplastic Lt Ht

-Fallot -Ebstein -Complete transposition of great vessels



NB: - Most common cong HT= biscuspid AV. - Most common isolated cong HT= VSD ((30%) - Most common cong in adult = ASD.

ASD  Most common cong in adult.  Complication; Paradoxical embolism-> stroke in young.  Associated; - fetal alcohol S, Down S , cong rubella, Noonan  Types; - 70% Osteum secondum - ass with MVP (10-20%) - RT vent dilatation  RBBB + RAD - 15% Osteum Primum - ass with MI, TI , VSD - - affect conduction system RBBB, LAD - picked early in childhood. - 15% sinus venosus - defect in upper septum - ass with anomalous pul venous drainage.

 Signs; -P; fixed splitting of S2, functional PS (ejection systolic murmur). - Lt parasternal heave. - PS. - in OP (MI, TI, VSD).  Invest.; - ECG; biatrial enlargement, RBBB, RAD. - ECHO; paradoxal septal motion (bidirectional movement through the defect), septal defect. - CXR; pulmonary plethora. - catheter; step up O2 in RT atrium(mean increased oxygen concentration in the RT atrium), PH, ↑RVP. NB; Best is TEE.  TTT; - antibiotic prophylaxis from IEC only in O Primum. - indication for surgery; ↑ pulm/systolic flow ratio > 1.5/1 - may be closed with a prothetic patch through cardiac catheter.

Patent foramen oval; - 25% of population. - slit- like dehiscence in fossa oval. - unlike ASD; no equalization of pressure between 2 atria. - like ASD; Paradoxical embolism. Holt-oram S - Rare S; ASD, triphalyngeal thumb, absent upper arm. - AD. Lutembacher S.  ASD + Rh MS silent MS(ASD decreased the load over the stenosed mitral area ,so no early diastolic murmer of MS)

VSD  Types; 1. Muscular (Roger’s dis); small defect.... close 2. Membranous; most common is memb., 30-50% spont. Closure. Signs; apex; hyperdynamic Palpable P2, parasternal thrill Auscult; inc. P2, parasternal pansystolic murmur; if eisenmenger murmur & thrill disappear, signs of PH +/- RVF.  NB; VSD↓ COP.  TTT; antibiotic prophylaxis from IEC (high risk) surgery at 3-6 yrs if pulm/systolic flow ratio > 1.5.

• -

PDA  Causes; - prematurity - cong rubella  Most common distal to LT subclav.  Signs; - general; peripheral signs of AI. - local; Lt infraclav thrill, enlarged lt Ht. ausc, Lt infraclav machinary mur. if eisenmenger diff cyanosis in LL, mur become short & soft. PH.  TTT; - Premature infantindomethacin (90% closure). - antibiotic prophylaxis

Eisenmenger  Sign; -general; clubbing, cyanosis, ↑ V wave dt TR. -local; Palp P2, Rt vent heave. ausc; ↓ pansyst murm & flow mur., PR (graham steel).

• Catheter; ↑RA, RV, PA pressures. Complications; - RVF, - hemoptysis, - cerebral embolism, abscess, - polythythemia, thrombosis, gout, - IEC (rare)

• TTT; - medical for HT F. - Ht lung transplantation

F3

Fallot   -

-ASD -PS -RVH

F4

-PS -RVH -Overridding aorta -VSD

F5 ASD + F4

Cyanotic spill=hypoxic syncope= ↑PS,↓periph resistance. Signs; general; cyanosis, squatting, clubbing, stunded growth local; RV heave, PS murmur. inversly related to pulm gradient, single loud A2.

 Invest; - CXR; pulm oligemia, coeur en sabot - ECG; RVH.  Complications;

-IEC, -polythythemia, thrombosis, gout. -paradoxical embolism, cerebral abcess. -Vent arrhysthmia.  TTT; blalock operation (BL from Lt subclav a to P) weak radial pulse.

NB; Ebstein anomaly; - Maternal intake of lithium in 1st trimester. - Cyanotic. - pulmonary atresia,TR, - ASD, Rt to lt shunt

Coarctation  2 - 5 times more common in males.  Most common distal to LT subclav.  Symptoms; - in infants Ht failure. - adult UL; shoulder pain, headache, HTN, epistaxis. LL; cold, intermittent claudications, weakness.  Signs. - general; HTN, radiofemoral delay or absent femoral pulse - Local; ins/palp; suzman sign= visible, palp interscapular collateral pulsation. auscul; - HTN; ↑ A2, S4 , A ejection click, AS , -Lt interscapular late syst mur. - syst or continuous mur of collaterals over the back.

 Invest; - CXR; - Roesler sign; 3-8 rib notching - - Ba swallow; reversed 3 or E sign of oesophagus.  Association; cardiac; - Bicuspid AV - PDA - mitral V dis. extra cardiac; - Berry’s aneurysm - renal abn. - Turner S.  Complications; - IEC - dissecting AA

- subarachnoid Hge

 TTT - surgical resection at 4-6 yrs. - balloon angioplasty if recurrent. - antibiotic prophylaxis & ttt of HTN.

- LVH.

Differential diagnosis  1. 2. 3.  1. 2.

Of systolic murmur over the apex; MI AS, PS (propagated from above). VSD (all over the precordium) Of diastolic murmur over the apex; MS AI

 1.

Of systolic murmur over the A1; AS (with all its causes; organic, functional)

 1.

Of systolic murmur over the P; PS (organic, functional).

 1. 2. 3. 4. 5.

Of Lt parasternal systolic murmur Posterior leaflet MI. TI VSD Subval. AS (HCM) Subvalv. PS.

Pressure in cardiac chambers; Values in mmHg

4-12 0-6 15-30 /0-6

90-140 /4-12

120 (90-140) /80 (60-90) 25 (15-30) /10 (8-15)

Vascular diseases

DVT Invest; - venous duplex rarely venogram - ankle-brachial pressure index +/arteriogram to detect ischemia which could contraindicates compression. TTT; - recent DVT  anticoagulation. - old DVT ttt of oedema, infection, compression after exclusion of ischemia.

PE C/P; 1.



Massive pulm embolism&Submassive pulm embolism - when > 50% of pulm vascular area is obstructed ↑ PAP. - retrosternal pain, dyspnea, shock, cyanosis, Rt sided failure. 2. Pulm infarction; uncommon, must have occlusion of bronchial vs & airways cough, hemoptysis, fever, jaundice, signs of atelectasis, rub, effusion. 3. Chronic pulm HTN; recurrent small pulm emboli no symptoms, cor pulmonale, recurrent episodes of dyspnea, fever, arrhythmias. NB; V/Q scan; - v=xenon, Q= macroaggregated albumin.(no iodine used.) - can be done during pregnancy (perfusion only is adequate). - sens =98%, specificity = 40% so if –ve virtually exclude PE. - in COPD & emphesema  matched defects. D Dimer ↑ in  PE, sepsis, MI, DIC.

 1. 2. 3.

Invest; D Dimer ↑ (non specific), good –ve no PE except if ↑ clinical suspicion. CT angio; only show large artery, same sens & specificity as VQ & angio. ECG; an S1, Q3, T3 pattern

5. 6.

sinus tachycardia T wave inversion in leads V1 - V3 RBBB, RAD, poor R progression. ABG; low or normal PCO2, hypoxia, resp. alkalosis..DD; acute severe asthma but PEFR is normal. V/Q; mismatch, not adequate if basal consolidation shown. Pulm angio; gold standard.

 1. 2. 3.

Diagnosis; ↑clinical probability + ↑ V/Q mismatch diagnostic. ↓clinical probability + ↓ V/Q mismatch  exclude. If any other investigate more.



Ttt; anticoag for high & moderate clinical probability; - heparin  5-10,000 unit IV bolus then 1000 IU/h (adjusted to keep PTT = 1.5-2.5 for 5 days at least or stop when INR = 2-3. (or twice daily SC LMWH).

4.

Acute pulmonary embolus ECG; The following, often transient, changes may be seen in a large pulmonary embolus;  an S1 Q3 T3 pattern  sinus tachycardia  T wave inversion in leads V1 - V3  Right Bundle Branch Block  low amplitude deflections

Acute pulmonary embolus

PE TTT;  Massive pulm embolism - TTT of DVT - Thrombolysis (or embolectomy) 2. Submassive - Anticoagulation - ttt of Rt sided HT failure. 3. Chronic recurrent; - Anticoagulation - IVC filters. NB; in pulm septic emboli; # thrombolysis for PE & surgery for the valve for IEC.

PE  1. -

TTT; Anticoagulation; LMWH twice daily SC. Or heparin 5-10.000 u IVbolus then 1300 u/h adjusted to keep PTT=1.5-2.5 times for at least 5 days & stopped when INR=2-3 Warfarin for 3-6 months. 6 wks if post poerative PE. 1 yr or lifelong if recurrent. 2. Thrombolysis; - indications; collapse dt massive embolism. - contraindicated if septic emboli as in RT sided IEC in drug abusers. - done through a peripheral vein to pulm artery, as effective as embolectomy (which is rarely done now). 3. IVC filters; - indications; when anticoagulation is # or failed (=continuous showers of emboli)

NB; Shock

With ↑ PCWP= -LVF -Temponade -MS

With ↓ PCWP= -RV infarction -PE -Hypovolemia -Septic shock

Aortic aneurysm Causes; 1. 2.



Atherosclerosis (commonest). Congenital; - cystic medial necrosis (Marfan, Ehler Danlos ) - osteogenesis imperfecta. - repair of coarct in Turner. 3. Trauma. 4. Inflammatory; - infectious; Mycotic (IEC), syphilis, TB. - Non- infectious; rheumatoid arthritis, takayasu, Giant cell sero-ve, Behcet, Reiter, ankylosing S. Site of Atherosclerotic aneurysm; 75% abdominal, 25% thoracic. Site of dissection; 2/3 ascending A, 1/5 descending.

 

C/P;  1. Thoracic; asympt, mediastinal compression, signs; supresternal pulsation. 2. Abdominal; asympt, majority below renal arteries, signs; abd mass, peripheral ischemia.  Prognosis; Mortality rates; 3% in elective excision. 18% in emergency excision. 50% in acute rupture.  TTT; 1. If < 5 cm, asymtomatic annual U/S, BB to achieve HT rate < 60b/min, optimal BP control. 2. If > 5 cm abd or > 6 cm thoracic, rapidly expanding, symptomatic, A thrombosis & peripheral embolism surgical excision. NB; in Marfan operate if > 5 cm thoracic.

Aortic dissection    1. 2. 3.

Type A= ascending. Type B= descending. Causes; cystic medial necrosis. HTN (70%) Atherosclerosis Congenital; coarct, bicuspid AV, Turner, Noonan.

 1. 2.

Sympt; Sudden severe chest pain radiate to the back. Vasovagal manifestations.

 1. 2. 3. 4.

Signs; HTN Loss of arterial pulse. Occlusion of important vs (stroke, paraparesis) Compression (mediastinal S).



Complications of ascending; AR, inferior MI, pericardial effusion, carotid dissection, ↓subclavian pulse.

Invest; 1. 2. 3. 4. 5.  1. 2. -



CXR; wide mediastinum. TOE (most imp); for diagnosis, severity of AR, LV function, pericardial effusion. CT does not identify site of tear, AR, coronary involvement. MRI does not allow monitoring, # if prothesis. Coronary angio to assess the need for concomitant CABG. TTT; Early; releive pain, Na nitroprusside & BB to ↓syst BP<120, ↓ cardiac contractility ↓shear stress of Aorta. Later; Ascending surgery. Descending -surgery if; impending rupture, compress major Vs, uncontrolled pain, continuing dissection, Marfan/ Aortic root> 5cm. - medical ttt with BB, CaCB & CT/6months if old dissection>2wks, stable, isolated arch, uncomplicated descending.

Classification of hypertension Classification According of BP level:  Normal <120/80  Prehypertension 120/80 – 139/89  Hypertension >140/90 Staging Hypertension:  Stage 1: 140-159/90-99  Stage 2 :> 160/100 Isolated systolic hypertension:  Grade 1 140-145/ < 80  Grade 2 > 160/ < 80

Causes of hypertension Secondary

Essential

Renal

Endocrine

Renovascular Reno-parenchymal Glomerulonephritis Collagen Disease, Henoch-Schonlein Purpura, Chronic Nephritis

Hyperaldosteronism Pheochromocytoma Hypo/Hyperthyroidism Cushing

Contraceptive pills Corticosteroids Mineralcorticoids Sympathomimetics -nasal decongestants -appetite suppressants Phenothiazine Antidepressants Cyclosporine Erthropiotin

Vascular Coarctationn

Pregnancy

Drugs Diet

See HTN in pregnancy

Licorice Tyramine rich food Salty food

Standing BP should be taking in: • First visit evaluation. • Elderly patients above 60 years. • Diabetic patients. • Patients with postural symptoms. • Patients on potent VD or large doses of diuretics.

Standing BP should be measured 2 minutes after standing.

Investigations (1st . visit & annually)

Urine exam proteinuria

Blood K+ Bl.sugar Lipid S.Creatinine Uric acid HB

ECG

Fundus

Hypertension Treatment  Life style modification  Stage 1: (140-159 / 90-99)  Start with thiazide or in special situations you can start with ACEI , ARB , BB ,CCB .

 Stage 2:≥ 160/100  Two drugs combinations

 If patient with diabetes or chronic kidney disease you start with 2 or more antihypertensive drugs to achieve goal BP  After 1 month if target BP is not reached: reach optimum doses or add additional drug  Inadequate response to antihypertensive drugs  BP < 10/5 after 15 days therapy

Resistant Hypertension •Office blood pressure >140/90 or 130/80 mm Hg in patients with diabetes or chronic kidney disease

and •Patient prescribed 3 or more antihypertensive medications at optimal doses, including if possible a diuretic

Arrhythmias Premature beats - loud S1. - TTT;  reassure if no sympt, young, not frequent, not multifocal, no structural HT dis.  if not or failed  BB.

Supraventricular tachy; Atrial rate 150-250. Types; 1) Atrial tachy (repeated abn. P) 2) MAT - 3 diff P - HR >100. - COPD due to hypoxia. - TTT= verapamil & TTT of COPD. - NB; digoxin ≠ (arrythmogenic) unless AF.

MAT

3) Reenterant tachy ; a) AVNRT - reenterant in or around AVN. - sudden onset- offset. - P wave inverted, just before or after or burried. - TTT; adenosine, carotid sinus massage terminate it. b) AVRT (in WPW) 1- orthodromic ( retrograde through acc path)Narrow complex. 2- antidromic ( retrograde through AVN) wide complex + delta wave. - P wave inverted & some time after complex. - TTT; amiodarone ( BB, flecainide) - NB; digoxin & verapamil ≠.

AVNRT

AVRT

Incisional tachy - PAT. - scar of corrected ASD. - gradual onset. - TTT= propafenone. Wondering atrial pacemaker; - as MAT but rate =95. - physiological.

    

WPW

♂, non familial. Types A tall R in V1 dt LT path. ECG ( short PR, delta wave, broad complex. Associations ( MVP, HCM, EBstein, thyrotoxicosis). TTT; Radiofrequency ablation if asymp no TTT, can participate in competitive sports.  Ttt of Complications; - treat narrow complex tachycardia (rate is usually 190) with vagal stimulation, cardioversion, verapamil or adenosine- same as any SVT. * AVRT orthadenosine. *AVRT antidromicamiodarone, flecainide, BB. - But never treat Acute AF or A flutter with digoxin, verapamil or BB. ( may lead to VT through acc path) DC or lignocaine or procainamide. but digitalis, verapamil, adenosine, are ≠.

Rt pathway activate from Rt to Lt from ant to post -ve in V1

Rt LT

Lt pathway activate from Lt to Rt from post to ant  +ve in V1

WPW

Atrial flutter A. Rate=250-350. NB; Regular tachy 150/min, narrow complex  A.flutter 2 :1 untill proved otherwise.  Best seen in inferior leads.  Uncover by adenosine or massage.  TTT; - DC ( most likely arrhyth. To respond) - Class III ( Ibutilide, amiodarone, sotalol)= medical cardioversion  60 % sinus. - DC + Ibutilide  100%. - Radiofrequency ablation 90%.  Low risk of thromboembolism but anticoag if prolonged.

AF  A. Rate=400-600.  Most common, ↑ with age.  C/P ( varing S1, absent a, pulsus deficit> 10, ↑ with exercise .  Causes; - MVD, LA > 4.5 cm. - IsHD, HTN, LVH, - ASD, SSS, WPW, a myxoma - myocarditis, const. peri., - PE, pneumonia, hypoxia, br. carcinoma. - thyrot, alcohol, coffee - lone, idiopathic

 TTT; - Paroxysmal if young event monitoring. if old patient, previous TIA anticoag, INR=2-2.5 + sotalol or amiodarone.

ttt of the attack stable Old> 1 y

unstable DC

recent

Anticoag + digoxin

TTE

Atria > 5 cm

atria< 5 cm

Anticoag + digoxin < 2 days Cardioversion without anticoag

> 2 days Anticoag 3 wks Cardioversion then anticoag 3 wks

TEE

thrombus Anticoag 6 wks then repeat

No thrombus Cardioversion without anticoag then anticoag

AF  Anticoag 3 wks before & after cardioversion.  after cardioversion Anticoag (most imp) + amiodarone or sotalol.  Propranolol or verapamil instead of digoxin in young or hyperdynamic unless Ht failure.  rate control is better than rhythm.  rhythm control ↑ mortality.  Pt with slow AF without TTT tend to be chronic.

 Risk factors for recurrence after cardioversion = indication for digoxin & anticoag. - long duration > 1 y. - Lt atrium > 5cm - old age > 75 y - Rh MVD - LV impairment.  Risk factors for thromboembolism.(5-7% annually); - Rh MVD - DM, HTN - LV impairment, Lt atrium enlargement. - previous CVA/TIA. if anyanticoag at all ages(↓risk to 1.6%) If not acc to the age(<65 = aspirin, 65-75= aspirin or warfarin, >75= warfarin)  Digoxin level ↑by – erythromycin, thiazides, amiodarone, verapamil, quinidine.  Digoxin ≠ in AVB, WPW, HCM, MAT, constrict. Cardio, myocarditis, prior to elective cardioversion.

VT 1) Monomorphic  Causes ( acute MI, DCM, chronic CAD, HCM, myocarditis.  Signs (regular pulse, 160, variable S1dt variable AVV position, abn splitting).  TTT; if unstable DC. if stableIV amiodarone (of choice) or lignocaine. if recurrent  pacing. if post-arrest  ICD.

Monomorphic VT

Features favoring VT  Concordance.  P waves.  Capture & fusion beats.  Very broad > 3.5 □. +  History of IsHD.  Variable S1, no decrease in rate with carotid sinus masage or adenosine.  Must be ttt as VT.

Non-sustained VT

if chronic recurrent

sustained

Poor LV funct. ICD

Good funct amiodarone + BB Or EPS + radiofreq ablation

not sustained ttt only if poor LVF & structural HT dis

VT induced by EPS

VT induced by exercise test

ICD +/- amiodarone

BB +/- amiodarone

NB; - if not sure VT/SVT with aberration adenosine diagnostic dose (↓SVT) & TTT as VT. - Sustained VT=> 3 runs of V beats<30 sec. - CCBs are absolutely ≠  ↓ BP. Do not ever use verapamil in wide complex tachy in the emergency setting (30% of those with V tac rapidly deteriorate)



Avoid verapamil with; 1. 2. 3.

 1. 2. 3. 4. 5. 6. 7.

AF or a flutter in WPW. Wide complex tachy With BB.

OK verapamil with; AF or a flutter in healthy HT. MAT PSVT (2nd choice ater adenosine) WPW with narrow complex tachy symptomatic ttt of HCM Severe concentric LVH HTN.

VT 2) Polymorphic (Torsade de points):  Causes - ↓ K, ↓Mg, ↓Ca, hypothyroid, hypothermia. -TCA, antipsychotics (phenothiazines) - clarithro, erythro, quinolones, cotrimoxasole, Ketoconasole, pentamidine. - antiarr; amiodarone, sotalol, class 1a. - IsHD, cong long QT S.  TTT 1- avoid or withdraw class Ia, c, III. 2- IV MG 1 gm or K channel opener. 3- BB ( not sotalol) IV in cong. Forms 4- temporary pacing & isoprenaline ( prevent brady & hence VT).  2ry prevention. 1) congBB & permanent pacing. ICD if life threatening arrhyth while on BB, FH od death in young. Lt stellate gangliectomy. 2) acquired ttt of the cause.  NB; Torsade de points is resistant to DC. -amiodarorone & class I a, c are ≠.

Torsade De pointes

Bradyarrhysmias  SSS.  WPW  AV block; - signs ( weak S1, variable in CHB, abn splitting, regular a wave, +/- prolonged V wave) - TTT; 1) atropine, isoprenaline. 2) ttt of the cause. 3) temporary pacing. 4) permanent pacing ( Mobitz II, CHB with wide complex. -NB; LT BBB is almost always associated with HT disease.

2nd Degree AV Block, Type I

LBBB and 2nd degree AV Block, Mobitz Type II

 CHB; - causes; 1) cong, unknown cause, minority due to maternal AID with anti Ro permanent pacing. 2) acquired; RCA dis or extensive ant MI temporary & rarely permanent pacing. NB: - most common cause of permanent pacing. - mortality 50% at 1 year esp. if age> 80y or non rheumatic.

SSS: 1. bradycardia. 2.sinuatrial block. 3. sinus node arrest. 4. Tachybrady syndrome. 5. AF.

Pacemakers  Nomenclature; 1st letter= chamber paced (V, A, D). 2nd letter= chamber sensed (V, A, D). 3 rd letter= pacemaker response to sensed impulse (T, I, T/I=atrially triggered, vent inhibited)  Uses of temporary pacing. 1) brady asystole, hemodynamic unstable, severe not responding to drug, post MI CHB, 2nd degree HB. 2) Tachy overdrive termination e.g.A flutter, VT prevention e.g. torsade. 3) before cardiac intervention to high risk ( LBBB, RCA angioplasty) vascular surgery, preop to trifascicular. 4) Post MI with trifascicular or RBBB+ LAH or LPH.

 Uses of permanent pacing; 1) brady; - SSS ( symptomatic S arrest > 3 sec or asymptomatic S arrest > 5 sec)AAI. - chr AV block, post AV ablation DDD or VVI. - syncope  DDD or VVI. - post cardiac transplant 2) others; HCM, DCM, long QT.  NB; most common pacemaker is DDD; most physiologic & provides better exercise tolerance. DDD maintain AV synchrony, + rate responsive models (R) if young energetics for Chronotropic incompetence.Most clinicians use DDD, unless the pt is in chronic slow AF - AAI are used e.g. in symptomatic sinus brady. -

 Pacemaker S; - with VVI. - short of breath at rest, relieved with exertion. - ECG= retrograde P. - TTT= DDD.

 Pacing in ant. MI; any except MOBITZ1 - 2nd or CHB. - new bifascicular. - new RBBB with preexisting 1st, LAH, LPH. - in LBBB with preexisting 1st AVB.  Pacing in Ht failure cardiac resynchronization therapy =CRT= bivent.or multisite pacing. if - EF<35% with optimal drug therapy.

ICD Overdrive pacing. Indications; - cardiac arrest dt VF,VT. - sustained VT + LVEF< 40% - non sustained VT + LVEF< 40% + syncope or post MI. - long QT; post arrest or FH of sudden death.

Antiarrhysmic drugs: Class

effect

site

use

A

Quinidine Disopyramide procainamide

(- ) Na channels ↑ AP

A, V, acc

WPW+ AF

B

Lignocaine Phenytoin Mexiletin

(- ) Na channels ↓ AP

V

Monomorph VT

C

Flecainide propafenone

(- ) Na channels No effect on AP

A, V, acc

AF

Class II

Propranolol Atenolol

BB

nodes

Stress, thyroid, sinus, cong long QT, VT

Class III

Amiodarone Sotalol Ibutilide

(- )Na, Ca, K channels ↑ plateau

A, acc ,V

AF, A flutter AVRT+ wpw VT

Class IV

verapamil

(- )Ca channels

AV node

SVT, MAT

Others

Adenosine digoxin

K opener, no(-) inotrop.

AV node

SVT, diag of flutter

Class I

Adenosine  Short acting.  IV, 6-12 mg  Uses (diag diff bet VT & SVT, therapy SVT)  Enhanced by disopyramide & inhibited by theophyllin.  Side effect; chest pain, bronkospasm, flushing, hypotension. Amiodarone  Side effects. most common after oral neurotoxicity, most common after IV hypotension. Lung toxicity (1-10%) IPF, ARDS, BOOP, pl effusion. others; hepatitis, throiditis, optic neuritis, corneal opacities, photosensitivity, ↑digoxin & anticoag level, ↑ PR, ↑QRS, ↑QT esp with 1a.  ≠ in Torsade de points. NB; no prophylactic use of lignocaine after MI ↑ mortality.

HT failure  EF= 50-70%.  5 ys survival; 65% if EF<40. 95% if EF>50.  Causes of High COP failure.  Diastolic HF; - preserved syst. function ( >40%). - ischemia. - transient in MI , permanent in restrictive cardiomyopathy & Vent Hypertrophy.  Systolic HF; EF< 40%.

TTT 1) 2) 3) 4)

Physical activity. Diet. Exercise. VD;

NB; ACEI ↓ mortality & hospitalization. of no benefit in – RVF. - obstructive valve lesion. - ≠ in HCM. 5) Digoxin- ↓renin, symp, hospital but not ↓ mortality. - used in Syst HF, S3, severe CHF. - ≠ AVB, asymtomatic HF, acute MI.

6)Diuretics e.g. spironolactone ↓ mortality & hospitalization & symptoms. used in severe CHF.

7) BB ( Meto, Biso, Carvi)  ↓ mortality & hospitalization & symptoms. not used in volume overloaded patients.

Syncope Definition; sudden transient loss of conscious dt cerebral ischemia. A) Neurocardiogenic 1) Vasovagaltilt table test, never biting tongue. 2) situational ( cough, micturition). 3) carotid sinus syndrome carotid sinus massage, ttt=DDD or sympathomimetic, fludro. 4) Pyschgenic (panic, hysteria). NB; carotid sinus massage; - 5 sec massage Rt then lt 30 sec apart while pt supine, if – ve repeat in upright. - +ve= >3 sec asystole, ↓ SBP > 50mmHg. - # in carotid bruit, recent MI (3 m), recent stroke (3m), previous VT.

B) Orthostatic hypotension 30% of syncope in elderly. Definition; ↑ HR> 30b/min, ↓SBP>20mmHg, ↓DBP>10mmHg after 3min up. (n= ↑ HR =10 b/min, ↓SBP=3mmHg, ↑DBP= 5mmHg,stabilize in 45 sec.)

causes; - hypovolemia. - drugs; anti HTN, diuretics. - addisson. - autonomic dysf. - HF or stenotic lesions. tilt table test, TTT; non pharmacological; avoid heavy meals, alcohol, postural training. pharmacological; sympathomimetics, MAOI-A, fludro.

C) Neurological e.g. Migraine, hyperventilation, vertebrobasilar TIA. D) Cardiac disorders at rest e.g. arrhyth, MI. exertional= mechanical obst e.g. AS, MS, HCM, dissection,PE, PS, PH, temponade. positional, ball & valve thrombus, myxomas.

JVP  Normally.  Kussmaul’s sign.  Absent HJR.  Absent & giant a wave.  Canon a; regular, irregular, regular but not constant.  Absent x, steep x.  Absent Y, rapid y.  Temponade compress ventricles, constrictive P compress atria.

Cardiac examination Apex;  Heaving, thrusting/hyperdynamic, Tapping.  Dyskinetic/displaced, diffuse.  Double apex, pericardial knock.  Parasternal heave, palpable S3. Diastolic shock. S1; loud, soft, split, variable. NB; PAC has long PR & loud S1 as it is premature=short diastole.

S2; loud, soft, wide split, fixed split, reversed split or single S2. NB;wide split, soft S2=PS. narrow split, loud S2=PH. wide split, loud S2=ASD.

Murmurs Systolic murmurs over Apex, A, P. Diatolic murmurs over Apex, A2. Continuous murmurs. NB; all murmurs ↓ by standing exept MVP & HCM. - Effect of respiration.

HT transplantation  Survival; 80% at 1 yr. 75% at 3 yrs. 505 at 10 yrs  Complications; - accelerated coronary small vs dis. - lymphoma, skin cancer - CRF dt cyclosporin.  Indications; 44% CHD, CM, myocarditis. NB; in myocarditis, transplantion does not worse the prognosis but may recur in the transplant.

ECG & arrhythmias

Comment on; 1) 2) 3) 4) 5) 6)

Rhythm. Rate Axis P wave PR QRS - R wave progression - amplitude. - duration. - Pathological Q. 7) ST. 8) T wave. 9) QT. 10) U wave.

Normal adult 12-lead ECG

1) Rhythm  Regular; - sinus (+ve P in II, -ve P in avR) - nodal ( no P or -ve P in II, +ve P in avR). - idoventricular (regular brady, broad complexes, variable PR).  Irregular - AF, - extrasystole, - respiratory sinus arrhyth.

Sinus Rhythm

Atrial Premature Beat

Ventricular premature beats Long QT interval

Atrial Bigeminy

Ventricular bigeminy There are also features of an acute inferior myocardial infarction.

Atrial fibrillation

Atrial fibrillation. Right axis deviation.

2) Rate if regular- 300/n. of large □bet R-R. N of complexes in 3 sec x 20 or in 2 sec x 30 or 6 sec x 10 (1 sec=5 □) if irregular.

3) Axis  N

I

II

III

Rt axis LT

r S

Confirm LT

LAH

r S

avR

avF

RBBB, old inferior MI

left anterior hemiblock ,First degree heart block

Left Anterior Fascicular Block

RBBB + LAFB(M pattern in v1,v2+lt axis deviation)

Bifascicular Block: RBBB + LAFB

RBBB + LPFB(M pattern in v1.v2+Rt axis deviation)

NB; Trifascicular  LAH + RBBB + long PR.  Rt axis(LPH) + RBBB + long PR. Bifascicular  LAH + RBBB  Rt axis(LPH) + RBBB

Trifasicular' block Complete Right Bundle Branch Block Left Anterior Hemiblock(lt axis deviation) Long PR interval

4) P wave N (2.5 x2.5 small □) Mitral Pulmonal Biatrial enlargement. in V1 (biphasic with larger –ve deflection in V1)  absent    

Right atrial hypertrophy A P wave in lead II taller then 2.5 mm (2.5 small squares). The P wave is usually pointed.

P mitrale

5) PR    

N (3-5 □) Short (WPW, nodal, LGL). Long ( 1st degree Ht block). Variable ( CHB, Mobitz I)

WPW

Lown Ganong Levine Syndrome

6) QRS(red flag for tall R wave in v1) 1. R wave progression V1

V2

V3

V4

V5

V6

Causes of tall R in V1; RVH, RBBB, dextrocardia, WPW type A, Posterior MI.

Posterior MI and Right Ventricular MI

2. Amplitude; N LVH S in V1 + R in V6> 7□. S+ R in any 2 chest leads > 5 □. +/- inverted T in lat leads (strain) RVH tall R in V1 & deep S in V6. NB:the sum of any tall R&deepS express VH

Left ventricular hypertrophy (LVH)

LVH with "Strain"

3. Duration n<2.5 □. Causes of wide complexes; - BBB - WPW - vent beats - pacemaker - hyperkalemia.

RBBB(when seen,detect the axis) 

r

R’

in V1

+ depressed ST & inverted T in Rt leads. (secondary T wave invertion) - RBBB + RAD or LAD=bifascicular.

RBBB With ST-T Wave Abnormalities

Right Bundle Branch Block

LBBB in V1, in V6. - no R. - T against QRS.(pseudo ischemia in V1,T wave upward &Q wave downward) NB; true ischemia T same=ischemia. ie:(inverted T with pathological Q)  

LBBB

Acute inferior myocardial infarction in the presence of left bundle branch block

Ventricular Pacemaker Rhythm  Broad complex.

Pacemaker; pacing spikes (best seen here in V4 - V6) will be seen - they may be subtle the paced QRS complexes are abnormally wide

Wolf-Parkinson-White syndrome left lateral pathway

WPW(delta wave &slurred upstrok of R wave)

Hyperkalemia     

Brady Absent P Broad complexes Hyperacute T Depressed ST

Hyperkalaemia

4. Pathological Q ( > ¼ R) normal Q only in avR & V5. differential diagnosis; - transmural infarction(old). - LBBB.(psudo infarction in case of upward T wave or T-same if T wave inverted in case of MI) - WPW.(slurred upstrok of R wave)

7) ST  Raised ST; - transmural infarction (>2 □ in chest leads, >1 □ in limb leads). - pericarditis.(also there is PR elevation &ST depression in aVR) - LBBB. - Depressed ST; - NST MI, angina. - digitalis.the concavity of ST is directed upward - RBBB.V1& V2 - post. MI(in V1)

DD of ST changes

Raised ST; - transmural infarction (>2 □ in chest leads, >1 □ in limb leads), with evolutional changes & reciprocal depression. - prinzmetal angina; transient without evolutional changes or reciprocal depression. - early repolarization pattern; young, stable ST elevation without evolutional changes or reciprocal depression. - pericarditis; special pattern, in all leads. - LBBB; with characteristic QS pattern in V1,2 & notched R in V5,6. - Depressed ST; - angina. - LVH with strain. - non-Q MI=NSTEMI= subendocardial infarction. - reciprocal depression in transmural infarction. - digitalis; scooping of ST-T. - Post. Wall infarction. 

Acute inferior myocardial infarction ST elevation in the inferior leads II, III and aVF reciprocal ST depression in the anterior leads

Acute anterior myocardial infarction ST elevation in the anterior leads V1 - 6, I and aVL reciprocal ST depression in the inferior leads

Old anterior MI

Old inferior myocardial infarction

Acute posterior myocardial infarction (hyperacute) the mirror image of acute injury in leads V1 - 3 (fully evolved) tall R wave, tall upright T wave in leads V1 -3 usually associated with inferior and/or lateral wall MI

inf-post-

Pericarditis(rasised ST in the chest leads &raised PR WITH depressed ST in aVR)

Digitalis effect shortened QT interval characteristic down-sloping ST depression, reverse stick appearence, (shown here in leads V5 and V6)

Digitalis effect

8) T wave  Hyperacute Hyperkalemia.  Flat  Hypokalemia.  Inverted  ischemia.

DD of T wave inversion Normally in avR, V1. Ischemia. Ventricular strain pattern. Pericarditis. Subarachnoid Hge (deep, wide + prolonged QT, U wave), may be due autonomic dysf.  BBB.  Ventricular Pacemaker.     

9) QT > ½ RR = prolonged; In; - Congenital; Jerwell-Lange-Nielson (AR,deafness). Romano ward (AD) - Electrolytes (Hypokalemia, hypocalcemia, hypoMg, hypothermia, hypothyroid). - Drugs ; antiarrhyth (Ia as quinidin &disopyramid, III as amiodaron &d-sotalol), antibiotics ( macrolids, quinolones, quinine, sutrim, antifungal, pentamidine - Subarachnoid Hge. - MVP, Ischemia, Rh carditis.

Long QT Interval

Long QT Interval

10) U wave  Hypokalemia

NB; Hypokalemia; - prolonged QT. - flat T. - U wave.

Hypokalemia

Bradyarrhythmias

Regular

Variable PR = CHB

Irregular If Absent P=slow AF. const PR =Mobitz II Variable PR=Mobitz I

Fixed PR= -sinus. -Nodal. no P wave.

2nd Degree AV Block, Type I(progressive prolongation of PR interval)

LBBB and 2nd degree AV Block, Mobitz Type II(dropped complex ¬ prececeded by progressive PR prolongation+M-shaped broad complex)

RBBB plus Mobitz II 2nd Degree AV Block(M-shaped R wave,depressed ST segment &inverted T wave)plus every 2 P waves followed by one complex

Trifascicular Block: RBBB, LAFB, and Mobitz II 2nd Degree AV Block(M-pattern in V1&rS pattern in II so LT axis deviation and LAFB&1 P:2R in both II&V1)

Mobitz II 2nd Degree AV Block With LBBB

Complete Heart Block(regular bradycardia with variable PR interval in II)

Sinus bradycardia Acute inferior MI(receprocal changes seen in I&aVL) and Right Bundle Branch Block(M-pattern in V1,V2 with depressed ST &inverted T) are also present

SSS:     

1. bradycardia. 2.sinuatrial block. 3. sinus node arrest. 4. Tachybrady syndrome. 5. AF.

Tachyarrhythmias

Broad

Narrow

Irregular = rapid AF

-VT -SVT + aberration -WPW + AF or SVT

Regular -Sinus tachy -SVT -A flutter 2:1 block

Sinus tachycardia

AVNRT

AVRT(WPW)short PR &delta wave

MAT

Atrial fibrillation with pre-existing left bundle branch block(absent P in II&M pattern in V5,V6)

Atrial flutter with 2:1 AV conduction

Atrial flutter

   

Broad Complex tachy. VT SVT + aberration WPW + AF or SVT

Wolf-Parkinson-White syndrome with atrial fibrillation

Ventricular tachycardia

Monomorphic VT

Features favoring VT  Concordance.(the same polarity of QRS coplex in all chest leads)  P waves.(AV dissociation may result in visible P which appear to march through the tachycardia)  Capture(intermittent narrow QRS complex owing to normal ventricular activation through AVN and conducting system) & fusion beats.  Very broad > 3.5 □. +  History of IsHD.  Variable S1, no decrease in rate with carotid sinus masage or adenosine.  Must be ttt as VT.

Polymorphous ventricular tachycardia (Torsade de pointes).

   

This is a form of VT where there is usually no difficulty in recognising its ventricular origin. wide QRS complexes with multiple morphologies changing R - R intervals the axis seems to twist about the isoelectric line

Torsade De pointes

Ventricular fibrillation bizarre, irregular, random waveform no clearly identifiable QRS complexes or P waves wandering baseline

Acute pulmonary embolus(SIQIIITIII &poor progression of R wave &strain pattern in chest leads&RBBB in V1)

 The following, often transient, changes may be seen in a large pulmonary embolus.  an S1 Q3 T3 pattern  a prominent S wave in lead I  a Q wave and inverted T wave in lead III

 sinus tachycardia  T wave inversion in leads V1 - V3  Right Bundle Branch Block

Arrhythmias Premature beats - loud S1. - TTT;  reassure if no sympt, young, not frequent, not multifocal, no structural HT dis.  if not or failed  BB.

Supraventricular tachy; Atrial rate 150-250. Types; 1) Atrial tachy (repeated abn. P) 2) MAT - 3 diff P - HR >100. - COPD due to hypoxia. - TTT= verapamil & TTT of COPD. - NB; digoxin ≠ (arrythmogenic) unless AF.

3) Reenterant tachy ; a) AVNRT - reenterant in or around AVN. - sudden onset- offset. - P wave inverted, just before or after or burried. - TTT; adenosine, carotid sinus massage terminate it. b) AVRT (in WPW) 1- orthodromic ( retrograde through acc path)Narrow complex. 2- antidromic ( retrograde through AVN) wide complex + delta wave. - P wave inverted & some time after complex. - TTT; amiodarone ( BB, flecainide) - NB; digoxin & verapamil ≠.

Incisional tachy - PAT. - scar of corrected ASD. - gradual onset. - TTT= propafenone(class Ic).

WPW ♂, non familial. Types A tall R in V1 dt LT path. ECG ( short PR, delta wave, broad complex). Complications; - AVRT orth(narrow complex tachy)adenosine. - AVRT antidromic(broad complex)amiodarone, flecainide, BB. - AF or flutter ( may lead to VT through acc path) DC or lignocaine or procainamide. but digitalis, verapamil are ≠.  Associations ( MVP, HCM, thyrotoxicosis).  TTT; Radiofrequency ablation if asymp no TTT, can participate in competitive sports.    

WPW

Atrial flutter A. Rate=250-350. NB; Regular tachy 150/min, narrow complex  A.flutter 2 :1 untill proved otherwise.  Best seen in inferior leads.  Uncover by adenosine or massage.  TTT; - DC ( most likely arrhyth. To respond) - Class III ( Ibutilide, amiodarone, sotalol)= medical cardioversion  60 % sinus. - DC + Ibutilide  100%. - Radiofrequency ablation 90%. - atrial pacing.  Low risk of thromboembolism but anticoag if prolonged.

AF    

A. Rate=400-600. Most common, ↑ with age. C/P ( varing S1, absent a, pulsus deficit> 10) Causes; - MVD, LA > 4.5 cm. - IsHD, HTN, LVH, - ASD, SSS, WPW, a myxoma - myocarditis, const. peri., - PE, pneumonia, hypoxia, br. carcinoma. - thyrot, alcohol, coffee - lone, idiopathic

 TTT; - Paroxysmal if young event monitoring. if old patient, previous TIA anticoag, INR=2-2.5 + sotalol or amiodarone.

ttt of the attack stable

unstable DC

TTE

Atria > 5 cm

atria< 5 cm

Anticoag + rate controlling < 2 days Cardioversion without anticoag

> 2 days Anticoag 3 wks Cardioversion then anticoag 3 wks

TEE

thrombus Anticoag 6 wks then repeat

No thrombus Cardioversion without anticoag then anticoag

AF  Anticoag 3 wks before & after cardioversion.  after cardioversion Anticoag (most imp) + amiodarone or sotalol.  Chronic AF  Propranolol or verapamil instead of digoxin in young or hyperdynamic unless Ht failure.  rate control is better than rhythm.  rhythm control ↑ mortality.  Pt with slow AF without TTT tend to be chronic.

 Risk factors for recurrence after cardioversion = indication for digoxin & anticoag. - long duration > 1 y. - Lt atrium > 5cm - old age > 75 y - Rh MVD - LV impairment.  Risk factors for thromboembolism.(5-7% annually); - Rh MVD - DM, HTN - LV impairment, Lt atrium enlargement. - previous CVA/TIA. if anyanticoag at all ages(↓risk to 1.6%) If not acc to the age(<65 = aspirin, 65-75= aspirin or warfarin, >75= warfarin)  Digoxin level ↑by – erythromycin, thiazides, amiodarone, verapamil, quinidine.  Digoxin ≠ in AVB, WPW, HCM, MAT, constrict. Cardio, myocarditis, prior to elective cardioversion.

VT 1) Monomorphic  Causes ( acute MI, DCM, chronic CAD, HCM, myocarditis.  Signs (regular pulse, around 160, variable S1 due to variable AVV position).  TTT; if unstable DC. if stableIV amiodarone (of choice) or lignocaine. if recurrent  pacing. if post-arrest  ICD.

Non-sustained VT

if chronic recurrent

sustained

Poor LV funct.

Good funct

ICD

amiodarone + BB Or radiofreq ablation

not sustained ttt only if poor LVF & structural HT dis

VT induced by EPS

ICD +/- amiodarone

NB;

- if not sure VT/SVT with aberration adenosine diagnostic dose (↓SVT) & TTT as VT. - Sustained VT=> 3 runs of V beats<30 sec. - CCBs are absolutely ≠  ↓ BP.

if unstable DC. if stableIV amiodarone (of choice) or lignocaine. if recurrent  pacing. if post-arrest  ICD.

2) 

 . 

. 

VT

Polymorphic (Torsade de points):

Causes -familial 90% - ↓ K, ↓Mg, ↓Ca, hypothyroid, hypothermia. -TCA, antipsychotics (phenothiazine) - clarithro, erythro, quinolones, cotrimoxasole, Ketoconasole, pentamidine. - antiarr; amiodarone, sotalol, class 1a. - IsHD, cong long QT S. TTT 1- avoid or withdraw class Ia, c, III. 2- IV MG 1 gm . 2ry prevention. BB ( not sotalol) IV in cong. Forms. Lt stellate gangliectomy ICD if life threatening arrhyth while on BB, FH of death in young. 2) acquired ttt of the cause. NB; Torsade de points is resistant to DC. -amiodarorone & class I a, c are ≠.

The recommendations guidelines:  

Lifestyle modification was recommended for all patients . Beta blockers — Beta blocker therapy was recommended for patients with QT prolongation and suggested for patients with a molecular diagnosis of congenital LQTS but a normal QT interval. Beta blockers are a mainstay of therapy in both asymptomatic and symptomatic patients with congenital LQTS, since they reduce both syncope and SCD [29] . Beta blockers interrupt the "trigger" for TdP and may shorten the QT interval by decreasing activation from the left stellate ganglion.



ICD implantation was recommended for survivors of a cardiac arrest who have a reasonable expectation of survival with a good functional status for at least one year . ICD implantation was suggested for patients who experience sustained VT and/or a syncopal event consistent with a tachyarrhythmia while on beta blocker therapy.



Beta blocker therapy should be initiated or continued in all patients who receive an ICD.



The guidelines also stated that evidence was less well established for the following: Left cardiac sympathetic denervation for patients with syncope, TdP, or cardiac arrest while receiving beta blockers [58] . ICD implantation combined with beta blocker therapy for patients in categories at an increased risk of SCD (eg, LQT2 or LQT3)

Bradyarrhysmias  SSS.  WPW  AV block; - signs ( weak S1, variable in CHB, abn splitting, regular a wave, +/- prolonged V wave) - TTT; 1) atropine, isoprenaline. 2) ttt of the cause. 3) temporary pacing. 4) permanent pacing ( Mobitz II, CHB with wide complex.

-NB;

LT BBB is almost always associated with HT disease.

 CHB;regular bradycardia with variable PR - causes; 1) cong, unknown cause, permanent pacing. 2) acquired; RCA dis or extensive ant MI temporary & rarely permanent pacing. NB: - most common cause of permanent pacing. - mortality 50% at 1 year esp. if age> 80y or non rheumatic.

Pacemakers  Nomenclature; 1st letter= chamber paced (V, A, D). 2nd letter= chamber sensed (V, A, D). 3 rd letter= pacemaker response to sensed impulse (T, I, T/I=atrially triggered, vent inhibited)

 Uses of temporary pacing.

1) brady asystole, hemodynamic unstable, severe not responding to drug, post MI CHB, 2nd degree HB. 2) Tachy overdrive termination e.g.A flutter, VT prevention e.g. torsade. 3) before cardiac intervention to high risk ( LBBB, RCA angioplasty) , preop to trifascicular. 4) Post MI with trifascicular or RBBB+ LAH or LPH.

Uses of permanent pacing 1) brady; - SSS ( symptomatic S arrest > 3 sec or asymptomatic S arrest > 5 sec)DDD. - chr AV block  DDD or VVI. - Neurocardiogenic syncope  DDD or VVI. - post cardiac transplant 2) others; HCM, DCM, long QT. 

NB; most pacemakers are VVI. - AAI are used e.g. in symptomatic sinus brady. - DDD maintain AV synchrony, + R if young.



Chronotropic incompetence mainly in young energetics rate responsive models (R).

 Pacemaker S; - with VVI. - short of breath at rest, - ECG= retrograde P. - TTT= DDD.

 Pacing in ant. MI; - 2nd or CHB. - new bifascicular. - new RBBB with preexisting 1st, LAH, LPH. - in LBBB with preexisting 1st AVB.  Pacing in Ht failure if - class 3, 4. - QRS > 130. - EF<35% with optimal drug therapy.

ICD  Overdrive pacing.  Indications; - cardiac arrest dt VF,VT. - sustained VT + LVEF< 40% - non sustained VT + LVEF< 40% + syncope or post MI. - long QT; post arrest or FH of sudden death.

Antiarrhysmic drugs:

Class

Class I

effect

site

use

A

Quinidine Disopyramide procainamide

(- )Na channels ↑ AP

A V acc

WPW+ AF

B

Lignocaine Phenytoin Mexiletin

(- )Na channels ↓ AP

V

Monomorph VT

C

Flecainide propafenone

(- )Na channels No effect

A V acc

AF

Class II

Propranolol Atenolol

BB

nodes

Stress, thyroid, sinus, cong long QT, VT

Class III

Amiodarone Sotalol Ibutilide

(- )Na, Ca, K channels ↑ plateau

A acc V

AF, A flutter AVRT+ wpw VT

Class IV

verapamil

(- )Ca channels

AV node

SVT, MAT

Others

Adenosine digoxin

K opener, no(-) inotrop.

AV node

SVT, diag of flutter

Adenosine  Short acting.  IV, 6-12 mg  Uses (diag diff bet VT & SVT , therapy SVT)  Enhanced by disopyramide & inhibited by theophyllin.  Side effect; chest pain, bronchospasm, flushing, hypotension. Amiodarone  Side effects. most common after oral neurotoxicity, most common after IV hypotension. Lung toxicity (1-10%) IPF, ARDS, BOOP, pl effusion. others; hepatitis, throiditis, optic neuritis, corneal opacities, photosensitivity, ↑digoxin & anticoag level, ↑ PR, ↑QRS, ↑QT esp with 1a.  ≠ in Torsade de points. NB; no prophylactic use of lignocaine after MI ↑ mortality.

Respiration

PFTs 1. PEFR (Peak exp flow rate); L/min for airway obst in asthma. 2. Spirometer; Flow rate. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), FEV1/ FVC = 7080%. obstruct  FEV1/ FVC < 70%. Restrict  FEV1/ FVC preserved , ↓ FVC 3. lung volumes - total lung capacity (TLC), - residual volume (RV). Decreased lung volumes suggest restrictive disease if accompanied by a normal FEV1/FVC ratio.

4. Gas transfer; Measurement of diffusing capacity for carbon monoxide (DLCO) assesses gas exchange. restrictive disease + ↓DLCO intrinsic lung disease, restrictive disease + normal DLCO  a non-pulmonary cause of restriction. (Extrinsic lung disease). Markedly ↓ DLCO + obstructive  emphysema, NB: KCO = DLCO/ VA (alveolar volume = Gas transfer corrected for lung volume. ↓KCO-emphysema, ILD, pulm vascular as Pulm HTN, emboli. ↑KCO pulm hge, polycythemia, Lt to Rt shunt, exercise, Br asth.

Flow-volume loops can identify upper airway obstruction, which can be impossible to detect from standard FVC measurements.

Interpretation of DLCO Low DLCO with obstruction Emphysema Cystic fibrosis Bronchiolitis

Low DLCO with restriction Interstitial lung disease Pneumonitis

Increased DLCO Polycythemia Pulmonary hemorrhage Left-to-right intracardiac shunting

Respiratory failure Inability to maintain adequate oxygenation & CO2 excretion. Type 1; ↓O2 with normal CO2, in restrictive dis ( diffusion defect). (neuro, muscular, alveolar), ttt by ↑O2 in inspired air. Type 2; ↓O2 & ↑ CO2, in obstructive dis, ttt by low flow O2 to maintain hypoxic drive, doxapram, may need mechanical ventilation

Age related changes of PFTs Decrease in FEV1 VC Po2 Increase in RV NO increase of Pco2

Obstructive sleep apnea C/P; snoring, AM headaches, unrefreshing sleep, day time drowsiness. O/E; systemic/pul HTN, ventricular arrhythmias, LL oedema 2ry to pul HTN/cor pulmonal. ABG; ↓pO2, ↑pCO2. Polycythemia 2ry to ↓pO2. RVF  LVF in late stages. TTT  nasal CPAP. CONTINUOUS POSITIVE AIRWAY PRESSURE Continuous positive airway pressure (CPAP) functions as a pneumatic splint to maintain upper airway patency throughout all phases of sleep breathing. It operates by means of a flow generator which delivers pressure through air tubing to a nasal or face mask worn overnight. Most patients require lifelong

Asthma Def; chronic inflammatory disorder of the airways ccc by variable reversible airway obst with hyperresponsiviness to a variety of stimuli leading to recurrent attacks of wheezes, SOB, cough. Precipitating factors; drugs (NSAIDs, BB), infection, cigarettes, fumes, perfumes, pets, pollen, grass, exercise, cold weather, humidity. C/P; sympt= variable reversible wheezes, cough, SOB. signs=tachypnea, hyperinflation, exp rhonchi.

Investigations

 > 25% PEFR variability on at least 3 days per week for 2 weeks.  > 15% PEFR improvement after BD.  Skin prick test Type I hypersens, ↑ IgE. Spirometer normal ---but on metacholine challenge test, FEV1↓by >20%. obstructive---BD-- FEV1↑by 12-15%.  ↑ lung volumes.  ↓ FEV1/FVC< 70%.

 TTT; - Cough variant asthma inhaled steroids (Budesonide) - exercise variant asthma diag. by spirometer before & after

TTT; preB2, leukotriene recep antagonist., pre exercise warming - TTT of acute severe asthma nebulized Ipratropium & salbotamol, O2, steroids30-40mg. Mg sulphate single dose.

Acute severe asthma. Signs; 1- speech impairment. 2- pulse >110 b/min. 3- RR> 25 br/min. 4- PEFR 33-50%predicted. TTT; high flow O2(40-60%), Nebulised Ipratrobium (0.5 mg 4-6 hourly) , Nebulised salbutamol, steroids tablets (40-50 mg /day prednisolone)or(100 mg /6hrs hydrocortisone) for at least 5 days, Single dose magnesium sulfate +/Ab.

Life threatening asthma. Signs; 1-confusion , exhaustion. 2- brady <60b/min. 3- ↓BP. 4- silent chest , cyanosis . 5-↓O2, n or ↑CO2, HCO3 is considered if base def > 8. 6- PEFR < 33%predicted. Do ABG & consult ICU NB; ABG done if O2 sat < 92%. CXR is necessary to exclude pneumothorax.

A 25-year-old gentleman, known asthmatic , presents with an acute dyspnea. He is usually well controlled on inhaled fluticasone and salbutamol inhaler. The patient admits to have been getting progressively short of breath over the last few days.

Arterial blood gases on air show: PaCO2 = 3.8 kpa PaO2 = 7.5 kpa pH = 7.49 Standard bicarbonate= 23 mmol/L

The casualty officer starts the patient on high flow oxygen and continuous nebulised salbutamol. He also gives the patient 200 mg of hydrocortisone IV and one dose of nebulised ipratropium bromide. No improvement is seen after 30 minutes of treatment.

BTS Guidelines on the Management of chronic Asthma Step I inhaled short acting B2 agonist on demand. Step II  Add inhaled steroid 200-800 mcg/d (small dose) Step III  Add inhaled long-acting B2 agonist . Step IV as before + ↑ inhaled steroid up to 2000 mcg/d (large dose) or leukotriene receptor antagonist or SR theophylline or B2 agonist tablet Step V Use daily steroid tablet in lowest dose

occupational asthma asthma induced or aggravated by work. The highest groups at risk include: spray painters (isocyanate) plastic makers (resins) farmers (grain dust) bakers (flour) Peak expiratory flow rate — Serial measurement of (PEFR) is useful in the investigation and assessment of occupational asthma (OA) . Monitoring is carried out by recording PEFR at least 4 times per day for a period of at least 2 weeks at work and during a similar period away from work;

COPD Definition; Chronic slowly progressive dis ccc by airway obst that does not markedly change over several months. Types;  Chronic bronchitis, Asthmatic bronchitis.  Emphysema.  Bronchiectasis.

Chronic bronchitis chronic cough &expectoration for most of the days, for at least 3 m, for 2 consecutive yrs. Emphysema; permanent enlargement of the airways distal to terminal bronchioles. Causes of COPD; Smoking, dust, air pollution (cadmium  emphysema, coal, cotton, cement), α1 antitrypsin def emphysema

Diagnosis The presence of airflow obstruction should be confirmed by performing postbronchodilator spirometry

- FEV1< 80% predicted, mild= 50-80%

moderate 30-50% severe < 30% - FEV1/FVC< 70% - Large lung volumes.

Differentiating COPD from asthma Clinical features

COPD

Asthma

Smoker or ex-smoker

Nearly all

Possibly

Symptoms under age 35

Rare

Often

Chronic productive cough

Common

Uncommon

Breathlessness

Persistent and progressive

Variable

Night time waking with Uncommon breathlessness and or wheeze

Common

Significant diurnal or day to day variability of symptoms

Common

[2004]

uncommon

Differentiating COPD from asthma: 2 If diagnostic uncertainty remains, the following findings should be used to help identify asthma: FEV1 and FEV1/FVC ratio return to normal with drug therapy a very large (>400ml) FEV1 response to bronchodilators or to 30mg prednisolone daily for 2 weeks serial peak flow measuremenst showing significant (20% or greater) diurnal or day-to-day variability.

TTT COPD The most imp. Is smoking cessation. Br.dilators ,Ipratrobium bromide ,B2 agonists, oral theophyllin Steroids 30 mg /d only for responsive. LTOT ↑ survival. Lung transplant does not ↑ survival, only improve quality of life TTT of acute exacerbation NB; should not receive more than 24-28% O2 without ABG monitoring, keeping PO2=50-60.

Managing stable COPD: Promote effective inhaled therapy In people with stable COPD who remain breathless or have exacerbations despite using short-acting bronchodilators as required, offer the following as maintenance therapy: – if FEV1 ≥ 50% predicted: either LABA or LAMA – if FEV1 < 50% predicted: either LABA+ICS in a combination inhaler, or LAMA

Offer LAMA in addition to LABA+ICS to people with COPD who remain breathless or have exacerbations despite taking LABA+ICS, ICS = inhaled corticosteroid irrespective of their FEV1 LABA = long-acting beta agonist 2

LAMA = long-acting muscarinic agonist

long-term oxygen therapy (LTOT) Indications for patients with chronic lung disease include : Arterial PO2 (PaO2) < 7.3 kpa, or an arterial oxygen saturation (SaO2) < to 88 %. PaO2 < 8 kpa , if there is evidence of cor pulmonale, or erythrocytosis (hematocrit >55 %). BENEFITS (LTOT improve any thing) . LTOT improve outcome measures, including quality of life, cardiovascular morbidity, depression, cognitive function, exercise capacity, and frequency of hospitalization . improved survival among patients that received LTOT.

Bronchiectasis Def; Abn. persistent dilatation of bronchi + suppuration. RT middle lobe S= TB, measles, whooping cough. Br sicca hemmorragica = Apical = DD: TB, Friedlander pneumonia (Klebsiella). Causes;

1. cong; - ciliary dysf  immotile cilia = infert, sinusitis.  kartagner = + dextro, infert, sinusitis.  Young’s = + infert, sinusitis. - 1ry hypogamaglobulinemia. - cystic fibrosis.

2.

Acquired; - infection= abs, TB, pneumonia ABPA - obst = LN, FB, tumor, chr bronchitis..

3. Idiopathic = 60%

C/P; chronic mucopurulent sputum. Inv; 1. high resolution CT diagnostic in > 90%. 2. CXR. 3. PFTs; obst/restrictive. 4. ↓IG level deficiency of humoral immunity. TTT;  Most important  postural drainage.  Nebulized tobramycin for pseudomonas.  immunization  surgery, transplant. complications; - hemoptysis. - chest pain - 2ry amyloidosis. NB; causes of upper lobe bronchiactasis; - ABPA. - cystic fibrosis. - TB.

Cystic fibrosis common AR, carrier rate (1/25). CFTR gene on chromosome 7. DF 508 median survival = 35 yrs. abnormal CL transport across cell membrane; - in sweat gland  failure to reabsorb Cl . - in airway  failure to secrete Cl (thick mucous), ( Mucovisidosis)

C/P; Pulmonary dis;  colonization by -children  H influenza. -teenage & adults  pseudomonas, ttt by ceftazidime.  upper lobe.  pneumothorax in 10%.  90% of death due to respiratory failure.  GIT;  pancreatic insufficiency in 90%, meconium ileus & adult equivalent S, pancreatitis, Biliary cirrhosis, gall stones, DM in 1/3, male infertility.

NB; - CF  survival adv from cholera due to abn Cl channels. Invest;  sweat test; pilocarpine iontopheresis at least 50 gm collected.  Genetic study.  TTT;  antibiotics nebulized tobramycin, tobramycin, continuous antistaph.  most important is postural drainage.  pancreatic enzyme supplements

 meconium ileus equivalent good hydration, 

regular oral gastrografin.

Transplantation; double lung or Ht/lung ↑ survival.

Restrictive lung diseases Extrinsic. (chest wall, pleural, neuromuscular). Intrinsic. ( IPF, pneumonitis). PFTs (Lung volumes, vital capacity ,FEV1,DLCO)

Interstitial pulm fibrosis 1. 2. 3.

4. 5.

Causes; 80% cryptogenic (ANA +ve) Collagen dis; SLE, RA & AS. Drugs; (Be tough) Bleomycin, Busulfan, cyclophosphamide, (not vincristine), methotrexate, melphalan, amiodarone, sulfasalazine, Gold, nitrofurantoin. Irradiation occupations

Cryptogenic Fibrosing alveolitis = idiopathic pul fibrosis Clinical; elderly men, Dyspnea + 5 C (dry cough, cyanosis, clubbing, crackles). CXR / HRCT ---- early (ground glass appearance) give steroids 30mg / d. Late (reticulonodular shadowing) in the periphery & base ABG= type 1 RF. PFTs= restrictive. ANA, RF +ve. Diagnosis; typical C/P + CT or Lung Biopsy (VATS or open) . NB: Transbronchial not helpful 5 yr survival = 50%. TTT; 20% respond to steroids, aza , cycloph , INFγ (all medical ttt does not ↑survival), lung rehabilitation, O2 therapy, single lung transplantation......... ↑survival.

Sarcoidosis multisystem non caseating granulomatous dis. granuloma composed of MQ, lymphocytes, epitheloid cells, multinucleated giant cells. chronic or acute. Patients who present with a classical Lofgren's syndrome of fever, erythema nodosum, arthralgias, and bilateral hilar lymphadenopathy do not require biopsy . Biopsy should be performed in most other cases of suspected sarcoidosis.

Acute

chronic

Lofgren’s= fever, arthritis, EN

Lung; stage 1; BHL stage 2; BHL + Pul infil stage 3; Pul infil

Uveitis, parotid enlargement

Ht = restrictive Cardiomyopathy.

Bilateral hilar LN

Abd = HSM, LN, renal stones, granulomatous IN. Neuro =meningitis, mononeuritis,,bil facial Locomotor = bone cysts in digits, arthritis Skin = lupus pernio, nodules Eye = uveitis, sjogren Endocrine= ↑Ca, ↓thyroid or ↓ pituitarism, DI. ↓ TSH, Hypergammaglobulinemia

Bad prognostic criteria;  age > 40. Male gender , sympt > 6 months.  Splenomegaly, absence of EN, > 3 organs  Moderate to severe loss of lung function at presentation  stage 3. or A predominance of honeycomb changes on (HRCT) scan Diagnosis;  CXR (BHL) + EN  CT chest  pulmonary function tests.  Transbronchial biopsy  24 hrs urine Ca  serum ACE, peripheral blood counts, serum chemistries  -ve tuberculin . TTT; stage 1; resolve spontaneous stage 2; ttt with steroid if progressive TTT with steroid or other immunosupressives as azathioprine or methotrexate if ↑Ca, ↑Calcuria, eye, cardiac,neuro .

combination therapy;  azathioprine (2 to 3 mg/kg per day),  low-dose glucocorticoids (usually less than 20 mg / d).  high-dose acetylcysteine (600 mg administered as effervescent tablets orally three times per day). Assess response to treatment after 3-6 months, reassess every 3 months continue treatment for 1-2 year. LTOT. early referral for lung transplantation evaluation, even before the outcome of medical therapy has been determined (Grade 2C).

Occupational IPF

Inorganic dust 1. 2. 3. 4.

Organic =Allergic pneumonitis

Asbestos (, clubbing, Br carc, mesothelioma) Silicosis (TB, PMF, egg shell) Coal worker pneumoconiosis Berryliosis ( as sarcoid, BALber lymph. )

Other occupational dis due to Inorganic dust ; •Occupational asthma Bysinosis= Monday fever =asthma without IPF

Extrinsic allergic alveolitis= Bird fancier (protein) Malt worker (Asp. Clavatus) Farmer (Hay, micropolyspora fani) Baggasosis (Sacchari) Mushrom worker Ventilation pneum or humidifier fever

Asbestos-related disease 1. 2. 3. 4. 5. 6.

Ship builder, fireproof. Effects; Pl plaques; calcify, not premalignant, asymptomatic or restrictive. Pl thickening; lung bases, dyspnea, restrictive, KCO normal. Pl effusions. Asbestosis (clubbing, lower zone fibrosis, restrictive, ↓KCO.) Untreatable, resp failure Malignancy Br carc, mesothelioma, Br carc ↑ by smoking but not mesothelioma.

Silicosis silicon dioxide. hard rock miners, civil engineers associated with TB. acute  dry cough, dyspnea. chronic  nodules, upper lobe, PMF, egg shell calcification of hilar LN. no effective TTT, compensatible. NB; DD of egg shell calcification  Silicosis & sarcoidosis.

Coal worker pneumoconiosis

-

Simple CWP asymtomatic, no IPF, small nodules<1.5 cm. PMF;( progressive massive fibrosis) > 3cm. Upper zones Cavitate. Resp. F. PFTs obst/ restrictive +ve ANA , +ve Rh F

Berylliosis prolonged even slight amount beryllium as high technology electronics, alloys. chronic interstitial infiltrates affecting mainly upper lobes +/- bil hilar LN as sarcoidosis ( non caseating grannuloma) Beryllium lymphocyte transformation test.

extrinsic allergic alveolitis Attacks of fever, cough, and dypsnea several hours after exposure to the agent. No wheezes. Clubbing. With repeated attacks---IPF Type III hypersensitivity. Invest. - no eosinophilia - CXR-fleeting infiltrates then upper zone fibrosis, no cavitation, no calcification, non caseating granuloma. - serum precipitins are non specific, indicate only exposure. - Increase of immunoglobulins except Ig E. - RF is +ve PFTs-- restrictive pattern TTT: avoidance + Steroids.

lower lung zone fibrosis; 1. 2. 3. 4.

Asbestos. Cryptogenic FA. CT dis. Drugs. any thing else -- upper zone fibrosis

Diseases affecting upper lung zones; examples 1. ABPA 2. Extrinsic Allergic alveolitis 3. Cystic fibrosis 4. Sarcoidosis 5. Silicosis 6. TB 7. PMF

Byssinosis = Monday fever cotton dust no IPF, only asthma. no ↓ VC. ↓ FEV1 during work specially on the first day.

spontaneous pneumothorax, In general, treatment depends upon the size of the pneumothorax, the extent of respiratory distress, and the presence or absence of underlying lung disease. The goals of treatment are to remove air from the pleural space and to prevent recurrence.

Observation —

Observation should be the treatment of choice for small closed pneumothoraces without significant breathlessness. Patients with small (<2 cm) (25 % of the hemithorax ) primary pneumothoraces not associated with breathlessness should be considered for discharge with early outpatient review. + Supplemental oxygen: The administration of humidified 100 % oxygen increased the rate of air resorption 6 times

Aspiration of the pleural space —Simple aspiration is recommended as first line treatment for all primary pneumothoraces requiring intervention. [ Evacuation of air is required for pneumothoraces that occupy (> 2Cm) more than 25 % of hemithorax or for patients with severe dyspnea, hypoxemia, or significant pain.

Thoracostomy tube — Patients who fail aspiration treatment or who have a recurrent spontaneous pneumothorax → thoracostomy tube.

Breathless and/or rim of air>2 cm on chest radiograph………..Aspiration.... If fail ….. Consider repeat aspiration…. Intercostal drain… if fail…. Referral to thoracic surgeon

2ry sp. Pneumothorax ---- Breathless + age > 50 years + rim of air>2 cm on chest radiograph I C tube if not try aspiration Simple aspiration is less likely to succeed in secondary pneumothoraces and, in this situation, is only recommended as an initial treatment in small (<2 cm) pneumothoraces in minimally breathless patients under the age of 50 years. Patients treated successfully with simple aspiration should be admitted to hospital for at least 24 hours before discharge.

A lateral chest or lateral decubitus radiograph should be performed if the clinical suspicion of pneumothorax is high, but a PA radiograph is normal.

Intercostal tube drainage •If simple aspiration or catheter aspiration drainage of any pneumothorax is unsuccessful in controlling symptoms, then an intercostal tube should be inserted. [B] Intercostal tube drainage is recommended in secondary pneumothorax except in patients who are not breathless and have a very small (<1 cm or apical) pneumothorax. [B]

Chest drain suction •Suction to an intercostal tube should not be applied directly after tube insertion, but can be added after 48 hours for persistent air leak or failure of a pneumothorax to re-expand. [B] •High volume, low pressure (–10 to –20 cm H2O)suction systems are recommended. [C] •Patients requiring suction should only be managed on lung units where there is specialist medical and nursing experience. [C]

Referral to thoracic surgeons In cases of persistent air leak or failure of the lung to re-expand, the managing respiratory specialist should seek an early (3–5 days) thoracic surgical opinion. [C] Open thoracotomy and pleurectomy remains the procedure with the lowest recurrence rate for difficult or recurrent pneumothoraces. Minimally invasive procedures, thoracoscopy (VATS), pleural abrasion, and surgical talc pleurodesis are all effective alternative strategies.

Pleural effusion Exudate Criteria

> 1 of the following; Pl fl/serum TP> 0.5. Pl fl /serum LDH > o.6 Pl fl LDH> 2/3 upper limlt normal serum

Causes

Malignancy TB Pneumonia PE Meig’s chylothorax

Transudate

Hypoalb CHF, nephrotic, LC Contrictive pericarditis PE iatrogenic

A low pleural fluid glucose concentration (less than 60 mg/dL (3.33 mmol/liter), or a pleural fluid/serum glucose ratio less than 0.5) narrows the differential diagnosis of the exudates to the following possibilities Rheumatoid pleurisy Empyema Malignant effusion Tuberculous pleurisy

All transudates and all other exudates have pleural fluid glucose concentration similar to that of blood glucose.

parapneumonic effusion In general, a parapneumonic effusion should be sampled if it meets any of the following criteria:  layers >10 mm on a lateral decubitus film.  It is loculated .  It is associated with thickened parietal pleura on CT scan. In general, a pH <7.20 or a glucose <60 mg/dL is an indication for drainage of the effusion

The indications for chest tube insertion in patients with infected pleural effusions are: presence of organisms on a Gram stain of the pleural fluid , a frankly purulent pleural fluid, pleural pH < 7.2 in the setting of an infected pleural effusion, loculated pleural effusions and poor clinical progress despite antibiotic treatment.

TTT of hepatic hydrothorax Diuretic & salt restriction. If resp distress large volume paracentesis. TIPSS & liver transplantation. Vidiothoracoscopy & talc pleurodesis.

But never Tube

Aspergillosis. Allergic bronchopulmonary aspergillosis Aspergilloma Invasive aspergillosis

Allergic bronchopulmonary aspergillosis The clinical picture of ABPA is dominated by asthma complicated by recurrent episodes of bronchial obstruction, fever, malaise, expectoration of brownish mucous plugs, peripheral blood eosinophilia. With fleeting shadows on CXR. A skin prick test should be the first step in an asthmatic being evaluated for ABPA. A negative prick skin test virtually excludes ABPA from consideration. A history of asthma Immediate skin test reactivity to Aspergillus antigens Precipitating serum antibodies to A. fumigatus Serum total IgE concentration > 1000 ng/mL Peripheral blood eosinophilia >500/mm(3) Lung infiltrates on chest x-ray or chest HRCT Central bronchiectasis on chest CT Elevated specific serum IgE and IgG to A. fumigatus. Pulmonary function testing — Most patients have airflow obstruction with reduced FEV1 and increased residual volume. Individuals with bronchiectasis or fibrosis may exhibit a mixed obstructive and restrictive pattern. glucocorticoid therapy.

Diagnosis is suspected based on history and imaging tests and confirmed by Aspergillus skin testing and measurement of IgE levels, circulating precipitins, and A. fumigatus– specific antibodies. Treatment is with corticosteroids and, in patients with refractory disease, itraconazole .

Aspergilloma. An Aspergilloma usually arises in a preexisting cavity in the lungs. Any condition that causes cavitation e.g tuberculosis or cystic fibrosis. Aspergillomas are masses of fungal mycelia that grow in preexisting lung cavities. Haemoptysis is a common symptom. They do not require treatment with either antifungals or steroids

Pneumonia Causes of community acquired Pneumonia; Strept pneumonie Atypical organisms. - Mycoplasma - legionella - chlamydia - coxciella - Others; staph aureus, G –ve as H influenza, viral, anaerobic, fungal (esp in IC, nosocomial).

Mycoplasma Pneumonia C/P; Pneumonia; Walker pneumonia, dry cough, in epidemics. + exrapulmonary (4 M, rashes, anemias) . - Myocarditis, pericarditis, - meningitis, encephalitis, - Myalgia , arthralgia. - Myringitis. - Erythema nodosum, E multiforms. - AAHA, thrombocytopenia Diagnosis; cold aglutinin in 50%, confirmed by rising Ab titre. TTT=macrolides, Doxy.

Legionella pneumonia

-

Outbreaks related to contaminated water cooling system, showers & air conditioners. C/P; (5 L) Lung Level of conscious disturbed. Liver enzymes, elevated. Lytes; hyponatremia dt SIADH. Loose motions & ARF. Lymphopenia or pancytopenia.

 Diagnosis; urine legonella Ag.  TTT= macrolides+/- rifampicine, levofloxacin.

Coxciella Rickettssia like. Minimal exposure to dust or milk of farm animals (cattle). By ticks C/P; - acute; fever, pneumonia. - Chronic; cardiac (myo & endocarditis), hepatitis, osteomyelitis, uveitis, clubbing.

 Diagnosis; Complement fixation test.  TTT; doxyciclin (+ rifampicin or clindamycin in chronic cases)

7 C cattle, chronic, cardiac, clubbing, CFT, doxyciclin, clindamycin.

Chlamydia psitassi C/P -Birds exposure. - As coxciella but ↑LFTs, ↓Na (as legionella)  TTT; tetracyclin, Azithromycin

 Indication of hospitalizations (Signs of severe pneumonia

(CURB-65 )) - altered mental state (confusion ) - vital data; BP < 90/60 - RR > 30 B/MIN - Fever > 39.5 - AF - age > 65yr, comorbidities. - Lab; WBC > 30, <4. urea > 7. - PO2 < 60  Poor prognostic factors; - PO2< 8 KPa. - multilobular. - comorbidities

Suppurative pneumonia staph au, Klebs, pseudo Lung abcess, anaerob Actinomycis, invasive aspergillosis Lobar pneumonia; - Strept pn. - Klebs. - H infl. Pneumonia + effusion - Bact (20% mycopl) - Fungal. - Parasitic. NB; not pneumocystis carinii. Pneumocystis carinii pneumonia. The history of exercise induced dyspnoea in a HIV positive male with no signs on chest X-ray with little other data would suggest PCP until proved otherwise.

Patients who present with pneumonia after influenzae or measles are at risk of Staphylococcal pneumonia. Look for cavitation on CXR. The BTS guidelines: state that amoxicillin should be first line therapy for all pneumoniae, with addition of flucloxacillin if there is risk of it being staphylococcal. Gentamicin may be indicated in severe hospital acquired pneumonia, rifampicin in severe atypical infections (e.g. legionella).

TTT community acquired Pneumonia  Mild amox + erythro  Severe 3rd generation cephalo +/- clarithrom  If risk of staph( after influenza, measles) add fluclox.  Shift to oral after 48 hrs, continue for 7-10 d, 14 d for G-ve, 21 d for legionella.  Nosocomial = 3 rd cephalosporin.

-Moderatecefotrioxone -Severe ceftazidine or Imipinem + genta  COPD, bronchiectasis H influenza,T= cefotrioxone.  Cystic fibrosispseudomonus, TTT= ceftazidine  Aspiration clinda, metronidazole.

Lung Abcess; Org; Anaerobes, strept, staph aureus, Klebs. TTT; - Clindamycin for 6 wks + postural drainage + Xray FU. - if failed --. Percutaneus drainage.

Empyema; - In 15% of comm-acq pn.  slow to improve, persistant fever, ↑WBCs. - Pl fluid PH < 7.2. - TTT; drainage , IV Ab , intrapleural streptokinase. if failed  decortication.

Pulmonary embolism. All patients with possible PE should have clinical probability assessed and documented.

D-dimer Blood D-dimer assay should only be considered following assessment of clinical probability. D-dimer assay should not be performed in those with high clinical probability of PE. A negative D-dimer test reliably excludes PE in patients with low or intermediate clinical probability; such patients do not require imaging for VTE.

Imaging CTPA is now the recommended initial lung imaging modality for non-massive PE. In patients with coexisting clinical DVT, leg ultrasound as the initial imaging test is often sufficient to confirm VTE. [B] CTPA or echocardiography will reliably diagnose clinically massive PE. [B] Thrombolysis is the first line treatment for massive PE [B] and may be instituted on clinical grounds alone if cardiac arrest is imminent [B]; a 50 mg bolus of alteplase is recommended.

Treatment •Thrombolysis should not be used as first line treatment in non-massive PE. [B] •Heparin should be given to patients with intermediate or high clinical probability before imaging. [C] •Unfractionated heparin (UFH) should be considered (a) as a first dose bolus, (b) in massive PE, •Otherwise, low molecular weight heparin (LMWH) should be considered as preferable to UFH, having equal efficacy and safety and being easier to use. [A] •Oral anticoagulation should only be commenced once VTE has been reliably confirmed. [C] •The target INR should be 2.0–3.0; when this is achieved, heparin can be discontinued. [A]

, primary pulmonary hypertension presents mostly after age 30s, and more commonly affects women. There is dyspnea , cyanosis,chest pain & right heart failure . treatment includes prostaglandin analogues (iloprost, epoprostenerol), sildenafil, bosentan and calcium channel blockers.

ARDS

Causes. Uremia. Pancreatitis Infection(viral pneum, pneumocystis,G-ve sepsis) Embolism (air, fat, amniotic). Irritant (gas, O2, drugs; opiates, aspirin overdose, IV B2 agonist, aspiration, drowning). Type I RF

DD Lung cavitation Cancer Autoimmune (wegner) Vascular (PE) Infection (staph au, Klebs, pseudo, anaerob, TB, histoplasma, nocardia) TB

Causes of pulmonary eosinophilia Extrinsic; 1. Parasitic; Tropical pulmonary eosinophilia  immune response to the

bloodborne microfilarial stages of the lymphatic filariae, Wuchereria bancrofti, 2. Fungal; ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS . 3. MEDICATIONS AND TOXINS NSAIDs and antimicrobials (eg,

nitrofurantoin, minocycline, sulfonamides and ampicillin) are the most common classes of drugs associated with pulmonary eosinophilia,

Intrinsic; 1. CHRONIC EOSINOPHILIC PNEUMONIA symptoms including cough,

fever, progressive breathlessness, weight loss, wheezing, CEP occurs predominantly in women and nonsmokers; The chest radiographic finding of bilateral peripheral infiltrates described as the "photographic negative" of pulmonary edema is pathognomonic but found in fewer than 1/3 of cases. 2. CHURG-STRAUSS SYNDROME a vasculitic disorder often characterized by sinusitis, asthma, and prominent peripheral blood eosinophilia 3. Hypereosinophilic syndrome

Tuberculosis 1 ry asymtomatic, EN, mild cough, wheeze. Reactivation or reinfection  persistant cough, wt loss, hemoptysis, pneumonia, pl eff. Miliary HSM, fever, wt loss, choroidal tubercles.

Diagnosis of tuberculosis

Clinical presentation Radiography Two stage Tuberculin skin testing or Interferon-γ assays measure IFN-g released by T cells in response to stimulation by MBT antigens not present in BCG ZN staining & sputum cultures by 1) Lowestein Jensen media (LJ) 2) BACTEC technique; It is a technique used in culture from liquid media, by measuring radioactive 14 CO2 liberated in the medium, gives results within 10-14 days, compared to average 24.03 days by conventional (LJ). adenosine deaminase test in pleural effusions. typically greater than 50 U/L in tuberculous pleural effusions, with a sensitivity of 90 to 100% and a specificity of 89 to 100%. Bronchoscopy & Biopsies; pl, LN, liver, BM. PCR test; urine, pl, sputum, CSF.

a positive test requires: 15 mm----- In people with no known risks for TB. 10 mm----- in people with known risks for tuberculosis -diabetes or kidney failure, leukemia, lymphoma, -carcinoma of H & N or lung, silicosis, -history of gastrectomy or jejunal bypass, -in health care workers, - drug abusers, -recent immigrants from countries with high TB prevalence). 5 mm----------in people -who have HIV, -who are taking steroid therapy (>15 mg pred. for 1 month), -organ transplant recipients, false-negative test : -up to 20% of people infected with TB. - IC (cancer, recent chemotherapy, AIDS) . -booster phenomenon

A) Definitions of Pulmonary Tuberculosis 1- Smear-positive pulmonary TB 1. 2 sputum +ve for AFB; 2. 1 sputum +ve + radiographic abnormalities consistent with pulmonary TB. 3. 1 sputum +ve + culture +ve for M. TB. 2- Smear-negative pulmonary TB radiographic abnormalities + lack of clinical response despite one week of a broad-spectrum antibiotic

Treatment of tuberculosis First-line anti-tuberculous drug All for 2 m rifampicin (rifampin ), RMP, 600 mg (10-20 mg/kg) Then R & INH for 4 m isoniazid , INH, 300 mg (5-10 mg/kg) If P not used 9 m Ethambutol, EMB, 1 gm (25 mg/kg) Pyrazinamide,PZA. 1 gm (20-35 mg/kg) Second-line drugs (SLDs) (less effective e.g., p-aminosalicylic acid) or, toxic e.g., cycloserine; or unavailable in many developing countries (e.g.,fluoroquinolones): aminoglycosides: e.g., amikacin (AK), kanamycin; Streptomycin, STM, 1 gm IM daily for 1-2 m. polypeptides: e.g., capreomycin, fluoroquinolones: e.g., ciprofloxacin (CIP), moxifloxacin (MXF); p-aminosalicylic acid (PAS or P).

NB; streptomycin active # extracellular org., while PZA active # intracellular org. Rifabutin substitute for RIF for patients who have experienced intolerance to rifampin. Rifapentine Rifapentine may be used once weekly with INH in the continuation phase . Side effects; Idiosyncrasy NeuropathyINH (so add pyridoxine) Hepatitis R, INH, PZA. Optic neuritis  ethambutol Irreversible ototoxicity (esp vestibular) streptomycin. Gout  PZA. At the beginning of therapy, LN may enlarge dt hypersensitivity, TTT by steroids

The continuation phase of treatment is given for either 4 or 7 months. -The 4-month continuation phase should be used in majority of patients. -The 7-month continuation phase is recommended only for three groups: 1- cavitary pulmonary tuberculosis . 2- patients whose initial phase of treatment did not include PZA; 3- patients being treated with once weekly INH and rifapentine .

Drug-induced hepatitis defined as a serum AST level >3 times in the presence of symptoms, or >5 times in the absence of symptoms. INH, RIF, and PZA should be stopped immediately. 2 or more anti- TB without hepatotoxicity, such as EMB, SM, amikacin may be used . in patients with known liver disease avoiding PZA + monitored regularly.

Renal disease 1) If GFR between 30-60ml  no change use standard drugs in lower ranges of dose . 2) If GFR <30  1/2 EMB (or avoided). 3/4 PZA dose . 3) on dialysis, daily during the initial phase, at the end of each haemodialysis session & 3 times /wk in the continuation phase.

Pregnancy Rifampicin is enzyme inducer for hormonal contraception. Untreated TB in pregnancy is associated with an increased risk of miscarriage and major foetal abnormality, and treatment of pregnant women should continue. The initial treatment regimen should consist of INH, RIF, and EMB+Pyridoxine supplementation (25 mg/day). For 9 months. avoid Streptomycin  congenital deafness . avoid PZA. Breastfeeding should not be discouraged for women being treated with the first-line antituberculosis agents because the small concentrations of these drugs in breast milk do not produce toxicity in the nursing newborn.

Contact tracing Tuberculin test -ve

+ve

Repeat after 1 wk

Sputum & CXR

+ve

-ve

+ve

Repeat after 6 wks

TTT

+ve

-ve

-ve

chemoprophylaxis

BCG

Preventive chemotherapy daily isoniazid for 6 month (5 mg/kg) or INH+ R for 3 m Target groups for preventive treatment 1. 2. 3. 4.

Infants of mothers with PTB Children under 5 years of age HIV-infected individuals for contact with recent tuberculin +ve conversion with no XR or clinical evidence of TB.



NB; BCG protect against leprosy & ttt of some cancer.

MDR-TB When to suspect.  Exposure to a person with active TB from areas with high prevalence of drug resistance.  with active TB with treatment failure or relapse. Treatment of MDR-TB must be done on the basis of sensitivity testing: it is impossible to treat such patients without this information. If treating a patient with suspected MDR-TB, the patient should be started on  One of 1st agents drugs to which the pt is partially sensitive .  One injectable agent.  One quinolone. For one year after culture negative. Or MDR resistant2 yrs.

Pulmonary nodules Benign

Malignant

size

< 2.5-3 cm

> 2.5-3 cm

Margins

smooth

Irregular, speculated

calcifications

Central/ diffuse, laminated

Eccentric, sparse

growth

-

+

Satellite lesions

-

+

CT with C

Less likely to enhance more likely to enhance

PET

No uptake

+

Bronchogenic carcinoma Predisposing factors; A; asbestos, aluminium, arsenic C; cryptogenic fibrosis, scleroderma, smoking.

Types; Adenocarcinoma; most common now (30-40%) Squamous cell carcinoma; was most common, related to smoking. (20-30%) Small cell carcinoma; (20%). Large cell (10%). Bronchoalveolar carcinoma; (5%).

      

      

Adenocarcinoma; (P) Most common Slowly growing Peripheral. Not smoking dependent Following asbestos HPOA Isolated brain, bone metastasis. Squamous cell carcinoma; (c, H) was most common, related to smoking. Horner, hyperCa, hyperthyroidism central, cavitating, clubbing. Late metastasis. Pancoast tumor Horner, shoulder pain, waisting of small ms of the hand.

Small cell carcinoma; (20%).  Central  Rapidly growing  Many paramalignant; SIADH, ACTH, Eaton lambert  SVC obstruction by LN.  Others; polymyositis, PN,cerebellar S, acanthosis nigricans, erythema gyratum repens. Large cell (10%) gynecomastia. Bronchoalveolar carcinoma;  Scleroderma, lung fibrosis.  Spread through bronchial tree  Present as chronic pneumonia (with air bronchogram)  Solitary nodule or diffuse nodular lesions.  ↑ mucous secretion , Bronchorrhea.  Suptype of adeno.

Intrathoracic complications  Pressure  Effusion  Destruction; collapse, pneumothorax.  Diagnosis;  Staging;  I  - hilar LN.  II  + hilar LN.  IIIA  ipsilateral med/subcarinal> 2cm from carina LN, pleura, pericardium, chest wall but not maignant cells in pleural effusion.  IIIB  contralateral or supraclavicular LN or malignant pl effusion (local invasion; HT, oesoph, vessels, carina or<2 cm.  IV  distant dis. NB; Horner does not mean extension beyond the lung.

Sputum cytology. A diagnosis may be made on sputum cytology which should be the initial investigation with a positive yield of approximately 70-80% four samples.

TTT Small cell limited (I-IIIA)  chemo + radio extensive  chemo only Non small I-IIIA surgery or chemo then surgery IIIB  extensive  chemo, radio Surgery is # if preop. FEV1<2L or expected post-op FEV1 <0.8L. If SVC obstruction radio, or high dose dexamethazone, or chemo if small cell. best ttt now is stent. Prognosis; Overall 5 yr survival is 15 %. Small cell, poor prognosis; few months

Mesothelioma ♂, 50-70 yrs. 85% asbestos ,latent period>30yrs. Diagnosis; pl biopsy by VATS. DD; adeno, pl thickening. TTT; unsatisfactory; drainage, pleurodesis, radio Median survival; 1 yr for pleural & 6 month for peritoneal.

Br adenoma = br carcinoid Young, male = female, non smoker. Central, broad base , highly vascular . Produce ACTH, GHRH, rarely 5HT. Complication; hemoptysis, collapse. Octreotide scan. urinary HIAA. ttt; resection, resist radio & chemo.

Pulmonary causes of clubbing ILD; IPF, asbestos Suppurative lung dis; lung abcess, asbestos, empyema, bronchiectasis, cystic fibrosis. Malignant lung dis; Br carc, mesothelioma

not TB not COPD 1. 2. 1. 2. 3.

Fleeting shadows; ABPA. Chronic esinophilic pneumonia. Calcifications LN; TB, Silicosis, Sarcoidosis. Pleural; Asbestos plaques, old hemothorax. Parenchymal; - infections; TB, fungal, old varicella - ↑ Ca; ↑ PTH, CRF, ↑ Vit D. - benign tumors.

Bronchiolitis obliterans with organizing pneumonia (BOOP) Seen when Bronchiolitis (inflammation & fibrosis) spread to adjacent parenchymal tissue. Causes; RA, viral infections, toxic inhalations, BMT, lung transplantation. CXR parenchymal infiltrates PFTs; restrictive pattern. Or mixed.

Ventilatory support NIPPV (non-invasive +ve pressure ventilation); - use securely fitting nasal or full face mask & a portable bilevel pressure support ventilators in general wards. - require conscious, alert cooperative pt. NIV should be considered in all patients with an acute exacerbation of COPD in whom a respiratory acidosis (pH <7.35, PaCO2 >6 kPa) persists despite immediate maximum standard medical treatment on controlled oxygen therapy for no more than one hour. CPAP (continuous +ve airways pressure): - use tightly fitting face mask  pneumatic splint to the airway, used in obstructive sleep apnea, may cause hypotension. conventional ventilators.

NIV is particularly indicated in: COPD with a respiratory acidosis pH 7.25–7.35 (H+45–56 nmol/l) Hypercapnic respiratory failure secondary to chest wall deformity (scoliosis, thoracoplasty) or neuro-muscular diseases NIV is not indicated in: • Impaired consciousness • Severe hypoxaemia • Patients with copious respiratory secretions • The benefits of an acute NIV service are likely to be: • Fewer patients referred to intensive care for intubation • Shorter stays on intensive care • Fewer deaths of patients with acute respiratory failure

A 65 year old man has had 5 kg weight loss. He is an ex smoker and used to work in a coal mine. Chest X ray shows a large right sided pleural effusion and several pleural plaques in both lung peripheries. Pleural aspiration reveals an exudate. What is the next best investigation? A.Bronchoscopy B. Lung function tests C. Spiral CT of the chest D. Thoracoscopy and biopsy E. Sputum for AFB

a malignant effusion., the best option would be thoracoscopy and biopsy to drain the fluid as well as confirm a diagnosis simultaneously. A video assisted thoracoscopy would help to do this.

A. B. C. D. E.

A 50 year old Afro-Caribbean man has a cough. He also has generalised arthralgia. There is an eruption of tender red areas on his shin. Which of the following is important to determine whether this condition is self limiting? Hilar lymphadenopathy and eosinophilia Response to Kveim test Hilar lymphadenopathy and erythema nodosum Serum calcium levels Serum ACE levels

A 35 year old man has significant wheezing and breathlessness. Recordings of peak flows shows diurnal variation. He was prescribed with salbutamol but continues to have frequent wheezy episodes. What is the next step in management? A.Phosphodiesterase inhibitors . B. Leukotriene antagonists . C. Oral antibiotics . D. Inhaled corticosteroids. E. Oral steroids.

An 18 year old girl with severe difficulty in breathing to A+E. She has had a history of asthma with two previous ITU admissions. Her peak flow is currently 100. She is unable to say more than a few words. She was given nebulised salbutamol and iv hydrocortisone 200mg by the paramedics.Which treatment should she now have? A. Further iv hydrocortisone 200 mg B. Iv magnesium 2g C. Intubation and ventilation D. Iv salbutamol E. Iv ipatropium

A 35 year old lady with systemic sclerosis has breathlesness on exertion. She has bilateral basal crepitations in the chests and corresponding interstitial shadowing on the CXR. Which is likely to be found on her lung function tests? A. P02 of 11 desaturating to 10 on exertion B. FEV1 to FVC ratio of 65% . C. Diffusion capacity (DLCO) of 17 (predicted 23) D. Increased residual volume E. FEV1 of 5 L

A. B. C. D. E.

A 45 year old woman has progressive shortness of breath. On examination she has O2 sats of 93% on air and finger clubbing was noticed. In assessing the potential diagnosis, which one of the following is a typical feature of cryptogenic fibrosing alveolitis? Dry cough B. Haemoptysis C. Haematuria D. Wheeze E. Abdominal pain

An 13 year old male has recent onset breathlessness. He wheezes particularly during the summer when the pollen count is high. Which of these tests would help to confirm the diagnosis? A. Trial of inhaled corticosteroids B. Trial of anticholinergics C. Serial peak flow measurements D. Lung function tests E. Chest X ray

3. A 25-year-old man presents with right-sided

facial weakness and parotid swelling. There is a right LMN facial nerve palsy but no other abnormalities on examination. Lumbar puncture findings are: Opening pressure18 cm, CSF Protein 0.9 g/l Glucose3.5 mmol/l, Microscopy 85 lymphocytes. What is the most likely diagnosis? A. Lyme disease B. Multiple sclerosis (MS) C. Guillain Barre syndrome (GBS) D. Neurosarcoidosis E. Ramsey Hunt syndrome

4.

A. B. C. D. E.

A 35-year-old woman complains of repeated painful rash on her legs. She also gives a 11 month history of dyspnoea on exertion. Her doctor arranged for her to have a chest X-ray and this shows bilateral hilar prominence & basal reticulonodular shadowing Examination of her legs reveals a purplish-red, maculopapular tender rash on her shins. Apart from few bi-basal crepitations on auscultation, systemic examination is normal. A pulmonary function test shows a moderately impaired DLCO. Which one of the following is the best investigation? Bronchoscopy High-resolution CT scan of the thorax Open lung biopsy Kveim test Serum ACE level

5. A 46-year-old woman is admitted to hospital with

a left basal, community-acquired pneumonia. She is on the appropriate antibiotics. She is still pyrexial four days after admission and a chest X-ray confirms a left pleural effusion. The house officer has performed a diagnostic tap. Which of the following is an indication to insert a chest drain? A. Pleural fluid protein level more than 50% of serum protein level B. Pleural fluid LDH more than 60% of serum LDH C. Haemorrhagic pleural fluid D. Pleural fluid pH < 7.2. E. Pleural fluid glucose < 1.6 mmol/l

A 60 year old miner has been in the occupation for 20 years. He presents with a cough and breathlessness. Chest XR shows diffuse interstitial shadowing. A sputum sample is positive for acid fast bacilli. Which of the following dusts is most likely to have predisposed the patient to tuberculosis? A. Beryllium B. Cadmium C. Coal D. Silica E. House dust

19) A 73-year-old male smoker presents with haemoptysis of 3 weeks duration. Examination reveals left supraclavicular lymphadenopthy. A chest radiograph reveals a left sided hilar mass. Which is the appropriate inital diagnostic test for this patient? 1 )Bronchoscopy 2 )CT guided biopsy 3 )Lymph node biopsy 4 )PET scanning 5 )Sputum cytology

15.A 43-year-old man with a past history of

hypothyroidism complains he has had pain and stiffness in the joints of his hand and feet for three months. He also gives a history of dyspnoea of that started six weeks ago. Examination shows swollen hand joints and signs of a right pleural effusion. A diagnosis of rheumatoid arthritis is made. Which one of the following is characteristic of a rheumatoid pleural effusion? A. It is a transudate B. It has a low glucose level C. Long-standing rheumatoid effusions have low cholesterol levels D. It has a high pH E. It should be treated by decortication

17.A 25-year-old male presents to A+E with shortness of

breath. One week ago, he developed influenza & become more short of breath & fatigued in last 24 hours. His temperature was 38.5oC, his SaO2 = 90% on 2L of oxygen, a Bl pressure 100/60 mmHg & heart rate 120/min. The CXR shows patchy consolidation. Which antibiotic therapy should you select for this man? 1 )Amoxicillin 2 )Amoxicillin Flucloxacillin 3 )Amoxicillin Gentamicin 4 )Amoxicillin Rifampicin 5 )Flucloxacillin

33- A teenage girl presents with Guillain-Barre syndrome. Her weakness continues to worsen after admission to hospital. Which of the following should be used to monitor her? 1) arterial blood gases 2) chest expansion size 3) FEV1/FVC ratio 4) PEFR 5) vital capacity

24) Which of the following statements is true of the PFTs VC; a) canno’t be measured by spirometer alone. b) ↑ in emphesema & ↓ in IPF. c) Is the max amount of air which can be exhaled after max. inspiration. d) Is the sum of tidal volume & inspiratory capacity. e) When reduced, is a specific indication of restrictive lung dis.

In asbestos related disorders which of the following statements is correct? 1 )basal fibrotic shadowing on CXR suggests coincidental idiopathic fibrosing alveolitis 2 )increased incidence of primary lung cancer 3 )pleural effusion develops more than 20 years after causative asbestos exposure 4 )pleural plaques are recognized precursors of mesothelioma 5 )the risk of malignant mesothelioma is greatly increased in smokers compared to nonsmokers

39) A 63-year-old woman presents a 5 day history of progressive shortness of breath. Her family brought her in because she was increasingly sleepy during the last 24 hours. She was diagnosed as Chronic Obstructive Pulmonary Disease 3 years ago with a FEV1 less than 50% of predicted. She has an oxygen concentrator at home. Examination revealed depressed consciousness & a respiratory rate of 24 br/min shallow breaths. There were decreased breath sounds with minimal air movement. If an arterial Bl gas on room air were to be performed, which of the following results would you expect? 1 )pH 7.16 paCO2 70 paO2 50 HCO3 24 2 )pH 7.24 paCO2 80 paO2 55 HCO3 30 3 )pH 7.32 paCO2 60 paO2 70 HCO3 30 4 )pH 7.41 paCO2 40 paO2 50 HCO3 24 5 )pH 7.48 paCO2 30 paO2 85 HCO3 24

25) A 20-year-old male student is assessed for shortness of breath that occurs whilst running. He has no other symptoms & does not smoke. Examination, full count, chest X-ray are normal. Which of following likely will be helpful in confirming the suspected diagnosis? 1 )Arterial Bl gas studies before & after exercise 2 )Determination of lung volumes & diffusing capacity 3 )Measurement of venous lactate before & after exercise 4 )Spirometry before & after administration of bronchodilators 5 )Spirometry before & after exercise

A 60-year-old farmer presented to the emergency department with a two week history of progressively worsening cough, breathlessness and myalgia. His symptoms had become particularly worse after he recently finished baling hay indoors, ready for the winter.He had no other previous medical history of note and was a lifelong nonsmoker. He recently purchased a budgerigar from an internet site. O/E his temperature was 38.4°C, bl.pr 160/100 mmHg, pulse 130 beats per minute and oxygen saturations of 86% on air. His heart sounds were normal and there were no audible murmurs. Auscultation of the chest revealed bronchial breath sounds at the right base. Abdominal examination revealed a soft and non-tender abdomen with no palpable masses or abnormal enlargement of organs.Laboratory investigations revealed:Hb14.5 g/dL(13.0-18.0)WBCs20.0 x109/L(4-11 x109)Neutrophils18.0 x109/L(1.5-7 x109)Lymphocytes1.0 x109/L(1.5-4.0 x109)Monocytes0.8 x 109/L(00.8 x109)Eosinophils0.2 x109/L(0.04-0.4 x109)Basophils0.01 x109/L(0-0.1 x109)Platelets390 x109/L(150-400 x109) ESR (Westergren)90 mm/1st hour(0-15 mm/1st hour)S.Na140 mmol/L(137-144)S. K4.2 mmol/L(3.5-4.9)S. urea13.7 mmol/L(2.5-7.5)S. cr.120 mol/L(60-110)Serum avian precipitins Positive Micropolyspora faeni precipitins Negative A chest radiograph revealed patchy consolidation in the right lower zone. What is the most likely diagnosis? 1. Avian influenza 2. Chlamydia psittaci pneumonia 3. Coxiella burnetii pneumonia 4. Extrinsic allergic alveolitis 5. Farmer's lung

True 2. This patient has acute pneumonia with a high white cell count, high inflammatory markers and chest radiograph changes suggestive of an infective process. The most likely pathogen in this case is Chlamydia psittaci, a pathogen acquired most commonly from birds. Extrinsic allergic alveolitis would be less likely to cause such acute symptoms, and chest radiograph changes are usually bilateral. Positive serum avian precipitins are not diagnostic of extrinsic allergic alveolitis (EAA), and only suggest the patient has had exposure to birds. Farmer's lung, a form of hypersensitivity pneumonitis, is now very rare since the majority of farmers no longer bale hay in wet conditions. When present, it is most commonly associated with positive Micropolyspora faeni antibodies.

A 35 year old woman is short of breath on exertion. Her oxygen saturation at rest is 99% but on exertion is 90%. Her CXR shows prominent pulmonary arteries. Echocardiography shows enlarged right heart and a right heart cathether measures the pulmonary arterial pressure to be 35mmHg. D-dimers are negative and inflammatory markers are not raised. What is the likely diagnosis? A. Pulmonary embolus B. Hereditary hemorrhagic telangiectasia C. Pulmonary hypertension secondary to anorectics D. Primary pulmonary hypertension E. Pneumocystis pneumonia

29) Which of the following statements is true of the diffusion capacity of carbon monoxide? 1 )Is a specific measure of lung perfusion. 2 )Depends on thickness of alveolar wall. 4 )Is increased in cigarette smokers. 5 )Is increased in emphysema.

1) The Mantoux reaction an example of which type of hypersensitivity reaction ? 1 )Type I hypersensitivity 2 )Type II hypersensitivity 3 )Type III hypersensitivity 4 )Type IV hypersensitivity 5 )Humoral Immune Response

Comments: 4 )Type IV hypersensitivity The tuberculin skin test is an example of a Type IV hypersensitivity, a delayed type hypersensitivity (DTH) reaction. This reaction develops when primed Th1 cells encounter their specific antigen. An inflammatory response evolves over 24-72 hours. In tuberculin skin test, injected antigen is protein derived from M.Tuberculosis. Th1 cells recognize peptide bound to MHC on APCs, are activated & secrete pro-inflammatory cytokines including IL2, IFN-gamma, TNF, chemokines as GM-CSF. There is recruitment of inflammatory cells predominantly macrophages at the site of antigen deposition, activation of phagocytes. Some cytokines (TNF) as well as macrophage derived lytic enzymes cause local tissue destruction. CD8+ T-cells have also been implicated in DTH responses. The result is an indurated erythematous lesion at the site of injection which indicates previous exposure to TB.

32) A 35-year-old man presents after 3 months of chronic cough with purulent sputum & shortness of breath on exertion. He gives a history of at least two sinus & bronchial infections per year requiring treatment with antibiotics. He also says he & his wife have been unable to have children. He smokes 15 cigarettes per day. Examination was normal except for some wheezing & an area of focal crackles at the left lung base. Chest X-ray shows patchy infiltrates at both bases. Investigations revealed FEV1 2.0 L, FVC 2.7 L, pH7.38, PaCO2 40 mmHg, PaO2 82 mmHg. What is the likely diagnosis? 1 )alpha-1-Antitrypsin (Antiprotease) deficiency 2 )Asthma 3 )Cystic fibrosis 4 )Hypogammaglobulinemia 5 )Immotile cilia syndrome

3.A 24-year-old man presents to the emergency room complaining of shortness of breath and right-sided chest pain. The symptoms began abruptly about 2 hours previously. The pain is worse with inspiration. He denies fevers or chills and has not had any leg swelling. He has no past medical history but smokes 1 pack of cigarettes daily. On physical examination, he is tachypneic with a respiratory rate of 24 breaths/min. His oxygen saturation is 94% on room air. Breath sounds are decreased in the right lung, and there is hyperresonance to percussion. A chest radiograph confirms a 3.5 cm pneumothorax of the right lung. What is the best approach for treatment of this patient? A. Needle aspiration of the pneumothorax. B. Observation and administration of 100% oxygen. C. Placement of a large-bore chest tube. D. Referral for thoracoscopy with stapling of blebs .

2.A 63-year-old male with a long history of cigarette smoking comes to see you for a 4-month history of progressive shortness of breath and dyspnea on exertion. The symptoms have been indolent, with no recent worsening. He denies fever, chest pain, or hemoptysis. He has a daily cough of 3 to 6 tablespoons of yellow phlegm. The patient says he has not seen a physician for over 10 years. Physical examination is notable for normal vital signs, a prolonged expiratory phase, scattered rhonchi, elevated jugular venous pulsation, and moderate pedal edema. Hematocrit is 49%. Which of the following is likely to prolong his survival?

A. Atenolol B. Enalapril C. Oxygen D. Prednisone E. Theophylline

1. A 52-year-old female presents with a community acquired pneumonia complicated by pleural effusion. Athoracentesis is performed, with the following results: Appearance Viscous, cloudy. pH 7.11. Protein 5.8 g/dL. LDH 285 IU/L. Glucose 66 mg/dL. WBC 3800/mm3, PMNs 93%. Gram stain Many PMNs; no organism seen Bacterial cultures are sent, but the results are not currently available. Which characteristic of the pleural fluidis most suggestive that the patient will require tube thoracostomy? A. Presence of more than 90% polymorphonucleocytes (PMNs). B. Glucose less than 100 mg/dL C. Presence of more than 1000 white blood cells D. pH less than 7.20. E. Lactate dehydrogenase (LDH) more than two-thirds of the normal upper limit for serum.

40) A 24-year-old asthmatic patient was admitted with acute severe asthma. Which of the following statements regarding the diagnosis is correct? 1 )Agitation should be managed with a benzodiazepine. 2 )A high inspired Oxygen concentration should be used routinely. 3 )Inhaled salmeterol is indicated as first line therapy. 4 )Normal arterial pCO2 is reassuring . 5 )Pulsus paradoxus is a reliable sign of severity.

10.A 38-year-old homosexual male who is known to be

infected with HIV virus presents with a week of fever & tachypnoea. Chest x-ray reveals bilateral alveolar infiltrates. Arterial Bl gas determination reveals a pO2 of 55mmHg, pCO2 of 33 mmHg on room air. Bronchoalveolar lavage reveals positively stained organisms with methenamine silver staining. Which of following statements is correct concerning his management? 1 )Tranbronchial biopsy should be carried out to confirm the diagnosis. 2 )Corticosteroids are contraindicated given the risk of other opportunistic infections. 3 )Aerosolised Pentamidine therapy would be appropriate if the patient had a known allergy to sulphonamides. 4 )Trimethoprim-sulfamethoxazole alone should be administered.

Comments:4 )Trimethoprim-sulfamethoxazole alone should be administered. Pneumocystis carinii pneumonia is an opportunistic infection which occurs in immunosuppressed populations, particularly AIDS. The classic presentation is non-productive cough, dyspnoea, fever, bilateral interstitial infiltrates & hypoxemia. Diagnostic methods of choice include sputum induction & bronchoalveolar lavage. The drug of choice for treatment & prophylaxis is trimethoprimsulfamethoxazole, but alternatives are often needed because of adverse effects or, less commonly, treatment failure. Adjunctive corticosteroid therapy may improve survival in moderate severe cases.

1. 2. 3. 4. 5.

A 62 yrs old smoker with 2 days history of cough & fever was admitted with a diagnosis pneumonia & of Lt sided pleural effusion up to the six intercostal space. Pleural fluid is aspirated & send for tests. Which of the following is an indication for insertion of a chest drain? Bl stained pleural fluid. pleural fluid pH< 7.2. Serous pleural fluid . pleural fluid LDH> 200IU/l. pleural fluid glucose > 2 mmol/l.

42) Regarding pneumonia caused by Legionella pneumophilia, which of the following is true? 1)is associated with hyponatremia 2 )is best treated with intravenous amoxicillin & clavulanic acid 4 )is readily diagnosed by standard aerobic culture of sputum 5 )should be managed on the ward in a respiratory isolation cubicle

36) A 16-year-old girl presents with a 2 day history of deteriorating breathlessness & dyspnoea. Blood gas analysis shows a pH of 7.25, a PCO2 of 7.0kPa, a PO2 of 8.5kPa, a base excess of ±4. Which of the following interpretations is correct? 1 )Results are consistent with IPF. 2 )Blood gases suggest type1 respiratory failure 3 )Immediate intubation is required. 4 )Results are consistent with late severe asthma. 5 )Bicarbonate may be necessary to correct the acidosis.

16.A 45-year-old solicitor had an onset of severe, crushing,

substernal chest pain while attending a football match. He collapsed on his way to the car. Bystander Cardiorespiratory Resuscitation was begun immediately and continued until arrival in Casualty where an endotracheal tube was inserted , ventilation was maintained on 100% oxygen. Investigations revealed:pH 7.13 PaO2 560 mmHg PaCO2 18 mmHg Bicarbonate 5.8 SaO298%. Based on these laboratory values, which of the following statements best fit his current pathophysiology? 1 )He is demonstrating a primary respiratory alkalosis 2 )He probably developed a large right to left intracardiac shunt 3 )His anion gap is probably normal 4 )His pulmonary artery pressure is probably elevated

21) A 63 year-old diabetic presents with a pyrexia, productive cough shortness of breath of 5 days. She has RLL consolidation & a small unilateral pleural effusion on CXR. Which is a marker of poor prognosis? 1 )Temp >38°C 2 )WCC > 15 3 )Her age 4 )Her CXR signs 5 )Her diabetes

14.A 26-year-old man with a history of alcohol &

drug abuse was admitted with a 14 day history of fever, cough & fatigue. He was emaciated. His temperature was 39.4°C. Cervical & axillary lymphadenopathy were present. Chest X-ray showed bilateral areas of pulmonary shadowing. Which of the following is the likely diagnosis? 1 )alcoholic cardiomyopathy 2 )pneumococcal pneumonia 3 )pneumocystis pneumonia 4 )pulmonary tuberculosis 5 )tricuspid endocarditis

8. A 35-year-old man, seen 6 months after a cadaveric

renal allograft. He receives azathioprine & prednisolone. He is feeling generally unwell past week , a pyrexia of 38.6oC, anorexia & a cough productive of thick green sputum. Chest x-ray reveals a left lower lobe nodule of approximately 5cm diameter & central cavitation. Analysis of sputum reveals long, crooked, branching & beaded gram-positive filaments. Which of the following antimicrobials is appropriate initial therapy for this patient? 1 )Ceftazidime 2 )Co-amoxiclav 3 )Co-trimoxazole 4 )Erythromycin 5 )Rifampicin & Isoniazid

Comments:3 )Co-trimoxazole [100] The likely diagnosis Norcardiasis. Nocardia are aerobic, Gram-positive branching filamentous bacteria which often appear beaded on staining. Nocardiosis can be diagnosed rapidly by examination of sputum, pus with Gram stain & a modified acid-fast stain. Pneumonia is typically found in the immunocompromised as in this case, may be a single lesion or extensive pneumonic consolidation. The drug of choice is trimethoprim-sulfamethoxazole.

13.A 54-year woman was admitted with acute

breathlessness. On examination she had a temperature of 37oC, a respiratory rate of 32 breaths per minute, a pulse of 120 beats per minute, a Bl pressure of 100/60 mmHg, a peak expiratory flow rate of 250 litres per minute. Auscultation of heart & chest was normal. The Chest X-ray was normal, AB gases on air showed: pH 7.35 (7.36 - 7.44), Pa02 6.0 kPa (11.3 - 12.6), PaC02 3.9 kPa (4.7 - 6.0), Serum bicarbonate 24 mmol/l (20 - 28). She was started on high flow oxygen. What is the important next treatment? 1 )amoxicillin intravenously 2 )aminophylline intravenously 3 )intravenous fluids 4 )low molecular weight heparin 5 )nebulised salbutamol

15-A 54-year woman was admitted with acute breathlessness. On examination she had a temperature of 37oC, a respiratory rate of 32 breaths per minute, a pulse of 120 beats per minute, a Bl pressure of 100/60 mmHg, a peak expiratory flow rate is normal . Auscultation of heart & chest was normal. The Chest X-ray was normal, AB gases on air showed: pH 7.35 (7.36 - 7.44), Pa02 6.0 kPa (11.3 - 12.6), PaC02 3.9 kPa (4.7 - 6.0), Serum bicarbonate 20 mmol/l (20 - 28). She was started on high flow oxygen. What is the important next treatment? 1 )amoxicillin intravenously 2 )aminophylline intravenously 3 )intravenous fluids 4 )low molecular weight heparin 5 )nebulised salbutamol

9. A 42 year-old restauranter who is HIV positive

from 8 years presents with progressive shortness of breath on exercise. The chest Xray was normal except for prominent pulmonary arteries. Pulse oximetry demonstrates that he desaturates on exercise. Which is the likely diagnosis? 1 )Pneumocystis carinii pneumonia 2 )Primary pulmonary hypertension 3 )Intracardiac shunt across an atrial septal defect 4 )Pulmonary embolic disease 5 )Anaemia

44) Which of the following statement is true of infections with Mycobacterium tuberculosis: 1 )non-sputum producing patients are noninfectious 2 )a positive tuberculin test indicates active disease 3 )lymph node positive disease requires longer treatment than pulmonary disease 4 )in pregnant women treatment should be given until after delivery 5 )pyrazinamide has high activity against active extracellular organisms

Comments: 1 )non-sputum producing patients are noninfectious Only untreated smear positive pulmonary TB is likely to be infectious. Active disease may be indicated by grade III/IV response tuberculin. 80% of individuals have history of BCG vaccination have grade I/II response. All forms of pulmonary TB may be treated equally except tuberculous pleural effusion which may require drainage (with large effusions causing breathlessness) with adjunct corticosteroids to delay reaccumulation. Length of treatment in other forms are bone TB 9 months, meningitis 1 year, drug resistance 2 years. Streptomycin has high activity against extracellular organisms whilst pyrazinamide has high activity against intracellular organisms.

A 65 year old woman with breathlessness has fibrotic changes on her CXR. She has arterial blood gases and lung function tests. Which one of the following features suggests progressive pulmonary sarcoid? A. high pCO2 . B. A fall in lung compliance C. A reduced maximum lung elastic recoil pressure D. An restrictive flow volume loop E. A normal helium dilution total lung capacity

Acid Base Balance

Arterial Blood Gases pH 7.35 -7.45 pCO2 4.6 – 6.1 Kpa pO2 9 -10.5 Kpa HCO3 22-28 mmol/l.

Cl AG

96-105 mmol/l. 12 ± 4 meq/L .

osmolar gap 10-15 mmol/L

Stepwise approach to interpreting the arterial blood gas. 1. History & Presentation: The H&P usually gives an idea of what acid base disorder might be present even before collecting the ABG sample. 2. Look at the pH: - If pH < 7.35, then acidemia - if pH > 7.45, then alkalemia - If pH within normal range: • then acid base disorder not likely present • pH may be normal in the presence of a mixed acid base disorder, particularly if other parameters of the ABG are abnormal.

3. Look at PCO2, HCO3: - If PCO2 is the initial chemical change, then process is respiratory. - if HCO3- is the initial chemical change, then process is metabolic.

Respiratory Acidosis

↑ PCO2

↑HCO3

Respiratory Alkalosis

↓ PCO2

↓ HCO3

Metabolic Acidosis

↓ HCO3

↓ PCO2

Metabolic Alkalosis

↑ HCO3

↑ PCO2

Acute Respiratory Acidosis : The [HCO3] will increase by 1 mmol/l for every 10 mmHg elevation in pCO2 above 40 mmHg.

Chronic Respiratory Acidosis : The [HCO3] will increase by 4 mmol/l for every 10 mmHg elevation in pCO2 above 40mmHg.

Acid-Base Physiology Bedside Rules for Assessment of Compensation

Metabolic Acidosis: Calculate expected pCO2 respiratory Acidosis : Calculate expected HCO3.

Metabolic Acidosis A metabolic acidosis is an abnormal primary process or condition leading to an increase in fixed acids in the blood. A decrease in plasma bicarbonate can be caused by two mechanisms: A gain of strong acid A loss of base

Anion Gap and Delta Ratio The anion gap is defined as the quantity of anions not balanced by cations. This is usually equal to 12 ± 4 meq/L and is usually due to the negatively charged plasma proteins as the charges of the other unmeasured cations and anions tend to balance out. Na + Unmeasured cations = Cl- + HCO3- + Unmeasured anions Anion gap = [Na] – ([Cl-] + [HCO3-])

Classification by Anion Gap A: High Anion-Gap Acidosis Ketoacidosis

.Lactic Acidosis

Diabetic ketoacidosis

Renal Failure

Toxins Ethylene glycol Methanol Salicylates

B:Normal Anion-Gap Acidosis (or Hyperchloraemic acidosis) Renal Causes Renal tubular acidosis Carbonic anhydrase inhibitors

GIT Causes Severe diarrhoea Uretero-enterostomy Drainage of pancreatic or biliary secretions Small bowel fistula

When high AG Delta AG Delta HCO3 > 1 ...... Concomitant metabolic alkalosis . Delta AG Delta HCO3 < 1 ...... Concomitant NG metabolic acidosis.

Osmolar Gap The Osmolar Gap is another important diagnostic tool that can be used in differentiating the causes of elevated anion gap metabolic acidosis. The major osmotic particles in plasma are Na+ , Cl- , HCO3-, urea and glucose and as such, plasma osmolarity can be estimated as follows: Plasma osmolarity = 2(Na) + glucose + BUN. Note that because Cl- and HCO3- are always bound to Na, their contributions to osmolarity are estimated by doubling the Na concentration. Plasma osmolality (Posm) can also be measured directly by freezing point depression.

The osmolar gap is the difference between the calculated serum osmolarity and the measured serum osmolarity Osmolar Gap = Measured Posm – Calculated Posm The normal osmolar gap is 10-15 mmol/L H20 .The osmolar gap is increased in the presence of low molecular weight substances that are not included in the formula for calculating plasma osmolarity. Common substances that increase the osmolar gap are ethanol, ethylene glycol, methanol, acetone, isopropyl ethanol.

In a patient suspected of poisoning, a high osmolar gap (particularly if ≥ 25) with an otherwise unexplained high anion gap metabolic acidosis is suggestive of either methanol or ethylene glycol intoxication.

Poisonings & Intoxications

 Although many drugs and toxins can be removed with extracorporeal techniques, few are indicated for this therapy e.g - Alcohol (methanol,ethylene

glycol, alcohol) - Lithium,salicylate,theophylline,metformin

Poisonings & Intoxications Methanol - solvents , varnish ,de-icing solutions -N/V,abdominal pain (pancreatitis), blurred vision (papilledema), CNS symptoms ,seizures ,coma, metabolic acidosis (increase anion gap).

Poisonings & Intoxications Methanol  Treatment:

- empty stomach contents - Ethanol/fomepizole (inhibit ETOH DeH) -Folic acid - Hemodialysis: severe metabolic acidosis, very high osmolar gap, methanol level>50 mg/dl & visual changes (disc hyperemia).

Poisonings & Intoxications Ethylene Glycol - Antifreeze ,solvents - not protein bound - EG→glycolic acid→glyoxylic acid→oxalic acid. - early : as methanol. - later : flank pain ,renal failure ,ca oxalate crystals.

Poisonings & Intoxications Ethylene Glycol Treatment:

- Empty stomach contents - Ethanol/fomepizole (inhibit ETOH DeH) - Thiamine 100 mg IM qid, B6 50 mg IM qid ; (glyoxalate → glycine) - Hemodialysis, CVVHD/F (severe metabolic acidosis , very high osmolar gap, level>20 mg/dl)

Poisonings & Intoxications Lithium - Acute /acute on chronic/ chronic - Not protein bound - C/P: lethargy ,tremor ,confusion ,seizure

Treatment: - Empty stomach - Replete volume/forced diuresis - Hemodialysis/ CVVHDF, Indications: - level > 4 mEq/L - Level > 2.5, severe CNS symptoms

Poisonings & Intoxications Salicylate - Acute or chronic intoxication - C/P: headache,tinnitus,confusion,n/v, hyperventilation, metabolic acidosis,cardiovascular collapse

Treatment; - Gastric emptying,activated charcoal. - IV fluids, alkaline diuresis. - Hemodialysis: level > 80 mg/dl with symptoms seizure, coma severe metabolic acidosis + renal failure

Metabolic Alkalosis A metabolic alkalosis is a primary acid-base disorder which causes the plasma bicarbonate to rise to a level higher than expected.

Causes of a metabolic alkalosis can be classified into several groups Gain of alkali in the ECF from an exogenous source (eg IV NaHCO3 infusion, citrate in transfused blood) Loss of H+ from ECF via kidneys (eg use of diuretics) via gut (eg vomiting, NG suction)

Respiratory Acidosis Respiratory failure type 2. COPD, CO2 retension.

Respiratory Alkalosis Hyperventilation. Tachypnea. ( fever ,pneumonia , PVC)

Biochemistry results: Na+ 127, K+ 5.2, Cl- 79, HCO3- 20, urea 50.5 & glucose 9.5 mmols/l. Anion gap 33 mmols/l Arterial Blood Gases pH 7.58 pCO2 21 mmHg pO2 154 mmHg HCO3 19 mmol/l

the acid-base diagnosis: 1. pH: pH>7.44 so an alkalaemia is present. The cause is an alkalosis 2. Pattern: pCO2 & bicarbonate are both low suggesting either a metabolic acidosis (with respiratory compensation) or a respiratory alkalosis (with renal compensation). As we know an alkalosis must be present then we would accept a respiratory alkalosis.

3. Clues: The anion gap is noted to be very high so there must be a high-anion gap metabolic acidosis present as well. To explore the causes of a HAGMA: 4. Compensation: Assessing the compensation for a respiratory alkalosis . The expected HCO3 is..........

Arterial Blood Gases (on supplemental O2 by face mask) pH 7.20 pCO2 39 mmHg pO2 277 mmHg HCO3 14.9 mmol/l

A previously well 55 year old woman is admitted with a complain of severe vomiting for 5 days. Physical examination reveals postural hypotension, tachycardia, and diminished skin turgor. The laboratory finding include the following: Electroyes: Na 140 , K 3.4, Cl 77 HCO3 9 , Cr 2.1 ABG: pH 7.23 , PCO2 3.3 kpa

2-A 44-year-old woman presents with 24 hours of unremitting emesis. She is dehydrated and hypotensive. Tests of her ABG show the following values: PaO2 = 11 Kpa , PaCO2 = 6 Kpa, HCO3- = 39 mEq/L, and pH = 7.49. What is the acid-base disturbance here?

A 50 year old insulin dependent diabetic woman was brought to the ED by ambulance. She was semicomatose and had been ill for several days. Current medication was digoxin and a thiazide diuretic for CHF. Lab results Serum chemistry: Na 132, K 2.7, Cl 79, HCO3 19 Glu 815, Lactate 0.9 urine ketones 3+ ABG: pH 7.41 PCO2 32 HCO3- 19

pO2 82

A 60 year old homeless man presents with nausea, vomiting and poor oral intake 2 days prior to admission. The patient reports a 3 day history of binge drinking prior to symptoms. Labs : Serum chemistry: Na 132, K 5.0, Cl 104, HCO3- 16 , BUN 25, Cr 1.3, Glu 75 ABG: pH 7.30 , PCO2 3.6 , HCO3- 16, PO2 9.2.

22 year old female with type I DM, presents to the emergency department with a 1 day history of nausea, vomiting, polyuria, polydypsia and vague abdominal pain. O/E. noted for deep sighing breathing, orthostatic hypotension, and dry mucous membranes. Labs: Na 138 , K 6.0, Cl 93, HCO3- 11 glucose 720, BUN 38, Cr 2.6. UA: pH 5, SG 1.010, ketones negative, glucose positive . Plasma ketones trace. ABG: pH 7.2 HCO3- 10 PCO2 2.7

Potasium Homeostasis 98 %of total body K is intracellular. Only 2% (about 70 mEq), is in the extracellular fluid, where the normal concentration of 3.5-5 mEq/L.

Hyperkalemia

Pseudohyperkalemia Hemolysis via small needle (traumatic Venipuncture) The most common cause is lysis of red cells in a phlebotomy specimen. Delayed analysis. Excessive tourniquet . Severe Thrombocytosis. Potassium released from platelets Severe Leukocytosis. Pseudohyperkalemia can be excluded by repeating the sample as atraumatically as possible .

Redistribution (ICF to ECF) Acidosis Hyperkalemic periodic paralysis. Insulin deficiency (DKA). Tissue damage (Tumor lysis ,Burn injury ,Crush injury, Surgery , Massive Hemolysis )

Medications: Beta Blockers Digitalis intoxication (Digoxin Toxicity)

Decreased renal excretion Renal Insufficiency or Renal Failure. Renal Tubular Acidosis(Type4) . Adrenal Insufficiency (Addison's).

Medication. Heparin . Cyclosporine ACE Inhibitor Potassium sparing Diuretics NSAIDS

The initial diagnostic approach begins with the clinical history, review of medications, and physical examination. Symptoms and signs include muscular weakness or flaccid paralysis, paralytic ileus, and characteristic ECG changes.

Symptoms and Signs 3 types of muscle fibres. May be asymptomatic Irregular heartbeat Fatigue Tingling, numbness, or paraethesia Weakness Paralysis Difficult breathing

ECG Mild hyperkalemia 5.5-6 mmol/L peaked T Moderate 6-8 mmol/L, peaked T + absent P wave

Severe > 8 mmol/L , peaked T absent P wave , wide QRS , Vent arrhythmia,VF,asystole

TARGET OF TREATMENT Minimize membrane depolarization Shifting k into cells Promote k loss Correction of acidosis D/C exogenous k sources , antikaliuretics.

Serious hyperkalemia = Plasma K> 7.5 mmol/L Profound weakness Absent P wave , wide QRS , vent arrhythmia. Intravenous calcium is administered to stabilize the myocardium; it lowers the threshold potential, thus counteracting the toxic effect of high potassium. Calcium does not have any effect on the serum potassium level. Improvement in the ECG changes should be visible within two to three minutes of administration of calcium

Medications Used in Acute Treatment of Hyperkalemia

Dosage

Onset

Length of effect

Calcium gluconate

10 to 20 mL of 10 percent solution IV over two to three minutes

Immediate

Insulin

Regular insulin 10 units IV with 50 mL of 50 percent glucose

15 to 30 minutes

Mechanism of action

Cautions

30 minutes

Protects myocardium from toxic effects of K; no effect on serum potassium level

Can worsen digoxin toxicity

Two to six hours

Shifts potassium out of the vascular space and into the cells; no effect on total body potassium

Consider 5 percent dextrose solution infusion at 100 mL per hour to prevent hypoglycemia with repeated doses. Glucose unnecessary if blood sugar elevated above 250 mg per dL

Albuterol (Ventolin)

10 to 20 mg by nebulizer over 10 minutes (use concentrated form, 5 mg per mL)

15 to 30 minutes

Two to three hours

Shifts potassium into the cells, additive to the effect of insulin; no effect on total body potassium

May cause a brief initial rise in serum potassium

Furosemide (Lasix)

20 to 40 mg IV, give with saline if volume depletion is a concern

15 minutes to one hour

Four hours

Increases renal excretion of potassium

Only effective if adequate renal response to loop diuretic

Sodium polystyrene Cation exchange resin

Oral: 50 g in 30 mL of sorbitol solution Rectal: 50 g in a retention enema

One to two hours (rectal route is faster) 1gm binds 1mmol k

Four to six hours

Removes potassium from the gut in exchange for sodium

Sorbitol may be associated with bowel necrosis. May lead to sodium retention

hemodiatysis

The most rapid and effective

PD is 15% as effective as HD

Hyporeninemic hypoaldosteronism( RTA type 4 ) should be considered in patients with diabetes and hyperkalemia, a trial of oral fludrocortisone to establish this diagnosis; potassium levels will return to normal in a day or two after initiation of fludrocortisone.

Hypokalemia

Manifestation of hypokalemia 1)Cardiac-ECG changes 2) Neuromuscular a) weakness of the limb muscles b) weakness of the trunk and resp. m. c) Smooth m. dysfunction ( gastric distension, ileus, urinary retention) d) Rhabdomyolysis. 3. Renal a) DI (polyuria) b) tubulointerstesial nephritis. c) Metabolic alkalosis. d) Hyponatremia

Etiology of hypokalemia (Loss or Shift) 1) Dietary Deficiency. 2) Redistribution. 3) Non renal losses. 4) Renal losses.

Redistribution -Cellular uptake Cellular uptake is controlled by the activity of Na+/K+ ATPase and H+ion conc.  Alkalosis  Insulin ß adrenergic stimulation.

Extrarenal losses of K+

B.Gastrointestinal losses Vomiting GI suction Diarrhea Rectal tumors Laxative abuse

Renal K+ loss Urinary K+ excretion > 20 meq/L Either associated with: Normotension Hypertension

Renal K+ loss Normotensive. 1) Drugs–Diuretics ,Amphotericin,cisplatine. 2) Renal tubular acidosis (type 1&2). 3) Bartter’s Syndrome,Gitelman Syndrome. 4) Magnesium deficiency. 5) Hypercalcemia.

Renal K+ loss Hypertensive A. Increased renin B. Decreased renin C. Normal renin

Renal K+ loss Hypertensive

A.Increased renin Malignant hypertension Renal artery stenosis Renin secreting tumor.

B. Decreased renin 1. Increased Aldosterone. Primary hyperaldosteronism (Conn’s disease). adrenal adenoma. adrenal hyperplasia. Adrenal carcinoma.

2. Decreased Aldosterone. (ap.miner.excess) Exogenous mineralocorticoid. Licorice ingestion. Liddle’s syndrome. 11 BHSD deficiency . 11-hydroxylase deficiency.

Normal Renin( Cushing) Cushing’s Syndrome (Adrenal adenoma, hyperplasia, carcinoma). Pitutary (Cushing’s Disease). Ectopic ACTH.

Renal tubular acidosis

Renal tubular acidosis (RTA)  hyperchloremic (normal anion gap) metabolic acidosis . high urine pH, bicarbonaturia, and reduced net acid excretion. frequently accompanied by hypokalemia.

Distal RTA Type 1

AR or acquired defect in H+ excretion & urinary acidification by the DCT hypercalcuria, Nephrocalcinosis.

Proximal RTA Type 2

AR or acquired Defect of HCO3 reabsorption from PCT, generally occurs as part of the renal Fanconi S. osteomalacia.

Bartter Syndrome AR affecting Na+-K-2Cl in TLOH salt wasting and hypokalemic, metabolic alkalosis. lasix like Failure to thrive, growth retardation, dehydration, low blood pressure, muscle weakness, tetany, paresthesias. Nephrocalcinosis. hypercalciuria and normomagnesemia  Nephrocalcinosis.

Gitelman Syndrome is a milder disorder. diagnosed in adolescents and adults. AR trait, inactivating mutations of thiazide sensitive Na-Cl cotransporter. Thiazide like. hypocalciuria due to ↑ Ca2+ transport in PCT. Hypomagnesemia remains unexplained.

Apparent Mineralocorticoid Excess  Deficiency in 11β-hydroxysteroid dehydrogenase enzyme. (11β HSD), responsible for the conversion of cortisol to the inactive metabolite , therefore protecting the mineralocorticoid receptors from cortisol intoxication.  Liddle Syndrome (psuedohyperaldosteronism).  Congenital Adrenal Hyperplasia(11hydroxylase def)

In AME . failure to thrive, salt retention, hypertension, and hypokalemic alkalosis, with a suppression of the RAA system.

Liddle Syndrome  AD,  HTN + hypokalemia  low plasma renin and aldosterone.  Activating mutations in the amiloride-sensitive

epithelial Na+ channel in the CD. Treatment Hypertension is not improved by spironolactone but can be corrected by ENaC antagonists (amiloride or triamterene).

Glucocorticoid-Remediable Hyperaldosteronism AD Fusion between aldosterone synthase and 11βhydroxylase, regulated by ACTH secrete aldosterone in response to ACTH, However, some subjects have early onset severe hypertension, hypokalemia, and metabolic alkalosis. diagnosis ; 18-hydroxycortisol metabolites in the urine. TTT= glucocorticoid administration can suppress excessive aldosterone secretion.

Acid-base and potassium balance metabolic alkalosis and hypokalemia suggest diuretic use or vomiting. metabolic acidosis and hypokalemia suggest diarrhea or laxative abuse or RTA type 1&2. metabolic acidosis and hyperkalemia suggest adrenal insufficiency or RTA type 4 . •On the other hand, the plasma bicarbonate and potassium concentrations are typically normal in the SIADH

Hyponatremia

Hyponatremia Defined as serum sodium less than 135. Very common in hospitalized patients. Severity of symptoms depends on acuity of change (1-3 days). neurological signs due to brain edema.

Clinical presentation Clinically significant hyponatremia present with nonspecific symptoms attributable to cerebral edema. Nausea and vomiting . Difficulty concentrating. Confusion. Lethargy. Agitation. Headache. Seizures. (Focal or generalized seizure).

–In those patients with acute severe hyponatremia, signs of brainstem herniation, including coma, unilateral, dilated fixed pupil.

Hyponatremia Hypovolemic Orthostatic changes BP/HR Dry mucous membranes.

Poor skin turgor Flat jugular veins

Hypervolemic Peripheral edema Elevated jugular venous pressure (signs of the cause,

Ascites

congestive heart failure , cirrhosis , or nephritic syndrome)

Euvolemic Absence of physical exam findings consistent with above .

Hypovolemic hyponatremia Excess fluid losses (eg, vomiting, diarrhea, excessive sweating, GI fistulas or drainage tubes, pancreatitis, burns) that have been replaced primarily by hypotonic fluids (GIT) . Salt-wasting nephropathy (Renal) . Cerebral salt-wasting syndrom (Renal). Check urine sodium <20 mEq/L –---

vomiting, diarrhea, third space loss

>20 mEq/L –---Diuretics, Mineralocorticoid deficiency, Bicarbonaturia, Salt losing nephritis

Euvolemic hyponatremia 1. Psychogenic polydipsia. 2. Administration of hypotonic intravenous fluids or

irrigation fluids to hospitalized pts. 3. SIADH . 4. hypoadrenalism & hypothyroidism.

Check urine osmolality <100 mOsm/kg –

Primary poydipsia

>100 mOsm/kg -

check TSH/FT4 & short synacten test .

Hypervolemic hyponatremia –acute or chronic renal failure. –hepatic cirrhosis, congestive heart failure, or nephrotic syndrome. Check urine sodium <20 mEq/L ------CHF, Cirrhosis, Nephrotic syndrome >20 mEq/L –----ARF, CRF

Syndrome of Inappropriate antidiuretic Hormone (SIADH) occurs when ADH is released in amounts far in excess of those indicated by plasma osmotic pressure. this syndrome is associated with diseases that affect osmoreceptors in the hypothalmus. is more common in the elderly. Causes: brain (hypothalamus) , pulmonary , Drugs.

SIADH is characterized by 1. Euvolemic hyponatremia. 2. serum hypo-osmolality. 3. concentrated urine. 4. Urinary sodium concentrations > 20 mEq/L. 5. Normal renal function. 6. Normal adrenal & thyroid function.

Treatment Acute hyponatremia (duration <72 h) can be safely corrected more quickly than chronic hyponatremia. Correction of serum sodium that is too rapid can precipitate severe neurologic complications, such as central pontine myelinolysis. More rapid therapy (1.5 to 2 mEq per hour) can be used in the first few hours if there is serious cerebral dysfunction. Otherwise, maximum rate of elevation: 1012 mEq during the first 24 hours

Treatment of hyponatremia Hypovolemic hyponatremia Normal saline 0.9 % till euvolemic

Hypervolemic hyponatremia Water restriction+ furesamide

Euvolemic hyponatremia Mild --.Water restriction+ ttt of cause’ .Demeclocycline .V2 receptor antagonist (vaptans) severe -- hypertonic saline

hypertonic saline Hypertonic saline is indicated if 1. Symptomatic hypona. 2.s.Na < 120 mEq Na needed = (120 – s.Na) x TBW Time needed = Na to be raised by 0.5 mEq /hr = 2 X (120 – s.Na) Na needed / hr = Na needed

Time needed Hypertonic solution needed/hr= Na needed / hr x2

Central Pontine Myelinolysis Due to rapid correction of Hyponatremia Possibly due to disturbance of blood brain barrier and damage by cytokines

No effective therapy

Presentation( neuro) •Dysarthria-Dysphagia Lethargy and coma Seizures-Nystagmus Ataxia emotional lability-akinetic mutism gait disturbance -myoclonus Behavioral disturbancesParaparesis or quadriparesis

Hypernatremia

Hypernatremia Hypernatremia is defined as a plasma [Na+] >145 mEq/L . Hypernatremia are almost caused by water loss rather than increase in total body sodium . So Sodium concentration is often used as an indicator of fluid status rather than salt imbalance .

Causes of ↑Na

Causes of Hypernatremia I)Hypovolemic Hypernatremia :A)

Non Renal Causes. Ur.Osmol >400 mosmol /kg . 1 ) GIT . 2 ) Skin :- High fever , heavy exercise …etc. 3 ) Respiratory : -Intubated Pts.

B) Renal causes. Polyuric States

( Ur.Osmol. May be low or high )

E.C.F. depletion & Intravascular depletion Skin turgor, sunken eyeballs, Dry mucus membranes. Hemodynamic effects.(BP, HR, JVP). Cool extremities..

II) Isovolemic Hypernatremia Central Diabetes Insipidus Any CNS Insult 1 ) Infiltration of post.pitutary. 2 ) Post Hypophysectomy. 3) Vascular Insult . 4)Encephalitis. 5)Neoplasms. 6)Taumatic. Ur.Osmol.<250 mosmol/kg . Treatmen Vasopressin + -Arginine Carbamazepine .

B) Nephrogenic Diabetes Insipidus 1 ) Inherited . 2 ) Acquired :-

Intrinsic renal disease : Sickle cell anemia , medullary cystic diseases. Obst. Uropathy.

Drug Induced. Electrolyte Disturbance.

Causes of Diabetes Insipidus Central DI Pituitary surgery Head trauma Tumors, Suprasellar or intrasellar leukemia Vascular (cerebral aneurysm, thrombosis, hemorrhage, Sheehan syndrome) Granulomas (sarcoidosis,Histocytosis, Wegener granulomatosis, tuberculosis) Infectious (encephalitis, meningitis, Guillain-Barré syndrome) Idiopathic (autoimmune) in 30%.

Nephrogenic DI Aquaired 1. Drugs - Lithium, demeclocycline, amphotericin B, 2. Electrolyte disturbances – ↓K, ↑Ca. 3. Conditions that impair medullary hypertonicity; obstructive uropathy, diuretic phase of ATN, osmotic diuresis. Congenital, - XLR V2 mutation.

Diabetes Insipidus ↑ Na Large urine volume Uosm excretion rate <700 mosm/d =DI 300-700 = partial

<300 Water deprivation

U osm <300 =complete DI

300-700 = partial

10 μg d DAVP IN

10 μg d DAVP IN

U osm ↑ > 50% = cranial

If less =nephrogenic

>10% ↑ =cranial

<10% =nephrog..

III ) Hypervolemic HypernatremiaA)Iatrogenic B) Miniralocorticoid Excess :-

Lab Studies There are 3 essential laboratory tests in the evaluation of patients with hypernatremia: 1. Serum osmolality 2. Urine osmolality 3. Urinary sodium

Treatment of hypernatremia Hypovolemic hypernatremia Normal saline 0.9 % till euvolemic

Hypervolemic hypernatremia D5W + furesamide

Euvolemic hypernatremia Hypotonic fluids (D5W, 0.45% Saline)-- water Deficit =

TBW(60%BW)

X

s.Na -140 140

Administer deficit over 48 h

Treatment of hypernatremia Treatment of hypernatremia

Hypovolemic

Euvolemic

Hypervolemic

Isotonic saline(0.9%) till euvolemia

Hypotonic fluids (D5W, 0.45%)

Frusemide + D5W or Oral

Furosemide - Na K 2 CL channels  ↓ medullary hypertonicity  ↑ free water loss from CD.

Specific management issues: central DI  intranasal desmopressin 5- 20μg (intranasal spray) x1-2/d. Nephrogenic DI  - low Na diet. - NSAIDs (↑ action of AVP). - Thiazide.

CALCIUM Ionized Calcium regulation is critical for: nerve conduction, muscle contraction, and muscle relaxation. membrane stability, bone & teeth mineralization , blood coagulation,

Body Calcium Distribution Calcium

(99%) Bone

50%

free (active) ionized form

<1%

intracellular (4/5) and extracellular fluid (1/5)

40%

bound to protein

(predominantly albumin)

10% complexed with anions

(eg, phosphate, carbonate, citrate, lactate, sulfate).

Calcium regulation Calcium regulation is maintained by parathyroid hormone (PTH), vitamin D, and calcitonin through complex feedback loops. These compounds act primarily at bone, renal, and GI sites. Calcium also is affected by magnesium and phosphorus.

HYPOCALCEMIA

Causes of hypocalcemia Hypoalbuminemia Pseudohypocalcemia. Parathyroid hormone related Hypoparathyroidism Pseudohypoparathyroidism Hypomagnesemia Vitamin D related Nutritional deficiency Impaired absorption Hepatic disease Renal failure Anticonvulsant vitamin D resistant Ca deposition Hungry bone syndrome Acute pancreatitis phosphate administration Hyperphosphatemia ( Rhabdomyolysis , tumor lysis, Renal failure) Critical illness and severe sepsis Medications and other causes

Parathyroid hormone related Hypoparathyroidism Acquired hypoparathyroidism Neck irradiation surgical removal Infiltrative disease ; hemachromatosis, granulomatous disease (sarcoidosis), amyloidosis, or metastatic malignant infiltration autoimmune disorder; adrenal failure. Mucocutaneous candidiasis, alopecia&vitiligo are associated (polyglandular autoimmune disease)(PGA I) Hereditary hypoparathyroidism . Sporadic, late-onset DiGeorge syndrome, associated with congenital heart disease, cleft palate/lip, and abnormal facies. Kearns-Sayre syndrome, which presents with heart block, retinitis pigmentosa, and ophthalmoplegia. Pseudohypoparathyroidism end-organ resistance to the effects of PTH. E.g. AHO.

Vitamin D related Nutritional deficiency. Impaired absorption ; Small bowel diseases, such as celiac disease, gastric bypass, steatorrhea, and pancreatic diseases. Hepatic disease . impaired 25-hydroxylation of vitamin D, decreased bile salts with malabsorption of vitamin D, decreased synthesis of vitamin D–binding protein, or other factors. Anticonvulsants Renal failure decreased conversion of 25-hydroxyvitamin D to its active form 1,25dihydroxyvitamin D.This results in an increase in PTH. Inherited conditions vitamin D dependent rickets (type I) or 1-alpha-hydroxylase deficiency . vitamin D dependent rickets (type II )--- Hereditary vitamin D resistance rickets.

Medications and other causes Proton pump inhibitors (PPIs) Cinacalcet (calcimimetic agent)--- inhibition of PTH release Amphotericin, Aminoglycosides. Chemotherapy Cisplatin -----Mg wasting Mg wasting Combination therapy with 5-fluorouracil and leucovorin ---decreasing calcitriol production Bisphosphonates .zoledronic acid -----suppressing the formation and function of osteoclasts Anticonvulsant therapy. Foscarnet---complexes ionized calcium Some radiographic contrast dyes may contain EDTA, which chelates calcium in serum, thereby reducing serum ionized ca.

Clinical picture Acute hypocalcemia The patient may complain of muscle cramping, shortness of breath secondary to bronchospasm, tetanic contractions, distal extremity numbness, and tingling sensations.

Latent tetany findings Chvostek sign: Tap over the facial nerve about 2 cm anterior to the tragus of the ear : twitching first at the angle of the mouth, then by the nose, the eye, and the facial muscles. Trousseau sign: Inflation of a blood pressure cuff above the systolic pressure causes local ulnar and median nerve ischemia, resulting in carpal spasm. Peroneal sign.

Chronic hypocalcemia cataracts, dry skin, coarse hair, brittle nails, psoriasis, chronic pruritus, and poor dentition, papilledema. basal ganglia calcification and extrapyramidal neurologic symptoms (in idiopathic hypoparathyroidism).

Brittle nails,

Alopecia Dry skin Coarse air

Lab Studies Serum albumin Corrected calcium (mg/dL) = measured total Ca (mg/dL) + 0.8 (4- serum albumin [g/dL]). Serum ionized calcium Serum phosphorus If low-------magnesium depletion (nutritional), vitamin D deficiency and hungry bone disease If high----hypoparathyroidism,pseudohypopara, or renal failure Serum magnesium Alkaline phosphatase: normal ------ PTH deficiencies . elevated ------------- osteomalacia and rickets. Elevated BUN and creatinine levels may indicate renal dysfunction.

Imaging Studies Skeletal x-rays. – Disorders associated with rickets or osteomalacia present with the pathognomonic Looser zones, better observed in the pubic ramus, upper femoral bone, and ribs. – Osteoblastic metastases from certain tumors (eg, breast, prostate, lung). CT scan of the head . may show basal ganglia calcification (in idiopathic hypoparathyroidism).

Treatment(Treat symptoms, not numbers) Acute hypocalcemia Promptly correct symptomatic or severe hypocalcemia with cardiac arrhythmias or tetany with parenteral administration. Administer 1-2 ampules 10% calcium gluconate (93 mg/10 mL) in 50-100ml over 5-10 minutes. Calcium chloride 10% solution (273 mg/10-mL ampule) delivers higher amounts of calcium and is advantageous when rapid correction is needed, but it should be administered via central venous access. NB:Patients with cardiac arrhythmias or patients on digoxin therapy need continuous ECG monitoring during calcium replacement because calcium potentiates digitalis toxicity.

Chronic hypocalcemia: Treatment of chronic hypocalcemia depends on the cause .(ca carbonate)

Hypercalcemia

Management of Acute Hypercalcemia 1.Hydration. Saline (0.9%) infusion, 2 -4 L over 24 hours

2.Inhibition of Bone Resorption. Bisphosphonate. Pamidronate(60 to 90 mg over 4 hours IV) or. Zoledronate(4 mg over 15 min IV). Calcitonin. 4 IU/kg to 8 IU/kg q12h sc or IM x 1 to 2 days

3.Calciuresis. Loop diuretics Furosemide10 to 20 mg IV every 6 to 12 hours

4.Glucocorticoids(when indicated) Hydrocortisone 200 -300 mg IV daily for 3 to 5 days

5.Dialysis in renal failure. 6. TTT. OF THE CAUSE.

PHOSPHORUS Homeostasis

Factors Regulating Phosphorus Homeostasis

Parathyroid hormone. 1 ,25(OH)2D3. Extracellular fluid volume. Dietary phosphate intake. phosphatonins . Renal function.

HYPERPHOSPHATEMIA .

CAUSES:

Increased renal reabsorption: Renal causes : Hyperphosphatemia occurs almost exclusively with

impaired glomerular filtration rate. Endocrinal causes : hypoparathyroidism, pseudohypoparathyroidism, acromegaly, thyrotoxicosis.

Extracellular shift :

DKA, Acidosis(Metabolic ,Respiratory). Execessive tissue damage : Massive release from intracellular stores: tumor lysis syndrome, rhabdomyolysis.

Iatrogenic causes : Overdose of vitamin-D derivatives, phosphatecontaining enemas.

pseudohyperphosphatemia: in paraprotenemias .

Lab Studies Serum total & ionized calcium Serum magnesium Alkaline phosphatase: BUN and creatinine levels . Parathyroid hormone levels. Vitamin D metabolites Urinary cAMP

HYPERPHOSPHATEMI A Treatment: Acute symptomatic hyperphosphatemia



Intravenous volume repletion with normal saline. ins/glu to enhancecellular uptake; dialysis but this is limited due to intracellular loca.



Chronic: ● Dietary restriction and phosphate binders.

Treatment (chronic) if possible treat the underlying cause . 1.phosphate Dietary restriction 2. Phosphate binders. 3. Dialysis .

Phosphate binders Calcium based Non-Calcium based

such as aluminum hydroxide,, lanthanum, and sevelamar (Renagel), reduce the amount of available phosphorus, thereby decreasing phosphate absorption and serum phosphate levels.

Hypophosphatemia

Major causes of hypophosphatemia Internal redistribution Increased insulin secretion, Acute respiratory alkalosis, Hungry bone syndrome Decreased intestinal absorption Inadequate intake, Antacids containing aluminum or magnesium, Steatorrhea and chronic diarrhea, Vitamin D deficiency or resistance Increased urinary excretion Primary and secondary hyperparathyroidism Vitamin D resistance,Hereditary hypophosphatemic rickets Oncogenic osteomalacia,Fanconi syndromeOther - osmotic diuresis, acetazolamide, acute volume expansion

Signs and symptoms of hypophosphatemia CENTRAL NERVOUS SYSTEM metabolic encephalopathy :Typical presenting symptoms include irritability and paresthesias, which can progress to confusion, seizures, delirium, and coma .

CARDIOPULMONARY SYSTEM — Myocardial contractility may be impaired with ATP depletion leading to congestive heart failure and respiratory failure due to weakness of the diaphragm .

SKELETAL AND SMOOTH MUSCLE — proximal myopathy (affecting skeletal muscle) and dysphagia and ileus (affecting smooth muscle). severe phosphate depletion can lead to rhabdomyolysis .

HEMATOLOGIC DYSFUNCTION (severe phosphate depletion ) Red blood cells — A reduction in intracellular ATP levels increases erythrocyte rigidity, predisposing to hemolysis . White blood cells — Diminished intracellular ATP levels reduces both phagocytosis and granulocyte chemotaxis . Platelets — Defective clot retraction and thrombocytopenia.

Magnesium Homeostasis Mg is present mainly intracellular. No hormonal regulation of intestinal or renal (re)absorption. LOH is the main site for Mg homeostasis. All diuretics cause ↓Mg especially loop diuretics, except acute thiazide or amiloride↑Mg. Hyperaldosteronism, volume expansion ↓Mg. Chronic metabolic acidosis ↓Mg. ↑ & ↓ PTH  ↓Mg ↓PTH. ↓Mg ↓K and ↓ Ca. Mg is a Ca CB, ↓Mg↑ intracellular Ca bronchospasm VC arrhythmias metabolic S. Mg has neuro-inhibitory action. Mg has favorable lipid profile, same action of statins. Mg has many therapeutic indications esp. eclampsia, acute severe asthma, arrhythmias, ms cramps, renal stones, antacids.

Hypomagnesemia In most cases of , hypomagnesemia is a result of renal or intestinal magnesium wasting ,which eventually leads tototal body magnesium depletion. In the majority of patients ,hypomagnesemia is the result of an acquired magnesium wasting disorder. Hereditary causes of hypomagnesemia are less frequent.

Causes of hypomagnesemia 1)Causes related to redistribution from extracellular to intracellular Hungry bone syndrome . H Treatment of diabetic ketoacidosis .D Ethanol withdrawal & dependence . E Refeeding syndrome .F Acute pancreatitis .B Total parenteral nutrition B

2)Causes related to gastrointestinal losses. Diarrhea .D Vomiting and nasogastric suction . G Gastrointestinal fistulas and ostomies Starvation ( intake ) . I

.G

3)Causes related to renal losses Inherited renal tubular defects Gitelman syndrome .G Classic Bartter syndrome . B Familial hypomagnesemia with hypercalciuria or hypocalcuria.

Drugs Diuretics -Loop diuretics, osmotic diuretics, and chronic use of thiazides Antimicrobials -Amphotericin B, aminoglycosides, capreomycin, vancomycin, foscarnet and pentamidine, . A & B Chemotherapeutic agents -Cisplatin .C Immunosuppressants -Tacrolimus and cyclosporine .C

Volume expansion. .E Primary hyperaldosteronism.( aldo ) .A Polyuric phase of acute tubular necrosis . Post obstructive diuresis. D hypoparathyroidism .H

A

Neuromuscular irritability & CNS hyperexcitability. -Hyperactive deep tendon reflexes. -Muscle cramps. -Muscle fibrillation. -Trousseau and Chovstek signs. -Dysarthria and dysphagia. -Irritability. -Disorientation. -Psychosis. -Ataxia, vertigo, nystagmus, and seizures.

DON’T FORGET *HYPOKALEMIA CANNOT BE CORRECTED UNLESS HYPOMAGNESEMIA HAS BEEN CORRECTED

Hypermagnesemia

Causes of hypermagnesemia Acute renal failure . chronic renal failure with Ingestion of Mg-containing substs such as vitami, antacids, cathartics, enemas . Excessive intravenous infusions of Mg in patients treated for eclampsia, asthma or cardiac arrhythmias. Release of intracellular magnesium e.g. tumor lysis syndrome, Rhabdomyolysis, massive hemolysis. Lithium intoxication decreases urinary excretion. C/P : Neuromuscular depression & inhibition.

GIT

Dysphagia

To solid & progressive =mechanical -Peptic stricture (+H burn) -Carcinoma (old)

To solid & fluid Intermittent =functional =oesophagial spasm (+ chest pain) Achalasia (+ resp distress)

Achalasia of the cardia • • • •

• • 1. 2. 3.

Failure of relaxation dt degeneration of the myenteric (Auerbach’s) plexus. In South America dt Chagas dis. ( Trepanosoma Cruzi). C/P; ♀, Intermittent functional dysphagia To solid & fluid. Inv; CXR absent gastric air bubble. Ba swallow parot beak appearance. manometry ↑LOS pressure > 30 mmhg. Complications; SCC. TTT; Botulinum injections are most effective of all the options for relieving a lower oesophageal sphincter. Nifedipine, nitrates or sildenafil are used but less effective. Surgically, Heller’s oesophageal myotomy via abdominal incision or laparascopically.

Achalasia

GERD • C/P; Ht burn, dysphagia, cough, asthma. • Oesophagitis is present in half of GERD patients. • Approach to pt with GERD; 1. Trial of PPI for 1 month, 2. If failed  Upper GI endoscopy. 3. PH monitoring; done pre &post-operative ,refractory. TTT: 1. PPI. 2. Fundoplication. • Complications; Barret’s oesophagus. • Alarm symptoms to do upper GIT endoscopy; Anemia, wt loss, dysphagia, odynophagia.

Barrett's oesophagus •

•

Columnar replaces Squamous in Barrett’s oesophagus. This is also known as small intestinal (columnar) metaplasia with goblet cells. There is increased risk of oesophageal adenocarcinoma.

•

Screening;

1. 2. 3. 4.

GERD with persistant symptoms at 50 years esp white male. Metaplasia /3 yrs. Low grade dysplasia /1 yrs. High grade dysplasia  radiofrequency ablation or endoscopic mucosal resection.

NB: does not regress with anti H pylori ttt.

The most common causes of infectious esophagitis include candida, cytomegalovirus (CMV), and herpes simplex virus. • Candida esophagitis endoscopy → white mucosal plaque-like lesions are noted. Confirmatory biopsy → yeasts and pseudohyphae .culture reveals Candida. • herpes simplex virus: upper endoscopy→ the earliest manifestation is a vesicle, although it is rarely seen. The lesions coalesce to form ulcers (usually less than 2 cm), frequently with normal-appearing intervening mucosa. The ulcers are well circumscribed . • CMV infection, ulcers tend to be linear or longitudinal and deeper & giant.

medication-induced esophagitis “Queen paid N Cash” • quinidine • potassium chloride • Alendronate . • iron sulfate . • doxycycline, tetracycline. • NSAIDs. • C vitamine.

Mallory-Weiss tear • caused by forceful or prolonged vomiting→ lower oesophageal tear. • vomiting bright red blood or by passing blood in the stool. • If vitally stable…. Discharge.

Cancer esophagus •

Predisposing factors;

1. 2. 3. 4. 5.

GERD. Barret’sadeno. Achalasia SCC. Plummer vinson $. smoking, alcohol. Coeliac dis Tylosis (familial palmar/planter icthyosis).

•

C/P; wt loss, progressive dysphagia To solid .

•

Pathology; ½ cases in the lower 1/3 , all scc except with barret’s.

• Inv; •

Ba swallow  shouldering .irregular filling defect, rat tail appearance, Oesphogoscopy & Biopsy

• Ttt surgery in only 1/3 suitable, if resectable. Palliative ttt for dysphagia→The best is stent insertion. rapid & effective than radio & chemo

Cancer oesophagus

Peptic ulcer diseases •

Causes;

1. 2. 3. 4. 5. • 1. 2. 3. 4. 5.

H pylori. NSAIDS. Infections; CMV, HSV, Drugs; bisphsphonate, KCl, steroids, MMF, cocaine, chemotherapy. Others; chron’s, ZES, ↑Ca, ischemia, irradiation. TTT; Acid supressing drugs; antacids, H2 blockers, PPI. Mucosal protecting agents; sucralfate, PG analogue. TTT of H pylori. Avoid NSAIDS. Surgery if complicated;

PPI irreversible inhibition of HK ATPase, before breakfast, side effect; 1-↓Ca↑hip fracture, 2- anemia dt ↓fe absorption, ↓ B12 dt ↓IF. 3-omeprazole, lanzo  enz inhibitors. 4-pneumonia 5- gynecomastia.

• 1. 2. -

Complications of surgery; Blind loop S; bact overgrowth. Dumping; early 15-30 min hypotension dt fluid shift 2ry to hyperosm. Content. - late 1-2 hr dt hypoglycemia. 4. Bile reflux gastropathy. • Complications of PU; 1. Bleeding 2. Perforation 3. Penetration 4. Gastric outflow obstruction.

H pylori • is a gram-negative microaerophilic rod • produce urease. Urease produces ammonia from urea. • Incidence; 80% in developing countries, 20% in industrialized. • Complications; 1. Chronic active gastritis. 2. Peptic ulcer disease. 3. MALT lymphomas. 4. Adenocarcinoma. 5. Extragastric; IsHD, enteropathic arthropathy, acne rosesea, urticaria.

• Diagnosis; 1. Non invasive; - stool Ag. - urea breath test(14C urea ingestion & breath Co2)FU after ttt. - serology; best screening but remain +ve after ttt for > 6 months so not a good indicator of acute infection. 2. invasive (endoscopy); - rapid urease (urea on specimen & pH colour indicator). - pathology→microscopic examination. -culture.

• TTT; • Triple therapy e.g. PPI 20 mg x2 + clarithromycin 500 mg x2 + amoxacillin1 g x2. • Or quadriple therapy (+ tetra). • For 14 days then continue PPI for another 2 wks in DU & 6 wks in GU.

New onset dyspepsia Ask about alarm symptoms

-ve Non invasive test for H pylori

+ve Refer for Ba or endoscopy

↑ +ve Eradication Ttt for 4 wks & confirm eradication by UBT If failed Ba or endos

- ve H2 blocker or PPI for 1 month

→If no response

New onset dyspepsia or GERD (ask if NSAIDs) If not do Non invasive test for H pylori

-ve H pylori Life style advise & Give PPI for 1months

+ve response Give the least dose which relief the symptoms or On demand TTT.

+ve H pylori Eradication Ttt for 4 wks & confirm eradication by UBT If failed Ba or endos

-Ve response refer for Ba or endos

MALT lymphoma • Low grade B cell lymphoma. • most commonly found in the gastrointestinal tract (stomach is the commonest). • associated Helicobacter Pylori infection. • TTT; respond in over 80% of cases to helicobacter eradication. • A proportion of patients will not respond to eradication therapy alone and will go on to more conventional anti-lymphoma therapies such as such as cyclophosphamide, chlorambucil, nucleoside analogues, or radiotherapy.

NSAID- PU • COX 2 inhibitors such as celecoxib are used as analgesics instead of NSAIDS in patients who are at high risk of upper GI dyspepsia or ulceration. However, there remains an increased risk of ulceration, though less so compared to NSAIDS. COX 2 inhibitors shown to increase the mortality rate of patients with CHD by blocking the antithrombotic effects of certain prostaglandins • Misoprostol (prostaglandin analogue) used in treatment of NSAIDs gastric ulceration. • .

ZES (Gastrinoma) • • • • •

GastrinomaPUD ( panc. head 60% & duod. 30%) Sporadic or MEN1. 60% malignant. 40% metastatic at presentation or multiple. C/P: Abdominal pain, Ulcers, diarrhea .

•

When to suspect.

• • • •

Recurrent DU. Postbulbar or multiple ulcers Resistant to TTT. Pt. with stigmata of MEN I.

•

Inv;

1. 2. 3.

Fasting gastrin level > 1200pg/ml+ low PH. (most sens. & specific). Secretin stimulation test.(secritin paradoxically incr. gastrin response). Tumour localization; CT, MRI, OCtreotide scan, Endo.US, laparotomy. TTT ; PPI, octreotide, surgery, chemotherapy.

•

Pernicious anemia • Autoimmune disease Ab to parietal cells ↓ HCl, intrinsic factor  gastric atrophy, achorhydria, macrocytic anemia dt B12 def., pancytopenia. • Incidence; 1 % of the population > 50 years. • C/P; ♀, FH, >50 years old, macrocytic anemia dt B12 def., pancytopenia other autoimmune manifestations; vitiligo, Addison, thyroid dis. • Complication; gastric cancer.

• Chronic gastritis • Type A; autoimmune, anemia, affect gastric body. • Type B; H pylori, antrum

Menetrier’s disease • Hyperplasia of mucin producing cells. • C/P; protein loosing enteropathy, hypochlorhydria. • Ttt; antacids for ulcerations, high protein diet, total gastrectomy. • DD of thick gastric folds; - Menetrier’s, ZES, - Lymphocytic, esinophilic , granulomatous gastritis. - Malignancy, MALT lymphoma. • Protein loosing enteropathy. • Gastric polyps; (rare & mostly benign). 1. Hamartomatous ; PJS.. 2. Adenomatous; pre-malignant

Gastric carcinoma • Predisposing factors; 1. 2. 3. 4. 5. 6. 7. • •

H pylori. Pernicious anemia. Adenomatous polyps. Partial gastrectomy. Bl group A. Smoking. Alcohol, spicy. Adenocarcinoma, antrum. Paramalignant; acanthosis, dermatomyositis.

Gastroparesis • 1. 2. 3.

Causes; DM. Autonomic Neuropathy. Vagotomy.

• C/P ;delayed gasric emptying , vomiting • Inv; isotope empting studies. •

TTT; prokinetics; metoclopramide, erythromycin, low fat diet ,low fibre , small frequent meals. feeding jejunostomy.

Vomiting Higher centers (see,smell) ↑ICT

CTZ 5HT3

D2

chemotherapy Drugs; -morphin, -digitalis, -estrogen, -ethanol

Metabolic -acidosis Hypoxia Uremia LCF ehtanol

Bact toxins

VC M1

5 HT3 Visceral aff (gastric, IO, ishemia)

H1 Vestibular syst preg, motion sickness

Malabsorption • Causes; 1. Preabsorptive; 1- gastric; post-gastrectomy. 2- pancreatic;e.g. chronic pancreatitis, Cystic fibrosis. 3- ↓ bile acid e.g.cholestasis, Ileal resection,Drugs as cholestyramine. 2) Absorptive; (Impaired mucosal absorption) - Intestinal resection or bypass - Inflammation, infiltration: Crohn's disease, Celiac sprue, Amyloidosis, Lymphoma,Radiation, - Infections; giardiasis, Tropical sprue, Whipple's disease - Genetic , Agammaglobulinemia, abetaliproteinemia. 3) Post absorptive; (Impaired nutrient delivery from intestine) - Lymphatic obstruction, ectasia, Lymphoma . - Circulatory disorders; Constrictive pericarditis, Mesenteric artery ath. - Endocrine Adrenal insufficiency Hyperthyroidism.

Management of malabsorption 1. 2.

Lab; CBC, Ca, Fe, folic acid, B12, cholesterol, Alb. To prove steatorrhea; - qualitative; sudan III - quantitative; stool fat>7 g/d or 6% of dietary fat. 3. endoscopic biopsy. - non caseating granuloma crhon’s - congo red +ve amyloidosis. - Malignant cells lymphoma. - PAS +ve org whipple, DD; M avium intracellular. -foamy intestinal mucosa  - clubbed villi, dilated lymph int lymphangectasia. - absent villi, no plasma cells Agammaglob - - absent villi, mononuclear infiltrate, hypertrophy of crypts celiac. 4- Urinary D Xylose test; assess CHO absorption from proximal SI, 25 g D xylose oral & collect urine for 5 hr, n=>4.5g D xylose in urine. NB; causes of villous atrophy; Celiac, tropical sprue, bact overgrowth, drugs as neomycin, laxative. Whipple, hypogamma, lymphoma.

• Other specific tests; 5- for Bacterial overgrowth; 6- for exocrine pancreatic function; - therapeutic test with pancreatic enzymes - secretin test (most sens) - fecal elastase. - serum trypsinogen.

Bacterial overgrowth •

Definition; Symdrome ccc by diarrhea, steatorrhea, macrocytic anemia dt proliferation of colonic bacteria in the small intestine e.g. E coli, bacteroids. • Pathogenesis; - decongugation of bile acids↓micelle formation steat. - consume B12 (not folate) - enterotoxins diarrhea • Causes; 1- Anatomical stasis; e.g. Afferent loop stasis/ blind loop/ strictures / fistulae. 2- functional stasis; DM, Scleroderma intestinal pseudoobstruction. • Diagnosis; - macrocytic anemia (↓B12, ↑folate). - jejunal aspirate for quantitative culture (> 105 ) .(gold standard) - H+ breath test (oral lactulose for early H+ detection in breath) - radioactive Carbon C14 breath test (oral bile salts  for early CO2 in breath). • TTT; surgical correction antobiotics; tetracyclin, metronidazole, ceph, amox/clav for 3 wks or 1 wk/month if recurrent. probiotics

Coeliac Disease • Coeliac disease (gluten sensitive enteropathy) is relatively common in Ireland, caucasiens, incidence1%. • Gluten is found in wheat, rye and barley . • C/P; asymptomatic diarrhea, steatorrhea, 2ry lactase def, anemia, bone dis. • Complications; GI & non GI cancer, intestinal lymphoma. • Associations; Dermatitis herpetiformis, IDDM, Ig A def, infertility, IBD, thyroiditis, fibrosing alveolitis, hyposplenism, Ig A nephropathy.

• Lab; - Folate levels are usually normal but not B12 in coeliac disease (in Crohns both are decreased).↓Fe, Ca - CBC: Macro or micro, howel jolly bodies. - antigliadin, antiendomesial, tissue transglutaminase, antireticulin • Jejunal biopsy in coeliac disease typically shows: hypertrophied crypts of Lieberkuhn, villus atrophy, an increase in intraepithelial lymphocytes. • TTT; gluten free diet , use rice, oat, potatoes, Fe Ca, Folic supplementation, if resistant steroid.

• Dermatitis herpetiformis - manifests as a pruritic rash. - Anti-endomysial antibodies may be present. - TTT; Dapsone (diaminodiphenyl sulfone) often is used initially; sulfapyridine is substituted in patients unable to tolerate dapsone.

Tropical sprue • Cause; infection as klebsiella, E coli . • Diagnosis; history of living in tropical areas + biopsy ( as celiac but less villous atrophy, more infiltration, same severity throughout intestine. • Ttt; tetracyclin for up to 6 months, folate.

Whipple disease • Chronic multisystem dis ass with; - GIT:diarrhea, steatorrhea., wt loss, - Arthoropathy: arthralgia, migratory large joint - CNS; oculomusticatory myorrhysmia, myoclonus, tremors, extra Δ& dementia. - Lymphadenopathy. • Cause; trophoryma whipplei (G+ve bacilli) • Biopsy; PAS +ve MQ in lamina containing the bacilli. (DD M. avium) • Ttt; sutrim DS for 1 year, .

Short Bowel S • • 1. 2. 3.

4. 5. •

Causes e.g. crohn’s, mesenteric Vascular dis, trauma, bariatric surgery. C/P; Diarrhea dt bile acid, ↓transit time, bact overgrowth Lactose intolerance Enteric hyperoxaluria dt - bile acid ↑colonic permeability - FA bind Ca ↑colonic Oxalate absorption. GB cholesterol stone dt ↓ bile acid Dumping S TTT; opiate, low fat, medium chain triglycerides (MCTs), low lactose, vit replacement, int. transplantation, trophic hormones as GLP-2.

Ileal dis

Mild Bile acid diarrhoea dt bile acid induced ↑ Cl secretion from the colon Ttt; cholestyramine

Severe FA steatorrhea Ttt; low fat diet, MCT

NB; Long chain FA> 12 C require micelle formation for absorption. • Medium chain FA 8-12 C does not need micelle formation, used in ttt of malabsorption e.g. coconut oil. • Short chain FA <8C - formed by colonic bacteria - e.g. acetate, propionate, butyrate. - Nutrient to the colon, -↓ with antibiotic use Ab induced colitis & diarrhea.

Lactase deficiency; • Causes; - 2ry e.g. celiac dis. - 1ry; 15% of Caucasians, 85-100% in blacks. • C/P; Asymptomatic, bloating, abd cramps • TTT; lactose free diet. • DD; IBS.

Acute diarrhoea

• <2 wks. • 90% infectious. • Toxigenic (watery); staph, B cereus , vibrio chol,.cl bot, cl perfring, E coli, • Invasive (bloody); (YES CAN CAUSE Vibrio parahemolyticus, vulnificus) yersinia, E coli, E coli o157, E hist, salm, shig, campylo, cl diff, vibrio parahemol, vulnificus, CMV colitis. • Traveler diarrhea E coli, campyl, shigella, salmonella, ttt; cipro, sutrim. • Hamburger E coli o157:H7 • Seafood vibrio, yersinia. • Fried rice B cereus. • Ttt; - symptomatic - metronidazole - cipro + culture

• Campylobacter; bloody, GBS ,ttt =erythro • Yersinia; Rt ileac, reactive arthritis, EN, myocarditis.ttt; quinolone • E coli o157:H7 HUS. • Amebic desentry metro . • Antidiarrheal should be avoided in febrile dysentery.

Chronic diarrhea 1. Watery; A) secretory i.e. does not ↓ with fasting, stool OG <25. e.g. stimulant laxative, toxins, resection, hormone producing tumors as VIPoma. B) osmotic; ↓ with fasting, stool OG > 50 eg. Osm laxative as Mg, lactase def, lactulose, sorbitol. 2. Inflammatory; pain, fever, bleeding, fecal leucocytes e.g. IBD, microscopic colitis, radiation, ischemic, malignancy. 3. Steatorrhea; sudan III, fecal fat > 7 g/d. 4. Dysmotility as IBS, DM, thyrotoxicosis. 5. Factitious e.g. Munchausen, eating disorders.

NB 1) stool osmolar Gap • Measured Stool osmolarity= 290-300 mosm/kg water • Calculated= 2(stool Na +K) • Stool osmolar Gap= Measured- Calculated if < 25= secretory diarrhea 25-50= mixed > 50= osmotic 2) Prolonged fasting > 24 hrs; if diarrhea↓ osmotic (diet) if not secretory.

• Investigations for laxative abuse; 1. ↓S. K 2. Melanosis coli on endoscopy. DD; carcinoid. 3. Ba enema; loss of haustration

Inflammatory Bowel disease UC

CD

site

Colon, wash back ilitis

All GIT, perianal except rectum

complications

Toxic megacolon

Fistulas, strictures

Macroscopic

pseudopolyps Narrow short colon with loss of haustrations

transmural Cobble stone Skip lesions

Microscopic

Crypt abcesses

Non caseating granuloma

lab

P ANCA 70% sens.

ASCA ; 90% specific, 70% sens.

Ba enema

loss of haustrations

Cobble stone, string sign

TTT

5ASA oral or rectal Steroid rectal, oral, IV Aza or 6MP IV cyclosporin or infleximab

Antibiotics Budezonide, Steroid oral, IV Aza or 6MP, Methotrexate Infleximab, IV cyclosporin

Ulcerative colitis

Crohn’s • affect any portion of the gastrointestinal tract from the mouth to the perianal area. • Its transmural inflammatory nature

• If suspecting IBD  upper GI series with small bowel followthrough (UGI/SBFT) and colonoscopy, with biopsies. • Features diagnostic of Crohn's disease include; - evidence of small bowel involvement on UGI/SBFT, or - non-caseating granulomas. - Significant perianal disease. • Extraintestinal feature include; -Skin., EN, clubbing, Pyoderma Gang., - Eye. uveitis, episcleritis, -Articular., osteoporosis, ankylosing spondylitis, sacroiliitis, peripheral arthritis,. -GIT., gall stones, PSC, cholangiocarcinoma, - Renal ,Ca oxalate urinary stone , amyloidosis. --- --Thromboembolism. Cancer risk in IBD; • Risk factors; duration, extent, FH. Screening; after 8-y of pancolitis or 15 y of lt sided colitis  colono + biopsy/1-3 yr.

C/p; majority has bloody diarrhea and mild cramping, with minimal systemic symptoms such as fever, weight loss, and anorexia. TTT depends upon both the extent of colonic involvement and the severity of the disease process at presentation. 1. for ulcerative proctitis = topical 5-aminosalicylate suppositories or steroid foams. 2. Patients with left-sided colitis often respond to topical enemas. 3. Pan colitis ( extends beyond the splenic flexure). A) mild to moderate; - oral 5-ASA or sulfasalazine + topical 5-ASA or steroid enemas . - add oral prednisone (40 to 60 mg/day) in: 1- more severe symptoms and 2- failed oral 5-ASA and topical therapy. These agents often require 3-6 weeks to exert their maximal benefit. Once remission is achieved, the drug dose can be tapered to maintenance levels. Disease severity

Medication

Daily dose

Mild-to-moderate disease Mesalamine suppository

1000mg at night

Mesalamine enema

4 g at night

Hydrocortisone enema

100 mg at night

Mesalamine e.g. Pentasa

500to 1000 mg PO 4 times /d

Sulfasalazine

1-1.5 g PO four times/ d

oral 5-ASA + 5-ASA enemas/steroid enema Prednisone

40 to 60 mg PO /d

Maintenance therapy in UC to reduce the risk of relapse Disease type

Medication

Dose

Proctitis

Mesalamine suppository

1000 mg /night to /3 night

Distal colitis

Mesalamine enema

4 g /night to / 3 night

Left-sided & pancolitis

Sulfasalazine 500 mg PO four times daily Mesalamine EC (Asacol*) 400 to 800 mg PO 3 times/d Olsalazine 500 mg PO twice daily Sulfasalazine/oral 5-ASA + 5-ASA enema

Steroid-dependent colitis Mercaptopurine Azathioprine Methotrexate

50 mg up to 1.5 mg/kg PO/day 50 mg up to 2.5 mg/kg PO/day 10 to 15 mg PO once per week

B) Severe active disease B) Severe active disease is a medical emergency defined as > 6 bloody stools/ day & signs of systemic toxicity (HR > 90, temp. 37.8 , Hb 10,5, ESR >30)

- Hospitalization &intensive inpatient TTT . - pulse IV steroid, either hydrocortisone 100 mg 4 times daily ,or methyle prednisolone 60 mg daily ….if no improvement by day 3 or there is subsequent deterioration…→

Disease severity

On steroids recently

Methylprednisolone 40 to 60 mg IV once daily Hydrocortisone 100 mg IV/ 6 hrs or IVI Cyclosporine Infliximab

Toxic megacolon

IV corticosteroids Broad-spectrum antibiotics

Chronic active disease (steroid refractory)

Mercaptopurine, Azathioprine Infliximab

surgery.2 mg / kg / day.

-IV fluids & electrolytes replacem. -IV antibiotics if infection is considered.

-surgery.

Daily dose

Severe active disease

-IV cyclosporine. As a rescue therapy before

-infliximab if cyclosporine is #contra.

Medicatio n

Toxic megacolon • Colonic diameter > 5.5cm or Caecum > 9 cm in abd plain X ray . • Management medical for up to 48 hrs • NPO. • Clinical, laboratory, & radiological monitoring. • IV fluids & electrolytes replacement . • IV antibiotics if infection is considered. • If no response within 48hrs→subtotal colectomy

Surgery; • UC Subtotal colectomy& end ileostomy or ileal pouch anal anastomosis (IPAAS).

• Indication; • intractable( not responding to intensive medical ttt.) • Fulminant , acute severe on top of chronic . • Poorly controlled Complicated extraintestinal. • Toxic mega colon, • Impact of colectomy on UC manifestations • Stay the same; sacroilitis, sclerosing cholangitis, uveitis. • Positive response; pyoderma, peripheral arthritis, perianal dis. Complication; pouchitis in 1/3. C/P; diarrhea, arthralgia, fever. Biopsy differentiate bet CD & true pouchitis. Prevention with probiotics. Ttt of pouchitis; antibiotics.Metronidazole 1x3or ciprofloxacin 250 1x2 • CD; - surgical resection is contraindicated. - stricturoplasty, diversion colostomy for perianal dis - total proctocolectomy & ileostomy (but IPAAS is contraindicated dt pouch failure)

Antiinflammatory drugs in CD, UC;

1. 5ASA; for induction & maintenance - e.g. - sulfasalazine (sulfapyridine + 5 ASA). Side effect; oligospermia, allergic, idiosyncrasy, agranulocytosis, rash, folate def. - Enteric coated; mesalazine (Pentasa, Asacol)2-4g. 2.Azathioprine 50 mg up to 2.5 mg/kg PO/day Is the best maintenance ttt for steroid dependent

3.Steroids; for induction only not maintenance.

Infliximab; • chimeric monoclonal antibody to TNF. • Used in; 1- refractory IBD, not fit for surgery. 2-perianal Fistulizing Crohn's; 3-RA, Psoriasis, cryo, not AS. • Dose; IV 5 mg/kg at 0, 2, 6 then /8 wks. • Side effects; - Ab to infliximabe resistance & reaction so given with Aza or methotrexate + hydrocortisone before the dose. - lymphoma. - allergic reactions, serum sickness - infection esp TB - demylenating disorders.

• Fistulizing Crohn's; - elemental diet is as effective as steroids in induction of remission in Crohn's not in UC, better than bowel rest & TPN. - antibiotics metronidazole or cipro. - Aza, metho - infliximab - TPN • Oral lesions ; Aphthous ulcerations are the most common , usually occur with coexistent intestinal disease.

TTT; - respond to treatment directed at the intestinal disease. - Topical therapy consisting of Topical hydrocortisone or carboxymethylcellulose or topical tacrolimus or topical sucralfate may be effective for local symptom relief.

IBD & pregnancy. - Dis activity not affected by pregnancy.But pt should be in remission for 6 months before conception. - CS is preferred in perianal dis. - Drugs; - 5 ASA, steroids safe but use folate with sulfas. - Aza, 6MP safe with consent.

VIPomas • VIPomas [vasoactive intestinal peptide (VIP)] . • C/P;WDHA - watery diarrhea, stool volume > 700 ml/d. - hypokalemia, N-AG acidosis - achlorhydria, + hyperglycemia , hypercalcemia in 2/3, flushing and hypokalaemia due to diarrhoea. • Treatment; correcting volume and electrolyte abnormalities by using potassium chloride and sodium bicarbonate. Octreotide controls diarrhea in 80% of cases. Glucocorticoids reduce symptoms in 50% of patients with VIPoma.

Carcinoid tumours C/P After hepatic metastasis; • Forgut cushing, acromegaly. • Midgut (ABCDEF); asthma, belly abd, cor pulm TR>TS, diarrhea, endocardial fibrosis, flushing (Carcinoid syndrome) • Bronchus; ACTH, GHRH. (cushing, acromegaly). Diagnosis; raised urinary 5-HT levels. A precursor of 5HT, tryptophan is highly metabolised and consequently niacin deficiency (pellagra) occurs. The three D's dementia, dermatitis and diarrhoea occur. Ttt; resection, octreotides, methysergide, cyproheptadine, phenoxybenzamine for flushing.

• Glucagonoma; WARDS - wt loss - anemia - rash. NME - DM, diarrhea - DVT. • Somatostatinoma SSS - sugar (DM) - steatorrhea - stones GB

Ischemic colitis • • • •

Non- occlusive Rectosegmoid Elderly, bloody diarrhea& pain . XR abd; thumb printing dt mucosal & submucosal oedema. • colonoscopy; narrowing, ulceration. • Angio; not usually indicated.

Pseudomembranous colitis • Antibiotics as clindamycin, ampicillin, cephalosporin, tetracyclin flurishing of Cl difficile toxins A, B. • C/P; fever , bloody diarrhea • Diagnosis; C difficile toxin in stool. • Ttt; discontinue the antibiotic. • Give metronidazole, oral vancomycin.

Irritable bowel syndrome • C/P; pain relieved by defecation, Never bleeding /rectum, Never wt loss, Never nocturnal. (ROME II criteria) 12 weeks or more in the last year of abdominal discomfort or pain that has two of the following three features:. (1)Relieved by defecation (2) Associated with a change in frequency of stool (3) Associated with a change in consistency of stool • Ttt; - dietary therapy; lactose free, high fibre. symptomatic ttt.

Chronic Colonic pseudo-obstruction • • 1. 2. 3. 4. 5. 6. 7.

C/P; of mechanical obstruction but without occlusion of the lumen. Causes; Endocrinal causes; DM, hypothyroidism, hypoparathyroidism, hypoadrenalism. Neurologic; parkinsonism, ms dystrophy, MS. Rheumatologic; progressive systemic sclerosis. Infection; Chaga’s dis. Medications; TCA, clonidine, phenothiazines, narcotics Amyloidosis Paramalignant.

Colonic polyps

Non-neoplastic Neoplastic 1. 2. 3. 4.

Adenomatous (FAP, Gardner) Papillary adenoma Villous papilloma carcinoid

1. Hamartomatous (jej polyps, PJS, cowden) 2. Hyperplastic. 3. Inflammatory. (Bilh, lymphoid, pseudopol of UC) 4. C.Tissue polyps (lipoma, fibroma, leimyoma)

• Familial adenomatous polyposis; - AD, chr 5 - > 100 polyps - 100% premalignant. - extracolonic tumours; thyroid, pancreatic, duodenal. - 1/3 has no FH. - polyps may occur in UGIT. - total colectomy should be performed as soon as possible following diagnosis.

• Gardner S= FAP when extracolonic tumours predominates as osteomas, fibromas, neurofibromas, lipomas, dermoid cysts, desmoid tumours, retroperitoneal fibrosis.

• cowden (1/3 has goitre,10%cancer, ¾ fibrocystic dis of breast) • Peutz-Jeghers syndrome; - AD. - dt gene mutation of the STK11 in most cases. - hamartomatous polyps + mucocutaneous melanocytic macules, perioral freckles, alopecia, nail dystrophy.

HNPCC • • • 1. 2. 3. 4. 5. •

AD, chr 2,3 Associations; other cancers; endometrial, ovarian, gastric Amesterdam criteria for genetic testing; 3 or more 1st degree family members with colorectal ca. Colon ca over 2 generations. At least 1 before<50yrs. Pt with CRC or endometrial ca below<40yrs Pt with CRC with 1st degree CRC or extracolonic ca If genetic testing +ve colonoscopy

Colorectal cancer •

Predisposing factors;

1. 2. 3. 4. 5. 6.

High fat diet, low fibre FAPC HNPCC UC, CD Adenomatous polyps Black race, male sex

•

Preventive measures;

1. 2. 3. • • •

NSAIDs High Ca diet HRT (E) C/P; include iron def anemia, sepsis with streptococcus bovis. Inv; double contrast Ba enema, colonoscopy, CEA. Ttt; resection anastomosis, abdominoperineal resection & colostomy for distal rectal tumours.

Cancer colon

Screening of colorectal cancer • People > 60 yrs  - colonoscopy/10 yr or - occult B in stool/ y + sigmoidoscopy /5 yr. • People who have adenoma removal & biopsy then according to the size & number 1 or 2 polyps < 1 cm→ colonoscopy/5 yr . 3 or 4 polyps < 1 cm or one > 1cm → colonoscopy/3yr. > 5 polyps < 1 cm or 3 or more > 1cm → colonoscopy/3yr. • PH of Ca colon,  - colonoscopy after 1 year then after 3years then /5 yr. • FH of two 1st degree relatives with colorectal cancer or FH of one 1st degree relative with colorectal cancer < 60 yr.  colonoscopy / 3-5 yr beginning 10 yrs younger than the youngest affected relative.

• PH of UC (8 yr pancolitis )or( > 15 yr Lt sided) colonoscopy then acc. Extensive colitis with mild inflammation→ colonoscopy every 3 yrs. Extensive colitis with moderate to severe inflamm→ colonoscopy /1 yr Lt sided colitis→ colonoscopy every 5 yrs. (colonoscopy + biopsy ) FH of FAP - Colonoscopy / 1-2 yr from puberty till 40 yr old then as average. - if polyps develop or genetic test +ve colectomy. FH of HNPCC  - colonoscopy 1-2 yrs from 21 yr ..

Constipation Types of Constipation and Causes Recent onset

•

DD;

Colonic obstruction

Neoplasm; stricture: ischemic, diverticular, inflammatory

Anal sphincter spasm

Anal fissure, painful hemorrhoids

Medications

Fe, Ca, Al HO, anticholinergics, opiates,diuretics

Chronic Irritable bowel

Constipation-predominant, alternating

Medications

blockers, antidepressants +2Ca

Disorders of rectal evacuation

Slow-transit constipation, megacolon, Pelvic floor (dysfunct,; rectal prolapse; rectocele.

Endocrinopathies

Hypothyroidism, hypercalcemia, pregnancy

Psychiatric disorders

Depression, eating disorders, drugs

Neurologic disease

Parkinsonism, multiple sclerosis, spinal cord injury

muscle disease

Progressive systemic sclerosis

Abdominal pain • -

Medical causes; alcohol, DKA, hyperlipidemia pancreatitis Hyperparathyroid, adrenal insufficiency FMF, porphyria, angioneurotic edema Lead toxicity, morphin withdrawal. Vasculitis as HSP. sickle cell an..

Gut Hormones • Secretin is produced by the jejunum. It relaxes the oesophageal sphincter and also stimulates pancreatic enzyme secretion. • Gastrin is secreted by the G cells of gastric antrum. It stimulates parietal cells produce hydrochloric acid. • Vasoactive intestinal peptide (VIP) promotes intestinal water and electrolyte secretion. • Chief cells pepsin. • Parietal cells HCl, intrinsic factor. • Surface cells-> HCO3, mucous.

GIT

Dysphagia

To solid & progressive =mechanical -Peptic stricture (+H burn) -Carcinoma (old)

To solid & fluid Intermittent =functional =oesophagial spasm (+ chest pain) Achalasia (+ resp distress)

Achalasia • • • •

• • 1. 2. 3.

Failure of relaxation dt degeneration of the myenteric (Auerbach’s) plexus. In South America dt Chagas dis. ( Trepanosoma Cruzi). C/P; ♀, functional dysphagia To solid & fluid. Inv; CXR absent gastric air bubble. Ba swallow parot beak appearance. manometry ↑LOS pressure > 30 mmhg. Complications; SCC. TTT; Botulinum injections are most effective of all the options for relieving a lower oesophageal sphincter. Nifedipine, nitrates or sildenafil are used but less effective. Surgically, Heller’s oesophageal myotomy via abdominal incision or laparascopically.

Achalasia

GERD • • • 1. 2. 3. 4.

C/P; Ht burn, dysphagia, cough, asthma. Oesophagitis is present in half of GERD patients. Approach to pt with GERD; Trial of PPI for 1 month, If failed  Upper GI endoscopy. If normal  Bernstein test. PH monitoring; done pre & post-operative refractory. TTT: 1. PPI. 2. Fundoplication • Complications; Barret’s oesophagus. • Alarm symptoms to do upper GIT endoscopy; Anemia, wt loss, dysphagia, odynophagia.

Barrett's oesophagus •

•

Columnar replaces Squamous in Barrett’s oesophagus. This is also known as small intestinal (columnar) metaplasia with goblet cells. There is increased risk of oesophageal adenocarcinoma.

•

Screening;

1. 2. 3. 4.

GERD with persistant symptoms at 50 years esp white male. Metaplasia /3 yrs. Low grade dysplasia /1 yrs. High grade dysplasia  FU /3 months.

NB: does not regress with anti H pylori ttt.

The most common causes of infectious esophagitis include candida, cytomegalovirus (CMV), and herpes simplex virus. • The diagnosis of Candida esophagitis is usually made at endoscopy when white mucosal plaque-like lesions are noted. Confirmatory biopsy shows the presence of yeasts and pseudohyphae .culture reveals Candida. • The diagnosis of herpes simplex virus: is usually established with an upper endoscopy. Lesions affect the squamous mucosa where the earliest manifestation is a vesicle, although it is rarely seen. The lesions coalesce to form ulcers (usually less than 2 cm), frequently with normal-appearing intervening mucosa. The ulcers are well circumscribed . • CMV infection, ulcers tend to be linear or longitudinal and deeper & giant.

medication-induced esophagitis “Queen paid N Cash” • quinidine • potassium chloride • Alendronate . • iron sulfate . • doxycycline, tetracycline. • NSAIDs. • C vitamine.

Mallory-Weiss tear • occurs in the mucous membrane typically in the lower oesophagus. • usually caused by forceful or prolonged vomiting or coughing. • vomiting bright red blood or by passing blood in the stool.

Cancer esophagus •

Predisposing factors;

1. 2. 3. 4. 5. 6. 7.

GERD. Achalasia SCC. smoking, alcohol. Plummer vinson. Barret’sadeno. Coeliac dis. Tylosis (familial palmar/planter icthyosis). C/P; wt loss, progressive dysphagia To solid . Pathology; ½ cases in the lower 1/3 , all scc exept with barret’s. Inv; Ba swallow  shouldering Ttt surgery in only 1/3 suitable, improve 5 yr surv to 10%.

• • • •

Cancer oesophagus

• 1. 2. 3. 4. 5. • 1. 2. 3. 4. 5.

Causes;

Peptic ulcer diseases

H pylori NSAIDS Infections; CMV, HSV, Drugs; bisphsphonate, KCl, steroids, MMF, cocaine, chemotherapy. Others; chron’s, ZES, ↑Ca, ischemia, irradiation. TTT; Acid supressing drugs; antacids, H2 blockers, PPI. Mucosal protecting agents; sucralfate, PG analogue. TTT of H pylori. Avoid NSAIDS. Surgery if complicated; • PPI irreversible inhibition of HK ATPase, before breakfast, side effect; 1-↓Ca↑hip fracture, 2- anemia dt ↓fe absorption, ↓ B12 dt ↓IF. 3-omeprazole, lanzo  enz inhibitors. 4-pneumonia 5- gynecomastia.

• 1. 2. -

Complications of surgery; Blind loop S; bact overgrowth. Dumping; early 15-30 min hypotension dt fluid shift 2ry to hyperosm. Content. - late 1-2 hr dt hypoglycemia. 4. Bile reflux gastropathy. • Complications of PU; 1. Bleeding 2. Perforation 3. Penetration 4. Gastric outflow obstruction.

H pylori • , is a gram-negative microaerophilic rod • produce urease. Urease produces ammonia from urea, • Incidence; 80% in developing countries, 20% in industrialized. • Complications; 1. Chronic active gastritis. 2. PUD 3. MALT lymphomas 4. Adenocarcinoma 5. Extragastric; IsHD, enteropathic arthropathy, hep enceph, acne rosesea, alopecia, urticaria, Raynauld’s.

• Diagnosis;

1. Non invasive; - stool Ag - urea breath test(14C urea ingestion & breath Co2)FU after ttt. - serology; best screening but remain +ve after ttt for > 6 months so not a good indicator of acute infection. 2. invasive (endoscopy); - rapid urease (urea on specimen & pH colour indicator). - pathology…… microscopic examination. -culture. • TTT; • Triple therapy e.g. PPI 20 mg x2 + clarithromycin 500 mg x2 + amoxacillin1 g x2. • Or quadriple therapy (+ tetra) • For 14 days then continue PPI for another 2 wks in DU & 6 wks in GU.

New onset dyspepsia (Exclude GERD, biliary, IBS, drugs) >40 yrs, alarm symp -ve Non invasive test for H pylori

+ve Ttt for 4 wks & confirm eradication by UBT If failed Ba or endos

+ve Refer for Ba or endoscopy

- ve H2 blocker or refer for Ba or endos

alarm symp; of ulcer complications, malig

MALT lymphoma • Low grade B cell lymphoma. • most commonly found in the gastrointestinal tract (stomach is the commonest). • associated Helicobacter Pylori infection. • TTT; respond in over 80% of cases to helicobacter eradication. • A proportion of patients will not respond to eradication therapy alone and will go on to more conventional anti-lymphoma therapies such as such as cyclophosphamide, chlorambucil, nucleoside analogues, or radiotherapy.

NSAID- PU • COX 2 inhibitors such as celecoxib are used as analgesics instead of NSAIDS in patients who are at high risk of upper GI dyspepsia or ulceration. However, there remains an increased risk of ulceration, though less so compared to NSAIDS. • Misoprostol (prostaglandin analogue) and cimetidine are used in treatment of gastro-oesophageal ulceration. • COX 2 inhibitors have also recently been shown to increase the mortality rate of patients with coronary artery disease by blocking the antithrombotic effects of certain prostaglandins.

ZES (Gastrinoma) • • • • •

GastrinomaPUD ( panc. head 60% & duod. 30%) Sporadic or MEN1. 60% malignant. 40% metastatic at presentation or multiple. C/P: Abdominal pain, Ulcers, diarrhea .

•

When to suspect.

• • • •

Recurrent DU. Postbulbar or multiple ulcers Resistant to TTT. Pt. with stigmata of MEN I.

•

Inv;

1. 2. 3.

Fasting gastrin level > 1200pg/ml+ low PH. (most sens. & specific). Secretin stimulation test.(secritin paradoxically incr. gastrin response). Tumour localization; CT, MRI, OCtreotide scan, Endo.US, laparotomy. TTT ; PPI, octreotide, surgery, chemotherapy.

•

Pernicious anemia • Autoimmune disease Ab to parietal cells ↓ HCl, intrinsic factor  gastric atrophy, achorhydria, macrocytic anemia dt B12 def., pancytopenia. • Incidence; 1 % of the population > 50 years. • C/P; ♀, FH, >50 years old, macrocytic anemia dt B12 def., pancytopenia other autoimmune manifestations; vitiligo, Addison, thyroid dis. • Complication; gastric cancer.

• Chronic gastritis • Type A; autoimmune, anemia, affect gastric body. • Type B; H pylori, antrum

Menetrier’s disease • Hyperplasia of mucin producing cells. • C/P; protein loosing enteropathy, hypochlorhydria. • Ttt; antacids for ulcerations, high protein diet, total gastrectomy. • DD of thick gastric folds; - Menetrier’s, ZES, - Lymphocytic, esinophilic , granulomatous gastritis. - Malignancy, MALT lymphoma. • Protein loosing enteropathy. • Gastric polyps; (rare & mostly benign). 1. Hamartomatous ; PJS.. 2. Adenomatous; pre-malignant

Gastric carcinoma • Predisposing factors; 1. 2. 3. 4. 5. 6. 7. • •

H pylori. Pernicious anemia. Adenomatous polyps. Partial gastrectomy. Bl group A. Smoking. Alcohol, spicy. Adenocarcinoma, antrum. Paramalignant; acanthosis, dermatomyositis.

Gastroparesis • 1. 2. 3.

Causes; DM. Autonomic Neuropathy. Vagotomy.

• C/P ;delayed gasric emptying , vomiting • Inv; isotope empting studies. •

TTT; prokinetics; metoclopramide, erythromycin, low fat diet ,low fibre , small frequent meals. feeding jejunostomy.

Vomiting Higher centers (see,smell) ↑ICT

CTZ 5HT3

D2

chemotherapy Drugs; -morphin, -digitalis, -estrogen, -ethanol

Metabolic -acidosis Hypoxia Uremia LCF ehtanol

Bact toxins

VC M1

5 HT3 Visceral aff (gastric, IO, ishemia)

H1 Vestibular syst preg, motion sickness

Malabsorption • Causes; 1. Preabsorptive; 1- gastric; post-gastrectomy. 2- pancreatic;e.g. chronic pancreatitis, Cystic fibrosis. 3- ↓ bile acid e.g. CLD, cholestasis, Bacterial overgrowth, Ileal resection,Drugs as neomycin, cholestyramine. 2) Absorptive; (Impaired mucosal absorption) - Intestinal resection or bypass - Inflammation, infiltration: Crohn's disease, Celiac sprue, Amyloidosis, Lymphoma,Radiation, - Infections; giardiasis, Tropical sprue, Whipple's disease - Genetic , Agammaglobulinemia, abetaliproteinemia. 3) Post absorptive; (Impaired nutrient delivery from intestine) - Lymphatic obstruction, ectasia, Lymphoma . - Circulatory disorders; Constrictive pericarditis, Mesenteric artery atherosclerosis, Vasculitis. - Endocrine Adrenal insufficiency Hyperthyroidism.

Management of malabsorption 1. 2.

Lab; CBC, Ca, Fe, folic acid, B12, cholesterol, Alb. To prove steatorrhea; - qualitative; sudan III - quantitative; stool fat>7 g/d or 6% of dietary fat. 3. endoscopic biopsy. - non caseating granuloma crhon’s - congo red +ve amyloidosis. - Malignant cells lymphoma. - PAS +ve org whipple, DD; M avium intracellular. -foamy intestinal mucosa  - clubbed villi, dilated lymph int lymphangectasia. - absent villi, no plasma cells Agammaglob - - absent villi, mononuclear infiltrate, hypertrophy of crypts celiac. 4- Urinary D Xylose test; assess CHO absorption from proximal SI, 25 g D xylose oral & collect urine for 5 hr, n=>4.5g D xylose in urine. NB; causes of villous atrophy; Celiac, tropical sprue, bact overgrowth, drugs as neomycin, laxative. Whipple, hypogamma, lymphoma.

• Other specific tests; 5- for Bacterial overgrowth; 6- for exocrine pancreatic function; - therapeutic test with pancreatic enzymes - secretin test (most sens) - fecal elastase, chemotrypsin - serum trypsinogen. - bentiromide test.

Bacterial overgrowth •

Definition; Symdrome ccc by diarrhea, steatorrhea, macrocytic anemia dt proliferation of colonic bacteria in the small intestine e.g. E coli, bacteroids. • Pathogenesis; - decongugation of bile acids↓micelle formation steat. - consume B12 (not folate) - enterotoxins diarrhea • Causes; 1- Anatomical stasis; e.g. Afferent loop stasis/ blind loop/ strictures / fistulae. 2- functional stasis; DM, Scleroderma intestinal pseudoobstruction. • Diagnosis; - macrocytic anemia (↓B12, ↑folate). - jejunal aspirate for quantitative culture (> 105 ) .(gold standard) - H+ breath test (oral lactulose for early H+ detection in breath) - radioactive Carbon C14 breath test (oral bile salts  for early CO2 in breath). • TTT; surgical correction antobiotics; tetracyclin, metronidazole, ceph, amox/clav for 3 wks or 1 wk/month if recurrent. probiotics

Coeliac Disease • Coeliac disease (gluten sensitive enteropathy) is relatively common in Ireland, caucasiens, incidence1%. • Gluten is found in wheat, rye and barley . • C/P; asymptomatic diarrhea, steatorrhea, 2ry lactase def, anemia, bone dis. • Complications; GI & non GI cancer, intestinal lymphoma. • Associations; Dermatitis herpetiformis, IDDM, Ig A def, infertility, IBD, thyroiditis, fibrosing alveolitis, hyposplenism, Ig A nephropathy.

• Lab; - Folate levels are usually normal but not B12 in coeliac disease (in Crohns both are decreased).↓Fe, Ca - CBC: Macro or micro, howel jolly bodies. - antigliadin, antiendomesial, tissue transglutaminase, antireticulin • Jejunal biopsy in coeliac disease typically shows: hypertrophied crypts of Lieberkuhn, villus atrophy, an increase in intraepithelial lymphocytes. • TTT; gluten free diet , use rice, oat, potatoes, Fe Ca, Folic supplementation, if resistant steroid.

• Dermatitis herpetiformis - manifests as a pruritic rash. - Anti-endomysial antibodies may be present. - TTT; Dapsone (diaminodiphenyl sulfone) often is used initially; sulfapyridine is substituted in patients unable to tolerate dapsone.

Tropical sprue • Cause; infection as klebsiella, E coli . • Diagnosis; history of living in tropical areas + biopsy ( as celiac but less villous atrophy, more infiltration, same severity throughout intestine. • Ttt; tetracyclin for up to 6 months, folate.

Whipple disease • Chronic multisystem dis ass with; - GIT:diarrhea, steatorrhea., wt loss, - Arthoropathy: arthralgia, migratory large joint - CNS; oculomusticatory myorrhysmia, myoclonus, tremors, extra Δ& dementia. - Lymphadenopathy. • Cause; trophoryma whipplei (G+ve bacilli) • Biopsy; PAS +ve MQ in lamina containing the bacilli. (DD M. avium) • Ttt; sutrim DS for 1 year, .

Short Bowel S • • 1. 2. 3.

4. 5. •

Causes e.g. crohn’s, mesenteric Vascular dis, trauma, bariatric surgery. C/P; Diarrhea dt bile acid, ↓transit time, bact overgrowth Lactose intolerance Enteric hyperoxaluria dt - bile acid ↑colonic permeability - FA bind Ca ↑colonic Oxalate absorption. GB cholesterol stone dt ↓ bile acid Dumping S TTT; opiate, low fat, medium chain triglycerides (MCTs), low lactose, vit replacement, int. transplantation, trophic hormones as GLP-2.

Ileal dis

Mild Bile acid diarrhoea dt bile acid induced ↑ Cl secretion from the colon Ttt; cholestyramine

Severe FA steatorrhea Ttt; low fat diet, MCT

NB; Long chain FA> 12 C require micelle formation for absorption. • Medium chain FA 8-12 C does not need micelle formation, used in ttt of malabsorption e.g. coconut oil. • Short chain FA <8C - formed by colonic bacteria - e.g. acetate, propionate, butyrate. - Nutrient to the colon, -↓ with antibiotic use Ab induced colitis & diarrhea.

Lactase deficiency; • Causes; - 2ry e.g. celiac dis. - 1ry; 15% of Caucasians, 85-100% in blacks. • C/P; Asymptomatic, bloating, abd cramps • TTT; lactose free diet. • DD; IBS.

Acute diarrhoea • <2 wks. • 90% infectious. • Toxigenic (watery); staph, B cereus , vibrio chol,.cl bot, cl perfring, E coli, • Invasive (bloody); (YES CAN CAUSE Vibrio parahemolyticus, vulnificus) yersinia, E coli, E coli o157, E hist, salm, shig, campylo, cl diff, vibrio parahemol, vulnificus, CMV colitis. • Traveler diarrhea E coli, campyl, shigella, salmonella, ttt; cipro, sutrim. • Hamburger E coli o157:H7 • Seafood vibrio, yersinia. • Fried rice B cereus. • Ttt; - symptomatic - metronidazole - cipro + culture

• Campylobacter; bloody, GBS ,ttt =erythro • Yersinia; Rt ileac, reactive arthritis, EN, myocarditis.ttt; quinolone • E coli o157:H7 HUS. • Amebic desentry metro . • Antidiarrheal should be avoided in febrile dysentery.

Chronic diarrhea • 1.

2. 3. 4. 5.

Causes; Watery; A) secretory i.e. does not ↓ with fasting, stool OG <25. e.g. stimulant laxative, toxins, resection, hormone producing tumors as VIPoma. B) osmotic; ↓ with fasting, stool OG > 50 eg. Osm laxative as Mg, PO4, lactase def, lactulose, polyethelene glycol, sorbitol. Inflammatory; pain, fever, bleeding, fecal leucocytes e.g. IBD, microscopic colitis, radiation, ischemic, malignancy. Steatorrhea; sudan III, fecal fat > 7 g/d. Dysmotility as IBS, DM, thyrotoxicosis. Factitious e.g. Munchausen, eating disorders.

NB 1) stool osmolar Gap • Measured Stool osmolarity= 290-300 mosm/kg water • Calculated= 2(stool Na +K) • Stool osmolar Gap= Measured- Calculated if < 25= secretory diarrhea 25-50= mixed > 50= osmotic 2) Prolonged fasting > 24 hrs; if diarrhea↓ osmotic (diet) if not secretory.

• Investigations for laxative abuse; 1. ↓S. K 2. Melanosis coli on endoscopy. DD; carcinoid. 3. Ba enema; loss of haustration

Inflammatory Bowel disease UC

CD

site

Colon, back flush ilitis

All GIT, perianal except rectum

Skip lesions

-ve

+ve

Macroscopic

pseudopolyps Narrow short colon with loss of haustrations

transmural Cobble stone

complications

Toxic megacolon

Fistulas, strictures

Microscopic

Crypt abcesses

Non caseating granuloma

lab

PANCA70% sens.

ASCA; 90% specific, 70% sens.

Ba enema

loss of haustrations

Cobble stone, string sign

TTT

5ASA oral or rectal Steroid rectal, oral, IV Aza or 6MP IV cyclosporin or infleximab

Antibiotics Budezonide, Steroid oral, IV Aza or 6MP, Methotrexate Infleximab, IV cyclosporin

Ulcerative colitis

Crohn’s • affect any portion of the gastrointestinal tract from the mouth to the perianal area. • Its transmural inflammatory nature

• If suspecting IBD  upper GI series with small bowel followthrough (UGI/SBFT) and colonoscopy, with biopsies. • Features diagnostic of Crohn's disease include; - evidence of small bowel involvement on UGI/SBFT, or - non-caseating granulomas. - Significant perianal disease. • Extraintestinal feature include; - EN, clubbing, Pyoderma Gang., - uveitis, episcleritis, - osteoporosis, ankylosing spondylitis, sacroiliitis, peripheral arthritis,. - gall stones, PSC, cholangiocarcinoma, - Ca oxalate urinary stone , amyloidosis, thromboembolism.

C/p; majority has bloody diarrhea and mild cramping, with minimal systemic symptoms such as fever, weight loss, and anorexia. TTT depends upon both the extent of colonic involvement and the severity of the disease process at presentation. 1. for ulcerative proctitis = topical 5-aminosalicylate (5-ASA) suppositories or steroid foams. 2. Patients with left-sided colitis often respond to topical enemas. 3. Pan colitis ( extends beyond the splenic flexure). A) mild to moderate; - oral 5-ASA or sulfasalazine + topical 5-ASA or steroid enemas . - add oral prednisone (40 to 60 mg/day) in: 1- more severe symptoms and 2- failed oral 5-ASA and topical therapy.

B) Severe active disease - pulse IV steroid, - IV cyclosporine • •

- surgery. These agents often require 3-6 weeks to exert their maximal benefit. Once remission is achieved, the drug dose can be tapered to maintenance levels of sulfasalazine (2 g/day), mesalamine (1.2 to 2.4 g/day), or olsalazine (1 g/day) .

Induction therapy of active UC Disease severity

Medication

Daily dose

Mild-to-moderate disease Mesalamine suppository

1000mg at night

Mesalamine enema

4 g at night

Hydrocortisone enema

100 mg at night

Mesalamine e.g. Pentasa

500to 1000 mg PO 4 times /d

Sulfasalazine

1-1.5 g PO four times/ d

oral 5-ASA + 5-ASA enemas/steroid enema Prednisone

40 to 60 mg PO /d

Severe active disease On steroids recently

Methylprednisolone 48 to 60 mg IV once daily Hydrocortisone 100 mg IV/ 6 hrs or IVI Cyclosporine Infliximab

Toxic megacolon

IV corticosteroids Broad-spectrum antibiotics

Chronic active disease (steroid refractory)

Mercaptopurine, Azathioprine Infliximab

Maintenance therapy in UC Disease type

Medication

Dose

Proctitis

Mesalamine suppository

1000 mg /night to /3 night

Distal colitis

Mesalamine enema

4 g /night to / 3 night

Left-sided & pancolitis

Sulfasalazine 500 mg PO four times daily Mesalamine EC (Asacol*) 400 to 800 mg PO 3 times/d Olsalazine 500 mg PO twice daily Sulfasalazine/oral 5-ASA + 5-ASA enema

Steroid-dependent colitis Mercaptopurine Azathioprine Methotrexate

50 mg up to 1.5 mg/kg PO/day 50 mg up to 2.5 mg/kg PO/day 10 to 15 mg PO once per week

• Fistulizing Crohn's; - elemental diet is as effective as steroids in induction of remission in Crohn's not in UC, better than bowel rest & TPN. - antibiotics - Aza, metho - infliximab - CAI - TPN • Oral lesions ; Aphthous ulcerations are the most common , usually occur with coexistent intestinal disease. TTT; - respond to treatment directed at the intestinal disease. - Topical therapy consisting of hydrocortisone in a carrier of pectin gelatin and carboxymethylcellulose or topical sucralfate may be effective for local symptom relief.

Antiinflammatory drugs in CD, UC;

1. 5ASA; - e.g. - sulfasalazine (sulfapyridine + 5 ASA). Side effect; oligospermia, allergic, idiosyncrasy, agranulocytosis, rash, folate def. - Enteric coated; mesalazine (Pentasa, Asacol)2-4g.

2. Steroids; for induction only not maintenance, less effective than topical 5 ASA.

Infliximab; • chimeric monoclonal antibody to TNF. • Used in; 1- refractory IBD, not fit for surgery. 2-perianal 3-RA, Psoriasis, cryo, not AS. • Dose; IV 5 mg/kg at 0, 2, 6 then /8 wks. • Side effects; - Ab to infliximabe resistance & reaction so given with Aza or methotrexate + hydrocortisone before the dose. - lymphoma. - allergic reactions, serum sickness - infection esp TB - demylenating disorders.

Surgery; • UC ileal pouch anal anastomosis (IPAAS). • Indication; intractable, fulminent, toxic, complicated, extraintestinal. • Stay the same; sacroilitis, sclerosing cholangitis, uveitis. • Improve; pyoderma, peripheral arthritis, perianal dis. • Complication; pouchitis in 1/3. C/P; diarrhea, arthralgia, fever. Biopsy differentiate bet CD & true pouchitis. Prevention with probiotics. Ttt; antibiotics. • CD; - surgical resection is contraindicated. - stricturoplasty, diversion colostomy for perianal dis - total proctocolectomy & ileostomy (but IPAAS is contraindicated dt pouch failure)

IBD & pregnancy; - sulfasalazine infertility dt oligospermia. - Fetal complication dt dis activity not medications. - Dis activity not affected by pregnancy. - But pt should be in remissionfor 6 months before conception. - CS is prefered in perianal dis. - Drugs; - 5 ASA, steroids safe but use folate with sulfas. - Aza, 6MP safe with consent. - infleximabe; propably safe.

Cancer risk in IBD; • Risk factors; duration, extent, FH, PSC, stricture, pseudopolyps, bypassed seg in CD. • Screening; after 8-10 y of pancolitis or 12-15 y of lt sided colitis  colono + biopsy/1-3 yr.

Gut Hormones • Secretin is produced by the jejunum. It relaxes the oesophageal sphincter and also stimulates pancreatic enzyme secretion. • Gastrin is secreted by the G cells of gastric antrum. It stimulates parietal cells produce hydrochloric acid. • Vasoactive intestinal peptide (VIP) promotes intestinal water and electrolyte secretion. • Chief cells pepsin. • Parietal cells HCl, intrinsic factor. • Surface cells-> HCO3, mucous.

VIPomas • VIPomas [vasoactive intestinal peptide (VIP)] . • C/P;WDHA - watery diarrhea, stool volume > 700 ml/d. - hypokalemia, N-AG acidosis - achlorhydria, + hyperglycemia , hypercalcemia in 2/3, flushing and hypokalaemia due to diarrhoea. • Treatment; correcting volume and electrolyte abnormalities by using potassium chloride and sodium bicarbonate. Octreotide controls diarrhea in 80% of cases. Glucocorticoids reduce symptoms in 50% of patients with VIPoma.

Carcinoid tumours C/P After hepatic metastasis; • Forgut cushing, acromegaly. • Midgut (ABCDEF); asthma, belly abd, cor pulm TR>TS, diarrhea, endocardial fibrosis, flushing (Carcinoid syndrome) • Bronchus; ACTH, GHRH. Diagnosis; raised urinary 5-HT levels. A precursor of 5HT, tryptophan is highly metabolised and consequently niacin deficiency (pellagra) occurs. The three D's dementia, dermatitis and diarrhoea occur. Ttt; resection, octreotides, methysergide, cyproheptadine, phenoxybenzamine for flushing.

• Glucagonoma; WARDS - wt loss - anemia - rash. NME - DM, diarrhea - thromboembolism • Somatostatinoma SSS - sugar (DM) - steatorrhea - stones GB

Constipation Types of Constipation and Causes Recent onset

•

DD;

Colonic obstruction

Neoplasm; stricture: ischemic, diverticular, inflammatory

Anal sphincter spasm

Anal fissure, painful hemorrhoids

Medications

Fe, Ca, Al HO, anticholinergics, opiates,diuretics

Chronic Irritable bowel

Constipation-predominant, alternating

Medications

blockers, antidepressants +2Ca

Disorders of rectal evacuation

Slow-transit constipation, megacolon, Pelvic floor (dysfunct,; rectal prolapse; rectocele.

Endocrinopathies

Hypothyroidism, hypercalcemia, pregnancy

Psychiatric disorders

Depression, eating disorders, drugs

Neurologic disease

Parkinsonism, multiple sclerosis, spinal cord injury

muscle disease

Progressive systemic sclerosis

Abdominal pain • -

Medical causes; alcohol, DKA, hyperlipidemia pancreatitis Hyperparathyroid, adrenal insufficiency FMF, porphyria, angioneurotic edema Lead toxicity, morphin withdrawal. Vasculitis as HSP. sickle cell an..

Ischemic colitis • • • •

Non- occlusive Rectosegmoid Elderly, bloody diarrhea& pain . XR abd; thumb printing dt mucosal & submucosal oedema. • colonoscopy; narrowing, ulceration. • Angio; not usually indicated.

Pseudomembranous colitis • Antibiotics as clindamycin, ampicillin, cephalosporin, tetracyclin flurishing of Cl difficile toxins A, B. • C/P; fever , bloody diarrhea • Diagnosis; C difficile toxin in stool. • Ttt; discontinue the antibiotic. • Give metronidazole, oral vancomycin.

Irritable bowel syndrome • C/P; pain relieved by defecation, alternating bowel habits, mucous (ROME II criteria). • Never bleeding /rectum, • Never wt loss, • Never nocturnal. • Ttt; - dietary therapy; lactose free, high fibre. symptomatic ttt.

Chronic Colonic pseudo-obstruction • • 1. 2. 3. 4. 5. 6. 7.

C/P; of mechanical obstruction but without occlusion of the lumen. Causes; Endocrinal causes; DM, hypothyroidism, hypoparathyroidism, hypoadrenalism. Neurologic; parkinsonism, ms dystrophy, MS. Rheumatologic; progressive systemic sclerosis. Infection; Chaga’s dis. Medications; TCA, clonidine, phenothiazines, narcotics Amyloidosis Paramalignant.

Colonic polyps

Non-neoplastic Neoplastic 1. 2. 3. 4.

Adenomatous (FAP, Gardner) Papillary adenoma Villous papilloma carcinoid

1. Hamartomatous (jej polyps, PJS, cowden) 2. Hyperplastic. 3. Inflammatory. (Bilh, lymphoid, pseudopol of UC) 4. C.Tissue polyps (lipoma, fibroma, leimyoma)

•

Familial adenomatous polyposis; - AD, chr 5 - > 100 polyps - 100% premalignant. - extracolonic tumours; thyroid, pancreatic, duodenal. - 1/3 has no FH. - polyps may occur in UGIT. - total colectomy should be performed as soon as possible following diagnosis. • Gardner S= FAP when extracolonic tumours predominates as osteomas, fibromas, neurofibromas, lipomas, dermoid cysts, desmoid tumours, retroperitoneal fibrosis. • cowden (1/3 has goitre,10%cancer, ¾ fibrocystic dis of breast) • Peutz-Jeghers syndrome; - AD. - dt gene mutation of the STK11 in most cases. - hamartomatous polyps + mucocutaneous melanocytic macules, perioral freckles, alopecia, nail dystrophy.

HNPCC • • • 1. 2. 3. 4. 5. •

AD, chr 2,3 Associations; other cancers; endometrial, ovarian, gastric Amesterdam criteria for genetic testing; 3 or more 1st degree family members with colorectal ca. Colon ca over 2 generations. At least 1 before<50yrs. Pt with CRC or endometrial ca below<40yrs Pt with CRC with 1st degree CRC or extracolonic ca If genetic testing +ve colonoscopy

Colorectal cancer •

Predisposing factors;

1. 2. 3. 4. 5. 6.

High fat diet, low fibre FAPC HNPCC UC, CD Adenomatous polyps Black race, male sex

•

Preventive measures;

1. 2. 3. • • •

NSAIDs High Ca diet HRT (E) C/P; include iron def anemia, sepsis with streptococcus bovis. Inv; double contrast Ba enema, colonoscopy, CEA. Ttt; resection anastomosis, abdominoperineal resection & colostomy for distal rectal tumours.

Cancer colon

Screening of colorectal cancer

• People > 50 yrs  - colonoscopy/10 yr or - occult B in stool/ y + sigmoidoscopy /5 yr.

• PH of adenoma, acromegaly  - after 1 year then /5-10 years according to the size. • PH of Ca colon,  - colonoscopy after 1 year then after 3years then /5 yr. • FH of two 1st degree relatives with colorectal cancer or adenoma or • FH of one 1st degree relative with colorectal cancer or adenoma < 60 yr.  colonoscopy / 3-5 yr beginning 10 yrs younger than the youngest affected relative. • PH of UC (8 yr pancolitis )or( > 15 yr Lt sided) - colonoscopy + biopsy /1-3 yr • FH of FAP - Colonoscopy / 1-2 yr from puberty till 40 yr old then as average. - if polyps develop or genetic test +ve colectomy. • FH of HNPCC  - colonoscopy /2 yrs from 21 yr till 40 yrs then annually thereafter.

Hematology

Anemia Hemoglobin= 13-16 gm/dl Causes of anemia according to MCV Microcytic anemia: (MCV <78 fL) Iron deficiency anemia. Thalassemic disorders. Anemia of chronic disease(late;uncommon 30% Sideroblastic anemia Copper deficiency, Lead poisoning, zinc poisoning, Al toxicity (rare) Punctate basophilia = chr lead poisoning.

Normocytic anemia: (MCV 78 to 100 fL) Acute bl loss. Hemolytic anemia. ( except thalassemia) Aplastic A. Anemia of chronic disease. 1- acute & chronic inflammation & malignancy. 2- chronic kidney disease. 3- - endocrine disease (↓pituitarism, ↓thyroidism, ↓adrenalism) Bone marrow infiltration. ( mylophthiathic An.)

macrocytic anemia: (MCV >100 fL) Megaloblastic A; - Folic acid & B12 deficiency . - others; drugs ↓DNA synthesis ( Arac, 6MP, hydroxyurea, Zidovudine, Methotrexate, Azathioprine, Capecitabine, Imatinib). Non- Megaloblastic. - CLD, Myxedema , Alcohol, MDS, Myeloproliferative, Reticulocytosis, some aplastic, sideroblastic.

Shapes of RBCs Target cell (central mass & peripheral ring of Hb) in thala, liver dis, post-splenectomy. Acanthocyte  post-splenectomy, liver dis. Schistocytes mechanical hemolysis,TMA. Tear drop cell myelofibrosis. Poikilocytosis=irregular shape. Anisocytosis=diff in size.

Reticulocytosis Hemolysis. Hge . Fe def. anemia. after starting ttt. B12 def. anemia. after starting ttt. leukoerythroblastic blood picture: presence of immature myeloid & erythroid cells in blood smear: causes 1.bone marrow infiltration with malignant cells (carcinoma, lymphoma, myeloma, leukemia) or fibrous tissue (myelofibrosis). 2.Severe hemolysis or severe hemorrhage .

Dimormphic Bl.Picture Presence of both normocytic cells & microcytic cells in blood film at the same time. Causes: combined def of fe ,B12 & folic a. (Coeliac disease). Iron def. An. treated by hematinics. B12 def. An. treated by hematinics. Iron def. An. treated by blood transfusion. Sideroblastic An.

Fe def anemia 50% of anemia. Causes; ↑demand; infant, preg, epo therapy. ↑loss; bl loss, donation. ↓intake; diet, malabs, inflammation Investigations; 1. (↓Ferritin) 2. ↓serum Fe, ↑TIBC. 3. ↓ TSAT 4. Anaemia early (normo), later (Micro) 4. ↓BM stainable Fe., ↓BM sideroblasts, n=20-40%, in Fe def <10 5. Serum transferrin receptor prot (TRP) which is released after interaction with transferrin.

Stages of Fe deficiency Fe indices

Normal

Fe deficiency anemia

MCV

NN

Micro/hypo

S. Fe (μg/dl)

50-150

<30

TIBC (μg/dl)

300-360

>400

TSAT

30-50%

<20%

S Ferritin (ng/ml)

30-200

<15

Fe deficiency anemiaearlyNN, Hb=10-13g/dl, laterMH, Hb<10g/dl.

In CKD, laboratory criteria of Iron deficiency are markedly different from those in patients with relatively normal renal function. Lab

TSAT (n=20-50%) Ferritin

Fe deficiency in Normal population <20% <15 ng/ml

Fe deficiency in CKD

<20%

<100 ng/mL predialysis < 200 ng/ml in HD This discrepancy reflect an underlying inflammatory state associated with advanced renal failure and dialysis.

TTT; Bl transfusion if;, CVS instability. 1unit packed RBCs ↑Hb 1 g/dl= 250 mg Fe. oral (Grade 1B), 200 mg elemental iron/d before meals Or IV total dose regimen= Fe sucrose(ferrosac) or dextran(cosmofer) BW x 2.3 x (15-pt Hb) . Retics ↑in 4-7 days, peak 1-2 wks. Side effects;. 1. Anaphylaxis (Fe dextran due to anti-dextran Ab). Contraindications; 1. Active infection. 2. Fe overload.

Refractory Iron deficiency anemia Wrong diagnosis. DD; 1- An of chr illness↓TIBC. 2- thalath ↑ serum Fe, Hb electroph. 3- sideroblastic  normal Fe, BM exam. Malabsorption. Chronic bl. Loss Chronic infection or inflammation Non compliance NB. Hypochromia(decreased HB) more marked in iron def. An. Microcytosis(decreased MCV) more marked in thalassemia.

An of chronic illness Causes; - chronic infection as TB - Chronic inflammation as RA, vasculitis. - Malignancy.  mechanism; ↑IL-1, TNF-α, INF-γ. leading to; defective iron mobilization from its stores, defective iron utilization by bone marrow.(IMP) ↑hepcidin release from the liver↓Fe absorption & release from stores. ↓Epo production

Sideroblastic anemia The MCV may be ↑(non megaloblastic an), ↓ or n congenital pyridoxine deficiency. Acquired: lead, alcohol, drugs eg INH. Pappenheimer iron-protein complex (sideroblastic granules) in Fe overload, hyposplenism.

Fe indices

S.Fe (μg/dl) TIBC (μg/dl)

Fe deficiency thalassemia anemia

An. Of chronic disease

Sideroblastic An.

decreas increase decrease increase increase decrease decrease Decrease

TSAT

decrease

increase decrease increased

S Ferritin

decrease

increase increased increased

MCV

decrease decrease normonor mo

variable

Megaloblastic Anemia Causes of B12 def; (the most IMP)  Gastric; gastrectomy, pernicious A.  Intestinal; bact overgrowth (bacteria consump B 12 to produce folic acid) ileal dis; resection, TB, chron’s, transcobolamin II def. Causes of Folate def;  ↓intake; - diet; elderly, alcohol. - malabsorption; tropical sprue, celiac. 2. ↑loss; A) excessive utilization, loss; - physiologic preg, lact, premature. - hemat/malig CHA, leuk, MM, carc. - inflam  Malaria, crhon’s, psoriasis, dermatitis. - HD, peritoneal dialysis. B) antifolate drugs; Alcohol, phenytoin, DHF reductase inhibitors (methotrexate, trimethoprine, pyrimethamine), sulphasalazine.

DHF reductase DHF (FOLIC ACID)

Methionine Methyl THF (Folinic acid)

Cob (B12)

THF

Methyl cob Homocysteine MM co A

-Give Folinic acid in case of using DHF reductase inhibitors as (methotrexate, trimethoprine, pyrimethamine), -Cob (B12) def lead to ↑ extracellular folate but ↓ intracellular folate. -In folate or B12 def ↑ Homocysteine & MM co A.

C/P;  Macrocytic anemia.  GIT; glossitis, diarrhea, wt loss.  Neural tube defect(in infants), SCD.  Hyperhomocystinemia.  In pernicious an other autoimmune dis ( vitiligo, MG, DM, addisson).

Investigations; Megaloblastic Anemia; CBC; RBCs ↑MCV > 100, anisopoikilocytosis. wbcs ↓n, Hypersegmented neutrophils (> 5)(it is the earliest) plat  ↓n but > 40,000. BM; RBCs large erythroblast, large nuclei, normal hemoglobinization. S. folic acid & B12. ↓ RBCs folate, high if Bl transfusion, retics. ↑ MMA , Hyperhomocysteinemia. ↑ unconj bil, LDH.(due to intramedullary heamolysis) Pernicious Anemia; ↑ s.gastrin, Antiparietal cell ab, Anti intrinsic factor ab, Check TFTs, High risk of gastric malignancy.

TTT; Cob 1000 Ug IM x 6 times in 3 wks then /3 month for life. + folate 5-15 mg for 4 months or for life or folinic acid. + kCl & aspirin during ttt response for expected hypokalemia & thrombocytosis.

Haemolytic anemia Haemolytic anemia

extracorpuscular

Intracorpuscular

congenital

acquired

Membrane defect; sphero Enzyme defect; G6PD, pyruvate K. Hb def; sickle, thalath.

PNH

immune Alloimmune Drug; Penicillin Methyldopa ,INH Autoimmune cold Ab; Mycoplasma, IMN,NHL Cold aglut dis, PCH. warm Ab; 3L & MDopa SLE, HL, CLL

Non immune

Mechanical; valve, march, TMA, burn Chemical; lead, benzene,drugs Infections; clost, malaria

Haemolysis can be intravascular or extravascular. Intravascular haemolysis: G6PD, PNH, cold Autoimmune, Non immune extracorpuscular . - bilirubin may be normal or mildly elevated. - hemosiderinuria, hemoglobinuria. - Fe loss. Extravascular haemolysis: in the reticuloendothelial system, destroyed by macrophages; warm Autoimmune & congenital except G6PD,.

Laboratory findings Evidence for Haemolysis Increased red cell breakdown:  Elevated serum bilirubin (unconjugated)  Excess urinary urobilinogin  Reduced plasma haptoglobin  Raised serum lactic dehydrogenase (LDH) Increased red cell production: - Reticulocytosis - Erythroid hyperplasia of the bone marrow - CBC; ↑MCV due to ↑retics & folic acid def. ↑nucleated cells. Specific Investigations Positive Coombs test

Hemoglobinopathies Hb A  Hb α2, ß2 (appear at 38 wks gestation) Hb A2  Hb α2, Δ2 Hb F  Hb α2, γ2 (appear at 10 wks gestation) Inheritance in hemolytic anemia; SpheroAD Pyruvate KinaseAR Thal, sickle AR G6PDx linked. Ineffective erythropoisis; thal, myelofibrosis, megaloblastic, MDS.

Thalathemia syndromes α thalath Type Silent

Gene def

Type of Hb HbA

H

Barts

1

98100%

-

2 Trait (microcyt without anemia) 3 Hb H (severe an) Hydrops 4

85-95% rare

70-95% 5-30%

-

Hb

MCV

-

15

90

-

12-13

70-80

6-10

60-70

5-10% 90-95% fatal

fetalis Hb H is diagnosed by staining RBCs with brilliant Cresel Blue . α thalath is diagnosed by globin chain synthesis assay not by Hb electro

ß thalath (10-15% of med & asia, 0.8% of africans) Type

Genetic abn

ß thalath major Homozygous.

C/P

TTT

-During

-Need Bl transf for survival -Folic acid -splenectomy -pneumovax vaccine

childhood -Hemosiderosis due to Bl transf

ß thalath intermedia

Homozygous. -As major - May survive + persistant fetal Hb or -Hemosiderosis. without Bl transfusion α thal

ß thalath minor Heterozygous.

Micro/hypochr< 75 Fl, Hct<30%,↑Hb A2 or F (3.57.5%)

-

Co-inheritance of α & ß thal trait ↓precipitated globin chain  ↓ severity of anemia. -TTT; repeated trans. Of packed RBCS 1. Desferoxamine before 5-8 yrs in thal major; side effects; deafness, cataract, yersinia, mucormycosis. 2. BM transplantation 3. Gene therapy.

Sickle cell dis

1. 2. 3. 4.

Abn Hb due to subst of glutamine by valine at position 6 from N terminal of beta chain. Types; Hb SS; homozygous (Sickle cell dis), sickle at PO2 5-6 KPa. Hb AS; hetezygous (Sickle cell trait) sickle at PO2 2.5-4 KPa. Hb SC; sickle at PO2 4 KPathrombosis, avascular necrosis, retinopathy & fetal loss. Hb S thal.

C/P;  Thrombotic stoke.  Acute chest S.  Splenic infarction ( hyposplenism) , mesenteric

vascular occlusions,Protected from malaria.  Kid; RTA, DI , Interst. Nephritis, FSGS, papillary necrosis, renal infarction, RCC.  Priapism.  Fetal loss.  Avascular necrosis, sickle dactilitis, osteomyelytis (salm, staph,Klebs). Gout, pseudogout, osteoarthritis.  Leg ulcers.  Proliferative retinopathy.

Diag; Hb electropheresis, sickling test (Na bisulfite test) turbidity in Hb s only. Diag of AS (trait) by Avascular necrosis & isothenuria. ttt; hydroxyurea, transfusion in aplastic or sequestration crises, exchange transfusion in sickle crises till Hb S<30%.in ……

Hb SC patients are more prone to proliferative retinopathy and chest crises, but otherwise run a more benign course than SS and have correspondingly better survival. Hb E; α2ß2 (26 glulys) is the most common Hb in south east asia & 2nd most common variant worldwide; - Hb E hetero microcytosis, no anemia. - Hb E homo mild microcytic anemia.

Spherocytosis AD May present in adultJaundice, Spl, Gall stones. Diagnosed by bl film & osmotic fragility. Ttt; splenectomy, folic acid, Bl transfusion.

G6PD; - Intravascular hemolysis upon exposure to; fava beans,

infections, drugs as; 1-antimalarials; primaqine, Dapson, chlorproguanil. 2-sulfa; s.methoxazole, dapson. 3- ab; nalidixic acid, nitrofurantoin,quinolones. 4- analgesic; phenazopyridine. Others; naphtalene, methylene blue. - Enzyme test done in between attacks as retics has higher enzyme level. Pyruvate kinase; 1:10.000 in newborn or delayed. extravascular hemolysis, Spleen. ttt=folic acid, bl transf, , BM transpl Heinz bodiesprecipitated globin chain in G6PD.

Paroxysmal nocturnal hemoglobinuria (PNH) Def; Red cell memb defect that render it liable to complement mediated lysis. Affected cell does not express glycosyl phosphatidyl inositol (GPI) & Decay accelerating factor (DAF) which degrade complement. Triad; intravascular hemolysis. pancytopenia or bicytop. thrombosis. Incidence; 1/million. C/P; morning hematuria, recurrent abd pain, budd chiari, aplastic an,… AML. Inv; - may be microcytic - BM; hypercellular+/-dyserythropeitic feature - flow cytometry – CD55,59 - sucrose hemolysis test & Ham test are unreliable. ttt; BM transpl, eculizumab (anti C5 A), if AA ATG & cyclosporine.

PCH; - rare, children, viral infection.IGg - diagnosed by; Donath-Landsteiner Ab test . Cold Agglutinin dis; - Elderly - React only at low temp - Ig M in high titre, regarded as waldenstrom or low grade B cell lymphoma. - Ttt; rituximab.

Treatment of Autoimmune hemolytic anemia. corticosteroids (Grade 1B) For patients not responding to corticosteroids, or for those who require large doses of corticosteroids to maintain their response, we suggest elective splenectomy (Grade 2B). For patients unwilling or unable to undergo splenectomy, we suggest the institution of immunosuppressive or cytotoxic agents (eg, azathioprine, cyclophosphamide, cyclosporine, rituximab) (Grade 2C). IVIG is sometimes effective in the treatment of autoimmune hemolytic anemia refractory to conventional therapy with prednisone and splenectomy

Aplastic anemia Aplastic anemia is due to injury to the pluripotent stem cell.

Causes  

Congenital; fanconi An. Acquired; Idiopathic. irradiation drug induced, benzene, chemo, chloramph, phenylbutazone, carbamazepine. viral infection; EBV, HIV, Parvo, hepatitis. Immune; SLE, Thymoma, GVHD. pregnancy PNH

C/P; - bleeding secondary to thrombocytopenia, - fatigue and pallor due to anemia, - fever and bacterial infections resulting from neutropenia. - No Spleen, or LN. - Short stature, café au lait patchesfanconi. Inv; - pancytopenia, ↓retics. - BM; fatty pale hypocellular of all three cell lines.  Fate relapse, MDS, leuk, PNH.

Treatment - withdrawal of offending agents (if any), - supportive care, Blood and platelet transfusions

(keep Hb > 7, Plat> 10.000). Any blood products should be irradiated and CMV-negative, and should not be from family members. - Hematopoietic cell transplantation (HCT) - intensive immunosuppressive therapy (antithymocyte globulin, cyclosporine, prednisone and recombinant human G-CSF or GM-CSF, sutrim )

Pure red cell aplasia (PRCA) Def; ↓Hb, ↓retics, BM= rare erythroid precursor cells. Causes; congenital; Diamond-Blackfan S. Acquired; - idiopathic. - thymoma - drugs; Epo, chloramphenicol, phenytoin, Azathioprine. - viruses; Parvo in IC, HTLV1, EBV, hepatitis. - CT dis; SLE, RA. - pregnancy. TTT; steroids & other immunosuppressant.

-

Parvo B 19; In children 5th dis. In adult polyarthralgia, repeated abortion. In CHA aplastic crises. In IC PRCA, diagnosed by BM………. giant pronormoblasts. PCR from Bl. Serology (but Ig G & M are commonly absent), ttt by IVIG for 5 days. & symptomatic

Major causes of pancytopenia 1. With hypocellular BM

Aplastic anemia.Others, aleuk leuk, lymphoma & fibrosis of BM. 2. With hypercellular BM 1ry; MDS, Megaloblastic, Myelophthysis, PNH, hairy cell L. 2ry; SLE, sepsis, hypersplenism.

Myelodysplastic syndromes

Def; dysmorphic cellular BM, ineffective erythropoiesis, peripheral cytopenias. C/P; old ♂, Spleen in 20%. Cause; cong; Down, FH. acq; irradiation, benzene, chemo. Invest; Bl. Pic. RBC=↑MCV, dysmorphic. wbc=↓granules, abn segmentation. plat=large, ↓granules. BM (↑cells) erythroid=Megaloblastoid (large nuclei, ↓Hb)+/TTT; stem cell transplantation immunosuppressant (linalidomide) G CSF, Epo. Classification; only reading RA =refractory anemia, RARS =refractory anemia with ring sideroblast, RCMD= refractory cytopenias with multilineage dysplasia RAEB= refractory anemia with excess blasts.

Hypersplenism Any cause of splenomegaly ……> pancytopenia , bicytopenia or monocytopenia Hereditary hemolytic anemias. Autoimmune cytopenia. Infection. (SBE, IMN, Malaria). Inflammation. (Felty). Infiltation. (amyloid, Gaucher, glycogen storage). Congestion. (Budd Chiari, CHF, LC, PVT).

Hyposplenism

This peripheral blood smear shows; Howell-Jolly bodies in two red cells (black arrows), Howel Jolly bodies  remnant of nuclear mat removed by the spleen. aim cells are also seen (blue arrows), another consequence of splenectomy.

Hyposplenism Diseases cause these appearances A : Amyloidosis, asplenia P: post splenectomy, post irradiation. C: Sickle , collagen, celiac, crhon’s, UC. D : dermatitis herpetiform. E : Essential thrombocytosis. Subjects with functional asplenia may show any of the following:

Mild degrees of thrombocytosis and leukocytosis. target cells, acanthocytes. Howell-Jolly bodies in circulating red cells Heinz bodies (precipitated globin chain,also in G6PD).

People with an absent or dysfunctional spleen are prone to infections from encapsulated organisms such as Streptococcus pneumonie, Haemophilus influenzae and Neisseria meningitides. They are also prone to Capnocytophaga canimorsus, a gram-negative bacillus which is present in the mouth of dogs. rapidly fatal. Protozoal illness like Falciparum malaria and babesiosis. The risk can be reduced by vaccination strategy, prophylactic antibiotics and health education.

blood lymphocytes 1.5-3.5.000 20-40% of WBCs

T-cells 60 to 80 %

Helper T-cells 60 to 70 % (CD4+ cells)

B-cells 10 to 20 %

Suppressor/ cytotoxic T-cells 30 to 40 % (CD8+ cells).

natural killer (NK) 5 to 10 %.

Causes of lymphocytosis Infections Viral Infections (EBV) , (CMV) , Mononucleosis syndrome (adenovirus type 12, herpes virus-6),Mumps, varicella, influenza, hepatitis, rubella, Infectious lymphocytosis (Coxsackie virus B2, enteroviruses including poliovirus) Bacterial Infections; Pertussis, tuberculosis, brucellosis. Protozoal; Toxoplasmosis & Babesiosis.

Malignancy; CLL,ALL, NHL,

lymphocyte counts >20,000/µL...referal.

Stress-induced lymphocytosis;Post trauma ,Post splenectomy Autoimmune;Rheumatoid arthritis Endocrine; Hyperthyroidism, addison.

Lymphocytosis (>4000/cmm) Reactive lymphocytosis medical conditions associated with lymphocytosis in which lymphocyte count normalizes within <2 months after resolution of this condition. Examples are viral infection and pertussis.

Malignant lymphocytosis refers to an acute or chronic lymphoproliferative disorder as CLL, ALL.

Atypical lymphocytosis; IMN, CMV, Hepatitis, NHL, leuk. Neutropenia with relative lymphocytosis; IMN, CMV, Hepatitis, Typhoid, TB, brucellosis,

agranulocytosis.

Lymphopenia 1.HIV. 2.Legionaire disease. 3.Steroid therapy , cytotoxics. 4.Hodgkin L. 5. Congenital immune def.

Monocytosis(>1000/cmm) n= 200-800 Infections: Viral Infections (EBV) , (CMV), Mononucleosis syndrome (adenovirus type 12, herpes virus6) Bacterial Infections; Typhoid, tuberculosis, brucellosis, IEC Protozoal Infections Toxoplasmosis, malaria, leishmania, trypanosomiasis. Chronic Inflammation : RA, UC, sarcoid. Heamatological malignancies: Acute monocytic leukemia, chronic myelogenous leukemia, Hodgkin lymphoma , MDS.

Neutropenia (<1500/cmm) n= 2000- 7.500 40-80% of WBCs severe < 500/microL.(agranulocytosis). The risk of infection begins to increase at an ANC below 1000/microL.

Causes of neutropenias( re. pancytopenia) Postinfectious neutropenia — the most common cause of acquired isolated neutropenia e.g. viral, typhoid. Drug-induced neutropenia & agranulocytosis; the second most common cause of neutropenia, Including ( clozapine, antithyroid,sulfasalazine) Primary immune disorders as SLE, Felty. Hypersplenism Nutritional deficiency ; Alcoholism , Vitamin B12 or folate deficiency Bone marrow disorders ; aplastic anemia, the leukemias & MDS. familial.

Effect of neutropenia pyogenic or enteric bacteria or certain fungi. from the skin and from the gastrointestinal and urinary tract. does not increase the susceptibility to viral or parasitic infection. Common sites of infection include the oral cavity and , the skin, genital areas & lung.  bacteremia patients with ANC of less than 500/microL  admit & give parenteral antibiotics. Neutropenic fever = fever > 38 measured 3 times/24h in a neutropenic patient . TTT ; broad spectrum b lactam Ab with antipseudomonus (ceftazidine) +/- vanco or Tienam , antifungal if fever persists after 7 days.

Neutrophilia Infections : Bacterial, fungal. Inflammation : gout, RA, UC, crhon’s,vasculitis, uremia, R fever, preeclampsia. Infarction ; PE, MI, sickle crises. Trauma; surgery, burns. Physiologic ; preg , exercise. Drugs ; steroids . BM emergency; bleeding , hemolysis . Myeloproliferative; CML, PRV, MF, ET. Malignancy; AML, CML, HL.

Leukomoid reaction excessive or reactive leuckocytosis. ↑TLC simulating leukemia usually not > 50.000. blast cells never > 5%. Shift to the left = ↑staff cells. Leucocytic Alk phosphatase ↑↑ due to mature WBC. The leukocyte alkaline phosphatase (LAP) is high in; 1. infection, 2. inflammation, and 3. polycythemia vera (PV) low in; 1. chronic myelogenous leukemia (CML) 2. paroxysmal nocturnal hemoglobinuria

Eosinophilia (>500/cmm) n= 20-500 ALLERGIC DISORDERS . commonly from atopic conditions and drug reactions.  Skin;contact, eczema, urticaria, dermatitis herp.  Resp; Allergic rhinitis & Asthma. Drug-induced eosinophilia; NSAIDs, Dantrolene ,gold, antimicrobials , tetracyclines, minocycline, sulfonamides penicillins, cephalosporins , Nitrofurantoin. and ampicillin Allopurinol, phenytoin ,) are the most common.

Other causes of eosinophilia; Infection; helminthes. Systemic dis; Adrenal insufficiency, Atheroembolic disease , celiac dis. Churg- Stauss S. Hematologic & neoplastic disorders; CML, eosinophilic leuk, HL, histiocytosis, Hypereosinophilic syndrome, Mastocytosis.

pulmonary eosinophilia  Extrinsic; Loafler pneumonia(Ascaris, toxocara, strongyloid. Tropical pulmonary eosinophilia —filaria, ABPA. 2. Intrinsic;. Chronic eosinophilic pneumonia; Churg- Stauss S. Idiopathic hyperesinophilic S.

Hypereosinophilic syndrome marked peripheral eosinophilia > 1.500 for > 6 months and involvement of multiple organs such as the heart, gastrointestinal tract, lungs, brain, and kidneys. Some cases are myeloproliferative disorders as eosinophilic variants of CML, or T cell lymphomas that produce large amount of IL-5. TTT; steroids, hydroxyurea. Chronic eosinophilic pneumonia; cough, fever, progressive breathlessness, weight loss, wheezing, predominantly in women and nonsmokers; following radiation therapy for breast cancer. CXR "photographic negative" of pulmonary edema is pathognomonic for the disease but found in <1/3of cases

Mastocytosis — Systemic mastocytosis is charact. by proliferation and accumulation of mast cells in various organs including the skin, liver, spleen,LN Patients present with organomegaly, hematologic or cutaneous abnormalities.bl. eosinophilia in up to 20 %.

1. 2. 3. 4. 1. 2. 3. 4.

1. 2.

Myeloproliferative disorders; CML PRV Essential thrombocytosis. Myelofibrosis Lymphoproliferative dis; CLL Hairy cell leuk Prolymphocytic leuk Lymphomas Immunoproliferative dis = monoclonal gamopathies= plasma cell dyscrasias; Benign (MUGS). Malignant; MM, plasmacytomas, waldenstrom, heavy chain dis, cryo, amyloid, lymphomas.

Polycythaemia Polycythaemia A)True = ↑ RC mass

1ry =PRV

↑ plat, TLC, LAP, B12, ↓epo Normal O2

B) Relative =normal RC mass & ↓ plasma volume 2ry to;

Hypoxia; altitude, COPD, cyanotic HT dis,Hb F. ↑epo; hydroneph, renal cysts, RCC, tumors as liver, uterine, cerebellum. cushing

↑ epo, ↓O2

PRV Criteria for diagnosis of PRV; 3A or 2A + 2B. A1=RC mass > 36ml/kg

↑plat

A2= normal ABG

↑WBC

A3= splenomegaly

↑NAP ↑B12

•C/P HTN, pruritis, thrombosis, PU, gout, 10% AML. •ttt; venesection, hydroxyurea, aspirin.

CML Middle age, male, massive spleen, tender sternum. Visual dist, priapism, deafness. TLC=100-500.000, Myelocytes, < 5% blast. Basophilia, esinophilia. ↑B12 (due to transcobolamin 1 released from neutrophils, but bind cob tightly, does not enhance tissue utilization). ↓NAP. 90% philadelphia chr t(9:22) +ve (good prognosis), bcr-abl gene in 5% of ph-ve cases. Ttt; Imatinib inhibit the abn tyrosine kinase produced by bcrabl gene, induce phil –ve haematopoisis, BMT. Hydroxyurea & Myleran (busulfan)↓count but does not modify the cytogenetics. FU by PCR for bcr-abl gene.

Thrombocytosis

normal platelet count =150,000 to 450,000/microL. Thrombocytosis defined as a platelet count >500,000/microL. reactive or a marker for the presence of a hematologic disorder.

1ry essential THROMBOCYTOSIS - Plat count > 0.6 million - C/P; hge (plat dysfunction), thrombosis,

hyposplenism (due to splenic infarcts) - TTT; if asymtomatic  no ttt. young,high riskanagrilide thrombosisAspirin. life threatening plasmapharesis, N2 mustard single dose.

REACTIVE THROMBOCYTOSIS much more frequent than essential thrombocytosis The causes of RT include:  Chronic Infection; osteomyelitis, TB  Malignancy; HCC, myeloproliferative  inflammatory conditions; RA, vasculitides , IBD.  Hge, hemolysis, surgery, Acute pancreatitis .  Iron deficiency .  Drugs; Vincristine, Epinephrine, steroids  Postsplenectomy state.

BM fibrosis

1ry = Myelofibrosis

2ry = Myelophsisic 1. 2. 3. 4.

Tumors; br, lung, prost Infections;TB, fungal,HIV Sarcoid, Gaucher, osteopetrosis Hemat; CML, MM, lymph, hairy cell

Path; BM fibrosis leukoerythroblastic blood picture-pancytopenia, dry tap of BM. ineffective erythropoesis. extramedullary erythropoesis CBC; RBCsnucleated, tear drop cells wbcs ↑myelocytes, promyelocytes & myeloblasts. plat giant.

Acute leukemia Wbcs=20-100.00, > 30% blasts.

ALL; - children - CNS involv common…. Methotr & CNS irrad - immunophenotyping T & B - CytochemestryPAS +ve. - >60% cure rate after chemo . - poor prognostic factors; age<2, >10, TLC >100, plat<25, L3-CNS infilt, ♂, cytogenetic abn, Tcell, response to ttt.

AML; - adult. - CNS involv uncommon. - morphologyM0----M7.

-

M0 undiff , M1minimal diff , M2 diff M3 promyelocyt, M4 Myelomonocytic, M5 mono, M6 erythroblastic, M7 megakarioblastic. Cytochemestry sudan Black, esterase. M3DIC during ttt, prevented by retinoic acid, Auer rods, t (15;17)RARA, ATRA, FFP, plat,good prognosis M5= gum hyperplasia. M4,5monocytosis. ttt; AraC . 80% remission, 30% cure rate.

immunophenotypingCD on lymphocytes e.g. CD10,19,

Cytogenetics (chr abnormality); sig; - markers of the dis, if relapseBM transpl. - prognostic, if good conventional ttt, badtransp. ALL  philad chr t(9;22) in ¾ of cases bad prognosis. CMLphilad chr t(9;22) good prognosis. AML; t (8,21)M2 good prognosis. t (15:17)M3 good prognosis.

CLL Commonest cause of lymphocytosis in elderly. 95% B cells, 5% t cells (poor prognosis). May confirm diagnosis by immunophenotyping from blood. May be associated with;….Richter lymphoma. - monoclonal gammopathy 5%. - hypogammaglob infection with encapsulated org. - AIHA 10%, AI thrombocytopenia 2%. Stages; A lymphocytosis& < 3 B; > 3 groups of LN. C. cytopenia.9BM failure Ttt indicated for; stage c, bulky dis > 10cm, short lymphocyte doubling time < 6 mth, disabling B symtoms.  chlorambucil or fludarabine + sutrim for pseudomonus prophylaxis. Ttt of cytopenias. Most common cause of death is infection.

Hodgkin lymphoma Lymphoproliferative dis, prognosis depend on; 1. Bulk of the dis; >10cm LN mass=bulky. 2. Staging;(1-4)A or B according to B symptoms. B symptoms= F, sweats, wt loss. NB; pruritis, abd pain are not B symtoms. -Stage 11 group of LN -Stage 22 group of LN, same side of diaphragm. -Stage 3LN on both side of diaphragm ( the spleen is considered a LN, not extranodal). -Stage 4extranodal 3. Histopathological type; Lymphocyte predominant best prognosis. Lymphocyte depleted worst. Nodular sclerosis most common 2/3 of cases. Mixed picture more extranodal;

C/P; age peak; 15-34 yrs. Investigations; -CBC; Neutrophilia, esinophilia, monocytosis, early lymphocytosis but no basophilia. - FU by LDH. - Staging clinically & CT +/- PET scan. No need for staging splenectomy with available imaging. TTT; early radio. late chemo ABVD (adria, bleom,vinblast,dacarbazine; MOPP (mustine or chlorambucil= less vomiting, onco, procarb, prednizone)  side effect; sterility, leukemogenic.

NHL T cell lymphomas makes up to 10-20% of NHL & have worst prognosis. Divided clinically acc to maturity of cells into; Low grade

High grade

Mature cells

Immature, rapidly progressive without ttt

Older age

Any age

More bone marrow involv

Less bone marrow involv

Less curable.

40% cure rate

Radio for stage 1 Chlorambucil for diffuse dis. IFN

CHOP monthly for 6 courses (cycloph, hydroxvdaunorubicin, oncovin, pred)

Gammopathies = diseases of γ globulins =immunoglobulin overproduction

Alb.= 3.3- 4.7 g/dl. α1 glob.=0.1-0.4 g/dl. α2 glob.=0.3-0.9 g/dl. ß2 glob.=0.7-1.5 g/dl. γ glob.=0.5-1.4 g/dl.

Monoclonal Gammopathy Polyclonal Gammopathy Due to proliferation of many B cell clones e.g. CLD, Chr. Inflammation, infection.

= Plasma cell dyscrasias =immunoproliferative diseases Due to proliferation of a single Clone of Ig-forming cells that produce homogenous excess of light, heavy chains or complete IG molecule. (M-protein, where the "M" stands for monoclonal).

MM

1.

2. 3.

Def; a malignant plasma cell tumour distributed at multiple sites of BM Most frequent hematologic malig (10%). Most common cause of death is infection. 5 yr survival 25%, 2 yrs from diagnosis. Cytokines released by MM cells; IGF1, IL-6, VEGF. Classification of plasma cell neoplasms; Symptomatic; monoclonal prot > 3 g/dl & plasma cell in BM > 10%, end organ damage (CRAB= ↑Ca, renal failure, anemia, bone osteolytic lesions). Asymptomatic; monoclonal prot > 3 g/dl & plasma cell in BM > 10%, but no CRAB, no ttt, progress in 20%/yrs. MUGS monoclonal prot < 3 g/dl, remain stable for long period, other Ig are normal & plasma cell in BM < 10%, but no CRAB, no ttt, progress in 2%/yrs.

Criteria for diagnosis of MM;(3 major or 1major & 1 minor) Major

Minor

BM plasma cell > 30%

BM plasma cell 10- 30%

Monoclonal Gammopathy (Ig Monoclonal Gammopathy (Ig G > 3.5, IgA >2, urine >1 g/24 G < 3.5, IgA <2, urine <1 g/24 h) h)

Plasmacytoma (tissue biopsy) Normal other Ig

Osteolytic lesions

C/P;  C; ↑Ca,  renal ; - Tubular; cast nephropathy, infiltration, ↑Ca, ↑uric C, contrast, nephrotoxic Antibiotics. - glomerular; hyperviscosity, cryo, amyloid, LCDD.  anemia, pancytop, infection  bone osteolytic lesions, pathologic fractures, soft tissue mass Others; hyperviscosity, PN, AN.

lab CBC; anemia, pancytop. ↑Ca, ↑P, normal Alk P. ↑TP, ↓Alb, ↑uric acid. Bone scan=normal, bone XR survey. ↑ B2 microglobilin (prognostic factor). Detection of monoclonal LC ( Lamda), most common Ig G> Ig A. Ig M. I. Serum protein electrophoresis May not pick up small bands or bands outside of the gamma region II. Urine protein electrophoresis Both serum and urine should be tested to increase detection to 95% III. Immunofixation A .detection of monoclonal protein after the proteins are separated by electrophoresis B. More sensitive than electrophoresis (detection limits 150-500 mg/L) IV. Serum free light chains (FLC) assay A. Most sensitive (detection limit of 0.5 mg/L) B. Assay does not detect monoclonality of the light chain but rather an abnormal ratio of kappa versus lambda (for AL amyloidosis FLC is 91% sensitive vs 69% with serum immunofixation and 83% for urine immunofixation) C. Sensitivity is 99% when FLC is combined with serum and urine immunofixation 1. 2. 3. 4. 5. 6.

1. 2. 3. 4. 5.

Poor prognostic factors; Old age. Ig A isotype Chromosomal abn. Hb <10, ↑ s. creat, LDH, CRP, B2 microglob. ↓Alb.

V. Treatment A. Restore intravascular volume B. Remove offending agents and nephrotoxic drugs . Hypercalcemia i. Volume repletion ii. Bisphosphonates in refractory cases. C. Reduce light chain levels 1. Chemotherapy i. Thalidomide plus dexamethasone, or ii. Bortezomib plus dexamethasone iii. Melphalan/pred, VAD. 2. D. Stem cell transplantation +/- kidney transplant is an option in selected patients.

Waldestrom’s macroglobulinemia a malignancy of lymphoplasmacytoid cells that secreted IgM. The light chain isotype is kappa in 80% of the cases. like myeloma; secret IgM, involves the bone marrow, In contrast to myeloma, Kappa LC in 80%, LN, HSM, hyperviscosity syndrome, no bone lesions or hypercalcemia, the size of the IgM paraprotein results in little renal excretion. Therefore, renal disease is not common. C/O; weakness, fatigue, and recurrent infections, epistaxis, visual disturbances, and neurologic symptoms such as peripheral neuropathy, dizziness, headache, and transient paresis . O/E; LN, HSM, fundus  vascular dilatation &engorge of the retinal veins Inv; normocytic, normochromic anemia, rouleaux formation and a positive Coombs' test.10% of macroglobulins are cryoglobulins. TTT; serious hyperviscosity symptoms  plasmapheresis, Rituximab, bortezomib and lenalidomide median survival is >3 years.

Bleeding tendency 1. Platelet defect; Thrombocytopenia Decreased platelet production ; viral infections, chemotherapy , radiation therapy, congenital, Vitamin B12 and folic acid deficiency, Myelophthysic. Increased platelet destruction; ITP, SLE, post-transfusion, TMA , drugs, Hypersplenism. Thrombathenia;  Hereditary defective adhesionBernard soulier. defective aggreg  glansman defective adhesion VWD.  Acquired; aspirin, uremia. Thrombocytosis (essential) 2. Coag factor defect; cong; hemophilia A, B, VWF. acquired; Ab mediated, CLD, Vit K def, drugs; anticoag, thrombolytic, DIC. 3. ↑Fibrinolysis; cong; PAI-1def. 4. Vascular; cong; HHT, EDS. acquired; palpable (vasculitic), non palpaple

Purpura 1. Thrombocytopenia Decreased platelet production ; viral infections, chemotherapy , radiation therapy, congenital, Vitamin B12 and folic acid deficiency, Myelophthysic. Increased platelet destruction; ITP, SLE, post-transfusion, TMA , drugs, Hypersplenism.

2. Thrombathenia; 



Hereditary defective adhesionBernard soulier. defective aggreg  glansman defective adhesion VWD. Acquired; aspirin, uremia.

3. Vascular purpura; palpable (vasculitic); HSP, cryo, Small vs vs. non palpaple; traumatic; senile, steroid, scurvy, easy bruising. inflammatory; sepsis, purpura fulminans, meningococ . hematologic Malig; drug reaction embolic; atheroemb, fat emb.

Thrombocytopenia Decreased platelet production     

bone marrow suppression by; viral infections (eg, rubella, mumps, varicella, parvovirus, HCV, and EBV). Decreased , live attenuated measles vaccination. Following chemotherapy , radiation therapy or drugs as thiazide, alcohol, E. congenital or acquired BM aplasia, such as Fanconi anemia & (TAR) syndrome. Vitamin B12 and folic acid deficiency. Myelophthysic.

Increased platelet destruction Immune mediated; ITP, SLE, post-transfusion due to anti-platelet Abs Consumption; TMA (TTP, HUS, DIC, APA , HELLP syndrome), Certain drugs, heparin, quinine, quinidine, and valproic acid Hypersplenism.

Dilutional thrombocytopenia — post transfusional with packed RBC so give platelet concentrates to patients receiving > 20 units of packed RBC in a 24 hour period.

Pseudothrombocytopenia  inadequate anticoagulation of the blood sample .  EDTA- dependent agglutinins which can lead to

platelet clumping and spurious thrombocytopenia

inherited thrombocytopenia Bernard-Soulier syndrome — The BernardSoulier syndrome is an autosomal recessive disorder presenting with mild thrombocytopenia, circulating "giant" platelets, marked platelet dysfunction, and bleeding. Wiskott-Aldrich syndrome — is a rare X-linked disorder which presents as a clinical triad of immunodeficiency, eczema, and moderate to severe thrombocytopenia with small (3 to 5 fL) platelets. TAR $

Drug induced thrombocytopenia Heparin Valproic acid Gold salts Quinine and quinidine Trimethoprim-sulfamethoxazole &other sulfonamides Interferons Nonsteroidal anti-inflammatory drugs (NSAIDs) Penicillin Ranitidine Measles-mumps-rubella vaccine Glycoprotein IIb/IIIa inhibitors (eg, abciximab) Diuretics.

Diagnosis of HIT Diagnosis of HIT depends on: 1. History of heparin administration for > 5 days. 2. Exclusion of other causes of thrombocytopenia. 3. Demonstration of HIT antibodies. TTT lepirudin (Refludan®) (Thrombexx®) 0.05 mg/kg (3 mg in total)

Idiopathic thrombocytopenic purpura (ITP) There are only two criteria required for making the diagnosis of ITP: 1. Thrombocytopenia, with an otherwise normal complete blood count and white blood cell differential, including a normal peripheral blood smear 2. No clinically apparent associated medical condition(s) or medications that may cause thrombocytopenia

Treatment Treatment should be restricted to those patients with moderate or severe thrombocytopenia with bleeding symptoms. Patients with mild, asymptomatic thrombocytopenia, discovered incidentally on a routine blood count, should not be treated. 1. glucocorticoids either prednisone (1 mg/kg per day PO) or dexamethasone 2. In patients with persistent symptomatic and severe thrombocytopenia (ie, a platelet count <10,000/microL) after initial treatment with glucocorticoids, or in those whose disease relapses after their withdrawal IVIG, or splenectomy (Grade 1B). 3. Refractory cases: Rituximab.

4. If life-threatening bleeding   Platelet transfusions,  IVIG at a dose of 1 gm/kg IV, repeated the following day if the platelet count remains <50,000/microL, Pulse methylprednisolone at a dose of 1 gm IV, repeated daily for three doses .  IV recombinant human factor VIIa.

C/P; spont, bl per orifices plat defect. deep, trauma coag f . Invest; 1. PT, PTT, plat count; - if ↑ PT only factor 7 def. - if ↑ PTT only with bleeding hemophilia, VWD. without bleedingfact 12 def. thrombosis lupus anticoag. - if ↑ PT, ↑ PTT vit K def, oral anticoag. - if ↑ PT, ↑ PTT, ↓plat  CLD, DIC. if ↑ PTT, ↓plat  lupus anticoag - if all normal thrombathenia. 2. Bleeding time; - if normal factor 13 def, HHT. - if high  plat funct tests. 3. Platelet function tests. Restocitin test test adhesion. ADP aggregation test test aggreg. Collagen aggregation test  test for plat release.

PRINCIPLES OF COAGULATION

-

citrate LMWH Direct thrombin inhibitors

(Fischer, Hemodialysis international, 2007)

-

-

anti Th III + heparin & indirect thrombin inhibitors

Hemophilia

1. 2. 3. 4. 5.

A= factor 8 def; synthesized by the liver, spleen, kid, placenta, carried in the circulation non covently to VWF. B= factor 9 def. XLR. C/P; deep hematoma, hemoarthrosis after trauma. Diag; ↑APTT, ↓factor 8 or 9. TTT; FFP Coag factor conc. factor 8 conc. DDAVP; ↑ factor 8 & VWF. Education, physiotherapy, vaccination.

VWD AD Female, menorrhagia. Bleeding dt coagulation defect & platelet defect. Inv; ↑PTT, bleeding time. TTT; factor 8, cryoppt, FFP.

DIC

1. 2. 3. 4. 5. 6. 7. 8.

Def; intravascular fibrin deposition due to activation of coag factors. Causes; Sepsis Malig. Obstetric; dead fetus, abruptio, septic abortion, amniotic fluid embolism. trauma; rabdomyol, fat mbolism, burn. Vascular; giant hemangioma. Immunology; acute hemolytic transfusion react, GVHD, transp rejection. Liver dis; acute fatty liver of preg. Drugs; fibrinolytics, warfarin, amphetamines.

1. 2.

1.

3. 4.

Chronic DIC; giant hemangioma, malignancy, dead fetus, LC. Invest; ↑ PT, ↑ PTT, ↓plat, ↑FDPs, ↑D dimers. DD; severe CLD; fact 8 is synthesized by spleen, kid so does not ↓ in CLD. TTP/HUS normal clotting factors & no fibrinolysis. TTT; if no bleeding  Ttt of underlying cause only. Control bleeding by; (target PT, PTT < 1.5 normal, fibrinogen > 100 mg/dl.) - FFP ( 1 U ↑ coag F 3%, dose 5-10 ml/kg) - cryoppt (fibrinogen, 8, VWF/ dose 10 U/2-3 FFP) - plat 1-2 U/10Kg. prot C conc. Fibrinolytic inhibitors; tranexamic acid (in bleeding & ↑ FDPs, APA, giant hemangioma).

Antithrombotic drugs

Antiplatelets

Anticoagulants

1) Aspirin Oral 2) anti ADP receptors Coumarin derivatives (clopidogril [plavix®], ticlopidine) 3) GPIIbIIIa antagonists (Abceximab, Tirofiban [Agrastat®]) 4) Anti Phosphodiesterase; Indirect Dipyridamol [Aggrenox®] thrombin inhibitors

Heparin LMWH e.g. enoxaparine Heparinoid e.g. Danaparoid Fondaparinux [Arixtra®] (Harrison's PRINCIPLES OF INTERNAL MEDICINE, 2008)

Fibrinolytics

IV

- strep., urokinase, - Anistreplase - alteplase

Direct thrombin inhibitors Lepirudin (Thrombexx®) Argatroban Binalirudin

Causes of Hypercoagulable states Inherited Factor V Leiden mutation 40 to 50 % Prothrombin gene mutation Protein S deficiency Protein C deficiency Antithrombin (AT) deficiency 4% Dysfibrinogenemia Hyperhomocysteinemia

Acquired disorders 1. ↑coag factors; pregnancy, OCP, HRT, Tamoxifen, smoking. 2. ↑ activity of coag factors; APA, PNH, vasculitis, Malignancy, Behcet $. 3. Loss of anticoag; nephrotic S. 4. ↑ viscosity; Myeloproliferative disorders, paraproteinemia (Waldenstrom's

macroglobulinemia, Multiple myeloma), diabetic hyperosmolarity. 5. Stagnant bl; immobility, Surgery, old age > 45yrs, VV.

Thrombophilia; = recurrent thrombosis without predisposing factors (verchow triad;) - May be due to cong or acquired cause as APA. - Should be tested for if; * recurrent venous * arterial * young < 45 yrs. * FH. * unusual site; CNS, Budd chiari, PV. Patients are either "strongly" or "weakly" thrombophilic:

 Strongly thrombophilic:  First idiopathic venous thrombosis before 50 years of age OR  History of recurrent thrombotic episodes OR  First-degree relative(s) with documented thromboembolism before age 50 .

♀, preg, or OCP, DVT suspect Factor V leiden.

Factor V leiden. ♀, preg, or OCP, DVT. 1/3 of cases. Diagnosed by activated prot C resistance test. - measure PT, PTT  normal. - add activated prot C  normally ↑PT, PTT. - in Factor V leiden  no ↑PT, PTT. Assay for Factor V by PCR.

Hyperhomocysteinemia may be; cong; ↓ cystathionine synthase, methionine synthase C/P; down lens disloc, Marfanoid, livido, MR, thrombosis. Acquired; aging, smoking, renal failure, myxedema, IBD, psoriasis, drugs; methotrexate, INH, antiepileptics. C/P; atherogenic & thrombophilic. Diag; ↑plasma methionine & homocyst. TTT; vit B6, B12, folate.

Graft versus host disease GIT : diarrhea , ANV. Liver : elevated liver enzymes. Skin: indurated erythema on palms & soles.

Immunology

Complement Complement pathway Classic pathway Mannose

+

lectin

from bact cell wall

C1qrs

- C1 inhibitor, +

immune complex

proteases C2,4 C3a, 5 a chemotaxis

C3

C3b opsonization

- C4 binding protein

Alternate pathway Factor B, (C3bBb) + bact. Lipopolysac C3 nephritic factor

- Membrane inhibitor of reactive lysis (MIRL)

C5,6,7,8,9 (MAC) cell lysis

- Decay accelerating factor (DAF), factor H.

Complement deficiency Def of Complement components; 1. 2. 3. 4.

Congenital def. of C2,4 ↓IC clearance SLE, vasculitis, polymyositis. C3 def Life threatening infection with encapsulated org. e.g. pneumococci. MAC (C5,6,7,8,9) disseminated neisserial infection. Acquired consumption occur in SLE, cryo, IEC, post infectious GN, MPGN.

Def of regulatory proteins; 1.

2. 3. 4. 5. 6.

Def of C1 inhibitor  hereditary angioneurotic edema dt ↑ vasoactive C2 fragment, ttt with epinephrine in the acute attack & danazole for prevention as it ↑ hepatic synthesis of C1 inhibitor & C4, SLE dt consumption of C2, 4. PNH; def of membrane GP (GPI) which bind the inhibitory comp DAF & MIRL compl mediated cell lysis. HUS; familial type dt def of Factor H compl activation & end. Injury. MPGN type 2; C3 nephritic factor, def factor H. ACEI C1 inhibitor def  angioedema. Cryo; ↓C4, preserved C3 dt ↑C4 binding protein inact of C3.

Immunoglobulin Ig G; - Monomer formed of a divalent molecule ( 2Fab). Most abundant. 2ry immune response. The only Ig that cross the placenta. MW; 150.000 dalton (25 for each LC & 50 for HC). 4 subclasses according to Fc.

Fab

Ig A; -

Monomer in serum, dimeric in secretion. Def chronic diarrhea, respiratory infection, autoimmune dis. IgA1 contain hinge region. Level undetectable at birth, reach adult level at puberty.

Ig M -

pentameric. 1ry immune response. Secretion do not need Th2. Include Bl group Ab. Against bacteria. Level undetectable at birth, reach adult level at 1 yr.

Ig D on B cell surface. Ig E; produced by plasma cell, attach to mast cell & basophils, responsible for type 1 hypersensitivity reaction.

Fc

Cells of the immune system 1. 2. 3.

1. 2.

PMN; Neutrophils phagocytosis, ≠ bacteria. basophils & mast cells; type 1 hypersensitivity, parasites. Eosinophils; allergy, helminthes, phagocytose IC. Mononuclear; Lymphocytes, monocytes.

blood lymphocytes 1.5-3.5.000 20-40% of WBCs

T-cells 60 to 80 %

Bind to class 2 MHC Ag on APC as MQ  IL1,6, TNF Active CD4 Th

Bind to class 1 MHC Ag On viral infected cells, cancer cells

IL2 IFNγ

th1

IL4 IL10

natural killer (NK) 5 to 10 %.

Suppressor/ cytotoxic T-cells 30 to 40 % (CD8+ cells).

Helper T-cells 60 to 70 % (CD4+ cells)

IL12, 18

B-cells 10 to 20 %

th2

Chronic granulomatous disease; - It is a defect in the production of NADPH ↓ H peroxide  ↓ phagocytic function of neutrophils (normal phagocytosis but defective intracellular killing) chronic granulomas & microabcesses in skin, bone & liver. - Diagnosed by nitroblue tetrazolium test (screening for reduced phagocytic capacity). - Ttt; INF γ

Hepatology

Functions of the Liver 

Main functions include: • Metabolism of CHO, protein, fat • Storage/activation vitamins and minerals • Formation/excretion of bile • Detoxifier of drugs/alcohol • Action as (bacteria) filter and fluid chamber • Conversion of ammonia to urea

Generally LFTs reflects 2 patterns of liver disease; 1. Cholestatic  Alk P, GGT. 2. Hepatocellular AST, ALT. Factors favouring hepatic origin of Alk P; 1. ↑ GGT. 2. ↑ 5’-nucleotidase.

Type of Hepatitis A

Route of transmission Chronic infection Prevention

fecal-oral

B

C

D

percutaneous percutaneous percutaneous permucosal permucosal permucosal

no

yes

pre/postexposure immunization

pre/postexposure immunization

yes

yes

blood donor pre/postscreening; exposure risk behavior immunization; modification risk behavior modification

E

fecal-oral

no

ensure safe drinking water

Hepatitis A - Clinical Features Is an RNA enterovirus  Incubation period: Average 30 days ( 2 - 6 wks )  Complications: Fulminant hepatitis. Cholestatic hepatitis. • Relapsing hepatitis • Prevention; - Immune Globulin IM, 0.02 mL/kg 

-

Pre-exposure (travelers to endemic regions/4-6months) & Post-exposure (within 2-4 wks)

-

for persons > 2 years old . provides long-lasting protection (20 years). (Havrix) use 3 doses at 0, 1, 6 months).

- Hepatitis A vaccines .

 TTT; bed rest, symptomatic ttt e.g. antiemetics, avoid hepatotoxic drugs.

Hepatitis B - Clinical Features  Hepa DNA virus.  Mode of transmission; Bl, sexual, perinatal.  Incubation period: Average (2 -6 ms). Chronic infection: 30%-90%.  Association/ complications of HBV; - Aplastic anemia. - Arthralgia/itis. - PAN.

- Glomerulonephritis; membranous., MP. - HCC. - urticaria, acrodermatitis.

Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Symptoms HBeAg

anti-HBe

Total anti-HBc

Titre

0

4

anti-HBs

IgM anti-HBc

HBsAg

8

12 16 20 24 28 32 36

Weeks after Exposure

52

100

Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course Acute (6 months)

Chronic (Years) HBeAg

anti-HBe HBsAg Total anti-HBc

Titre

IgM anti-HBc

0 4 8 12 16 20 24 28 32 36

52

Weeks after Exposure

Years

Diagnosis serological tests ;  HBsAg - used as a general marker of active infection, persistance > 6 m= chronic infection.  HBsAb - used to document recovery and/or immunity to HBV infection.  HBc Ag is not detected in the blood.  anti-HBc IgM - marker of acute infection, may be the only marker in the window period.  anti-HBc IgG - past or chronic infection. It can distinguish past infection from previous vaccine.  HBeAg - indicates active replication of virus and therefore infectiveness.  Anti-Hbe - virus no longer replicating= no longer infectious .  HBV-DNA - indicates active replication of virus, more accurate than HBeAg

HBsAg +ve

Repeat HBs Ag after 6 m to confirm, if HBs Ag become -ve  resolved if HB sAg still +ve

HBe Ag -ve ALT =n =carrier

observe

HBe Ag +ve =chr active

biopsy & TTT

TTT of HBV

HBsAg +ve

+ve HBc Ig M =acute

+ve HBc IgG =chronic

HBsAg after 6 months

-ve =resolved

+ve =chronic

1. If acute symptomatic ttt 2. If HBsAg +ve after 6 mths, HBeAg +ve or -ve, HBeAb _ve, PCR>105, enzymes >2folds antiviral ttt. 3. If HBsAg +ve after 6 mths, HBeAg gray zone or normal enzymes  biopsy  hepatitis activity index > 4  antiviral ttt. 4. If HBeAg-ve, HBeAb +ve, PCR+ve, normal enzymes  Carrier (no ttt). 5. Liver cirrhosis nucleozide analogue only.

Treatment  -

-

Interferon Peg INF α2a (high mw, long ½ life) Mechanism; immune distruction of virally infected cells clear the virus. Dose; 180 Ug/wk Duration; 6 mth for eAg +ve, 12 mths for eAg _ve (mutant form) Indications; chr hepatitis NB; not for normal biopsy or LC (lead to decompensated liver) Response rate is 30 to 40%. Side effects; common; flu like S, N, V, wt loss, loss of hair, depression, mild BM suppression. less common; thyroiditis, BM suppression, seizures, retinopathy, tinitus, teratogenic.

# to IFN therapy; Asolute;  Poorly controlled medical condition, DM  Anaemia, thrombocytopenia.  Poor medication compliance.  Alcohol, IV drug abuse, Severe depression. Relative;  Autoimmune dis (SLE, Rh, IBD, psoriasis)  Neuropathy.  Thyroiditis.

Nucleotide analogues;  







Lamivudine, Adefovir, entecavir, tenofovir Mechanism; reverse transcriptase inhibitorinhibit viral replication, decrease enzymes but does not clear the virus. Adv; oral, no hep decompensation, delay the progression of LC & HCC. Disadv; relapse , drug resistance mutant strains, no viral clearance. Duration; 1-3 yrs.

NB; there are 8 genotypes for HBV (AH).better response with A &B. HBe Ag-ve mutant forms are more drug resistant but less HCC, common in Egypt.

Response to ttt; 1) virologic; Early response (12 wks) End of ttt response (at 24 or 48 wk) Sustained response (after 6 mths) Non responder (at the end) Breakthrough (reappear while on ttt) Relapse (-ve at the end but +ve during FU). 2) biochemical (normal ALT). 3) Histologic (>2 Hist. A ct. Ind improvement). Predictors of good response; Viral; genotype, titre. Liver; minimal fibrosis, moderate enzymes. Patient; female, Caucasian, lean, compliant, not IC, no alcohol, no other CLD.

Prevention 

Vaccination

-

highly effective recombinant vaccines. given to those who are at increased risk ; health care workers, neonates.

-





HBIG post exposure to hepatitis B. It is particular efficacious within 48 hours, to neonates whose mothers are HBsAg and HBeAg positive. Other measures - screening of blood donors, blood and body fluid precautions, All pregnant women .

Natural History of HCV  



Incubation period: Average 6-7 wks (2-6 ms) Chronic HCV----------Cr-------HCC 20-30 y 5-10 y The rule of 20; - 20% of pts with acute infection are symptomatic. - 20% of pts with acute infection clear the virus. - 20-40% with chronic HCV develop C after 20 yrs. - Crr---20%--HCC - 20%-55% of Chronic who receive IFN will obtain a sustained rresponse.

Extrahepatic manifestation of HCV 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

PCT. Cryo. Leukocytic vasculitis. MPGN. Thyroiditis. Sjogren’s. Lichen planus. Vitiligo. IGT (type II DM). B cell lymphoma.

Laboratory Diagnosis 

HCV antibody (by EIA or RIBA; more sensitive) – appear at least 4 weeks after infection.

HCV-RNA –( in the acute phase), (monitoring the response to antiviral therapy). EIA detect anti-HCV by 4- 10 wks of exposure, while PCR as early as 1-2 wks. 

Diagnostic tests for HCV Category

ALT

EIA

RIBA

HCV RNA

False +ve EIA

N

+

_

_

Resolved infection

N

+

+

_

HCV carrier

N

+

+

+

If a low risk patients with normal LFTs has a +ve EIA  Only 30-40% will be RIBA +ve. However, in high risk individuals, PPV of ELISA> 95%.

HCV genotypes  



6 genotypes. Genotype 1 most common in US, low response rates to TTT, 30% 1 year. Genotype 2,370% response after 6 ms.

TTT guidelines for HCV Pt ccc

Recommendation

PCR +ve, ↑ ALT, liver biopsy with inflammation, bridging necrosis PCR +ve, ↑ ALT,

INF+ ribavirin

Normal ALT Compensated C decompensated C

Observe. Observe, consider TTT Consider transplantation

INF+ ribavirin or do liver biopsy

Treatment 

Interferon - may be considered for patients with chronic active hepatitis. The response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment.



Ribavirin - combination of interferon and ribavirin is more effective than interferon . ↓progression even in absence of viral response; side effect; teratogenic, hemolysis esp in renal insufficiency..

Hepatitis D - Clinical Features  Coinfection with HBV – severe acute disease. – low risk of chronic infection.  Superinfection – usually develop chronic HDV infection. – high risk of severe chronic liver disease. – may present as an acute hepatitis.

Hepatitis E - Clinical Features As HCV



Incubation period: Pregnant women Illness severity:



Chronic sequelae:

None identified

 

Increased with age

Alcoholic Liver Disease, Alcoholic hepatitis, and Cirrhosis • Diseases resulting from excessive alcohol ingestion characterized by fatty liver (hepatic steatosis), hepatitis, or cirrhosis . • Prognosis depends on degree of abstinence and degree of complications • C/P; N/V, anorexia, abd pain, ↓ wt. Malnutrition often an issue in these patients • TTT; abstinence, good nutrition.

Lab;  ↑ GGT.  ↑ MCV (macrocytosis).  AST/ALT > 2/1.  Ig A.  Mallory bodies; dense perinuclear esinophilic fragments in hepatocytes (DD; PBC, wilson).  thrombocytopenia.  Blood alcohol Bleeding tendency in alcoholic Cirrhosis; 1. ↓ synthesis of coagulation factors. 2. Plat. Function defect. 3. Thrombocytopenia ( hyperslenism, BM suppression).

NAFLD   -

   -

Spectrum; steatosis, NASH, cirrhosis. Etiology; 1ry; obese, DM, hyperlipidemia. 2ry; drugs; amiodarone, tamoxifen, steroid, tetracyclin rapid wt loss, malnutrition, jej bypass, TPN. Inv; U/S, MRI, AST/ALT<1, ANA, ASMA +ve in 40%,hyperlipidemia in 20%. TTT; orlistat, wt loss UDCA, antioxidents, Vit E, betaine Statin, gemfibrozil Thiazolidenidione, Metformin.

Autoimmune liver disease Autoimmune

Primary Biliary Cirrhosis

Hepatitis(AIH)

(PBC)

Primary Sclerosing Cholangitis (PSC) Autoimmune

Overlap

Cholangitis (AIC)

Syndromes

The diagnosis requires: exclusion of major causes of liver damage, including alcoholic, viral, drug- and toxin-induced, hereditary metabolic, and NAFLD. 

Autoimmune Hepatitis  

 





 



Young women (10-20 yrs) Typically present with malaise, artharalgia, tender hepatomegaly, 2 ry amenorrhea,. Patients may be asymptomatic AIH may present as acute hepatitis, chronic hepatitis, or well-established cirrhosis , Investigation. Type 1, ASMA ,ANA ,Anti-actin, Type 2, Anti-LKMA nti-liver-kid., Type 3, Anti-Soluble liver- antigen ,↑ γ globulins,

Without therapy, most patients die within 10 years of disease onset. With TTT,10 yrs survival = 93%. TTT=steroids + aza for pt with or without Cirrhosis70% remission in 2 yrs. Relapse after remission=50% at 6 ms, 80% at 3 yrs.

Primary Biliary Cirrhosis Middle aged females  C/P; pruritis,Jaundice, steatorrhea( 2ry to cholestasis), hyperpigmentation, xanthelasma.  PBC frequently is associated with other autoimmune disorders , such as Sjögren syndrome, Hashimoto thyroiditis, AIHA, arthritis. 

 

Criteria for the diagnosis include:

(1) A cholestatic serum enzyme pattern, Alk. Phosph. (2) Presence of AMAs antimitochondrial. (3) Elevated serum IgM, (4) bile duct lesion of mid-sized IHBD (1),(2) & a compatible histology are regarded as mandatory for the diagnosis of PBC. Liver biopsy lymphocytic portal infiltration. TTT; UDCA, colchicine, transplant.

Primary Sclerosing Cholangitis 

Criteria for the diagnosis :

1- RUQ pain , jaundice , pruritis & wt loss A cholestatic enzyme pattern; 2- histologically ., large bile duct (intra & extrahepatic) stenosis & dilatations without prior bile duct surgery or 2ry SC ; mild to moderate portal infiltration. 3- concomitant IBD ( before, during, after UC mainly) in 70 % of the patients, detected by asympt ↑Alk P. but in case of UC, 3% have PSC. 4- presence of pANCAs in > 70% of patients.  MRCP, ERCP beading of intra & extrahepatic bile duct.  ↑ risk of cholangiocarcinoma, retroperitoneal fibrosis.  TTT; supportive (UDCA, colchicine), , transplantation.

Autoimmune Cholangitis 



AIC (AMA – ve PBC) shares many features with PBC including : 1- F>M, 2- fatigue and pruritus, 3- a cholestatic serum enzyme pattern, 4- bile duct lesions (histology), & 5- a slowly progressive course leading to fibrosis and cirrhosis of the liver. Patients with AIC are by definition AMA -ve & often present with serum ANA and/or ASMA.

Criteria

AIH

PBC

PSC

AIC

F:M

4:1

9:1

1:2

9:1

Predominant liver test

ALT, AST (7-10 times) ALP (1-3 times)

ALT, AST (1-3 times) ALP (6-10 times), γ-GT

ALP, γ-GT

ALP, γ-GT

Auto antibodies

ANA, ASMA, LKM, SLA,

p ANCA

ANA, ASMA

Histology

interface hepatitis

Diagnosis

Hepatocellular enzyme pattern,

AMA AMA-M2

Florid bile duct Fibrosing bile lesion duct lesion

Florid bile duct lesion

AMA-M2, cholestatic enzyme pattern, compatible

BD st./dilat. (choigraphy), cholestatic enzyme pattern,

Cholestatic AMA-ve, ANA or ASMA +ve, histology compatible

histology

IBD, p ANCA

with PBC

Overlap Syndromes 



    

Patients with overlap syndromes present with both hepatitic and cholestatic biochemical and histological features of AIH, PBC, and/or PSC, and usually show a progressive course toward liver cirrhosis . AIH-PBC overlap syndromes ...reported in almost 10% of adults with AIH or PBC. AIH-PBC Overlap Syndrome AIH-PSC Overlap Syndrome AIH-AIC Overlap Syndrome Coexistence of PBC and PSC Coexistence of AIH and Chronic HCV

Wilson’s Disease  



AR. Genetic defect in copper transport ( ATP7B gene on ch 13) ↓ hepatic excretion Cu organ deposition. Presentations :

Hepatic, chronic hepatitis, macronodular C, mallory bodies. Neurological;(BG) flapping, chorea, dysarthria, tremors parkinsonism Kayser Fleicher ring Renal; RTA Haematological; coomb’s –ve HA. Endocrinal; hypoparathyroidism pseudogout.

Wilson’s Disease  1. 2. 3.  -

Inv; Low serum ceruloplasmin High urinary copper. Liver biopsy with orcein stain. TTT; penicillamine for life + pyridoxine, oral Zn Transplantation Family screening with ceruloplasmin.

KF ring

Hemochromatosis   

   1. 2. 3. 4. 5. 6.  

AR, mutation of HFE gene on chr 6. Homozygous C282Y or hetero C282Y/ H63D. Exessive Fe absorption & deposition in various organs; - heart  restrictive cardiomyopathy, - pancreas  DM, - pituitary hypogonadism, - joints  pseudogout, - skin  bronzed colour. ↑ risk of malignancy HCC. Cause of death; HCC, restrictive cardiomyopathy. Lab; screening by TSAT > 60% in males & 50% in females. Ferritin > 500 ↑ Fe, ↓ TIBC. Hepatic iron conc (HIC), hepatic iron index (HII), MRI. Liver biopsy staining with prussian blue. Genetic study. TTT; phlebotomy/1-2 wks for 2-3 yrs to Hb<10, ferritin<350,then every 3-4-m for life. Desferroxamine. Irreversible complications are arthropathy, hypogonadism, cirrhosis.

α1 antitrypsin 

 



Inhibit neutrophil elastase, its absence emphysema & LC. AR, Pi ZZ phenotype Inv; PAS +ve globules in periportal hepatocytes. Ttt; hepatic transplantation, stop smoking.

Drug induced liver disease acetaminophen

Acute hepatitis.

Estrogen

Budd chiari.

Amoxiclave, chlorpromazine, erythro, OCP,

Cholestasis.

Amiodarone,allopurinol

Hepatic granuloma.

OCP,

Adenomas +/- intraperitoneal rupture. Cholelithiasis, cholestasis HV thrombosis Peliosis hepatis

Methyl dopa, INH, nitrofurantoin

CAH.

MeThotreX, amiodarone, vit A

Cryptogenic C.

Cocaine

Massive ischemic necrosis

Anabolic steroids , OCP

Peliosis hepatis

Cirrhosis Etiology

Diagnosis

TTT

Alcoholic C.

GGT, MCV, AST/ALT

Abstinence

HBV

serology

INFα-2b Lamivudine

HCV

serology

INFα ribavirin

Hemochromatosis

TSAT, Ferritin, hepatic Fe index, HFE gene

Phlebotomy, desferroxamine

AIH

ASMA, anti LKM, SLA, ANA

Prednisone, azathioprine

PBC

AMA

ursodiol

wilson

Serum& urine Cu, ceruloplasmin

D-penicillamine, Zn

α1 antitrypsin

α1 antitrypsin level

Enzyme replacement, transplantation

Fulminant Hepatic Failure 

- Def; Rapid, severe acute liver injury with

encephalopathy within 8 weeks in someone with a previously normal liver. - pathology; massive necrosis, severe fatty degeneration. - Causes; HEV in pregnancy, Reye’s, IV tetracycline, paracetamol toxicity, ecstasy, halogenated anathesia, wilson, viral, Alcohol, mushroom poising, shocked liver. - C/P; enceph, hypoglycemia, ↓Na, bleeding tendency, renal failure. - Ttt; as hep. enceph. - Poor prognostic factors; - Paracetamol; Ph<7.3, s creat>300, PT>100, grade3,4 enceph.

Reye’s Syndrome 





 

It is acute encephalopathy + fatty degeneration of the liver Pathogenesis: loss of mitochondrial function …………. Disturbed FAO + carnitine def Clinical picture: Acute fulminant hepatitis. age 4-12 yrs URTI or chicken pox Mortality 50% Ttt; supportive

The Child-Turcotte-Pugh Classification

 1. 2. 3. 4. 5. 6. 7. 8.

Complications of LC; Portal HTN ov, hypersplenism, ascites. Ascites HCC Hep encephlopathy HRS Malnutrition Coagulopathy Endocrinal; amenorrha, testicular atrophy.

Portal hypertension Def; PV pressure > 12 mmhg. Types According to site of obstruction Prehepatic eg PVT Hepatic: presinusoidal eg CHF sinusoidal eg Cir, postsinusoidal eg VOD Posthepatic eg Budd Chiari synd Clinical Picture       

Hematemesis Melena Splenomegaly Hypersplenism Dilated abdominal wall veins Ascites Encephalopathy

upper GIT bleeding; 1.

2.

3.

4.

Ulcers; - high risk ulcers= active bleeding, visible vessel, adherent clot. - Hospitalization for 3 days. - PPI infusion - endoscopy electrocoag, heater probe, injection of absolute alcohol or 1: 10.000 epin. Mallory Weiss; self limiting. Esoph. Varices; - octoreotide -ligation better than injection sclerotherapy - quinolone Ab - chronic non selective BB - decompressive surgery as distal splenorenal shunt in class A & B lower rate of intervension than TIPS. - TIPS; less bleeding, equal mortality but more encephalopathy than endoscopy. Others; gastric or esophageal erosions, malignancy

Management

A) Of an acute attack of hematemesis 1-Resuscitation 2-anti shock measures; IV cannula, line, Ryle, IV crystalloids, colloids, Blood, FFP. 3- hemostatic drugs; Vit K, tranexamic acid, ethamsylate. 4- PPI infusion in PU. 5- Octreotide for esophageal varices. 6- anticoma measures; lactulose, metronidazole, enemas. 7- UGIE for band ligation or injection sclerotherapy + quinolone. 8- sengestaken-blackmore tube for massive uncontrolled bleeding from OV. 9-if still uncontrolled  TIPS for high risk,, emergency surgery for low risk. 10- if massive bleeding, source unknown (obscure) enteroscopy or angiography. B) IN between the attacks; 1- PPI for PU 2- non selective BB; propranolol, quinolone for prophylaxis from SBP, UGI Band ligation or injection sclerotherapy for OV.

Lower GI bleeding SI bleeding  Causes; 1. 2. 3. 4. 5. 6.

  -

Hemorroids Anal fissure Adolescent IBD, jej. Polyp Adult diverticula Elderly vascular ectasia, malignancy Others; dysentry, ischemia, vasculitis, intussuception.

C/P;

If facial, oral telangectasia HHT Acanthosis nigricans Malignancy Perioral pig spots PJS. Investigation; UGIE Colonoscopy Push enteroscopy Videocapsule enteroscopy TC labelled RBC scan (during bleeding) Angiography (tumour, Vs malformation)

Occult bl in stool; - benzidine, guaiac tests False +ve; meat, NSAIDs False –ve; vit C, cauliflower (peroxidase containing) Iron darken the test. 

PVT 



Aetiology: intra abdominal infection umbilical catheterization hypercoagulable state invasion by tumors idiopathic Clinical picture: splenomegaly no hepatomegaly normal LFTs

Veno occlusive disease 



Thickening and fibrosis of small hepatic venules and centrilobular veins Aetiology: * Herbs. * toxins (aflatoxin). * drugs . Azathiprine * bone marrow tx

Budd Chiari Syndrome 

 1. 2. 3.

Obstruction of the main hepatic veins or IVC : Acute onset of abd. Pain& ascites , jaundice with no LL oedema. Risk factors; Chemotherap Irradiation alkaloids

Hepatic Encephalopathy Def; neuropsychiatric S that may complicate CLD, fulminant LCF & portosystemic shunts. Pathogenesis; protein in the colon  bact flora neurotoxins e.g. NH3, mercaptans, false neurotransmitors as octopamine & tyramine dt ↑ aromatic & ↓ branched chain aa, ↑ GABA. Role of ammonia; 1. Bind glutamic acid glutamine  - CNS. 2. Bind αketoglutarate ↓CNS energy. Ttt by binding to lactic acid.

Precipitants of Hepatic Encephalopathy Drugs •Benzodiazepines •Narcotics •Alcohol

Dehydration •Vomiting •Diarrhea •Hemorrhage •Diuretics •Large volume paracentesis

Increased Ammonia Production, Absorption or Entry Into the Brain •Excess Dietary Intake of Protein •GI Bleeding •Infection •Electrolyte Disturbances (ie., hypokalemia) •Constipation •Metabolic alkalosis

Primary Hepatocellular Carcinoma

• neurologic symptoms  Cognitive impairment  Inverted sleep rhythm  Neuromuscular disturbance  Altered consciousness

Stages of Hepatic Encephalopathy Stage

Symptoms

I Apathy

Slow mentation (Mild Confusion, agitation, irritability, sleep disturbance, decreased attention)

II lethargy

Easy arousable, disorientation, inappropriate behavior, drowsiness

III stupor

Somnolent but difficult arousal by vigorous stimuli; pain & voice, slurred speech, confused, aggressive

IV coma

Light Coma; respond to pain only Deep coma; no response

DD of flapping tremor; 1. Hepatic Encephalopathy. 2. Wilson’s dis. 3. Uremia. 4. CO2 narcosis. DD of irritable coma; 1. Hypoglycemia 2. Subdural hematoma 3. Acute alcohol intoxication 4. Delerium tremens; dt balcohol withdrawal, visual hallucinations, paranoid psychosis, tremors, agitation, pyrexia, tachycardia, sweating, dilated pupil within 3-1 wks, ttt; sedation that ↑GABA as BDZ. 5. Wernicke’s encephalopathy 6. Drug intoxication 7. Meningitis 8. wilson

Treatment of Hepatic Encephalopathy 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

Control precipitating factors. Lactulose Antibiotics Enema/4 hr Protein restriction BCAA supplementation Flumazenil (Anexate) BDZ receptor antagonist. Ldopa or bromocriptine ; dopamine agonist; improve NM transmission. Zinc Artificial liver support (hemoperfusion, artificial liver device. Liver transplantation

Definition

Ascites

The presence of free fluid in the peritoneal cavity.

Differential diagnosis F F F. Causes : 1. Portal HTN; SAAG> 1.1g/dl

23-

Prehepatic eg PVT Hepatic: presinusoidal eg CHF, constrictive pericarditis, TI sinusoidal eg Cirrhosis,metastasis, fibrosis, AFL. postsinusoidal eg VOD Posthepatic eg Budd Chiari synd Hypoalbuminemia. SAAG< 1.1g/dl - nephrotic, protein loosing entero, malnutrition. Local causes; SAAG< 1.1g/dl Diseased peritoneum; malignant as P carcinomatosus, mesotholioma, infections as TB, fungal, bact,others; FMF, vasculitis as HSP, granulomatous, esinophilic. Normal peritoneum pancreatic, chylous, myxedema, Meig’s S.

Paracentesis Transudates

Exudates

Ascitic protein

<3g

>3g

Ascitic LDH

<200

> 200

Modified Light criteria Ascitic/serum LDH

<0.6

> 0.6

Ascitic/serum protein

<0.5

> 0.5

Examples

CHF/ cirrhosis/ nephrosis Portal HTN Hypoalb. Meig’s S Contrictive pericarditis

TB Fungal SBP Cansers Budd Chiari S

Serum-Ascitic Albumin gradient ( SAAG ratio); SAAG <1.1 =abn cap. permeability Nephrotic S

SAAG >1.1 = portal HTN mediated CHF/

Pancreatitis

Budd Chiari

Peritoneal TB

cirrhosis

Peritoneal carcinomatosis Serositis, CT dis. Causes of unilateral shifting dullness; 1. TB; lobulated type. 2. Dilated intestinal loop 3. Psoas abcess 4. Subcapsular splenic hematoma

Hepatic ascites  -

 -

Mechanism of hepatic ascites; Hypoalb PHT Renal Na retension Lack of distruction of Est, aldosterone, ADH Complicated; PVT, SBP, HCC, HRS. TTT of ascites Dietary Na restriction; 2 g/d Oral diuretics. Fluid restriction is not necessary unless serum sodium is < 120 mmol/L. A single 4-to-6 L abdominal paracentesis should be performed in patients with tense ascites. Urine sodium excretion can assist in determining patient compliance with diet and diuretic-resistance. Liver transplantation should be considered in eligible patients with cirrhosis and ascites.

 1) 2)

Refractory ascites;

Diuretic resistant= can not be mobilized despite Na restriction & max dose of oral diuretics; 400mg spironolactone + 160 mg frusemide. Intractable ascites= can not be mobilized dt diuretic induced complications.

Ttt;

Large volume parasentesis+ an albumin infusion of 8-10 g/ liter of fluid removed 2) TIPS 3) Portosystemic shunt 4) Peritoneovenous shunt 5) Ascites ultrafiltration & reinfusion 6) Liver transplantation 7) Novel ttt; ANP, dopamine, docarbamine, Ve2 receptor antagonists e.g. tolvaptan. Sudden ↑ in ascites in previously stable ascites; SBP.,Budd-chuari.,HCC., HRS. Sudden deterioration of liver functions; e.g. sepsis, Hge, alcohol binge.  Hepatic hydrothorax; 70% RT dt opening of lymphatic channels through the diaphragm Inv; diagnostic paracentesis must be done to disclose SB empyema (in 10%). 1)

Ascitic fluid clues of specific causes of ascites Causes of ascites Ascitic fluid clues Peritoneal Carcinomatosis Tuberculous ascites Chylous ascites

Mucinous Pancreatic ascites

Cytology  malignant cells WBC > 500/mm3 with lymphocyte predominance -TG in ascites > serum (usually > 200mg/dL) - milky, clear by ether - sudan staining - dt intestinal lymph e.g.TB, filaria, nephrotic, ectasia, - dt pseudomyx perit, Amylase in ascites > serum (often > 1000 U/L)

TIPS  1.

2.  1. 2. 3.

Indications Resistant, recurrent refractory ascites. Recurrent variceal bleeding. contraindications of TIPS HV thrombosis. SBP Mild to moderate ascites.

SBP def; An infection of the peritoneal fluid in the absence of a

known or suspected intra-abdominal surgical source of the infection.

Risk factors; GI hemorrhage. previous SBP. ascitic fluid TP < 1gm/dL, S. bilirubin > 3.2 mg/dL low platelet count < 98,000 cells/mm³. fulminant hepatic failure. diagnosis; 1. C/P; fever, abd pain, tenderness, ascites 2. a PNL in ascites ≥ 250 cells/mm³ (or WBCs >500/mm3). 3. a positive ascitic fluid culture (usually of a single organism; enterobacteriaceae 63%, step pneum 15%, enterococci 610%) but often culture –ve.

of SBP Treatment

• empiric antibiotic therapy, e.g., 2g of cefotaxime i.v. every 8 hours,or other 3rd G ceph or Amoxacillin-clavulonate • or quinolone if not on quinolone prophylaxis for 5 days • 1.5g albumin/kg BW within 6 hours of detection and 1g/kg on day 3. Prophylaxis; Oral norfloxacin 400mg 1x2 1ry or 2ry prevention for high risk patients for short term (7d) as 1ry prophylaxis, long term for 2ry prophylaxis

Variants of ascitic fluid infection according to ascitic fluid characteristics Category

Ascitic fluid analysis Count

Organism(s)

SBP

PMN ≥ 250/mm³

Single

Culture-negative neutrocytic ascites

PMN ≥ 250/mm³

Negative culture

Secondary bacterial peritonitis

PMN ≥ 250/mm³

Multiple

Jaundice Isolated unconjugated hyperbil (direct<15%) Hemolysis Ineffective erythropoiesis Drugs e.g. rifampin, Inherited e.g. gilbert, Cr Najar.  Hepatocellular (↑ALT, AST) - viral, wilson, autoimmune, alcohol, drugs e.g. INH, acetaminophen, toxins as vinyl chloride. Isolated conjugated Rotor, DJ.  Cholestatic (↑ALK P > 4 times) - extrahepatic; U/S dilated bile ducts CT, ERCP. e.g. malignancy, stones, stricture, PSC, parasitic as ascaris, AIDS cholangiopathy. - Intrahepatic serology, biopsy.e.g.viral, alcoholic, PBC, PSC, GVHD, infiltrative dis as TB, lymphoma, sarcoid, amyloid, drugs as OCP, anabolic steroids (pure cholestasis), erythromycin (cholestatic hepatitis). 

Gilbert’s  1 ry cause of isolated ↑ indirect bili.  Usually caused by fasting states  Nicotinic acid test delay & high peak of biliribin ( 3 hrs).

DD  

 -

 

Cholestasis in ICU shock liver, sepsis, TPN. Jaundice after BM transplantation  venoocclusive dis, GVHD. AIDS cholangiopathy; Picture of PSc. Cholangitis. Dt infection with CMV or cryptosporidia. ALK =800 but bil often normal. GGT ↑ in alcohol, phenytoin,, pancreatitis, cholestasis. Cholestasis; ↑Alk P fractionate, 5’nucleotidase, GGT.

DD of jaundice in 3rd trimester of pregnancy 1. 2. 3. 4. 5.

Viral hepatitis (hep E). Herpes hepatis. HELPS. Acute fatty liver of pregnancy Intrahepatic cholestasis.

Pruritis gravidarum; dt intrahepatic cholestasis. Ttt; mild  reassurance . Severe  cholestyramine, ursodeoxycholic acid.

HCC  -



  1. 2.

3. 4. 5. 6.

Predisposing factors;

LC esp hemochromatosis & alcoholic C. HBV, HCV Aflatoxin (fungal metabolite in food) Androgenic steroids & rarely OCP. Fibrolamellar carcinoma; a microscopic variant consisting of large polyclonal cells arranged in trabiculae separated by parallel bundles of collagen, in young females, of better prognosis. Inv; AFP>400 ng/ml, carboxyprothrombin, spiral CT. TTT; Surgery; resection, transplantation if < 3 cm, good liver function Percutaneous ttt; if < 5cm or 3 <3 cm with no vascular or extrahepatic invasion. e.g. ethanol, acetate injection, cryoprecipitate, hot saline, laser photocoagulaton, radiofrequency ablation, intralesional injection of chemo (cisplatinum). Chemoembolisation; if not fit for surgery or percut but fit liver functions. Systemic; hormonal e.g. Tamoxifen or chemo e.g. capecitabine. Radiotherapy Targeted immunotherapy; anti AFP Ab.

Liver transplantation Elevated liver enzymes after transplantation;  Early few wks to ms 1. Allograft rejection. 2. Drug toxicity. 3. Art. Thrombosis.  After 1st yr  recurrence of initial dis

HRS

Post-cholecystectomy S;  1. 2. 3. 4.  1. 2. 3. 4. 5.  1. 2.

Causes; Oesophagitis, pancreatitis, radiculopathy Functional BD (hepatic flexure S) Stone in CBD, stricture CBD, FB granuloma Sphincter iof odd dysfunction Management; Liver FTs Abd U/S UGI endoscopy. Biliary manometry Biliary scan TTT; If LFTs , abd U/S normal symptomatic pain releif. If LFTs abnormal, U/SCBD dilatationERCP with manometry or sphincterotomy.

Acute PANCREATITIS  1.

2. 3. 4. 5.

6. 7. 8. 9.

Causes; Gall stones 50%; 75% of pt with unexplained pancreatitis has microlithiasis(microscopic stone dis). Alcoholism Infections; Coxsackie, mumps, ECHO & hep viruses Tumours Drugs; PD FAST VET (pentamidine, didanosine, frusemide, azathioprine, steroids, sulfa, thiazide, valproate, OCP, tetracyclin) Hypertrigyceridemia Hypercalcemia Iatrogenic e.g. ERCP Idiopathic.

C/P; Abd pain, N, V. MOF, shock • Cullen's sign (periumbilical discolouration) • Grey Turner's sign (flank discoloration) Inv; 1. ↑s. amylase 4 times,levels does not correlate with the severity, macroamylasemia (bound to Ig), ↑ urinary amylase/creat. 2. ↑s. lipase; specific, remain high for long time (10d) 3. s trypsin 4. Leuckocytosis, ↑AST, ALP, ↓Ca. 5. Imaging; CT Scan TTT; 1. Bowel rest 2. Analgesic; pethidine 3. Antibiotics; tienem, 3rd G ceph. 4. Correct fluid & electrolytes. 5. Somatostatin IV 6. Plat activating Fact antagonist (lexipafant)

poor prognostic indicators in acute pancreatitis: During 48 hrs “ Ranson’s BASline BUNdle Sure Can Help Out” Base deficit > 4 meq/l BUN ↑> 5 mmol/l Sequestration of fluid>6L Calcium < 2.0 (<8mg/dl) Hct ↓>10% PaO2 <8 (60 mmHg)

 1. 2. 3. 4. 5. 6. 7. 8.

Complications of acute pancreatitis; Plegmon; a mass of inflamed pancreatic tissue. Pseudocysts. Hypocalcemia Pancreatic abcess; 2-4 wks after ARDS. MOF. Splenic or portal vein thrombosis varices--. Hematemesis. DM, exocrine pancreatic insufficiency.

Pseudocysts; Fluid collections. In 15 % of acute panc. Body & tail Do not have epithelial lining. resolve spontaneously within wks If > 5 cm, remain for > 6 wks drainage.

Causes of a raised amylase are:  acute/chronic pancreatitis  pancreatic cysts and carcinoma  perforated duodenal ulcer  ovarian carcinoma .  ectopic pregnancy  gallstones  salivary tumour  adenitis ,mumps  diabetic ketoacidosis

Chronic Pancreatitis Causes; 1. Alcohol 2. Cystic fibrosis 3. Hemochromatois 4. Others; traumatic, autoimmune, Hypertrigyceridemia 5. Hypercalcemia

C/P;

•

abd. Pain. Steatorrhoea, B12 deficiency, trypsin is required in the processing of dietary B12 which enables absorption . DM

Inv;

CT calcifications. • ERCP (of choice)..... Chain of lakes • Test for exocrine pancreatic functions; - therapeutic test with pancreatic enzymes - secretin test (most sens) - fecal elastase, chemotrypsin - serum trypsinogen. TTT: analgesics, DM, steatorrhea. •

Pancreatic cancer

 1. 2. 3. 4.  

 

Risk factors; Smoking, advanced age, male gender, black race. Type I DM, chronic pancreatitis. Familial pancreatitis Industrial exposure to petroleum components & leather tanneries. Pathology; adeno, 80& in the head. C/P; cachexia, obst jaundice with palpable GB (courvoisier law), ascites, abd pain, thrombophlebitis ( trousseau sign) Inv; CT, MRI., ERCP. TTT; whipple radical surgery or palliative surgery, chemo, radio.

A 40 year old diabetic lady presents with a hot swollen left leg. On examination has a temperature of 39°C and her leg is tender to compression. She was treated with intravenous flucloxacillin and benzylpenicillin. However, the erythema has spread even further after 3 days, she is persistently hypotensive with a systolic BP of < 90 mmHg. Which of the following antibiotics should be added? A. Gentamicin B. Tazocin C. Chloramphenicol D. Clindamycin E. Amoxycillin

clindamycin. There is suspicion that this lady may have Streptococcus A infection with toxic shock syndrome. Clindamycin has effects of reducing protein synthesis and exotoxin production by the bacteria.

A 32 year old sailor is admitted to hospital with a 3 day history of fever, generalised lymphadenopathy and a macular rash over the trunk and legs. Which of the following diseases may present in this way? A. Infectious mononucleosis B. Sarcoidosis C. MumpsD. Primary syphillis E. Familial mediterranean fever

A 30 year old man presented with bloody diarrhoea. This started 2 days ago. He returned from a business trip to Egypt recently 1 week ago. What is the most likely causative organism? A.Cholera B. E coli C. Giardiasis D. Shigella E. Crytosporidiosis

Shigella. The common causes of bloody diarrhoea include Salmonella , Shigella , Campylobacter and amoebiasis. E. coli type E 0157 can also cause bloody diarrhoea with Haemolytic uraemic syndrome.

35 year old man has lymphopenia on his white cell differential. He complains of headaches. A CT scan of his brain showed a 5 cm ring enhancing lesion in the frontal lobe. Which is the likely infective organism? A. Cryptosporidia B. Toxoplasma gondii C. Aspergillus D. Cryptococcus neoformans E. Mycobacterium avium intracellulare

toxoplasma gondii. The lymphopenia suggests HIV infection. Ring enhancing lesions in the brain suggest either cerebral toxoplasmosis or lymphoma.

A 25 year old male man has urethral discharge. Gram stain of the discharge sample shows gram negative intracellular diplococci. The patient is treated with cefotaxime as a 500mg single intramuscular dose. A week later, the patient still has urethral discharge. Which of the following organisms is likely to be responsible? A. Neisseria gonorrhoeae B. Ureaplasma C. Chlamydia trachomatis D. Staphyloccocus aureus E. Escherichia coli

chlamydia trachomatis. Although the diplococci are likely to be gonorrhoea, this patient has been treated. Recommended treatment options for gonococcal infection are ceftriaxone 250mg single im dose OR cefotaxime (Claforan) 500mg single im dose for gonorrhoea. Persistent discharge suggests another organism, in this case likely chlamydia. Doxycycline would is therefore recommended.

A 18 year old man was admitted to the emergency room due to fever, headache, vomiting, irritability, and myalgia that had begun 24 hours ago. There was no evidence of previous infection in the upper airways. On examination, the patient was lethargic, disoriented and hypotensive, with petechiae in the legs and upper limbs, and he had conjunctival suffusion. Cerebrospinal fluid (CSF) was turbid, with 5300 cells/mm3 (97% neutrophils and 3% monocytes)and protein was 0.9 (<0.5). What is the treatment of choice? A.Erythromycin B. Gentamicin C. Ceftriaxone D. Metronidazole E. Hydrocortisone

c) ceftriaxone. The patient has meningococcal meningitis (suggested by the purpuric rash). Until the organism (Neisseria meningitidis) is isolated and sensitivities tested, the patient should be on a cephalosporin or benzylpenicillin.

A 20 year old man has recently returned from holiday in Spain. He has fever and a sorethroat. Examination reveals palpable lymphadenopathy in the cervical and inguinal areas. Blood tests show: Hb 11.0 g/dl WCC 12 x 10^9/l platelets 145 x 10^9/l urea 7 μmol/l creatinine 80 μmol/l sodium 140 mmol/l potassium 4.2 mmol/l bilirubin 22 μmol/l AST 90 U/l ALP 280 U/l albumin 32 g/l CRP 110 mg/l What is likely diagnosis? A. CMV infection B. Typhoid fever C. Infectious mononucleosis D. Yellow fever E. Schistosomiasis

Answer: c) infectious mononucleosis. Ebstein Barr virus can cause a pharyngitis, palpable lymphadenopathy, thrombocytopenia and deranged liver function tests. Heterophil antibodies will be positive and there may also be lymphocytosis.

30 year old lady presents with headache and neck stiffness. Her temperature is 38.5 °C, BP 100/65 and she has a petechial rash in the thigh. CSF examination reveals gram negative diplococci. Which is the best antibiotic therapy? A.Gentamicin B. Flucloxacillin C. Cefuroxime D. Ciprofloxacin E. Benzylpenicillin

e) Benzylpenicillin. The diagnosis is meningococcal meningitis (it would be pneumococcal meningitis if gram positive diplococci were seen). Intravenous ceftriaxone or benzylpenicillin are treatment of choice.

An 8 year old child develops fevers, myalgia, lethargy and joint pains over 5 days, having been in contact with another child with a similar illness. She has a temperature of 39 ‫؛‬C. On examination, she has a cheek rash, synovitis of the hand and knee joints, and palpable lymph nodes in the cervical area. Which is a likely diagnosis? A. Infectious mononucleosis B. Lyme disease C. Listeriosis D. Leptospirosis E. Parvovirus B19

A 25 year old lady returned from West Africa (she had been there for 6 months). 6 weeks after she returned to the UK and she complained of fever. On examination, temperature was 39.6 C. There was a generalized petechial rash in the lower part of the body. What is the most likely diagnosis? A. Acute HIV infection B. Tyhoid fever C. Lassa virus D. Dengue fever E. P falciparum malaria

34 year old patient has a CD4+ count of 80/mm. He has had a generalised seizure recently. An MRI scan is performed, it shows multiple 1 cm white matter lesions. Which of these diagnoses is likely? A. Progressive multifocal leukoencephalopathy B. Demyelination C. Calcified tubers D. Behcet's disease E. Systemic lupus erythematosus

A 75 year man has severe headaches and photophobia. Examination reveals a temperature of 40°C and neck stiffness. Fundoscopy and CT scan reveal no abnormalities. CSF examination shows Gram positive diplococci. What is the diagnosis? A. Listeria meningitis B. TB meningitis C. Meningococcal meningitis D. Pneumococcal meningitis E. Mycoplasma infection

A 25 year old man presented to an emergency department with a 1-day history of fever, headache and myalgia. Two weeks before his presentation, he had returned from a 10-day trip to Costa Rica, where he had injured the sole of his foot on coral. After injuring his foot, he had swum in freshwater rivers. Thick and thin blood films examined at the time for malaria parasites were negative. What is the likely diagnosis? A. Amoebiasis B. Leishmaniasis C. Schistosomiasis D. Leptospirosis E. Brucella abortius

40 year old diabetic lady presents with a hot swollen left leg. On examination has a temperature of 39°C and her leg is tender to compression. She was treated with intravenous flucloxacillin and benzylpenicillin. However, the erythema has spread even further after 3 days, she is persistently hypotensive with a systolic BP of < 90 mmHg. Which of the following antibiotics should be added? A. Gentamicin B. TazocinC. ChloramphenicolD. ClindamycinE. Amoxycillin

An 75 year old man presents to hospital unwell with diarrhea. He has a BP of 100/70, heart rate 110 and Temp 38 °C. A diastolic murmur is heard in aortic area. His bloods show: Hb 9.0 g/dl MCV 85 fl WCC 13 x 10^9/l platelets 270 x 10^9/l urea 6 μmol/l creatinine 80 μmol/l sodium 140 mmol/l potassium 3.8 mmol/l ESR 80 mm/hr CRP 220 mg/l Which organism is likely to grow in the blood cultures? A. Streptococcus mitis B. Staphylococcus aureus C. Streptococcus bovis D. Escherichia coli E. Brucella melitensis

There was an outbreak of Methicillin Resistant Staph Aureus in the surgical ward. What is the most appropriate measure? A. Antibiotic treatment of the culture positive patients . B. Application of chlorhexidine to the walls and floors of the ward C. Closure of the ward to new admissions for one month. D. Regular handwashing by ward staff . E. Screening of ward staff and exclusion of those with positive cultures.

If there is an open wound then the patient should be isolated into a separate room.

A 35 year old woman presented with a nonhealing genital ulcer. She had travelled through Africa 3 years previously. On examination, An indurated 1.5 cm ulcer was present on the inner aspect of the left labia majoris. Skin biopsy of the lesion revealed a granuloma surrounding a schistosome egg. Schistosoma haematobium eggs were detected in terminal urine collected between midday and 2 pm. What should she be treated with? A. Quinine B. Benzylpenicillin C. Tetracycline D. Flucloxacillin E. Praziquantel

Which of the following is the commonest world wide cause of traveller's diarrhoea? A. E coli B. Giardia C. Shigella D. Salmonella E. Campylobacter

A 40 year old man presented 14 days after return from a 6-week field trip to Papua New Guinea. He had a six day history of high fevers and rigors. On the day of presentation, he had become vague and confused. He had taken antimalarials as prophylaxis, but ceased when he found that local people did not take them. His temperature was 40oC, pulse rate 140 bpm, respiratory rate 28 per minute, and blood pressure 100/60 mmHg. He had dry mucous membranes, mild jaundice, pallor, splenomegaly and generalised crackles in both lungs. Full blood examination revealed: 6.5 g/dL WCC 2.5 x 10^9/L Platelet 10 x 10^9/L bilirubin 60 μmol/L(3–20 μmol/L) lactate dehydrogenase 489 U/L (100–225 U/L) creatinine 250 umol/l What is the likely diagnosis? A. Leishmaniasis B. Tick bite fever C. Endocarditis D. Falciparum malaria E. Viral haemorrhagic fever

A 42 year old man presented 10 days after returning from a 8-week holiday in South-East Asia. He had an eight-day history of malaise, chills, headache, sore throat and generalised rash. He had reported many mosquito bites. He had fever, a macular rash and generalised lymphadenopathy with mild splenomegaly, but no meningism and no eschar present. Full blood examination revealed lymphocytosis with numerous atypical lymphocytes and thrombocytopenia. Blood cultures and malaria films were negative. Liver function tests revealed marginally elevated serum transaminase levels. Serological testing revealed past infection with Epstein–Barr virus and cytomegalovirus and was negative for Q fever, dengue, rubella, measles and rickettsial infection. What is the most likely diagnosis? A. HIV B. Dengue fever C. Syphilis D. Lyme disease E. Malaria

A 65 year old man had been on holiday to Arizona in the united states 6 weeks ago. He was brought to hospital with high fever, rigors, malaise, and mild confusion. He had a generalised, non-pruritic maculopapular rash, predominantly on the trunk but also on the extremities, including the palms and soles. There was no history of animal or arthropod exposure, but his house was on the edge of forest. What is the most likely diagnosis? A. Falciparum malaria B. Rickettsial spotted fever C. Tuberculosis D. Allergic bronchopulmonary aspergillosis E. Schistosomiasis

A 30 year old lady presents with headache and neck stiffness. Her temperature is 38.5 °C, BP 100/65 and she has a petechial rash in the thigh. CSF examination reveals gram negative diplococci. Which is the best antibiotic therapy? A. Gentamicin B. Flucloxacillin C. Cefuroxime D. Ciprofloxacin E. Benzylpenicillin

Answer: e) Benzylpenicillin. The diagnosis is meningococcal meningitis (it would be pneumococcal meningitis if gram positive diplococci were seen). Intravenous ceftriaxone or benzylpenicillin are treatment of choice. Meningococcal Rash

A 40 year old man has been to Malaysia for 6 months. He has an erythematous, serpiginous, pruritic, cutaneous eruption on the medial side of the ankle. What is the diagnosis? A. Lyme disease B. Cutaneous larval migrans C. Leishmaniasis D. SarcoidosisE. E. Tuberculosis

Answer: b) cutaneous larval migrans. Cutaneous larva migrans is caused by the penetration through intact skin of larval animal hookworms (e.g. Ancylostoma braziliense). Diagnosis is predominantly clinical. Treatment is often necessary because of intense pruritus, long duration (over a year) and complications, such as impetigo and allergic reactions. Therapy comprises ivermectin, albendazole or thiabendazole.

20 year old man has recently returned from holiday in Spain. He has fever and a sorethroat. Examination reveals palpable lymphadenopathy in the cervical and inguinal areas. Blood tests show: Hb 11.0 g/dl WCC 12 x 10^9/l platelets 145 x 10^9/l urea 7 μmol/l creatinine 80 μmol/l sodium 140 mmol/l potassium 4.2 mmol/l bilirubin 22 μmol/l AST 90 U/l ALP 280 U/l albumin 32 g/l CRP 110 mg/l What is likely diagnosis? A. CMV infection B. Typhoid fever C. Infectious mononucleosis D. Yellow fever E. Schistosomiasis

A 22 year old man had been to a Greek island on holiday 2 months ago. He presented with a 2-week history of dry cough, diarrhoea, lethargy, anorexia and fever. He had a past history of cutaneous vasculitis of uncertain aetiology. He was not taking any regular medication. On examination, the patient’s temperature was 37.5°C, but no other abnormalities were evident. Investigations showed that he had pancytopenia, raised erythrocyte sedimentation rate and hypergammaglobulinaemia. A second bone marrow biopsy at this time revealed occasional macrophages containing amastigotes. Further history revealed that he had been bitten by sandflies. What is the diagnosis? A. Schistosomiasis B. Cutaneous leishmaniasis C. Visceral leishmaniasis D. Malaria E. Dengue fever

30 year old man presented with bloody diarrhoea. This started 2 days ago. He returned from a business trip to Egypt recently 1 week ago. What is the most likely causative organism? A. Cholera B. E coli C. Giardiasis D. Shigella E. Crytosporidiosis

patient with HIV takes several different drugs is concerned about changing facial appearance. Which drug is most likely to cause lipodystrophy? A. Lamivudine (3TC) B. Zidovudine (AZT) C. Didanosine (DDI) D. Nevirapine E. Saquinavir

A 30 year old man had a tender painful leg with fevers and a year later, progressively develops a swelling in the left leg. Which organism is likely to be responsible? A. Loa loa B. Wuchereria bancrofti C. Schistosomiasis D. Leishmaniasis E. Toxoplasmosis

Wuchereria bancrofti. There is filarial involvement of the lymphatics causing lymphedema or 'elephantiasis'. The organisms are commonly wuchereria bancrofti or brugia malayi. In acute infection, organisms can be detected on a blood film, and filarial serology can be sent. Treatment is with diethylcarbamazepine (DEC) or ivermectin.

Which of the following is the commonest world wide cause of traveller's diarrhoea? A. E coli B. Giardia C. Shigella D. Salmonella E. Campylobacter

E coli. Traveller's diarrhoea is an extremely common occurrence, affecting up to half of travellers to high risk areas such as Africa, Asia and South America. The commonest infective cause worldwide is Escherichia coli. Other bacterial causes include Shigella, Salmonella and Campylobacter, all of which can cause dysentery (diarrhoea with blood).

A 23 year old student has just returned from India having been on a holiday. He was bitten by flies whilst he was there. He has been lethargic for two months and has a fever. Clinical examination reveals hepatosplenomegaly. Ultrasound of the abdomen reveals lymphadenopathy. One of the lymph nodes are biopsied (a smear shows amastigotes within a macrophage). What is the diagnosis? A. Kala azar B. Babesiosis C. Schistosomiasis D. Malaria E. Amoebiasis

Infectious Diseases

Viral Infections

Lab.diagnosis of Viral Infections Immunologic Studies - Antibody titer ; a > 4 fold rise is considered evidence of disease . - Antigenic detection is used for certain viruse( HBsAg, CMV, HIV)  Molecular Techniques; - PCR (eg, HCV and herpesvirus)  Microscopic Methods - search of specific cytopathic changes (eg, multinucleated giant cells at the base of herpes lesions, . 

DNA Viruses AHP

Adeno virus. 1.Acute pharyngitis. 2. Acute follicular conjuctivitis. 3.Acute GE.

Herpes viruses Latent infections, giant cells by Tzanck smear.  HSV-I.  HSV-II.  Varicella (Chickenpox) & Herpes Zoster V. 1. Epstein–Barr Virus (Infectious Mononucleosis). 2. Cytomegalovirus. 3. Human Herpes viruses 6, 7, & 8 .

HSV-I. Dormant in trigeminal ganglion      

oral cavity; stomatitis, herpes labialis (cold sores). Esophagitis; in immunocompromised Eye; Keratoconjunctivitis. CNS; Encephalitis and Meningitis. Skin; Erythema Multiforme . Disseminated Infection.

TTT; Acyclovir 200 mg 5 times for 5 ds.

Herpes simplex encephalitis:. There is more inflammation around the temporal lobe, and the EEG changes .  Acyclovir should be commenced upon clinical suspicion as PCR result may be a few days. 

MENINGITIS       

Meningococcal meningitis: Immunisation is available against strains A &C . (young age) Rifampicin ,ciprofloxacin and ceftriaxone can be used for prophylaxis.

Naisseria Meningitis: Gram negative diplococci. Presentation: fever, BP, DIC, palpable puprpura (purpura fulminans). Treatment  PenG; Don’t wait for cultures if you suspect! Prophylaxis for exposure (close contact): Options    







Cipro 500 mg PO once Rifampin 600 mg q12h x 4 dose Ceftriaxone 250 mg IM x 1

Pneumococcal meningitis (adult) is caused by gram positive diplococci.IV penicillin or ceftriaxone should be given. Dexamethasone is indicated in early infection to prevent neurological sequelae. Tuberculous meningitis: Symptoms are headache, vomiting, photophobia, and fever. The duration of presenting symptoms may vary from 1 day to 9 months. CSF typically shows elevated protein level, markedly low glucose, and lymphocytes. Treatment of TBM includes (INH), (RIF), (PZA), and ethambutol (quadruple therapy). Steroids are usually also indicated.

Listeria Monocytogenes     



Small, gram +, motile rod (bacilli); Causes aseptic meningitis/ septicaemia in neonates, elderly , immuno-suppressed and pregnant women. Associated with consumption of contaminated milk, ice cream, undercooked hot dogs & pate. Rx  Amp + Gent. Also sulfonamides.

Listeria meningitis is generally associated with multiple cranial nerve deficits, particularly of the VIth and VIIth nerves, as well as hemiparesis, ataxia and respiratory abnormalities often leading to respiratory arrest. High dose (eg 2g qds IV) ampicillin & gentamycin are the treatment of choice or sulfa.

Aseptic meningitis 

Aseptic meningitis refers to patients who have clinical and laboratory evidence for meningeal inflammation with negative routine bacterial cultures. The most common cause is enterovirus.



Many causes, but usually viral. Usually self-limited CSF plenocytosis (monos), negative bacterial cultures.

 

 

Additional etiologies include other infections, (mycobacteria, fungi, spirochetes), parameningeal infections, medications, and malignancy. MENINGITIS VERSUS ENCEPHALITIS — The presence or absence of normal brain function is the important distinguishing feature between encephalitis and meningitis.





Important Indications for Steroids in Meningitis  To control the inflammation in adults with acute bacterial meningitis  TB meningitis  Altered mental status or other signs of elevated intracranial pressure Viral meningitis: A combination of lymphocytosis, normal or mildly elevated protein and normal glucose suggests viral meningitis. Common causes include enterovirus and mumps.

HSV-II. genital ulcers; multiple, superficial, painful.  Latent in sacral ganglia. 

Varicella (Chickenpox) & Herpes Zoster (Shingles).    

 1. 2. 3. 4.

  

IP=14–21 days, Latent in dorsal root & cranial N ganglia . face, scalp, and trunk, and later involves the extremities. Rash: pruritic, centrifugal, papular, changing to vesicular, pustular, and finally crusting (polymorphic) different stages of the eruption are usually present simultaneously. Complications; Interstitial pneumonia is more common in adults Encephalitis (1:1000),cerebilitis, Cerebellar ataxia (1:4000). Reye's syndrome, Ramsy Hunt S. In pregnancy; 1st 20 wksCongenital Varicella S. laterH Zoster. peripartumfatal. Inv; EM, IF, serology. Prophylaxis; ZIG IC, pregnancy, Newborn. TTT; Acyclovir if; IC, pregnancy, within 72 hs for patients aged > 16 y.

Congenital Varicella S; lesions of an extremity, growth retardation, microcephaly microphthalmia, cataracts, chorioretinitis and deafness.  Ramsy Hunt S; (geniculate ganglion) pain, vesicles at EAM, facial palsy, loss of taste from ant. 2/3 of tongue. 

Epstein–Barr Virus & Infectious Mononucleosis (IM) Latent in B lymphocytes. C/P; IM should be suspected when an adolescent or young adult complains of;  fever, sore throat, malaise.  Cervical lymphadenopathy, splenomegaly.  Palatal petechiae,  a maculopapular rash in 90% after ampicillin or amoxicillin. 

Complications: - hepatitis, myocarditis, - GBS, encephalitis, - hemolytic anemia, thrombocytopenia, - Lymphoproliferative disorder; Burkitt's lymphoma or nasopharyngeal carcinoma, Oral hairy leukoplakia, B cell lymphomas among immunodeficient patients.

Investigations Hematologic findings -

lymphocytosis > 50% (most common). atypical lymphocytosis, > 10 % of total lymphocytes. DD of atypical lymphocytes ; toxoplasmosis, rubella, roseola, viral hepatitis, mumps, CMV, acute HIV infection.

Heterophile agglutination tests -

detect Heterophil antibodies that agglutinate sheep red blood cells ( Paul-Bunnell test), horse red blood cells ("Monospot" test). The sensitivity approach 85 % = sensitive screening tests.

-

false-positive heterophile tests; leukemia, lymphoma, SLE, HIV ,viral hepatitis. If the heterophile test is positive, no further testing is necessary if the clinical scenario is compatible with typical IM. If the heterophile test is negative, but there is still a strong clinical suspicion, ask for IgM and IgG VCA and EBNA antibodies.

EBV-specific antibodies  Viral capsid antigen& Nuclear antigen - IgM and IgG antibodies directed against the Epstein-Barr viral capsid antigen Nuclear antigen are usually present at the onset of illness & have high sensitivity and specificity(97 and 94 %). - IgM is a good marker of acute infection. - IgG VCA & NA antibodies persist for life and are a marker of old EBV inf.

TTT; self limiting, steroid in Hemat & neuro.

Differential diagnosis: - Streptococcal pharyngitis. - CMV. - acute HIV . - toxoplasma infection. - HHV-6, HBV. • The most important diagnosis to exclude is primary HIV infection; this can be done with both quantitative HIV RNA and HIV antibody testing.

Cytomegalovirus 1.congenital infection jaundice, HSM, thrombocytopenia,microcephaly, periventricular CNS calcifications,mental retardation motor disability & Hearing loss.

Cytomegalovirus 2.

Disease in immunocompetent hosts

- asymptomatic. - IMN like, but Monospot test –ve. - latent in endothelium & T lymphocytes. 3.

Disease in immunocompromised hosts;

- retinitis ("pizza-pie" retinopathy). - Gastrointestinal and hepatobiliary; -Esophagitis, colitisgiant ulcers & bloody diarrhea, AIDS cholangiopathy. - pneumonitis. - Neurologic; polyradiculopathy, transverse myelitis,, and focal encephalitis. - In transplanted liver hepatitis, which can mimic organ rejection. - in renal transplant “nephritis" = which can mimic organ rejection. NB; CMV is not an oncovirus.

CMV

Cytomegalovirus Inv; - serology; Ig M. - Histology; Owl eye inclusions. - PCR o TTT; in IC; - ganciclovir, 5 mg/kg intravenously every 12 hours for 14–21 days. - foscarnet, and cidofovir (nephrotoxic). - Valganciclovir. 

Which of the following is NOT a potential treatment for cytomegalovirus (CMV) infection?  A : Ganciclovir.  B : Foscarnet.  C : Cidofovir.  D : Valganciclovir.  E : Aciclovir. 

HHV-6 (< 2 years) children  roseola infantum,, aseptic meningitis. - In ICencephalitis and pneumonitis.  HHV- Diseases as HHV-6.  HHV-8 - Kaposi's sarcoma in AIDS patients. - Castleman's disease (Fever, GLN, HSM). - primary effusion lymphoma (body cavity lymphoma). TTT of all herpes group = ganciclovir. 

Hepadna viruses HBV.  HDV. 

Papova Viruses 1. -

Human papilloma virus. Warts (genital, planter, flat) Cervical cancer (type 16, 18). Oral leukoplakia (16). SCC in IC. Condyloma accumunata.

Polyoma Viruses; BK virus in IC tubulinterstial Nephritis &graft rejection . JC virus PML;(memory changes , mood changes,visual) MRI (perivent. White matter non enhancing lesions), PCR , HIV Ab. Testing. 2.

Progressive multifocal leukoencephalopathy (PML) 







is caused by chronic infection with JC virus, and causes white matter lesions in the brain. A CD4+ of <100 predisposes to the condition . JC virus invades oligodendrocytes, which manufacture myelin, causing demyelination. Hemiparesis, aphasia, cortical blindness, ataxia and altered mental state may occur with an insidious onset of dementia. Anti-retroviral therapy including a protease inhibitor is the main treatment for PML.

Parvovirus B19 by age 15 years about 50% of children have detectable IgG  In children, an exanthematous illness "fifth disease," erythema infectiosum = slapped cheek appearance.  In ch H Anemia aplastic crisis and PRCA.  Middle-aged persons (especially women) symmetric polyarthritis that mimics SLE and RA, involving the proximal IP joints of the hands, wrists and knees.  In pregnancy , recurrent fetal loss .  Inv; - IgM anti-parvovirus antibodies in serum - PCR. TTT; symptomatic. 

Pox viruses 1.Smallpox (Variola ). 2.vaccinia ; vaccine for smallpox. 3.Monkey, Cow pox ( Zoonotic diseases). 4.Orf (contagious pustular dermatitis, or ecthyma contagiosa) occupational disease acquired by contact with sheep & is self limiting . 5.Molluscum contagiosum; - transmitted sexually or by other close contact . - Discrete, raised, solid, skin colored,1-2 mm in diameter,

central umblication, not surrounded by erythema. - Kobner phenomenon. - if giant or multiple  suspect HIV.

TTT: curettage, cryo, liquid nitrogen , CO2 laser therapy, trichloroacetate.

Human ORF

RNA Viruses

Poliomyelitis

     -

-

At least 95% of infections are asymptomatic, abortive poliomyelitis (minor illness), fever, headache, vomiting, diarrhea, and sore throat. nonparalytic poliomyelitis, signs of meningeal irritation. paralytic poliomyelitis in 0.1% asymmetric, pure motor. Prevention in the developed world , the inactive (Salk) parenteral vaccination (IPV) is used for all four doses (at ages 2,4 ,6 and 18 months.

In the developing world; Oral vaccines (OPV as sabin) ease of administration, effective local gastrointestinal and circulating immunity, The interval between oral polio vaccine doses should probably be longer than 1 month. Intramuscular injections should be routinely avoided during the month following oral poliomyelitis vaccination to prevent provocation paralysis.

Coxachie, Cutanuous & Oropharyngeal Herpangina, Hand, foot & mouth dis. ( type A Coxachie).  Neurological ( aseptic meningitis & encephalitis)  Cardiac ( Myocarditis, pericarditis, pleurisy with type B Coxachie).  Muscle (Bornholm dis = intercostal myositis as pleurisy with type B Coxachie) 



ECHO, Entero 68-71- aseptic meningitis.

Coxsackie (Hand, Foot and Mouth disease)

Influenza Types; A,B ,C  H1-5 & N1,2 are 2 glycoproteins on cell surface. H (Hemagglutinin for viral attachement) N (Neuraminidase for viral budding). C/P; F, headaches, sore throat, limb aches, persistent dry cough. Complications; 1) Strept pneumoniae, H influenza, staph areus. 2) Postinfectious encephalomyelitis, ADEM. 3) Viral pneumonia, pericarditis, myocarditis, myositis & GBS. TTT; Bed rest, paracetamol. Antibiotics for patients with chronic bronchitis, cardiac & renal. Zanamivir, Oseltamivir ( neuraminidase inhibitor ) for pt > 65 yrs , IC, Used for prophylaxis or infection within 2 days. Prophylaxis; 1- inactivated influenza Vaccine. 2-Amantadine. Given for pt > 65 yrs/year, CHD, CRF, chronic lung dis., DM. 

Respiratory syncytial V. - outbreaks of pneumonia in eldery & IC. - TTT; ribavirin.

Measles= robeola Prodrome of fever, cough, conjunctivitis, malaise, irritability, photophobia, Koplik's spots.  Rash: red, maculopapular; onset 3–4 days after onset of prodrome; begins on the face and proceeds "downward and outward," affecting the palms and soles last.  Complications 1) Postinfectious encephalomyelitis, ADEM,SSPE . 2) Respiratory ; bronchopneumonia or bronchiolitis . 3) Gastroenteritis Measles during pregnancy is not known to cause congenital abnormalities of the fetus. However, it is associated with spontaneous abortion and premature delivery. 



Prevention;

-

MMR at 12–15 months and a second at age 4–6 years. IG within 5 ds of exposure……. to; pregnant, child< 3y, IC. Inv; Ig M after 2 ds of rash. TTT; Vit A ↓ mortality.

o

Mumps  

  

Painful, swollen salivary glands, usually parotid. commonly, orchitis (affecting fertility in around 5% of bilateral cases), aseptic meningitis, encephalomyelitis, pancreatitis, and oophoritis. Mumps is an RNA virus. Its IP is 7 days. Prevention over age 1 year, vaccines(eg, in MMR). A second dose is recommended for children prior to starting school.

Rubella= German measles(Toga viruses) Prodrome; mild symptoms (fever, malaise, coryza) coinciding with eruption.  Posterior cervical and postauricular lymphadenopathy 5–10 days before rash.  Fine maculopapular rash of 3 days duration; face to trunk to extremities.  Complications; 1.fetal infection during the first trimester congenital rubella $ in at least 80% of fetuses. cataracts, microphthalmia, glaucoma, hearing deficits, PDA. 2.Postinfectious Encephalopathy, 1–6 days after the rash. Contact during the first trimester. -immediate rubella antibody level should be obtained. If +ve=immunity. - If –veclinical observation and serologic follow-up & therapeutic abortion. Inv; Hemagglutination rubella antibody Prevention; MMR not in pregnancy, at least 3 months before pregnancy. 

Dengue( in Asia, Africa, America )  

Ades Agypti. C/P; A) classic Dengue: Fever, rash, back pain, LN . severe musculoskeletal pain is the prominent feature. B) Dengue Hgic fever :

 

Diagnosis; IgM Ab by Elisa. TTT; supportive (IV fluids, bl. Transfusion , correct coagulopathy , no role for steroids).

Lassa fever Subsahara west Africa (Nigeria)  CP; as dengue (Fever, rash, back pain, LN , Hgic F). 



Reservoir; rats (urine).

Diagnosis; Ig M, PCR.  TTT; Ribavirin 

Yellow fever (Not in Asia) Jungle YF; Ades Africanus (in africa). (America).  Urban YF; Ades Agypti.  C/P; mild as influenza. severe; 3 phases – fever, flushing, conjuctival suffusion. - remission. - Hgic shock.  Diagnosis; clinical.  Prevention; live attenuated vaccine (17 d chicken embrio V.) protection > 10yrs.  TTT; supportive. 

Rift Valley Fever  Africa (south, east).  Fever, hgic F, meningoencephalitis.  Diagnosis :serology- Ig M.

West nile F;    

common, endemic in north America. Transmitted by Mosquito. Fever, headache,1% encephalitis. Diagnosis; CSF & serum IgM.

Japanese encephalitis;    

In east asia. Wt loss, encephalitis Diagnosis; Ig M by Elisa. Vaccine; inactivated mouse brain V.

Hanta Virus Europe, America.  Wild rodents by Aerosolized excreta.  Hgic fever, renal failure, pulmonary$ (pulmonary oedema, resp. failure). 

Haemorrhagic fever Causes: 

  

Arbo viruses; yellow F , Dengue, Rift valley fever, West nile, Japanese encephalitis. Other viruses; Hanta, Lassa, Ebola. Rickettsia; Tuphus Spirochetes; relapsing fever (borrelia).

C/P; Fever, conj. Suffusion. Liverhepatitis, jaundice, bleeding from all orifices, DIC. Bloodpancytopenia (hgic shock), postural drop of BP. Kid ATN, ARF.

Rabdoviruses (Rabies) Urban

Sylvian (wild)

Dogs, cats

Bats

classic

paralytic

Hyperreflexia, spasticity Sympathetic overactivity, aero & hydrophobia ,agitation, hallucination, bezare behaviour,convulsions,

Ascending paralysis as GBS

Death within 2 wks

Rabies •virus travel along peripheral nerve to CNS. •Diagnosis;- Ag in salivary secretions - Negri bodies in hippocampus & cerebellum postmortum. •IP; 1-2 months up to several yrs. •Management; If animal captured watch it for 10 days. If not1- Human diploid cell Vaccine. 2- wash wound with soap. 3- human rabies Ig. 4- antibiotics.

Retroviruses 

Contain reverse transcriptase; RNADNA.

Lentivirus HIV-1

Oncovirus HTLV-1 -Adult

T cell lymphoma. -Tropical spactic paraparesis

(a demyelinating disease that causes spasticity and weakness usually in middleaged women).

HIV-2 - restricted to west Africa

HTLV-2 - Myelopathy

Human immunodeficiency virus (HIV) HIV is a retrovirus infecting T-helper cells Transmission  Sexual (60-70%). Other causes: iv drug abuse (3%); infected blood products; mother to child; accidental exposure (e.g. needle stick injuries). Clinical disease  Primary HIV Early HIV Most patients are asymptomatic Symptoms: glandular-fever like syndrome of diffuse maculopapular rash, fever, fatigue, night sweats and generalized lymphadenopathy. Rarely, acute neurological symptoms (aseptic meningitis, transverse myelitis, encephalitis). FBC may show atypical lymphocytes. Advanced HIV  Accompanied by immunosuppression or AIDS (if CD4 count <200 cells/mm3). Patients are at risk from opportunistic infections (e.g. pneumococcal infection, TB, CMV, Pneumocystis carinii, toxoplasmosis, and cryptosporidial diarrhoae) and AIDS-associated malignancies (e.g. Kaposi's sarcoma, lymphoma). 

Prevention Prevention of transmission from mother to child ,risk can be dec. to <5% by treatment with zidovudine given to the mother antenatally, during delivery, and to the neonate for 1st 6wk.; elective LSCS; and advising against breast-feeding Antiviral drugs 3 groups:  Nucleoside analogues (e.g. zidovudine)  Non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine)  Protease inhibitors (e.g. indinavir).  HAART (highly active antiretroviral therapy) is a combination of 3 drugs. Adherence to therapy is essential to avoid resistance. consideration for HAART  Patients who present with clinical manifestations of HIV(acute HIV $),  CD4 counts <350cells/mm3, or  viral loads > 30,000 copies. 

Prophylaxis against opportunistic infection    

Patients with low CD4 counts are started on prophylactic antibiotics: <200 cells/mm”Pneumocystis carinii (co-trimoxazole) <100 cells/mm”toxoplasmosis (co-trimoxazole) <50 cells/mm ”Mycobacterium avium (azithromycin)& CMV



RECOMMENDATIONS FOR INDIVIDUAL PATHOGENS

Pneumocystis  TMP-SMX as first-line preventive therapy (one DS tablet or one SS tablet daily)  intolerance or allergy to TMP-SMX, dapsone (100 mg given once daily) (Grade 1A).  In patients who cannot tolerate TMP-SMX or dapsone,  aerosolized pentamidine  during the first trimester, pregnant women should be treated with aerosolized pentamidine rather than systemic prophylaxis Toxoplasma  TMP-SMX as first-line preventive therapy (one double strength tablet/ day)  who are allergic to TMP-SMX, dapsone plus pyrimethamine plus leucovorin . Pyrimethamine is teratogenic and should not be used during pregnancy.

Mycobacterium avium complex; macrolides for the primary prophylaxis of MAC infection in patients with a CD4 count < 50 cells/microL (Grade 1A). E.g. weekly azithromycin rather than daily clarithromycin Histoplasmosis; itraconazole (200 mg daily) for the prophylaxis of histoplasmosis in patients with a CD4 count <100 cells/microL who are at risk due to occupational exposure or who live in a community with a histoplasma. Candida; Do NOT use systemic therapy for the primary prophylaxis for vaginal, oropharyngeal, or esophageal candidiasis due to cost and potential for drug interactions (Grade 1A). Cryptococcus; antifungal prophylaxis NOT be used routinely to prevent cryptococcosis because of the relative infrequency of cryptococcal disease, lack of survival benefits associated with prophylaxis, Cytomegalovirus; Risk of CMV disease occurs mainly due to reactivation of latent infection in the setting of advanced immunosuppression, especially when CD4 counts are less than 50 cells/microL. However, we do NOT suggest routine prophylaxis due to cost, risk of resistance, and lack of proven survival benefit (Grade 2A). Cryptosporidium, Do NOT administer prophylaxis for cryptosporidium (Grade 2C).

Kaposi sarcoma     

Caused by HHV-8. Purple papules or plaques on skin or mucosa of any organ. Metastasizes to lymph nodes: Associated with AIDS or transplant patients commonly, skin or pulmonary lesions. Fatal. Incidence decreased with HAART.

AIDS dermatology Kaposi sarcoma.  Herpes Zoster.  Oral hairy leukoplakia; EBV in advanced AIDS, premalignant .  Molluscum contagiosum  Bacillary angiomatosis. 

Epstein Barr virus

Antiretrovrial therapy 

is initiated in asymptomatic patients when the CD4 count approaches 200. It is also initiated in patients with symptomatic disease and higher CD4 counts and considered in symptomatic seroconversion illness.



Nucleoside reverse transcriptase inhibitors (NRTIs) such as (zidovudine) are associated with lactic acidosis, peripheral neuropathy, pancreatitis, bone marrow suppression, discolouration of the nails& proximal myopathy. Lamivudine is the least likely agent to cause symptoms and is generall well tolerated. DDI (Didanosine) causes pancreatitis.



Non-nucleoside reverse transcriptase inhibitors (NNRTIs) inhibit reverse transcriptase non-competitively. Nevirapine may cause Stevens Johnsons syndrome/ rash and deranged LFTs. Protease inhibitors, such as , saquinavir, ritonavir and indinavir are associated with lipodystrophy, insulin resistance, and disturbed fat and glucose metabolism Indinavir crystallises in the renal tract stones





Bacterial infections

Impetigo Crusted golden yellow erosions.  On nose & cheek, lips, chin.  Staph aureus, group A strept. 

Erysipelas Erythema + raised sharp demarcated borders, group A strept( more commonly), & staph.  Shin of tibia & face. 

Scarlet fever   

   

Gp.A haemolytic streptococcus infection. Incubation: 2-4 d. Presentation: Fever, malaise, headache, tonsillitis, rash (fine punctate erythema sparing face,palm & sole)& heal by desquamation& pealing. facial flushing with circumoral pallor. strawberry tongue Treatment: Penicillin V 250-500mg qds for 10d. Complications: Rheumatic fever & acute glomerulonephritis

Methicillin-resistant Staph. aureus (MRSA) 







MRSA acts in exactly the same way as any other Staph. aureus”it causes a range of infections. It is only different due to its multiple resistance to antibiotics. Often contracted in hospital. Wash hands thoroughly with an appropriate antibacterial preparation if they appear soiled. If hands appear clean, wash with an alcoholic rub between each and every patient contact.

2 Toxic shock syndrome Staph aureus toxin mediated (TSST-1, enterotoxin).  Fever, hypotension, generalised skin & mm erythema ,vomiting, diarrhea, confusion & MOF.  In menstrual & non menstrual patterns, barrier contraception, puerpurium, septic abortion, surgery, burns.  TTT; staph IV nafcillin or oxacillin. strept pen. G + clinda IV 

Streptococcus bovis usually enters the bloodstream via the gastrointestinal tract. Nearly all patients with St. bovis endocarditis are older than 50 years, and there is also an association with malignancy of the GI tract.  Treatment is with penicillin or vancomycin and gentamicin. 

Haemophilus influenzae Meningitis(60%); 8- 11% have permanent neurological sequelae; Epiglottitis(15%)  Septicaemia(10%)  Osteomyelitis.  Septic arthritis  Pneumonia.  Pericarditis.  Management  Admit patients with severe infections. Organisms are often penicillin-resistant and treatment is usually with iv cefotaxime.  Prevention  Vaccination is routinely offered to all children ,In addition, to all unimmunized asplenic patients (preferably 2wk. prior to splenectomy) and HIV +ve patients.

Diphtheria: 



Corynebacterium diphtheriae causes diphtheria. It is a gram positive rod. It may present with sore throat, fever and lymphadenopathy, heart failure or neurological damage. A greyish pseudomembrane can also form on pharynx and conjunctivae. The illness is still present in Eastern Europe and Russia. Treatment is with diphtheria antitoxin, penicillin or erythromycin.

Anthrax 



 

is caused by a gram positive, aerobic, bacillus called Bacillus anthracis. In humans, cutaneous anthrax commonly causes a painless, black, indurated eschar Inhalational anthrax characteristically causes a haemorrhagic mediastinitis. The prodrome includes high fever and rapid deterioration follows. Mortality of inhalational anthrax is 90% if untreated. Treatment is with IV penicillin. Prophylaxis is with ciprofloxacin.

Pseudomonas Aeruginosa  







Common organism leading to infections complicating burns Cause of malignant otitis externa in diabetics. when P.aeruginosa penetrates the epithelium overlying the floor of the external auditory canal and invades underlying soft tissue, cartilage, and bone. Peudomonas aerugionosa and Staph aureus are the most common causes of otitis externa among patients in general. May cause ecthyma gangrenosum in neutropenic patients with bacteremia &common cause of pneumonia and septicaemia. In immunocompetent patients may cause UTI, wound infections.

ecthyma gangrenosum

fish tank granuloma

fish tank granuloma



 

most commonly causes a localized cutaneous eruption, on the fingers or hands of fishermen or seafood packers who suffer minor trauma while handling contaminated shrimp, crab, or fish. Handling fish. Ethambutol plus rifampin appears more useful than minocycline in treating cutaneous M marinum infection. Granuloma and staining for acid-fast bacteria yielded positive results in(63%).

Erysipeloid

Similar to fish tank granuloma. BUT  Erysipelothrix rhusiopathiae is gram-positive bacillus.  Violaceous eythematous cellulitis to the hand.  TTT : .... penicillin V (500 mg/6 h) or ciprofloxacin ,or erythromycin for 7days. 

Occupational infectious diseases Human ORF (virus)-------sheep handlers.  Sporotrichosis (fungal)-------------gardener  fish tank granuloma----- (MB marinum) fish handler.  erysipeloid (Erysipelothrix rhusiopathiae) ------fishing 

Clostridium Botulinum (‘Botulism’) 

Botulism is caused by the neurotoxins of Clostridium botulinum which interferes with presynaptic Ach release, causing the 6D’s  Dilated fixed pupil; Diplopia; Dysphagia; Dyspnea; Descending paralysis. 

It may be acquired by ingestion of toxin or more commonly in the UK wound infection as a result of intravenous drug use.

Therapy consists of approximately 10,000 IU of antibodies against toxin types A, B, and E(antitoxin) 

also supportive care (e.g. ventilation).

Tetanus  

    

manifested by uncontrolled spasms, due to the introduction of Clostridium tetani toxin into tissues. Skin punctures, contaminated wounds with soil, dust, neurotoxin (tetanospasmin) which causes severe spasm---- painful muscle contraction and laryngeal spasm which interfere with breathing . The incubation period is typically between 1-2 weeks. Vaccination with tetanus toxoid proved to be effective . TTT: Tetanus antitoxin. Booster immunization for those who the last immunization received was about 10 years or more. supportive along with penicillin,

Pasteurella Multocida  Cat (>dog)bite is the #1 mode of transmission.  Pen G best, but Amox or Augmentin fine. Capnocytophagia  Dog (>> cat) bites  Give Augmentin or Clindamycin  May cause bacteremia in immunosuppressed patients, splenectomized patients, and alcoholics.

Cat scratch disease Bartonella henselae, Benign self limiting.  1ry skin then tender LN  In IC-----Bacillary angiomatosis; vascular papules or nodules, bartonella henselae& quantana, transmitted by cats.  TTT: erythromycin or Doxycycline. 

Cat scratch disease

Necrotizing fascitis Anaerobe& aerobe.  DM & abd. Surgery.  C/P ---pain ,erythema,crepitus.  TTT: Debridement + pen G + clindamycine. Hyperbaric oxygen. 

Gas gangrene:  Clost. 

Perifringes

TTT: Debridement + pen G + clindamycine. Hyperbaric oxygen.

Pseudomembranous colitis (Clostridium difficile) common with clindamycine & is rare with aminoglycosides, probably because they have little activity against anaerobic gut flora.  Toxins mediated A or B.  TTT: metronidazole if not responding....... Vancomycin. 

Pertussis (whooping cough)   

  

 

Caused by Bordetella pertussis. Incubation: 7d. Symptoms:  Catarrhal stage. symptoms and signs of URTI; lasts 1-2wk.  Coughing stage- increasingly severe and paroxysmal cough with spasms of coughing followed by a whoop; associated with vomiting& cyanosis. Lasts 4-6wk., then cough improves. Examination: Chest is clear between coughing bouts. FBC---lymphocytosis. Complications: Pneumonia, bronchiectasis, convulsions, subconjunctival haemorrhages.

Treatment with Erythromycin. Prevention with DPT.

Enterobacteria Examples include:  Salmonella  Shigella  Escherichia  Klebsiella  Enterobacter  Proteus  Yersinia

Some are normal gut commensals. Others are pathogenic causing:  Diarrhea .  UTI . frequently E. coli; Proteus species are associated with bladder stones.  Intra-abdominal infections. including peritonitis and hepatobiliary infection.  Septicaemia.  Chest infection. Klebsiella may cause a severe form of pneumonia. 

Traveller's diarrhoea is an extremely common occurrence, affecting up to half of travellers to high risk areas such as Africa, Asia and South America. The commonest infective cause world-wide is Escherichia coli.  Shigella, salmonella, campylobacter and amoebic dysentery may be bloody. ( Yes Can Cause)  Cholera (profuse rice-water stools – several litres/day) and Giardia (explosive) diarrhoea are never bloody.  The common causes of bloody diarrhoea include Salmonella , Shigella , Campylobacter and amoebiasis. E. coli type H7: E 0157 can also cause bloody diarrhoea with Haemolytic uraemic syndrome 

The common causes of watery diarrhoea 



Giardia lamblia infection can present with abdominal pains and diarrhoea or steatorrhoea. Duodenal aspirate +biopsy can confirm the diagnosis. Villous atrophy is associated. Bacillus cereus food poisoning is caused by toxin release. There are two types of toxin, - the Diarrhoeal (causing diarrhoea) and the Emetic (causing vomiting). Symptoms are nausea, cramp like abdominal pains hours after ingestion usually of rice and watery diarrhoea. Cryptosporidium is water borne and is a protozoan parasite. Swimming in hot tubes and pools, lakes are risk factors. It can also be spread via uncooked food. Treatment is conservative. Symptoms typically last for 1-2 weeks but longer in immunocompromised e.g. HIV.

Typhoid fever   





Caused by Salmonella typhi and Salmonella paratyphi. Spread: By the faeco-oral route. Incubation: 3d-3wk..

Symptoms: Usually presents with malaise, fever, headache, constipation (or diarrhoea), bruising, and/or abdominal pain. Examination: Pyrexia; relative bradycardia; rose-coloured spots on the trunk (40%); splenomegaly; CNS signs (coma, delirium, meningism).

Legionnaires’ Disease 

Clinical:  “Lung/Liver/Lytes/Loose BMs” 

   

Lung  Bilateral patchy infiltrates; relatively nonproductive cough; Patients with community-acquired Legionnaires’ disease are much more likely than patients with pneumonia from other causes to be admitted to the ICU upon presentation. Liver  LFTs increase Lytes  Hyponatremia, hypophosphatemia Loose BMs  diarrhea. Lymphopenia.

   





Weakness, malaise, high fever, cough. The most common risk factors for Legionnaires’ disease are cigarette smoking, chronic lung disase, advanced age and immunosuppression. Laboratory Diagnosis: b. √ Urine Antigen-1: Antigen in urine is detectable 3 days after the onset of clinical disease, even if specific therapy has been started; furthermore, urinary antigen persists for several weeks after antibiotic therapy. c. √ Ab with IFA (Indirect fluorescent Ab) test; > 1:256 or a 4-fold ↑ is pos.

Treatment: Another clue to recognizing this disease is failure to respond to -lactams (PCN or cephalosporins) or aminoglycosides. Treatment options include  erythro + rifampin; fluoroquinolone; or azithromax.

Mycoplasma 

    

Mycoplasma pneumoniae causes epidemics of lower respiratory tract infection every 3-4y. Spread by droplet infection. Incubation :14 d. Presentation :Dry, persistent cough ±‫آ‬ arthralgia. CXR shows bilateral, patchy consolidation. Infection is confirmed with serology. Management :Erythromycin 500mg qds for 2wk. (alternative is tetracycline).

Mycomplasma Pneumoniae (“Walking Pneumonia”)      

Community-acquired pneumona, esp in young patients Cold agglutinin production + hemolytic anemia Erythema multiforme, Stevens-Johnson syndrome Neurological effects-Guilliain-Barre, cranial nerve palsies, polio-like syndrome, aseptic meningitis Mononeuritis multiplex Erythromycin is the drug of choice in the young patient with fever/dry cough/patchy bilateral interstitial infiltrates, and relatively benign exam, don’t give PCN.

Chlamydial infection  



 

3species: C. trachomatis :Includes 15 serotypes. Causes trachoma and inclusion conjunctivitis; sexually transmitted diseases. C. pneumoniae :community-acquired pneumonia, especially in children and young adults. May be clinically indistinguishable from pneumonia caused by Mycoplasma . Treat with tetracycline or erythromycin po for 2wk. or azithromycin 500mg od for 3d. C. psittaci :Infects many animals, but human infection is closely related to contact with birds. Treat as for C. pneumoniae)

Chlamydia Psittacosis 



   

Most patients with psittacosis have a history of contact with birds, e.g. poultry workers cleaning out bird cages. Clamydia psittaci infection of humans most commonly presents as fever of abrupt onset, severe headache, and dry cough , rigors, sweats, and myalgias in a patient with a recent history of bird exposure; AST ↑ in nearly half of patients; hyponatremia common. Serology via the complement fixation test is the test traditionally used to make the diagnosis. Doxycycline and TNC are the drugs

Q fever 



 

is a worldwide zoonosis & due to Coxiella burnetii and In humans, is acquired via animal contact or exposure results from inhalation of contaminated aerosols . in farming communities . Clinical signs of Q fever are often extremely mild or absent. Patients may be asymptomatic or can present acutely with one of three clinical presentations: A self-limited flu-like illness Pneumonia. Hepatitis Chronic infection most commonly involves the heart as endocarditis. Aortic valve.& uvitis. Treatment is with prolonged courses of tetracyclines

Brucellosis is caused by G –ve coccobacilli which spread through untreated milk and raw beef and may affect all systems.  B. abortus (cattle), B. suis (swine), B. melitensis (goats), B. canis (dogs) are the different organisms. Persons at risk – Acquired via contact with animal tissues or after ingestion of unpasteurized milk or cheese. • Farmers; dairymen; meat packers • Veterinary surgeons. diagnosis  Cultures of blood or other sites, especially bone marrow or liver biopsy specimens Detection of brucella requires extended blood culture of up to 6 weeks. . So, if you suspect it, ask the lab to hang on to the cultures for a longer period.  CBC: Leucopenia is common.  Serology : Brucella agglutinins also helps confirm the diagnosis. C/P; Spondylitis or osteomyelitis, endocarditis, pneumonia, liver granuloma and jaundice and pyelonephritis. 



Brucellosis 

Brucellosis is a well-documented cause of fever origin.

of unknown



Virtually any organ system can be involved with brucellosis; most commonly however:

• Osteoarticular, especially sacroiliitis – 20 to 30 percent. • Genitourinary, especially epididymoorchitis – 2 to 40 percent of males. 



Presentation – • Fever, chills • Headache • Back pain, Arthralgias • Orchitis • Cough • Hepatomegaly/Splenomegaly,Endocriditis Treatment: 2 accepted regimens: • Doxycoycline 100 mg PO twice daily for 6 wks plus streptomycin 1 gram IM daily for the first 14 to 21 days. • Doxycycline 100 mg PO twice daily plus rifampin 600 to 900 mg PO once daily for six weeks.

 Neisseria

Gonorrhea

Gram negative diplococci  Look out for the 20 y.o man or woman with fever + swollen knee  >80% of women are asymptomatic; only 2% of men asymptomatic.  Disseminated gonorrhea most likely to occur in menstruating females; 2 phases…  a) Bacteremic phase: tenosynovitis; skin lesions; joint cultures negative  b)Nonbacteremic phase: monoarticular arthritis of knee/wrist/ankle; joint culturemay be positive.  Remember, if a patient has a history of recurrent infections, she probably has a deficiency in late complement components (C5-8).  Patients with GC should also be empirically treated for Chlamydia because of the high risk of co-occurrence. 

Rickettsial Infections    

   

Endemic typhus, epidemic typhus, Rocky Mt. spotted fever All these infections have an insect vector. They all yield a rash. Rocky Mt. spotted fever (RMSF)  erythematous and hemorrhagic macules and papules begin peripherally (wrists/forearms, ankles) and spread (to trunk, face). Fever, H/A, myalgia. Rash begins on the 4th day of the fever. Na+ is seen in half the cases. transmitted by the American dog tick. History of tick bite given in >80% of cases. Doxycycline IV or PO BID x 7 days.

Typhus fever FAHMRT.  Rash ---Measles like.  Multisystem affection. 

Serology.  Doxycyclines. 

Spirochetal infections T. pallidum -------syphilis  Leptospira-------- Leptospirosis.  Borrelia.-------relapsing fever & Lyme dis. 

Leptospirosis Leptospirosis is a zoonosis caused by the spirochet,Leptospira interrogans. 

  

  

Humans most often become infected after exposure to animal urine, contaminated water or soil, or infected animal tissue through abraded skin, mucous membranes or conjunctiva. toxic phase: abrupt onset of fever, rigors, myalgias and Conjunctival suffus. Immune phase: meningitis, myocarditis, arthritis,ARF,Jaundice. NB .Conjunctival suffusion in a patient with a nonspecific febrile illness should raise suspicion for the diagnosis of leptospirosis

Cultures of blood. Serology. TTT: penecillin G.

Lyme Disease: 



         

Causes by the spirochete bacteria Borrelia Burgdorferi, which is carried by the Ixodes dammini tick (the vector). It is seen primarily in summer and fall. Stage I  few days after the tick bite  Flu-like illness  ECM (Erythgema Chronicum Migrans; 60%) Stage II Weeks to months following bite. 10-15% develop neurologic abnormalities (e.g. Bell’s palsy) and/or carditis) Carditis and facial palsy are commonly reversible. Stage III Can become chronic Arthritis develop in 30-50% Usually oligo or monoarticular of large joints. diagnosis with serology Lyme test should be used only for confirmation if suspect the disease, and not for screening, because of false positives and false negative.

Complications by system…     

Treatment:    



Skin lesions (ECM). Neurological- Cranial nerve palsies; peripheral neuropathies; meningitis. Cardiac- AV block; myopericarditis Arthritis-large joints, asymmetric; often affects the knee. Early (ECM)  Doxy or Amox x 2-3 wk; Arthrisis  Doxy or Amox – duration unknown. Carditis  Ceftriaxone/Cefotaxime x 2-3 weeks. Meningitis  Ceftriaxone IV x 3 weeks

Pregnant women  No doxycycline

Erythema chronicum migrans (ECM) Rapid expanding ring with clearing middle in trunk & axilla.

Relapsing fever Borrelia Duttoni.  Rodents.  Tick born.  C/P----- (Haemorrahgic fever) FAHMRT, Jaundice, HSM, Bleeding.  Diagnosis: microscopic demonstration of spirochetes in blood during fever.  Serology.  TTT: Tetracyclines 

Actinomyces Israelii 

is a gram positive bacillus which behaves like a fungus, causing actinomycetoma – deep tissue infection which is granulomatous. Nodules develop under the skin and erupt to discharge Sulfur granules.

Anaerobic, gram +, branching, filamentous.  May present with 

Paramandiblar infection with a chronic draining sinus usually preceded by dental extraction.  Pulmonary abscess.  Rib destruction.  Chest wound infection. 



Check anaerobic culture for diagnosis.



TTT: penecillin G.

Nocardia 

    

Nocardia is another branching, filamentous gram positive bacillus which may appear acid-fast. It causes infection in immunosuppressed. Causing “fungal-like” activity of mycetoma. It is treated with co-trimoxazole. Presents as chronic pneumonitis and lung abscess. In patients with chronic pneumonia who develop neurologic symptoms  rule out nocardia brain abscess.

A 26-year-old female presents with a short history of confusion, diarrhoea and breathlessness. On examination she is pyrexial at 38.5 C, pulse 120 bpm, Bp 80/60 and respiratory rate 26 breaths/min. She has a faint blanching macular rash across the trunk. She is disorientated without meningism. Which of the following diagnoses is most likely? A : Salmonella enteritidis infection. B : Pneumococcal meningitis. C : Anaphylaxis. D : Ecstasy overdose. E : Toxic shock syndrome. 

A 40-year old man from Saudi Arabia (in UK 4 days) presents with painful episodes of trismus. He has never been vaccinated against tetanus and sustained a slight cut to his foot while walking barefoot in his garden in Saudi Arabia 3 days before arriving in the UK. You suspect tetanus and he then has an episode of generalised tetanus with respiratory arrest. Which of the following is incorrect as part of his management? A : Admit to side ward in intensive care unit. B : IV gentamicin to kill any Clostridium tetani bacteria left in wound. C : Tetanus toxoid as he will not be immune to tetanus even after recovery from infection. D : Clean, debride and dress his foot lesion. E : IM tetanus antitoxin. 

Fungal infections Systemic

Subcutaneous

Superficial

Candidiasis

sporotrichosis

Pityriasis versicolor

Histoplasmosis

Subcut. Zygomycosis

Cryptococcus

Mycetoma=madura foot

Coccidiodomycosis Aspergillosis Blastomycosis Zygomycosis=mucor mycosis

Superf. Candidiasis Dermatophytosis

Candidiasis          

Most common fungal inf. In human, by candida Albicans. Pt usually IC. Candida infection commonly causes mucosal disease (eg. Vulvovaginitis). Candidal oesophagitis.(small superficial erosions) Cutaneous Candidiasis (intertriginous areas). Endopthalmitis (causing blindness if not rapidly diagnosed) and IV line related sepsis can also occur. Hepatic candidiasis in neutropenic pt after BMT. Chronic mucocutaneous candidiasis; rare, in children, + endocrinopathies e.g. hypoadrenalism & hypoparath.(PAC). The diagnosis can usually be made on blood cultures but the organisms can be seen in the lesions on biopsy. TTT; mild oral Nystatin. severe Amphotericine, itraconazole IV.

Histoplasmosis  

 





As TB,

May occur in immunocompetent individuals. causative agent, Histoplasma capsulatum, non encapsulated fungus, transmitted by inhalation of spores in bird droppings. found worldwide, particularly in North and Central America. Histoplasmosis remains asymptomatic in most healthy individuals following low level exposure. Symptomatic infection usually produces self-limited pulmonary illnesses, erythema nodosum, or pericarditis, Individuals at the extremes of age or with underlying immunosuppressive conditions can develop progressive disseminated or diffuse pulmonary disease with cavity formation.

Major clinical forms Asymptomatic pulmonary Histoplasmosis; +ve skin test. Acute diffuse pulmonary histoplasmosis- Following more extensive exposure in areas with large amounts of bird droppings. In such cases, antigen testing and cultures are often positive.

Chronic pulmonary histoplasmosis —in Patients with underlying lung disease  productive cough, dyspnea, chest pain, fevers, and sweats and have fibrotic apical infiltrates with cavitation. Serology (complement fixation titers) is positive in nearly all cases.

Disseminated histoplasmosis as Disseminated TB; fevers, LN, HSM, neutropenia, thrombocytopenia in infant, transplant, HIV.  Differential diagnosis sarcoidosis , tuberculosis , malignancy. Diagnosis; demonstration of fungus histologically. CFT after 3 wks.(serology). TTT : Itraconazole, fluconazole and amphotericin B.

When to suspect pulmonary histoplasmosis — 1. 2. 3.

Pneumonia with mediastinal or hilar lymphadenopathy. Mediastinal, hilar masses, Pulmonary nodule suggestive of malignancy Cavitary lung disease suggestive of tuberculosis.

Shared findings with sarcoidosis include ; 1. 2. 3. 4.

5.

diffuse pulmonary infiltrates, mediastinal lymphadenopathy, erythema nodosum, hepatic enzyme elevation, splenomegaly. Serum angiotensin converting enzyme concentrations are elevated, noncaseating granulomas are a shared pathologic finding.

Coccidiomycosis Coccidiomycosis manifests similar to histoplasmosis and spreads to the lymph nodes.  In south America.  60% asymptomatic, 1%pulm cavities, fibrosis in IC.  Diagnosis; 1- Intradermal tests are diagnostic. 2- latex agglutination & precipitation test (Ig M). 3- CFT (Ig G).  Treatment is with Itraconazole, fluconazole & amphotericin 

Cryptococcus neoformans  

  1. 2. 3.  1. 2.

Route; inhalation of fungal spores blood to the CNS, particularly in patients with advanced AIDS. Cryptococcal meningoencephalitis is the most frequently encountered manifestation of cryptococcosis. Symptoms typically begin in an indolent fashion, usually over a period of 1-2 weeks. The three most common symptoms are fever,confusion, and headache. Stiff neck, photophobia, papilloedema and vomiting are seen in 25- 30% of patients. Pulmonary cryptococcosis (pl effusion, cavitation, fibrosis) is rare. Diagnosis; CSF +ve cryptococcal polysaccharideantigen Ag testing (90% sensitive). Culture will almost always establish the diagnosis (100% sensitive). The CSF WBC count is typically low (<50/microL) with a mononuclear predominance and the protein and glucose conc. are only slightly abnormal. TTT; Induction therapy -- amphotericin B + flucytosine for 2 weeks. Maintenance therapy — fluconazole for at least 4 months.

DD of chronic meningitis 1. TB.  2. $  3.cryptococcal 

4.sarcoidosis.  5. Behcet.  6.Malignant. 



CP ----Meningism & inc. ICT

Aspergillosis Major clinical forms 1. ABPA. 2. Invasive pulmonary aspergillosis. 3. Aspergilloma

ABPA The major diagnostic features of classic ABPA 1. history of asthma. 2. Immediate skin test +ve to Aspergillus antigens. — A skin prick test should be the first step in an asthmatic being evaluated for ABPA. A negative prick skin test virtually excludes ABPA from consideration. 1. Precipitating serum antibodies to A. fumigatus Serum. 2. total IgE concentration greater than 1000 ng/mL . 3. Peripheral blood eosinophilia >500/mm(3). 4. Lung infiltrates on chest x-ray or chest HRCT . 5. Central bronchiectasis on chest CT. 6. Elevated specific serum IgE and IgG to A. fumigatus.

Radiographic features. 

  

CXR  parenchymal infiltrates (usually involving the upper lobes), atelectasis due to mucoid impaction, and a number of findings characteristic of bronchiectasis . These include: Migratory pulmonary infiltrate. "Parallel Tram lines" due to the presence of ectatic bronchi. Ring shadows due to mucus-filled bronchi.

 TREATMENT aims to control episodes of acute inflammation and to limit progressive lung injury. Glucocorticoids are most commonly used,  increasing evidence of benefit from combined therapy with itraconazole.

Aspergilloma 







caused by a "ball" of fungal mycelia that can occur within a cavity, usually within the parenchyma of the lung Patients with pulmonary aspergilloma can be asymptomatic. The most frequent symptom is hemoptysis, in 75 % of patients . Less commonly, chest pain, dyspnea, malaise, wheezing, or fever which may be 2ry to the underlying disease or bacterial superinfection of the cavity. CXR mass within a cavity surrounded by a radiolucent crescent (crescent sign) TREATMENT — When required, surgery is the mainstay of therapy.

Invasive pulmonary aspergillosis in the neutropenic (AML, CML, Hodgkin ) or HIV-infected patient.  The major manifestation is fever that is unresponsive to broad spectrum antibiotics.  TTT : voriconazole is superior to Amphotericin.  We recommend voriconazole as initial therapy in patients with invasive aspergillosis (Grade 1B). 

Pityriasis versicolor (also called tinea versicolor) is a skin infection caused by a fungus called Malassezia furfur.  The treatment is topical selenium sulphide or miconazole cream. 







POTASSIUM HYDROXIDE PREP — Potassium hydroxide (KOH) can be used to microscopically identify fungus or yeast from epidermal skin scrapings. KOH dissolves epidermal keratinocytes, allowing for easier demonstration and identification of organisms. KOH prep is indicated to identify fungal infections (eg, tinea pedis, manus, corporis, cruris, capitis; onychomycosis) and yeast infections (eg, tinea versicolor, candidiasis). WOOD'S LAMP EXAMINATION (BLACK LIGHT) — A Wood's lamp examination is used to aid in the diagnosis of tinea capitis, Certain specimens will fluoresce when examined under a Wood's lamp. FUNGAL CULTURE — Fungal cultures are used to confirm the diagnosis of fungal or yeast infection when the KOH test is negative,

 Griseofulvin is not active against Candida

albicans or aspergillus. It is active against trichophytons (tinea or ringworm) and other dermatophytes. It is metabolised in liver (hence caution in liver rather than renal failure).

Sporotrichosis Ulceronodular dermatosis.  Sporotrhrix schenckii (soil fungus)  Gardner, farmer, florist.  + chronic nodular lymphangitis & LN. 

Sporotrichosis

Mucormycosis: The hallmark of the disease is vascular invasion with marked hgic necrosis.  Common in diabetics & DKA.  The commenst is Rhinocerebral.  Nasal stiffness, necrosis, black turbinates, facial oedema.  Biopsy is confirmatory.  Ttt. Amphotericin B for 10-12 wks . Pulm. , gastrointestinal, cut.,also occur. 

Pneumocystis carinii (PCP)      

May be classified as a protozoan or fungus. Causes pneumonia in immunocompromised patients. Presentation: Fever, breathlessness, tachypnoea, dry cough, respiratory failure (‫آ‬± cyanosis). Investigation: CXR----- normal or reticulonodular pattern or ground glass appearance. BAL & sputum culture may be diagnostic (sputum Induction). Treatment : cotrimoxazole , clindamycine, IV pentamidine+ steroids 40 mg X 2 if O2 < 70. Prevention: Prophylactic antibiotics are given to AIDS patients with low CD4 counts< 200 continue till CD4 counts> 200 for 3 months.

Protozoal infections Blood Protozoa

Tissue Protozoa GIT Protozoa

Malaria

Leishmania

Giardia

Trypanosomiasis

Toxoplasma

Amebiasis

Babesiosis

cryptosporidiosis Microsporidiosis Balantidiasis

MALARIA     

IP=10-14 d. ♀ Anopheles mosquito. Plasmodium falciparum malignant subtertian malaria. Plasmodium vivax and ovale  benign tertian malaria(every 48. Plasmodium malariae quartan malaria. (every 72 hours )

Stages; 1. 2.

3.

Preerythrocytic stage (liverall). erythrocytic stage; RBCs infected by micromerozoites  trophozoites  schizontsmerozoites (release from ruptured RBCs) gametes. exo erythrocytic stage, only P. vivax and ovale remain in the liver to cause relapse.

Plasmodium vivax and ovale only infect reticulocytes  falciparum infects erythrocytes of all stages (severe)  malariae infects mature erythrocytes.  NB; severe parasitemia= > 1% of RBCs are infected. C/P; Fever, rigor, sweating, hemolytic anemia, splenomegaly. People partially protected from severe malaria; 1. Repeated infection. 2. Certain Hb e.g. Hb AS (sickle trait), G6PD. 

Severe Falciparum malaria  1. 2.

Parasitized RBCs; are less flexible sequested in splenic post cap venules. Develop knobs which bind adhesion molecules on cap endothelium specially venules of brain, liver, spleen, kid .

C/P; 1. 2. 3. 4. 5. 6.

(MOF)

Cerebral malaria is only caused by Plasmod. falciparum. hepatitis, gastrointestinal symptoms(diarrhoea), spl.rupture. GN/acute tubular necrosis and blackwater fever. ARDS. Severe anemia & DIC. Hypoglycemia & met. Acidosis.



Diagnosis;

Thin & thick Bl film stained with giemsa, wright or leishman stain.2-3 Bl films over 2-3 d.antimalarial should be stopped. Repeatedly –ve exclude malaria. 2. Serological tests should not be relied on for malaria diagnosis bec. Ab tests can remain +ve for months or years after infection. TTT; 1. Chloroquine; 600 mg300mg after 6 hrs300 mg/24 hrs for 3 days. 2. Chloroquine resistant; Fansidar (sufadoxine 1.5 gm + pyrimethamine 75 mg) 3 tab as a single dose. 3. Chloroquine & Fansidar resistant; Quinine sulfate 600 mg 1x3x5 + Fansidar 3 tab single dose. 4. Chl & Quinine resistant; mefloquine 20 mg/kg in 2 divided dose 8 hrs apart. 5. TTT of severe malaria  Intravenous quinine is indicated in complicated malaria e.g. cerebral malaria and hyperparasitaemia (>2%). Hypoglycaemia is an important side effect of quinine therapy (causes insulin release) 6. For eradication & prevention of relapses (vivax & ovale); Chloroquine followed by primaquine 7.5 mg/d for 14 d. 1.

Chemoprophylaxis 1 wk before, during , 6 wks after.  Chloroquine sensitive 300 mg/wk.  Chloroquine resistant Mefloquine 250 mg/wk.(# with BB, neuropsychiatric).  Mefloquine resistant Doxycycline. 

Trypanosomiasis 1) African Trypanosomiasis Sleeping sickness. Tryp gambiense & Rhodesience. Fever, LN, HSM, CNS. -

Diagnosis;

1.

thick, thin bl film with giemsa stain. Serology. TTT; suramin, eflornithin.

2. -

2) American Trypanosomiasis = Chaga’s disease Blood sucking bugs Tryp. cruzi. Infection occur through rubbing bug over skin abrasions or conjunctiva, bl transfusion & transplacental. Acute chaga’s firm reddish papule, fever, regional LN.the parasite remain dormant in autonomic ganglia. Chronic chaga’s; (immune mediated tissue damage). Heart conduction abnnormalities, aneurysm formation & cardiac dilatation. GIT mega oesophagus dysphagia & aspiration. mega colon constipation. Diagnosis; 1. Bl film in acute. 2. Serology in chronic. TTT; acute benznidazole. chronicsymptomatic.

Tissue protozoa

Leishmaniasis



Leishmaniasis (Kala Azar) is spread by bites from female sandflies. Multiply in macrophage & cells of RES then released into circulation after cell rupture.



Visceral leishmaniasis;=kala azar= black fever.



Main animal reservoir in Europe & asiadogs & Foxes.

-

IP=1-2 months. - Leish donovani, Many infections are subclinical, but the classic presentation is with fever, weight loss, hepatosplenomegaly, LN, pancytopenia and hypergammaglobulinaemia.



Diagnosis.



in Africarodents

1- Demonstrating of parasite form aspirate from BM, spleen, LN. Splenic puncture is the most sensitive means of obtaining a diagnosis (98%), but biopsy of the bone marrow and liver is almost as good show Donovan bodies (amastigotes of Leishmania donovani). 2- culture form these aspirate. 3- serology +ve in 95%. 4- pancytopenia, hypoalb, hypergamaglob. 5- Leishmanin skin test (CMI) -ve.

TTT, 1-Pentavalent antimony compounds IV I resistance is developing. 2- Amphotericin IV can achieve 98% long-term cure 3- pentamidine IV. 4- new oral drug; meltifasin.



This usually requires an invasive procedure to obtain a tissue aspirate or biopsy. Both staining and culture should generally be performed because lesions can be smear negative and culture positive or vice versa . An alternative diagnostic approach is to use immunologic based tests, such as skin testing or serology.

Cutaneous leishmaniasis Old World (Africa, Mediterranean, Afghanistan) and the New World (Central and South America). - Cutaneous leishmaniasis can be caused by several Leishmania; torpica, mexicano, brasiliensis. - Multiply in dermal macrophages. Painless nodules->ulcerate with raised bordercrustheal. - Leishmanin skin test (CMI) + ve. Treated with intra-lesional sodium stibogluconate therapy. or ,( Na stibogluconate IV ) . -

Toxoplasmosis  

Intracellular protozoan. Ingestion of contaminated food, undercooked meat containing cysts, bl transfusion or transplacental.

 C/P; - Asymptomatic - cervical LN; asymetrical, most pt have IMN like illness. - Generalized LN. - Myocarditis, hepatitis, uveitis, chorioretinitis. - Neurological dis in IC (neck stiffness, headache, CSF; high protein, CT; ring enhancing lesions). - Cong toxoplasmosis (micro or hydroceph, MR, motor imp, jaundice). o TTT, pyremethamine & sulfadiazine, o if pregnant spiramycin.

Toxoplasma choroidoretinitis

Babesiosis (as malaria but in America)         

As malaria in north America & europe. Tick transmitted (Ixodes scapularis, Dammini). Zoonotic disease in rodents & cattles & transmitted to man. Babesia microti (rodents) & Babesia divergent (cattle). In healthy individuals mild illness, recover spontaneously. In asplenic pt or IC  severe overwelming infection. C/P; (as malaria) constitutional sympt, hemolytic anemia, Hburia, renal failure, jaundice, HSM, abd pain, dark urine. Lab; -thick & thin bl film. -serology. TTT; clindamycin +/- exchange transfusion.

Giardiasis Common flagellate protozoan.  Most common parasitic infestation in travellers returning to UK.  Path; villous atrophy +/- bact. Overgrowth.  C/P; watery diarrhea, distension (explosive diarrhoea); no fever, steatorrhea.  IP (2wk.);  Stool microscopy may be +ve.  Duodenal aspirate---- flagellate protozoan.  Duodenal Biopsy.  If suspected, treat with metronidazole 2g single doses daily for 3d.. Rapid response is diagnostic.

Amoebic dysentery  





 

May begin years after infection. C/P; Diarrhoea begins slowly, becoming profuse and bloody ± fever ± malaise. Chronic colitis liver abcess (through portal v), ameboma of caecum, rectosigmoid. Diagnosis is confirmed by microscopy of fresh stool. (trophozoite) Colonoscopy ---discrete flask shaped ulcers. TTT; metronidazole 500 mg 1x3x5 ( x10-14 d in liver abcess) followed by diloxanide furoate (luminal amebeside).

Amoebic Liver abscess Right lobe affected in 90% of cases.  Males in 80% of cases.  Single & unloculated abscess in 70% of cases.  Normal liver function tests.  aspiration -- chocolate syrup (anchovy sauce).  Pt with hepatic abscess usually do not have diarrhea.  Serology : CFT is positive in 90% of cases. 

Balantidiasis( as amoeba) Balantidium coli.  Reservoir pigs.  TTT. Metro or tetra 

Cryptosporidium Protozoan causing diarrhoeal disease.  C. parvum causes most cases.  Route of inf. Direct person-to-person contact , or waterborne transmission (faeces of cattle contaminating water supply & swimming pools).  travellers to foreign countries, & IC patients are at high risk.  Incubation: 2-5d.  Symptoms: profuse watery diarrhea, abdominal cramp nausea, anorexia, fever, and malaise.  Most common cause of watery diarrhea in HIV pt. Diagnosis-- stool microscopy with modified acid fast stain.  Treatment is supportive. Usually symptoms last 1-2wk. Immunocompromised patients develop profuse intractable diarrhoea which is difficult to clear and may continue intermittently for life.In HIV—HAART) 

Microsporidiosis Diarrhea in HIV.  Diag; trichrome on fluorescent stain of spores in stool.  TTT;Albendazole. 

Helminthic infections 

  



  

Neurocysticercosis is caused by Taenia solium (pork tapeworm). This disease is found in South America and Asia. Neurocysticercosis typically is benign, and most lesions resolve spontaneously within 2-3 months. Diagnosis: seizures (65-80%) due to localised inflammation that accompanies their degeneration in the cerebral cortex when calcified cysts occur. Increased intracranial pressure (due to hydrocephalus, which can occur in 15-25% of cases) causes headache, nausea, and vomiting. CT or MRI of the head may show granulomatous cysts. ELISA of serum may confirm diag. Albendazole is the recommended treatment.

Note: Tissue invasive helminth (worm) infections may cause eosinophilia.  Protozoan parasites e.g. malaria, amoebae do not. 

Toxocariasis, 



granuloma forms around the larvae which are spread by dogs and cats. Fever, hepatomegaly and respiratory symptoms constitute visceral larval migrans. Treat with thiabendazole.

 'Elephantiasis' affects the lymphatic system, causing

swollen legs. The organisms are filariae called Wuchereria bancrofti.   

can be detected on a blood film, and Oesinophilia. filarial serology can be sent. Treatment is with diethylcarbamazepine (DEC) or ivermectin.

Echinococcus is the cause of hydatid cysts. It is ingested into the gut after handling of dogs (dog tapeworm) and enters both portal and pulmonary circulation. Hydatid cysts and alveolar cysts form.  Treatment of choice is surgical excision plus Albedazole and praziquantel with a high risk of cystic rupture with metastatic spread of organisms and anaphylaxis. 

Schistosomiasis 







Schistosoma haematobium infection is associated with eosinophilia. The sexual replication stage may occur in humans or other animal hosts. Although most of the eggs are laid by the parasite in the bladder (cystitis, granulomas, haematuria), The larvae can travel to the lungs and cause pulmonary hypertension. some are deposited in the rectum and a rectal biopsy may yield the diagnosis. The larvae can travel to the liver and cause periportal fibrosis, portal hypertension. Hepatomegaly is more typical of S mansoni and S japonicum rather than haematobium.

Scabies 

is spread by Sarcoptes scabei. It is spread by contact only. Effective agents are benzyl benzoate, ivermectin and permethrin.

Genitourinary infections  





Primary syphillis causes a chancre and inguinal lymphadenopathy in the first weeks.(dark field examination) Secondary syphillis (following few months) manifests as generalised lymphadenopathy, maculopapular rash (affecting hands and feet), fever, infectious papules around the perinanal regions (condylomata lata) and snail track ulcers in the mucous membranes of the mouth. In tertiary syphillis (usually >2 years), gumma formation (granulomas) Cardiovascular syphilis may lead to aortic regurgitation as a result of a dilated aortic root and neurological sequelae including general paralysis of the insane, focal neurology (syphilis is the “great imitator” and dementia. Successful therapy may be monitored by a fall in VDRL or rapid plasma reagin (RPR) titre (if these were initially positive – 75% have positive VDRL in primary, 99% secondary)

There are two types of serologic tests for syphilis:

 Nontreponemal

tests such as

-Venereal Disease Research Laboratory (VDRL) test and Rapid Plasma Reagin (RPR) test.

 specific     



-

treponemal tests such as

fluorescent treponemal antibody absorption (FTA-ABS) test Treponema pallidum hemoagglutination assay (TPHA). Microhemagglutination test for antibodies to Treponema pallidum (MHA-TP) The use of a single serologic test to diagnose syphilis is generally inadequate because of the potential for false-positive results . Thus, the usual testing algorithm is to screen with a nontreponemal test such as the VDRL; a reactive specimen is then confirmed as a true positive with a treponemal test such as the FTA-ABS. TTT: Benzathine penecillin.

urethritis 

Gonorrhoeae infection. Can cause penile discharge



and knee effusions with rash. The discharge and knee aspirate may grow gram negative diplococci. Treatment is with ceftriaxone IM single dose. Concurrent treatment for chlamydia should be given for 3-6 weeks(oral doxycycline 100 mg twice a day).





A patient presenting with urethral discharge may have gonococcal or non-gonococcal urethritis (NGU). If there are no gram negative diplococci seen on microscopy, it is likely to be NGU. The organisms causing NGU are as follows: Chlamydia trachomatis 40% Ureaplasma urealyticum 20-40% Trichomonas vaginalis (rare) < 2% Candidasis (rare) < 2% Herpes simplex (rare) < 2%





Lymphogranuloma venereum is a sexually transmitted disease caused by chlamydia trachomatis. It causes a papule or ulcer that may occur on the penis, urethra or cervix. Proctocolitis may also be present. Confirmation of a diagnosis of LGV requires serological tests or PCR on genitourinary specimens. Prolonged treatment with doxycycline or roxithromycin for 3 weeks is required for affected patients.

The differential diagnosis of genital ulceration

chancroid, lymphogranuloma venereum , granuloma inguinale, also herpes simplex virus infection and primary syphilis .  Multiple painful genital ulcers with localised lymphadenopathy may suggest chancroid, which is caused by Haemophilus ducreyi.  Treponema pallidum infection causes (syphilis), which presents as a solitary painless chancre.  Chlamydia trachomatis causes lymphogranuloma venereum, which presents as a painless ulcerating papule and regional lymphadenopathy.  Trichomaonas vaginalis is a protozoan. It is a very common sexually transmitted infection in the developing world. Men are only mildly symptomatic with urethritis and it is not a cause of genital ulceration. ( greenish discharge in females). 



Herpes simplex virus infection

The standard assay for detecting antibodies to HIV is an enzyme immunoassay (EIA). (+ve within 3 month).  A confirmatory Western blot is performed on EIA-positive specimens to exclude a false positive test. (+ve within one month). 



The diagnostic accuracy of serologic testing is generally very high.



false negative  the "window period" prior to seroconversion  HIV RNA testing in this situation. Rapid serologic tests offer several advantages including fast turnaround times and



 

DDX of Fever + Purpura (“MERSA”. Might also help you recall endocarditis & sepsis; use  as upside-down A)     

     

M eningococcemia E ndocarditis R MSF S epsis ascultitis

Key Tick-Borne Disease (“B aLERT” on the exam!) Babesiosis . Lyme disease . Erlichiosis. RMSF . Tularemia.

Nephrology

Urine analysis; physical exam Appearance; colour, odour. Sp Gravity; n= 1003 – 1030 Chemical exam; pH, protein, glucose, ketones, bl, urobilinogen. Microscopic exam; crystals, casts, cells, organisms. NB; nitrite test detect G –ve Bact. leukocyte esterase detect WBC (5-15/HPF) RBC casts acute GN ( nephritic) wbc cast  interstitial N, pyelon. tubular cell cast ATN. Granular cell cast  chronic GN, pyelo. hyaline  proteinuria fatty Nephrotic hematuria = rbcs > 3. pyuria = wbcs > 4.

Red urine • • • • •

Hematuria. Hemoglobinuria. Myoglobinuria. Porphyrins. Drugs; ΑMD, L-dopa, desferoxamine, metronidazol. Cyclophosphamidehgic cystitis, Beetroot,. • Orange brown; direct bil, drugs; phenazopyridine, nitrofurantoin, Fe, B1, rifampicin, phenytoin.

Approach for hematuria • If heavy proteinuria >1 gm/24h , RBCs casts , dysmorphic RBCs >70% glomerular serology, KFTs, U/S, renal biopsy. • If proteinuria <1 gm/24h, no RBCs casts, dysmorphic RBCs <30%  Non glomerular urine cytology, spiral CT or IVP, cystoscopy, or MRA. • In between manage according to clinical & lab clues e.g.; PT, PTT, TB test, PCR for TB, urine Ca.

Approach for proteinuria • If proteinuria >2 gm/24h, hypoalbuminemia, dysmorphic RBCs  glomerular serology, renal biopsy. • if ↓K, ↓P, ↓ uricemia, glucosuria, aminoaciduria tubular urine B2 microglobulin, heavy metal screen. • If proteinuria >2 gm/24h,disparity bet dipstick & prot/creat, anemia , ↑Ca , ↑ globulins  overflow (= ↑ plasma LMWP as MM, Hb, myogl urine electrophoresis, BM biopsy, radiological survey.

Functional proteinuria Causes • fever. • Exercise. • Congestive heart failure (renal ischemiaAgII). Orthostatic proteinuria; - young male - Regress in 5-10 yrs. - Diagnosed by early morning sample & by 12 hrs ambulatory & 12 hrs overnight.

Choice of imaging procedure • RAS. - for screening duppler, MRA, CTA. - to assess function ACEI renogram (renal scan) • Chronic pyelonephritis & reflux nephropathy IVP, DMSA scan. • Medullary sponge  IVP. • Neoplasm  US , CT, MRI for staging.

Dynamic renal scans are used to; 1) Measure GFR DTPA. A split GFR can be obtained for each kidney, which is not possible with the creatinine clearance method. 2) Assess renal blood flow (RBF) in

patients with suspected renal artery stenosis  hippuran/ MAG3 + ACEI renogram.

3) differentiate between obstructive versus non obstructive causes of hydronephrosis MAG3 + Lasix renogram.

Lasix renogram Non obstructive dilatation +++

Outflow delay Parenchymal Normal transit time (PTT) after = immediate fall in time IVI of 40 mg activity curve frusemide

Obstructive dilatation +++ delayed = .fall less .does not fall

2) Static renal scan

•

It consists of imaging of a radiotracer (dimercaptosuccinic acid =DMSA) that is taken up & retained by the renal proximal tubular cells, providing a static image of functioning nephrons. • Value,. 1. renal size, position, and axis. 2. focal renal parenchymal abnormalities, e.g. scars appear as bites.

Renal biopsy • 1. 2. 3. 4.

Indications; Nephrotic S Unexplained RF with normal Kid size. Failure of recovery from ARF. Asymptomatic prot., hematuria.

• 1. 2. 3. 4. 5. • 1.

Contra indications; Obese, oedema. Uncontrolled HTN. Bleeding tendency. Shrunken kid. Single kid except transplanted. Complications; Pain, hematoma, hematuria(in 20%, severe in 1-3%, need intervension in 1;400) AV aneurysm in in 20% but insignificant. Infection Mortality 0.1%.

2. 3. 4.

Glomerulopathies

Normal Glomerulus (PAS)

Granular mesangial

Linear Capillary

Granular

Clinical Presentations * Asymptomatic proteinuria * Nephrotic syndrome * Nephritic syndrome * Hypertension * Hematuria which may be microscopic or macroscopic * rapidly progressive renal failure * chronic kidney disease. • Rapidly Progressive GN (or Crescentic) - Pauci-immune ( ANCA associated Gn) = - idiopathic cresentic. - Microscopic Polyangiitis - Wegener's Granulomatosis - Churg-Strauss Syndrome. - Immune complex e.g Post Streptococcal, IEC, lupus nephr. - Goodpasture’s.

Hematuric Syndromes (Isolated Hematuria, nephritic, or RPGN) -Mesangioproliferative GN (eg, IgA nephropathy) -Focal proliferative GN (eg, lupus nephritis WHO III, infective endocarditis)

Proteinuric Syndromes (Isolated Proteinuria, Nephrotic)

Nephritic and Nephrotic Features

-Minimal change disease

-Membranoproliferative GN

-Focal and segmental glomerulosclerosis(FSGS)

-Mesangial proliferative GN -Fibrillary glomerulopathies

-Membranous nephropathy

-Diffuse proliferative GN -Diabetic glomerulosclerosi (eg, post- streptococcal GN, lupus nephritis WHO IV) -Amyloidosis. -Crescentic GN ( severe IC, pauci-immune nephritis, anti-GBM nephritis)

-Light-chain deposition disease

-Hereditary nephritis (Alport syndrome)

What is this lesion encroaching the glomerular tuft. What serious clinical condition is it associated with Slide no 14

normal

Crescentic GN - (Trichrome Stain)

IgA Nephropathy • • • •

• • • •

(Berger dis)

one of the most common forms of GN worldwide. male /female 2/1. 2nd and 3rd decades of life. Causes, -1ry -2 ry;, celiac, dermatitis herpetiformis, IBD, psoriasis, alcoholic C ankylosing spondylitis, mycosis fungoides, HIV. - familial. Pathogenesis; IgA deposited in the mesangium(polymeric , IgA) C/P; children  synpharyngetic macroscopic hematuria during adults asymptomatic microscopic hematuria. Prognosis; benign disease , progression to renal failure in 25– 30% over 20–25 years; Recur in 50% posttransplant but good Graft survival.

● IF: mesangial IgA and C3 ± IgG or IgM

IgA Nephropathy

<10 %

40 to 50 %

30 to 40 %

hematuria

CKD + proteinuria,

No Treatment Monitoring /6 -12 m.

Acute or RPGN.

progressive or severe disease. 0.5 - 1g/day

ACEI & ARBS + fish oil + statins.

1.0 -3.5 g/day

( s creat. >1.5 mg/dL,or rising , a GFR decline>15% /y, nephrotic proteinuria, marked proliferation without crescents

6-months course of steroids

Combined immunosuppressives ; prednisone + cyclophosphamide for 2 yrs.

As RPGN

What is this disease in a patient with abdominal pain, hematuria, and renal impairment and a palpable rash on thighs

Slide no 11

What is the most common glomerular lesion on light microscopy of this patient when a biopsy is taken

Henoch-Schönlein purpura • distinguished clinically from IgA nephropathy by; - prominent systemic symptoms, - a younger age (<20 years old), - preceding infection, and - abdominal complaints. C/P; skin, arthritis, abd pain, Renal. Ttt; arthralgias NSAIDs, severe abd pain, renal steroids.

• • • • • • • •

Poststreptococcal Glomerulonephritis acute endocapillary proliferative glomerulonephritis ages of 2 -14 years, throat infections with particular strains of streptococci (nephritogenic strains); After impetigo by 2–6 weeks and 1–3 weeks after pharyngitis. subepithelial "humps“. C/P; acute nephritic picture ↓ C3 with normal levels of C4. TTT; eradication of infection. Postinfectious glomerulonephritis can occur in patients with Subacute Bacterial Endocarditis , ventriculoatrial and ventriculoperitoneal shunts; pulmonary, intra-abdominal, pelvic, or cutaneous infections; and infected vascular prostheses.

ANCA associated GN

pauci-immune glomerulonephritis • C-ANCA= anti-proteinase 3 (PR3) in Wegener's • P-ANCA= anti-myeloperoxidase (MPO) more common in microscopic polyangiitis, and Churg-Strauss syndrome. TTT; • Induction therapy usually includes some combination of methylprednisolone, and cycloph. • plasmapheresis in case of pulm hge. • Maintenance, steroid tapering & give cyclophosphamide for up to 2 years after remission.

1) Idiopathic Crescentic GN

• Renal-limited glomerular capillaritis Pauci-immune crescentic GN. • Both pANCA and cANCA +ve. 2) Microscopic Polyangiitis • Renal + systemic vasculitis. 3) Wegener's Granulomatosis • Renal + vasculitis + granulomas • nasal ulcers, sinus granuloma, hemoptysis • CXR...... nodules , cavities. • Biopsy of involved tissue  small-vessel vasculitis and noncaseating granulomas. 4) Churg-Strauss Syndrome • Renal + vasculitis + granulomas + eosinophilia. • Asthma, fleeting pulmonary infiltrates • May be associated with leukotriene receptor antagonists.

Antiglomerular Basement Membrane Disease

• Autoantibodies directed against GBM collagen IV. • focal or segmental necrosis with crescent. • IF; linear immunofluorescent staining for IgG • TTT; 8–10 treatments of plasmapheresis accompanied by oral prednisone and cyclophosphamide in the first 2 weeks.

Goodpasture Syndrome:

• Causes of pulmonary-renal S; 1. 2. 3. 4. 5. 6.

Microscopic Polyangiitis. Wegener's Granulomatosis. Good pasture $. SLE. Churg-Strauss Syndrome. HSP, cryo.

Membranoproliferative GN=mesangiocapillary GN Types; Type I Disease (Most Common) 1ry. 2ry; SBE, SLE, HCV, cryo, HBV, solid malignancy. Type II Disease (Dense Deposit Disease) C 3 nephritic factor-associated Partial lipodystrophy Type III Disease Idiopathic Complement receptor deficiency

Pathology; 1. 2. 3. 4.

Subendothelial deposits mesangioproliferative changes mesangial interposition between the capillary BM and endothelial cellsThickening of the GBM with a double contour . lobular segmentation

Lab: low serum levels of C3 are typical.

TTT; • Long term alternate day steroids (prednisone 2 mg/kg) for one year, followed by slow tapering to a maintenance dose of 20 mg every other day for 3 to 10 years. • The role of aspirin and dipyridamole is unclear. DD of MPGN; • cryoglobulinemia • Lupus nephritis class IV.

Nephrotic Syndrome •

• 1. 2. 3. 4.

Heavy proteinuria> 3.5 gm/d/1.73 m2, minimal hematuria, hypoalbuminemia, hypercholesterolemia, edema, and no hypertension. TTT; lipid-lowering agents diuretics inhibitors of the renin-angiotensin system can lower urinary protein excretion. +/- anticoagulants.

Minimal Change Disease •

70–90% of nephrotic syndrome in childhood but only 10–15% of nephrotic syndrome in adults. • Causes; 1 ry or 2ry to Hodgkin's disease, NSAIDs, IFN, IMN, lead. • Lab; selective proteinuria= LMWP. • Pathology; LM, IF=nil EM=effacement of the foot process. • TTT: 1. Prednisone 60 mg/m2/d for 4 wks then 40 mg/m2/d for 4 wks then gradual tapering over 4 wks.

2. and other immunosuppressive drugs, such as cyclophosphamide, chlorambucil, and mycophenolate mofetil, are saved for frequent relapsers, steroid-dependent, or steroid-resistant patients. Prognosis; • complete remission (<0.2 mg/24 h of proteinuria) • Relapses occur in 70–75% of children after the first remission • steroid-dependent=relapse as their steroid dose is tapered. • steroid-resistant patients fail to respond to steroid therapy.

Membranous • Causes; • 1 ry =70-80%. • 2 ry; - Malignancy; solid, NHL. - Infection; HBV, HCV, P malari, S, leprosy. - syst; SLE, MCTD, sickle. -drugs; gold, penicillamine, captopril. • Patho; • LM& EM Thick BM, supepithelial deposits. IF; granular Ig G, C3 • Prognosis; 40% spont remission 30% persistant proteinuria 30% progress to RF. need cytotoxic therapy • TTT Alternate monthly for 6-12 months; - pulse steroid then 0.5 mg/kg/d - chlorambucil or oral cyclophosphamide.

Membranous GN :

Focal Segmental Glomerulosclerosis • segmental glomerular scars in some glomeruli. • 1/3 of cases of nephrotic syndrome in adults and 1/2 of cases of nephrotic syndrome in African Americans. • poor outcome in; - Nephrotic range proteinuria, - African-American race, - renal insufficiency. • Causes; 1. 1ry 2. 2ry - genetic (cong nephrotic S, steroid resistant, familial FSGS, Alport, Nail & patella) - infection; HIV ,Parvo B19 , Bilh. - drugs; Heroin, lithium, pamidronate. - Glom. HTN dt long standing nephron loss; sickle, single, obesity, HTN, rejection, reflux.

PAS

perihilar

• Path; • LM; FSGS. • EM; 1rydiffuse efface of foot process. 2 ry patchy efface of foot process. • IF; -ve except for Ig M & C3 trapped in sclerotic lesions • TTT • 2ry as any nephrotic, TTT of the cause. • 1ry steroid 1mg/kg/d for 3-4 months then - if complete responsetaper after 1-2 wks over 3 months. - if partial response (>50%)taper over 6-9 months. - if little response add cyclosporin & switch to alternate day then taper over 3 wks.

Hereditary nephropathies ALPORT'S SYNDROME & Thin GBM Transmisson; 1) 80%XL --------------------------♂ Alport, ♀ Thin GBM = mutation in type IV collagen fibrils fragile GBM. 2) 15%AR, --------------------------- homozygous Alport , heterozygous Thin GBM mutation in type IV collagen fibrils 3) 5% AD. Clinical picture; • Alport: Microscopic hematuria; begins at about 5 to 7 years of age. Nephrotic proteinuria, HTN, ESRD late adolescence. Extrarenal manifestations; 1- sensorineural deafness, start gradually in childhood, handicap by 20 years of age. 2- Ocular abnormalities;lenticonus, Dot-and-fleck retinopathy; not interfere with vision. 3- esophageal leimyomas . • Thin GBM= Benign familial hematuria represent 25% of patients with microscopic hematuria.

Nail-Patella Syndrome AD. Clinical picture; appear at any age. 1) proteinuria to nephrotic syndrome. 2) nail dysplasia. (absent thumb nails) 3) Skeletal manifestations; absent patella, elbow dysplasia. 4) Eye manifestations; Heterochromia of the iris, cataracts.

• •

FABRY'S DISEASE

XLR inborn error of glycosphingolipid metabolism. defective activity of the lysosomal enzyme a-galactosidase A accumulation of neutral glycosphingolipid in cellular lysosomes. • endothelial damage contributes to much of the pathology in Fabry's disease. • TTT= Enzyme replacement therapy. • C/P; 1) Renal Manifestations;  progressive proteinuria & decline of renal function. 2) Skin symptoms; Anhidrosis, Angiokeratoma. 3) Visual symptoms; cornea verticillata, 4) Neurological symptoms; PN, Hearing deficit . 6) Other symptoms: coarse facial features.

diabetic nephropathy Incidence • The risk for ESRD is 12 times as high in type 1 diabetes compared to type 2 diabetes. • About 80% type 1 will progress to proteinuria and ESRD compared to only 20% of type 2. Stages; 1. Renal hypertrophy & hyperfiltration. 2. Normoalbuminuria, but detectable glom lesions. 3. Microalbuminuria (30-300 mg/24h= 20-200Ug/min= U alb/creat 0.03-0.3). 4. Overt proteinuria & azotemia. 5. ESRD.

Microalbuminuria • 30-300 mg/24h = 20-200 Ug/min = U alb/creat 0.03-0.3. • Affects 25-30% of diabetics. • Progress in - 80% of type 1 & 20% of type 2 without ttt. • Develop after 5-10 yrs of DM. • Screening for Microalbuminuria is recommended in  All type 2 diabetes at diagnosis.  Type 1 diabetes 5 years after diagnosis, at puberty.  Annually for all patient after.

Histopathology • LM; - Thick BM. - Mesangial expansion (diffuse, nodular=Kimmelstiel-Wilson lesion). - Aff & eff arteriolar hyalinosis. • EM; -fibrin cap (esinophilic focal thickening of a peripheral cap loop)& - capsular drop (esinophilic focal thickening of bowman’s capsule). • IF; psuedolinear deposition of alb & Ig G along BM.

Preventive Strategies in Diabetic Nephropathy. 1. Tight glycemic control (A1C <7%). 2. Aggressive control of hypertension. Goal; DM <130/80 Diabetic nephropathy (>1g proteinuria/day) <125/75 3. Protein restriction. 4. Control of dyslipedemia. 5. Encourage smoking cessation. 6. Prevent sudden deterioration of kidney function. 7. Recent strategies in future.

Antihypertensives 1) ACEI; • Acute rise of serum creatinine of up to 30-35%, stabilize after 2 months, may occur in proteinuric patients with serum creatinine >1.4mg/dl. • greater increase of serum creatinine should raise the possibility of RAS. • Albuminuria, serum creatinine and K should be checked monthly till 2-3 months. 2) DHP CCBs (nefedipine- amlodipine): – may increase proteinuria and accerelate the progression of diabetic nephropathy. 3) NDHP CCBs (deltiazem, verapamil) may reduce proteinuria.

Lupus Nephritis (WHO) classification & clinical presentation I—Normal;-------------------Mild proteinuria II— Mesangial proliferation;---------------------asymptomatic hematuria or proteinuria III— Focal proliferative (FPGN); <50% of all glomeruli----active generalized SLE -----------------------mild-to-moderate renal disease IV— Diffuse proliferative (DPGN);-------Nephritic nephrotic + active generalized SLE V—Membranous;-----------nephrotic syndrome, usually without manifestations of active SLE. VI— Advanced sclerosis , >90% of glomeruli------------significant renal insufficiency Lab of lupus nephritis activity; +ve anti DNA,↓C3, ↓C4 , +ve anti C1q(most specific), antinucleosome Ab , urine (hematuria, RBCs casts). Value of renal biopsy; poor correlation between C/P & histopath., associated pathology e.g. drug induced AIN, TMA.

Characteristic lesions

LM;  Wire-loop lesion = massive subendothelial immune deposits  Hyaline thrombi = large intracapillary immune deposits  Fibrinoid necrosis = intimal immune and fibrin deposits IF: full-house” with IgG, IgA, IgM, C1q, C3, fibrin, and light chains. EM:  All level dense deposits II—mesangial; III and IV —mesangial,subendothelial, V—subepithelial  Fingerprint subtructure immune deposits ,  Tubuloreticular inclusions, present also in HIV, most diagnostic.

Therapy ● Class I: no specific therapy. ● Class II: if proteinuria > 1 g/dprednisone (20-40 mg/d) for 1-3 months. • Classes III and IV; Induction; pulse steroid +IV cyclophosphamide or MMF Maintenance; prednisone 1 mg/kg/d gradual tapering to 5-10 mg/d for 2 years + azathioprine or MMF. • Class V: as 1ry membranous. Renal affection in rheumatoid arthritis; - Drug toxicity; NSAIDs AIN+nephrotic. - 2ry amyloidosis.

Gammopathies = diseases of γ globulins =immunoglobulin overproduction

• • • • •

Alb.= 3.3- 4.7 g/dl. α1 glob.=0.1-0.4 g/dl. α2 glob.=0.3-0.9 g/dl. ß2 glob.=0.7-1.5 g/dl. γ glob.=0.5-1.4 g/dl.

Monoclonal Gammopathy Polyclonal Gammopathy Due to proliferation of many B cell clones e.g. CLD, Chr. Inflammation, infection.

= Plasma cell dyscrasias =immunoproliferative diseases Due to proliferation of a single Clone of Ig-forming cells that produce homogenous excess of light, heavy chains or complete IG molecule. (M-protein, where the "M" stands for monoclonal).

MECHANISMS OF RENAL INJURY I. Tubular precipitation; cast nephropathy (in MM) II. Deposition; Amyloidosis, LCDD III. Hyperviscosity; Waldenström macroglobulinemia & Myeloma dt ↑ Igs. IV. Glomerular reactions; MPGN, Pamidronate induced FSGS V. Tubular toxicity; ATN (NSAIDs, Iodinated contrast), Fanconi syndrome.

DIAGNOSTIC APPROACH TO RENAL DYSFUNCTION IN PLASMA CELL DYSCRASIA I. Serum protein electrophoresis - Monoclonal proteins will appear as a spike in the pattern - Sensitivity (500-2000 mg/L) - May not pick up small bands or bands outside of the gamma region II. Urine protein electrophoresis - Both serum and urine should be tested to increase detection to 95% III. Immunofixation - using Anti-serums to light chains. - More sensitive than electrophoresis (detection limits 150-500 mg/L) IV. Serum free light chains (FLC) assay Most sensitive (detection limit of 0.5 mg/L) Sensitivity is 99% when FLC is combined with serum and urine immunofixation V. Bone survey VI. Bone marrow biopsy VII. Abdominal pad of fat aspirate; 80% sensitive for AL amyloidosis VIII. Renal biopsy A. Should be performed on all cases if risk permits B. Only way to distinguish between various kidney diseases

Multiple Myeloma = CAST NEPHROPATHY Precipitating factors 1. Volume depletion 2. Hypercalcemia 3. NSAIDs 4. Intravenous contrast 5. Infections Pathogenesis A. Increased tubular concentration of light chains enhanced by decreased urine flow and furosemide. B. Binding and co-aggregation with Tamm- Horsfall proteintubular cast in the distal tubule then the proximal tubule C/P; • Acute renal failure • 10% to 15% present with ESRD • > 75% have sub–nephrotic range proteinuria 1. Mainly Bence-Jones proteinuria 2. Often dipstick negative

V. Treatment A. Restore intravascular volume B. Remove offending agents and nephrotoxic drugs 1. Hypercalcemia i. Volume repletion ii. Bisphosphonates in refractory cases. C. Reduce light chain levels 1. Chemotherapy i. Thalidomide plus dexamethasone, or ii. Bortezomib plus dexamethasone D. Stem cell transplantation +/- kidney transplant is an option in selected patients. VI. Management of ESRD A. Survival on dialysis is significantly decreased in patients with dysproteinemia who reached ESRD. 1. Median survival was 2 -4 years for LCDD, & AL amyloidosis and 1 year for multiple myeloma.

What are these homogenous deposits with light microscopy in this renal biopsy of a patient with long standing rheumatoid arthritis who has recently developed nephrotic syndrome

Slide no 12

AMYLOIDOSIS TYPES OF AMYLOIDOSIS 1. AL amyloidosis 2. AA amyloidosis 3. Dialysis-related amyloidosis 4. Heritable amyloidoses e.g. heritable neuropathic and/or cardiomyopathic amyloidosis due to deposition of fibrils derived from transthyretin (also referred to as prealbumin). 5. Organ-specific amyloid — Amyloid deposition can be isolated to a single organ, such as the skin, eye, heart, pancreas, or genitourinary tract, resulting in specific syndromes.

Renal Amyloidosis 1. 1. 2. 3. 2. -

Congo red +ve. Biopsy of involved liver or kidney is diagnostic 90% , abdominal fat pad aspirates are positive about 70%. SAP (serum amyloid P) scanning can identify the distribution of amyloidSensitivity = 90 % & ; the specificity is 93 %. AL amyloidosis, also called primary amyloidosis; 75% are of the lambda LC. 10% of these patients have overt myeloma. nephrotic syndrome is common, and about 20% of patients progress to dialysis. treatment ; melphalan+ dexamethazone, 4d courses/28 d for up to 9 courses. autologous hematopoietic stem cell transplantation . Thalidomide/dexamethazone. AA amyloidosis is sometimes called secondary amyloidosis nephrotic syndrome, 40–60% of patients progress to dialysis. It is due to deposition of ß-pleated sheets of serum amyloid A protein, an acute phase reactant. 40% 2ry to rheumatoid arthritis, 10% have ankylosing spondylitis or psoriatic arthritis, FMF treatment  of the primary disease, Colchicine in FMF, Eprodisate.

Light Chain Deposition Disease • kappa light chains that do not form amyloid fibrils. Instead, they self-aggregate and form granular deposits along the glomerular capillary and mesangium, tubular basement membrane, • nephrotic syndrome , 70% of patients progress to dialysis. • not fibrillar and do not stain with Congo red, • IF + anti-light–chain antibody. • EM granular deposits. • Treatment = Melphalan/prednisone for 2 years as MM. DD of nodular sclerosis; • Diabetic glomerulosclerosis • LCDD. • Amyloidosis. • Idiopathic.

Antiphospholipid antibody Syndrome •

Def & pathogenesis; auto Ab to phospholipids on endothelial cells & LDL endothelial injury thrombotic microangiopathy. • Diagnostic criteria; 1 clinical (thrombosis arterial or recurrent venous/ recurrent miscarriage before 34 wks of normal fetus) + 1 lab (anticardiolipin/ lupus anticoagulant) • C/P; 1. livedo reticularis, thrombosis; CNS, CVS, adrenal insufficiency, lung, GIT, Kidney, ARF, TMA, HTN. 2. Catastrophic form => 3 organs simultaneously (Kid, lung, CVS). • Lab; ↑ PTT, +ve anticardiolipin/ lupus anticoagulant, false +ve VDRL. • Ttt; APA +ve without previous thrombosis  no ttt or aspirin. • APA +ve & previous clinical event  long term warfarin, INR=2-3. • APA +ve & pregnancy heparin.

scleroderma Renal failure in scleroderma; - renal crises. - TMA - Membranous. Path; as TMA but affect arcuate & interlobular arteries, onion skin appearance, hypertrophy of JGA. Marker of Scl renal crises; anti-RNA polymerase III C/P; diffuse systemic scl + new onset severe HTN or RPRF. TTT; ACEI Prognosis; continue ACEI after dialysis as 50% may recover over 3-18 months.

Sickle cell; • Glomerular; hematuria , FSGS. • Tubular; DI , RTA , papillary necrosis. • Renal cell carcinoma. Sarcoidosis; Ca stones, granulomas, TIN. Sjogren $; Membranous, RTA.

Cryglobulinemia • • •

Cryglobulins are proteins ((Ig & Ag) that precipitate on cooling to 4o Precipitate in small cool Bvs in the peripheries complement activation Raynauld’s, vasculitis. 33% is called essential cryo (uknown cause, discovered to be mostly related to HCV)

Type I

Type II

Type III

Monoclonal

Mixed Mono Ig M against poly Ig G (RF activity)

Mixed polyclonal

causes

Waldenstrom MM

HCV Plasma cell dyscrasia

- Autoimmune; SLE, hepatobiliary, GN. - Lymphoproliferative - Chronic infection

C/P

Hyperviscosity, Raynauld’s, cutaneous ulcers, Purpura, arthralgia, LN, HSM, peripheral neuropathy, GN; HTN, acute nephritic, nephrotic less common.

Gn; • LM: Marked leukocytic infiltration, intraluminal deposits, vasculitis with fibrinoid necrosis, TI infiltration. • IF; Ig M&G, C3. • Lab; ↓C4, C1q,+ve cryo, RF, HCV Ab. • Poor prognostic factors; 1. Old age. 2. Recurrent purpura. 3. High s creat. 4. High cryo titre; Clinical and histologic activity does not always correlate directly with detection of circulating cryoglobulins. 5. Low C3 • TTT; - steroids (pulse then 0.5 mg/kg for 6 months) + TTT of HCV. - If severe; add cyclophosphamide, - plasmapharesis& Rituximab.

• Hypocomplementemic GN; - Lupus nephritis - Post infectious. - MPGN - Cryoglobulinemia. HCV associated nephropathy; 1. MPGN +/- cryoglobulin 2. Membranous GN 3. FSGS 4. Prolif, TMA, fibrillary.

Thrombotic microangiopathies (TMA) • Def; group of disorders ccc by fibrin deposition in the lumen & wall of arterioles & glomerular cap. • Path; • LM; - intraluminal fibrin & plat. - double contour of cap wall. - fibrinoid necrosis of arterioles. • EM; tactoids of fibrin(subendothelial), swollen endo. • IF; no IC. • Lab; ↓platelets, hemolytic anemia, shistocytes. • TTP more platelet. • HUS: more RBCs & cortical necrosis.

Thrombotic thrombocytopenic purpura (TTP) • Pathogenesis;↓activity of VWF cleaving protein to < 5% large VWF platelet adhesion dt; - Familial ADAMTS13 mutation. - Acquired Ig e.g. with ticlopedine,peripartum,sepsis,malig. • C/P; pentade; • fever, hemolytic anemia, thrombocytopenia, CNS, mild renal . • TTT; FFP, plasmapharesis,. • NB: platelet transfusion & antiplatelet e.g. aspirin are contraindicated. • FU by LDH level. • Prognosis; mortality 90% if untreated, 90% survival if ttt.

Hemolytic Uremic Syndrome (HUS) • 1. 2. 3. • • •

Pathogenesis; endothelial injury; By shiga toxins of Eoli O157 H7 (Diarreal form D+HUS). Complement mediated in familial form dt ↓factor H. Complement mediated in the acquired form by a triggering factor e.g.pregnancy, malignancy, drugs. C/P; triad of hemolytic anenia, thrombocytopenia, severe renal failure. Ttt; supportive, recombinant factor H. Poor prognostic factors; old, pregnant, D-HUS, shigella, pneumococcal, HTN, cortical necrosis, marked leuckocytosis, anuria, persistent proteinuria.

• 1. 2. 3. 4. 5. 6.

Uses of plasmapharesis in renal dis; Good pasture. ANCA +ve dis. Idiopathic cresentic Gn. Cryo. MM with hyperviscosity. TTP & HUS.

Tubulointerstitial diseases

Acute interstitial nephritis • 1. 2. 3. 4. • • • •

Causes; Drugs; antibiotics, diuretics, NSAIDs.PPI. Infections e.g.bact, viral as CMV, Hanta V, fungal. Immune dis; SLE, Sjogren, sarcoid, cryo, acute transplant rejection. Idiopathic. C/P; Fever, rash, arthralgias +/- flank pain, hematuria. Lab; Serum.., KFTs, & electrolytes. Urine.....RBCs , WBCs, White cell casts, eosinophiluria, Eosinophilia, tubular defects, proteinuria<1g. TTT; stoppage of offending agent high dose steroid for 2-3 wks for drug induced & systemic dis. not for infection.

Chronic interstitial nephritis • 1. 2. 3. 4.

Causes; Drugs; analgesics, lithium, heavy metals as lead, calcinurin inhibitors. Infections e.g. EBV. Immune dis; SLE, Sjogren, sarcoid, cryo, chronic transplant rejection. Obstructive uropathy.

CP.....> CKD,HTN, PCT defects, marked acidosis, hypo or hyperkalemia. Lead; renal, blue line in gum, gout, wrist & foot drop. diagnosis; lead mobilization test. TTT; chelation with EDTA or oral succimer. Lithium; DI; ttt; stop it , give amiloride , thiazide , endomethacin,carbamazepine RTA, CIN, FSGS, ARF in acute intoxication, hypothyroidism, goiter, hypercalcemia.

Effect of NSAIDS • • • • • •

Vasomotor ARF. Acute interstitial nephritis + nephrotic S. Acute papillary necrosis. Nacl retension. ↑K in low RAA as DM, ACEI. CKD; either NSAIDS- induced CKD.

NSAIDS- induced CKD

♀= ♂ age> 60 less Does not occur with low dose aspirin

analgesic nephropathy Mixture; aspirin, paracetamol, caffeine ( 2-3) Kg). ♀ 40-50 Anemia out of proportion Diagnosed by non-contrast CT papillary necrosis & medullary calcification, small kidneys, irregular contour.

RENAL FANCONI SYNDROME • generalized dysfunction of the PCT. • phosphate, glucose, amino acid, and bicarbonate wasting by the proximal tubule. C/P; • in children is usually rickets and impaired growth. • In adults, osteomalacia and osteoporosis. + polyuria, renal salt wasting, hypokalemia, acidosis, hypercalciuria, and LMW proteinuria.

Papillary necrosis

• Age > 60yrs except sickle. • Due to ↓medullary blood flow. Causes; • DM • UT obstruction. • Analgesic nephropathy. • Sickle cell anemia. • Graft rejection • Pyelonephritis, TB. • Hyperviscosity syndromes. C/P; hematuria , necroturia , loin pain, UTI, sepsis, renal failure. Diagnosis; IVP (best). signs;calyceal irregularities, sinus tract, ring sign, clubbing, filling defects. prevention; ACEI are protective. TTT; control B sugar, avoid analgesics & drugs that ↓ Bl flow as thiazides, BB, ↑fluids,

Vesicoureteric reflux • Not inherited. • Most common cause of ESRD in children. • Child with UTI 30% VUR. NB; • Most common inherited cause of ESRD  ADPKD. • Most common inherited cause of ESRD in childrennephronophthisis (as medullary cystic dis). • Reflux nephropathy=VUR + CIN. Grades; I ureter II  ureter & pelvis ( without dilatation). III pelvic dilatation, preserved forniceal angles. IV  blunting of forniceal angles. V  clubbing of forniceal angles.

• Diagnosis; - early micturating cystography, dynamic renal scan. - late U/S, DMSA scan. • Screening for VUR in: ♂: 1st attack of UTI at any age. ♀: 2nd attack or- 1st with family history, - abn. Voiding, - HTN, - poor growth, • TTT; • Grade I nothing. • Grade II, III  till puberty antibiotics TMP-SMX or nitrofurantoin, cephalexin. • Grade IV, V  Long-term antibiotics or surgery. NB: Surgical correction of VUR in children have failed to show significant benefit in terms of renal function & progressive scarring. Surgical correction is reserved for the child who, in a 2- to 4-year period, appears to be not responding to medical therapy.

Cystic diseases of the kidneys 1. 2. -

Hereditary; ADPKD. ARPKD. Tuberous sclerosis Von Hippel-Lindau disease (VHL) Juvenile nephronophthisis and medullary cystic disease. Acquired renal cysts; Medullary Sponge Kidney. acquired cystic disease. Simple cysts.

cystic Kidney Disease Inherited Cystic Kidney Disease

Mode of Inheritance

Renal Abnormalities

Extra-Renal Abnormalities

ADPKD

AD

Cortical and medullary cysts

Cerebral aneurysms; liver cysts, othera

Nephronophthisis

AR

Small fibrotic kidneys; medullary cysts

Retinitis pigmentosa

Medullary cystic kidney disease

AD

Small fibrotic kidneys; medullary cysts

None

Tuberous sclerosis

AD

Renal cysts; angiomyolipomas;

Adenoma sebaceum; CNS hamartomas

Von Hippel-Lindau disease

AD

Renal cysts; renal cell carcinoma

Retinal angiomas; CNS hemangioblastomas; pheochromocytomas

Adult Polycystic disease • • • 1.

Commonest inherited kidney disease. Accounts for 5-10% of (ESRD). Clinical Picture Renal disease; Abdominal pain , hematuria, Palpable kidneys, Recurrent UTI,stones, Hypertension, Renal Failure . 2. Extra renal disease; Cerebral Aneurysm (Berry’s) (5-10%), Hepatic, Pancreatic cysts, Mitral Valve Prolapse (26%),diverticulosis. • Diagnostic radiological criteria If +ve Family history – < 30 years ----- 2 cysts in at least one kidneys. – 30 - 59 years ----- 2 cysts in each kidney. – > 60 ---4 cysts in each kidney. If -ve Family history 5 cysts in each kidney. • TTT; 1. ACEI, ARBs 2. If Hge; analgesics, rest, hydration. 3. If infected; bl culture not urine,sutrim, cipro, vanco not ceph nor aminogly.

APKD

Tuberous sclerosis AD, hamartin (tumor suppressor)multiple hamartomas.

Clinical Picture; • CNS epilepsy in 80%, Mental retardation. • SkinFacial adenoma sebaceum, “Shagreen patches” (lower back), Ash leaf (Hypomelanotic macules). • Periungual fibromas. • Renal (60%) cysts, Angiomyolipomas. • Retinal hamartoma (50%), is almost always asymptomatic. • Liver ( 40% ), angiomyolipomas and cysts. • Heart (rhabdomyoma). • Lung (lymphangiomyomatosis; affects females)

Acquired renal cysts Medullary Sponge Kidney - dilatation of collecting ducts, – Benign course. – Calcify nephrocalcinosis, Nephrolithiasis and UTI. – Defective concentrating ability & RTA. – Diagnosed by IVPradial, linear striations in the papillae or cystic collections of contrast . Dialysis Cysts= acquired cystic disease. – the size of the kidneys is usually not markedly increased, Precancerous. Simple cysts - Fluid filled, may enlarge to 10 cm. - Single or multiple. - Common 2% of people< 50y, up to 20% > 70yrs.

Acquired cystic disease of the kidney

Acquired cystic disease of the kidney

Vascular renal diseases

Renovascular HTN • Clues; - abrupt onset, accelerated HTN. - recurrent flash pulmonary edema. - Deterioration in renal function with BP reduction and/or ACE inhibitor therapy. - Generalized atherosclerosis obliterans. - asymmetrical kidneys.

• Causes; - RAS (narrowing > 50%) - vasculitis - TMA.

Atherosclerotic renal artery disease (ASO-RAD) • • • •

5th to 7th decades of life. 70-80% ostial stenosis. Tend to progress, renal impairement. TTT; anti HTN, lipid lowering,antiplat. interfere if; > 60% stenosis. progressive↓KFTs evidence of salvageability; - normal Kid size - good function in renal scan - RI<80 TTT  percutaneous angioplasty +stent . if failed surgical revascularization

114

Classification of renal artery stenosis: 1. Atherosclerotic renal artery disease (60 - 80%) 2. Fibrous dysplasias (20 - 40%).

FMD • • • • •

Female, 30-50 yrs. Slow progression. Renal functions preserved. 1% of HTN. Most frequent is medial dysplasia with multiple contiguous stenosis ‘string of beads’. • TTT; ACEI, percutaneous angioplasty (curable, low restenosis), if failed surgical revascularization

Hypertensive Nephrosclerosis • 27% of ESRD patients. • risk factors for progression to ESRD include age, sex, race, smoking, hypercholesterolemia, duration of hypertension, and preexisting renal injury. • Kidney biopsies (not needed); arteriolosclerosis, chronic nephrosclerosis, and interstitial fibrosis in the absence of immune deposits . • TTT; Treating hypertension <130/80 mmHg if there is preexisting diabetes or kidney disease, most patients begin therapy with two drugs, classically a thiazide diuretic and an ACE inhibitor.

Renal vein thrombosis • Etiology; History of nephrotic syndrome or pulmonary embolism. • C/P; Flank pain. • Urine analysis; Mild proteinuria Occasional hematuria. • Renal venogram or MR venogram are diagnostic.

Atheroembolic disease • Def; separation of cholesterol crystals from atheromatous plaques to small renal arteries. • Etiology; Vascular disease; classically occurs within days– weeks of manipulation of the aorta or other large vessels as coronary angio, or in the setting of anticoagulation.

• Clinical picture; Retinal plaques, palpable purpura, livedo reticularis, slow deterioration of renal function. • Lab; Eosinophilia, Hypocomplementemia, Eosinophiluria • Diagnosis; Skin or renal biopsy ccc clefts, concentric intimal fibrosis, FSGS. • TTT; stop anticoagulation, low dose steroids.

Urinary tracts

Urinary Tract Infection The infecting organism • E coli =80-95% • Staph. Sapro. = 5-10% • Enterococci (Strept. fecalis) =5-14% • Others; proteus = 2-3%,Klebsiella = 2-3%, Pseudomonas, candida esp in complicated cases. Uncomplicated UTI= healthy young woman. 1. Uncomplicated cystitis; - C/P; dysuria, frequency, suprapubic pain. - diagnosis; history, urine analysis pus cells>4/HPF. - TTT; 3 daysTMP/SMX or Quinolones or 5d Nitrofurantoin. - if recurrent long term small dose postcoital or 3 times/wks at bed time. 2. Uncomplicated pyelonephritis; - C/P; fever, loin pain. - diagnosis; urine culture; bact count >104 - TTT; TMP/SMX or Quinolones (IV if vomiting) till culture sensitivity for a total of 14 days.

• Complicated UTI; - In structural or functional abn e.g. anatomic abnormality, Instrumentation, Medical condition; as Pregnant, Diabetic CKD, transplant,Nosocomial,Childhood UTI, symp.> 7d, Drugs; antibiotics, immunosup. - Elderly, men & children. diagnosis; bact count >105. TTT; 7 days for lower & 14 days for upper UTI with broader spectrum Ab covering pseudomonas e.g. Piperazin/tazobactam, Cefepime, Imipenem, Meronem,. if recurrentlong term suppressive therapy ie full dose then ½ dose when culture –ve.

Catheter-Associated UTI Asymptomatic patient • no therapy is indicated. (as relapse is very common). In symptomatic patient antibiotics is based on the Gram's stain of urine or the antimicrobial sensitivity patterns. Prophylactic antimicrobial therapy • In case the time of catheterization is clearly limited (e.g., in gynecologic , vascular surgery, kidney transplantation).

UTI in Men • In men > 50 years with UTI, - Intensive therapy for at least 4 to 6 weeks up to 12 weeks is recommended due to deep tissue invasion of the prostate & the kidneys even in the absence of overt signs of infection at these sites. • Treat Relapse (1) long-term antimicrobial suppression (2) surgical removal of the infected prostate.

Asymptomatic bacteriuria in Pregnancy • Screening for asymptomatic bacteriuria by urine culture at the first prenatal visit (12-16 wks pregnancy) is mandatory (for fear of pyelonephritis that develop by the end of the second trimester & so may lead to premature delivery). • If +ve  repeat to confirm then treat with 5- 7 days of nitrofurantoin (100 mg twice daily) , amoxacillin (500 mg PO three times daily ) cephalexin (500mg twice daily). FU culture 1 week after and then monthly until the completion of the pregnancy.

• • 1. 2.

Fungal Infection of the Urinary Tract

Candida AlbicansFluconazole, itraconazole or 5 flurocytosine. Treat if: symptomatic, Asymptomatic only if neutropenia, or urinary tract manipulation or repeated culture counts > 10.000. otherwise rapid recurrence is common, selection of resistant Candida, and clinical outcomes do not appear to be improved . • Regimens: 1. Catheter-associated candidal UTI, removal of the preceding catheter, insertion of a three-way catheter, and infusion of an amphotericin rinse for a period of 3 to 5 days . 2. Without catheter,  fluconazole, 200 mg/day for 10 to 14 days, (insertion of a catheter for an amphotericin rinse carry risk of bacteriuria). Success is increased if such contributing factors as hyperglycemia, corticosteroid use, and antibacterial therapy can be eliminated.

Etiology of Urolithiasis • Anatomical causes - ureteropelvic junction (UPJ) obstruction, - Horseshoe or ectopic kidney - vesicoureteral reflux, - calyceal diverticula - medullary sponge kidney • Metabolic causes - low urinary volume, - hypercalcuria (25%–40%), - hyperoxaluria (10%–50%), - hyperuricosuria(8%–30%) and - hypocitraturia (5%–30%)

Major Causes of Renal Stones Stone Type and Causes

Etiology

Diagnosis

Treatment

Alkali supplements +

Calcium stones 85% ,

Idiopathic hypercalciuria 50%

Hereditary(?)

Normocalcemia, unexplained hypercalciuria ( > 300 mg / 24 hrs ).

diet; thiazide

1ry hyperPTH

Neoplasia

Unexplained hypercalcemia

Surgery

Distal RTA

Hereditary

Hyperchloremic acidosis, minimum urine pH >5.5

Alkali replacement

hyperoxaluria

High oxalate or low calcium diet Bowel surgery Hereditary

Urine oxalate >45 mg per 24 h

Low oxalate diet Cholestyramine pyridoxine

Hypocitraturia

Hereditary (?), diet

Urine citrate <320 mg per 24 h

Alkali supplements

%Occurrence

Etiology

Diagnosis

Treatment

Uric acid stones 5-10% Hereditary Intestinal, habit

Clinical diagnosis Uric acid stones, Urine uric acid >750 mg /d (women), >800 mg /d (men)

Alkali and allopurinol if urine uric acid >1000 mg/d

Cystine stones 1%

Hereditary

Stone type; elevated cystine excretion

Massive fluids, alkali , D-penicillamine

Struvite stones 5-10%

Infection

Stone type

Antimicrobial agents

Hyperuricosuria

50% Gout 50 % Idiopathic Dehydration

Acetohydroxamic acid judicious surgery

Dietary modification • Increase fluid intake to maintain urine output of 2-3 l/day: • Decrease intake of animal protein • Restrict salt intake • Normal calcium intake. • Decrease dietary oxalate;

RENAL STONES • Calcium oxalate stones are the commonest kind of stones. • Calcium phosphate stones are the second commonest and associated with 1ry hyperpara, d RTA, CAI (alkaline urine). • Uric acid stones (5% of all stones) are associated with high purine metabolism, chronic diarrhoea, gout. • cystine stones associated with amino aciduria; a disorder of proximal tubular cells. (COAL – cystine, ornithine, arginine, lysine) . • Proteus splits urea into ammonia, causing alkaline urine  struvite stones (magnesium ammonium phosphate). • Radiopaque stones are: Calcium oxalate, calcium phosphate, triple phosphate, cystine stones. • Radiolucent stones are: Uric acid, xanthine stones.

comprehensive metabolic evaluation • serum calcium, bicarbonate, creatinine, chloride, potassium, magnesium, phosphate, and uric acid. • 24 hour urine collections for: volume, pH, calcium, oxalate, citrate, uric acid, phosphate, sodium, potassium, and creatinine. • Na nitroprusside test & 24 hour measurement of cystine • Intact PTH and 1,25 dihydroxycholecalcifirol in hypercalcaemic patients. Indicated for; 1. Patients with multiple stones at first presentation, 2. Patients with family history of urinary stones. 3. Patients with recurrent urinary stone. Noncontrast helical Computed Tomography (CT) 91% sensitive and 98% specific in detecting urolithiasis

Beverage type

risk

Coffee and tea

Decreased

Alcohol

Decreased

Milk

Decreased

Lemon juice

Decreased

Grapefruit juice

Increased

Cranberry juice

Increased

Carbonated beverages

Increased

Cola

Increased

Promotors & Inhibitors of stone formation Dietary factor

Proposed mechanism(s)

Promotors Oxalate

Increased urinary oxalate excretion

Sodium

Increased urinary calcium excretion

Animal protein

Increased urinary calcium and uric acid excretion; reduced urinary citrate excretion

Vitamin C

Increased oxalate generation and excretion

Inhibitors Dietary calcium

Binding of dietary oxalate in gut

Potassium

Increased urinary citrate excretion; reduced urinary calcium excretion

Phytate

Inhibition of calcium oxalate crystal formation

Magnesium

Reduced dietary oxalate absorption; inhibition of calcium oxalate crystal formation

Urinary citrate

oppose crystal formation by thermodynamic and kinetic mechanisms

Vitamin B6

Vitamin B6 deficiency may increase oxalate production and oxaluria

Hyperoxaluria • urinary excretion of oxalate in excess of 45 mg/day. Primary (Inherited) Hyperoxaluria. Rare AR , excessive oxalate production and systemic deposition of calcium oxalate  tissue damage e.g. heart, bone, retina, kidneys Nephrocalcinosis. Secondary (Enteric) Hyperoxaluria. - Reduced availability of free calcium to bind intestinal oxalate in malabs. - The colon absorbs unbound oxalate. - increased colonic permeability in IBD. - Contributing factors include a low urinary citrate concentration, decreased urine volumes, and a low urinary pH, all due to diarrhea and consequent loss of fluid and bicarbonate in the stool. NB; Renal stones are primarily composed of calcium oxalate when the ileum is involved (e.g., ileocolonic Crohns disease), and uric acid when patients have copious diarrhea or small bowel ostomies.

Retroperitoneal fibrosis • • 1. 2. 3. 4. 5. • • • • •

Definition; ureter embedded in dense fibrous tissue Causes; Idiopathic (♂, 40th-50th) Trauma, surgery, radiation. Inflammation; infection, granuloma, autoimmune (sclerosing cholangitis) Neoplastic; lymphoma, Cx, bladder. Drugs; methysergide, bromocriptine, ergotametrine ,αMD, hydralazine, BB. C/P; insidious onset of dull aching pain. IVP & U/Smedial indrawing of ureter at junction of middle & lower part. CT; periaortic mass. ESR very high. TTT; surgical releave of ureter, steroid for idiopathic type.

Acute Renal Failure •

Def; Acute renal failure (ARF) is characterized by a rapid decline in glomerular

filtration rate (GFR) over hours to days. 1. Prerenal (60-70%) - ↓ESF volume; renal loss e.g,diuretics, extrarenal e.g. diarrhea, burns - ↓effective bl volume; ↓COP , VD , oedematous states. - intrarenal VC; cyclosporin, NSAIDs, ACEI, HRS. 2. Intrinsic renal (25-40%); - ATN; ischemic, toxic e.g. G-ve sepsis/ Endogenous as rhabdomyolysis, hemolysis, cast neph, tumour lysis / exogenous toxins; aminoglycosides, amphotericin, cisplatinum,cyclosporin. - tubular obstruction; Endogenous: myeloma proteins, uric acid (tumor lysis syndrome). Exogenous: acyclovir, gancyclovir, methotrexate, indinavir, ethylene glycol. - AIN. - vascular; TMA e.g. DIC, malignant hypertension, preeclampsia. - glomerular; acute nephritis. 3. Postrenal ARF (Obstruction) I. Ureteric (bilateral, or unilateral in the case of one kidney): calculi, blood clots, sloughed papillae, cancer, external compression (e.g., retroperitoneal fibrosis) II. Bladder neck: neurogenic bladder, prostatic hypertrophy, calculi, blood clots. III. Urethra: stricture or congenital valves

• Prerenal ARF; - High BUN/CR ratio>20. - FENa < 1 % -UNa <10 mmol/L - high urine osmolarity > 500 mosm/l. - SG >1.018. •

Renal (Acute tubular necrosis); - Muddy brown granular or tubular epithelial cell casts - FENa > 1 % - UNa > 20 mmol/L - low urine osmolarity < 500 mosm/l. - SG <1.015

Diagnosis

cause

serum

urine

ttt

Rhabdomyolysis (Myoglobinuria)

Physical Metabolic & elect. Drugs. infections

Increased U/A positive for myoglobin, heme but no ↑CPK,creatinine, RBCs P, K, uric acid, high AG MA, ↓Ca. BUN/creat<10

Hemolysis: recent blood transfusion, G6PD, PNH, cold Ab

Fever, other evidence of transfusion reaction

Pink plasma, Increased LDH

Pink, hemeAs Myoglob. positive urine without hematuria, hemosiderinuria

Tumor lysis

recent chemotherapy

Hyperuricemia, increased LDH

Urate crystals ↑urine uric acid/u creat>1

Fluid therapy forced alkaline diuresis with HCO3, mannitol in dextrose

alkalinization of urine, allopurinol, uricase, fuboxostat

Hepatorenal syndrome •

• 1. 2. 3. 4. 5. • 1. 2. 3. 4.

It is a functional impairement in kid functions 2ry to intrarenal VC in LC with S. creat > 1.5 mg/dl or GFR < 40 ml/min in the absence of any other cause of kid dysfunction. Major criteria for diagnosis; LCF with portal HTN. S creat > 1.5 mg/dl or GFR < 40 ml/min No improvement after stopping diuretics & fluid chalenge of 1.5 L. Absence of shock, infection, nephrotoxins. Proteinuria <0.5 gm/dl, US normal, no obst or parenchymal change. Minor criteria; S Na < 130 meq/l Urine Na< 10 meq/l Urine/P osm>1 Urine volume<1 l.

Contrast nephropathy • Non oliguric ATN acute rise of serum creatinine 24-48 hrs after administration of IV contrast, peak = 3-5 days, baseline = 7-10 days. • Risk factors; DM, CKD, MM, ACEI, NSAIDS, prerenal failure, high dose. • Pathophysiology; VC & tubular toxicity. • Prevention; 1. Use of low osmolality, non ionic contrast agent e.g. gadopentate dimeglumine (ultravest). 2. Least dose. 3. IV infusion of ½ NS 1-2 hrs before to 24 hrs after at a rate of 1 ml/kg/hr. 4. Acetylcysteine 600 mg sachet/12 hr 2 days before. 5. +/- theo 2 ds before, nefidipine 10 mg subluigual before. 6. # mannitol, frusemide, dopamine, ANP. TTT; fluid chart, electrolytes, HD. NB; Gadolinium in MRInephrogenic systemic fibrosis.

Chronic Kidney Disease Classification of Chronic Kidney Disease (CKD) Stage

GFR, mL/min per 1.73 m2

1

> 90b

2

89–60

3

59–30

4

29–15

5

< 15

• bWith demonstrated kidney damage (e.g., persistent proteinuria, abnormal urine sediment, abnormal blood and urine chemistry, abnormal imaging studies). • Cockcroft-Gault equation; GFR e= (140-age) x BW/s. creat x 72 X 0.85 for women

Clinical and Laboratory Manifestations of CKD and Uremia Fluid and electrolyte disturbances Volume expansion ↓Na, ↑ K,↑P Endocrine-metabolic disturbances Secondary ↑ PTH Adynamic bone dis. Vitamin D–deficient osteomalacia Carbohydrate resistance Hyperuricemia Hypertriglyceridemia. Decreased HDL Protein-energy malnutrition Impaired growth Infertility and sexual dysfunction Amenorrhea

Neuromuscular disturbances Fatigue, Sleep disorders Headache, Impaired mentation Lethargy, Asterixis Muscular irritability PN, Myoclonus, Myopathy Restless legs syndrome Seizures, Coma Muscle cramps Dialysis disequilibrium Cardiovascular and pulmonary disturbances Arterial hypertension CHF Pericarditis,Hypertrophic or dilated cardiomyopathy , Accelerated atherosclerosis Hypotension and arrhythmias Vascular calcification(

Dermatologic disturbances Pallor, Hyperpigmentation Pruritus Ecchymoses Nephrogenic fibrosing dermopathy ,Uremic frost Gastrointestinal disturbances Anorexia, Nausea and vomiting, Peptic ulcer Gastrointestinal bleeding Idiopathic ascites. Hematologic and immunologic disturbances Anemia Bleeding diathesis Increased susceptibility to infection Leukopenia Thromboathenia

Treatment * Slowing the Progression of CKD 1. 2.

3. 4. 5. 6.

Protein Restriction, between 0.60 and 0.75 g/kg per day. Reducing Intraglomerular Hypertension and Proteinuria; ACE inhibitors and ARBs, target blood pressure in proteinuric CKD patients=125/75 mmHg. Slowing Progression of Diabetic Renal Disease; hemoglobin A1C should be < 7%. Managing Other Complications of Chronic Kidney Disease. Medication Dose Adjustment. Preparation for Renal Replacement Therapy.

* Renal replacement therapy.

Dialysis in the Treatment of Renal Failure Hemodialysis • •

Hemodialysis relies on the principles of solute diffusion across a semipermeable membrane. Movement of metabolic waste products takes place down a concentration gradient from the circulation into the dialysate.

Complications during Hemodialysis;

1. 2. 3. 4.

Hypotension. Muscle cramps. Anaphylactoid reactions to the dialyzer. Disequilibrium S.

Peritoneal Dialysis • In peritoneal dialysis, 1.5–3 L of a dextrosecontaining solution is infused into the peritoneal cavity and allowed to dwell for a set period of time, usually 2–4 h. • As with hemodialysis, toxic materials are removed through a combination of ultrafiltration and down a concentration gradient. • The major complications of peritoneal dialysis are peritonitis, catheter-associated infections, weight gain and other metabolic disturbances, and residual uremia.

Anemia of CKD •

2. 3. 4.

Develops when the GFR < 60 mL/min, symptomatic only when GFR<30 ml/min due to increase 2,3DPG & LVH. normocytic and normochromic. due to; reduced renal erythropoietin production (reduction in functioning renal mass) and, shortened red cell survival (60-90d vs. 120d). Hemolysis, bl loss during HD. Bleeding tendency & Fe deficiency.

•

Anemia may be a risk factor for progression of CKD.

• • 1.

• TTT 1.

• 1. 2. • 1. 2.

Correct Fe deficiency if ferritin <200 ng/ml & TSAT<20%. Target ferritin 200-500 ng/ml & TSAT=20- 50%. For predialysis oral 200mg elemental Fe/d or IV 200mg/1-3 months. for HDIVI, 100mg for 10 sessions then /wk. Side effects; free Fe reaction; N,V,↓BP, back pain. Anaphylaxis (Fe dextran due to anti-dextran Ab). Contraindications; Active inflammation. Fe overload.

2) Erythropoietin • • • • • • • 1. 2. 3. 4.  • • •

When Hb of < 11 g/dL . Target Hb= 11 to 12 g/dL , NOT above 13 g/dL (adverse CVS effects, increase risk for hypertension ) . EPO α, ß, Darbipoitin. Dose= 80-120 U/Kg/wk SC, ↑dose by 30-50% iv. SC rather than IV ; stable level, more biologically active but PRCA with EPOα. ↓dose by 25% when target reached. Benefit; regression of left ventricular hypertrophy. aerobic capacity, cognitive and sexual function. Side effects Hypertension Headache PRCA; due to neutralizing anti-erythropoietin antibodies

• Causes of EPO resistance; 1. Iron deficiency (most common ) 2. Bone disease due to 2ry hyperparathyroidism. 3. Occult malignancy 4. vitamin B12 and folic acid deficiency. 5. Multiple myeloma/myelofibrosis/myelodysplastic syndrome. 6. Chronic inflammation. 7. Aluminum toxicity. 8. Hemoglobinopathies. 9. ACEI or ARBs. 10.pure red cell aplasia with neutralizing anti-erythropoietin antibodies esp. with SC EPO α. 11.HIV infection.

Renal Osteodystrophy • A systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: - Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism - Abnormalities in bone turnover, mineralization, volume, linear growth, or strength -Vascular or other soft tissue calcification

Renal Osteodystrophy •

•

A systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: - Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism - Abnormalities in bone turnover, mineralization, volume, linear growth, or strength -Vascular or other soft tissue calcification Pathogenesis; ↑PO4 ↓Vit D ↓Ca

Bone ↑PTH

Normal pulsatile action+ osteoblast Continuous high downregulate osteoblast receptors unopposed osteoclastCa/P efflux

• Classification; 1. High turnover disease (2 ry ↑PTH > 300 pg/ml or osteitis fibrosa). 2. low turnover (adynamic) bone disease ( PTH<150 pg/ml ) due to Ca load= overtreated. 3. Osteomalacia ( defective mineralization) due to Alm. Toxicity, ↓Vit D, metabolic acidosis, ↓P. 4. Mixed uremic osteodystrophy; 2 ry ↑PTH + Osteomalacia

• 1. 2. • 1. 2. 3. 4. 5. 6.

N

C/P; Bony aches, reccurent pathological fractures. Soft tissue calcifications; vascular, valvular, skin. calcifications in atherosclerotic plaques, arteriosclerosis, calciphylaxis. Diagnosis; Intact PTH= full length PTH (1-84)(active) + PTH fragment (7-84)( inactive accumulate in RF). Bone specific ALK P (osteoblastic act). Bone biopsy. X rays. DEXA. Desferoxamine test for Alm tox.

C 1

7

PTH

84

TTT • 1.

2.

3.

Best= sevelamer + Vit D analogue. ↓P; - dietary restriction - Ca based P binders; Ca carbonate, acetate. - if ↑ Ca AL OH, sevelamer, lanthanum carbonate. ↓PTH; - Vit D (calcitriol). - Vit D analogues (1 α, paricalcitol) - calcimimetics (cinacalcet= CaSR agonist) - PTH dectomy if; PTH > 800 + ↑Ca or ↑P despite medical TTT. calciphylaxis severe sympt. Transplantation.

This is a patient with end stage renal disease, with severe uncontrolled hyperparathyroidism. What is the skin lesion

Slide no 9

Transplantation • Tissue Typing; 1. ABO(O) blood groups 2. human leukocyte antigen (HLA) class I (A, B, C) or class II (DR) antigens 3. Punnel of reactive antibodies (PRA) 4. cross-match of recipient serum with donor T lymphocytes

Hyperacute

Accelerated acute

Acute

Chronic

immediate

5 days

5 d-4 m

> 4m

Mechanism Humoral

cellular & humoral

cellular

cellular & humoral

Effector

memory T cells

T cytotoxic

T helper & B lymphocytes

Interstitial tissue mononuclear & neutrophyl infiltration & vasculitis

Interstitial tissue mononuclear infiltration

Chronic interstitial nephritis & fibrosis

onset

preformed Ab

Pathology Intravascular thrombosis

Immunosuppressive Treatment 1. Induction therapy with Antibodies to Lymphocytes; Depleting Ab e.g. - ATGAM, OKT3 - Thymoglobulin is the most common agent currently in use. - Alemtuzumab non- Depleting Ab e.g. - anti CD25 (IL2 receptors); Basiliximab & Daclizumab. - Belatacept (costimulatory pathway blockade) 2. Maintenance Immunosuppressive Drugs

Agent

Mechanisms

Side Effects

Glucocorticoids

Binds heat shock proteins. Blocks transcription of IL-1,-2,-3,6, TNFα and IFN γ

Hypertension, glucose intolerance, dyslipidemia, osteoporosis

Cyclosporine CsA

calcineurin --block IL-2 production; however, stimulates TGF production

Nephrotoxicity, HTN, dyslipidemia, glucose intolerance, hirsutism/ hyperplasia of gums

Tacrolimus (FK506)

Similar to CsA, but hirsutism/hyperplasia of gums unusual, and diabetes more likely

Azathioprine

inhibit purine synthesis

Marrow suppression (WBC > RBC > platelets)

Mycophenolate mofetil (MMF)

Inhibits purine synthesis

Diarrhea/cramps; dose-related liver and marrow suppression is uncommon

Sirolimus

blocks p70 S6 kinase in the IL-2 receptor pathway for proliferation

Hyperlipidemia, thrombocytopenia

The Most Common Opportunistic Infections in the Renal Transplant Recipient Peritransplant (<1 month) Wound infections Herpes virus Oral candidiasis Urinary tract infection Early (1–6 months) Pneumocystis carinii Cytomegalovirus Legionella Listeria Hepatitis B Hepatitis C

Late (>6 months) Aspergillus Nocardia BK virus (polyoma) Herpes zoster Hepatitis B Hepatitis C

BK virus • BK virus nephropathy & ureteral stenosis. • Urothelial carcinoma,vasculopathy. • Biopsy; patchy interstitial infiltration, IF; Ab to simian v. 40. • Urine cytology +ve for decoy cells(tubular cells appear malignant due to viral inclusions. • PCR. • TTT; reduce IS, leflunamide, cidofovir.

Malignancy • The incidence of tumors in patients on immunosuppressive therapy is 5–6%, or approximately 100 times greater than that in the general population of the same age range. • The most common lesions are cancer of the skin and lips and carcinoma in situ of the cervix, as well as lymphomas such as non-Hodgkin's lymphoma. • The risks are increased in proportion to the total immunosuppressive load administered and time elapsed since transplantation. • Surveillance for skin and cervical cancers is necessary.

Slide no 2 • This skin lesion appeared 2 months after a successful renal transplant • What is the most likely diagnosis

Rate of relapse & graft loss Glomerular disease recurrence

graft loss

FSGS

15%

50%

Membranous

10%

50%

Ig A

50%

15%

MPGN

50%

Alport

anti-GBM

Pregnancy related kidney diseases ARF in pregnancy; 1st trimester; hyperemesis, septic abortion. 2nd trimester; TTP (any time). 3rd trimester; acute fatty liver, HELLP, post renal dt enlarged fibroid, stones, Gravid uterus, Polyhydramnios. Post partum; HUS, bil cortical necrosis.

TTP

HELLP

Acute fatty liver

HUS

Cortical necosis

timing

2nd, 3rd trimester

3rd trimester

3rd trimester (more common)

postpartum

postpartum Hge e.g. abruptio placentae

C/p

Fever neuro

-Mild renal failure -Proteinuria -HTN

-ANV abd pain -Hepatic encephalopathy - hypoglycemia -Jaundice - DIC -Severe renal failure

-Severe renal failure - Poor renal prognosis

Oliguria Hematuria Flank pain

Lab

-↓plat, ↓Hb -↑uncong. bilirubin -shistocytes

-↑liver enz -↑uric acid Hypocalcuria -↑PT, PTT, ↓plat

-↑liver enz -↑PT, PTT, ↓plat -↓fibrinogen -↑congugated bil - hypoglycemia

ttt

plasmapharesis

termination

termination

Hypo or hyper echoic areas in US

Supportive dialysis

dialysis

Hypertensive disorders in pregnancy; 1.Pre-eclampsia (27%); de novo, after 20th week gestation, resolve within 3 months + proteinuria. 2.Chronic HTN (23%); before pregnancy, before 20th week gestation, does not resolve post partum (essential 19% or 2ry 4%) 3.Pre-eclampsia superimposed upon underlying HTN(7%) 4.Gestational HTN (43%); mild, de novo, after 20th week gestation, resolve within 3 months without maternal organ dysfunction.

• NB; preeclampsiaafter 20 wks, ↑liver enzymes, normal Complement. • Lupus activity ↓complement.

Neurology

Dementia    1.    2.    3. 

Definition; acquired progressive loss of cognitive function. Most common cause is Alzheimer’s dis., then lewy body 20%, multi-infarct 20%. Classification; Ant. Dementia; fronto temporal lobe lesion, antisocial personality & behavior. e.g. pick, metabolic. Post. Dementia; Parietotemporal. Memory, conc, orientation e.g. Alzheimer’s. Subcortical; lewy body, multi-infarct, Parkinson, PSP, normal pressure hydrocephalus, Huntington, wilson, MS, HIV.

Pick disease; atrophy of frontal & or temporal lobe, pick bodies, language, behavioral, frontal lobe features.  Alzheimer’s dis;  20% familial (AD),  loss of recent memory,,  Histopath. senile plaques, neurofibrillary tangles,  Biochemical. loss of cholinergic neurons.  mutation of presenilin 2 on chro 1, presenilin 1 on chro 14 .  Associated with Down S, . TTT; Donepezil (cholinesterase inhibitor). if aggressive  valproate. if severe; stop Donpezil & give Melatonine 

Lewy body Dementia; 

 



Intermittent dementia within 2 month of Parkinsonism Visual hallusinations, paranoid delusions Marked sensitivity to neuroleptics (may be fatal, so antipsychotic are #). Intranuclear inclusions in the cortex.

Atherosclerotic= Vascular =Multiinfarct;   

Stepwise fashion. Marked rigidity, shuffling gait & pseudobulbar palsy + risk factors

Normal pressure hydrocephalus; Dementia + gait abnormalities (wide based) + urinary incontinence (unaware, indifferent).  No headache, no papilledema.  Defect in CSF absorption, may be post meningitic or trauma.  CT= hydrocephalus, no cerebral atrophy..  CSF= normal pressure (intermittently high).  TTT; ventriculoperitoneal shunt. Parkinson plus syndromes; 1. Progressive supranuclear palsy; (PSP)  Parkinson + ophthalmoplegia (vertical gaze defect) + freq. falls Dementia (late), pseudobulbar palsy. 2. Multiple system atrophy;  Parkinson + autonomic distur (aware) + cerebellar & Δ.  Early age (50 y), median survival=6-9 yrs.  Ttt; dopaminomimetic, good response but lead to orthostatic hypotension. 

Huntington Chorea; - AD, Chr 4 , CAG trinucleotide repeat. Anticipation refers to the increase in severity with subsequent generations. - ↓Ach, GABA in caudate. - in contrast to parkinson; dopamine is normal. - age; 30-40 yrs.- triad; Chorea + dementia + (antisocial behavior) +opthalmoplegia. + FH - genetic testing. - no specific ttt. phenothiazines (haloperidol) for symptomatic control. ( haloperidol)

Progressive multifocal leukoencephalopathy 

(PML) is caused by chronic infection with JC virus, and causes white matter lesions in the brain. A CD4+ of <100 predisposes to the condition .



JC virus invades oligodendrocytes, which manufacture myelin, causing demyelination.



Hemiparesis, aphasia, ataxia and altered mental state with an insidious onset of dementia.



Anti-retroviral therapy including a protease inhibitor is the main treatment for PML with HIV.

Progressive Multifocal leuckoencephalopathy; P M L esions ↑ CSF protein Male white matter PCR memory hypodense Papova virus (JC) mood areas esp. motor occip cortex MRI

Chronic Subdural haemorrhage 



Bleeding is from bridging veins between cortex and venous sinuses, resulting in accumulation of blood between dura and arachnoid. Risk factors age, alcohol, fallstrauma (may be trivial). epilepsy, anticoagulant therapy.

Presentation Often insidious and history may go back several weeks:  Fluctuation of conscious level (35%).  Sleepiness ,Headache ,Personality change.  Unsteadiness on feet  Slowly evolving hemiparesis.  Sympoms/signs of inc.ICP.  dementia. Differential diagnosis Stroke , cerebral tumour,  TTT: If suspected, admit as a medical emergency for further investigation. Evacuation of clot is possible even in very elderly patients and results in full recovery. 

Creutzfeldt-Jacob dis; Def; prion dis, caused by abn prion protein which accumulate in the brain which is thought to be an infectious agent, resistant to heat& autoclaving. C/P; vague sensory manifestations. then Dementia, ataxia, myoclonic jerks. CSF; normal, mild ↑ in protein. 

Normal CT brain.

Dis duration 1/2 yr -2 yrs EEG; biphasic high-amplitude Sharpe waves. Most common is sporadic (85%), other forms are familial, new variant. new variant (BSE)

sporadic

age

Young (30 yr)

Old (60 yr)

C/P

Ataxia cerebellar signs

The same.

(motor, Δ) sensory , occipital blindness,Psyhatric dementia Personality, behaviour, ECG

Not specific

specific; periodic biphasic Sharpe waves in deep brain e.g. thalamus

MRI

high signal in T2. bilateral

High signal in T2 in putamen & caudate

posterior thalamic ( pulvinar)

Prion diseases Variant (20-30 yrs,)BSE From introduction of infected brain tissue to another hostthe abnormal prion protein trigger the conversion of the normal protein into the atypical isoform accumulation of amyloid plaques spongiform change of the brain.

 1.

2. 

Transmission; Dural or corneal grafts, neurosurgical instruments, human derived hormones as GH. Food from infected cattle with bovine spongiform encephalopathy. Pathology; gliosis, small vaculation, plaques containing protease resistant PrP .

Differentiation of depression from dementia Onset,course duration C/O of memory loss O/E

depression

dementia

Acute, rapid, short

Gradual, slow, long

yes Detailed history giving, poor effort at testing, pick on faults, global memory loss,

+ve sympt of depression

No Vague history Good Pleased Recent



Transient global amnesia;

-sudden confusion & amnesia. -Antegrade & retrograde amnesia for recent up to years memories. -Self identification is preserved. -dt transient vascular insuff of both hippocampi.

Demylenating diseases 1. 2. 3. 4. 5.

MS. Diffuse sclerosis. ADEM. Neuromylitis optica. Central pontine mylenolysis.

Multiple sclerosis 

Def; a cell-mediated autoimmune dis against myelin. Subtypes;

1.

Relapsing/ remitting; (80-85%), acute attacks for 4-8 wks, relapse



rate= 0.8/y. 2.

2 ry progressive; after 10 y of Relapsing/ remitting, progressive with less prominent relapses.

3.  

 1. 2. 3. 4.

1ry progressive; (10-20%). Aetiology unknown. C/P; mainly UMNL, LMNL is rare dt rare affection of ant horn cells. Optic neuritis; - in isolated ON  40-60% MS. - painful loss of vision. - early affected colour vision. - ttt; pulse Methyl Prednisolone. Good prognostic factors; Young. Female Relapsing/ remitting. Sensory.

Diagnosis; disseminated lesions in time & place in brain & SC .MRI; demyelinated plaques, gadolinium-enhancing lesions, affection of corpus callosum is pathognomonic. if free relapse rate is 16%, if >3 plaques, relapse rate is 50%. .Delayed VEP. .CSF; oligoclonal bands in 50%. DD of oligoclonal bands in CSF=IG synthesis in the CSF; Neurosarcoid, SLE, CNS lymphoma ,ADEM , GBS ,Subarachnoid Hge,







Internuclear opthalmoplegia: The medial longitudinal fasciculus (MLF) connects the sixth nerve to the third & fourth nerves of opposite site. There is nystagmus in the abducting eye (mnemonic NAB) and limited movement in the adducting eye on the same side. Upward gaze is not affected. Internuclear opthalmoplegia can be caused by: Multiple Sclerosis ,stroke (basilar artery) post circ. Encephalitis, lyme disease, phenothiazines, TCA.



TTT of MS;

During acute attack pulse steroid for 3-5 ds. 2. To prevent relapses INFß.  SC  prevent activated T lymphocytes from crossing BBB.  # in pregnancy.  criteria for INF therapy; &Glatiramer - Relapsing/ remitting or 2 ry progressive - 2 disabling relapses in the previous 2 yrs. - - able to walk at least 100 m (+/-assistance) - Effects; ↓ frequency, severity of relapses, delay progression to disability,.  ↓ brain lesions on MRI.  Side effects; flu-like, teratogenic, neutralizing Ab. 3. Glatiramer. 4. IVIG. 5. Symtomatic; - fatigueamantadine, methylphenidate. - bladder dysfunction anticholinergic, catheter. - spacticity baclofen, dantrolene, BDZ. - neuralgic pain carbamazipine, gabapentine. 1.

End stage of MS; dementia, quadriplegia, blindness, recurrent respiratory & UTI.  Life expectancy = 20-30 yrs.  Death dt; renal failure, bronchopneumonia. NB; baclofen; - site of action is the spinal cord. - -- synaptic transmission. 

Diffuse sclerosis; severe form of MS.  ADEM (acute disseminated encephalomylitis); - autoimmune, - 2 wks after viral (EB,CMV, exanthems, mumps, influenza,) - mycoplasma - vaccine (rabies) - monophasic i.e. no relapses. - disseminated neurological symp, rare sensory. - MRI; white matter lesions, CSF;… oligoclonal bands. - ttt; short course of high dose steroid, plasmapharesis. 

• Neuromylitis optica - Transverse myelitis + optic neuritis. - 1ry or 2ry to – SLE - ADEM - TB. - Recovery is poor - Monophasic or relapsing.

Central Pontine Myelinolysis Due to rapid correction of Hyponatremia Possibly due to disturbance of blood brain barrier and damage by cytokines





Causes;

- rapid correction of ↓Na. - Alcohol, Liver cirrhosis. -Malnutrition, Malignancy, hyperemesis gravidarum. 

MRI shows change in pons, but not diagnostic.



Fatal, No effective therapy.

Central pontine mylenolysis C/P; Pons -, quadriplagia. Pontocerebellar  cerebellar. Vasomotorhypotension Consciousness is usually impaired. 

Presentation          

•Dysarthria-Dysphagia ,nuclei 4,5,6; Pseudobulbar Paraparesis or quadriparesis Lethargy and coma Seizures-Nystagmus Ataxia emotional lability-akinetic mutism gait disturbance -myoclonus Behavioral disturbancesFatal, no ttt.

Dysmylenating diseases = leucodystrophies (reading only Adrenoleukodystrophy

Metachromatic leukodystrophy

X-linked

AR

MR, OA, paraparesis

MR, OA, paraparesis

Adrenal insufficiency

PN as HMSN type 1

- Confirmed by ↑serum VLCFA (very long chain FA)

--↑urinary sulphatides biopsy; metachromatic inclusions

Ttt; BMT

Ttt; BMT

Causes of polyneuropathy 

Inherited



Inflammatory



Metabolic



Vasculitis PAN ,Rheumatoid arthritis,Wegener's granulomatosis. Malignancy Paraneoplastic syndromes (esp small cell lung cancer)



Refsum's syndrome,Charcot-Marie-Tooth syndrome (mostly motor),Porphyria Guillain-Barr‫ ©أ‬syndrome (mostly motor),Chronic inflammatory demyelinating polyneuropathy (CIDP) DM (mainly sensory),Renal failure (mainly sensory), Hypothyroidism

Paraproteinaemias e.g. multiple myeloma, amyloidosis    

Infection Leprosy (mainly sensory) Syphilis,Lyme disease,HIV. Vitamin deficiency Lack of B1, B6, B12 (e.g. alcoholic) Toxins Lead (mostly motor),Arsenic Drugs Alcohol,Cisplatin,Isoniazid,Vincristine,Nitrofurantoin.

Mononeuropathy 

Lesions of individual peripheral (including cranial) nerves .Causes : trauma, compression, DM, lepros, HZV,PAN, DM .



Common mononeuropathies



Median nerve C5-T1 Inability to flex the terminal phalanx of the thumb and loss of sensation over lateral 3 ½‫ آ‬fingers and palm. Wasting of the thenar eminence .Common causes :trauma (especially wrist lacerations), carpal tunnel syndrome Ulnar nerve C8-T1 Weakness and wasting of interossei muscles (weakness of abduction of fingers) and wasting of hypothenar eminence, sensory loss over medial 1 ½‫آ‬ fingers and ulnar side of the hand. Flexion of 4th and 5th fingers is weak .Common causes :trauma or compression at the elbow, trauma at the wrist. Radial nerve C5-T1 Sensory loss is variable but always includes the dorsal aspect of the root of the thumb. This nerve opens the fist .Common causes :compression against the humerus, trauma. Sciatic nerve L4-S2 Weakness of hamstrings and all muscles below the knee (foot drop), loss of sensation below the knee laterally .Common causes :back injury, pelvic tumours. Common peroneal nerve L4-S2 ”Inability to dorsiflex the foot (foot drop), evert the foot, extend the toes. Sensory loss over dorsum of the foot .Common causes :trauma. Tibial nerve S1-3 Inability to stand on tiptoe, invert the foot, or flex toes. Sensory loss over sole.









 

Carpal tunnel syndrome Pain in the radial 3 ½‫ آ‬digits of the hand ±‫ آ‬numbness, pins and needles, and thenar wasting. Due to compression of the median nerve as it passes under the flexor retinaculum. Worse at night. Symptoms are improved by shaking the wrist.Associations: Pregnancy , hypothyroidism, obesity ,acromegaly , amyloidosis and Rh arthritis. 

Investigations.





Phalen's test. hyperflexion of wrist for 1min. triggers symptoms Tinnel's test. tapping over the carpal tunnel causes paraesthesiae Nerve conduction studies.



Management.



steroid injection, US waves , Laser therapy. surgery to divide the flexor retinaculum is curative in mild/moderate disease.





Causes of mononeuritis multiplex      

DM. Amyloidosis. Sarcoidosis. Leprosy. Vasculitis. ( PAN). Carcinomatosis.

C/P of polyneuropathy Motor : LMNL( hypotonia ,hyporeflexia , marked wasting ) Weakness Distal > proximal , LL>UL , Bilateral & symmetrical, Foot & Wrist drop .high steppage gait.

Sensory : Superficial:Glove&stock hyposthesia& parasthesia Deep :Sensory ataxia(dec sense of position , sense of movement, sense of vibration)

Autonomic: skin , GIT,GU .

Management of Autonomic neuropathy  

Treat any underlying cause. Advice:    



stand slowly raise head of the bed at night eat little and often avoid alcohol intake.

Fludrocortisone (100mg/d., increasing prn) may help those most severely affected.

Mainly Motor Polyneuropathy     

GB$. Diphteria . Porpheria. Lead poisoning. CIDP.

Mainly Sensory Polyneuropathy  DM.  Uremic N.  Amyloidosis.  Vitamin deficiency. 

 

Carcinomatosis. Leprosy.

Acute polyneuropathy 

GB$. Lead poisoning . Alcohol toxicity.



Polyneuropathy with bilateral facial paralysis.





Sarcoidosis. GB$. Bilateral Bell s palsy. Bilateral acoustic neuroma. Lyme disease.



Polyneuropathy with proximal weakness.

 

Diabetic amytrophy (weakness,wasting & pain of thigh muscles & pelvic girdles.) for few months, no effective ttt GB$



CIDP.

 

  

Guillain Barre syndrome 

    



is acute post-infectious polyneuropathy preceded by diarrhoea (e.g. campylobacter) and chest infections (e.g. mycoplasma) in two thirds of cases. Demyelination & mainly motor. Weakness begins in the legs and ascends to involve the trunk, upper limbs and finally the bulbar muscles. Symmetrical involvement being typical & asymmetry is present in only 9% of patients. Autonomic dysfunction and hyporeflexia are associated. Bulbar involvement occurs in 50%, Studies have shown that plasma exchange and IVIg are equally effective in treating people within two to four weeks of onset of GBS The dissociation between a high CSF protein and a lack of cellular response with normal glucose in a person with an acute or subacute polyneuropathy is diagnostic of Guillain Barré Syndrome

Miller Fisher Syndrome In the, Miller Fisher Syndrome a variant of GBS there is external ophthalmoplegia, ataxia and areflexia. Clinical symptoms usually improve within 2-3 weeks. It usually follows antecedent infections. Serum IgG antibody to the ganglioside GQib is present in more than 95% of patients. It is highly specific for the syndrome.



Pellagra: A triad of dementia, diarrhoea and dermatitis. Niacin

(nicotinamide or nicotinic acid) deficiency causes pellagra only if tryptophan, an amino acid, is also deficient. Encephalopathy usually follows. It is ccc by confusion, disorientation,, and memory loss. Pyramidal tract. Peripheral nerve.  Subacute Combined Degeneration of the cord: Vitamin B12 deficiency causes PN, posterior column cord damage (Loss of vibration sense and proprioception), spasticity, extensor plantars and neuropsychiatric symptoms. Pyramidal tract. Peripheral nerve. posterior column.



HMSN 1. is the most common form of hereditary

neuropathy. Severely and uniformly slowed (NCVs) and primary hypertrophic myelin pathology. Motor symptoms predominate over sensory symptoms. Often, patients report loss of balance, muscle weakness, and foot deformities. Onset in the first decade of life.

HMSN 2. on the other hand, represents the



nondemyelinating neuronal type with relatively normal NCVs and primary axonal pathology. weakness often is less marked and onset of this neuropathy is delayed. Peripheral nerves are not enlarged. Patients experience sensory loss in the distal extremities, and foot deformities (ie, pes cavus) .

Neurofibromatosis.  NF1 (NF gene 1 defect) is found on chromosome 17 Lisch nodules (pigmented spots) of the iris are present in more than 90% of patients with neurofibromatosis type 1. The diagnosis is suggested by six or more café au lait spots. Although the condition is autosomal dominant, almost half of all cases are new mutations. 

NF2 gene defect is on chromosome 22.



Tuberous sclerosis. This is an inherited (autosomaLD)

Bilateral acoustic neuromas are a hallmark feature of neurofibromatosis type 2

hamartomatous condition facial angiomas (adenoma sebaceum) skin changes such as shagreen patches and ashleaf macules, subungual fibromas ,kidney angiomyolipomas, cardiac rhabdomyomas,,. 

von Hippel Lindau. disease is associated with cerebellar haemiangioblastomas and retinal angiomas and polycystic liver or kidneys. Ectopic erythropoietin secretion by the haemangioblastomas.RCC

Slide no 6

This female patient sufferred convuslions in childhood. She experienced several attacks of hematuria recenly. Proteinuria was less thn 1gm/24hrs and her RFTs were normal. 1. What is her condition. 2. What is the most likely lesion of her CT scan

Myasthenia gravis 



    

It is a neuromuscular disorder and therefore does not cause any lower motor neuron signs such as fasciculations, wasting, and loss of reflexes. Pupils are always normal. diurnal variation. Myasthenia gravis is well known to be associated with other autoimmune disease such as pernicious anaemia, thyroid disease and rheumatoid arth. is commoner in females (it is an autoimmune disease). The commonest features include ptosis, diplopia and ophthalmoplegia. Electromyography. Repetitive stimulation in myasthenia gravis leads to a decrement of evoked muscle action potentials in myasthenia gravis the tendon reflexes are characteristically normal. The list of drugs which may make myasthenia worse are: propranolol Aminoglycosides, Quinidine, Procainamide, Magnesium, Lithium . In myasthenia gravis, there are positive anti-Ach antibodies.

MYASTHENIA 



Pyridostigmine is an anticholinesterase which reduces acetylcholine breakdown and hence improve symptoms of fatiguability in myasthenia gravis. Thymectomy improves the prognosis in patients below 40 years and in those with positive receptor antibodies. Following thymectomy, 60 % of patients will improve. Thymectomy is usually recommended because of the risk of malignancy.



  

In Lambert Eaton myasthenic syndrome, 60% of cases are paraneoplastic (small cell lung ca is most associated 50% of the cases ). The clinical features are proximal weakness, loss of tendon reflexes and autonomic dysfunction is common (e.g. dry mouth).. reflexes normalize with repetitive muscle contraction Ptosis and ophthalmoplegia are rare. the condition improves by repetitive stimulation. It results when IgG autoantibodies blockade the voltage-gated calcium channels of peripheral cholinergic nerves.

DD of purely motor disease    

Myopathy. Myasthenia graves. Motor neuron disease. Extrapyramydal.

DD of mixed UMNL & LMNL. MS. MND.( Motor neuron disease). Cervical cord compression (mylopathy).



Causes of Myopathies           

Inherited : Duchenne's muscular dystrophy Becker's muscular dystrophy Facioscapulohumeral dystrophy Inflammatory : Polymyositis & dermatomyositis. Chronic inflammatory demyelinating polyneuropathy (CIDP). Metabolic : DM ,Renal failure, hypoK , hyperk . Endocrinal : hypothyroidism ,hyperthyroidism , cushing ,addison dis. acromegaly. Vasculitis: Rheumatoid arthritis,Wegener's granulomatosis Malignancy : Paraneoplastic syndromes (especially small cell lung cancer) Infection: coxsachi virus. Vitamin deficiency: Lack of vit. D. Toxins: Alcohol Drugs Alcohol, Cortisone, penecillamine, thiazides, carbexenolone. Lovastatin , Cocaine, Colchicine.

Classification 1)Muscular dystrophies 1-X-linked Duchenne Baker 2-Autosomal

2)Channelopathies

3)Congenital

1)Cl -->Myotonias 2)Na-->Hyperkalemic PP 3)Ca-->hypokalemic PP

Glycogen storage Acid maltase MP Lipid storage CPT Mitochondrial Kearn Sayre MERRF MELAS

Facioscapulohumeral Limb girdle Myotonia dystrophica

5)Endocrinal

Toxic

Inflammatory

Addison

Alcohol (acute or chronic) licorice Drugs

Polymyositis Inclusion body Sarcoidosis connective tissue Infectious

disease, Cushing disease Hypothyroidism (CK may be mildly elevated) Hyperthyroidism (CK may be normal) Hyperparathyroidism acromegaly

Steroids Lovastatin Cocaine Colchicine

4)Metabolic

Trichinosis

Coxsackie A and B

Cysticercosis (T solium) Toxoplasmosis

HIV Influenza

Lyme disease Staphylococcus aureus

C/P of Myopathies Motor : LMNL( hypotonia ,hyporeflexia , wasting ) Weakness proximal > Distal , Bilateral & symmetrical , Waddling gait .

NO Sensory affection: NO autonomic affection. NO fasiculations. NO cranial nerve. NO sphencteric affection.

Investig. CPK, EMG, Ms biopsy.

MUSCLE DISEASES Mutation in the dystrophin gene causes deficiency of dystrophin in  Duchenne's muscular dystrophy. XL R Patients develop progressive upper and lower limb weakness with pseudohypertrophy of calves and quadriceps.  Becker's muscular dystrophy. XL R Later presentation & milder form.  Facioscapulohumeral dystrophy (FSHD) is one of the most common types of muscular dystrophy. It is of autosomal dominant inheritance. Onset is usually age 20 years. Initial weakness is seen in facial muscles, starting in the orbicularis oculi, orbicularis oris, and zygomaticus. Shoulder weakness is the presenting symptom in more than 82% of patients. Winging of the scapula is the most characteristic sign. Creatine kinase levels are raised.

Mitochondrial diseases

All mitochondria of the fetus are derived from the ovum (Maternally Derived). Mutations in mitochondria accumulate in cells and can be transferred to the offsprings

Examples : 

MELAS : myopathy, encephalopathy, lactic acidosis & stroke like episodes. Lactic acidosis may be provoked by exercise & induce nausea, Vomiting,& coma. Present in early childhood



MERRF: Present in adults, with proximal muscle weakness ataxia & seizures



Kearn Sayre $: present in childhood with ptosis, ophthalmoplegia, retinitis pigmentosa, epilepsy, cardiac conduction defect,& proximal weakness. DM, hypothy.

MITOCHONDRIAL MYOPATHIES 

 



Chronic progressive external ophthalmoplegia (CPEO) is a disorder characterized by slowly progressive paralysis of the extraocular muscles. Patients usually experience bilateral, symmetrical, progressive ptosis, followed by ophthalmoparesis months to years later. Leber's Hereditary Optic Neuropathy is a rare condition cause loss of central vision. It usually affects men in the late 20s or early 30s,. MELAS (myopathy, encephalopathy, lactic acidosis and stroke like episodes). Lactic acidosis is a very important feature of this disorder, as measured by a high lactate to pyruvate ratio. Patients have a proximal myopathy, seizures and stroke like episodes. MERRF (myoclonic epilepsy, ragged red fibres). The most characteristic symptom of MERRF syndrome is myoclonic seizures that are usually sudden, brief, jerking, spasms that can affect the limbs or the entire body. Ataxia as well As Dysarthria, optic atrophy, short stature, hearing loss, dementia and nystagmus may also occur.

Acid maltase deficiency Mc cardle disease. Acid maltase deficiency typically presents with insidious onset of proximal myopathy and early respiratory muscle weakness. Respiratory failure.

Inclusion body myositis:  





Old male > 50 yrs. In this condition, dysphagia and respiratory involvement can also occur. Muscle biopsy shows intracellular inclusions (amyloid precursor protein, ubiquitins) and inflammatory infiltrates. Clinical suspicion for -IBM should be very high when the pattern of weakness affects both P& D. inclusion body myositis is the commonest in >50 years old

Neuroleptic malignant syndrome is the most likely diagnosis. Its major features are: rigidity, altered mental state, autonomic dysfunction, fever, and high creatinine kinase. It is usually caused by potent neuroleptics. The treatment of choice is dantrolene and bromocriptine. Withdrawal of neuroleptic is mandatory. Rhabdomyolysis and acute renal failure are potential complications.

Seizure 

 

A Seizure= paroxysmal event dt abnormal excessive discharge from an aggregate of CNS neurons, prevalence 5% in the population. Epilepsy= a clinical syndrome of recurrent Seizures (2 or more unprovoked Seizure) dt a chronic underlying pathology, prev=0.5%.

NB; risk of recurrence of 1st seizure = 35% at 2 yrs, so do not give antiepileptics except for high risk patients ( neurologic insult, abn EEG).

Causes of seizures 1. 2. 3. 4. 5. 6. 7. 8.

Idiopathic. Traumatic. Infection. Br tumor. Alcohol withdrawal. Illicit drug use. Metabolic; uremia, LCF, electrolytes, hypoglycemia, hypoxia). Drugs; Alkylating (chlorambucil, busulfan), immunomodulators ( cyclosporin, Tacrolimus, OKT3, ), antimalarial , antibiotics ( B lactam, quinolones, INH, acyclovoir, gancyclovoir), antidepressant, antipsychotic, withdrawal,(alcohol, barb, BDZ), abuse (Amphetamine, cocaine), radiocontrast, theophylline, flumazenil.

 -

DD; TIA. Syncope. Sleep disorders (narcolepsy/ cataplexy). Movement disorders (tics, myoclonus, choreoathetosis).

Types of epilepsy Partial Seizure= within discrete area of the brain. A) simple =fully conscious. B) complex = impaired consciousness. Generalized = from both cerebral hemisphere simultaneously without detectable focal onset. 1) Absence s = lapses of consciousness without loss of posture control, no post ectal confusion. 2) Tonic clonic. 3) Myoclonic. 4) Atonic. 5) partial with 2 ry generalization.

Generalized Epilepsy  -

• •

Absence seizures; Infant , child. Blinking of eye, myoclonic jerks of arms Never acquired. May develop generalized S in adult. Myoclonic. (jevenile epilepsy); Commonest of idiopathic Generalized. Chr 6. Occur within 1 hr of waking up. Ppting factors; alcohol, menses, sleep deprivation. Ttt : Na valproate, lamotrigine, topiramate. Life long ttt to prevent relapses. Atonic = Akinetic = sudden loss of tone.

NB: status epilepticus= fit > 30 min or recurrent without regaining consciousness in bet.

Partial Seizure  -

• -

Simple ( e.g. motor, sensory, Autonomic, psychic) Followed by todd’s paralysis If in the frontal lobe conjugate deviation of eye to other side. Complex; typically medial temporal, Aura (e.g. déjà vu, smell, abd sens) Autonomic, psychic (déjà vu), motor (grimacing), sensory (vertigo) Followed by loss of consc.

Antiepileptic drugs 1. 2. 3. 4. 5. 6. 7. 8.

Phenytoin (all except absence). Valproate (generalized). Carbamazepine (partial). Lamotrigine, Topiramate (generalized) Gabapentine (partial) Clonazepam (Myoclonic). Ethusuximide ( Absence). Vigabatrine, levitiraceticam.

   

Tonic clonic  Phenytoin, Valproate, Lamotrigine, Topiramate. Absence  Valproate, Ethusuximide. Myoclonic  Valproate, Clonazepam. Partial  Carbamazepine, Gabapentine

NB; in Myoclonic, Valproate is most effective but use Clonazepam, Lamotrigine, Topiramate better for fear of hepatotoxicity. - Begin with low dose. - Try monotherapy, if failed  another mono, if failed  combination.

uses

Drug interaction

Phenytoin

Valproate

Carbamazepine

Tonic clonic all except absence

All generalized

-Partial

Enz inducer ↓level of; -OAC -ACP --cyclosporine -Other antiepil

Not ↓phenobarbital metab

-5th

neuralgia -Diab neurop -Migraine -DI Enz inducer If uses with phenytoin ↑dose of phenytoin

Phenytoin

Valproate

Carbamazepine

CNS depression

√

√

√

hepatotoxic

Hepatitis, granuloma

Fatty, Reye S

GIT upset

√

√, pancreatitis

√

Blood

Megaloblastic an LN, gum ↑

↓plat thrombathenia

pancytopenias

skin

Lupus, Hirsutism Serum sickness

Gynecomastia Rash, alopecia

Toxic epidermal necrolysis

endocrine

DM, DI

Wt gain, PCO

SIADH hypercholestrolemia

Bone (osteomalacia)

√

√

√

Neuro

PN, enceph Chorea, Nystag Cereb ataxia,

Ataxia tremors

Headache, diploplia

teratogenic

Fetal hydantoin (cleft, cong ht)

Neural tube defect

Toxic epidermal necrolysis

Side effects

Gabapentine; - used as add on drug - in partial, general. - not enz inducer. - Dose adj in renal failure.





Lamotrigine  rash TEN.



Vigabatrine irreversible constriction of visual field.

Levitiraceticam - oral - Safe, fewer side effects - used for partial seizures. - No effect on liver enz - Dose adj in renal failure.





Phenobarbitone 1st line in infants.



Paraldehyde may be given IVI or rectally or IM in extreme circumstances because it cause tissue damage & slughing.

 -

• -

Epilepsy & driving; After 1 seizure or lost consc not allowed for 1 year. For vocational licence free for 10 yrs of 1- attacks 2- medications 3- liability (e.g. structural br lesion). Epilepsy & pregnancy; Continue antiepileptics as effect of epilepsy & hypoxia is more dangerous. Folic acid supplementation.

Sleep disorders Narcolepsy;  1. 2.

3. 4.





is a clinical syndrome of; daytime sleepiness, cataplexy, emotionally-triggered, transient muscle weakness. Most episodes are triggered by strong, generally positive emotions such as laughter, joking, or excitement, result from loss of the neuropeptides orexin-A and orexin-B. TTT; a REM sleep-suppressing medication (eg, venlafaxine, clomipramine, fluoxetine) . hypnagogic hallucinations, are vivid, often frightening hallucinations that occur just as the patient is falling asleep or upon awakening. sleep paralysis; is a complete inability to move for one or two minutes immediately after awakening. Only about 1/3 of patients will have all four symptoms; thus, the diagnosis of narcolepsy should be considered even in patients with sleepiness alone. The HLA association is DQB1,







 1. 2. 3.

Diagnostic testing for narcolepsy includes an overnight polysomnogram (PSG) followed by a Multiple Sleep Latency Test (MSLT). In Narcolepsy, REM sleep occur at the onset of nocturnal sleep. Daytime attacks also consist of periods of REM sleep occurring out of context. Secondary Narcolepsy can occur with rare lesions of the posterior hypothalamus and midbrain. Tumors, vascular malformations, strokes, Prader-Willi syndrome, Niemann-Pick disease type C, and paraneoplastic syndromes. All patients with secondary narcolepsy have obvious neurologic deficits, with cognitive, motor, and/or eye movement abnormalities . TTT of narcolepsy; Creating a sleep time table & ↓alcohol intake. CNS stimulant as modafinil, methylphenidate or amphetamines. Clomipramine is a tricyclic antidepressant

Hyperkinetic movement disorders Tics; brief, repeated, stereotyped ms contractions that are often suppresible.  Myoclonus; sudden, brief, shock like, ms twitches that interfere with normal movement & are not suppressible. Types; 1. Normal while falling asleep. 2. Jevenile myoclonic epilepsy, Variant CJD. 3. Static myoclonic encephalopathy (hypoxia after cardiac arrest). 4. Drugs as amitryptiline, TCA. 5. Metabolic (LCF, RF). TTT; clonazipam, valproate.  Fasciculations = visible contraction of a group of ms fibres. Causes; anxiety ,fatigue, (↓Ca), MND.  Fibrillation; invisible contraction of individual ms fibrils. 



Chorea; rapid, semiperpuseful, dancelike, non-patterned, involuntary mov, proximal > distal.

causes; Hereditary; Huntington. 2. Metabolic; wilson, abetalipoproteinemia, thyrotoxicosis. 3. Inflammatory; Rh fever (Sydenham’s), SLE, APA. 4. Drugs; phenytoin, L-dopa, anticholinergics (TTT of parkinson) Alcohol, cocaine, amphetamine. (illicit drugs) OCP, pregnancy.(♀). 5. Toxins; Cu, Mercury, ↓Mg. TTT; neuroleptics; Haloperidol, tetrabenazene. Sydenham’s Chorea; + hypotonia. + pendular or sustained reflexes.  It is mostly observed in young girls and presents as involuntary movements of face, tongue and upper extremities. emotional instability 3% of acute rheumatic fever ttt; rest, diazepam, Haloperidol. 1.

•

Wilson’s Disease

•

Definition

It’s a neurodegenerative disease of copper metabolism characterized by accumulation of copper in different tissues mainly in the liver, brain , kidney & cornea due to inability of the liver to excrete copper in bile which is the main pathway for copper elimination. NeuroPsychiatric: are the most common initial presentation in adults. Kayser-Fleisher rings are almost always present when the patient has neurological symptoms Irritability, psychosis, mania, abnormal behavior Personality changes, depression. Parkinsonian symp, rigidity, bradykinesia , tremors, dysarthria. Dystonia, incoordination.

•

   

Investigations: No one test is completely reliable Low serum copper level (may be normal) Low serum ceruloplasmin (Normal in 20%) Increase 24 hrs urinary copper MRI Brain: bilateral degeneration in basal ganglia with caudate atrophy.



Liver biopsy: increase in hepatic copper by quantitative essay

Neuroacanthocytosis 





This AR syndrome = features of acanthocytosis (i.e.spiked RBCs), chorea & Personality changes ,Progressive cognitive impairment& normal betalipoproteins. It begins in adult life 20-50 yrs old and more common in men. course is progressive. Deg. of Basal ganglia is a feature. caudate atrophy.

hypobetalipoproteinemia: 



 

it results from homozygous or heterozygous mutation in APO B gene with impaired APO B synthesis and decreased LDL cholesterol level. ABL is an AR condition while FHBL shows codominance.

GIT symptoms: malabsorption,diarrhea and distension. Neurologic symptoms:   



Slow intellectual development. Peripheral neuropathy. Absent deep tendon reflexes. Intension tremors, ataxia. Chorea.

Ophthalmic:  

  



 visual acuity. retinitis pigmentosa. CBC: Acanthocytosis + thrombocytopenia low fasting cholesterol levels  LFTs And  PT due to vitamin K def. ttt; IM vit E.



Hemiballismus; violent form of chorea, wild large amplitude mov of one side of the body or 1 limb only, due to contralateral subthalamic hge or infarction.ttt; tetrabenazine.



Athetosis; slow distal snake-like involuntary mov mainly in the hand, in putamin .



Dystonia = twisting mov & abn posture dt contraction of both agonists & antagonists e.g. torticollis, writer cramp. ttt; haloperidol.

Myotonia dystrophica.         

AD,Presents at 3rd decade. Myotonic facies,Frontal baldness Ptosis, cataract, mild cognitive impairment. Wasting of face, sternomastois, arm, legs, ↓ reflexes. Myotonia (delayed muscular relaxation after contraction). Endocrine; DM, gynecomastia, testicular atrophy. Cardiomyopathy, ECG changes. Diagnosis; myotonic discharge on EMG. Ttt; phenytoin for the myotonic phenomena.

Myotonia dystrophica

Tremors; rhythmic oscillation of a body part dt intermittent ms contraction. TREMORS

Coarse

STATIC -Parkinson (4-8 hz) -LCF -CRF -RF -Wilson

KINETIC =INTENSION •Benign essential. •Cerebellar. •MS.

Fine •Alcohol. •Senile. •Thyrotoxicosis. •Anxiety. •Hysterical. •Drugs; theoph, B2 agonist,. amiodarone, valproate cyclosporin

Benign essential Tremors -most common tremor.

-Elderly. -AD. -Coarse (8 Hz) tremors& UL mainly. -Postural & appear immediately on mov (but cerebellar tremors appear after 1st part of vol mov) -Titubition( MS also has titubition & intension tremors). --↑by anxiety. -↓ by alcohol. -ttt; BB.

Parkinsonism (↓ dopamine in substantia nigra) Refers to a triad of; 1. Resting tremors (4-6 Hz), pill rolling, ↑by stress, ↓by sleep & mov. 2. Bradykinesia; difficult starting walking, short steppage gait, micrographia. 3. Rigidity. (flexors); gorilla like attitude.  Loss of emotional & associated mov; mask face, monotonus speech, loss of arm swinging, can not resist retropulsion &propulsion,pers glabellar reflex.  NB; No sensory, no fasciculation, no weakness, no sphincteric disturbance.

Akinetic rigid syndromes (Parkinsonism) Cause

History

1-Idiopathic

asymetrical tremors, good response to L-dopa

2-Heredofamilial (wilson).

Age<40

3-Traumatic (boxers) 4- Inflammatory; postencephalitic, syphilis.

Sudden onset

5-Vascular; atherosclerotic (multiinfarct dementia) 6- Toxic; drugs (reserpine, PZN, valproate) antidopamenrgic, M ( C Monoxide, Mn).

7- Parkinson plus+

Lack of tremors

* Progressive supranuclear Palsy

ophthalmoplegia, peudobalbar palsy (falls as 1st symp)

* Multiple System Atrophy

autonomic,

* Lewy body dementia.

Intermittent consciousness , visual hallucin, early dementia.

Ttt of Parkinsonism 1.

2.

3.

4. 5. 6. 7.

Anticholinergics for tremors e.g. benzhexol; side effect(atropin like action); urine retension, hallucination, tachycardia, dry mouth. Dopamine agonist for bradykinesia (ropirinole, pramipexole, cabergoline, pergolide)(cause galactorea).side effects; less effective ,GIT upset, VC, arrythmias, # PVD, IsHD, mental. Levodopa (Sinemet=Ldopa +carbidopa which prevent peripheral decarboxilation). side effect; on & off , wear off, psychosis, chorea, GIT, tachy, # in narrow angle glaucoma. MAO B inhibitor (Selegiline); inhibit dopamine catabolism in the brain but not neuroprotective, may ↑ mortality. COMT(catechol o methyl transferase) inhibitor (Tolcapone, Entacapone) Presynaptic Dopamine uptake inhibitor (Amantadine) Surgery.

(Sinemet=Ldopa +carbidopa  -

-

on & off phenomenon Fluctuation of drug response with prolonged therapy= chorea, immobility. Ttt;- shortening the interval between doses , ↑dose, restrict dietary protein, give L dopa 1 hr before meals , selegiline , Dopamine agonist , drug holidays. Apomorphine(facelitate the effect of sinemet)

• wear off; end of dose phenomena; • ttt; controlled release prep, ↑ frequency, or ↓dose.

Drug induced neurological symptoms 1. Drug induced extra Δ symptoms;e.g Dystonia e.g. antipsychotic e.g., antiemetic.(anti dopaminergic drugs) ttt; stop the drug, give anticholinergic for tremors e.g. Benztropine or benzhexson procyclidine.(® akeniton tab 1x1, parkinol) 2.

Tardif(=delay) dyskinesia;

-

Antipsychotic as chlorpromazine(largectil) & Haloperidol, unusual with newer agents(=atypical antipsycotic) as olanzapine, clozapine(clozapex). After 6 months of the drug intake. 50 % irreversible, progressive. C/P; orofacial dyskinesia e.g. chewing, lip smacking. ttt; stop & give tetrabenazine(used in TTT of hemibalismus) - valproate. - baclofen 10, 25 mg 1x2, diazepam. Malignant neuroleptic S; C/P; altered mental state, rigidity, autonomic dysf, fever, high CPK Cause; potent neuroliptics e.g. haloperidol. ttt; dantrolene, bromocriptine. Complications; Rabdomyolysis, ARF.

-

3. -

DD of hypotonia. Chorea , Cerebellar disease , Shock stage of Δ., Post.Col , Polyneuropath , myopathies.

DD of hypertonia

Spasticity (Δ) Clasp knife FL of UL EXT of LL

Rigidity (extra Δ) Lead pipe or cogwheel (interrupted by tremors) flexors

Ataxias = incoordination = loss of orchestration & fluidity of mov.

Ataxias hysterical

Motor =cerebellar

Sensory(pathway of deep sensation 1. 2. 3. 4. 5.

PN Tabes dorsalis. PC. Medial lemniscus (Br stem) Thalamic S

Vestibular e.g. minieres dis Labyrinthutus Acoustic neuroma



Vestibular ataxia; post. circulation

-

+ vertigo, Nystagmus. Stamping gait. Rombergism. Drop attacks — Drop attacks are attributed to a sudden loss of tone mediated by vestibulospinal reflexes. Unlike presyncope and seizures, there is no faintness or loss of consciousness with drop attacks. Patients with drop attacks of vestibular origin often have a sensation of being pushed or pulled to the ground

-

-

Sensory ataxia

- Rombergism - Stamping gait. - Deep sensory loss. - No crainial n, no dysarthria or nystagmus.

Cerebellar Ataxia Causes;  Hereditary; - Friedriech ataxia. - Ataxia telangectasia - Vit E def; spinocerebellar deg dt abetalipoproteinemia. - Acquired ; 1. Cong; Arnauld chiari malformtion. 2. Vascular; hge, infarction. 3. Demyelinating dis; MS. 4. Infective; encephalitis , AIDS, polio, coxsachi, lyme, HZV. 5. Metabolic; ↓Na, ↓B1, ↓B12, ↓vitE . 6. Toxic; Alcohol , phenytoin , valproate, lithium , mercury. 7. Neoplastic ; paraneoplastic , tumors ,2ries.

 -

Friedriech AR, frataxin gene, trinucleotide repeat GAA.(as CAG in Huntington chorea) Age = 5-15 yrs. Ataxia + PC, PN, Δ.i.e(ataxia +SCD) Optic atrophy, deafness. Cardiomyopathy, DM. skeletal=; pes cavus, kyphoscoliosis. Inv; ECG, vit E, DNA testing.

Ataxia telangiectasia. -AR, childhood. -Ataxia,Telangiectasia; face, conjunctiva. -Recurrent infection. -Malignancy e.g. leuk, lymph. Inv; ↓Ig A & other Igs, ↑αFP. Ataxia with vit E def; -AR, defect of α-tocopherol transferase gene. - As Friedriech + hypobeta lipoproteinimia ↓fat soluble vit & retinopathy dt vit A def. ttt; oral or IM vit E. Cerebrotendinous xanthomatosis. -inherited. -Accumulation of cholesterol in tissues (brain, PN, tendons) -C/P; early dementia, ataxia, large tendon xanthomas. -ttt; chenodeoxycholic acid.

Paraneoplastic syndrome – severe ataxia, dysarthria, vertigo, nystagmus. -May preceed tumors esp small cell lung C, ovarian ,lymphoma -50-75% antineuronal Ab; anti Yo (# cerebellar perkinjie), anti Hu (# wider range of neurons).

. Anti Yo antibodies & Anti Hu antibodies are found in around half of all patients with paraneoplastic cerebellar degeneration. Associated with small cell carcinoma, ovarian tumours and Hodgkin’s lymphoma. It is usually associated with sensory neuropathy.

Benign paroxysmal positional vertigo  is probably the most commonly recognized cause of vertigo. commonly attributed to calcium debris within the posterior semicircular canal  Classically, patients describe a brief spinning sensation brought on when turning in bed or tilting the head . The dizziness is quite brief, usually seconds.  Ear pain, hearing loss, and tinnitus are absent.  The diagnosis of BPPV is generally made by history. The Hallpike maneuver can support its presence, but is positive in only 50 to 80 %  The natural history of BPPV is one of repeated, brief vertiginous episodes that continue for weeks or months.  TTT: Vestibular sedatives. (betahistidine).

Vestibular neuritis or neuronitis 









is believed to be a viral or postviral inflammatory disorder, affecting the vestibular portion of the 8th cr.N. Vestibular neuritis is characterized by the rapid onset of severe, persistent vertigo, nausea, vomiting, and gait instability. A diagnosis of vestibular neuritis is largely based on clinical information. There are no specific diagnostic tests. However, the clinical features of cerebellar hemorrhage or infarction may be similar and brain imaging is therefore often required to rule this out . Recovery may be hastened with corticosteroid therapy.

Herpes zoster oticus (Ramsay Hunt syndrome)  

is believed to represent activation of latent herpes zoster infection of the geniculate ganglion. In addition to acute vertigo and/or hearing loss, ipsilateral facial paralysis, ear pain, and vesicles in the auditory canal and auricle are typical features.TTT by acyclover

Meniere's disease is a peripheral vestibular disorder attributed to excess endolymphatic fluid pressure, which causes episodic inner ear dysfunction.  Affected patients present with spontaneous episodic vertigo lasting for minutes to hours, usually associated with unilateral tinnitus, hearing loss, and ear fullness. 

Headache. Acute recurrent headache . 

Episodic migraine.



Cluster headache. Trigeminal neuralgia. Intense stabbing pain lasting seconds in trigeminal nerve distribution. Glaucoma .Red eye, haloes, visual acuity, pupil abnormality.

 

Subacute headache. Temporal (giant cell) arteritis>50y., scalp tenderness, ESR, rarely visual.

Chronic headache. Tension type headache : Band around the head, stress, low mood. Cervicogenic headache : Unilateral or bilateral, band from neck to forehead, scalp tenderness. Medication overuse headache: Rebound headache on stopping analgesics. intracranial pressure: Worse on waking/sneezing, neurological signs,BL Pr.

Headache Causes 1. Extracranial; eye, sinuses, ear, dental, TMJ, cx osteoarthritis. 2. Vascular; migraine(VC followed by VD), cluster, HTN, occlusion. 3. Intracranial; artritis, pituitary, ↑ICT. 4. Tension; common tension H, conversion reaction, depression.



Headache.

The skill lies in deciding which headaches are benign, requiring no intervention, and which require action. 

History.         

When did the headaches start? New or recently changed headache. How often do they happen? Do they have any pattern (e.g. constant, episodic, daily)? How long do they last? Nature and quality of the pain. Site and spread of pain. Associated symptoms e.g. nausea/vomiting, visual dist., photophobia, neuro S. Predisposing and/or trigger factors. and/or relieving factors. Family history

Examination.  BP.  Brief neurological examination including fundi and visual acuity.  Palpation of the temporal region/sinuses for tenderness.  Examination of the neck.(cervical spine lesion) Investigation.  Often not needed. Consider ESR if temporal arteritis is suspected.  CT scan if....

Migraine. 10-24 hrs              

Cause,Disturbance of cerebral blood flow under the influence of 5-HT. basilar migraine (affect the post. Circulation) visual chaos (e.g. zig-zag lines, jumbling of print, dots); hemianopia; hemiparesis; dysphasia;; dysarthria; ataxia. Classical migraine :Aura lasting 10-30min. followed by unilateral throbbing Pulsating headache ±‫ آ‬nausea or vomiting ±‫ آ‬photophobia. Episodic migraine (common migraine): Unilateral throbbing headache ±‫ آ‬nausea or vomiting ±‫ آ‬photophobia but without aura often premenstrual. Trigger factors ½‫آ‬have a trigger for their migraine. .Psychological factors :Stress ; anxiety/depression; extreme emotions e.g. anger . Food factors :Lack of food; specific foods e.g. chocolate, cheese; alcohol. Sleep :; changes in sleep patterns (e.g. late nights, weekend lie-in, shift work, holidays); long-distance travel. Environmental factors :Loud noise; bright/flickering lights; strong perfume; Management Management of an acute attack Advise to rest in a quiet, dark place and sleep if possible. Analgesia ibuprofen 400mg, or soluble paracetamol 1g at 1st signs of an attack ±‫آ‬ antiemetic e.g. domperidone 20mg. consider 5HT 1agonists e.g. sumatriptan(sumagrain,emegrain) 50-“100mg po, stops 70-85% attacks”start with lowest dose and as needed; do not give if ergotamine(migranil,no migrain) taken <24h. Previously.

Management of chronic migraine 



Reassure about the benign nature of migraine. Instruct patients about management of an acute attack. Ask the patient to keep a diary to identify possible trigger factors, assess headache frequency, severity, and response to treatment. Avoid trigger factors where possible. Give advice on relaxation techniques and stress management to all patients. Stop the OC pill if migraine starts or worsens when the pill is started.



Prophylaxis.

  

Consider if >4 attacks/mo. or very severe attacks. Try a drug for 2mo. If effective, continue for 4-“6mo. then dec. dose slowly before stopping. 

B.blockers :e.g. atenolol 25-100mg bd. Patients who do not respond to oneB-blocker may respond to another.

 

Sodium valproate(depakin) Start at 300mg bd. Tricyclic antidepressants e.g. amitriptyline 10-75mg once. Start at low dose and inc.



Pizotifen(antihistamenic drug).

Cluster headaches 



Clusters of extremely painful headaches focused around 1 eye with associated autonomic symptoms (drooping eyelid, red watery eye, runny or blocked nose). May occur at any age. 6:1 male to female.More common in smokers.Pain lasts up to 1-2 hr. and occurs once every day for 4-12wk. then disappears for 1-2y. Recurrences affect the same side.

Management  Acute attack:  



%100 oxygen at a rate of 7-12 l/min(to releif the VD). 5HT agonists e.g. sumatriptan (6mg s/cut) stops 75% attacks within 15min.

Prophylaxis : Consider if attacks are frequent, last >3wk. or cannot be treated effectively .Options:



Verapamil stops 66% attacks(BBin migrain).



Lithium. Methysergide(ergometrin).effective but use limited by sideeffects. Only used if other drugs are contraindicated, not tolerated, or ineffective.



Benign intracranial hypertension=psudotumer cerebri) is most common in women between the ages of 20 and 50 yrs.  BIH is likely due to high pressure caused by the buildup or poor absorption of CSF in the subarachnoid space.  Symptoms include headache, nausea, vomiting, and pulsating intracranial noises, closely mimic symptoms of brain tumors. Papilloedema.  Obesity ,pregnancy, Behcet $ , SLE , Hypopara.  Vitamin A, prednisolone , minocycline(used in TTT of acne), OCP ,Nitrofurantoin(uvamin retard) and cyclosporine.  Diagnosed by CT & fundus examination. TTT:  Wt reduction.  Acetazolamide(Diamox):carbonic anhydrase inhibitor is used to treat BIH.  VP shunt.  Repeated Lumbar puncture. 

Subarachnoid haemorrhage 

Spontaneous bleeding into the subarachnoid space.Frequently fatal, 85% of IC aneurysms are located in Ant. Circuation.mostly ant. Cumminicat.

Causes:     

No cause (15%). Rupture of congenital berry aneurysm (70%). Arterio-venous malformation (15%). Bleeding disorder., cocaine & amphetaine. Mycotic aneurysm 2‫آ‬° to endocarditis (rare).

Risk factors

Smoking, alcohol, †‘BP, lack of oestrogen (less common pre-menopause).  Associations (Berry aneurysm)polycystic kidneys(do screening by MRA if there is +ve FH of IC hge , coarctation of the aorta, Ehlers-Danlos syndrome, fibromuscular dysplasia RAS, PAN. Complications: rebleeding , focal ischemic injury dt cerebral vasospsm, hydrocephalus, SIADH 

Presentation

Typically presents as a sudden devastating headache often occipital.  Vomiting and collapse with loss of consciousness ‫آ‬± fitting ‫آ‬± focal neurology follow. Examination  May be nothing to find initially. Neck stiffness takes 6h& Focal neurology  Papilloedema.  Retinal and other intraocular hemorrhages.  Inv. CT & Lumbar puncture(xanthochromia ie RBCs in the CSF).  TTT(nimodepin) (nimotop which is Cch Bs act selectively on the cerebral BV)  If suspected, admit immediately as a medical emergency. 

Trigeminal neuralgia Paroxysms of intense lansinating , burning electric shock type pain lasting seconds to minutes in the trigeminal (V) nerve distribution. 96% unilateral. Mandibular/maxillary > ophthalmic division. Between attacks, there are no symptoms.  Frequency of attacks is variable up to hundreds of attacks/d. Pain is often provoked by movement of the face (talking, eating, laughing) or by touching the skin (shaving, washing). Can occur at any age but more common >50y.‚  Causes: DM,HZV, MS. Management :  Spontaneous remission may occur.  Carbamazepine100-400mg tds po dec.frequency and intensity of attacks  treatment with lamotrigine, phenytoin, or gabapentin, or clonazepam.  Thermocoagulation.  surgical intervention. 

paraparesis

Spastic paraplegia

With sensory level 1. Trans. Myelitis 2. Cord compression 3. Ant spinal art occ

Flaccid 1. PN e.g. GBS, CIDP 2. Myopathies 3. radiculomyelitis

Without 1. 5 syst dis (MS, pellaga, SCD, friedriech, MND) 2. Occlusion of unpaired ACA, Parasagital meningioma 3. Familial, tropical (HTL2)

paraparesis Paraparesis with sensory level. 1.Vascular. 2.Traumatic. 3.Inflammatory. 4.compression. Extramedulary lesion. root pain Intramedulary lesion. Sphincteric dysf.

Paraparesis without sensory level.

Transverse Myelitis Causes; 1. Infection; - viral; exanthema, EBV, influenza. - Bact; pyogenic. 2. Immune; - collagen; SLE, sjogren. - demylinating; MS, ADEM. 3. Iatrogenic; post vaccine, radiotherapy.  C/P; mainly lower thoracic. Acute or sub acute + fever + back pain + sensory loss with level, sphincteric dis, flaccid paraparesis then spastic. Inv; MRI; cord swelling , plaques in MS. CSF; normal protein, oligoclonal bands in MS. Ttt; Pulse steroids then full dose.

• •

Epidural abscess



Spinal epidural abscess is a rare disease, The infection can originate via contiguous spread from infections of skin and soft tissues or as a complication of spinal surgery . Other cases of epidural abscess arise from a remote site via the bloodstream. Diabetes, alcoholism, and HIV infection are risk factors. The most common pathogen is Staphylococcus aureus, 2/3 of cases The classic clinical triad consists of fever, spinal pain, and neurologic deficits.. MRI is the preferred test and is highly sensitive for this diagnosis. Blood cultures and/or aspirate of abscess contents to identify the etiologic organism. Surgical decompression and drainage with systemic antibiotic therapy is the treatm.



Epidural metastasis

 

    

Usually >50 years ,Subacute, may worsen abruptly,Segmental cord syndrome,MRI. Gliomas  Young adults ,Slowly progressive  Central Intramedullary cord tumor syndrome  MRI with gadolinium enhancement .

Syringomyelia 









Children, young adults , Slowly progressive, Central intramedullary cord lesion. is chronic disorder characterised by the presence of gliallined cavities situated in the central part of the spinal cord. Recognised causes include Chiari type I malformation, central cord tumours, basal arachnoiditis and trauma. There may be sensory loss, wasting of the small hand muscles, uni- or bilateral Horner’s syndrome, abnormalities of sweating, development of Charcot’s joints and Chiari I malformation (due to arachnoiditis). MRI

Ant. Spinal artery occlusion. 

 

Infarction Usually >60 years, Abrupt onset Anterior cord syndrome intact PC, intact deep sensation. MRI .

Dissociated sensory loss; = preserved touch, lost P & T.Dt; - Brown Sequard S - ant sp art occlusion. - lat medullary S. - early syringomyelia. 

Motor neuron disease:  UMN signs include muscle spasticity,

weakness especially in the extensors of the upper limb and flexors of the lower limb muscles, pseudobulbar palsy.  LMN features include muscle wasting and





fasciculation, depressed reflexes and bulbar palsy. Onset of the disease is usually in mid to late adult life with the incidence increasing with age. ALS: Usually >60 years ,Slowly progressive , Pure motor syndrome,

Hereditary spastic paraparesis 

often classified based upon spasticity occurs with or without other neurologic abnormalities {mental retardation; deafness or retinopathy; ataxia and dementia}. (complicated Vs simple HSP).

Bulbar & Pseudobulbar palsy(bulb=medulla)

Causes

C/P

Bulbar palsy

Pseudobulbar palsy

LMNL of 9-12 cr ns (nuclear of infranuclear)

Bilateral UMNLof 9-12 cr ns (supranuclear)

1- Br stem; - infarction, - syringobulbia - MND - 2- Jugular foramen; - nasopharyngeal carcinoma - Fracture base.

-MND

dysarthria Hoarseness Nasal regurgitation Dysphagia Lost reflexes

(spastic Bulbar palsy) Spastic dysarthria Hoarseness Nasal regurgitation Dysphagia Exaggerated jaw reflex Preserved palatal pharyngeal reflexes

MS - Bil Stroke - Severe head injury -

Quadriparesis 1. 2. 3. 4. 5. 6.

Cx myelopathy above C4 (sens level) MND (U & L) MS (mainly upper) Bilateral stoke (upper & sens) PN ( peripheral, sens) Myopathy ( proximal)

Dermatomes

1. insular cortex 2. lenticular nucleus (globus palladus) 3. lenticular nucleus (putamen) 4. corpus callosum (genu) 5. caudate nucleus (head) 6. internal capsule -- anterior limb 7. internal capsule -- posterior limb 8. thalamus 9. internal capsule -retrolenticular portion 10.optic radiations

Lesions of the frontal lobe include 1. Difficulties with task sequencing and executive skills. 2. Contralateral motor. 3. Expressive aphasia . 4. Primitive reflexes , Loss of bladder control. 5. Preseveration=(repeatedly asking the same question or performing the same task). 6. Anosmia and changes in personality. Epilepsy; 50% of pts presented with status epilepticus. without history of epilepsy, have frontal lobe tumors.

Lesions of the parietal lobe include    

Cortical sensory loss or inattention. Apraxias, astereognosis (unable to recognise an object by feeling it) Visual field defects (typically homonymous inferior quadrantanopia). Alcalculia (inability to perform mental arithmetic).

Lesions of the temporal lobe cause;     

Visual field defects (typically homonymous superior quadrantanopia), Wernike's (receptive) aphasia, Auditory agnosia. Psycomotor seizures. Hallucinations; auditory, visual, gustatory. Lip smacking, grimacing.

Lesions of the Occipital lobe; Occipital lobe lesions include cortical blindness (blindness due to damage to the visual cortex and may present as Antony syndrome where there is blindness but the patient is unaware or denies blindness visual agnosia (seeing but not percieving objects - in agnosia the objects are seen and followed but cannot be named). homonymous hemianopia ( macular sparing)

Transient ischaemic attack  

History is as for stroke but recovery takes place within 24h. of initial symptoms. Patients with a history of TIA have 20% risk of stroke in the following month, with highest risk in the first 72h.



Investigations.



CT or MRI scan to confirm diagnosis. Carotid dopplers. Echocardiogram (if recent MI, CCF/LVF, or murmur.( ECG, CXR. blood, FBC, ESR, U&E, Cr, lipids, glucose, PT & PTT

     

Management of TIA. Once all symptoms have stopped, start aspirin 50-300mg od. Start treatment for risk factors e.g. advise to stop smoking, start antihypertensives .

L

M

ACA ACA

Face UL LL sensation LGG to optic R

Anterior circulation

Posterior circulation 

 

PCA cortical B.C.HH with macular sparing. capsular B.Thalamic S (C.hemiplegia, hyperpathia, choreoathetosis) PICA or vertebral  Lat. Medullary S. BS branches( crossed H)Midbrain ipsi 3, 4, C. hemiplegia  Pons ----------------- ipsil 6, 7+ C. hemiplegia.  Medulla -----------------ipsil 9,12+C. hemiplegia

Vertebrobasilar insufficiency 1.

2. 3. 4. 5.

6.

Cranial nerve palsies. (Diplopia, dysarthria, dysphagia, hiccup). Gait ataxia. dizziness, nausea, vomiting, Motor deficit ,Coma. Bilateral signs suggest basilar artery disease. Drop attacks  vertebrobasilar insufficiency.

Acute stroke syndromes 

Anterior cerebral artery :



Motor and/or sensory deficit (LL >> face, UL)

 

C. hemiplegia +7,12+LL cortical sens. Loss personality, primitive reflexes,(Grasp, suckling reflexes), urine incontinence.



Middle cerebral artery:



Dominant hemisphere: aphasia, motor and sensory deficit (face, UL>LL) homonymous hemianopia.



Apraxia, alexia, anosognosia.  C. hemiplegia UL>LL+7,12 +hemihypothesia. ICA  as MCA + ipsilateral blindness (ophth. A.). 



Posterior cerebral artery.

Homonymous hemianopia,; visual hallucinations, (thalamus) sensory loss, choreoathetosis, spontaneous pain; ( midbrain) III nerve palsy, paresis of vertical eye movement, motor deficit. Bilateral PCA cortical blindness ( Antony S).

hemiplegia

No cranial N Dissociated sens. loss

Brown sequard S

Other crossed cranial N

+ 7, 12 Capsular MCA

Br.Stem br. Of post. circ.

main stem MCA main stem ACA

L M

Frontal pathways

Corticobulbar T Corticospinal T

Retrolentiform . LGG to optic R sublentiform

Spinothalamic T

PCA

MCA

ACA



Lacunar infarctions <1.5 cm2 Small penetrating vessels. 1- Pure motor hemiparesis. (classic lacunar syndromes) 2- Pure sensory deficit . 3- Hemiparesis & ataxia. 4- Dysarthria/clumsy hand.

•

hemiplegia without sensory, visual, or cognitive abnormalities (pure motor stroke) favors lacunar infarction or a small ICH. Abnormalities of language, the presence of motor and sensory signs on the same side of the body suggest anterior circulation disease. Vertigo, loss of consciousness, diplopia, deafness, crossed symptoms suggest posterior circulation dis. The sudden onset of impaired consciousness in the absence of focal neurologic signs is characteristic of SAH.

•

• •

Lacunar infarction

LT thalamic lacunar Infarction

Stroke in young; - Cardiac embolization. - Vasculitis. - Familial hypercholestrolemia. - Hypercoagulable state. - Patent foramen oval. - Vertebral or carotid A dissection. - Cocaine.  Superior sagital sinus thrombosis; Pregnant, OCP , dehdration in children , - Biparietal or bifrontal hgic infarction. - Multiple scattered lesions. - Prominent epileptic fits. 

Internal carotid artery dissection 

Headache, including neck and facial pain,  

   

is commonly ipsilateral to the dissected artery. usually precedes a cerebral ischemic event, unlike a headache of stroke, which follows the ischemic event.

Transient episodic blindness, or amaurosis fugax. a partial Horner syndrome (Ptosis with miosis)is painful . Neck swelling, isolated ipsilateral neck pain 25%. Focal weakness.

An acute Horner's syndrome associated with pain of the neck or face suspect carotid ar diss.  ....>An axial MRI of the neck and MRA will detect most internal carotid artery dissections .  However, conventional angiography remains the gold standard.

Vertebral artery dissection 

Patient history may include the following:    

Ipsilateral facial dysesthesia (pain and numbness)- Most common symptom. Dysarthria or hoarseness (cranial nerves IX and X). Dysphagia (CN IX &X). Vertigo,Disequilibrium ,Unilateral hearing loss. Diplopia. Nausea and vomiting, Hiccup.

Examination. 

Depending upon which areas of the brain stem or cerebellum are ischemic:



Limb or truncal ataxia. .Nystagmus. Ipsilateral Horner syndrome in 1/3 of patients (ie, impairment of descending sympathetic tract) Contralateral impairment of pain and thermal sensation in the extremities (ie, spinothalamic tract) Lateral medullary syndrome.

  

lateral medullary syndrome 8

sympathetic

5

9, 10

    

Ipsilateral 5,8,9,10. Horner. cerebellar. Ipsilateral loss of pain & temp of face. Contralateral loss of pain & temp of the trunk. (spinothal tract)

lateral medullary syndrome Vestibulocerebellar symptoms and signs.  Sensory symptoms and signs. Pain or unpleasant feelings in the face are sometimes the earliest and most prominent feature of the lateral medullary syndrome. 

Contralateral loss of pain & temp of the trunk.   

Bulbar muscle weakness . Respiratory dysfunction. Autonomic dysfunction — The anatomic basis is thought to be involvement of the dorsal motor nucleus of the vagus nerve.

Horner’s S Central (B.S., S.C.) =1st order neuron. Br. Stem. e.g.syringobulbia, pontine glioma. 

 Loss of sweating from face, upper chest.

Peripheral preganglionic (ant root of C8-T3, sympathetic chain) =2nd order neuron. Root of Neck e.g. pancoast tumour, cervical rib, LN, thyroidectomy.  wasting of small ms of hand (T1 root).  Loss of sweating from face only. 

Peripheral postganglionic (internal carotid art) =3rd order neuron. I C art. e.g. ICA dissection, cavernous sinus $, orbital apex S.  + bulbar S if at jugular foramen.  Loss of sweating from forehead only. 

NB: 1% Hydroxyamphetamine or pholedrine eye drops releases stored norepinephrine from the postganglionic adrenergic nerve endings. One hour after instillation, a normal pupil and a first or second-order Horner's pupil will dilate, whereas a third-order Horner's pupil will not dilate.

Pancoast S;  Triad; Horner + waisting of small ms of the hand+ pain in axilla.  Causes; apical Br C, subclavian Art aneurysm.

Radiological evaluation    



Non contrast CT. MRI is more sensitive than CT for the early brain infarction , lacunar & br. Stem infarction. Small subarachnoid hemorrhages can be missed by either CT or MRI. Lumbar puncture may be needed to make the diagnosis of subarachnoid hemorrhages .

Cardiac studies Transthoracic echocardiogram may miss a clot in the atrial appendage & a patent foramen ovale.

TEE.  Vascular studies  



Anterior circulation  duplex ultrasound of the neck and transcranial Doppler (TCD) of the intracranial arteries,MRA of the neck and head arteries. Posterior circulation, duplex of the origins of the vertebral arteries. CTA and MRA of the neck vertebral arteries do not adequately show the origins of the vertebral arteries

Initial assessment of acute stroke : 1.Classification of stroke.  Transient brain ischemia. 87%.  Ischemia:(Thrombosis,Embolism,Syst.hypoperf.)  Intracerebral hemorrhage. 10%.  Subarachnoid hemorrhage. 3%. 2. vital signs. 3. Decide if thrombolytic therapy is warranted (first 3-4.5 hrs). 4. Immediate laboratory studies  Serum glucose.  CBC ,Cardiac enzymes. Electrolytes,bl. urea, creat. PT,INR, PTT.O2 sat. Lipid profile.

ACUTE THERAPY •

Thrombolytic therapy: administered within three hours of the onset of symptoms significantly reduces long-term disability despite risk of bleeding. Before Thrombolytic therapy is started, SBP ≤ 180 mmHg and DBP is ≤ 110 mmHg.

•

Antithrombotic therapy; Guidelines issued in 2007 anticoagulation is not recommended for the treatment of patients with acute ischemic stroke because of limited efficacy and an increased risk of bleeding complications.



•

We do not recommend the routine use of unfractionated or low molecular weight heparin in patients with AF presenting with an acute ischemic stroke except after 2 weeks .



We recommend early anticoagulation for :

Cardioembolism from intracardiac thrombus associated with significant valvular disease, severe congestive heart failure, or prosthetic heart . 2. Large artery atherosclerotic stenosis with intraluminal thrombus. 3. Dissection of a cervical or intracranial large artery. Among patients with large infarcts, the initiation of warfarin therapy should be delayed for two weeks because of the potential risk of hemorrhagic transformation. A similar delay is recommended in patients with poorly controlled hypertension. 1.



Full-dose anticoagulation should not be used for patients with a large infarction , uncontrolled hypertension , or other bleeding conditions.

For secondary prevention of stroke 



• • •

 

Noncardioembolic stroke  antiplatelet agent (Grade 1A). clopidogrel (75 mg daily) as monotherapy, or the combination of aspirin plus ER-DP, rather than aspirin alone (Grade 2A) 50 to 100 mg daily (Grade 1B). For patients having carotid endarterectomy, we recommend aspirin (81 to 325 mg daily) started before surgery and continued indefinitely in the absence of a contraindication (Grade 1A). Lipid lowering therapy initiation. Blood pressure reduction, once the acute phase of ischemic stroke has passed. Smoking cessation along with management of obesity, diabetes, and metabolic syndrome. Cardioembolic stroke  oral anticoagulation . PREVENTION OF MEDICAL COMPLICATIONS. Aspiration pneumonia UTI, DVT, Dehydration, Malnutrition, Pressure sores, Orthopedic complications and contractures.

ICH 





target BP = 160/90 mmHg using intermittent or continuous IV medication. lowering by 15 % during the first 24 hours. may be delayed until 24 hours after stroke onset. NOT be treated acutely unless SBP >220 mmHg or DBP >120 mmHg, or the patient has active ischemic coronary disease, heart failure, aortic dissection, hypertensive encephalopathy. Labetalol, nicardipine, enalapril, hydralazine, and nitroglycerine are useful intravenous agents.

Cranial nerves 1.

2.

Olfactory N; - Pathway; bipolar olf cells cribriform plate olf bulb-> temporal lobe. - olfactory halucination  Temporal lobe epilepsy. Optic nerve; - tested by; 1- visual acuity 2- visual field 3- light reflex 4- pupil size, 5- colour vision, fundus.

Optic neuritis central or paracentral scotoma Papilledema--. Enlargement of blind spot

The pathway of the pupillary light reflex consists of:  Superior quandrantinopia is seen in damage to the temporal part of optic radiation lesions.  Inferior quandrantinopia is seen in damage to the parietal part of optic radiation lesions  Bitemporal hemianopia is seen in optic chiasmic lesions.  Contralateral homonymous hemianopia, is seen in any lesion from optic chiasma till occipital cortex.  Contralateral homonymous hemianopia with macular sparing is seen in .....Occipital cortex . Optic neuropathy causes a central scotoma. optic tract lesion → incongruous homonymous hemianopia. occipital lobe lesion → congruous homonymous hemianopia 

Causes of Central Scotoma → optic neuritis & Papillitis.

The pathway of the pupillary light reflex consists of:

 -

•

light reflex; Absent direct & consensual optic n lesion. Absent direct only or consensual only  occulomotor n lesion. Pupil size;

Causes of Miosis; -

Pontine Hge. Horner’s S. Drugs; opiates, pilocarpine,; organophosphates. Argyll Robertson pupil; bil small irregular pupil, does not react to light but can accommodate, in DM, MS, Syphilis, autonomic neuropathy.

Causes of Mydriasis;

-

Adie’s pupil; 70% in females, (+hyporeflexia esp ankle =Holmes Adie’s S) 3rd n palsy. Trauma; rupture sphincter pupillary. Drugs; antidepressant, amphetamine, CO, ethylene glycol.

3.

Cr n 3,4,6; (eye movement)

Tested by; - ocular motility (H) - nystagmus - ptosis - accommodation reflex;



Causes of bilateral ophthalmoplegia;

1.

6.

Grave’s dis Myathenia gravis, myositis. GBS(Miller-Fisher S)Ataxia , ophthalmoplegia ,areflexia. Basal meningitis as TB Wernick’s encephalopathy. Midbrain tumour or infarction.



Causes of Internuclear ophthalmoplegia;

2. 3. 4. 5.

1- MS (commonest, may be bilateral) 2-other br stem lesions; vascular, trauma. 3- SLE, Miller-Fisher S, wernicke’s enceph. 4-drug overdose; barbiturate, phenytoin, amytriptyline.

Causes of impaired vertical conjugate gase; 1. 2. 3. 4.

Progressive supranuclear palsy (impaired down dev). Parinaud S; dt midbrain lesion upgaze defect, does not react to light but can accommodate. Grave’s dis. Myathenia gravis

 -

3rd n palsy; C/P; ptosis, eye deviated down (SO4) & out (LR6), dilated fixed pupil. Types; n

n

3rd n palsy

ptosis Central (at the nucleus)  incomplete  Bil ptosis

1. 2. 3. 4. 5.

Peripheral (nerve)  Complete unil ptosis

Medical= vascular e.g. DM, atherosclerosis Pupillary sparing

Surgical Dilated fixed pupil

Causes; DM, arteriosclerosis (pupillary sparing). Orbital apex dis as graves, cellulitis, granuloma (+ 2, 3,4 n affection). Cavernous sinus (+ 4,5,6 n affection). Posterior communicating art aneurysm. Uncal herniation; dt ↑IC tension.

 





 -

-

4th (trochlear) nerve palsy Causes as 3rd. trauma (30%), DM (30%), tumour, idiopathic. + whiplash injury dt dorsal brainstem exit difficult looking down & in vertical diploplia. Superior oblique paralysed. Diplopia ‫آ‬± ocular torticollis (holding head tilted), eye cannot look down and in. 6th (abducens) nerve palsy Causes: as 3rd + ↑IC tension (false localizing sign) tumour, trauma to base of skull, vascular.  medial deviation of the eye …Diplopia. NB; constrictor pupillae supplied by parasympathetic through 3rd n. Dilator pupillae, sympathetic, through OPTIC N.

DISORDERS OF CONJUGATE GAZE Tonic conjugate deviation to paralyzed side  Frontal Area 8. the patient will recover,  Tonic conjugate deviation to normal side  Pontine centre. Recovery is unusual. 

(Internuclear ophth.) • Medial longitudinal fasciculus; Each medial longitudinal fasciculus connects the 3 & 4TH nerve nuclei of one side to the contralateral 6 -nerve nucleus & pontine centre. - Interruption of one MLB prevents adduction of the eye on the side of the lesion (Internuclear ophth.) & nystagmus in the contralateral abducting eye..

Trigeminal nerve (deep sens) Motor nucleus

(touch) (P&Temp)

Causes of 5th cr. Nerve lesion. 

Nuclear or infranuclear ( LMNL).

 Central. (Nuclear) Brain stem lesion( infarction ,MS, syringobulbia ).  Peripheral.( infranuclear)    

cerebellopontine angle lesions.(acoustic neuroma). Apex of petrous bone. (petrositis...5th& 6th ns). Cavernous sinus.(CST ,ICA aneurysm , pit. tums extension) Peripheral branches. ( DM, HZV)

petrous osteitis (Gradenigo S) but is now more likely the result of a meningioma or nasopharyngeal carcinoma of the petrous apex{5 (maxil),6}.  The cavernous sinus thrombosis consists of variable involvement of: oculomotor, trochlear, abducens, trigeminal (ophthalmic and maxillary division) and oculo-sympathetic nerves. Classic presentations are abrupt onset of unilateral periorbital edema, headache, and (proptosis). Ptosis, chemosis, cranial nelve palsies (III, IV, V, VI). Sixth nerve palsy & Sensory deficits of the ophthalmic and maxillary are common. impaired corneal reflex may be noted. Papilledema, retinal hemorrhages, Fever, tachycardia and sepsis may be present. The cause is usually from a spreading infection in the nose, sinuses, ears, or teeth. Staphylococcus aureus and Streptococcus are often the associated bacteria. 



The superior orbital fissure syndrome is similar to the cavernous 3,4,5,6,

Facial n 1. 2. 3. 4.

M; facial expression, stapedius. Parasympath to lacrimal, submandibular, subligual. taste of ant 2/3 of tongue. Somatic sensation from the external auditory canal and pinna.

NB; lesion proximal to internal auditory meatus Motor& taste sensation affected. - lesion distal to internal auditory meatus(e.g. in the auditory canal as Bell’s palsy)motor affection only (taste is spared).

    

ANATOMY OF THE FACIAL N. The facial nerve is a mixed nerve, containing Fibers for motor output to the facial muscles. Parasympathetic fibers to the lacrimal, submandibular, and sublingual salivary glands. Afferent fibers for taste from the anterior two thirds of the tongue . Somatic afferents from the external auditory canal and pinna.

Causes  LMN

:

Nuclear : Br. Stem ( infl., vas. , neoplastic , demylinating,deg.). Infranuclear : Bell's palsy, otitis media , skull fracture, foreceps injury, cerebellopontine angle tumours, parotid tumour,HZV(Ramsay Hunts),GB$  UMN : stroke, tumour.

UMN lesion lower 1/2 face affected only; since upper facial structures receive bilateral innervations, the emotional movement is preserved .

LMN lesion such as Bell's Palsy,all one side of face affected, absence of both voluntary and spontaneous emotional movement .

C/P; facial weakness and droop. Ask to raise eyebrows, show teeth, puff out cheeks, inability to close the eye, disappearance of the nasolabial fold, and the mouth drawn to the non affected side. Decreased tearing, hyperacusis, and/or loss of taste sensation on the anterior two-thirds of the tongue which is used more as an indicator of severity than anatomical diagnosis.

Bell's palsy Facial palsy without other signs. Unknown cause?? viral. Peak age: 10-40y.  Presentation.  Usually sudden onset of unilateral facial paralysis; may be preceded by pain around the ear. Other possible symptoms: facial numbness; noise tolerance;+/- disturbed taste on the anterior part of the tongue.  Management  ~70% recover completely; 13% have insignificant sequelae; the remainder have permanent deficit. 85% improve in < 3wk.  reassure.many neurologists advocate the use of oral prednisolone(1mg/kg/d. max 80mg/d.)and aciclovir (800mg 5x/d.for 5d. (though,no evidence base)

Bulbar & Pseudobulbar palsy(bulb=medulla)

Causes

C/P

Bulbar palsy

Pseudobulbar palsy

LMNL of 9-12 cr ns (nuclear of infranuclear)

Bilateral UMNLof 9-12 cr ns (supranuclear)

1- Br stem; - infarction, - syringobulbia - MND - Polio 2- Jugular foramen; - nasopharyngeal carcinoma - Fracture base.

-MND

dysarthria Hoarseness Nasal regurgitation Dysphagia Lost reflexes

(spastic Bulbar palsy) Spastic dysarthria Hoarseness Nasal regurgitation Dysphagia Exaggerated jaw reflex Preserved palatal pharyngeal reflexes

MS - Bil Stroke - Severe head injury -

7

Encephalitis

Herpes simplex encephalitis . is associated with high signal in one or both temporal lobes (limbic encephalitis).  Seizures are commonly present in HSE.  Herpes Simplex Virus type 1 is the causative virus PCR for herpes simplex virus on CSF is specific test.  There is more inflammation around the temporal lobe, and the EEG changes .  Acyclovir should be commenced upon clinical suspicion as PCR result may take a few days.

MENINGITIS 

Meningococcal meningitis: (meningogoccus = gram negative diplococci). Immunisation is available against strains A&C however strain B is the most often implicated in meningococcal meningitis in the UK. Rifampicin , ciprofloxacin and ceftriaxone can be used for prophylaxis. (young age)



Pneumococcal meningitis (adult) is caused by gram positive diplococci Nerve deafness is likely, paralysis can occur and mortality rate is high among the elderly. IV penicillin or ceftriaxone should be given. Vancomycin and rifampicin can also be used. Dexamethasone is indicated in early infection to prevent neurological sequelae.



Tuberculous meningitis: Symptoms are headache, vomiting, photophobia, and fever. The duration of presenting symptoms may vary from 1 day to 9 months (insidious onset). CSF typically shows elevated protein level, markedly low glucose, and lymphocytes. Treatment o (INH), (RIF), (PZA), and ethambutol (quadruple therapy). Steroids are usually also indicated.









Viral meningitis: A combination of lymphocytosis, normal or mildly elevated protein and normal glucose suggests viral meningitis. Common causes include enterovirus and mumps. Listeria meningitis ( gram +ve bacilli, cheese, pate, elderly, pregnant, immunocomprmised) is generally associated with multiple cranial nerve deficits, particularly of the VIth and VIIth nerves,(br. Stem involvement) as well as hemiparesis, ataxia and respiratory abnormalities TTT. High dose (eg 2g qds IV) ampicillin & gentamycin are the treatment of choice. Or sulphoneamides (cephalosporines are ineffective).

Aseptic meningitis 

Aseptic meningitis refers to patients who have clinical and laboratory evidence for meningeal inflammation with negative routine bacterial cultures. The most common cause is enterovirus.



Many causes, but usually viral. Other infections, medications & malignancy Usually self-limited CSF pleocytosis (monos), negative bacterial cultures.

 





MENINGITIS VERSUS ENCEPHALITIS — The presence or absence of normal brain function is the important distinguishing feature between encephalitis and meningitis. Important Indications for Steroids in Meningitis  To control the inflammation in acute bacterial meningitis  TB meningitis  Altered mental status or o signs of ICT.

Cryptococcus neoformans



Route; inhalation of fungal spores blood to the CNS, particularly in patients with advanced AIDS. Cryptococcal meningoencephalitis is the most frequently encountered manifestation of cryptococcosis. Symptoms typically begin in an indolent fashion, usually over a period of 1-2 weeks. The three most common symptoms are fever , confusion, and headache. Stiff neck, photophobia and papilloedema are seen in 25- 30% of patients. Pulmonary cryptococcosis (pl effusion, cavitation, fibrosis) is rare.



Diagnosis;

1.

CSF — +ve cryptococcal polysaccharide antigen Ag testing (90% sensitive). Culture will almost always establish the diagnosis (100% sensitive). The CSF WBC count is typically low (<50/microL) with a mononuclear predominance and the protein and glucose conc. are only slightly abnormal.

 



2.



TTT;

1.

Induction therapy -- amphotericin B + flucytosine for 2 weeks. Maintenance therapy — fluconazole for at least 4 months.

2.

DD of chronic meningitis Infectious.  1. TB.  2. $  3.cryptococcal Non-infectious.  4.sarcoidosis.  5. Behcet.  6.Malignant.  

CP ----Meningism & inc. ICT DD..of acute meningitis.

Toxoplasmosis -

o

Neurological dis in Immunocompromized (neck stiffness, headache, CSF; high protein). CT.....> ring enhancing lesions). TTT, pyremethamine & sulfadiazine, if pregnant spiramycin.

Tetanus manifested by uncontrolled spasms, due to the introduction of Clostridium tetani toxin into tissues.  Skin punctures, contaminated wounds with soil, dust, neurotoxin (tetanospasmin) which causes severe spasm---painful muscle contraction and laryngeal spasm.  The toxin tetanospasmin doesn't cross the BBB.  absence of a wound does not exclude tetanus.  The incubation period is typically between 1-2 weeks. Vaccination with tetanus toxoid is effective . TTT:  Tetanus antitoxin.  Booster immunization to whom has been injured & received the last immunization 10 years or more.  supportive along with penicillin, is still the most effective treatment. 

Clostridium Botulinum (‘Botulism’) 

is a paralytic disease caused by the neurotoxins of Clostridium botulinum which interferes with presynaptic Ach release, causing the 6D’s  Dilated fixed pupil; Diplopia; Dysphagia; Dry tongue; Descending paralysis. It may be acquired by ingestion of toxin or more commonly in the UK wound infection as a result of intravenous drug use. associated with trauma, surgery, subcutaneous heroin injection



typically produces a descending paralysis which starts with diplopia or blurred vision due to cr.nr. progresses to involve muscles of the neck, arms, and legs.. The botulinum toxin assay confirm the diagnosis



Therapy consists of approximately 10,000 IU of antibodies against toxin types A, B, and E to neutralize serum toxin concentrations, and also supportive care (e.g. ventilation).(antitoxin)

Lyme disease.

Coma definition Coma is defined as a sleeplike state with total absence of awareness of self and the environment, even after vigorous external stimulation. Coma results from one of two pathophysiologic mechanisms: a diffuse insult to both cerebral hemispheres or a focal lesion involving the ascending reticular activating system (ARAS) located in the upper pons & midbrain.

 1. 2. 3.

CH.CH.:

Metabolic coma

Reactive pupils. Absence of focal neurologic signs. No evidence of increased intracranial pressure.

AW

AR

coma Structural or surgical

metabolic or medical

Decorticate rigidity (flexion & adduction of arms, extension of legs supratentorial lesion. Decerebrate rigidity (extention of neck, back, arms, internal rotated flexed wrists) pontine. Vegetative form (awake coma)  global damage of CC.

. Glasgow Coma Scale Eye opening (E)

Score

Spontaneous

4

To speech

3

To pain

2

No response

1

Best motor response (M) Obeys

6

Localizes

5

Withdraws

4

Abnormal flexion posturing

3

Extension posturing

2

No response

1

Verbal response (V) Oriented

5

Confused conversation

4

Inappropriate words

3

Incomprehensible sounds

2

No response

1

Total score = E + M + V

_______

Range of possible scores = 3-15 A score of 13 to 15 indicates mild coma. A score between 9 and 12 points to moderate coma, and a score of 8 or less indicates severe coma.



Weakness of small ms of the hand;

-

T1 root e.g. cervical rib, pancoat, sub art aneurysm.  all small ms of the hand.

-

-

lower trunk of Br plexus injury  all small ms of the hand + long flex & ext of fingers (C8). ulnar n all small ms of the hand except 2 lateral lumbricals & thenar group (T1 through median n).

Peroneal neuropathy usually presents with acute foot drop. The foot and ankle weakness on neurological examination is restricted to ankle and toe dorsiflexion and ankle eversion. Ankle reflex (Tibial nerve mediated) and knee reflex (Femoral nerve mediated) are intact. Sensory involvement may include the lower two thirds of the lateral leg and dorsum of foot.



Retinal vein occlusion.



, there is rapid visual loss in one eye, the fundus looks like a stormy sunset (haemorrhages and engorged veins). Branch retinal vein occlusion causes partial visual loss. Causes :glaucoma, arteriosclerosis, †‘BP, polycythaemia, hypercholesterolaemia, †‘ homocystein.



Retinal artery occlusion.



Usually due to thromboembolism .Signs :Sudden visual loss in 1 eye (counting fingers or light perception), afferent pupil defect . Retina appears white ±‫ آ‬cherry red spot at the macular. Treatment If the patient presents <1h. after onset”applying then releasing firm eyeball pressure can sometimes dislodge an embolus into one of the smaller branches and thus preserve some vision. Refer for confirmation of diagnosis. There is no reliable treatment

 



Vitreous haemorrhage.



Signs :sudden †“ in vision, loss of red reflex, difficulty visualizing the retina .Risk factors : DM with new vessel formation, bleeding disorders, retinal detachment, central retinal vein occlusion, trauma. Management Treat the cause (e.g. photocoagulation of new vessels). Most bleeds disperse spontaneously in <3mo. Vitrectomy may be required to remove persisting blood.

 



Optic neuritis.

Presentation :loss of vision (over hours or days); painful eye movements; ↓ colour discrimination (red desaturation); optic disc swelling (papilloedema). Recovery usually occurs over 2-6wk. but ~50% develop multiple sclerosis) .  Treatment is with high-dose steroids. Other causes of sudden loss of vision. Migraine ,Stroke , Amaurosis fugax , Temporal arteritis . 

Papilloedema.  Swollen optic disc with blurred disc margins. Can be due to ↑ ICP , malignant hypertension , cavernous sinus thrombosis or optic neuritis. Optic atrophy. Signs: gradual visual loss; pale optic disc. Causes: glaucoma, MS, ischaemia (e.g. retinal artery occlusion), retinal damage (choroiditis, retinitis pigmentosa), toxic (tobacco ambylopia,methanol, arsenic)

Background retinopathy 



Microaneurysms (dots), microhaemorrhages (small blots), hard exudates not affecting the macula Venous abnormalities, large blot haemorrhages, cotton wool spots (small infarcts) Leakage in macular region ‫آ‬± macular oedema,



Proliferative retinopathy though complications cause visual loss. New vessel formation either at the disc (NVD) or elsewhere.

passmedicine.com

Page 1 of 1

passmedicine.com

Reference ranges Return to session summary

Acute coronary syndrome: prognostic factors sqweqwesf erwrewfsdfs adasd dhe The 2006 Global Registry of Acute Coronary Events (GRACE) study has been used to derive regression models to predict death in hospital and death after discharge in patients with acute coronary syndrome Poor prognostic factors age development (or history) of heart failure peripheral vascular disease reduced systolic blood pressure Killip class* initial serum creatinine concentration elevated initial cardiac markers cardiac arrest on admission ST segment deviation

*Killip class - system used to stratify risk post myocardial infarction Killip class Features

30 day mortality

I

No clinical signs heart failure 6%

II

Lung crackles, S3

17%

III

Frank pulmonary oedema

38%

IV

Cardiogenic shock

81%

Comment on these notes

mhtml:file://D:\books\last resources\mrcp\MRCP\MRCP\PassTest Note 2011\Cardiology\...

8/13/2014

psychiatry

Anxiety disorders • • • • • • •

Generalized anxiety disorder GAD Panic disorder Phobic Disorders Post-traumatic stress disorder (PTSD) Mixed anxiety and depression Somatization disorder Obsessive-compulsive disorder (OCD)

Generalized anxiety disorder (GAD) • Long-term condition, fluctuating in severity and nature, often beginning In adolescence. Lifetime prevalence 5%.

Clinical features • • • • • • • • • • • • •

Psychological Apprehension ‫ﺧوف‬ Irritability Dizziness Poor concentration Worrying thoughts Insomnia. Nightmares. Depression. Obsessions.

Physical Dry mouth Tremor Headache Parasthesiae Tinnitus Frequent or loose motions Chest discomfort Difficulty breathing/ hyperventilation Palpitations Frequency or urgency of micturition Erectile dysfunction Menstrual problems

• Associations -

Other psychiatric illness :Panic attacks; depression; and alcohol dependence. Physical illness :Thyrotoxicosis; hypoglycemia; chronic fatigue syndrome; stroke; Cushing's disease; phaeochromocytoma.

• Management. 1. pharmacological; SSRIs(e.g. paroxetine 20 - 40mg, for 12 wk, if effective continue for 6mo.), BDZ e.g. diazepam 2 5mg tds prn not >2-4wk, BB , TCA , buspirone (5-HT1A partial agonist) 2. Psychological = CBT. 3. General measures :Check TFTs. Avoid caffeine. 4. Refer for specialist if significant symptoms despite treatment with 2 interventions (CBT, medication) or if considering initiation of venlafaxine.

Panic disorder (non situational) • Panic attacks are very common, but panic disorder is uncommon. • Intense feeling of apprehension or impending disaster. Anxiety builds up quickly and unexpectedly without a recognizable trigger and patients often present with any combination of these physical symptoms: • Shortness of breath, Choking. • Palpitations, Chest pain • Sweating • Dizziness • Nausea or abdominal pain • Numbness or tingling sensations • Flushes or chills,tremors • Fear of dying • Panic attack: 4 symptoms listed above in 1 attack. • Panic disorder: > 4 attacks in 4wk. or 1 attack followed by a persistent fear of having another. TTT; SSRIs (paroxetine and citalopram 10mg). For 6mo., then discontinue slowly over 4-6mo.TCA (imipramine, clomipramine). Don't use BDZless good outcome in the long term. • CBT.

Phobias (Situational but out of proportion). Same symptoms as GAD but limited to certain situations & fear out of proportion to the situation  . • 2 main features: 1. Avoidance of the circumstances that provoke anxiety. 2. Anticipatory anxiety when there is prospect of encountering these circumstances. Simple phobia. • anxiety in the presence of a specific object/situation e.g. flying, enclosed spaces, spiders. Social phobia. • fear and avoidance of social situations (e.g. meeting people in authority, using a telephone, speaking in front of a group). Agoraphobia. • fear in crowds, away from home, or in situations from which escape is difficult. • TTT; 1. Behavioural therapy e.g. exposure, desensitization. 2. Drug treatment :SSRIs (citalopram and paroxetine are licensed); TCAs (imipramine and clomipramine are commonly used).

Post-traumatic stress disorder (PTSD) •

is a delayed and/or protracted response to an exceptionally stressful event e.g. major accident, fire, military combat. • 3 main symptom clusters: 1. Intrusive recollections of thoughts, nightmares, flashbacks; 2. Avoidance behaviour. 3. anxiety and irritability, insomnia, poor concentration. • TTT; • CBT, • SSRIs reserve for those with continuing symptoms despite trauma-focused psychological therapy or who have refused therapy for those with continuing symptoms.

Obsessive-compulsive disorder (OCD) Features • Obsessional thinking; recurrent persistent thoughts causing anxiety or distress. • Compulsive behaviour; repetitive behaviours, rituals done to prevent the anxiety. • Treatment ; patient education, SSRI or clomipramine, and CBT.

Unexplained physical symptoms 1. Somatoform disorders; (Somatization). >2y history of multiple symptoms with no adequate physical explanation. persistent requests for medical investigations & -ve results. Reassurance have little effects. Pt refuses the possibility of psychological cause.

2. Hypochondrial disorder. • •

• •

Persistent belief of the presence of one serious illness e.g. cancer or AIDS. Management; acknowledging that the symptoms exist and taking the symptoms seriously, offering any necessary examination and investigations, enquiring about psychosocial problems, and explaining the link between symptoms and stress. Treat comorbid psychiatric problems (e.g. depression, anxiety, panic). Senario: A professional man aged 50, previously well, cannot rid himself of the conviction that he has bowel cancer despite reassurance that no disease has been discovered with full investigations.

Conversion disorder; = intolerable psychic stress is unconsciously converted to physical symptoms with loss of physical function. 1ry gain= reduction of the stress. 2ry gain= attention of others. TTT; psychotherapy.

Munchausen syndrome (factitious disorder) • • • •

Intentional production of physical or psychological symptoms to assume the sick role ( hospital admission, willing to receive invasive procedure). Can be difficult to detect. Differs from malingering as there is no external reward (e.g. financial), no convincing secondary gain (occasionally said to be due to attention seeking behaviour). may be harmed. Associated with personality disorder.

• Common presentations; 1. Physical :Dermatitis artefacta, bruising disorders, diarrhoea of unknown cause, neurological symptoms e.g. pseudoparalysis or pseudofits (neurologica diabolica), abdominal pain (laparotomophilia migrans), chest pain 2. Psychological :psychosis, factitious bereavement, factitious overdose. •

TTT; psychotherapy, Often difficult to detect and treat.

Malingering • •

Intentional production of physical or psychological symptoms to assume the sick role for a known external purpose. Malingering is not considered mental illness or psychopathology,

• 1. 2. 3. 4. 5. 6.

Common motivating factors Avoidance of going to jail or release from jail. Avoidance of work. Avoidance of family responsibility Desire to obtain narcotics. Desire to be awarded money . Need for attention

. • 1. 2.

Forms:: Pure malingering; the individual falsifies all symptoms. Partial malingering; the individual has symptoms but exaggerates the impact they have upon daily functioning.

• Management • Difficult. As doctors we tend to believe our patients. • Exclude causes for the presenting symptoms through careful history/examination. • Avoid prescribing drugs for symptoms and unnecessary referrals as these might perpetuate symptoms. • Avoid certifying the patient as unfit to work or perform activities; if the patient is unhappy about this, suggest a second opinion.. • Differential diagnosis 1. True medical or psychiatric illness yet to be diagnosed 2. Somatization disorder (unconsciously) 3. Factitious disorder/Munchausen syndrome (severe personality disorder, consciously, but no gain) 4. Malingering (consciously, with gain)

Deliberate self-harm (DSH) •

• • • 1. 2.

3. 4.

Self-harm is often aimed at changing a situation (e.g. to get a boyfriend back) a sign of emotional distress, or may be a failed genuine suicide attempt. 90% DSH is due to self-poisoning and it accounts for 20% of admissions to general medical wards. Paracetamol or aspirin are the most common drugs used. Management ; Assess the situation and admit to A&E as necessary. Ask about present circumstances: Ask the patient to explain his feelings and reasons for the act of DSH/attempted suicide. Assess psychiatric state: Depression, agitation, early schizophrenia Refer for psychiatric assessment

Assessment of suicide risk •

Ask about suicidal ideas and plans. It is a common misconception that asking about suicide can plant the idea into a patient's head. Evidence is to the contrary.

• 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

Risk factors for suicide male> female; 3:1. Age 40-60 y. Living alone. Divorced > widowed > single > married. Unemployment. Chronic physical illness. Past psychiatric history. Recent admission to psychiatric hospital History of suicide attempt/ self-harm. Alcohol/drug misuse.

suicide

Non-fatal Self-harm

sex

♂

♀

age

40-60

<35

Physical illness

+ (handicap, pain, terminal illness) Depression 60%, Alcohol 20% good

-

Psychiatric illness Premorbid Personality setting precipitants

Planed , alone. Guilt , hopeless.

Depression 10% Antisocial, borderline Impulsive, with others situational

Mood (affective) disorders Depression • 1. 2. 3.

Risk factors ( Depression is commoner in women and in urban areas. Children < 14 yrs living at home, &Adolescents. Lack of employment outside the home. lack of a confidant.

• C/P; 1. Mood; lowered, worse in am (diurnal variation) 2. Thought & speech; slow, poor attention, pessimistic, ↓self esteem, self harm. 3. Behavior, insomnia (early morning awakening), loss of libido, ↓ appetite, ↓wt, ↓enjoyment (anhedonia). 4. Psychotic symptoms; mood congruent, delusion of guilt, auditory hallucinations.

Bipolar disorder or manic depression •

Consists of episodes when the patient has mania (bipolar I) or hypomania but no manic episodes (bipolar II) against a background of depression. Lifetime prevalence [approximate, equals]1%.

•

In dysthymic disorder, the patient’s mood is chronic depression with never a manic or hypomanic episode, for at least two years.

•

Sodium valproate and carbamazepine are efficacious as first line treatment in the prophylaxis of manic and depressive episodes in bipolar I disorder. Lithium may be used if these anticonvulsants are ineffective. However, in the initial stages of manic episodes, the addition of drugs with potent sedative effects are often required e.g. clonazepam, lorazepam and haloperidol. These drugs can be tapered and then discontinued as soon as the initial phase of the manic episode has subsided and the effects of the anticonvulsants or lithium are seen clinically.

Increased risk of suicide in depression if • social isolation- lives alone • elderly males – • terminal medical illness. • recent bereavement • unemployed • alcohol intake

Causes /comorbidity 1. Psychiatric disorders e.g. anxiety disorders, alcohol abuse, substance abuse, eating disorders. 2. Physical disorders e.g. parkinson, MS, dementia, endocrine disease (thyroid disorders, Addison's disease , hypercalcaemia), rheumatoid arthritis, SLE, cancer, AIDS and other chronic infections, 3. Drugs ;B blockers , anticonvulsants, corticosteroids , OCP , antipsychotic drugs, drugs used for parkinson (e.g. Levodopa).

• Diagnosis depressed mood and/or lack of interest or pleasure, which must be disabling to the patient .+ 5 symptoms from following list present most of the time for 2wk:. • Change in appetite or weight (Poor appetite or overeating) • Insomnia or hypersomnia. • Fatigue or loss of energy. • Poor concentration or difficulty making decisions. • Low self-esteem. • Sense of worthlessness or guilt. • Recurrent thoughts of death or suicide. • Feelings of hopelessness.

•

TTT;

pharmacological; The suicide risk can increase early in antidepressant therapy. - antideppressants; Major groups are: • Selective serotonin re-uptake inhibitors (SSRIs) e.g. fluoxetine 20mg is usually 1st choice as less likely to be discontinued due to side-effects. Gl side-effects including dyspepsia are common .Withdrawal of SSRIs; headache, nausea, paraesthesia, dizziness, and anxiety.

venlafaxine •

Tricyclic antidepressants (TCAs)e.g. lopramine 70mg od/bd/tds, titrate dose up. Common side-effects include drowsiness, dry mouth, blurred vision, constipation, urinary retention, and sweating.

•

Monoamine oxidase inhibitors (MAOIs) e.g. phenelzine 15mg tds.(drug ineraction).

•

MAOIs should not be started until at least 1-2wk. after a tricyclic has been stopped. Other antidepressants should not be started for 2wk. after treatment with MAOIs has been stopped .Withdrawal of MAOIs; nausea, vomiting, anorexia, headache, chills, insomnia, anxiety/panic, and restlessness.

•

In patients with recurrent relapses, antidepressants should be continued indefinitely.

- ECT; Severe depression (melancholia) is the most frequent indication for ECT. Patients experience sadness and despair,, lose appetite and weight, sl ,and often think of suicide. • hazardous effects of ECT: partial loss of memory events over weeks following ECT, cardiac arrhythmia and minor musculoskeletal trauma. • Contraindications; ↑ICT, CVA, cardiopulmonary dis.

Psychological = cognitive behavioral therapy. Social; for adaptation for the patient & relatives.

Mania; •

usually part of manic depressive (bipolar); Bipolar disorder is equally common in men and women. Symptoms are evident before age 30 years, Hypomania is a mild form of mania, and can occur in bipolar disorder. Olanzepine or benzodiazepines are more effective during episodes of hypomania C/P; 1. Mood; elated 2. Thought & speech; fast, Pressure of speech and flight of ideas (quick succession of thoughts) poor attention, optimistic, grandiose. 3. Behavior; over activity, insomnia, loss of sexual inhibition, ↑appetite, ↓wt. 4. Psychotic symptoms; mood congruent. Auditory H

•

TTT;

During acute episode; Acute management • • •

Treatment in hospital is usually required for the 1st episode or acute relapses. If unwilling to accept voluntary admission, use compulsory admission . use chlorpromazine 50-100mg po or 50mg im - antipsychotics; clozapine, Olanzepine or BDZ are more effective during episodes of hypomania. - lithium, (plasma level=1mmol/l) - ECT.

Long term;

• • •

- depot antipsychotics, - anticonvulsants; Valproate, carbamazipine, lamotrigine, - lithium (plasma level=0.5 mmol/l) is the drug of choice. Check levels weekly until the dose is constant for 4wk., then monthly for 6mo., then every 3mo. Check plasma creatinine and TFTs every 6mo.. Toxic effects :blurred vision, D&V, ↑K+, drowsiness, ataxia, coarse tremor, dysarthria, fits, psychosis, coma, and shock.

Grief reaction • Normal bereavement can manifest as intense symptoms that subside slowly . • Grief reaction symptoms of depression & thoughts about dying . Symptoms last for up to 6 months. suicidal thoughts 4 weeks after bereavement. • feeling that the dead person is still present 1 month after their death. • absence from work after bereavement usually no more than 2 weeks . • Feelings of hopelessness, guilt and worthlessness may signify depression rather than grief reaction.

Depression in elderly; • C/P; physical symptoms more than depressed mood, insomnia, agitation, cognitive impairement (can present with features suggestive of dementia) • . DD; dementia.

Differentiation of depression from dementia depression

dementia

Onset,course duration

Acute, rapid, short

Gradual, slow, long

C/O of memory loss

yes

no

O/E

Detailed history giving, poor effort at testing, pick on faults, global memory loss, variable concentration

Vague history Good Pleased Recent Consistently poor

+ve sympt of depression

Cortical neuro deficit; apraxias,

Post partum psychotic disorders 1.

PP blues; - tears - 3-4 days after delivery. - primigravada. - TTT; reassurance. - good prognosis.

2.

PP depression; - depression - 2 weeks after delivery. - young age. - marital conflicts.

3.

Puerperal psychosis - psychosis - 2 weeks after delivery, usually acute onset. - is more common primigravada, older age, CS. - The prognosis is good, - recurrence rate = 14-20%. - past history or FH of psychosis. - Treatment is with antipsychotics (be cautious of breast feeding) or ECT.

Puerperal psychosis • A usually begins after the second week of the puerperium • B often takes the form of schizophrenia. • C recurrence of perperal psychosis in subsequent pregnancies is 15 - 20 % . • D the onset is usually acute . • E the prognosis is usually good.

Schizophrenia •

• • 1. 2. • 1. 2. 3. 4.

Definition; disorder ccc by disturbance of - thought; loss of insight ‫ﻏﯾر ﻣدرك‬ - mood; incongruous ‫ﻏﯾر ﻣﺗﻼﺋم ﻣﻊ اﻷﺣداث‬ - perception; delusions ‫ﺗﮭﯾؤات‬ - personality. Epidemiology; prevalence= 1%, early onset in men, genetic predisposition. Symptoms; +ve Symptoms; delusion, hallucinations. -ve Symptoms; flat affect, ↓motor (catatonia), ↓ speech, ↓ self care. Diagnostic criteria;(1st rank Symptoms) (ATPD) (aim to pass definitely) Auditory hallucinations; 3rd person (hearing 2 persons speaking about the patient). Passivity of Thoughts; his Thoughts are under external control; withdrawal, insertion, broadcasting. Passivity of body experiences; his actions, feelings are under external control. Delusional perception; self referential delusions ‫ﺣدث ﻋﺎم إﻧﻣﺎ ﻛﺎن ﻣن أﺟﻠﮫ‬

• The 4 main subtypes of schizophrenia are; 1. catatonic, describes patients whose clinical presentation is dominated by profound changes in motor activity, negativism. 2. paranoid, describes patients who have a prominent preoccupation with a specific delusional symptoms. 3. disorganized, in which disorganized speech and behavior are accompanied by a superficial or silly affect. 4. residual. negative symptomatology exists in the absence of delusions, hallucinations, or motor disturbance. •

schizoaffective disorder is used for those who manifest symptoms of schizophrenia and independent periods of mood disturbance.

• -

Good prognostic criteria; Old age, good premorbid, married. acute onset, +ve precipitant , +ve symptoms. Prominent mood disorder, FH of mood disorder.

• Bad prognostic criteria; - young, male, single, low IQ, abn premorbid personality. Insiduous onset, -ve precipitant, -ve symptoms. Neurological signs, FH of Schizophrenia. • 1.

TTT; pharmacological; A) Atypical antipsychotic; as clozapine, olansapine, resperidone  less side effects as extraΔ, cardiac, more effective for –ve symptoms. B) traditional antipsychotic; chlorpromazine, haloperidol, trifluoperazine  tardive dyskinesia, cardiac, more effective for +ve symptoms. electrocompulsive therapy (ECT) for catatonic stupor. 2. Psychological = cognitive behavioral therapy. 3. Social; for adaptation for the patient & relatives.

Acute schizophrenia • Typically presents in young people with +ve symptoms (delusions, hallucinations, and/or thought disorder) delusions of reference, blunt affect, auditory hallucinations, Olfactory or gustatory hallucinations, persecutory delusions, suspiciousness, hostility, social withdrawal and thought echo . • The patient lacks insight.

Organic Psychiatry organic brain disorder can mimic other functional mental disorders. Features that raise the possibility of organic disorder; 1. Visual perceptual abnormalities e.g. hallucinations, 2. Cognitive deficit. 3. Neurological signs. 4. Fluctuating symptoms. Acute confusional states (delirium)

• Delirium or acute confusional state is a transient global disorder of cognition. Delirium is defined as a transient, usually reversible, cause of cerebral dysfunction and manifests clinically with a wide range of neuropsychiatric abnormalities. • • • • • • •

Common condition seen in general practice, particularly amongst elderly patients due to break of the BBB. Presentation Global cognitive deficit with onset over hours/days. Fluctuating conscious level typically worse at night/late afternoon Impaired memory on recovery, amnesia of the events is usual Disorientation in time and place Odd behaviour may be underactive, drowsy, and/or withdrawn or hyperactive and agitated

Possible causes • Infection ; particularly UTI, pneumonia. Rarely encephalitis, meningitis. • Drugs; opiates, sedatives, L-dopa, anticonvulsants, recreational drugs, Alcohol or drug withdrawal. • Metabolic; hypoglycaemia, uraemia, liver failure, hypercalcaemia. • Hypoxia e.g. severe pneumonia, exacerbation of COPD, cardiac failure. • Cardiovascular; Ml, stroke, TIA. • Intracranial lesion; SOL,↑ ICP, head injury (especially subdural haematoma). • Thyroid disease. • Carcinomatosis. • Epilepsy; temporal lobe epilepsy, post-ictal state.

Differential diagnosis • Dementia; longer history and lack of fluctuations in conscious level. • Primary mental illness e.g. schizophrenia

Physical diseases assiciated with psychiatric disorder; (depression, dementia) 1. 2. 3.

Neurologic; Parkinson, Huntington’s chorea, syphilis, epilepsy, MS, wilson’s, prion, br tumour, MG, MND. Endocrine; cushing, addison, ↓↑TH, pheochromocytoma. Other systemic diseases; SLE, B12 def, porphyria, paraneoplastic. 4)

Chronic alcohol abuse • Chronic alcohol abuse is associated with • parotid gland enlargement • gynaecomastia c-and loss of body hair and testicular atrophy particularly common in alcoholic liver disease • dementia • macrocytosis • atrial fibrillation hypertriglycerdiaemia neurological features – intoxication, coma, delirium tremens, alcoholic fits, alcoholic amblyopia, myopathy, painful peripheral neuropathy, severe rhabdomyolsis, subdural haematoma • cerebellar degeneration& ataxia • Wernicke-Korsakoff syndrome, • central pontine myelinolysis – • Other notable effects -cardiomyopathy, hypoglycaemia,Chronic pancreatitis,

Alcohol withdrawal Delirium Tremens

cocaine • Cocaine is also known as "ice." • Through central effects cocaine induces sweating, pyrexia and also adrenergic mediated hypertension. • It may also be responsible for coronary(chest pain) and cerebral artery spasm causing infarction .

• The classic withdrawal syndrome for heroin appears within four to 12 hours, peaks at 48 to 72 hours, and subsides • There is often a period of several hours before frank withdrawal symptoms begin, during which the addict becomes agitated and anxious. • Characteristic withdrawal symptoms include aching muscles and joints, dysphoria, insomnia, agitation, diarrhoea, shivering, yawning, and fatigue. • More objective measures include • Tachycardia • Hypertension • Lacrimation • Rhinorrhoea • Dilated pupils, and • 'Insomnia (with increase in REM sleep) • Opiate withdrawal is not usually life threatening • Methadone is a synthetic orally effective opiate with a longer half life than heroin (24 to 36 h, making it suitable for daily administration. It is the mainstay of treatment for heroin dependency in the Western world. • Methadone may be used as substitute opiate drug, prescribed long term with the aim of achieving stable (non-injecting) opiate dependence (methadone maintenance) or it may be prescribed in the short term to aid withdrawal. • symptomatic relief may be given with clonidine and benzodiazepines. Opiate withdrawal is not usually considered to be life threatening. • Cannabis abuse is associated with an amotivational state.

.

• Methamphetamine is a sympathomimetic with a variety of stimulant, anorexiant, euphoric, and hallucinogenic effects. • Clinicians should consider the diagnosis of methamphetamine intoxication in any diaphoretic patient with hypertension, tachycardia, severe agitation, and psychosis. • Agitation, tachycardia, hypertension, and psychosis are among the most frequent findings. •

• •

• • •

Patients with methamphetamine intoxication range from the virtually asymptomatic to those in sympathomimetic crisis with imminent cardiovascular collapse. Methamphetamine can cause a host of respiratory, cardiovascular, psychiatric . The differential diagnosis includes a poisonings and medical conditions with characteristics of the sympathomimetic signs of adrenergic excess. We suggest severely intoxicated patients be treated immediately with parenteral benzodiazepines (Grade 2B). initial doses include lorazepam 4 mg IV or diazepam 5 to 10 mg IV. These doses can be repeated every eight to ten minutes based on patient response; IV administration is strongly preferred; i (IM) injection may be used initially when IV access is unavailable. Atypical antipsychotic agents are used as adjuvant therapy. Amphetamine dependence drug induced Schizophrenia.

Dementia •

Definition; global deterioration of higher mental functioning 2ry to progressive neurodegenerative disease.

• 1. 2. 3. 4. 5.

C/P;(fully conscious) Episodic memory loss Deterioration of self care skills Apraxia Temporal & topographic disorientation Personality changes.

• 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

Causes; Alzheimer’s dis; Pick disease; Lewy body; Vascular =Multiinfarct; Normal pressure hydrocephalus; Progressive supranuclear palsy; (PSP) Multiple system atrophy Huntington Chorea; Progressive multifocal leukoencephalopathy Creutzfeldt-Jacob dis; Chronic Subdural hematoma.

Alzheimer’s dis

Multiinfarct

onset

gradual

acute

course

Slowly progressive

stepwise

cognitive impairment

diffuse

patchy

insight

-

+

personality

Lost early

preserved

Focal neuro sign, seizures

-

+

Previous TIA, stroke, HTN, IsHD

-

+

Time of death

Early 2-5 ys

Later 4-5 yrs

Sleep disorders Narcolepsy; is a clinical syndrome of; 1. daytime sleepiness, 2. cataplexy, emotionally-triggered, transient muscle weakness. Most episodes are triggered by strong, generally positive emotions such as laughter, joking, or excitement, result from loss of the neuropeptides orexin-A and orexin-B. TTT; a REM sleep-suppressing medication (eg, venlafaxine, clomipramine, fluoxetine) . 3. hypnagogic hallucinations, are vivid, often frightening hallucinations that occur just as the patient is falling asleep or upon awakening. These are not due to psychiatric disease, but probably result from a mixture of REM sleep dreaming and wakefulness. 4. sleep paralysis; is a complete inability to move for one or two minutes immediately after awakening. •

Only about 1/3 of patients will have all four symptoms; thus, the diagnosis of narcolepsy should be considered even in patients with sleepiness alone.

• Diagnostic testing for narcolepsy includes an overnight polysomnogram (PSG) followed by a Multiple Sleep Latency Test (MSLT). • In Narcolepsy, REM sleep occur at the onset of nocturnal sleep. Daytime attacks also consist of periods of REM sleep ocuring out of context. • Secondary Narcolepsy can occur with rare lesions of the posterior hypothalamus and midbrain. Tumors, vascular malformations, strokes, Prader-Willi syndrome,, and paraneoplastic syndromes. All patients with secondary narcolepsy have obvious neurologic deficits, with cognitive, motor, and/or eye movement abnormalities . • TTT of narcolepsy; 1. Creating a sleep time table & ↓alcohol intake. 2. CNS stimulant as modafinil, methylphenidate or amphetamines.

• TTT of Hyperkinetic attention deficit  methylphenidate. • TTT of restless leg S  correction of anemia, bromocriptine.

Eating disorders • Target groups for screening for eating disorders; 1. Young women with low BMI compared with age. 2. Patients consulting with weight concerns who are not overweight. 3. Women with menstrual disturbances or amenorrhoea. 4. Patients with symptoms/signs of starvation, sensitivity to cold, constipation, low BP, bradycardia, hypothermia. 5. Patients with physical signs of repeated vomiting, pitted teeth , dental caries, general weakness, cardiac arrythmias. • Screen target populations with simple screening questions 1. Do you worry excessively about your weight? 2. Do you think you have an eating problem?

Anorexia nervosa • Prevalence 0.02- 0.04%. ♀>♂. Usually begins in adolescence. Peak prevalence at 16-17y . • Diagnostic criteria: 1. Self induced loss of wt (>15% BW) avoid eating, vomiting, exercise or laxative abuse. 2. nervosa psychopathology= overvalued idea that fatness is a dreadful state. Disturbed experience of body weight or shape. 3. 2ry endocrinal disturbance; delayed puberty, Amenorrhea, loss of sexual interest, ↓2ry sexual ccc. 4. Other features; Depression and social withdrawal are common. • Prognosis; poor, mortality 20%, full recovery only 20%. • Treatment involves psychotherapy, and possible admission for refeeding.

• Features of anorexia nervosa are lanugo hair (fine hair on the back, arms and face) • Metabolic effects in anorexia nervosa metabolic alkalosis, elevated plasma amylase, hypercholesterolaemia, hypoglycaemia, high cortisol, hyponatraemia and hypokalaemia, impaired glucose tolerance, beta-hydroxybutyric acid increase, protein deficiency, zinc deficiency.

↑QT

↓Ht size Relative lymphocytosis

• Neuro; seizures, PN, AN, EEG changes

Bulimia nervosa • Prevalence 1-2%. Mainly ♀ aged 16-40y. • Diagnostic criteria : 1. Recurrent episodes of binge eating, far beyond normally accepted amounts of food. 2. Inappropriate compensatory behaviour to prevent weight gain e.g. vomiting; use of laxatives, diuretics, and/or appetite suppressants. 3. nervosa psychopathology. 4. Normal menses and normal weight. If low BMI, classified as anorexia. • TTT; psychotherapy, Antidepressant medication; fluoxetine 60mg od is the drug of choice.

Some Memory disorders • Frontal lobe damage  poor memory, perseveration (repeating behavior), personality change, disinhibition, euphoria, apathy, aphasia, reduced activity,, inability to plan ahead. • Transient Global Amnesia or TGA - sudden confusion & Antegrade & retrograde amnesia for recent up to years memories.. - The attack lasts for hours, sometimes a whole day. - preceded by physical or emotional stress, for example hot baths, cold swims and personal dramas. - Despite patchy memory loss about the recent past, distant memories remain. - Self identification is preserved. - The lost memories come back, but events that took place during TGA are never recalled. • The underlying cause is proposed to be vascular insufficiency to the memory areas - hippocampi. • Korsakoff’s psychosis is typically associated with short term memory loss and then confabulation by patient when he is unable to accurately describe something.

chronic fatigue syndrome • 1) 2)

•

Diagnostic criteria are : severe chronic fatigue of six months or longer duration Have four or more of the following symptoms: - substantial impairment in short-term memory - poor concentration - sore throat - tender lymph nodes - muscle pain - multi-joint pain without swelling redness - headaches of a new type pattern severity - unrefreshing sleep - post-exertional malaise lasting more than 24 hours Treatment; CBT, Low dose antidepressants.

IGT, DKA

Antidepressants • 1. 2. 3.

Indications; Depression Anxiety disorders; panic, phobic Obsessional illness.

Antidepressants SIADH

↓BP

↑BP (Selective serot & NE reuptake inhibitors)

(Reversible inhibitor of monoamine oxidase A) Has both NE & 5HT activiry, used if SSRI is ineffective or poorly tolerated

Benzodiazepines •

Indications; for short term relief of; 1. severe anxiety( only for 2-4 wks), 2. agitation in acute psychosis or mania. 3. Disabling insomnia. •   

BDZ toxicity  hypersalivation. BDZ withdrawal syndrome insomnia, perspiration, anxiety, tremors, tinnitus, ↓appetite, ↓wt &perceptional disturbance auditory hallucinations only. BDZ suppress REM sleep, so BDZ withdrawal  REM sleep rebound  night mares, insomnia. So to avoid BDZ withdrawal syndrome change to equivalent dose of diazepam, ↓1/8 of the dose/ 2wks.

Lithium • ACE Inhibitors & Angiotensin II Receptor Blockers& Calcium Channel Blockers (Nondihydropyridine)&NSAIDs : May increase the serum concentration of Lithium. • Carbamazepine, Phenytoin, TCA, SSRI, Methyldopa, MAO Inhibitors enhance the toxic effect of Lithium. • Thiazide Diuretics: May decrease the excretion of Lithium. • Amphetamines: Lithium may diminish the stimulatory effect of Amphetamines. • Sodium Bicarbonate, Sodium Chloride, Theophylline Derivatives : May increase the excretion of Lithium.

Lithium •

Cardiovascular: Cardiac arrhythmia, hypotension, sinus node dysfunction, flattened or inverted T waves (reversible), edema, bradycardia, syncope

•

Central nervous system: Dizziness, vertigo, slurred speech, blackout spells, seizure, sedation, restlessness, confusion, psychomotor retardation, stupor, coma, dystonia,, lethargy, headache, pseudotumor cerebri.

•

Dermatologic: Dry or thinning of hair, folliculitis, alopecia, exacerbation of psoriasis.

•

Endocrine & metabolic: Euthyroid goiter and/or hypothyroidism, hyperthyroidism, hyperglycemia, diabetes insipidus

•

Gastrointestinal: Polydipsia, anorexia, nausea, vomiting, diarrhea, xerostomia, metallic taste, weight gain, salivary gland swelling.

•

Genitourinary: Incontinence, polyuria, glycosuria, oliguria, albuminuria.

•

Hematologic: Leukocytosis.

•

Neuromuscular & skeletal: Tremor, muscle hyperirritability, ataxia, choreoathetoid movements, hyperactive deep tendon reflexes, myasthenia gravis (rare)

•

Ocular: Nystagmus, blurred vision, transient scotoma

Rheumatology

*

SYNOVIAL FLUID ANALYSIS

FEATURE

Normal

NONINFLAMMATORY (eg osteoarthritis)

WBCs/m m3

<200

200- 2000

INFLAMMATORY (eg RA, crystal-induced, spondyloarthropathies, connective tissue dz, HOA)

2000 -50.000

SEPTIC

>100,000

Polymalgia Rheumatica Diagnostic Criteria for PMR • Age >50. • ESR>40mm/h. • Neck/bilateral shoulder / pelvic girdle AM stiffness. Symptomatic episodes > 1h in duration. Clinical history >1 month duration. • Response to low-dose (15mg/day) steroids.

• Remember, PMR patients complain more of stiffness than pain. • • • • • • •

Minor criteria include: Weight loss; fever; night sweats,Synovitis. Symmetrical proximal muscle tenderness( no weakness). Alk phos / GGT. Normocytic anemia. Normal CPK, EMG, muscle biopsy. 50% of all PMR patients (±TA symptoms) will be found to have giant-cell arteritis on TA biopsy.

fibromyalgia • • • • • • •

Diagnosis of exclusion. Female > male . Pain must be present for > 3m. Multiple tender points at least 11points . Pts are poorly able to localize the pain. Nervousness is frequent concomitant. TTT: Aerobic exercise. TCA. ( Tricyclic antidepressant).

DD OF MORNING STIFFNESS/ PAIN WORSE IN AM • Rheumatoid arthritis. Difficulty doing up buttons • Ankylosing Spondylitis. LBP + stiffness radiating to buttocks and thighs • polymaylgia Rheumatica (PMR) Difficulty getting out of bed • Fibromyalgia

Osteoarthritis • Bouchard’s nodes are proximal interphlangeal nodes. • Heberden's nodes are distal interphalangeal nodes. • X ray features of osteoarthritis are: joint space narrowing ,osteophytes , subchondral sclerosis & subchondral cysts.

Rheumatoid arthritis

Seven diagnostic criteria for Rheumatoid arthritis • • • • • • • •

Morning stiffness. Arthritis of ≥3 joint area. Arthritis of the hand joint. Arthritis symmetric. Rheumatoid nodules. Serum Rheumatoid factor. Radiographic changes. * In order to have RA, you must have 4 of the 7 criteria present for at least 6 weeks.

Symptoms and signs • Predominantly peripheral joints are affected symmetrical joint pain, effusions, soft tissue swelling, early morning stiffness. Progression to joint destruction and deformity.

Nodes and nodules in rheumatic diseases 1. Heberden's nodes DIP osteophytes in 1ryOA. 2. Bouchard's nodes PIP osteophytes in 1ry OA. 3. Rheumatoid nodules. 4. Gouty tophi (elbow, ears, heels, PIPs, DIPs). 5. Xanthomata.

Investigations • Check FBC (normochromic normocytic ), ESR, and/or CRP, platelets &WCC are increased. • Rheumatoid factor and anti-CCP antibodies are +ve in the majority 60- 70%. A minority have a +ve ANA titre. • X-rays normal, periarticular osteporosis or soft tissue swelling in the early stages; • Later---- loss of joint space, erosions, and joint destruction.

RHEUMATOID ARTHRITIS

OSTEOARTHRITIS

ETIOLOGY

Autoimmune disease

Degenerative disease

PATTERN of symptoms

Morning stiffness

Worse after effort or as activity progresses, relived by rest

Predominant HAND joint involvement

PIP, MCP, wrists (symmetric)

CMC, PIP, DIP

LAB

+RF, ESR and C-reactive protein

Normal RF, ESR, CRP

XRAY findings

1. Periarticular osteopenia. 2. Marginal bony erosions. 3.Symmetrical narrowing of the joint space.

1. Osteophyte formation 2. Subchondral sclerosis (no periarticular osteopenia) 3. Joint space narrowing.

DD of symmetrical polyarthropathy • • •

Rheumatoid Arthritis. Viral arthropathy. Psoriatic polyarthropathy.

DMARDs (Disease- modifying antirheumatoid drugs): 2 Key Points: • Do not wait to start patients on DMARDs until they have failed multiple courses of NSAIDs but, as soon as the diagnosis of RA is confirmed. • Methotrexate is the DMARD of choice in patients with severe disease. Start therapy with 7.5mg weekly and raise the dosage at 1intervals until peak efficacy is achieved.

* DMARD Therapy for RA ("GOLD PILE SCAM") DMARD

Potential Toxicities Requiring F/U

Monitoring Studies

Gold IM and PO

Myelosouppression, proteinuria

CBC and urine dipstick for protein

Penicillamine

Myelosuppression, proteinuria

CBC and urine dipstick for protein

Infliximab (Remicade)

Flu-like sx, auto-Abs; for patients not responding to methotrexate; given IV

None

Leflunomide (Avara)

Thrombocytopenia, hepatotxicity, diarrehea

CBC and AST

Etanercept (Enbrel) (a TNF – blocker)

Reactions at site of SQ injection, flu-like sx

None

Sulfasalzine

Myelosuppression

CBC, AST, creatinine

Cyclophosphamide

Myelosuppression, myeloproliferative disorders, malignancy, hemorrhagic cystistis

CBC, urinalysis, and urine cytology

Cyclosporine

Renal insufficiency, anemia, HTN, hirsutism

creatinine, CBC, K+, LFTs

Azathioprine

Myelosuppression, hepatotoxicity, lymphoproliferative disorders

CBC

Antimalarials (Hydroxycholorquine)

Macular damage

Yearly fundus exams

Methotrexate

Myelosuppression, hepatic fibrosis, pulmonary infiltrates or fibrosis

Minocycline

Photosensitivity, skin discoloration, GI upset, druginduced hepatitis, dizziness

cirrhosis,

CBC, AST, albumin

None

Juvenile chronic arthritis • is rheumatoid factor negative. • Different classifications are systemic, pauciarticular and polyarticular. • Commonest type is Still’s disease.( Systemic onset juvenile R.A ). Peaks of disease are about 5 years and 15 years of age. • Typical diagnostic criteria include High spiking fevers; arthralgias/ macular rash, hepatomegaly, splenomegaly, lymphadenopathy, serositis (pleuritis, pericarditis), seronegativity (-veRF; -ve ANA); leucocytosis. Thrombocytosis. • Very high serum ferritin.

Diagnosis of Felty's Syndrome • Neutropenia caused by hyperslenism and antineutrophil antibodies in a patient with long term rheumatoid arthritis. • Triad of Neutropenia; Seropositive RA; Splenomegaly /hyperslenism. • Frequent concomitants • Serious infections • Anemia, thrombocytopenia. • Leg ulcers • LN, Hepatomegaly • Sjogren's synd. • Weight loss.

Still's Disease

Felty's Syndrome

WBC--inc

WBC---dec

Fever

No fever necessary

Seronegative RA

Seropositive RA

Splenomegaly

splenomegaly

Systemic lupus erythematosus • • • • • • • •

9:1.and Asians. Onset 15-40y. Presentation is variable multisystem involvement must be demonstrated to make a diagnosis: Joints (95%)arthritis, arthralgia, myalgia, tenosynovitis Skin (80%)photosensitivity, facial butterfly rash, vasculitis, hair loss, urticaria, discoid lesions Lungs (50%)pleurisy, pneumonitis, effusion, fibrosing alveolitis Kidney (50%)proteinuria, BP, glomerulonephritis, renal failure Heart (40%)-pericarditis, endocarditis CNS (15%)depression, psychosis, infarction, fits, cranial nerve lesions. Blood; anaemia, thrombocytopoenia, splenomegaly

Diagnostic criteria for SLE • 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

4 of 11 for 6 weeks; butterfly rash discoid rash. Photosensitivity Oral ulcer Arthritis Serositis Nephrological; lupus nephrotis Neurological Hematologic; lymphopenia, thrombocytopenia. Immunological; anti DNA ANA

• • • •

Treatment; Skin only chloroquine. JOINT only; NSAIDs. Other extraarticular; steroid & other immunosuppressants.

Drug-induced lupus • Occurs with minocycline, isoniazid, hydralazine, procainamide,BB, chlorpromazine, sulfasalazine, losartan, and anti-convulsants. Remits slowly when drug is stopped but may need steroid treatment to settle. • No nephrological, no neurological, • DNA –ve • Anti histone Ab +ve.

TYPES OF ANTINUCLEAR ANTIBODIES (ANA) Following detection of a high titer of ANAs (e.g. 1:160), various subtypes are determined. Examples include: • Anti-dsDNA (double-stranded DNA) specific for SLE • Anti- histones Drug induced lupus • Anti-chromatin= anti-nucleosome antibodies. • Anti-ENA (Extractable nuclear antigen)=non-DNA = RNP – – – – – –

Anti-Ro (SS-A) Anti-La (SS-B) Anti-Sm (Smith antigen) Anti-U1RNP (nuclear ribonucleoproteins) Anti Scl-70 (topoisomerase I) Anti-Jo

• Antinucleolar20% of systemic sclerosis . • Anti-centromere • Antibodies to nuclear pore proteins as anti-gp- APA.

Anti-ENA (Extractable nuclear antigen) • Ro/SSA  Sjögren's syndrome , 40% SLE, ANA -ve SLE, subacute cutaneous LE & neonatal LE. • La/SSB 1ry Sjogren. • Anti- Smith (Sm) Ab is very specific for SLE, but only in 25 % . • Antibodies to U1-RNP 100% of MCTD, 30-40 % of SLE (+ anti- Smith) & small proportion of patients with localized (linear) scleroderma. • Antibodies to topoisomerase I (Scl-70), RNA polymerases I and III  systemic sclerosis related disorders. • Anti-Jo1 PM especially with IPF.

• Chromatin= histones + DNA. •

Anti-chromatin= anti-nucleosome antibodies.

DD of sponylitis 1. Sero –ve Spondyloarthoropathies. 2. infections. ( TB , Brucella ).

Spondyloarthoropathies A- HLA-B27 Rheumatic Diseases:

1. 2. 3. 4. 5.

Ankylosing Spoondylitits (<90% are HLA-B27). Reiter's Syndrome or Reactive arthritis (<80%). Enteropthic spondylitis (75%). Psoriatic Spondylitis (50%).

B- Characteristis: • 1- Sacroiliac joint involvement. • 2- Peripheral arthritis (usually asymmetric and oligarticular). • 3- Seronnegativity (absence of RF or other autonatibodies). • 4- Association with HLA-B27. • 5- Relatively early age of onset (<40). • 6- Enthesopathy. • 7- Anterior uveitis. • 1- Radiographic findings: • a) Erosions. • b) Syndesmophytes. • c) Bamboo spine. • D) fusion. • 2- Enthesopathic involvement • a) Plantar fasciitis. • b) Achilles tendonitis. • 3- Iritis (an important clue in spondyloarthropathies).

ankylosing spondylitis

Schober's test

• Schober's test assesses the amount of lumbar flexion. In this test a mark is made at the level of the posterior iliac spine on the vertebral column, i.e. approximately at the level of L5. The examiner then places one finger 5cm below this mark and another finger at about 10cm above this mark. The patient is then instructed to touch his toes. If the increase in distance between the two fingers on the patients spine is less than 5cm then this is indicative of a limitation of lumbar flexion.

• TTT; 1. Symptoms modifying; NSAIDS 2. Disease modifying; infliximab, methotrexate.

• Reactive arthritis Often asymmetrical aseptic arthritis Occurs 2-6wk. after bacterial infection elsewhere e.g. gastroenteritis (salmonella, campylobacter), GU infection (chlamydia, gonorrhoea). • Management: NSAIDs, physiotherapy, and steroid joint injections. Recovery usually occurs within months. A minority develop chronic arthritis requiring disease-modifying drugs. • Reiter's syndrome: Polyarthropathy, urethritis, conjuctivitis. Affects men with HLA B27 genotype. Commonly follows GU or bowel infection. Joint and eye changes are often severe. characteristic mucocutaneous changes oral ulcers , circinate balanitis , keratoderma blenorragicum.

• Enteropathic spondylarthropathy Oligoarticular or polyarticular arthritis linked to inflammatory bowel disease. Includes sacroiliitis, plantar fasciitis, inflammatory spinal pains, and other enthsitides (insertional ligament/tendon inflammation). Arthritis may evolve and relapse/remit independently of bowel disease. NSAIDs may help joint pain but aggravate bowel disease.

circinate balanitis

Psoriatic arthritis • Psoriatic arthritis • Inflammatory arthritis associated with psoriasis. RhF -ve. Presentation variable. Disease modifying drugs (e.g. methotrexate) may improve both skin and musculoskeletal symptoms . presents as several forms: • Symmetrical polyarthritis. • Arthritis involving DIP joints. • Asymmetrical oligoarthritis including dactylitis (70%) • Ankylosing Spondylitis type. • Arthritis mutilans.

Among the differentials of ank. Spond. Is DISH. (Diffuse Idiopathic Skeletal Hyperostosis, a form of 1ry osteoarthritis). • a) Patients with DISH are often obese and 60% have diabetes; • b) 'stiffness' at the spine' yet relatively well-preserved spinal motion. • c) Criteria for DISH…' – 'Flowing' ossification along the anterolateral aspects of 4 contiguous verterbral bodies with preservation of disk height. – Absence of SI joint involvement. – Intervertebral disk spaces are preserved.

• Marked calcification and ossification of paraspinous ligaments occur in DISH. Ligamentous calcification and ossification in the anterior spinal ligaments give the appearance of "flowing wax" on the anterior vertebral bodies. However, a radioucency may be seen between the newly deposited bone and the vertebtral body, • Differentiating DISH from the marginal osteophytes in spondylosis.

Diffuse idiopathic skeletal hyperostosis =DISH

vasculitis Group of diseases in which tissue ischemia and necrosis occur as a consequence of inflammation of blood vessels, either as a primary event or secondary to a systemic disease .1.Autoimmune dis. 2. Infection

•

3.Malignancy

4. drugs .

Large vessel vasculitis: chronic granulomatous reaction affecting the aorta and major branches.

•

Medium vessel vasculitis: necrotizing arteritis affecting visceral arteries renal artery leading to renal infarction .

•

Small vessel vasculitis: capillaries, venules, arterioles (glomeruli)leading to glomerulonephritis

..

Clinical Presentation

Constitutional symptoms. • Skin: purpura,ulcers , livedo reticularis , nail bed infarcts ,digital gangrene. • Eye :episcleritis ,ulcers and vision loss. • Lung: dyspnea, hemoptysis. • Cardiac: angina, myocardial infarction , heart failure. • GIT: abdominal pain, mesenteric ischemia,malabsorpt. • Kidney: hematuria, proteinuria, acute/chronic renal failure • CNS: Mononeuritis multiplex, sensorymotor neuropathy , convulsions, hemiplegia.

Names and definitions of vasculitides

Large vessel vasculitis • Giant cell (temporal) arteritis Granulomatous arteritis of the aorta and its major branches, with a predilection for the extra cranial branches of the carotid artery. Often involves the temporal artery. Usually occurs in patients older than 50 and often is associated with polymyalgia rheumatica. Presentation (classical) of Temporal Arteritis – Headache, scalp tenderness; jaw claudication; sudden visual loss.

• 50% of TA patients have symptoms of PMR. • Flase-negative biopsies may occur 2o to presence of "skip lesions" (if a 2cm biopsy is taken the false-neg rate is >5%; therefore a 3-5cm segment biopsy is recommended).

Takayasu's arteritis Granulomatous inflammation of the aorta and its major branches. Usually occurs in patients younger than 50. Middle aged women ½ 0f patients presents with initial systemic illness of malaise, fever, night sweats, weight loss, arthralgia, and fatigue then subside with more gradual vascular changes. The other half of patients with Takayasu's arteritis present with only late vascular changes, without an antecedent systemic illness. It is also known as "Pulseless disease" because pulses on the upper extremities, such as the wrist pulse, may not be able to be felt.

Medium sized vessel vasculitis • Polyarteritis nodosa. (classic polyarteritis nodosa) Necrotizing inflammation of medium-sized without glomerulonephritis or vasculitis in arterioles, capillaries, or venules.

• Kawasaki disease . Arteritis involving medium sized , and associated with mucocutaneous lymph node syndrome.

Fever of ≥5 days' duration associated with at least 4† of the following 5 change. Bilateral nonsuppurative conjunctivitis One or more changes of the mucous membranes of the upper respiratory tract, including pharyngeal injection, dry fissured lips, injected lips, and "strawberry" tongue One or more changes of the extremities, including peripheral erythema, peripheral edema, periungual desquamation.

Polymorphous rash, primarily truncal Cervical lymphadenopathy >1.5 cm in diameter its most serious effect is on the heart where it can cause severe coronary artery aneurysms in untreated children.

Differential diagnosis, including scarlet fever, toxic shock syndrome, juvenile idiopathic arthritis. • There is no specific laboratory test for this condition • Blood tests • CBC reveal normocytic anemia and eventually thrombocytosis • ESR will be elevated • CRP will be elevated • Other optional tests

• Electrocardiogram may show evidence of ventricular dysfunction or, occasionally, arrhythmia due to myocarditis . TTT: 1.Intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki disease[ 2.Salicylate therapy, particularly aspirin, remains an important part of the treatment

• • • • •

Polyarteritis nodosa Necrotizing vasculitis causing microaneurysms in the medium sized arteries. HBsAg Constitutional symptoms: Fever , abdominal pain,weight loss, arthralgia. Cardiac: coronary arteritis , hypertension , heart failure ,pericarditis. CNS: mononeuritis multiplex, sensorymotor polyneuropathy. seizures, hemiplegia.

• • • • • • • •

GIT: abdominal pain, malabsorption Skin : purpura, urticaria, infarcts, livedoreticularis. Blood: eosinophilia ,anaemia , ESR , CRP. Kidney: hypertension, hematuria, proteinuria, renal failure, intrarenal aneurysms. Testicular pain. ANCA is –ve. Diagnosis by nerve biopsy of affected nerve . If affected tissue not accessible ....visceral Angio.

Small vessel vasculitis ANCA Positive: • Wegener's granulomatosis Granulomatous inflammation involving the respiratory tract, and necrotizing vasculitis (Necrotizing glomerulonephritis is common). • Churg Strauss syndrome Eosinophil-rich and granulomatous inflammation, necrotizing vasculitis involving the respiratory tract, with asthma and eosinophilia. Microscopic polyangiitis (microscopic polyarteritis) Necrotizing vasculitis, with no immune deposits, affecting small vessels . Necrotizing glomerulonephritis is very common. Pulmonary capillaritis often occurs.

Small vessel vasculitis ANCA Negative: • Henoch Schönlein Purpura. Vasculitis, with IgA-dominant immune deposits. Typically involves skin, gut, and glomeruli, and arthralgia or arthritis. • Essential cryoglobulinaemic vasculitis. Vasculitis, with cryoglobulin immune deposits, affecting small vessels, and associated with cryoglobulins in serum. Skin and glomeruli are often involved. Cutaneous leucocytoclastic angiitis . Isolated cutaneous leucocytoclastic angiitis without systemic vasculitis glomerulonephritis.

What is ANCA? • Autoantibodies against intracellular neutrophil antigens. • C-ANCA cytoplasmic anti PR3. • P-ANCA perinuclear anti MPO.

vasculitis with a predilection for renal involovement? • Small vessel vasculitis.

• Medium vessel vasculitis : PAN • How does vasculitis affect the kidney? • Urine analysis shows RBCs ,red cell casts and proteinuria common but usually < 3 gm. • Pathology The shared glomerular lesion of the pauci-immune smallvessel vasculitides is a necrotizing glomerulonephritis with crescent formation. Early lesions have segmental fibrinoid necrosis with or without an adjacent small crescent. Severe lesions have global necrosis with large circumferential crescents. Renal arteritis affecting the interlobular arteries.

Wegner granulomatosis Necrotizing granuloma in the respiratory tract(nasal ulcers, epistaxis , sinus involvement, otitis media, oral ulcers ,proptosis). hemoptysis Rapidly progressive glomerulonephritis. C-ANCA +ve in 70%

Wegener Granulomatosis Clinical Presentation • upper respiratory tract • Lung involvement in 80%; transient infiltrates or nodular densities may be seen on (CXR) Histopathology (1) vasculitis of small vessels, (2) granulomatous changes, (3) focal necrosis LM :segmental necrotizing. crescents ● IF: Pauci-immune GN; crescents; tubulointerstitial granulomas ● EM: No immune deposits are seen Laboratory Diagnosis cANCA is specific and sensitive 20% to 30% have pANCA

Segmental fibrinoid necrosis with nuclear debris and glomerular basement membrane disruption, typical of early stage of pauci-immune crescentic glomerulonephritis

Well-developed cellular crescent with collapse of small amount of remaining glomerular tuft with segmental fibrinoid necrosis and extracapillary fibrin and necrosis

Churg-Strauss Vasculitis • • • • • • • • • • •

Small vessel vasculitis . eosinophilic pulmonary infiltrates Allergic rhinitis. Nasal polyposis. Asthma Eosinophilia Necrotizing inflammation Almost no kidney affection glomerulonephritis is usually (but not always) mild. Associated with leukotriene antagonist therapy, P-ANCA Usually in 60%. (MPO) positive. +ve

• • • •

Microscopic polyangitis Small vessel vasculitis Absence of asthma ,eosinophilia,necrotizing inflammation. P-ANCA is +ve in 50% Kidney : Rapidly progressive glomeruloneph.

Treatment for ANCA-associated disease ● combination of glucocorticoids (1 mg/kg/d) and IV or oral cyclophosphamide (2 mg/kg/d) for 1 year after remission. ● methylprednisolone at 7 mg/kg/d IV for 3 days, then oral prednisone at 1 mg/kg/d. plasmapheresis in who RPGN or pulm Hge. ● Sulfamethoxazole/trimethaprim may diminish relapse rates. Course and Prognosis ● 90% 1-year mortality if left untreated, 90% remission if treated. ● Relapse occurs in 25% to 50% of patients followed up for 3 to 5 years

Henoch-Schönlein purpura systemic vasculitis mostly seen in children. It is a multisystem disorder involving the skin, joints ,gastrointestinal and renal tracts. •

Aetiology is unknown, but the syndrome is often preceded by infections such as Group A beta hemolytic streptococcal

•

Pathology

•

Patients often present with a skin(palpable purpuric eruption purpuric rash usually involving the buttocks and lower limbs, arthralgia and severe colicky abdominal pain and tenderness caused by vasculitis-induced thrombosis in the gut. Renal involvement commonly presents as microscopic haematuria and proteinuria Hematuria 50%/asymptomatic hematuria proteinuria 40%, nephrotic

•

is due to intravascular deposition of IgA immune complexes.

syndrome ,acute and chronic renal failure.

•

•

Similar to IgA nephropathy , but crescents, are more frequent Immunoflorescence :IgA mesangial deposition.

Course. ● Overall good renal outcome; complete recovery

Therapy. ● Symptomatic for mild cases. ● For severe nephritis, treatment is steroids+/-cyclophosphamide.

Can complement levels help diagnosing vasculitis?

• Exclude infection. • Low in SLE ,Cryoglobulinemia . • Normal in ANCA +ve vasculitis.

essential mixed cryoglobulinemia • essential mixed cryoglobulinemia was appropriate. complexes in which one component, usually IgM, exhibits antibody activity against IgG (i.e., mixed cryoglobulins). • The diagnosis of mixed cryoglobulinemia is typically made from the history, skin purpura, low complement levels, and demonstration of circulating cryoglobulins.

CLINICAL PRESENTATION of Mixed Skin manifestations CGs • • • • • •

Palpable purpura (80% in mixed types) Ischemic necrosis ( 020% in mixed types) Livedoid vasculitis (1% in type I, 14% in type III) Cold-induced urticaria (15% in type I, 10% in type III) Acrocyanosis Nailfold capillary abnormalities

Musculoskeletal manifestations • Arthralgias (5% of type I, 20-58% of mixed) • Frank arthritis and progressive joint deformity (distinctly rare)

such as arthralgias and myalgias are common in the mixed CGs, but frank arthritis or myositis are rare to uncommon., especially affecting the metacarpophalangeal, proximal phalangeal, knees, and ankles, • Neuropathy — Sensorimotor neuropathy affects a high percentage of mixed, but clinically significant neuropathy is uncommon., Visual disturbances

Renal manifestations • • • •

Membranoproliferative glomerulonephritis described in all types (more common in type II) Intraluminal cryoglobulin deposition Hypertension Nephrotic-range proteinuria with resultant edema

Pulmonary manifestations • • • •

Dyspnea Cough Pleurisy Pleural effusions

Gastrointestinal manifestations • • •

Abdominal pain (2-22%) Hemorrhage Hepatomegaly or signs of cirrhosis (ie, palmar erythema, abdominal wall collateral vessels, spider angiomata)

• abnormal liver function tests • •

Splenomegaly lymphadenopathy

Cryoglobulinemic Glomerulonephritis can be differentiated from idiopathic MPGN by the following findings . • (1) Intracapillary thrombi the presence of large deposits filling the capillary lumen. • (2) Massive infiltration of capillary spaces by monocytes and polymorphonuclear cells (the exudative component ). • (3) possibly some vasculitis in small and mediumsized renal arteries .(25% to 33%). • The combination of vasculitis and glomerular thrombi should suggest cryoglobulinemic nephropathy, but proliferative lupus nephritis with associated vasculitis is also in the differential diagnosis.

• Aggressive therapy in idiopathic mixed cryoglobulinemia reserved for patients with acute severe disease (manifested by progressive renal failure, distal necroses requiring amputation, or advanced neuropathy). • plasmapheresis (remove the circulation cryoglobulins) with steroids (1000 mg of intravenous methylprednisolone daily for three days , followed by oral prednisone) and cyclophosphamide. • Rituximab is a promising alternative treatment option for severe cryoglobulinemic vasculitis and nephritis.

( Hughes Syndrome),

Anti-Phospholipid Syndrome

• disorder characterized by multiple different antibodies that are associated with both arterial and venous thrombo.

.

• There are three primary classes of antibodies associated with the antiphospholipid antibody syndrome: • 1) anticardiolipin antibodies. • 2) the lupus anticoagulant . • 3) antibodies directed against beta-2glycoprotein 1.

Sensitivity and Specificity for APS APL Test

Sensitivity

Specificity

ACL

80-90%

Low

LA

Moderate

High

2-GP I

74%

85%

APhL

91%

99%

Harris. Lupus, 1998.

• A patient must meet at least one clinical and one laboratory criterion for a diagnosis of APS

Thrombosis • • • •

Venous and arterial circulations Embolic risk high Venous > Arterial Occurs in any system or organ with any part of vascular tree involvement possible(Largesmall) • Single or multiple vessel involvement • Recurrent events common

Catastrophic anti-phospholipid syndrome (CAPS)

• This syndrome, termed "catastrophic antiphospholipid syndrome," is defined by the clinical involvement of at least three different organ systems over a period of days or weeks with histopathological evidence of multiple occlusions of large or small vessels.

• steroids or aggressive immunosuppression is not used unless recurrent thrombotic or ischemic events despite high intensity warfarin therapy. • High dose steroid is reserved for treatment of underlying active lupus and not for lab antiphospholipid AB.

Rituximab • Is a humanized mouse monoclonal antibody against the B cell antigen CD20 that results in the prolonged depletion of B cells. • CD20 is relatively selectively expressed on preB and mature B cells, but not plasma cells or T cells, and may selectively treat antibodymediated disorders with less immune suppression than other treatment regimens.

Vasculitis mimickers

• • • • • •

Subacute bacterial endocarditis. Left atrial myxoma HIV Paraneoplastic syndrome Cholesterol embolization Cocaine and amphetamine use.

•

• • •

Treatment Combined treatment with steroids and cyclophosphamide induces remission in 75% of ptns at 3months and 90% at 6 months. Pulse steroid therapy 7mg/kg for 3 days(IV methyl prednisone) IV cyclophosphamide therapy 0.5g/m2 monthly reaching 1g/m2 based on the leucocyte count. Role of plasma exchange is controversial ,beneficial in dialysis dependant renal failure patients and those with pulmonary hge .

Crystal induced Arthropathy

A 48-year-old gentleman presented with arthritis of rigt ankle for one day. .. S.uric acid : 7.8 .. Synovial fluid : inflammatory with MSU crystals .. 24-h urine uric acid : 1200 mg. The most likely cause. 1- hyperparathyroidism 3- MPD 5- thiazide therapy

2- hypothyroidism 4-Lactic acidosis

A 52-year-old lady , diagnosed to have gouty arthritis two years back with synovitis right MTP1., subsided with local steroid injection. .. No further attacks since then ..s.Uric acid ranging from 6.8 – 8.2 ..s.cr : o.8 , No renal stones .. No tophi. .. She has to start Allopurinol ** YES ** NO

A 58-year-old gentleman , first attack of gout in R knee persistent in the last 6 days .. The drug to be least effective at this stage : 1- NSAID 3- Colchicin 5- Oral PDN

4- local steroids

A 52-year-old gentleman upon the first attack of gouty arthritis in L MTP1, started Colchicin for the last 2 weeks. Inflammation subsided .. S.uric acid now is 13 , supposed to start Allopurinol .. You will combine Colchicin until : 1) 3 months 2) 6 months 3) s.U.A < 6 4)s.U.A < 7 5) 6-months after s.U.A < 6

A 48-year-old lady accidentally discovered to have s.UA of 8 mg% .. 24-h urine uric acid was found 1200 mg .. Best way of management : 1) Start Colchicin 2) Observation with regular monitoring 3) Start Prebencid 4) Start Allopurinol 5) Start Allopurinol & Colchicin

A 54-year-old male , diagnosed as gouty arthritis, first attack. .. S.UA : 8 .. S.creatinin : 1.8 .. C.cr : 35 ml/min Best way of managemeent : 1) Colchicine 0.5 mg OD 2) Colchicine 0.5 mg BD 3) Avoid Colchicine

A 52-year-old lady, four weeks after first attack of gouty arthritis, lab. Investigations revealed : .. S.UA : 10 .. S.cr : 1.9 .. Ccr : 40ml/min Best way of management : 1) Start Allopurinol 50mg/d,increase to 100 after 2w 2) ,, ,, 100mg/d ,, 200 ,, 3) ,, ,, 300 mg/d 4) ,, ,, 100mg/d, build up to 300mg 5) No need for Allopurinol.

Hyperuicemia Gout – negatively birefringent crystals Hyperuicemia is either 2ry to overproduction (> 800mg / d) 10% or underexcretion (<600mg / 24hrs) 90% . Causes of underexcretion . HARD to .. HTN. Hypothyroidism. Hyperparathyroidism. Acidosis. Renal insuffeciency. Drugs( thiazides duiretics, Alcohol)

Causes of overproduction • Tissue damage . (Rhabdomy, tumor lysis, hemolytic process, exercise). • Proliferative disorders.( mylo& lymphoprolif, psoriasis) • Gout is associated with : Hypertriglyceridaemia, diabetes, obesity.

serum hyperuicemia is neither necessary nor sufficient to make the diagnosis of gout. A synovial fluid aspirate is necessary for definitive diagnosis. Always remember, for definitive diagnosis, to send the synovial fluid for crystal analysis, gram stain. • Alcohol/diet/diuretics are the most common cause of acute gout in the outpatient population. • Gout is very uncommon among premenopausal women.

When to treat asymptomatic hyperuricemia? ** Three specific circumstances warrant at least consideration for institution of hypouricemic drugs : 1) Persistent s.urate >13mg/dl in men and >10 mg/dl in women 2) Excretion of U.uric acid >1100 mg/d is associated with 50% risk of uric acid calculi. 3) Patient about to receive radio or chemotherapy that is likely to result in extensive tumour lysis

• Renal disease is a limitation for both allopurinol & colchicine. With allopurinol, there is a consensus that you need to start with a lower dose and only gradually increase it. • Uricosurics are not effective if the serum urate is over about 12 mg/dL, Uricosurics also increase the risk of nephrolithiasis. • colchicine works only if you use it fairly early in the attack.

• Benzbromarone — Benzbromarone, a uricosuric agent that reduces serum uric acid levels in transplant recipients with hyperuricemia and gout. • Benzbromarone is an effective uricosuric, even in patients with creatinine clearances as low as 20 mL/min

1. Treat acute flares with antiinflammatory drugs; NSAIDs, colchicine or steroids. 2. Initiate urate lowering drug (Allopurinol) weeks after any acute flare. 3. Choose effective & safe drug e.g. allop allergy, renal disease. 4. Protect against flare from urate lowering drug by adding anti-inflamatory for 6 months after achieving the target. 5. Continue life style modification 6. Monitor/ 2-4 wks till target uric acid< 6 mg/dl. 7. Then Monitor every 6-12 months.

Pseudogout • Inflammatory arthritis due to deposition of pyrophosphate crystals. Chondrocalcinosis may be seen on X-ray (calcification of articular cartilage). Knee, wrist, and shoulder are most commonly affected. causes are: • Haemochromatosis. • wilson's disease . • Hypothyroidism. • hyperparathyroidism. • hypomagnesaemia. • hypophosphataemia • Amyloidosis. • Aging.DM • Chronic renal failure on dialysis. • Acute attacks can be triggered by intercurrent illness and metabolic disturbance. Attacks are less severe than gout and may be difficult to differentiate from other types of arthritis. Presence of joint crystals confirms diagnosis. • Pseudogout – positively birefringent crystals .

Pseudogout (calcium pyrophosphate "CPPD") • Can mimic and coexist with gout. • similar to gout, surgery, trauma, and alcohol may precipitate. • Treatment options are similar to gout, except for allopurinol. • Pseudo gout, is Positively birifringent under polarized light microscopy.

A 68-year old man presented with sudden severe pain and swelling in the left knee. Synovial fluid analysis shows abundant calcium pyrophosphate dihydrate (CPPD) crystals. Which of the following tests is NOT appropriate for further assessment of this patient illness? A : Creatinine kinase B : Serum calcium C : Thyroid function test D : Serum ferritin level E : Hb AIc.

Crystal Analysis: Gout Versus Pseudogout Feature

Gout

Pseudogout

Monosodium urate

Calcium pyrophosphate

Color under polarized light

Yellow

Blue

Shape of crystal

Needle

Rhomboid

Negative (counterclockwise)

Positive (clockwise)

Crystal

Birefringence/ rotation under polarized light direction

PseudoPseudogout ( calcific tendinitis) • Pain on adduction more with active movement. • Characterized by deposition of hydroxy appetite crystals within rotator cuff muscle near humeral attachment most commonly involve supraspinatus tendon. • Severe shoulder pain localized mainly to humorous diffusely around antrolateral shoulder. • Palpation or compression around the greater tubercle of the humerus causes tenderness. • X ray : linear calcific density in supraspinatus tendon. • Ttt: intralesional steroids & physiotherapy.

70 years old lady complaining of gradually progressive bilateral lower limb oedema

Paget disease of bone

Paget disease of bone

Paget disease of bone • What are the manifestations? • What are the serious complications? • What are the biochemical abnormalities? • What is the treatment?

Paget's disease of bone • • • • • • • • • • • • • • • • •

Accelerated, disorganized bone remodelling due to abnormal osteoclast activity. Affects up to 1:10 of the elderly but only a minority are symptomatic. Presentation. Skeletal Pain ,deformity & fracture. Deformity bowing of weight-bearing bones, especially tibia, femur, Frontal bossing. High COP failure. Complications Pathological fractures; O Arthropathy of adjacent joints. cranial nerve compression., neurological symptoms e.g. deafness, bone sarcoma (10% of those affected >10y.). Investigation. X-ray Distinctive changes; Alk phos--->very high. normal Ca2+, PO4, PTH, bone scan...diffuse density. Urinary hydroxyproline. Management pain and long-term complications with bisphosphonates (e.g. risedronate 30mg/d. for 2mo.).

Paget disease of bone •Pain,deformities,fractures. •Hyperdynamic circulation •Marked increase of alkaline Phosphatase •Bone scan

Bone scan Normal:

The radioactive tracer is evenly distributed among the bones. No areas of abnormally high or low accumulation are seen.

Abnormal:

The tracer may accumulate in certain areas of the bone, indicating one or more hot spots. Hot spots may be caused by a fracture that is healing, bone cancer, a bone infection (osteomyelitis), arthritis, or a disease of abnormal bone metabolism (such as Paget's disease).

Bone scintigraphy

Normal bone scan.

Bone metastasis

Bone metastasis Paget disease of bone

Pulmonary osteodystrophy

• Hypertrophic osteoarthropathy (or hypertrophic pulmonary osteoarthropathy when there is mesothelioma or bronchogenic carcinoma associated) • X rays show periosteal reaction at the ends of the radius and ulnar bones suggestive of periostitis.

Osteomalacia • Osteomalacia is characterized by a low serum calcium and phosphate with elevated serum alkaline phosphatase. Osteomalacia may be caused by deficiency of vitamin D or phosphate deficiency. • Skeletal x-rays – osteomalacia present with the pathognomonic Looser zones are linear areas of low density surrounded by sclerotic borders, – better observed in the pubic ramus, upper femoral bone, and ribs.

• Treatment is with a daily dose of calciferol (20-25 micrograms).

Vitamin D deficiency (osteomalacia)

• Nutritional deficiency • Impaired absorption ; Small bowel diseases, such as celiac disease, gastric bypass, steatorrhea, and pancreatic diseases.

• Hepatic disease impaired 25-hydroxylation of vitamin D, decreased bile salts with malabsorption of vitamin D, decreased synthesis of vitamin D–binding protein, or other factors. vitamin D dysfunction.

• Anticonvulsants • Renal failure decreased conversion of 25-hydroxyvitamin D to its active form 1,25dihydroxyvitamin D. This results in an increase in PTH.

• Inherited conditions vitamin D dependent rickets (type I) or 1-alpha-hydroxylase deficiency . vitamin D dependent rickets (type II )--- Hereditary vitamin D resistance rickets.

X-linked hypophosphataemic Vit D resistant rickets. • serum phospate is low and urine phosphate is high due to inappropriate renal phosphate wasting. • Serum parathyroid levels are usually slightly elevated. Clinically, growth retardation that causes very severe rickets, especially in affected males. • Treatment is with oral phosphate and high dose activated Vitamin D.

Bone Disease

osteoporosis osteomalacia Paget disease Primary hyperparathyroidism

Renal osteodystrophy

X-linked hypophosphat aemic Vit D resistant rickets.

Serum calcium

Serum phosphorus

Alkaline phosphatase

Behcet's Syndrome • Immune mediated vasculitis, venulitis. • Equal sex affection but more severe in males ,Eastern Mediterranean and Asia . C/P; • Painful Genital ulcers. • Painful Oral ulcers (98%). • Ocular disease ( 80%); more common in HLA B5 men; eg uveitis. iritis, retinal vessel occlusions and optic neuritis can be found. Hypopyon uveitis • Skin; E.nodosum ( 80%); (F
Behcet’s

Sjögren syndrome • • •

•

Sjögren syndrome (SS) is a systemic chronic inflammatory disorder characterized by lymphocytic infiltrates in exocrine glands. C/P; sicca symptoms; xerophthalmia (dry eyes), xerostomia (dry mouth), dyspareunia fatigue and parotid gland enlargement. extraglandular features ; arthralgia, arthritis, Raynaud phenomenon, myalgia, pancreatitis, leukopenia, anemia,LN, neuropathy, vasculitis, RTA, and later lymphoma (suspected if low C4, cryo, persistent parotid enlarg, purpura & leukopenia). Primary Sjögren syndrome occurs in the absence of another underlying rheumatic disorder, whereas secondary Sjögren syndrome is associated with another underlying rheumatic disease, such as SLE, RA, or scleroderma.

Inv; • ANA 90%, Anti RO & Anti La in 1ry SJ, • ESR, CRP, RF, hypergammaglobulinema in 80%. • Schirmer's test Management • artificial tears , cool drinks, artificial saliva sprays or sugar-free gum. • pilocarpine • NSAIDs, hydroxycholoquine for arthritis.

Dermatomyositis C/P; • proximal muscle weakness, tenderness. • Skin; Raynauld’s, Gottron's papules , heliotrope rash around the eye, calcinosis, periungual telangiectasia, mechanics hand, v shaped, shawl sign. • Others; • Dysphagia. • cardiomyopathy, • IPF. • The condition is associated with carcinoma of the breast, lung, ovary and bowel in old age only. Inv : • elevation of muscle enzymes; CPK, LDH, AST. • EMG; myopathic pattern (high frequency, low amplitude). • ESR, CRP ↑ in 5 % only. • Autoantibodies; - ANA - anti-jo-1(IPF, mechanics hand, Raynauld’s) - anti M2 (classic) - anti SRP (severe rapidly progressive) severe form with cardiac affection. • muscle biopsy; inflammatory changes . TTT; steroids rapid ↓CPK but power takes weeks+/- methotrexate, cyclophosphamide.

Scleroderma

Inv; • ANA in 90%, • RF in 30% • Anti-topoisomerase (= anti Scl 70, specific, in 30%) in diffuse scleroderma. • Anticentromere in 50-90% of limited & 10% of diffuse sclero. • Anti-RNA polymerase III in renal crises. Patterns; 1. Limited systemic; CREST S (calcinosis, raynaulds, esophageal dysmotility, scleroderma, telangiectasia), tight skin limited to face, neck, distal extremities. cause of death; pulmonary HTN. 2. Diffuse systemic; cause of death; renal crises, worse prognosis. 3. Localized to the skin; morphea (plaques), coup de sabre (linear). TTT; NSAIDs, PPI, antibiotics for bact overgrowth, VD, PG, Dpenicillamine, ACEI for renal crises.

Overlap Syndromes • E.g. mixed CT disease; SLE, Sclero, PM. +ve anti RNP.

Osteoporosis **A disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture . **Bone mineral density (BMD) T-score < –2.5

What are the major risk factors for osteoporosis? Non-modifiable 1) 2) 3) 4) 5) 6)

Age. Race ( Caucasian,Asian). Gender (female). Early menopause(<45) Slender built. Positive family history.

Modifiable 1) low ca. intake 2) low vit-D intake 3) estrogen deficiency 4) sedentary life 5) smoking 6) alcohol(>2drinks/d) 7) caffeine(>2serving/d 8) medications: (steroids-thyroxine)

Other conditions with low bone mass ** hyperparathyroidism ** Celiac d. ** hyperthyroidism ** Liver d. ** hypogonadism ** I.B.D ** cushing s. ** myeloma ** osteomalacia ** Renal failure ** Drugs : .. Steroids – thyroxine – cyc,A - heparin

How to interpret BMD

H

1)T-score : comparison of patient’s bone mass to that of young normal subject(age 30) 2)Z-score : comparison of patient’s bone mass to that of age-matched subject

indications for BMD:

**

1)Women aged 65 years and older . 2)Postmenopausal women< 65 years with risk factors for osteoporosis 3)Men aged 70 years and older . 4)Adults with fragility fracture . 5)Adults with a disease or associated with low bone mass or bone loss. 6)Adults taking medication associated with bone loss. 7)Anyone being considered for pharmacological osteoporosis therapy .

Pharmacologic therapy of osteoporosis • • 1. 2.

Ca, vit D Drugs that decrease bone resorption; HRT (E↑uterine cancer& breast cancer). SERM (selective Estrogen receptor modulators)= agonist on bone & antagonist on breast↓ osteoporosis, br cancer & IsHD. Side effects; flushes, DVT. - Raloxifen (Evista®)used in postmenopausal osteoporosis. 3. STEAR= selective tissue estrogenic activity regulator e.g. Tibolon (Levial ®) 4. Bisphosphonate (oral alendronate) 5. Calcitonin ; anabolic bone effect, Side effects; nasal congestion, rash. • Drugs that increase bone formation; 1. Synthetic PTH (Teripatide). 2. Strontium ranelate (Protelos) dual mechanism , incr bone formation & decrease bone resorption. 3. Others; GH, GHRH, IGF1, anabolic steroids, statins.

•

Ca, vit D; - ca alone; small effect on BMD, no antifracture effect. - Vit D alone; unknown effect in pt without vit D def. - Ca + Vit D; may ↑BMD, ↓fracture. • Raloxifen (Evista ®) 60 mg once daily - TTT & prevention postmenopausal osteoporosis. - adv; ↓vertebral fracture,but not non vert fracture, ↓ br cancer & ↓ IsHD. - Side effects; increase risk of DVT. not effective against non vert fracture. • Calcitonin; nasal spray, SC; ↓vertebral fracture ( weak evidence) , small ↑BMD.

HRT Thromboembolism, breast cancer, ↑TG, ↓ risk of fracture, cancer colon, ↑ HDL  ↓ coronary. Contraindications; - Absolute; • E dependant tumours; breast, endometrium. • Thromboembolic disorder. • Abn vaginal bleeding. - Relative; • FH of br cancer, • GB disease. • Endometriosis

• Alendronate (oral daily 10 mg or weekly 70 mg) - mech; taken up by osteoclast  apoptosis. - adv; effective against all fractures, long term benefit (10 yrs). - disadv; poor upper GIT tolerance. - contraindications; hypocalcemia, osteomalacia, renal failure, bed ridden, serious oesophageal dis. - side effects; hypocalcemia, ↑PTH, skin rash oral; esophagitis, ulceration. IV; flu like, arthralgia, myalgia, fever, leukopenia, eye inflammation etidronate; ↑phosphate, osteomalacia. • Teriparatide; rh PTH - daily SC, 1st anabolic, ↓ all fractures, marked & rapid ↑BMD. - disadv; daily SC, use restricted to high risk pts, osteosarcoma in toxicologic studies. - contraindication; bone dis; paget dis, Hx of bone metastasis or cancer, growing child, bone, hypercalcemia, pregnant, lactation.

The following subjects are candidates for BMD except : 1) A lady of 68 years 2) An obese lady at age of 52(menopause) 3) A man of 74 years age 4) A lady 34-year age with 1ry hyperparathyroidism

A 54-year-old lady advised to do BMD for persistent spine pain, Which revealed : ** T-score .. L.spine : -2.6 .. F.neck : -1.7 ** All are possible except : 1)Osteoporosis 2)Hyperparathyroidism 3)I.B.D 4)Hypothyroidism 5)Cushing d.

A 52-year-old lady, menopause for 3 years on longterm steroids for her uncontrolled chronic asthma ** BMD done for her revealed : T-score L.spine : -2.0 F.neck : -1.2 ** suggested treatment : 1)Calcium + vitamin-D 2)Calcium + vitamin-D + Alendronate 3)Calcium + vitamin-D + Alendronate + Calcitonin 4) No TTT

A 62-year-old lady presented with severe back pain , she lost about 2 inches of her height. Plain XR revealed farcture of T12 and wedged L3. She is immobile for severe knee OA and on steroids for ILD ** BMD advised revealing : T-score L.spine : -4.2 F.neck : -2.8 ** Best TTT is : 1) Ca + vit-D + Alendronate 2) Ca + vit-D + Calcitonin 3) Ca + vit-D + Teriparatide (PTH) 4) Ca + vit-D + Alendronate + Calcitonin

A 58-year-old lady admitted for fracture neck-femur ** BMD revealed : T-score L.spine : -1.6 F.neck : -2.8 ** The drug being least effective is : 1)Alendronate 2) HRT 3) PTH 4) Raloxifene ( SERM)

Gonoccocal arthritis is a common cause of septic arthritis in which the organism cannot be cultured on routine culture media. Occur in disseminated gonococcal infection. C/P; • sexually active individuals, ♀;♂ (4:1), ↑ during menstruation and pregnancy. • fever, chills, skin rashes( pustular) , polyarthralgias, and tenosynovitis  persistent monoarthritis or oligoarthritis, Inv; • The mean synovial fluid WBCs = 50,000 cells/mm3. • Cultures of synovial fluid tend to be positive in < 50 % of cases of gonococcal arthritis • The joint aspirate should be cultured for N. gonorrhoeae when the history is suggestive. ( chocolate agar or Thayer-Martin medium) • cultures from clinically appropriate sites (eg, the pharynx, urethra, cervix, rectum, and skin lesions). • Blood cultures are often positive in patients presenting with tenosynovitis and skin lesions alone, • PCR • screening test for HIV and a syphilis. • TTT; , the initial therapy of choice is ceftriaxone (1 gm either IV or IM) or another 3rd G cephalosporin. • Fluoroquinolones .

• • • • • •

Relapsing polychondritis Associated with autoimmune disease in 30%. Leads to fever, arthralgias, episcleritis, swollen floppy ears. Nasal Septum collapse (the other 'saddle nose' deformity, i.e. not just Wegener's). laryngeal disease – hoarseness; respiratory obstruction. Tracheobroncial degeneration – recurrent infections, AI/MVP/ Aneurysm in 10%.

Causes of avascular necrosis • SLE . • vasculitis & any hypercoagulable state. • long term steroids . • sickle cell disease. • Hip involvement. • MRI is the best diagnostic tool.

• Causes of Charcot’s joints: • • • •

diabetic neuropathy, syphillis syringomyelia leprosy

• Causes of Iritis: • • • •

Behcet's disease Reiter's syndrome ankylosing spondylitis sardoidosis

• Eosinophilic fasciitis is a disorder characterized by peripheral eosinophilia and fasciitis. Swelling and progressive induration of the skin associated with aching of the extremities and occasional morning stiffness develop over a period of weeks. The distribution most often is in the upper extremity, proximal and distal to the elbow, and in the lower extremity, proximal and distal to the knee. Onset may be acute following some sort of strenuous exercise, or it may be subacute. The diagnosis is confirmed by deep biopsy from skin to muscle.

Eosinophilic fascitis

Eosinophilic fascitis

Rheumatologic Manifestations of sickle cell disease • Gout. • Sickle lower extremity arthralgias (knees and ankles most common), myalgias, synovitis. • 2ry hemochromatotic (Fe overload 2o to frequent transfusions). • Septic arthritis (or osteomyelitis), esp due to Salmonella, particularly if hyposplenic. • Aseptic (avascular) necrosis.

Familial Mediterranean fever • AD • is an inherited condition characterized by recurrent episodes of painful inflammation in the abdomen, chest, or joints, fevers and rash. • The first episode usually occurs by the age of 20 years, but in some cases, later in life. • FMF primarily affects populations originating from the Mediterranean region. • A buildup of amyloid. AA amyloidosis commonly involves the kidneys, spleen and GI tract. • Colchicine given prophylactically in FMF offers some protection against the development of amyloidosis in most patients.

De Quervain's tenosynovitis • is inflammation of the abductor pollicis longus and extensor pollicis brevis. • Finkelstein's test is positive. This is performed with the thumb flexed across the palm of the hand, asking the patient to move the wrist into flexion and ulnar deviation. This stresses the tendons of abductor pollicis longus and extensor pollicis brevis and reproduces the pain of de Quervain's tenosynovitis.

• A 15-year-old boy presented with arthralgia, skin rash and haematuria. Renal biopsy showed focal • necrotising glomerulonephritis with diffuse mesangial IgA deposits. What is the most likely diagnosis? • A : Systemic lupus erythematosus (SLE) • B : Henoch–Scholein purpura • C : Juvenile rheumatoid arthritis • D : Post-streptococcal glomerulonephritis • E : Goodpasture's syndrome

• 24. A 64-year-old man presents to A&E with a 2day history of increasing pain and swelling of • his left knee. He denies a history of trauma. On examination, the knee is hot, red, swollen and • extremely tender. Which of the following investigations is most important? • A : Plain radiograph of the knee • B : Blood cultures • C : C-reactive protein (CRP) • D : Joint aspiration • E : Plasma uric acid level.

64-year-old man with congestive heart failure presents to the emergency room complaining of acute onset of severe pain in his right foot. The pain began during the nightand awoke him from a deep sleep. He reports the pain to be so severe that he could not wear a shoe or sock to the hospital.His current medications are furosemide, 40 mg twicedaily, carvedilol, 6.25 mg twice daily, candesartan, 8 mg once daily, and aspirin, 325 mg once daily. On examination, he is febrile to 38.5°C. The first toe of the right foot is erythematous and exquisitely tender to touch. There is significant swelling and effusion of the first metatarsophalangeal joint on the right. No other joints are affected. Which of the following findings would be expected on arthrocentesis? A. Glucose level of <25 mg/dL B. Positive Gram stain C. Presence of strongly negatively birefringent needleshaped crystals under polarized light microscopy D. Presence of weakly positively birefringent rhomboidal crystals under polarized light microscopy E. White blood cell (WBC) count >100,000/μL

A 36-year-old woman presents with deteriorating nocturnal paraesthesia affecting both hands. It improves during the morning. Which of the following tests is least likely to be helpful in establishing the cause? • A : Thyroid function test • B : Rheumatoid factor • C : Tinels test • D : MRI scan hands • E : Urinary hCG.

A 25-year-old woman with a history of 3-second trimester fetal losses is planning a fourth pregnancy. She has evidence of the primary anti-phospholipid syndrome (strongly positive cardiolipin antibody, positive lupus anticoagulant but no evidence of lupus). Which of the following treatment regimens offer her the best chance of having a successful pregnancy? • A : Steroids alone • B : Steroids combined with low-dose aspirin • C : Low-dose aspirin alone • D : Low-dose aspirin combined with low molecular weight heparin • E : Intravenous immunoglobulin.

Serum biochemistry of a 60 year old man revealed calcium of 1.98 mmol/l and phosphate of 0.55 mmol/l with an alkaline phosphatase of 450 IU/l. Which among the following most suits with the above serum biochemistry? • 1) Osteoporosis • 2) Osteomalacia • 3) Pagets Disease • 4) Secondary Hyperparathyroidism • 5) Renal failure

A 36-year old woman is referred with a 1-year history of muscle pain, tiredness and sleep disturbance. She denies fever, weight loss and arthralgia. Examination reveals tenderness over her occiput, trapezius and lumbar area. Her blood results show a normal ESR, CRP, FBC, a weakly positive ANA 1:80 and normal complement. Which is the most likely diagnosis? A : Polymyositis B : System lupus erythematous (SLE) C : Sjogren’s syndrome D : Polymyalgia rheumatica E : Fibromyalgia.

A 58-year-old female presents complaining of right shoulder pain. She does not recall any prior injury butnotes that she feels that the shoulder has been getting progressively more stiff over the last several months. She previously had several episodes of bursitis of the right shoulder that were treated successfully with NSAIDs and steroid injections. The patient’s past medical history is also significant for diabetes mellitus, for which she takes metformin and glyburide. On physical examination, the right shoulder is not warm or red but is tender to touch. Passive and active range of motion is limited in flexion, extension, and abduction. A right shoulder radiogram shows osteopenia without evidence of joint erosion or osteophytes. What is the most likely diagnosis? • A. Adhesive capsulitis • B. Avascular necrosis • C. Bicipital tendinitis • D. Osteoarthritis • E. Rotator cuff tear

A 45-year-old woman is admitted with a spiking temperature and sweats. She has been unwell for the last 3 weeks with flitting arthralgia and lethargy. There is a rash over her trunk which is most prevalent in the mornings. Blood cultures are sterile. Her recent transthoracic echocardiogram is normal. ESR 56mm/hour. Her ferritin is elevated at 6000(g/l. Autoimmune screen is negative. • 1) bacterial endocarditis • 2) systemic lupus erythematosus • 3) rheumatoid arthritis • 4) adult onset Stills disease • 5) meningitis

A 60-year-old accountant complains of recurrent attacks of exquisite pain and swelling in the left big toe. Which of the following conditions is NOT likely to be associated with this disorder? A : Chronic alcoholism B : Obesity C : Rheumatoid arthritis D : Diabetes mellitus E : Diuretic therapy.

A 68-year-old woman with longstanding congestive cardiac failure (ejection fraction 20%) presents with a hot, swollen right knee. The following results are obtained: FBC normal, Urea 11mM, Creatinine 196ul. Synovial fluid: many monosodium urate crystals seen on microscopy, culture sterile. What is the best treatment for her acute arthritis? • A : Allopurinol • B : Colchicine 0.5mg every 2-4 hours • C : Indomethacin 50mg tds • D : Co-codamol 30/500 every 6 hours • E : Intra-articular corticosteroids

A 34-year-old man presents with severe low back pain, which has forced him to stop work as a bus driver. He has had back pain on and off for many years, on occasion with right-sided sciatica. The pain used to be helped by rest, but is now present more or less all the time and is stopping him from sleeping properly. The most likely diagnosis is: A : mechanical back pain. B : ankylosing spondylitis. C : myeloma. D : osteoporosis. E : osteoarthritis.

‘Red flag’ symptoms, requiring urgent investigation to exclude sinister pathology, include: • · age >55 or <18 years • · progressive pain • · night pain • · systemic symptoms • · progressive neurological deficit • · past history of malignancy or immunosuppression • recent trauma.

A 50 year old man presents with a 6 week history of general malaise and a 2 day history of a right foot drop, a left ulnar nerve palsy and a widespread purpuric rash. He complains of arthralgia but has no clinical evidence of inflammatory joint disease. Echocardiogram is normal, blood cultures are negative, ESR 100 mm/hr, ANCA negative, ANA negative, rheumatoid factor strongly positive, C3 0.8 g/l (0.75 - 1.6), C4 0.02 g/l (0.14 - 0.5). Dipstick urinalysis shows blood ++ but no protein. • 1) ANA negative SLE • 2) Cryoglobulinaemia • 3) Infective endocarditis • 4) Polyarthritis nordosa • 5) Rheumatoid arthritis

• A patient with primary Sj ِ◌gren’s syndrome that was diagnosed 6 years ago and treated with tear replacement for symptomatic relief notes continued parotid swelling for the last 3 months. She has also noted enlarging posterior cervical lymph nodes. Evaluation shows leukopenia and low C4 complement levels. What is the most likely diagnosis? • A. Chronic pancreatitis • B. Secondary Sj ِ◌gren’s syndrome • C. HIV infection • D. Lymphoma • E. Amyloidosis

A 64-year-old man with coronary artery disease an atrial fibrillation is referred for evaluation of fevers, arthralgias, pleuritis, and malar rash. The symptoms have developed over the past 6 months. The pleuritis has responded to steroid therapy, but prednisone has been unableto be tapered off due to recurrence of symptoms at daily steroid doses <15 mg of prednisone. His medications include aspirin, procainamide, lovastatin, prednisone, and carvedilol. At this stage antibodies directed against which of the following proteins is most likely to be positive? • A. Cardiolipin. • B. Double-strand DNA. • C. Histone. • D. Ribonucleoprotein (RNP). • E. Ribosomal .

•

A 69-year-old woman with a 5-year history of intermittent left knee pain owing to osteoarthritis presents to your office 5 days after vacationing in Greece, where she developed increased knee pain and swelling. She says that she had been walking and climbing more than usual on this vacation. She and some of the vacationers in her group developed watery diarrhea around the same time, but there were no chills or fever. She had been treated with naproxen until 2 years ago, when she developed atrial fibrillation. She now takes acetaminophen as needed for knee pain and takes warfarin for the atrial fibrillation. Physical examination shows a temperature of 38 °C (100 °F). There is a large effusion in the left knee, with increased warmth but no redness. There is moderate tenderness and pain on motion, and she walks with a limp, which she did not have before. The other joints are unchanged. Laboratory studies Hemoglobin 13.7 g/dL Hematocrit 42% Leukocyte count 10,000/µL Neutrophils 80% INR 2.1 Left knee radiograph reveals changes of osteoarthritis and an effusion. Which of the following would you do next? (A) Obtain stool culture and start treatment with ciprofloxacin. (B) Reduce warfarin dose and start treatment with celecoxib. (C) Order MRI of left knee. (D) Perform arthrocentesis. (E) Admit to hospital and start treatment with intra- venous ceftriaxone.

A 28-year-old woman presented with fatigue and extreme tiredness. Physical examination revealed facial skin rash and tenderness across the small joints of the hands. She was concerned that she might have systemic lupus erythematosus (SLE). Which of the following tests when NEGATIVE will virtually exclude the diagnosis of SLE? • A : Antinuclear antibody (ANA) • B : Anti-double stranded DNA (Ads-DNA) • C : Anti-Sm antibodies • D : Anti-histone antibodies • E : Anti-Ro/SSA antibodies.

35. A 60-year-old-man complained of pain in both wrist evolving over 8 weeks. He noted swelling around that area but denied stiffness. On examination there was swelling and tenderness just proximal to the wrist joints without limitation of movement. There was also prominent finger clubbing. Radiographs revealed periosteal reaction over the lower end of the radius and ulnar. Each of the following disorders could be the cause behind this patient complain EXCEPT? • A : Mesothelioma • B : Bronchiectesis • C : Diabetes mellitus • D : Crohn's disease • E : Whipple's disease.

THANK YOU

Rheumatology

*

SYNOVIAL FLUID ANALYSIS

FEATURE

Normal

NONINFLAMMATORY (eg osteoarthritis)

WBCs/m m3

<200

200- 2000

INFLAMMATORY (eg RA, crystal-induced, spondyloarthropathies, connective tissue dz, HOA)

2000 -50.000

SEPTIC

>100,000

Polymalgia Rheumatica Diagnostic Criteria for PMR • Age >50. • ESR>40mm/h. • Neck/bilateral shoulder / pelvic girdle AM stiffness. Symptomatic episodes > 1h in duration. Clinical history >1 month duration. • Response to low-dose (15mg/day) steroids.

• Remember, PMR patients complain more of stiffness than pain. • • • • • • •

Minor criteria include: Weight loss; fever; night sweats,Synovitis. Symmetrical proximal muscle tenderness( no weakness). Alk phos / GGT. Normocytic anemia. Normal CPK, EMG, muscle biopsy. 50% of all PMR patients (±TA symptoms) will be found to have giant-cell arteritis on TA biopsy.

fibromyalgia • • • • • • •

Diagnosis of exclusion. Female > male . Pain must be present for > 3m. Multiple tender points at least 11points . Pts are poorly able to localize the pain. Nervousness is frequent concomitant. TTT: Aerobic exercise. TCA. ( Tricyclic antidepressant).

DD OF MORNING STIFFNESS/ PAIN WORSE IN AM • Rheumatoid arthritis. Difficulty doing up buttons • Ankylosing Spondylitis. LBP + stiffness radiating to buttocks and thighs • polymaylgia Rheumatica (PMR) Difficulty getting out of bed • Fibromyalgia

Osteoarthritis • Bouchard’s nodes are proximal interphlangeal nodes. • Heberden's nodes are distal interphalangeal nodes. • X ray features of osteoarthritis are: joint space narrowing ,osteophytes , subchondral sclerosis & subchondral cysts.

Rheumatoid arthritis

Seven diagnostic criteria for Rheumatoid arthritis • • • • • • • •

Morning stiffness. Arthritis of ≥3 joint area. Arthritis of the hand joint. Arthritis symmetric. Rheumatoid nodules. Serum Rheumatoid factor. Radiographic changes. * In order to have RA, you must have 4 of the 7 criteria present for at least 6 weeks.

Symptoms and signs • Predominantly peripheral joints are affected symmetrical joint pain, effusions, soft tissue swelling, early morning stiffness. Progression to joint destruction and deformity.

Nodes and nodules in rheumatic diseases 1. Heberden's nodes DIP osteophytes in 1ryOA. 2. Bouchard's nodes PIP osteophytes in 1ry OA. 3. Rheumatoid nodules. 4. Gouty tophi (elbow, ears, heels, PIPs, DIPs). 5. Xanthomata.

Investigations • Check FBC (normochromic normocytic ), ESR, and/or CRP, platelets &WCC are increased. • Rheumatoid factor and anti-CCP antibodies are +ve in the majority 60- 70%. A minority have a +ve ANA titre. • X-rays normal, periarticular osteporosis or soft tissue swelling in the early stages; • Later---- loss of joint space, erosions, and joint destruction.

RHEUMATOID ARTHRITIS

OSTEOARTHRITIS

ETIOLOGY

Autoimmune disease

Degenerative disease

PATTERN of symptoms

Morning stiffness

Worse after effort or as activity progresses, relived by rest

Predominant HAND joint involvement

PIP, MCP, wrists (symmetric)

CMC, PIP, DIP

LAB

+RF, ESR and C-reactive protein

Normal RF, ESR, CRP

XRAY findings

1. Periarticular osteopenia. 2. Marginal bony erosions. 3.Symmetrical narrowing of the joint space.

1. Osteophyte formation 2. Subchondral sclerosis (no periarticular osteopenia) 3. Joint space narrowing.

DD of symmetrical polyarthropathy • • •

Rheumatoid Arthritis. Viral arthropathy. Psoriatic polyarthropathy.

DMARDs (Disease- modifying antirheumatoid drugs): 2 Key Points: • Do not wait to start patients on DMARDs until they have failed multiple courses of NSAIDs but, as soon as the diagnosis of RA is confirmed. • Methotrexate is the DMARD of choice in patients with severe disease. Start therapy with 7.5mg weekly and raise the dosage at 1intervals until peak efficacy is achieved.

* DMARD Therapy for RA ("GOLD PILE SCAM") DMARD

Potential Toxicities Requiring F/U

Monitoring Studies

Gold IM and PO

Myelosouppression, proteinuria

CBC and urine dipstick for protein

Penicillamine

Myelosuppression, proteinuria

CBC and urine dipstick for protein

Infliximab (Remicade)

Flu-like sx, auto-Abs; for patients not responding to methotrexate; given IV

None

Leflunomide (Avara)

Thrombocytopenia, hepatotxicity, diarrehea

CBC and AST

Etanercept (Enbrel) (a TNF – blocker)

Reactions at site of SQ injection, flu-like sx

None

Sulfasalzine

Myelosuppression

CBC, AST, creatinine

Cyclophosphamide

Myelosuppression, myeloproliferative disorders, malignancy, hemorrhagic cystistis

CBC, urinalysis, and urine cytology

Cyclosporine

Renal insufficiency, anemia, HTN, hirsutism

creatinine, CBC, K+, LFTs

Azathioprine

Myelosuppression, hepatotoxicity, lymphoproliferative disorders

CBC

Antimalarials (Hydroxycholorquine)

Macular damage

Yearly fundus exams

Methotrexate

Myelosuppression, hepatic fibrosis, pulmonary infiltrates or fibrosis

Minocycline

Photosensitivity, skin discoloration, GI upset, druginduced hepatitis, dizziness

cirrhosis,

CBC, AST, albumin

None

Juvenile chronic arthritis • is rheumatoid factor negative. • Different classifications are systemic, pauciarticular and polyarticular. • Commonest type is Still’s disease.( Systemic onset juvenile R.A ). Peaks of disease are about 5 years and 15 years of age. • Typical diagnostic criteria include High spiking fevers; arthralgias/ macular rash, hepatomegaly, splenomegaly, lymphadenopathy, serositis (pleuritis, pericarditis), seronegativity (-veRF; -ve ANA); leucocytosis. Thrombocytosis. • Very high serum ferritin.

Diagnosis of Felty's Syndrome • Neutropenia caused by hyperslenism and antineutrophil antibodies in a patient with long term rheumatoid arthritis. • Triad of Neutropenia; Seropositive RA; Splenomegaly /hyperslenism. • Frequent concomitants • Serious infections • Anemia, thrombocytopenia. • Leg ulcers • LN, Hepatomegaly • Sjogren's synd. • Weight loss.

Still's Disease

Felty's Syndrome

WBC--inc

WBC---dec

Fever

No fever necessary

Seronegative RA

Seropositive RA

Splenomegaly

splenomegaly

Systemic lupus erythematosus • • • • • • • •

9:1.and Asians. Onset 15-40y. Presentation is variable multisystem involvement must be demonstrated to make a diagnosis: Joints (95%)arthritis, arthralgia, myalgia, tenosynovitis Skin (80%)photosensitivity, facial butterfly rash, vasculitis, hair loss, urticaria, discoid lesions Lungs (50%)pleurisy, pneumonitis, effusion, fibrosing alveolitis Kidney (50%)proteinuria, BP, glomerulonephritis, renal failure Heart (40%)-pericarditis, endocarditis CNS (15%)depression, psychosis, infarction, fits, cranial nerve lesions. Blood; anaemia, thrombocytopoenia, splenomegaly

Diagnostic criteria for SLE • 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

4 of 11 for 6 weeks; butterfly rash discoid rash. Photosensitivity Oral ulcer Arthritis Serositis Nephrological; lupus nephrotis Neurological Hematologic; lymphopenia, thrombocytopenia. Immunological; anti DNA ANA

• • • •

Treatment; Skin only chloroquine. JOINT only; NSAIDs. Other extraarticular; steroid & other immunosuppressants.

Drug-induced lupus • Occurs with minocycline, isoniazid, hydralazine, procainamide,BB, chlorpromazine, sulfasalazine, losartan, and anti-convulsants. Remits slowly when drug is stopped but may need steroid treatment to settle. • No nephrological, no neurological, • DNA –ve • Anti histone Ab +ve.

TYPES OF ANTINUCLEAR ANTIBODIES (ANA) Following detection of a high titer of ANAs (e.g. 1:160), various subtypes are determined. Examples include: • Anti-dsDNA (double-stranded DNA) specific for SLE • Anti- histones Drug induced lupus • Anti-chromatin= anti-nucleosome antibodies. • Anti-ENA (Extractable nuclear antigen)=non-DNA = RNP – – – – – –

Anti-Ro (SS-A) Anti-La (SS-B) Anti-Sm (Smith antigen) Anti-U1RNP (nuclear ribonucleoproteins) Anti Scl-70 (topoisomerase I) Anti-Jo

• Antinucleolar20% of systemic sclerosis . • Anti-centromere • Antibodies to nuclear pore proteins as anti-gp- APA.

Anti-ENA (Extractable nuclear antigen) • Ro/SSA  Sjögren's syndrome , 40% SLE, ANA -ve SLE, subacute cutaneous LE & neonatal LE. • La/SSB 1ry Sjogren. • Anti- Smith (Sm) Ab is very specific for SLE, but only in 25 % . • Antibodies to U1-RNP 100% of MCTD, 30-40 % of SLE (+ anti- Smith) & small proportion of patients with localized (linear) scleroderma. • Antibodies to topoisomerase I (Scl-70), RNA polymerases I and III  systemic sclerosis related disorders. • Anti-Jo1 PM especially with IPF.

• Chromatin= histones + DNA. •

Anti-chromatin= anti-nucleosome antibodies.

DD of sponylitis 1. Sero –ve Spondyloarthoropathies. 2. infections. ( TB , Brucella ).

Spondyloarthoropathies A- HLA-B27 Rheumatic Diseases:

1. 2. 3. 4. 5.

Ankylosing Spoondylitits (<90% are HLA-B27). Reiter's Syndrome or Reactive arthritis (<80%). Enteropthic spondylitis (75%). Psoriatic Spondylitis (50%).

B- Characteristis: • 1- Sacroiliac joint involvement. • 2- Peripheral arthritis (usually asymmetric and oligarticular). • 3- Seronnegativity (absence of RF or other autonatibodies). • 4- Association with HLA-B27. • 5- Relatively early age of onset (<40). • 6- Enthesopathy. • 7- Anterior uveitis. • 1- Radiographic findings: • a) Erosions. • b) Syndesmophytes. • c) Bamboo spine. • D) fusion. • 2- Enthesopathic involvement • a) Plantar fasciitis. • b) Achilles tendonitis. • 3- Iritis (an important clue in spondyloarthropathies).

ankylosing spondylitis

Schober's test

• Schober's test assesses the amount of lumbar flexion. In this test a mark is made at the level of the posterior iliac spine on the vertebral column, i.e. approximately at the level of L5. The examiner then places one finger 5cm below this mark and another finger at about 10cm above this mark. The patient is then instructed to touch his toes. If the increase in distance between the two fingers on the patients spine is less than 5cm then this is indicative of a limitation of lumbar flexion.

• TTT; 1. Symptoms modifying; NSAIDS 2. Disease modifying; infliximab, methotrexate.

• Reactive arthritis Often asymmetrical aseptic arthritis Occurs 2-6wk. after bacterial infection elsewhere e.g. gastroenteritis (salmonella, campylobacter), GU infection (chlamydia, gonorrhoea). • Management: NSAIDs, physiotherapy, and steroid joint injections. Recovery usually occurs within months. A minority develop chronic arthritis requiring disease-modifying drugs. • Reiter's syndrome: Polyarthropathy, urethritis, conjuctivitis. Affects men with HLA B27 genotype. Commonly follows GU or bowel infection. Joint and eye changes are often severe. characteristic mucocutaneous changes oral ulcers , circinate balanitis , keratoderma blenorragicum.

• Enteropathic spondylarthropathy Oligoarticular or polyarticular arthritis linked to inflammatory bowel disease. Includes sacroiliitis, plantar fasciitis, inflammatory spinal pains, and other enthsitides (insertional ligament/tendon inflammation). Arthritis may evolve and relapse/remit independently of bowel disease. NSAIDs may help joint pain but aggravate bowel disease.

circinate balanitis

Psoriatic arthritis • Psoriatic arthritis • Inflammatory arthritis associated with psoriasis. RhF -ve. Presentation variable. Disease modifying drugs (e.g. methotrexate) may improve both skin and musculoskeletal symptoms . presents as several forms: • Symmetrical polyarthritis. • Arthritis involving DIP joints. • Asymmetrical oligoarthritis including dactylitis (70%) • Ankylosing Spondylitis type. • Arthritis mutilans.

Among the differentials of ank. Spond. Is DISH. (Diffuse Idiopathic Skeletal Hyperostosis, a form of 1ry osteoarthritis). • a) Patients with DISH are often obese and 60% have diabetes; • b) 'stiffness' at the spine' yet relatively well-preserved spinal motion. • c) Criteria for DISH…' – 'Flowing' ossification along the anterolateral aspects of 4 contiguous verterbral bodies with preservation of disk height. – Absence of SI joint involvement. – Intervertebral disk spaces are preserved.

• Marked calcification and ossification of paraspinous ligaments occur in DISH. Ligamentous calcification and ossification in the anterior spinal ligaments give the appearance of "flowing wax" on the anterior vertebral bodies. However, a radioucency may be seen between the newly deposited bone and the vertebtral body, • Differentiating DISH from the marginal osteophytes in spondylosis.

Diffuse idiopathic skeletal hyperostosis =DISH

vasculitis Group of diseases in which tissue ischemia and necrosis occur as a consequence of inflammation of blood vessels, either as a primary event or secondary to a systemic disease .1.Autoimmune dis. 2. Infection

•

3.Malignancy

4. drugs .

Large vessel vasculitis: chronic granulomatous reaction affecting the aorta and major branches.

•

Medium vessel vasculitis: necrotizing arteritis affecting visceral arteries renal artery leading to renal infarction .

•

Small vessel vasculitis: capillaries, venules, arterioles (glomeruli)leading to glomerulonephritis

..

Clinical Presentation

Constitutional symptoms. • Skin: purpura,ulcers , livedo reticularis , nail bed infarcts ,digital gangrene. • Eye :episcleritis ,ulcers and vision loss. • Lung: dyspnea, hemoptysis. • Cardiac: angina, myocardial infarction , heart failure. • GIT: abdominal pain, mesenteric ischemia,malabsorpt. • Kidney: hematuria, proteinuria, acute/chronic renal failure • CNS: Mononeuritis multiplex, sensorymotor neuropathy , convulsions, hemiplegia.

Names and definitions of vasculitides

Large vessel vasculitis • Giant cell (temporal) arteritis Granulomatous arteritis of the aorta and its major branches, with a predilection for the extra cranial branches of the carotid artery. Often involves the temporal artery. Usually occurs in patients older than 50 and often is associated with polymyalgia rheumatica. Presentation (classical) of Temporal Arteritis – Headache, scalp tenderness; jaw claudication; sudden visual loss.

• 50% of TA patients have symptoms of PMR. • Flase-negative biopsies may occur 2o to presence of "skip lesions" (if a 2cm biopsy is taken the false-neg rate is >5%; therefore a 3-5cm segment biopsy is recommended).

Takayasu's arteritis Granulomatous inflammation of the aorta and its major branches. Usually occurs in patients younger than 50. Middle aged women ½ 0f patients presents with initial systemic illness of malaise, fever, night sweats, weight loss, arthralgia, and fatigue then subside with more gradual vascular changes. The other half of patients with Takayasu's arteritis present with only late vascular changes, without an antecedent systemic illness. It is also known as "Pulseless disease" because pulses on the upper extremities, such as the wrist pulse, may not be able to be felt.

Medium sized vessel vasculitis • Polyarteritis nodosa. (classic polyarteritis nodosa) Necrotizing inflammation of medium-sized without glomerulonephritis or vasculitis in arterioles, capillaries, or venules.

• Kawasaki disease . Arteritis involving medium sized , and associated with mucocutaneous lymph node syndrome.

Fever of ≥5 days' duration associated with at least 4† of the following 5 change. Bilateral nonsuppurative conjunctivitis One or more changes of the mucous membranes of the upper respiratory tract, including pharyngeal injection, dry fissured lips, injected lips, and "strawberry" tongue One or more changes of the extremities, including peripheral erythema, peripheral edema, periungual desquamation.

Polymorphous rash, primarily truncal Cervical lymphadenopathy >1.5 cm in diameter its most serious effect is on the heart where it can cause severe coronary artery aneurysms in untreated children.

Differential diagnosis, including scarlet fever, toxic shock syndrome, juvenile idiopathic arthritis. • There is no specific laboratory test for this condition • Blood tests • CBC reveal normocytic anemia and eventually thrombocytosis • ESR will be elevated • CRP will be elevated • Other optional tests

• Electrocardiogram may show evidence of ventricular dysfunction or, occasionally, arrhythmia due to myocarditis . TTT: 1.Intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki disease[ 2.Salicylate therapy, particularly aspirin, remains an important part of the treatment

• • • • •

Polyarteritis nodosa Necrotizing vasculitis causing microaneurysms in the medium sized arteries. HBsAg Constitutional symptoms: Fever , abdominal pain,weight loss, arthralgia. Cardiac: coronary arteritis , hypertension , heart failure ,pericarditis. CNS: mononeuritis multiplex, sensorymotor polyneuropathy. seizures, hemiplegia.

• • • • • • • •

GIT: abdominal pain, malabsorption Skin : purpura, urticaria, infarcts, livedoreticularis. Blood: eosinophilia ,anaemia , ESR , CRP. Kidney: hypertension, hematuria, proteinuria, renal failure, intrarenal aneurysms. Testicular pain. ANCA is –ve. Diagnosis by nerve biopsy of affected nerve . If affected tissue not accessible ....visceral Angio.

Small vessel vasculitis ANCA Positive: • Wegener's granulomatosis Granulomatous inflammation involving the respiratory tract, and necrotizing vasculitis (Necrotizing glomerulonephritis is common). • Churg Strauss syndrome Eosinophil-rich and granulomatous inflammation, necrotizing vasculitis involving the respiratory tract, with asthma and eosinophilia. Microscopic polyangiitis (microscopic polyarteritis) Necrotizing vasculitis, with no immune deposits, affecting small vessels . Necrotizing glomerulonephritis is very common. Pulmonary capillaritis often occurs.

Small vessel vasculitis ANCA Negative: • Henoch Schönlein Purpura. Vasculitis, with IgA-dominant immune deposits. Typically involves skin, gut, and glomeruli, and arthralgia or arthritis. • Essential cryoglobulinaemic vasculitis. Vasculitis, with cryoglobulin immune deposits, affecting small vessels, and associated with cryoglobulins in serum. Skin and glomeruli are often involved. Cutaneous leucocytoclastic angiitis . Isolated cutaneous leucocytoclastic angiitis without systemic vasculitis glomerulonephritis.

What is ANCA? • Autoantibodies against intracellular neutrophil antigens. • C-ANCA cytoplasmic anti PR3. • P-ANCA perinuclear anti MPO.

vasculitis with a predilection for renal involovement? • Small vessel vasculitis.

• Medium vessel vasculitis : PAN • How does vasculitis affect the kidney? • Urine analysis shows RBCs ,red cell casts and proteinuria common but usually < 3 gm. • Pathology The shared glomerular lesion of the pauci-immune smallvessel vasculitides is a necrotizing glomerulonephritis with crescent formation. Early lesions have segmental fibrinoid necrosis with or without an adjacent small crescent. Severe lesions have global necrosis with large circumferential crescents. Renal arteritis affecting the interlobular arteries.

Wegner granulomatosis Necrotizing granuloma in the respiratory tract(nasal ulcers, epistaxis , sinus involvement, otitis media, oral ulcers ,proptosis). hemoptysis Rapidly progressive glomerulonephritis. C-ANCA +ve in 70%

Wegener Granulomatosis Clinical Presentation • upper respiratory tract • Lung involvement in 80%; transient infiltrates or nodular densities may be seen on (CXR) Histopathology (1) vasculitis of small vessels, (2) granulomatous changes, (3) focal necrosis LM :segmental necrotizing. crescents ● IF: Pauci-immune GN; crescents; tubulointerstitial granulomas ● EM: No immune deposits are seen Laboratory Diagnosis cANCA is specific and sensitive 20% to 30% have pANCA

Segmental fibrinoid necrosis with nuclear debris and glomerular basement membrane disruption, typical of early stage of pauci-immune crescentic glomerulonephritis

Well-developed cellular crescent with collapse of small amount of remaining glomerular tuft with segmental fibrinoid necrosis and extracapillary fibrin and necrosis

Churg-Strauss Vasculitis • • • • • • • • • • •

Small vessel vasculitis . eosinophilic pulmonary infiltrates Allergic rhinitis. Nasal polyposis. Asthma Eosinophilia Necrotizing inflammation Almost no kidney affection glomerulonephritis is usually (but not always) mild. Associated with leukotriene antagonist therapy, P-ANCA Usually in 60%. (MPO) positive. +ve

• • • •

Microscopic polyangitis Small vessel vasculitis Absence of asthma ,eosinophilia,necrotizing inflammation. P-ANCA is +ve in 50% Kidney : Rapidly progressive glomeruloneph.

Treatment for ANCA-associated disease ● combination of glucocorticoids (1 mg/kg/d) and IV or oral cyclophosphamide (2 mg/kg/d) for 1 year after remission. ● methylprednisolone at 7 mg/kg/d IV for 3 days, then oral prednisone at 1 mg/kg/d. plasmapheresis in who RPGN or pulm Hge. ● Sulfamethoxazole/trimethaprim may diminish relapse rates. Course and Prognosis ● 90% 1-year mortality if left untreated, 90% remission if treated. ● Relapse occurs in 25% to 50% of patients followed up for 3 to 5 years

Henoch-Schönlein purpura systemic vasculitis mostly seen in children. It is a multisystem disorder involving the skin, joints ,gastrointestinal and renal tracts. •

Aetiology is unknown, but the syndrome is often preceded by infections such as Group A beta hemolytic streptococcal

•

Pathology

•

Patients often present with a skin(palpable purpuric eruption purpuric rash usually involving the buttocks and lower limbs, arthralgia and severe colicky abdominal pain and tenderness caused by vasculitis-induced thrombosis in the gut. Renal involvement commonly presents as microscopic haematuria and proteinuria Hematuria 50%/asymptomatic hematuria proteinuria 40%, nephrotic

•

is due to intravascular deposition of IgA immune complexes.

syndrome ,acute and chronic renal failure.

•

•

Similar to IgA nephropathy , but crescents, are more frequent Immunoflorescence :IgA mesangial deposition.

Course. ● Overall good renal outcome; complete recovery

Therapy. ● Symptomatic for mild cases. ● For severe nephritis, treatment is steroids+/-cyclophosphamide.

Can complement levels help diagnosing vasculitis?

• Exclude infection. • Low in SLE ,Cryoglobulinemia . • Normal in ANCA +ve vasculitis.

essential mixed cryoglobulinemia • essential mixed cryoglobulinemia was appropriate. complexes in which one component, usually IgM, exhibits antibody activity against IgG (i.e., mixed cryoglobulins). • The diagnosis of mixed cryoglobulinemia is typically made from the history, skin purpura, low complement levels, and demonstration of circulating cryoglobulins.

CLINICAL PRESENTATION of Mixed Skin manifestations CGs • • • • • •

Palpable purpura (80% in mixed types) Ischemic necrosis ( 020% in mixed types) Livedoid vasculitis (1% in type I, 14% in type III) Cold-induced urticaria (15% in type I, 10% in type III) Acrocyanosis Nailfold capillary abnormalities

Musculoskeletal manifestations • Arthralgias (5% of type I, 20-58% of mixed) • Frank arthritis and progressive joint deformity (distinctly rare)

such as arthralgias and myalgias are common in the mixed CGs, but frank arthritis or myositis are rare to uncommon., especially affecting the metacarpophalangeal, proximal phalangeal, knees, and ankles, • Neuropathy — Sensorimotor neuropathy affects a high percentage of mixed, but clinically significant neuropathy is uncommon., Visual disturbances

Renal manifestations • • • •

Membranoproliferative glomerulonephritis described in all types (more common in type II) Intraluminal cryoglobulin deposition Hypertension Nephrotic-range proteinuria with resultant edema

Pulmonary manifestations • • • •

Dyspnea Cough Pleurisy Pleural effusions

Gastrointestinal manifestations • • •

Abdominal pain (2-22%) Hemorrhage Hepatomegaly or signs of cirrhosis (ie, palmar erythema, abdominal wall collateral vessels, spider angiomata)

• abnormal liver function tests • •

Splenomegaly lymphadenopathy

Cryoglobulinemic Glomerulonephritis can be differentiated from idiopathic MPGN by the following findings . • (1) Intracapillary thrombi the presence of large deposits filling the capillary lumen. • (2) Massive infiltration of capillary spaces by monocytes and polymorphonuclear cells (the exudative component ). • (3) possibly some vasculitis in small and mediumsized renal arteries .(25% to 33%). • The combination of vasculitis and glomerular thrombi should suggest cryoglobulinemic nephropathy, but proliferative lupus nephritis with associated vasculitis is also in the differential diagnosis.

• Aggressive therapy in idiopathic mixed cryoglobulinemia reserved for patients with acute severe disease (manifested by progressive renal failure, distal necroses requiring amputation, or advanced neuropathy). • plasmapheresis (remove the circulation cryoglobulins) with steroids (1000 mg of intravenous methylprednisolone daily for three days , followed by oral prednisone) and cyclophosphamide. • Rituximab is a promising alternative treatment option for severe cryoglobulinemic vasculitis and nephritis.

( Hughes Syndrome),

Anti-Phospholipid Syndrome

• disorder characterized by multiple different antibodies that are associated with both arterial and venous thrombo.

.

• There are three primary classes of antibodies associated with the antiphospholipid antibody syndrome: • 1) anticardiolipin antibodies. • 2) the lupus anticoagulant . • 3) antibodies directed against beta-2glycoprotein 1.

Sensitivity and Specificity for APS APL Test

Sensitivity

Specificity

ACL

80-90%

Low

LA

Moderate

High

2-GP I

74%

85%

APhL

91%

99%

Harris. Lupus, 1998.

• A patient must meet at least one clinical and one laboratory criterion for a diagnosis of APS

Thrombosis • • • •

Venous and arterial circulations Embolic risk high Venous > Arterial Occurs in any system or organ with any part of vascular tree involvement possible(Largesmall) • Single or multiple vessel involvement • Recurrent events common

Catastrophic anti-phospholipid syndrome (CAPS)

• This syndrome, termed "catastrophic antiphospholipid syndrome," is defined by the clinical involvement of at least three different organ systems over a period of days or weeks with histopathological evidence of multiple occlusions of large or small vessels.

• steroids or aggressive immunosuppression is not used unless recurrent thrombotic or ischemic events despite high intensity warfarin therapy. • High dose steroid is reserved for treatment of underlying active lupus and not for lab antiphospholipid AB.

Rituximab • Is a humanized mouse monoclonal antibody against the B cell antigen CD20 that results in the prolonged depletion of B cells. • CD20 is relatively selectively expressed on preB and mature B cells, but not plasma cells or T cells, and may selectively treat antibodymediated disorders with less immune suppression than other treatment regimens.

Vasculitis mimickers

• • • • • •

Subacute bacterial endocarditis. Left atrial myxoma HIV Paraneoplastic syndrome Cholesterol embolization Cocaine and amphetamine use.

•

• • •

Treatment Combined treatment with steroids and cyclophosphamide induces remission in 75% of ptns at 3months and 90% at 6 months. Pulse steroid therapy 7mg/kg for 3 days(IV methyl prednisone) IV cyclophosphamide therapy 0.5g/m2 monthly reaching 1g/m2 based on the leucocyte count. Role of plasma exchange is controversial ,beneficial in dialysis dependant renal failure patients and those with pulmonary hge .

Crystal induced Arthropathy

A 48-year-old gentleman presented with arthritis of rigt ankle for one day. .. S.uric acid : 7.8 .. Synovial fluid : inflammatory with MSU crystals .. 24-h urine uric acid : 1200 mg. The most likely cause. 1- hyperparathyroidism 3- MPD 5- thiazide therapy

2- hypothyroidism 4-Lactic acidosis

A 52-year-old lady , diagnosed to have gouty arthritis two years back with synovitis right MTP1., subsided with local steroid injection. .. No further attacks since then ..s.Uric acid ranging from 6.8 – 8.2 ..s.cr : o.8 , No renal stones .. No tophi. .. She has to start Allopurinol ** YES ** NO

A 58-year-old gentleman , first attack of gout in R knee persistent in the last 6 days .. The drug to be least effective at this stage : 1- NSAID 3- Colchicin 5- Oral PDN

4- local steroids

A 52-year-old gentleman upon the first attack of gouty arthritis in L MTP1, started Colchicin for the last 2 weeks. Inflammation subsided .. S.uric acid now is 13 , supposed to start Allopurinol .. You will combine Colchicin until : 1) 3 months 2) 6 months 3) s.U.A < 6 4)s.U.A < 7 5) 6-months after s.U.A < 6

A 48-year-old lady accidentally discovered to have s.UA of 8 mg% .. 24-h urine uric acid was found 1200 mg .. Best way of management : 1) Start Colchicin 2) Observation with regular monitoring 3) Start Prebencid 4) Start Allopurinol 5) Start Allopurinol & Colchicin

A 54-year-old male , diagnosed as gouty arthritis, first attack. .. S.UA : 8 .. S.creatinin : 1.8 .. C.cr : 35 ml/min Best way of managemeent : 1) Colchicine 0.5 mg OD 2) Colchicine 0.5 mg BD 3) Avoid Colchicine

A 52-year-old lady, four weeks after first attack of gouty arthritis, lab. Investigations revealed : .. S.UA : 10 .. S.cr : 1.9 .. Ccr : 40ml/min Best way of management : 1) Start Allopurinol 50mg/d,increase to 100 after 2w 2) ,, ,, 100mg/d ,, 200 ,, 3) ,, ,, 300 mg/d 4) ,, ,, 100mg/d, build up to 300mg 5) No need for Allopurinol.

Hyperuicemia Gout – negatively birefringent crystals Hyperuicemia is either 2ry to overproduction (> 800mg / d) 10% or underexcretion (<600mg / 24hrs) 90% . Causes of underexcretion . HARD to .. HTN. Hypothyroidism. Hyperparathyroidism. Acidosis. Renal insuffeciency. Drugs( thiazides duiretics, Alcohol)

Causes of overproduction • Tissue damage . (Rhabdomy, tumor lysis, hemolytic process, exercise). • Proliferative disorders.( mylo& lymphoprolif, psoriasis) • Gout is associated with : Hypertriglyceridaemia, diabetes, obesity.

serum hyperuicemia is neither necessary nor sufficient to make the diagnosis of gout. A synovial fluid aspirate is necessary for definitive diagnosis. Always remember, for definitive diagnosis, to send the synovial fluid for crystal analysis, gram stain. • Alcohol/diet/diuretics are the most common cause of acute gout in the outpatient population. • Gout is very uncommon among premenopausal women.

When to treat asymptomatic hyperuricemia? ** Three specific circumstances warrant at least consideration for institution of hypouricemic drugs : 1) Persistent s.urate >13mg/dl in men and >10 mg/dl in women 2) Excretion of U.uric acid >1100 mg/d is associated with 50% risk of uric acid calculi. 3) Patient about to receive radio or chemotherapy that is likely to result in extensive tumour lysis

• Renal disease is a limitation for both allopurinol & colchicine. With allopurinol, there is a consensus that you need to start with a lower dose and only gradually increase it. • Uricosurics are not effective if the serum urate is over about 12 mg/dL, Uricosurics also increase the risk of nephrolithiasis. • colchicine works only if you use it fairly early in the attack.

• Benzbromarone — Benzbromarone, a uricosuric agent that reduces serum uric acid levels in transplant recipients with hyperuricemia and gout. • Benzbromarone is an effective uricosuric, even in patients with creatinine clearances as low as 20 mL/min

1. Treat acute flares with antiinflammatory drugs; NSAIDs, colchicine or steroids. 2. Initiate urate lowering drug (Allopurinol) weeks after any acute flare. 3. Choose effective & safe drug e.g. allop allergy, renal disease. 4. Protect against flare from urate lowering drug by adding anti-inflamatory for 6 months after achieving the target. 5. Continue life style modification 6. Monitor/ 2-4 wks till target uric acid< 6 mg/dl. 7. Then Monitor every 6-12 months.

Pseudogout • Inflammatory arthritis due to deposition of pyrophosphate crystals. Chondrocalcinosis may be seen on X-ray (calcification of articular cartilage). Knee, wrist, and shoulder are most commonly affected. causes are: • Haemochromatosis. • wilson's disease . • Hypothyroidism. • hyperparathyroidism. • hypomagnesaemia. • hypophosphataemia • Amyloidosis. • Aging.DM • Chronic renal failure on dialysis. • Acute attacks can be triggered by intercurrent illness and metabolic disturbance. Attacks are less severe than gout and may be difficult to differentiate from other types of arthritis. Presence of joint crystals confirms diagnosis. • Pseudogout – positively birefringent crystals .

Pseudogout (calcium pyrophosphate "CPPD") • Can mimic and coexist with gout. • similar to gout, surgery, trauma, and alcohol may precipitate. • Treatment options are similar to gout, except for allopurinol. • Pseudo gout, is Positively birifringent under polarized light microscopy.

A 68-year old man presented with sudden severe pain and swelling in the left knee. Synovial fluid analysis shows abundant calcium pyrophosphate dihydrate (CPPD) crystals. Which of the following tests is NOT appropriate for further assessment of this patient illness? A : Creatinine kinase B : Serum calcium C : Thyroid function test D : Serum ferritin level E : Hb AIc.

Crystal Analysis: Gout Versus Pseudogout Feature

Gout

Pseudogout

Monosodium urate

Calcium pyrophosphate

Color under polarized light

Yellow

Blue

Shape of crystal

Needle

Rhomboid

Negative (counterclockwise)

Positive (clockwise)

Crystal

Birefringence/ rotation under polarized light direction

PseudoPseudogout ( calcific tendinitis) • Pain on adduction more with active movement. • Characterized by deposition of hydroxy appetite crystals within rotator cuff muscle near humeral attachment most commonly involve supraspinatus tendon. • Severe shoulder pain localized mainly to humorous diffusely around antrolateral shoulder. • Palpation or compression around the greater tubercle of the humerus causes tenderness. • X ray : linear calcific density in supraspinatus tendon. • Ttt: intralesional steroids & physiotherapy.

70 years old lady complaining of gradually progressive bilateral lower limb oedema

Paget disease of bone

Paget disease of bone

Paget disease of bone • What are the manifestations? • What are the serious complications? • What are the biochemical abnormalities? • What is the treatment?

Paget's disease of bone • • • • • • • • • • • • • • • • •

Accelerated, disorganized bone remodelling due to abnormal osteoclast activity. Affects up to 1:10 of the elderly but only a minority are symptomatic. Presentation. Skeletal Pain ,deformity & fracture. Deformity bowing of weight-bearing bones, especially tibia, femur, Frontal bossing. High COP failure. Complications Pathological fractures; O Arthropathy of adjacent joints. cranial nerve compression., neurological symptoms e.g. deafness, bone sarcoma (10% of those affected >10y.). Investigation. X-ray Distinctive changes; Alk phos--->very high. normal Ca2+, PO4, PTH, bone scan...diffuse density. Urinary hydroxyproline. Management pain and long-term complications with bisphosphonates (e.g. risedronate 30mg/d. for 2mo.).

Paget disease of bone •Pain,deformities,fractures. •Hyperdynamic circulation •Marked increase of alkaline Phosphatase •Bone scan

Bone scan Normal:

The radioactive tracer is evenly distributed among the bones. No areas of abnormally high or low accumulation are seen.

Abnormal:

The tracer may accumulate in certain areas of the bone, indicating one or more hot spots. Hot spots may be caused by a fracture that is healing, bone cancer, a bone infection (osteomyelitis), arthritis, or a disease of abnormal bone metabolism (such as Paget's disease).

Bone scintigraphy

Normal bone scan.

Bone metastasis

Bone metastasis Paget disease of bone

Pulmonary osteodystrophy

• Hypertrophic osteoarthropathy (or hypertrophic pulmonary osteoarthropathy when there is mesothelioma or bronchogenic carcinoma associated) • X rays show periosteal reaction at the ends of the radius and ulnar bones suggestive of periostitis.

Osteomalacia • Osteomalacia is characterized by a low serum calcium and phosphate with elevated serum alkaline phosphatase. Osteomalacia may be caused by deficiency of vitamin D or phosphate deficiency. • Skeletal x-rays – osteomalacia present with the pathognomonic Looser zones are linear areas of low density surrounded by sclerotic borders, – better observed in the pubic ramus, upper femoral bone, and ribs.

• Treatment is with a daily dose of calciferol (20-25 micrograms).

Vitamin D deficiency (osteomalacia)

• Nutritional deficiency • Impaired absorption ; Small bowel diseases, such as celiac disease, gastric bypass, steatorrhea, and pancreatic diseases.

• Hepatic disease impaired 25-hydroxylation of vitamin D, decreased bile salts with malabsorption of vitamin D, decreased synthesis of vitamin D–binding protein, or other factors. vitamin D dysfunction.

• Anticonvulsants • Renal failure decreased conversion of 25-hydroxyvitamin D to its active form 1,25dihydroxyvitamin D. This results in an increase in PTH.

• Inherited conditions vitamin D dependent rickets (type I) or 1-alpha-hydroxylase deficiency . vitamin D dependent rickets (type II )--- Hereditary vitamin D resistance rickets.

X-linked hypophosphataemic Vit D resistant rickets. • serum phospate is low and urine phosphate is high due to inappropriate renal phosphate wasting. • Serum parathyroid levels are usually slightly elevated. Clinically, growth retardation that causes very severe rickets, especially in affected males. • Treatment is with oral phosphate and high dose activated Vitamin D.

Bone Disease

Serum calcium

Serum phosphorus

Alkaline phosphatase

osteoporosis

n

n

n

osteomalacia

↓

↓

↑

Paget disease

n

n

↑↑

Primary

↑

↓

hyperparathyroidism

↑

Renal osteodystrophy

↓

↑

↑

X-linked hypophosphat aemic Vit D resistant

n

↓

↑

Behcet's Syndrome • Immune mediated vasculitis, venulitis. • Equal sex affection but more severe in males ,Eastern Mediterranean and Asia . C/P; • Painful Genital ulcers. • Painful Oral ulcers (98%). • Ocular disease ( 80%); more common in HLA B5 men; eg uveitis. iritis, retinal vessel occlusions and optic neuritis can be found. Hypopyon uveitis • Skin; E.nodosum ( 80%); (F
Behcet’s

Sjögren syndrome • • •

•

Sjögren syndrome (SS) is a systemic chronic inflammatory disorder characterized by lymphocytic infiltrates in exocrine glands. C/P; sicca symptoms; xerophthalmia (dry eyes), xerostomia (dry mouth), dyspareunia fatigue and parotid gland enlargement. extraglandular features ; arthralgia, arthritis, Raynaud phenomenon, myalgia, pancreatitis, leukopenia, anemia,LN, neuropathy, vasculitis, RTA, and later lymphoma (suspected if low C4, cryo, persistent parotid enlarg, purpura & leukopenia). Primary Sjögren syndrome occurs in the absence of another underlying rheumatic disorder, whereas secondary Sjögren syndrome is associated with another underlying rheumatic disease, such as SLE, RA, or scleroderma.

Inv; • ANA 90%, Anti RO & Anti La in 1ry SJ, • ESR, CRP, RF, hypergammaglobulinema in 80%. • Schirmer's test Management • artificial tears , cool drinks, artificial saliva sprays or sugar-free gum. • pilocarpine • NSAIDs, hydroxycholoquine for arthritis.

Dermatomyositis C/P; • proximal muscle weakness, tenderness. • Skin; Raynauld’s, Gottron's papules , heliotrope rash around the eye, calcinosis, periungual telangiectasia, mechanics hand, v shaped, shawl sign. • Others; • Dysphagia. • cardiomyopathy, • IPF. • The condition is associated with carcinoma of the breast, lung, ovary and bowel in old age only. Inv : • elevation of muscle enzymes; CPK, LDH, AST. • EMG; myopathic pattern (high frequency, low amplitude). • ESR, CRP ↑ in 5 % only. • Autoantibodies; - ANA - anti-jo-1(IPF, mechanics hand, Raynauld’s) - anti M2 (classic) - anti SRP (severe rapidly progressive) severe form with cardiac affection. • muscle biopsy; inflammatory changes . TTT; steroids rapid ↓CPK but power takes weeks+/- methotrexate, cyclophosphamide.

Scleroderma

Inv; • ANA in 90%, • RF in 30% • Anti-topoisomerase (= anti Scl 70, specific, in 30%) in diffuse scleroderma. • Anticentromere in 50-90% of limited & 10% of diffuse sclero. • Anti-RNA polymerase III in renal crises. Patterns; 1. Limited systemic; CREST S (calcinosis, raynaulds, esophageal dysmotility, scleroderma, telangiectasia), tight skin limited to face, neck, distal extremities. cause of death; pulmonary HTN. 2. Diffuse systemic; cause of death; renal crises, worse prognosis. 3. Localized to the skin; morphea (plaques), coup de sabre (linear). TTT; NSAIDs, PPI, antibiotics for bact overgrowth, VD, PG, Dpenicillamine, ACEI for renal crises.

Overlap Syndromes • E.g. mixed CT disease; SLE, Sclero, PM. +ve anti RNP.

Osteoporosis **A disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture . **Bone mineral density (BMD) T-score < –2.5

What are the major risk factors for osteoporosis? Non-modifiable 1) 2) 3) 4) 5) 6)

Age. Race ( Caucasian,Asian). Gender (female). Early menopause(<45) Slender built. Positive family history.

Modifiable 1) low ca. intake 2) low vit-D intake 3) estrogen deficiency 4) sedentary life 5) smoking 6) alcohol(>2drinks/d) 7) caffeine(>2serving/d 8) medications: (steroids-thyroxine)

Other conditions with low bone mass ** hyperparathyroidism ** Celiac d. ** hyperthyroidism ** Liver d. ** hypogonadism ** I.B.D ** cushing s. ** myeloma ** osteomalacia ** Renal failure ** Drugs : .. Steroids – thyroxine – cyc,A - heparin

How to interpret BMD

H

1)T-score : comparison of patient’s bone mass to that of young normal subject(age 30) 2)Z-score : comparison of patient’s bone mass to that of age-matched subject

indications for BMD:

**

1)Women aged 65 years and older . 2)Postmenopausal women< 65 years with risk factors for osteoporosis 3)Men aged 70 years and older . 4)Adults with fragility fracture . 5)Adults with a disease or associated with low bone mass or bone loss. 6)Adults taking medication associated with bone loss. 7)Anyone being considered for pharmacological osteoporosis therapy .

Pharmacologic therapy of osteoporosis • • 1. 2.

Ca, vit D Drugs that decrease bone resorption; HRT (E↑uterine cancer& breast cancer). SERM (selective Estrogen receptor modulators)= agonist on bone & antagonist on breast↓ osteoporosis, br cancer & IsHD. Side effects; flushes, DVT. - Raloxifen (Evista®)used in postmenopausal osteoporosis. 3. STEAR= selective tissue estrogenic activity regulator e.g. Tibolon (Levial ®) 4. Bisphosphonate (oral alendronate) 5. Calcitonin ; anabolic bone effect, Side effects; nasal congestion, rash. • Drugs that increase bone formation; 1. Synthetic PTH (Teripatide). 2. Strontium ranelate (Protelos) dual mechanism , incr bone formation & decrease bone resorption. 3. Others; GH, GHRH, IGF1, anabolic steroids, statins.

•

Ca, vit D; - ca alone; small effect on BMD, no antifracture effect. - Vit D alone; unknown effect in pt without vit D def. - Ca + Vit D; may ↑BMD, ↓fracture. • Raloxifen (Evista ®) 60 mg once daily - TTT & prevention postmenopausal osteoporosis. - adv; ↓vertebral fracture,but not non vert fracture, ↓ br cancer & ↓ IsHD. - Side effects; increase risk of DVT. not effective against non vert fracture. • Calcitonin; nasal spray, SC; ↓vertebral fracture ( weak evidence) , small ↑BMD.

HRT Thromboembolism, breast cancer, ↑TG, ↓ risk of fracture, cancer colon, ↑ HDL  ↓ coronary. Contraindications; - Absolute; • E dependant tumours; breast, endometrium. • Thromboembolic disorder. • Abn vaginal bleeding. - Relative; • FH of br cancer, • GB disease. • Endometriosis

• Alendronate (oral daily 10 mg or weekly 70 mg) - mech; taken up by osteoclast  apoptosis. - adv; effective against all fractures, long term benefit (10 yrs). - disadv; poor upper GIT tolerance. - contraindications; hypocalcemia, osteomalacia, renal failure, bed ridden, serious oesophageal dis. - side effects; hypocalcemia, ↑PTH, skin rash oral; esophagitis, ulceration. IV; flu like, arthralgia, myalgia, fever, leukopenia, eye inflammation etidronate; ↑phosphate, osteomalacia. • Teriparatide; rh PTH - daily SC, 1st anabolic, ↓ all fractures, marked & rapid ↑BMD. - disadv; daily SC, use restricted to high risk pts, osteosarcoma in toxicologic studies. - contraindication; bone dis; paget dis, Hx of bone metastasis or cancer, growing child, bone, hypercalcemia, pregnant, lactation.

The following subjects are candidates for BMD except : 1) A lady of 68 years 2) An obese lady at age of 52(menopause) 3) A man of 74 years age 4) A lady 34-year age with 1ry hyperparathyroidism

A 54-year-old lady advised to do BMD for persistent spine pain, Which revealed : ** T-score .. L.spine : -2.6 .. F.neck : -1.7 ** All are possible except : 1)Osteoporosis 2)Hyperparathyroidism 3)I.B.D 4)Hypothyroidism 5)Cushing d.

A 52-year-old lady, menopause for 3 years on longterm steroids for her uncontrolled chronic asthma ** BMD done for her revealed : T-score L.spine : -2.0 F.neck : -1.2 ** suggested treatment : 1)Calcium + vitamin-D 2)Calcium + vitamin-D + Alendronate 3)Calcium + vitamin-D + Alendronate + Calcitonin 4) No TTT

A 62-year-old lady presented with severe back pain , she lost about 2 inches of her height. Plain XR revealed farcture of T12 and wedged L3. She is immobile for severe knee OA and on steroids for ILD ** BMD advised revealing : T-score L.spine : -4.2 F.neck : -2.8 ** Best TTT is : 1) Ca + vit-D + Alendronate 2) Ca + vit-D + Calcitonin 3) Ca + vit-D + Teriparatide (PTH) 4) Ca + vit-D + Alendronate + Calcitonin

A 58-year-old lady admitted for fracture neck-femur ** BMD revealed : T-score L.spine : -1.6 F.neck : -2.8 ** The drug being least effective is : 1)Alendronate 2) HRT 3) PTH 4) Raloxifene ( SERM)

Gonoccocal arthritis is a common cause of septic arthritis in which the organism cannot be cultured on routine culture media. Occur in disseminated gonococcal infection. C/P; • sexually active individuals, ♀;♂ (4:1), ↑ during menstruation and pregnancy. • fever, chills, skin rashes( pustular) , polyarthralgias, and tenosynovitis  persistent monoarthritis or oligoarthritis, Inv; • The mean synovial fluid WBCs = 50,000 cells/mm3. • Cultures of synovial fluid tend to be positive in < 50 % of cases of gonococcal arthritis • The joint aspirate should be cultured for N. gonorrhoeae when the history is suggestive. ( chocolate agar or Thayer-Martin medium) • cultures from clinically appropriate sites (eg, the pharynx, urethra, cervix, rectum, and skin lesions). • Blood cultures are often positive in patients presenting with tenosynovitis and skin lesions alone, • PCR • screening test for HIV and a syphilis. • TTT; , the initial therapy of choice is ceftriaxone (1 gm either IV or IM) or another 3rd G cephalosporin. • Fluoroquinolones .

• • • • • •

Relapsing polychondritis Associated with autoimmune disease in 30%. Leads to fever, arthralgias, episcleritis, swollen floppy ears. Nasal Septum collapse (the other 'saddle nose' deformity, i.e. not just Wegener's). laryngeal disease – hoarseness; respiratory obstruction. Tracheobroncial degeneration – recurrent infections, AI/MVP/ Aneurysm in 10%.

Causes of avascular necrosis • SLE . • vasculitis & any hypercoagulable state. • long term steroids . • sickle cell disease. • Hip involvement. • MRI is the best diagnostic tool.

• Causes of Charcot’s joints: • • • •

diabetic neuropathy, syphillis syringomyelia leprosy

• Causes of Iritis: • • • •

Behcet's disease Reiter's syndrome ankylosing spondylitis sardoidosis

• Eosinophilic fasciitis is a disorder characterized by peripheral eosinophilia and fasciitis. Swelling and progressive induration of the skin associated with aching of the extremities and occasional morning stiffness develop over a period of weeks. The distribution most often is in the upper extremity, proximal and distal to the elbow, and in the lower extremity, proximal and distal to the knee. Onset may be acute following some sort of strenuous exercise, or it may be subacute. The diagnosis is confirmed by deep biopsy from skin to muscle.

Eosinophilic fascitis

Eosinophilic fascitis

Rheumatologic Manifestations of sickle cell disease • Gout. • Sickle lower extremity arthralgias (knees and ankles most common), myalgias, synovitis. • 2ry hemochromatotic (Fe overload 2o to frequent transfusions). • Septic arthritis (or osteomyelitis), esp due to Salmonella, particularly if hyposplenic. • Aseptic (avascular) necrosis.

Familial Mediterranean fever • AD • is an inherited condition characterized by recurrent episodes of painful inflammation in the abdomen, chest, or joints, fevers and rash. • The first episode usually occurs by the age of 20 years, but in some cases, later in life. • FMF primarily affects populations originating from the Mediterranean region. • A buildup of amyloid. AA amyloidosis commonly involves the kidneys, spleen and GI tract. • Colchicine given prophylactically in FMF offers some protection against the development of amyloidosis in most patients.

De Quervain's tenosynovitis • is inflammation of the abductor pollicis longus and extensor pollicis brevis. • Finkelstein's test is positive. This is performed with the thumb flexed across the palm of the hand, asking the patient to move the wrist into flexion and ulnar deviation. This stresses the tendons of abductor pollicis longus and extensor pollicis brevis and reproduces the pain of de Quervain's tenosynovitis.

• A 15-year-old boy presented with arthralgia, skin rash and haematuria. Renal biopsy showed focal • necrotising glomerulonephritis with diffuse mesangial IgA deposits. What is the most likely diagnosis? • A : Systemic lupus erythematosus (SLE) • B : Henoch–Scholein purpura • C : Juvenile rheumatoid arthritis • D : Post-streptococcal glomerulonephritis • E : Goodpasture's syndrome

• 24. A 64-year-old man presents to A&E with a 2day history of increasing pain and swelling of • his left knee. He denies a history of trauma. On examination, the knee is hot, red, swollen and • extremely tender. Which of the following investigations is most important? • A : Plain radiograph of the knee • B : Blood cultures • C : C-reactive protein (CRP) • D : Joint aspiration • E : Plasma uric acid level.

64-year-old man with congestive heart failure presents to the emergency room complaining of acute onset of severe pain in his right foot. The pain began during the nightand awoke him from a deep sleep. He reports the pain to be so severe that he could not wear a shoe or sock to the hospital.His current medications are furosemide, 40 mg twicedaily, carvedilol, 6.25 mg twice daily, candesartan, 8 mg once daily, and aspirin, 325 mg once daily. On examination, he is febrile to 38.5°C. The first toe of the right foot is erythematous and exquisitely tender to touch. There is significant swelling and effusion of the first metatarsophalangeal joint on the right. No other joints are affected. Which of the following findings would be expected on arthrocentesis? A. Glucose level of <25 mg/dL B. Positive Gram stain C. Presence of strongly negatively birefringent needleshaped crystals under polarized light microscopy D. Presence of weakly positively birefringent rhomboidal crystals under polarized light microscopy E. White blood cell (WBC) count >100,000/μL

A 36-year-old woman presents with deteriorating nocturnal paraesthesia affecting both hands. It improves during the morning. Which of the following tests is least likely to be helpful in establishing the cause? • A : Thyroid function test • B : Rheumatoid factor • C : Tinels test • D : MRI scan hands • E : Urinary hCG.

A 25-year-old woman with a history of 3-second trimester fetal losses is planning a fourth pregnancy. She has evidence of the primary anti-phospholipid syndrome (strongly positive cardiolipin antibody, positive lupus anticoagulant but no evidence of lupus). Which of the following treatment regimens offer her the best chance of having a successful pregnancy? • A : Steroids alone • B : Steroids combined with low-dose aspirin • C : Low-dose aspirin alone • D : Low-dose aspirin combined with low molecular weight heparin • E : Intravenous immunoglobulin.

Serum biochemistry of a 60 year old man revealed calcium of 1.98 mmol/l and phosphate of 0.55 mmol/l with an alkaline phosphatase of 450 IU/l. Which among the following most suits with the above serum biochemistry? • 1) Osteoporosis • 2) Osteomalacia • 3) Pagets Disease • 4) Secondary Hyperparathyroidism • 5) Renal failure

A 36-year old woman is referred with a 1-year history of muscle pain, tiredness and sleep disturbance. She denies fever, weight loss and arthralgia. Examination reveals tenderness over her occiput, trapezius and lumbar area. Her blood results show a normal ESR, CRP, FBC, a weakly positive ANA 1:80 and normal complement. Which is the most likely diagnosis? A : Polymyositis B : System lupus erythematous (SLE) C : Sjogren’s syndrome D : Polymyalgia rheumatica E : Fibromyalgia.

A 58-year-old female presents complaining of right shoulder pain. She does not recall any prior injury butnotes that she feels that the shoulder has been getting progressively more stiff over the last several months. She previously had several episodes of bursitis of the right shoulder that were treated successfully with NSAIDs and steroid injections. The patient’s past medical history is also significant for diabetes mellitus, for which she takes metformin and glyburide. On physical examination, the right shoulder is not warm or red but is tender to touch. Passive and active range of motion is limited in flexion, extension, and abduction. A right shoulder radiogram shows osteopenia without evidence of joint erosion or osteophytes. What is the most likely diagnosis? • A. Adhesive capsulitis • B. Avascular necrosis • C. Bicipital tendinitis • D. Osteoarthritis • E. Rotator cuff tear

A 45-year-old woman is admitted with a spiking temperature and sweats. She has been unwell for the last 3 weeks with flitting arthralgia and lethargy. There is a rash over her trunk which is most prevalent in the mornings. Blood cultures are sterile. Her recent transthoracic echocardiogram is normal. ESR 56mm/hour. Her ferritin is elevated at 6000(g/l. Autoimmune screen is negative. • 1) bacterial endocarditis • 2) systemic lupus erythematosus • 3) rheumatoid arthritis • 4) adult onset Stills disease • 5) meningitis

A 60-year-old accountant complains of recurrent attacks of exquisite pain and swelling in the left big toe. Which of the following conditions is NOT likely to be associated with this disorder? A : Chronic alcoholism B : Obesity C : Rheumatoid arthritis D : Diabetes mellitus E : Diuretic therapy.

A 68-year-old woman with longstanding congestive cardiac failure (ejection fraction 20%) presents with a hot, swollen right knee. The following results are obtained: FBC normal, Urea 11mM, Creatinine 196ul. Synovial fluid: many monosodium urate crystals seen on microscopy, culture sterile. What is the best treatment for her acute arthritis? • A : Allopurinol • B : Colchicine 0.5mg every 2-4 hours • C : Indomethacin 50mg tds • D : Co-codamol 30/500 every 6 hours • E : Intra-articular corticosteroids

A 34-year-old man presents with severe low back pain, which has forced him to stop work as a bus driver. He has had back pain on and off for many years, on occasion with right-sided sciatica. The pain used to be helped by rest, but is now present more or less all the time and is stopping him from sleeping properly. The most likely diagnosis is: A : mechanical back pain. B : ankylosing spondylitis. C : myeloma. D : osteoporosis. E : osteoarthritis.

‘Red flag’ symptoms, requiring urgent investigation to exclude sinister pathology, include: • · age >55 or <18 years • · progressive pain • · night pain • · systemic symptoms • · progressive neurological deficit • · past history of malignancy or immunosuppression • recent trauma.

A 50 year old man presents with a 6 week history of general malaise and a 2 day history of a right foot drop, a left ulnar nerve palsy and a widespread purpuric rash. He complains of arthralgia but has no clinical evidence of inflammatory joint disease. Echocardiogram is normal, blood cultures are negative, ESR 100 mm/hr, ANCA negative, ANA negative, rheumatoid factor strongly positive, C3 0.8 g/l (0.75 - 1.6), C4 0.02 g/l (0.14 - 0.5). Dipstick urinalysis shows blood ++ but no protein. • 1) ANA negative SLE • 2) Cryoglobulinaemia • 3) Infective endocarditis • 4) Polyarthritis nordosa • 5) Rheumatoid arthritis

• A patient with primary Sj ِ◌gren’s syndrome that was diagnosed 6 years ago and treated with tear replacement for symptomatic relief notes continued parotid swelling for the last 3 months. She has also noted enlarging posterior cervical lymph nodes. Evaluation shows leukopenia and low C4 complement levels. What is the most likely diagnosis? • A. Chronic pancreatitis • B. Secondary Sj ِ◌gren’s syndrome • C. HIV infection • D. Lymphoma • E. Amyloidosis

A 64-year-old man with coronary artery disease an atrial fibrillation is referred for evaluation of fevers, arthralgias, pleuritis, and malar rash. The symptoms have developed over the past 6 months. The pleuritis has responded to steroid therapy, but prednisone has been unableto be tapered off due to recurrence of symptoms at daily steroid doses <15 mg of prednisone. His medications include aspirin, procainamide, lovastatin, prednisone, and carvedilol. At this stage antibodies directed against which of the following proteins is most likely to be positive? • A. Cardiolipin. • B. Double-strand DNA. • C. Histone. • D. Ribonucleoprotein (RNP). • E. Ribosomal .

•

A 69-year-old woman with a 5-year history of intermittent left knee pain owing to osteoarthritis presents to your office 5 days after vacationing in Greece, where she developed increased knee pain and swelling. She says that she had been walking and climbing more than usual on this vacation. She and some of the vacationers in her group developed watery diarrhea around the same time, but there were no chills or fever. She had been treated with naproxen until 2 years ago, when she developed atrial fibrillation. She now takes acetaminophen as needed for knee pain and takes warfarin for the atrial fibrillation. Physical examination shows a temperature of 38 °C (100 °F). There is a large effusion in the left knee, with increased warmth but no redness. There is moderate tenderness and pain on motion, and she walks with a limp, which she did not have before. The other joints are unchanged. Laboratory studies Hemoglobin 13.7 g/dL Hematocrit 42% Leukocyte count 10,000/µL Neutrophils 80% INR 2.1 Left knee radiograph reveals changes of osteoarthritis and an effusion. Which of the following would you do next? (A) Obtain stool culture and start treatment with ciprofloxacin. (B) Reduce warfarin dose and start treatment with celecoxib. (C) Order MRI of left knee. (D) Perform arthrocentesis. (E) Admit to hospital and start treatment with intra- venous ceftriaxone.

A 28-year-old woman presented with fatigue and extreme tiredness. Physical examination revealed facial skin rash and tenderness across the small joints of the hands. She was concerned that she might have systemic lupus erythematosus (SLE). Which of the following tests when NEGATIVE will virtually exclude the diagnosis of SLE? • A : Antinuclear antibody (ANA) • B : Anti-double stranded DNA (Ads-DNA) • C : Anti-Sm antibodies • D : Anti-histone antibodies • E : Anti-Ro/SSA antibodies.

35. A 60-year-old-man complained of pain in both wrist evolving over 8 weeks. He noted swelling around that area but denied stiffness. On examination there was swelling and tenderness just proximal to the wrist joints without limitation of movement. There was also prominent finger clubbing. Radiographs revealed periosteal reaction over the lower end of the radius and ulnar. Each of the following disorders could be the cause behind this patient complain EXCEPT? • A : Mesothelioma • B : Bronchiectesis • C : Diabetes mellitus • D : Crohn's disease • E : Whipple's disease.

THANK YOU

A 35-year-old nurse developed Raynaud's phenomenon six months ago . The antinuclear antibody (ANA) test was positive at 1:1000 with a speckled staining pattern. She came to the out-patient department complaining of excessive tiredness and lethargy. The creatine phosphokinase (CPK) was three times higher than the upper normal limits, and the hand joints radiographs showed no erosions. Which one of the following tests would you request to establish the diagnosis? A : Anti-U1 RNP B : Anti-ds DNA C : Anti-Scl 70 D : Anti-centromere antibodies E : Anti-PM-Scl

Serum biochemistry of a 60 year old man revealed calcium of 1.98 mmol/l and phosphate of 0.55 mmol/l with an alkaline phosphatase of 450 IU/l. Which among the following most suits with the above serum biochemistry? 1) Osteoporosis 2) Osteomalacia 3) Pagets Disease 4) Secondary Hyperparathyroidism 5) Renal failure

A 25-year-old woman with a history of 3-second trimester fetal losses is planning a fourth pregnancy. She has evidence of the primary anti-phospholipid syndrome (strongly positive cardiolipin antibody, positive lupus anticoagulant but no evidence of lupus). Which of the following treatment regimens offer her the best chance of having a successful pregnancy? A : Steroids alone B : Steroids combined with low-dose aspirin C : Low-dose aspirin alone D : Low-dose aspirin combined with low molecular weight heparin E : Intravenous immunoglobulin.

A 58-year-old female presents complaining of right shoulder pain. She does not recall any prior injury bu tnotes that she feels that the shoulder has been getting progressively more stiff over the last several months. She previously had several episodes of bursitis of the right shoulder that were treated successfully with NSAIDs and steroid injections. The patient’s past medical history is also significant for diabetes mellitus, for which she takes metformin and glyburide. On physical examination, the right shoulder is not warm or red but is tender to touch. Passive and active range of motion is limited in flexion, extension, and abduction. A right shoulder radiogram shows osteopenia without evidence of joint erosion or osteophytes. What is the most likely diagnosis? A. Adhesive capsulitis B. Avascular necrosis C. Bicipital tendinitis D. Osteoarthritis E. Rotator cuff tear

A 70-year-old female has a 17-year history of rheumatoid arthritis. She presents with recurrent attacks of red congested eyes with a sensation of grittiness. The most likely cause of her red eyes is likely to be: A : scleritis B : episcleritis C : keratitis D : keratoconjunctivitis sicca E : choroiditis.

24. A 64-year-old man presents to A&E with a 2-day history of increasing pain and swelling of his left knee. He denies a history of trauma. On examination, the knee is hot, red, swollen and extremely tender. Which of the following investigations is most important? A : Plain radiograph of the knee B : Blood cultures C : C-reactive protein (CRP) D : Joint aspiration E : Plasma uric acid level.

A 72-year-old man with longstanding rheumatoid arthritis (RA) presents with a 3-day history of numbness and clumsiness of both hands and difficulty walking more than a few yards because of weakness and unsteadiness of his legs. Which of the following causes of his deterioration seems most likely? A : Carpal tunnel syndrome B : Peripheral neuropathy C : Secondary osteoarthritis D : Systemic vasculitis E : Cervical myelopathy.

A 15-year-old boy presented with arthralgia, skin rash and haematuria. Renal biopsy showed focal necrotising glomerulonephritis with diffuse mesangial IgA deposits. What is the most likely diagnosis? A : Systemic lupus erythematosus (SLE) B : Henoch–Scholein purpura C : Juvenile rheumatoid arthritis D : Post-streptococcal glomerulonephritis E : Goodpasture's syndrome

A 70-year-old diabetic had problems with decreased mobility of his back. The problem had progressively worsened over the last seven years. His lumbar spine was remarkable for loss of the normal lordosis and decreased range of motion in all planes. He had no pain on percussion over the spine or sacroiliac joints. He was otherwise in good health, and the erythrocyte sedimentation rate (ESR) was normal The most probable diagnosis is: A : Ankylosing spondylitis (AS) B : Alcaptonuria C : Osteoporosis D : Spondylolisthesis E : Diffuse idiopathic skeletal hyperostosis (DISH)

A 30-year-old teacher presents with a 6-month history of swelling and pain involving the distal interphalangeal joints of the hands. The ESR is 65 mm in the first hour. What is the most likely diagnosis? A : Generalised osteoarthritis B : Rheumatoid arthritis C : Psoriatic arthritis D : Systemic lupus erythematosus (SLE) E : Gout.

A 28-year-old woman presented with fatigue and extreme tiredness. Physical examination revealed facial skin rash and tenderness across the small joints of the hands. She was concerned that she might have systemic lupus erythematosus (SLE). Which of the following tests when -ve will virtually exclude the diagnosis of SLE? A : Antinuclear antibody (ANA) B : Anti-double stranded DNA (Ads-DNA) C : Anti-Sm antibodies D : Anti-histone antibodies E : Anti-Ro/SSA antibodies.

An 8-year-old has been admitted for a third time with haemolytic-uraemic syndrome and is found to have a low C3. Which of the following is the most likely diagnosis? A : Lupus B : Gram-negative septicaemia C : Factor H deficiency D : Factor I deficiency E : C3 deficiency.

A 69-year-old woman with a 5-year history of intermittent left knee pain owing to osteoarthritis presents to your office 5 days after vacationing in Greece, where she developed increased knee pain and swelling. She says that she had been walking and climbing more than usual on this vacation. She and some of the vacationers in her group developed watery diarrhea around the same time, but there were no chills or fever. She had been treated with naproxen until 2 years ago, when she developed atrial fibrillation. She now takes acetaminophen as needed for knee pain and takes warfarin for the atrial fibrillation. Physical examination shows a temperature of 38 °C (100 °F). There is a large effusion in the left knee, with increased warmth but no redness. There is moderate tenderness and pain on motion, The other joints are unchanged. Laboratory studies Hemoglobin 13.7 g/dL Hematocrit 42% Leukocyte count 10,000/µL Neutrophils 80% INR 2.1 Left knee radiograph reveals changes of osteoarthritis and an effusion. Which of the following would you do next? (A) Obtain stool culture and start treatment with ciprofloxacin. (B) Reduce warfarin dose and start treatment with celecoxib. (C) Order MRI of left knee. (D) Perform arthrocentesis. (E) Admit to hospital and start treatment with intra- venous ceftriaxone.

13-year-old boy was hospitalised because of a purpuric rash involving the legs (see image) associated with abdominal pain and fever (38°C). The patient also complained of arthralgiainvolving the knees and ankles. Urinalysis showed proteinuria with microscopic haematuria. A biopsy of the purpuric lesion revealed leucocytoclastic vasculitis in the small vessels. Which of the following statements is true about this boy's illness?

A.The urine abnormality and fever is most probably related to a recent urinary tract infection B : In such cases blood cultures are often positive for Pseudomonas aerogenosa C : Renal biopsy typically shows mesangial IgA deposition D : Bilateral small kidneys are a constant feature on ultrasound of the kidneys E : Untreated, up to 50% will develop chronic renal failure.

A 67-year-old woman was referred to a specialist rheumatology clinic. She had poorly controlled rheumatoid arthritis. For the last fifteen years she had been treated with various disease-modifying drugs including sulphasalazine and methotrexate. Blocking the biologic function of which of the following molecules will provide significant antiinflammatory effect in RA? A : Interleukin-10 (IL-10) B : Interleukin-4 (IL-4) C : Interleukin-1 (IL-1) D : Soluble TNF receptors E : Transforming growth factor-beta (TGF-beta).

A 32-year-old man presents with a 4-month history of back pain. The pain is worse in the morning and after sitting watching TV. Plain radiograph of the spine/pelvis shows evidence of sacroiliitis. Each of the following clinical features might be identified on clinical examination of this patient EXCEPT? A : Keratoderma blenorhegica B : Rheumatoid nodule C : Onycholysis D : Uveitis E : Urethritis.

A 36-year-old woman presents with deteriorating nocturnal paraesthesia affecting both hands. It improves during the morning. Which of the following tests is least likely to be helpful in establishing the cause? A : Thyroid function test B : Rheumatoid factor C : Tinels test D : MRI scan hands E : Urinary hCG.

35. A 60-year-old-man complained of pain in both wrist evolving over 8 weeks. He noted swelling around that area but denied stiffness. On examination there was swelling and tenderness just proximal to the wrist joints without limitation of movement. There was also prominent finger clubbing. Radiographs revealed periosteal reaction over the lower end of the radius and ulnar. Each of the following disorders could be the cause behind this patient complain EXCEPT? A : Mesothelioma B : Bronchiectesis C : Diabetes mellitus D : Crohn's disease E : Whipple's disease.

Comment : Hypertrophic osteoarthropathy (HOA) is a syndrome characterized by proliferative changes in the skin and skeleton. Proliferative periostitis of the radius and fibula and digital clubbing 97%). Secondary HOA was initially described in association with chronic suppurative infection and malignancy of the lung and pleura. Therefore it used to be called hypertrophic pulmonary osteoarthropathy (HPOA). Pleural causes include pleural fibroma and mesothelioma. Pulmonary causes include bronchogenic carcinoma, pulmonary tuberculosis; pulmonary abscesses, bronchiectasis, emphysema; and Pneumocystis carinii infection in patients with AIDS, Hodgkin’s disease, metastases, or cystic fibrosis. Cyanotic heart disease with a right-to-left shunt is the only cardiac cause described. Abdominal causes include liver cirrhosis, ulcerative colitis, Crohn disease, Whipple disease,.

A 36-year old woman is referred with a 1-year history of muscle pain, tiredness and sleep disturbance. She denies fever, weight loss and arthralgia. Examination reveals tenderness over her occiput, trapezius and lumbar area. Her blood results show a normal ESR, CRP, FBC, a weakly positive ANA 1:80 and normal complement. Which is the most likely diagnosis? A : Polymyositis B : System lupus erythematous (SLE) C : Sjogren’s syndrome D : Polymyalgia rheumatica E : Fibromyalgia.

A 40-year-old woman presents with a 6-month history of a purpuric rash on her legs, nonspecific joint pains and vague ill health. Initial investigations reveal a positive rheumatoid factor. The GP makes a tentative diagnosis of rheumatoid arthritis and refers her to hospital. Results of further investigations are as follows: Urinalysis: red cell casts, protein+, ANA 1/80, anti-DNA negative, anti-ENA negative, serum C3 1.02 g/l (NR 0.75-1.65), C4 <0.02 g/l (0.20-0.65), CRP <5mg/l (NR <5), creatinine 145 (NR 50140). what is the most likely diagnosis?

A 60-year-old accountant complains of recurrent attacks of exquisite pain and swelling in the left big toe. Which of the following conditions is NOT likely to be associated with this disorder? A : Chronic alcoholism B : Obesity C : Rheumatoid arthritis D : Diabetes mellitus E : Diuretic therapy.

A 34-year-old man presents with severe low back pain, which has forced him to stop work as a bus driver. He has had back pain on and off for many years, on occasion with right-sided sciatica. The pain used to be helped by rest, but is now present more or less all the time and is stopping him from sleeping properly. The most likely diagnosis is: A : mechanical back pain. B : ankylosing spondylitis. C : myeloma. D : osteoporosis. E : osteoarthritis.

‘Red flag’ symptoms, requiring urgent investigation to exclude sinister pathology, include: · age >55 or <18 years · progressive pain · night pain · systemic symptoms · progressive neurological deficit · past history of malignancy or immunosuppression recent trauma. A:

Which one of the following musculoskeletal disorders is NOT associated with diabetes mellitus? A : Dupuytren's contracture B : Chondrocalcinosis C : Scleroderma D : Carpal tunnel syndrome E : Frozen shoulder.

A 68-year old man presented with sudden severe pain and swelling in the left knee. Synovial fluid analysis shows abundant calcium pyrophosphate dihydrate (CPPD) crystals. Which of the following tests is NOT appropriate for further assessment of this patient illness? A : Creatinine kinase B : Serum calcium C : Thyroid function test D : Serum ferritin level E : Hb AIc.

Which one of the following antibodies, when present in high titre, is NOT regarded as diagnostic of the disease indicated? A : Anti-Sm antibodies in systemic lupus erythematosus (SLE) B : Ads-DNA antibodies in systemic lupus erythematosus (SLE) C : Anti-centromere antibodies in limited systemic sclerosis D : Rheumatoid factor in rheumatoid arthritis (RA) E : Anti-Scl 70 antibodies in diffuse systemic sclerosis

Which one of the following rheumatological disorders is NOT associated with increased incidence of malignancy? A : Dermatomyositis B : Polymyalgia rheumatica C : Sjogren's syndrome D : Diffuse systemic sclerosis E : Hypertrophic pulmonary osteoarthropathy

A 40-year-old woman suddenly develops severe Raynauds that is troublesome in the summer as well as the winter. She starts to develop swelling of the fingers and feels tired. She also develops reflux oesophagitis and has difficulty swallowing. She has noticed that she has become more breathless. On examination, she has skin thickening affecting her hands, face and trunk. Which of the following is most likely to be positive? A : Ds DNA antibody B : Ro antibody C : Anticentromere antibody D : Jo-1 antibody E : Scl-70 antibody

A 77-year-old man presents with persistent head ache and progressive deafness. On examination the patient has frontal bossing of the forehead and conductive deafness, more severe in the right ear. His serum alkaline phosphatase is significantly raised at 870 u/L. Which of the following statements is most accurate about this disease? A : It usually affects a single bone. B : The skull is the most commonly affected bone. C : Bone pain is the most common presenting feature. D : Hearing loss is often due to involvement of the middle ear ossicles leading to conductive deafness. E : Bone pain is typically increased with rest and on weight bearing.

A 50 year old man presents with a 6 week history of general malaise and a 2 day history of a right foot drop, a left ulnar nerve palsy and a widespread purpuric rash. He complains of arthralgia but has no clinical evidence of inflammatory joint disease. Echocardiogram is normal, blood cultures are negative, ESR 100 mm/hr, ANCA negative, ANA negative, rheumatoid factor strongly positive, C3 0.8 g/l (0.75 - 1.6), C4 0.02 g/l (0.14 - 0.5). Dipstick urinalysis shows blood ++ but no protein. 1) ANA negative SLE 2) Cryoglobulinaemia 3) Infective endocarditis 4) Polyarthritis nordosa 5) Rheumatoid arthritis

A patient with psoriatic arthritis has active joints and troublesome plaque psoriasis. Which of the following will improve both the joint and skin problems? A : Sulphasalazine B : Hydroxychloroquine C : Gold D : Methotrexate E : Penicillamine

A 45-year-old woman is admitted with a spiking temperature and sweats. She has been unwell for the last 3 weeks with flitting arthralgia and lethargy. There is a rash over her trunk which is most prevalent in the mornings. Blood cultures are sterile. Her recent transthoracic echocardiogram is normal. ESR 56mm/hour. Her ferritin is elevated at 6000(g/l. Autoimmune screen is negative. 1) bacterial endocarditis 2) systemic lupus erythematosus 3) rheumatoid arthritis 4) adult onset Stills disease 5) meningitis

Which of the following has the greatest specificty for Wegener's granulomatosis? 1) pANCA and positive antibodies to myeloperoxidase 2) atypical ANCA and positive antibodies to myeloperoxidase 3) cANCA and positive antibodies to myeloperoxidase 4) cANCA and positive antibodies to proteinase 3 5) cANCA and positive antibodies to lactoferrin

A 29-year-old woman has a 3-year history of arthralgia and Raynaud's phenomenon. A year ago she had a miscarriage at 29 weeks, complicated by a deep vein thrombosis. Investigations show:Hb11.2Wcc 4.3 Platelets 145,ANA positive1/160,DNAnegative,ENA Ro positive, Anticardiolipin antibodies present at moderate titre, lupus anticoagulant present. Which statement is true? A : She has primary antiphospholipid syndrome. B : She should be anticoagulated for a further 6 months. C : She has active lupus. D : A high C reaction protein (CRP) and erythrocyte sedimentation rate (ESR) would be consistent with active lupus. E : Hydroxychloroquine may improve her arthralgia

A 34-year-old man is admitted to the hospital for evaluation and treatment of renal failure and an abnormal CT of the chest. For the past 2 months, he has had fatigue, malaise, and intermittent fevers to as high as 38.2°C. About 3 weeks ago, he sought treatment from his primary provider for sinus pain and congestion with a purulent and bloody nasal discharge. He was treated for 2 weeks with ampicillinsulbactam, but his symptoms have only minimally improved.When he returned to his physician, a basic metabolic panel was performed which showed a creatinine of 2.8mg/dL. A urinalysis showed 1+ protein with 25 red blood cells per high-power field. Red blood cell casts were present. His chest CT is shown below. Which of the following tests would be most likely to be positive in this individual A. Antiglomerular basement membrane antibodies B. Antiproteinase-3 antibodies C. High titers of antibodies to antistreptolysin O D. Perinuclear antineutrophil cytoplasmic antibodies E. Positive blood cultures for Staphylococcus aureus

56-year-old patient presented with 6-month history of excessive tiredness, stiffness and pain across the upper and lower limbs. On examination he has proximal muscle weakness. The creatinine kinase was 10 times the upper limits of normal. The skin lesions shown in the image are most likely to be: tendon xanthoma Gottron's papules rheumatoid nodules gouty tophi.

A 75-year-old retired farmer has been seen in the outpatient clinic. He has been generally unwell for the last month with fever and weight loss, examination reveals this rash (see image). While in the clinic he starts to cough up blood and becomes acutely breathless. He is admitted and initial investigations reveal a serum creatinine of 170 micromol/l, a positive myeloperoxidase (MPO) ELISA, negative proteinase 3 (PR3) ELISA, negative GBM ELISA, a negative ANA and normal complement levels. Red cell casts are seen on microscopy of his urine. Which two of the following diagnoses are most compatible with the clinical picture? A : Sjogren’s syndrome B : Goodpasture’s disease C : Lupus D : Henoch schonlein purpura E : Cryoglobulinaemic vasculitis F : Polyarteritis nodosa G : Anti-phospholipid syndrome H : Wegener's granulomatosis I : Microscopic polyangiitis J : Takayasu’s arteritis

Which one of the following drugs does NOT cause proximal muscle weakness? A : Corticosteroid B : D-penicillamine C : Methotrexate D : Chloroquine E : Colchicine

A 42-year-old man is evaluated because of right renal colic and microhematuria. He has had three previous episodes of calcium nephrolithiasis. Diagnostic studies show a 4mm calcified stone in the middle right ureter. Which of the following laboratory test results is not a risk factor for calcium nephrolithiasis? (A) Urinary calcium of 315 mg/24 h (B) Serum uric acid of 10.5 mg/dL (C) Urinary citrate of 100 mg/24 h (normal 300-700 mg/24 h) (D) Urinary oxalate of 72 mg/24 h (normal < 40 mg/24 h) (E) Serum calcium of 11 mg/dL and serum phosphorus of 2.1 mg/dL

A 50 year old woman presents with dry eyes, a dry mouth, an erythematous rash and polyarthralgia. Investigations: ANA strongly positive (1:1600), anti-Ro/SSA antibodies strongly positive, rheumatoid factor positive, IgG markedly elevated at 45 g/l (normal - <15 g/l), IgM and IgA levels are normal and the kappa/lambda ratio is normal. What is the most likely diagnosis? 1) Hyperviscosity syndrome 2) Myeloma associated vasculitis 3) Primary Sjogren's Syndrome 4) Rheumatoid arthritis with secondary Sjogren's Syndrome 5) Systemic Lupus Erythematosus

Serum biochemistry of a 60 year old man revealed calcium of 1.98 mmol/l and phosphate of 0.55 mmol/l with an alkaline phosphatase of 450 IU/l.Which among the following mosts suits with the above serum biochemistry? 1) Osteoporosis 2) Osteomalacia 3) Pagets Disease 4) Secondary Hyperparathyroidism 5) Renal failure

A 31-year-old woman presents to your clinic complaining of painful arthritis that is worse in the mornings when she wakes up. She was recently evaluated by an ophthalmologist for uveitis in her right eye. A recent laboratory report shows an erythrocyte sedimentation rate of 48 mm/h. Which of the following will be helpful in distinguishing relapsing polychondritis from rheumatoid arthritis (RA)? A. Arthritis associated with RA is nonerosive. B. Eye inflammation is absent in relapsing polychondritis. C. Relapsing polychondritis will not present with vasculitis. D. Relapsing polychondritis will present with high-titer rheumatoid factor. E. The arthritis of relapsing polychondritis is asymmetric

A 42-year-old obese male presents to your office with complaints of paresthesias in the right hand that are worst in the fourth and fifth fingers. Symptoms have been present intermittently for the last 4 months. He has no other past medical history and takes no medications. The examination is significant for an intact neurologic examination of the right upper extremity but mild wasting of the intrinsic muscles on inspection of the right hand. Laboratories show a normal white blood cell count, hemoglobin, and sedimentation rate. Electrolytes and creatinine and liver function tests are normal except for a serum glucose of 148 mg/dL. What is the most likely etiology of this patient’s symptoms? A. Diabetes mellitus B. Cholesterol emboli C. Churg-Strauss disease D. Cervical spondylosis E. Neurogenic thoracic outlet syndrome

A 54-year-old man is admitted for persistent lower abdominaland groin pain that began 7 months previously.Two months before his present admission, he required exploratorylaparoscopy for acute abdominal pain and presumedcholecystitis. This revealed necrotic omental tissueand pericholecystitis necessitating omentectomy and cholecystectomy.However, the pain continued unchanged. Hecurrently describes it as periumbilical and radiating into hisgroin and legs. It becomes worse with eating. The patient has also had episodic severe testicular pain, bowel urgency, nausea,vomiting, and diuresis. He has lost ~22.7 kg over thepreceding 6 months. His past medical history is significantof hypertension that has recently become difficult to control.Medications on admission include aspirin, hydrochlorothiazide,hydromorphone, lansoprazole, metoprolol,and quinapril. On physical examination, the patient appearscomfortable. His blood pressure is 170/100 mmHg,his heart rate is 88 beats/min, and he is afebrile. He hasnormal first and second heart sounds without murmurs,and an S4 is present. There are no carotid, renal, abdominal,or femoral bruits.His lungs are clear to auscultation. Bowel sounds are normal.Abdominal palpation demonstrates minimal diffusetenderness without rebound or guarding. No masses arepresent, and the stool is negative for occult blood. Duringthe examination, the patient develops Raynaud's phenomenonin his right hand that persists for several minutes. Hisneurologic examination is intact. Admission laboratorystudies reveal an erythrocyte sedimentation rate of 72 mm/h, a BUN of 17 mg/dL, and a creatinine of 0.8 mg/dL. The patienthas no proteinuria or hematuria. Tests for antinuclearantibodies, anti-double-stranded-DNA antibodies, and antineutrophilcytoplasmic antibodies are negative. Liverfunction tests are abnormal with an AST of 89 IU/L and anALT of 112 IU/L. Hepatitis B surface antigen and e antigenare positive. Mesenteric angiography demonstrates smallbeaded aneurysms of the superior and inferior mesentericveins. What is the most likely diagnosis?

A. Hepatocellular carcinoma B. Ischemic colitis C. Microscopic polyangiitis D. Mixed cryoglobulinemia E. Polyarteritis nodosa

A 64-year-old African-American male is evaluated inthe hospital for congestive heart failure, renal failure, and polyneuropathy. Physical examination on admission was notable for these findings and raised waxy papules in the axilla and inguinal region. Admission laboratories showeda BUN of 90 mg/dL and a creatinine of 6.3 mg/dL. Total protein was 9.0 g/dL, with an albumin of 3.2 g/dL. Hematocrit was 24%, and white blood cell and platelet countswere normal. Urinalysis was remarkable for 3+ proteinuriabut no cellular casts. Further evaluation included an echocardiogram with a thickened left ventricle and preserved systolic function. Which of the following tests ismost likely to diagnose the underlying condition? A. Bone marrow biopsy B. Electromyogram (EMG) with nerve conduction studies C. Fat pad biopsy D. Right heart catheterization E. Renal ultrasound

A 66-year-old woman with a history of rheumatoid arthritis and frequent pseudogout attacks in her left knee presents with night sweats and a 2-day history of left knee pain. On physical examination, her temperature is 38.6°C, heart rate is 110 beats/min, blood pressure is 104/78 mmHg, and oxygen saturation is 97% on room air. Her left knee is swollen, red, painful, and warm. With 5° offlexion or extension, she develops extreme pain. She hasevidence of chronic joint deformity in her hands, knees,and spine. Peripheral white blood cell (WBC) count is16,700 cells/μL with 95% neutrophils. A diagnostic tapof her left knee reveals 168,300 WBCs per microliter,99% neutrophils, and diffuse needle-shaped birefringentcrystals present. Gram stain shows rare gram-positivecocci in clusters. Management includes all of the following except A. blood cultures B. glucocorticoids C. needle aspiration of joint fluid D. orthopedic surgery consult E. vancomycin

A 41-year-old female presents to your clinic with 3 weeks of weakness, lethargy. and depressed mood. She notes increasing difficulty with climbing steps, rising fro a chair, and combing her hair. She has no difficulty buttoning her blouse or writing. The patient also notes some dyspnea on exertion and orthopnea. She denies rash, joint aches, or constitutional symptoms. She is on no medications, and the past medical history is otherwise uninformative.The family history is notable only for coronarartery disease. The physical examination is notable for an elevated jugular venous pressure, an S3, and some bibasilar crackles. The neurologic examination shows some marked proximal muscle weakness in the deltoids and biceps and the hip flexors. Distal muscle strength is normal. Sensoryexamination and reflexes are normal. Laboratories are unremarkable except for a negative antinuclear antibody screen and a creatinine kinase of 3200 IU/L. You suspect a diagnosis of polymyositis. All the following clinical conditions may occur in polymyositis except A. an increased incidence of malignancy B. interstitial lung disease C. dilated cardiomyopathy D. dysphagia E. Raynaud’s phenomenon

64-year-old man with congestive heart failure presents to the emergency room complaining of acute onset of severe pain in his right foot. The pain began during the nightand awoke him from a deep sleep. He reports the pain to be so severe that he could not wear a shoe or sock to the hospital.His current medications are furosemide, 40 mg twicedaily, carvedilol, 6.25 mg twice daily, candesartan, 8 mg once daily, and aspirin, 325 mg once daily. On examination, he isfebrile to 38.5°C. The first toe of the right foot is erythematous and exquisitely tender to touch. There is significant swelling and effusion of the first metatarsophalangeal joint on the right. No other joints are affected. Which of the following findings would be expected on arthrocentesis? A. Glucose level of <25 mg/dL B. Positive Gram stain C. Presence of strongly negatively birefringent needleshaped crystals under polarized light microscopy D. Presence of weakly positively birefringent rhomboidal crystals under polarized light microscopy E. White blood cell (WBC) count >100,000/μL

A 58-year-old female presents complaining of right shoulder pain. She does not recall any prior injury butnotes that she feels that the shoulder has been getting progressively more stiff over the last several months. She previously had several episodes of bursitis of the right shoulder that were treated successfully with NSAIDs and steroid injections. The patient’s past medical history isalso significant for diabetes mellitus, for which she takes metformin and glyburide. On physical examination, the right shoulder is not warm or red but is tender to touch. Passive and active range of motion is limited in flexion, extension, and abduction. A right shoulder radiogram shows osteopenia without evidence of joint erosion or osteophytes. What is the most likely diagnosis? A. Adhesive capsulitis B. Avascular necrosis C. Bicipital tendinitis D. Osteoarthritis E. Rotator cuff tear

A patient with end-stage renal disease on hemodialysis presents to your office wit hand pain and you diagnose carpal tunnel syndrome. A serum thyroid-stimulating hormone level is normal. You also note bilateral knee effusions, which the patient states have been there for many months.Suspecting an amyloid deposition disease, you perform a fat pad biopsy. Which protein do you expect to find on immunohistochemical staining? A. β2-Microglobulin B. Fibrinogen α-chain C. Immunoglobulin light chain D. Serum amyloid A E. Transthyretin

A 48-year-old male has a long-standing history of ankylosing spondylitis. His most recent spinal film shows straightening of the lumbar spine, loss of lordosis, and “squaring” of the vertebral bodies. He currently is limited by pain with ambulation that is not improved with nonsteroidal antiinflammatory medications. Which of the following treatments has been shown to improve symptoms the best at this stage of the illness? A. Celecoxib B. Etanercept C. Prednisone D. Sulfasalazine E. Thalidomide

A 64-year-old man with coronary artery disease an atrial fibrillation is referred for evaluation of fevers, arthralgias, pleuritis, and malar rash. The symptoms have developed over the past 6 months. The pleuritis has responded to steroid therapy, but prednisone has been unableto be tapered off due to recurrence of symptoms at daily steroid doses <15 mg of prednisone. His medications include aspirin, procainamide, lovastatin, prednisone, and carvedilol. At this stage antibodies directed against which of the following proteins is most likely to be positive? A. Cardiolipin B. Double-strand DNA C. Histone D. Ribonucleoprotein (RNP) E. Ribosomal P

A 68-year-old woman with longstanding congestive cardiac failure (ejection fraction 20%) presents with a hot, swollen right knee. The following results are obtained: FBC normal, Urea 11mM, Creatinine 196ul. Synovial fluid: many monosodium urate crystals seen on microscopy, culture sterile. What is the best treatment for her acute arthritis? A : Allopurinol B : Colchicine 0.5mg every 2-4 hours C : Indomethacin 50mg tds D : Co-codamol 30/500 every 6 hours E : Intra-articular corticosteroids

A 68-year-old woman with longstanding congestive with a 3-month history of fatigue. She has read about lupus on the world wide web and asks her GP to carry out appropriate blood test(s) to rule out lupus. Which single blood test is best suited to screen for lupus in this situation? A : Antinuclear antibody B : Serum Immunoglobulin levels C : Anti-cardiolipin antibodies D : Anti-DNA antibodies E : Anti-ENA antibodies.

A 25-year-old woman with a history of 3-second trimester fetal losses is planning a fourth pregnancy. She has evidence of the primary anti-phospholipid syndrome strongly positive cardiolipin antibody, positive lupus anticoagulant but no evidence of lupus. Which of the following treatment regimens offer her the best chance of having a successful pregnancy? A : Steroids alone B : Steroids combined with low-dose aspirin C : Low-dose aspirin alone D : Low-dose aspirin combined with low molecular weight heparin E : Intravenous immunoglobulin.

A 78-year-old man presents with a 2-day history of severe headache localising to his right temple. He also feels tired and lethargic. He denies any eye problems and pain on chewing. The biopsy of his right temporal artery is shown (see image). Which of the following statements fit best?

A : This is a normal temporal artery biopsy. B : This man should be treated with 60 mg prednisolone. C : There is no need to consider bone protection. D : 50% of patients with this condition develop permanent visual loss. E : An ESR of less than 40mm/hr excludes Giant Cell Arteritis (GC

A 72-year-old woman presents to the emergency room for an episode of vision loss in her right eye. The vision loss came on abruptly and is described as a curtain falling across her visual field. She immediately called her daughter and upon arrival to the emergency room 40 min later, her vision had returned to normal. Recently she also has been experiencing dull throbbing headaches for which she is taking acetaminophen, with limited relief. She has a past medical history of hypercholesterolemia and coronary artery disease, undergoing angioplasty and stenting of the right coronary artery 8 years previously. She does not smoke currently but has a 40-pack-year history of tobacco, quitting only after her diagnosis of coronary artery disease. On review of systems, the patient recalls pain in her scalp with combing her hair, particularly on the right side, and occasional pain with chewing food. She has also recently noticed stiffness and pain in her hips, making it difficult to stand from seated position. On examination, she has 20/30 visual acuity in the left eye, and 20/100 visual acuity in the right eye. Funduscopic examination suggests anterior ischemic optic neuropathy. There are no carotid bruits present, but palpation of the temporal arteryis painful. The neurologic examination is otherwise normal. The erythrocyte sedimentation rate (ESR) is 102 mm/h. The hemoglobin is 7.9 g/dL, and hematocrit is 25.5%. A head CT shows no acute ischemic event. Which of the following is the next most important step in the management of this patient?

A. Initiate treatment with indomethacin, 75 mg twice daily. B. Initiate treatment with prednisone, 60 mg daily. C. Initiate treatment with unfractionated heparin D. Perform magnetic resonance angiography of the brain. E. Perform a temporal artery biopsy.

A patient presents with 3 weeks of pain in the lower back. All the following are risk factors for serious causes of spine pathology except A. age more than 50 years B. urinary incontinence C. duration of pain more than 2 weeks D. bed rest without relief E. history of intravenous drug use

A 43-year-old male presents to your office complaining of weakness in the right hand for 2 days. He reports that he had been in excellent health until 2 monthsago, when he was diagnosed with hypertension. Since that diagnosis, he has lost 20 lb unintentionally and complains of frequent headaches and abdominal pain that is worse after eating. He previously was an injection drug user but now is maintained on methadone. His only medications are hydrochlorothiazide 25 mg/d, methadone70 mg/d, and lisinopril 5 mg/d. On physical examination,the patient appears well developed and without distress. Blood pressure is 148/94. He is not tachycardic. The examination is otherwise notable only for the inabilityto extend the right wrist and fingers against gravity.Laboratory studies show an erythrocyte sedimentation rate (ESR) of 88 mm/h, an aspartate aminotransferase (AST) of 154 IU/L, and an alanine aminotransferase(ALT) of 176 IU/L. Which of the following tests is most useful in establishing a diagnosis? A. Hepatitis B surface antigen B. Hepatitis C viral load C. Anticytoplasmic neutrophil antibodies D. Mesenteric angiography E. Radial nerve biopsy

36. A 23-year-old woman was diagnosed with systemic lupus erythematosus based upon the presence of polyarthritis, malar rash with photosensitivity, and oral ulcerations. Antibodies to double-stranded DNA, Smith protein, and antinuclear antibodies were present in high titers. A urinalysis is normal.. What is the best choice for initial therapy in this individual? A. Hydroxychloroquine, 200–400 mg daily B. Methotrexate, 15 mg weekly C. Physical therapy only D. Prednisone, 1 mg/kg daily E. Quinacrine, 100 mg three times daily

A 25-year-old female presents with a complaint of painful mouth ulcerations. She describes these lesions as shallow ulcers that last for 1 or 2 weeks. The ulcers have been appearing for the last 6 months. For the last 2 days, the patient has had a painful red eye. She has had no genital ulcerations, arthritis, skin rashes, or photosensitivity. On physical examination, the patient appears well developedand in no distress. She has a temperature of 37.6°C (99.7°F), heart rate of 86, blood pressure of 126/72, and respiratory rate of 16. Examination of the oral mucosa reveals two shallow ulcers with a yellow base on the buccal mucosa. The ophthalmologic examination is consistent with anterior uveitis. The cardiopulmonary examination is normal. She has no arthritis, but medially on the right thigh there is a palpable cord in the saphenous vein. Laboratory studies reveal an erythrocyte sedimentation rate of 68 s. White blood cell count is 10,230/mm3 with a differential of 68% polymorphonuclear cells, 28% lymphocytes, and 4% monocytes. The antinuclear antibody and antidsDNA antibody are negative. C3 and C4 are normal. What is the most likely diagnosis? A. Behçet’s syndrome. B. Systemic lupus erythematosus. C. Discoid lupus erythematosus. D. Sj ِ◌gren’s syndrome. E. Cicatricial pemphigoid.

What is the best initial treatment for this patient? A. Topical glucocorticoids including ophthalmic prednisolone B. Systemic glucocorticoids and azathioprine C. Thalidomide D. Colchicine E. Intralesional interferon α

A 63-year-old white female is admitted to the hospital complaining of hemoptysis and shortness of breath.She had been well until 3 months ago, when she noted vague symptoms of fatigue and a 10-lb unintentional weight loss. Past medical history is notable only for osteoporosis.Her current symptoms began on the day of presentation with the expectoration of >200 mL of red blood in the emergency department. On physical examination ,the patient is in marked respiratory distress with a respiratory rate of 44 breaths per minute. Oxygen saturationis78% on room air and 88% on non re breather mask. Pulse is 120 beats/min, with a blood pressure of 170/110. There are diffuse crackles throughout both lung fields, and thecardiac examination is significant only for a regular tachycardia. There are no rashes or joint swellings. Laboratory studies reveal a hemoglobin of 10.2 mg/dL with amean corpuscular volume (MCV) of 88 μm3 (fL). The white blood cell count is 9760/mm3. Blood urea nitrogen (BUN) is 78 mg/dL, and creatinine is 3.2 mg/dL. The urinalysis shows 1+ proteinuria, moderate hemoglobin, 25to 35 red blood cells (RBC) per highpower field, and occasiona lRBC casts. Chest computed tomography (CT) shows diffuse alveolar infiltrates consistent with alveolar hemorrhage. The antimyeloperoxidase titer is positive at126 U/mL (normal <1.4 U/mL). What is the most likelydiagnosis? A. Goodpasture’s disease B. Wegener’s granulomatosis C. Microscopic polyangiitis D. Polyarteritis nodosa E. Cryoglobulinemia

A 42-year-old man presents to your clinic complaining of left shoulder soreness that has been bothering him for 8 months. He experiences intermittent pain that is worse at night. Active abduction of his left arm over his head causes extreme pain. He describes his pain as a dull ache in his shoulder. He cannot identify a specific trauma that led to his pain but notes that he lifts weights and plays sports on a regular basis. On physical examination, he has tenderness over the lateral aspect of the humeral head and pain with arm abduction. Which of the following is the most likely cause of his symptoms? Acromioclavicular arthritis B. Bicipital tendonitis C. Inflammation of the infraspinatus tendon D. Inflammation of the supraspinatus tendon E. Subluxation of the left humeral head

A 60-year-old woman with a history of Sj ِ◌gren’s syndrome diagnosed 20 years ago presents to her primary care doctor complaining of facial swelling. Her xerostomia dry eye symptoms have not changed. She is known to be positive for rheumatoid factor in addition to Ro and La antibodies but is not thought to have rheumatoid arthritis. She previously had cutaneous vasculitis requiring treatment with prednisone, but she has been off steroids for 5 years without evidence of recurrence. She is currently using artificial tears and cevimeline, 30 mg three times daily. On physical examination, her right parotid gland is enlarged. It is not tender, but is firm and hard to touch. It is noted that the right parotid gland was similarly enlarged on a visit 3 months ago. She denies systemic illness or any new symptoms. What is the most likely diagnosis? A. Adenoid cystic carcinoma B. B cell lymphoma C. Impacted sialolith D. Mumps E. Recurrent vasculiti

66. An 84-year-old man is seen by his primary care provider, and chronic = kidney disease. He is taking pravastatin, aspirin, furosemide, metolazone, lisinopril,and metoprolol XL. His baseline creatinine is 2.4 mg/dL, and uric acid level 9.3 mg/dL. His most recent with symptoms of acute gouty arthritis in the first great toe and ankle on the left. He has a prior history ofgout presenting similarly. His past medical history is significant for myelodysplasia, congestive heart failure ,hypercholesterolemia complete blood count results are white blood cell count 2880/μL, hemoglobin 8.2 g/dL, hematocrit 26.2%, and platelet 68,000/ μL. Which of the following medication regimens are most appropriate for the treatment of this patient?

A. Allopurinol, 100 mg once daily B. Colchicine, 1 mg IV once, then 0.5 mg IV every 6 h until improvement C. Indomethacin, 25 mg three times daily D. Prednisone, 40 mg once daily E. Probenecid, 250 mg twice daily

A patient with primary Sj ِ◌gren’s syndrome that was diagnosed 6 years ago and treated with tear replacement for symptomatic relief notes continued parotid swelling for the last 3 months. She has also noted enlarging posterior cervical lymph nodes. Evaluation shows leukopenia and low C4 complement levels. What is the most likely diagnosis? A. Chronic pancreatitis B. Secondary Sj ِ◌gren’s syndrome C. HIV infection D. Lymphoma E. Amyloidosis

A 23-year-old man seeks evaluation for low back pain. He states that when he first awakens there is a dull aching pain in his lower lumbar and gluteal region. When he first noticed the pain about 6 months ago, he thought the pain might be related to his mattress, but it has worsened even after buying a new mattress. Most mornings, it takes about 45–60 min to loosen up after he has awakened, but the pain will recur if he is idle. He is currently in law school and finds it increasingly difficult to remain in classes because of back pain. When he exercises, the pain lessens. There are occasional nights that the pain will awaken him from sleep, and he will have to move around and stretch his back to improve the pain. On physical examination, there is pain with palpation at the iliac crests, ischial tuberosities, greater trochanters, and heels. With maximal inspiration, the chest expands 4 cm, and there is decreased flexion of the lumbar spine. A radiograph of the pelvis shows erosions and sclerosis of the sacroiliac joints bilaterally. Which of the following tests is most likely to be positive in this individual? A. Alkaline phosphatase B. Antibodies directed against cyclic citrullinated peptides (CCP) C. Antinuclear antibodies D. HLA-B27 E. Rheumatoid factor

A 46-year-old woman is referred to your clinic by her primary care physician. She describes fatigue and diffuse muscle aches that have been worsening over a period of 6 months. She also has not been sleeping well. Her primary doctor evaluated her and sent screening laboratory tests, which returned with a positive rheumatoid factor. She has read about rheumatoid arthritis on the Internet and is very concerned that she has the disease based on her symptoms and her positive test. Which of the following is true in regard to diagnosing rheumatoid arthritis (RA)? A. 10% of healthy individuals will test positive for antibodies to cyclic citrullinated polypeptides (anti-CCP). B. B. Erythrocyte sedimentation rate (ESR) is elevated in 70% of patients with active disease. C. In early disease, rheumatoid factor is more accurate than anti-CCP. D. Fewer than one-third of unselected patients with positive rheumatoid factor will have RA. E. Radiographs should be performed in this patient to help with diagnosis.

A 53-year-old woman presents to your clinic complaining of fatigue and generalized pain that have worsened over 2 years. She also describes irritability and poor sleep and is concerned that she is depressed. She reveals that she was recently separated from her husband and has been stressed at work. Which of the following elements of her presentation meet American College of Rheumatology criteria for fibromyalgia? A. Diffuse chronic pain and abnormal sleep B. Diffuse pain without other etiology and evidence of major depression C. Major depression, life stressor, chronic pain, and female gender D. Major depression and pain on palpation at 6 of 18 tender point sites E. Widespread chronic pain and pain on palpation at 11 of 18 tender point sites

What is the most common extraarticular manifestation of ankylosing spondylitis

A. Anterior uveitis B. Aortic regurgitation C. Cataracts D. Inflammatory bowel disease E. Third-degree heart block

?

A 52-year-old female has poorly controlled rheumatoid arthritis on prednisone 5 mg daily and etanercept 50 mg weekly by subcutaneous injection. Despite this, she has ongoing symptoms with severe pain in the wrists, hands, feet, and ankles. She also has destructive arthritis causing swan-neck and boutonnière deformities in the hands as well as plantar subluxation of the metatarsal heads that prevents ambulation. She has subcutaneous nodules on the extensor surfaces of the arms. She presents to the emergency room complaining of fevers and dysuria. On physical examination temperature is 39.1°C (102.3°F). Heart rate is 112, and blood pressure is 122/76. The examination is unremarkable except for right costovertebral angle tenderness and splenomegaly. Laboratory studies at the time of presentation reveal a white blood cell count of 2300/mm3 with 15% polymorphonuclear cells, 75% lymphocytes, 8% monocytes, and 2% eosinophils. She is also anemic with a hemoglobin of 9.2 mg/dL and a hematocrit of 28.7%. The mean corpuscular volume is 88 fL. The platelet count is 132,000/mm3. A peripheralblood smear shows normocytic anemia without anisocytosis or poikilocytosis. She is found to have Escherichiacoli bacteremia related to a urinary tract infection. She is treated with ceftriaxone and does well. However, she remains anemic and neutropenic. The patient undergoes a bone marrow biopsy that shows hypercellularity with a lack of mature neutrophils. What is the most likely diagnosis? A. Acute myelogenous leukemia B. B cell lymphoma C. Disseminated Mycobacterium tuberculosis infection D. Felty’s syndrome E. Idiosyncratic reaction to etanercept

A 42-year-old female presents to the physician with 3 months of worsening dyspnea on exertion, malaise, and weakness. She reports that the symptoms have worsened gradually and are associated with low-grade fever, anorexia, and an 8-lb weight loss. She has trouble climbingstairs because of leg weakness and shortness of breath. Recently she has noticed that her arms tire while she is brushing her teeth or combing her hair. Her mother also commented that the patient seems to have difficulty rising from the couch. Her writing is normal, and she has no sensory symptoms. Physical examination is notable for a temperature of 37.8°C (100°F), bilateral lung crackles and diminished strength in the deltoids, quadriceps, and psoas muscles. Laboratory studies are notable for an elevated creatine kinase. Chest radiography shows bilateral interstitial infiltrates, and lung volumes are reduced to70% of the predicted values. Which of the following autoantibodies is most likely to be present in this patient? A. Antiglomerular basement membrane antibody B. Antihistone antibody C. Anti-Jo-1 antibody D. Antimicrosomal antibody E. Antineutrophil cytoplasmic antibody (

A 42-year-old Turkish man presents to his physician complaining of recurring ulcers in the mouth and on his penis. He states that the ulcers are painful and last for about 2 weeks before spontaneously resolving. In addition, he intermittently gets skin lesions that he describes as painful nodules on his lower extremities. You suspectthat he has Behçet’s syndrome. A pathergy test is performed. What response would you expect after injecting 0.3 mL of sterile saline under the skin? A. Development of 10 mm of induration with overlying erythema after 72 h B. Development of a 2- to 3-mm papule at the site of insertion in 2–3 days C. Development of granulomatous inflammation 4–6 weeks after the injection D. Development of an urticarial reaction within 15 min E. No reaction

A 35-year-old female presents to her primary care doctor complaining of diffuse body and joint pain. When asked to describe which of her joints are most affected, she answers, “All of them.” There is no associated stiffness, redness, or swelling of the joints. No Raynaud’s phenomenon has been appreciated. Occasionally she notes numbness in the fingers and toes. The patient complains of chronic pain and poor sleep quality that she feels is due to her pain. She previously was seen in the clinic for chronic headaches that were felt to be tension-related. She has tried taking overthe-counter ibuprofen twice daily without relief of pain. She has no other medical problems. On physical examination, the patient appears comfortable. Her joints exhibit full range of motion without evidence of inflammatory arthritis. She does have pain with palpation at bilateral suboccipital muscle insertions, at C5, at the lateral epicondyle, in the upper outer quadrant of the buttock, at the medial fat pad of the knee proximal to the joint line, and unilaterally on the second right rib. The erythrocyte sedimentation rate is 12 s. Antinuclear antibodies are positive at a titer of 1:40 in a speckled pattern. The patient is HLA-B27-positive. Rheumatoid factor is negative. Radiograms of the cervical spine, hips, and elbows are normal. What is the most likely diagnosis? A. Ankylosing spondylitis B. Disseminated gonococcal infection C. Fibromyalgia D. Rheumatoid arthritis E. Systemic lupus erythematosus

A 45-year-old African-American woman with systemic lupus erythematosus (SLE) presents to the emergency room with complaints of headache and fatigue. Her prior manifestations of SLE have been arthralgias, hemolytic anemia, malar rash, and mouth ulcers, and she is known to have high titers of antibodies to double stranded DNA. She currently is taking prednisone, 5 mg daily, and hydroxychloroquine, 200 mg daily. On presentation, she is found to have a blood pressure of 190/110 mmHg with a heart rate of 98 beats/min. A urinalysis shows 25 red blood cells (RBCs) per high-power field with 2+ proteinuria. No RBC casts are identified. Her blood urea nitrogen is 88 mg/dL, and creatinine is 2.6mg/dL (baseline 0.8 mg/dL). She has not previously hadrenal disease related to SLE and is not taking nonsteroidalanti-inflammatory drugs. She denies any recent illness, decreased oral intake, or diarrhea. What is the most appropriatenext step in the management of this patient A. Initiate cyclophosphamide, 500 mg/m2 body surfacearea IV, and plan to repeat monthly for 3–6 months. B. Initiate hemodialysis. C. Initiate high-dose steroid therapy (IV methylprednisolone, 1000 mg daily for 3 doses, followed by oral prednisone, 1 mg/kg daily) and mycophenolate mofetil, 2 g daily. D. Initiate plasmapheresis. E. Withhold all therapy until renal biopsy is performe

A 32-year-old pregnant woman presents to clinic with right thumb and wrist pain that has worsened over several weeks. She has pain when she pinches her thumb against her other fingers. On physical examination she has mild swelling and tenderness over the radial styloid process, and pain is elicited when she places her thumb inher palm and grasps it with her fingers. A Phalen maneuver is negative. Which condition is most likely? A. Carpal tunnel syndrome B. DeQuervain’s tenosynovitis C. Gouty arthritis of the first metacarpophalangeal joint D. Palmar fasciitis E. Rheumatoid arthritis

Which of the following is true concerning a 68 year old male with type 2 diabetes diagnosed with type IV renal tubal acidosis? 1) Aminoaciduria would be expected. 2) Fludrocortisone treatment is effective 3) Increased Glomerular filtration rate is expected. 4) Increased urinary bicarbonate would be expected. 5) Normal renal handling of K+ and H+

Factors predisposing to urinary stone formation includes all of the following EXCEPT – – – –

Increased consumption of Calcium rich foods Increased consumption of oxalate rich foods Hypocitraturia Water deprivation

All are indications of renal biopsy except: Failure to recover from acute renal failure Diagnosis of systemic diseases with renal involvement Nephrotic syndrome Uncontrolled hypertension

statistics

Types of studies •

Experimental;

- Individuals are divided into groups; 1 group taking a new drug & the other group take old drug or placebo (control gr). Which is either; 1. Double blind (doct & pt). 2. Single blind (pt). 3. Unblinded.

•

Crossover;

-

Each pt receive ttt & placebo, one following the other. Use small no of patients. Used in chronic dis & ttt that lead to temporary relief.

•

Observational;

• 1.

Only observe what happens without intervention. Cohort prospective; follow up study. e.g. take 1 group of smokers & non smokers & f.u. who will get the cancer. Case control; search in the past e.g. take cancer pt & search who was smoker in the past. (healthy control). Cross sectional; e.g. present pt on pills, how much have endometrial cancer?

2. 3.

Types of studies Cohort (prospective) study; one group with an exposure of interest is selected and compared over time with another cohort without that exposure. to study short period disease e.g. smokers & follow them, use incidence. • Disadv; expensive, liable to losses, drop out. • Adv; 1. ideal to study disease causal relationship & temporal relationship between disease & risk exposure, 2. ↓recall bias. 3. To see multiple outcomes. Cross sectional study; use prevalence to study the prevalence of disease. also called prevalence studies, look at the number of cases of a disease at a particular point in time. They are not useful for investigating rare diseases or exposures. Case control (retrospective) study; • Adv; 1. To study rare diseases 2. Suitable for dis of long latent period 3. Less costly , easy, rapid. • Disadv; 1. More prone to bias. 2. Difficult to prove temporal relationship between dis & exposure (risk)

• Meta analysis; when you combine data of 2 or more large previous studies to conclude new database regard the point of research. Advantage; rapid, cheap. • Sequential trial; data are analyzed after each participant individual results become available, so the trial is continued until clear benefit is seen in one of comparing groups. Advantage ;shorter than fixed length trial, used when outcome of interest is known relatively quickly. • factorial trials test two or more treatments simultaneously.

•

Ecological study; (Geographical studies) does not give data on individuals but give idea about average values on groups of people . (use prevalence or incidence) e.g. incidence of Ca colon in certain population. • Screening test; 1. Should identify pts who require further investigations or ttt. 2. Should be safe, acceptable.

Q; A researcher is trying to design a study to find out the cause (or causes) of a rare disease, about which very little is known. What study design is most likely to be appropriate? A : Geographical B : Cross-sectional C : Cohort D : Intervention E : Case control.

Concerning cohort studies, which one of the following statements is true? A : They can only be used to compare two groups with one another. B : They are particularly useful with rare outcomes. C : Cohort studies are retrospective. D : They are better than other study designs for measuring prevalence of a disease in a population. E : They are better than other study types for measuring the incidence of a disease in a population.

Regarding case-control studies, which one of the following statements is FALSE? A : They are good for investigating rare diseases. B : They may be un-interpretable if controls are selected poorly. C : They are good for identifying rare causes of disease. D : They can examine multiple risk-factors for a single disease. E : They compare exposures of interest in cases and controls.

• Case-control studies compare exposures of interest in cases and controls. Two of their great strengths is that they can be used with rare diseases (because cases are pre-selected), and can examine multiple risk-factors (exposures). They are not good at identifying rare exposures. • If the question is whether or not a rare exposure causes a disease then the appropriate design is a cohort study, where one group with the particular exposure of interest is compared with a control group without that exposure. The greatest difficulty in designing case-control studies is selection of an appropriate control group, and poor control selection often makes otherwise well-conducted studies uninterpretable.

Regarding crossover trial design, which one of the following statements is true? A : It can be used to compare treatments for an acute infection. B : It is a good method for comparing analgesics in arthritis. C : It cannot be double-blinded. D : It cannot be randomized. E : Tends to need more patients than are required with other trial designs to get adequate statistical power.

• B: • The principle of a crossover design is that a patient has one drug or treatment, then a washout period, and then another drug, and the effect is compared between the two in a single individual. • For this reason it is a good study design for treatment of chronic conditions, but not appropriate for acute conditions. It is just as easy (or difficult) to randomize and double-blind as for other study designs. Because each person is acting as their own control, it is usually possible to use smaller numbers to get the same power.

Interpreting Randomized controlled trials of therapeutic interventions (= experimental studies) Types of errors; 1. Confounding; ‫ﺗﺎﺛﯾرﻋﻧﺻر ﻣﺧﺗﻠف ﻋﻠﻲ اﻟﻧﺗﯾﺟﺔ‬ in which a measured effect attributed to a particular variable is in fact dt an unmeasured co- variable. e.g. age is a Confounding factor in a study of effect of folic acid supp. During pregnancy on neural tube defects. i.e. older women will have ↑ risk of neural tube defect irrespective of folic acid supp. Avoided by matching individuals in the groups acc. To potential confounders. 2. Bias; ‫اﺧﺗرت ﻣﺟﻣوﻋﺎت و ﺗﺟﺎھﻠت ﺷرﯾﺣﺔ ﻣن اﻟﻧﺎس‬ -Systemic differences bet groups that distorts the comparisons between those groups = non randomized sampling. Bias means a flaw in study design that leads to a built-in likelihood that the wrong result may be obtained. E.g. TB in Cairo. Avoided by random sampling & choose a reasonable study. 3. Sampling error; Arise because not all the population is examined but only a sample is taken. So the bigger the size of the sample, the smaller the sample error.

Types of data; 1. Qualitative data; proportion in the population 2. Quantitative data; mean, mode, median & standard deviation. Mean= is the arithmetic average.(sum/ n) Median= is the middle value.(1st + last /2) Mode= is the value that occurs most often.

mean

mode median

Distribution;

80 100

70

90

60

80 70

50 East

60 East Line 2 Line 3

40 50

30

40

20

30 20

10

10

0 1st Qtr

2nd Qtr

3rd Qtr

4th Qtr

Skewed distribution = asymmetrical

5th

0 1st Qtr

2nd Qtr

3rd Qtr

4th Qtr

Normal distribution

5th

Mean Mean= X = (sum of all observed values) (n of sample size) It is a measure of the overall magnitude of the observations.

Standard deviation - It is a measure of the variability of the values -is a measure of the scatter of observations about the mean - is the square of the variance SD= √ variance . - If the values are normally distributed, then: • Approximately 68% of the values lie within +/- 1 SD of the mean. • Approximately 95% of the values lie within +/- 2 SD of the mean. • i.e. x +/- 2 SD should include about 95% of the observation.

• Mode is the value that has the largest frequency distribution (most frequent value). • The median is the value above & below which ½ of the values lie. (‫)اﻟﻘﯾﻣﺔ اﻟوﺳطﯾﺔ‬ • In the normal distribution the mean, mode, median all have the same value ( so we use the mean) • but in the Skewed distribution, we prefer the median.

Q: If data are skewed, then they should be summarized in the form: A : mean and standard deviation. B : median and range C : mean and range D : median and standard deviation E : mean and 95% confidence intervals.

• B: • Comment : Skewed data should always be summarized using the median and range. Standard deviation is based on the mean, which is not appropriate for skewed data. • How do you decide if data are skewed? Plot them out and look at them, or find the median and calculate the mean: if these are more than slightly different, then the data is skewed.

Q: If a characteristic is normally distributed in a population; A this means that most of the population is composed of normal individuals B there will be equal numbers who have more or less of the characteristic than the mean C the median value will be greater than the mean D ten percent of individuals will be beyond two standard deviations from the mean .

• answer true = b a- nonsense b- i.e. the values will be symmetrical about the mean c- median =mean in normal distribution d-about 5% mode = mean

• The standard error is a measure of how precisely the sample mean approximates the population mean. • standard error = standard deviation √n as n ↑, standard error ↓.

Confidence intervals • The interval (mean +/- 2 st error) is an approximate 95% confidence interval for the pop. mean i.e. we are 95% confident that the true mean lies inside this interval. • The interval (mean +/- 1.64 st error) is a 90% confidence interval. NB; • SD gives a measure of the spread of the data values. • S error is a measure of how precisely the sample mean approximates the pop. Mean. • E.g. FEV1 in 100 students Mean = 4.5 liter SD = 0.5 liters. - The interval where 95% of values lie is = mean +/- 2 st dev. =4.5 +/- 1 =3.5- 5.5 - The 95% confidence interval for pop mean= mean +/2 SE = 4.5 +/- 2 (0.5/ √ 100) = 4.5 +/- 2 (0.05)= 4.5 +/- 0.1= 4.4- 4.6 liters.

NB: • the larger the sample size, the narrower the confidence interval. • An outcome which varies widely in the pop will produce a wider confidence interval.

Correlation & regression • • •

It is the relationship between 2 variables in the same individual (X & Y). r= correlation coefficient, r is never <-1 or >1, if r= +/- 1=perfect+/-=all pairs lie on the line, values near 1 or -1 show significant correlation. b= regression coefficient= measure the average increase in y/ unit increase in X= slope of the line.

0
-1
+ve correlation R=0 B=0

-ve correlation

R=0 B=0

No association

Non linear association

Q: The following statements are correct: A A correlation coefficient (r) of 0.04 is almost certainly significant. B The values of chi-squared range from 0 to +1. C The standard error of the mean is always less than the standard deviation. D A p value of 0.001 for the difference between two sample means is more significant than one of 0.01 E A confidence interval is the mean +/- 2 standard deviations.

• answer true = d a- values near 1 or -1 show significant correlation. b-probability (p) ranges from 0 to +1, c- standard error of the mean = standard deviation / square root of n. e-for a normal distribution a confidence interval for a mean can be given by +/1.96 standard errors of the mean.

How large was the difference between the intervention & the control groups in Randomized control trials •Control event rate (CER) = absolute risk. = risk of outcome (e.g. mortality) in the control group •Experimental event rate (EER) = risk of outcome (e.g. mortality) in the Experimental gr .relative risk of avoiding the event= 100-EER. •Absolute risk reduction (ARR) = CER-EER •Relative risk reduction (RRR) = CER-EER/CER •Number needed to treat (NNT)= 1/ARR

If 9.4% of patients given aspirin after myocardial infarction die (EER), compared with 11.8% of those not given aspirin (CER), then the absolute risk reduction (ARR) produced by aspirin is 11.8 – 9.4 = 2.4%, the relative risk reduction (RRR) when taking aspirin is 2.4/11.8 = 0.2 (20%), and the Number needed to treat (NNT) is 1 divided by 0.024 = 42, meaning that 42 patients with myocardial infarction must be treated with aspirin to prevent one death.

• the relative risk of avoiding the event (e.g.mortality) in experimental group = 100- EER= 100- 9.4=90.6%. • The odds of avoiding the event (mortality) in experimental group = RR of avoiding / EER = 90.6/9.4= • the relative risk of avoiding the event (e.g.mortality) in the control group =100- 11.8= 88.2% . • The odds of avoiding the event (e.g.mortality) in the control group =RR of avoiding /CER= 88.2 / 11.8 = . • Odd ratio (OR)= odds of E/C NB: In general, ORs & RRs tend to be rather similar when the CER < 20%, above this point, the figures divert (OR tends to be higher).

Q: A placebo-controlled study randomized 10 000 patients undergoing surgery for hip fracture to 160 mg aspirin / day, started preoperatively and continued for 35 days. About 1.5% of the patients allocated aspirin had DVT or pulmonary embolism (PE), compared with about 2.5% allocated placebo. Which one of the following statements about this trial is true? A : Aspirin produced a 1.5% absolute risk reduction in DVT/PE. B : Aspirin produced a 40% absolute risk reduction in DVT/PE. C : Aspirin produced a 1% proportional risk reduction in DVT/PE. D : Aspirin produced a 40% proportional risk reduction in DVT/PE. E : The Number Needed to Treat (NNT) to prevent one DVT/PE is 100/1.5 = 67.

• D: • Comment : In this study aspirin reduces the risk of DVT/PE from 2.5% to 1.5%: this is an absolute risk reduction of 1% and a proportional (or relative) risk reduction of 1/2.5 = 40%. • The NNT to prevent one DVT/PE is 1/absolute risk reduction = 1/0.01 = 100.

Q: In a study of patients with myocardial infarction, the death rate of those given aspirin is 8%,compared with 10% in those not given aspirin. This means that: A : the relative risk of death after myocardial infarction is 1.25 in those given aspirin B : the relative risk reduction produced by aspirin is 2% C : the number needed to treat with aspirin to prevent one death is 8 D : the number needed to treat with aspirin to prevent one death is 10 E : the absolute risk reduction produced by aspirin is 2%.

• Absolute risk reduction (or increase) = (Risk in group 1) minus (Risk in group 2), which is 2% in this example. • Relative risk reduction is the difference of outcome in one group compared to another = (Risk in group 1) divided by (Risk in group 2). In this case aspirin reduced relative risk by 20%. • The Number Needed to Treat = 1 divided by (Absolute Risk Reduction), which is 1/0.02 or 50 in this example.

• Probability (P) = Prevalence= % = diseased/population.

• To convert probability to odd; Odd= P/1-P. e.g. 20% probability= 20/1-0.2 or 20/100-20= 20/80= 1/4= 0.25.

• To convert odd to probability: P= O/1+O. e.g. if odd = 1:3, prob= 1/1+3=1/4=25%. Means that for every 3 healthy there is 1 diseased so there is 1 dis among total of 4 so the diseased are 25%.

• P value is the probability of no difference (similarity) (null hypothesis). • The smaller the P value, the bigger the difference. ( the more significant the difference) less likely of null hypothesis is true. • If P value >0.05 the results would be found by chance in more than 1:20. • The conventional cut-off for significance is P=0.05, or a 1-in-20 chance. Hence if 20 trials were conducted, you would expect to get one that was ‘positive’ by chance alone. • null hypothesis= non significant difference. • Type I error; reject the null hypothesis while it is actually true. Help to determine sample size, In practice this means that the study claims to find a difference that does not really exist. • Type II error; acceptance of the null hypothesis while it is false. Power of the study= 1- Type II error

• Sensitivity is the probability that a test will be positive when a patient has the condition. Sensitivity= true +ve /all diseased. • Specificity is the probability that a test will be negative when a patient does not have the condition. Specificity = true -ve /all non diseased (healthy). • Positive predictive value of a test (PPP)= post test probability of a +ve test = true+ve/ all +ves. • negative predictive value of a test (NPP)= post test probability of a -ve test = true-ve/ all -ves. Diseased

non

New test +ve

True +ve

False +ve

New test -ve

False -ve

True -ve

Q: The specificity of a test is defined as follows: A : The number of true negatives detected by the test divided by the number of all true negatives& false positive in the population tested. B : The number of true positives detected by the test divided by the number of all true positives in the population tested. C : The number of true positives detected by the test divided by the total number of true positives in the population tested. D : The number of true negatives detected by the test divided by the total number of true negatives in the population tested. E : The number of true negatives detected by the test divided by the total number of true positives in the population tested.

• Likelihood ratio of a +ve test (LR+ve)= Sensitivity /1-specificity. • Likelihood ratio of a -ve test (LR-ve)= 1-Sensitivity /specificity • Pretest probability= prevalence in the population= diseased/ total no. • Pretest odds= convert probability above to odds (Odd= P/1-P). • Postest odds= Pretest odds X LR+ve • Postest probability= convert above odds to probability (Postest P= O/1+O). • Accuracy= all true results/ all results = probability of correct results. • reliability is the ability of a test to produce the same result when repeated under identical conditions. • The validity of the test is defined as the relevance of the test to the activities being treated. • Efficacy= the effect of something under ideal or lab conditions.

• A clinical investigation examined the effectiveness of a new test in diagnosing Pancreatic carcinoma. The sensitivity was reported as 70%. Which one of the following statements is correct? 1 )70% of people will be correctly classified as having the disease 2 )70% of people with an abnormal test result will have the disease 3 )70% of people with a + test result will not have the disease 4 )70% of people with the disease will have an abnormal test result 5 )70% of people with the disease will have a - test result

Q: The statistical reviewer of a paper states

that they are concerned that the findings are biased. In statistical terms, ‘bias’ means: A : There is a flaw in study design that leads to a builtin likelihood that the wrong result may be obtained. B : There is a flaw in statistical analysis leading to a likelihood that the wrong result may be obtained. C : There is reason to believe that the authors wanted to obtain the result that the study showed. D : Both study design and statistical analysis are flawed, leading to a likelihood that the wrong result may be obtained. E : The study is not of sufficient statistical power to exclude the missing of a significant effect.

A • Bias means a flaw in study design that leads to a built-in likelihood that the wrong result may be obtained. It cannot be controlled for at the analysis stage. It can be extremely difficult to design studies without potential bias, particularly when there are complex interactions between exposures under study. Techniques such as restriction and stratification are commonly used to reduce potential for bias.

A 95% confidence interval means: A : 95% of the data fall within the confidence interval. B : there is a 95% chance that two groups are different C : that p=0.05 D : there is a 95% chance that the true value falls within the confidence interval E : there is a 95% chance that the finding is clinically significant.

• D: • Comment : The 95% confidence intervals (95% CI) around a value are the range within which there is a 95% chance that the true value lies. • Similarly, the 95% CIs around a difference are the range in which there is a 95% chance that the true difference lies. • If the means of two groups have overlapping 95% CIs, then the two groups are not statistically significantly different. If the 95% CI of the difference between two groups overlaps zero, then the difference between the two groups in not statistically significant. • Statistical and clinical significance should not be confused. A very large study can generate very narrow 95% CIs (or very small p values) for very small differences, which may be of no clinical significance at all. • By contrast, a small study may fail to show a statistically significant effect even if the effect is both large and clinically important.

Parametric tests means that the data will be of normal distribution. 1. Paired test or student T test is used if the members of the groups are well matched = paired. E.g. each diseased pt is matched with healthy individual of same age & sex. 2. Unpaired T test is used to compare the average values of 2 independent groups e.g. pts with & without disease/ treated vs. placebo. When you compare independent or diff groups, use unpaired t test. • 1. 2. •

Non- Parametric tests means that the data will be of Skewed distribution. Wilcoxon or Mann-Whitney U-test Chi-square test  Used to compare % or proportion between 2 groups. In correlation coeffecient (r)  r takes values between -1 & 1. the closer it is to zero, the less linear association.

• Chi-squared tests are used to compare 2 (%) or 2 proportions= used to test the difference between 2 nominal variables (count data). • The larger the value X2 the smaller the p value, the more significant the test. • Chi 2= X2= (observed-expected)2/expected to be compared with standard critical or standard table for determined degree of freedom. • degree of freedom= (raws-1)x(columns-1). • It assume that all table cells have expected freedum >1. • It assume that 80% of table cells have expected freedum >5.

Regarding the description and comparison of two groups of data, which one of the following statements is true? • A : Categorical data should be described as percentages and compared using a Student’s t-test. • B : Normally distributed continuous data should be described as median and range and compared using a Chisquared test. • C : Skewed continuous data should be described as median and range and compared using a Wilcoxon ranksum test. • D : Normally distributed continuous data should be described as mean and standard deviation and compared using a Chi-squared test. • E : Skewed continuous data should be described as mean and standard deviation and compared using a Student’s ttest.

• C • Comment : Categorical variables are not continuous, e.g. drug / placebo, dead / alive. They should be described as percentages or proportions and compared with a Chisquared test. • Normally distributed continuous data should be described as mean and standard deviation and compared with a Student’s t-test. • Skewed continuous data should be described as median and range and compared using a test such as the Wilcoxon rank-sum test or the Mann-Whitney U-test.

• researcher compared the mean scores of nausea on a rating scale between standard therapy & a new drug in the treatment of chemotherapy induced nausea. • Which one of the following is the appropriate statistical test? 1 )Chi-square test 2 )Paired T-test 3 )Life table analysis (log rank test) 4 )Pearson correlation 5 )Unpaired T-test

• Answer 5: • The two-sample unpaired t test is used to test null hypothesis in two populations corresponding to two random samples are equal. • For a paired t test, the data are dependent, i.e. there is a one-to-one correspondence between values in the two samples. For example,the same subject measured before & after a process change, & the same subject measured at different times.

Q: To compare two groups of categorical data, e.g. dead / alive by drug / placebo, the correct test is: A : Student’s t-test B : Analysis of variance (ANOVA) C : Wilcoxon rank-sum D : chi-squared E : p value

• D: • Comment : Chi-squared tests (and variants there of) are widely used to compare percentages or proportions of categorical data. From the chi-squared statistic a p value is read off a statistical table to give the degree of significance. Traditionally a p value of less than 0.05, indicating a less than 5% probability that a result has arisen by chance, is taken (arbitrarily) as indicating that chance alone is not responsible for the difference between groups. • Normally distributed data can be compared with a Student’s t-test (with correction for multiple comparisons when appropriate). • Skewed continuous data can be compared with a Wilcoxon rank-sum test or a Mann-Whitney U-test.

In a trial of a new drug the following results were obtained:treatment group 44 improved 16 not improved, placebo group 36 improved 26 not improved. A the results so obviously show the benefit of treatment that statistical analysis is not required. B the data could be evaluated using the chi-squared test C Pearson's coefficient of linear regression would be an appropriate significance test D the numbers are too small to draw any conclusions E a Student t-test could be used

• answer true = b a-Nothing is ever that obvious surely. b-This data would be ideal for a chi-squared test. c-nonsense there is no linear regression to plot e-We are comparing proportions not means.

Q: Concerning the statistical power of studies, which one of the following statements is FALSE? A : International journals do not publish studies that are underpowered. B : A power calculation must always be performed before conducting randomized clinical trials. C : A type II error occurs if it is claimed two treatments are the same when the study is not large enough to detect equivalence. D : A type I error is where the null hypothesis is falsely rejected. E : The smaller the difference you want to detect, the larger a study must be.

• A: • Comment : It is only ethical to conduct a clinical trial if it is capable of detecting a meaningful difference between two treatments to guide future practice. If a trial is underpowered it cannot detect a statistically significant difference. • It is therefore mandatory to do a proper power calculation before exposing patients to a clinical trial. The rather daunting formal definition of a type I error means that a study falsely (but not deliberately) appears to find a difference between two groups which has actually arisen by chance alone. The conventional cut-off of p <0.05 will arise by chance alone one time in twenty. • As many thousands of studies are published every month, type I errors are not rare. • A type II error is formally where the null hypothesis is falsely accepted. To claim two treatments are ‘equivalent’ requires huge numbers, and most studies are underpowered (too small) to reliably rule out a small difference between one treatment and another. • Most published studies are small enough that type I and type II errors are a real possibility, and examples are published in good journals every week.

Q: A report of a clinical trial of a new analgesic states "In a comparison between the new drug and a placebo a higher proportion of patients taking the new drug obtained relief from pain (p<0.05)". It follows that:A the trial was well designed B amongst 100 patients treated with the drug five would be expected to have a placebo response C the result may have occurred by chance alone on less than one in 20 occasions D the probable error of the observations is +/- 5%

• answer true = c

Q: Regarding a randomized trial in which a new treatment for Clostridium difficile diarrhea is compared with an established treatment. A reviewer states that they are concerned that there might be type 2 statistical error. What does this mean? A : That the method of statistical analysis used is inappropriate. B : That the study has shown a difference between the treatments that is statistically significant but which is unlikely to be clinically significant C : That the study claims to find a difference that does not really exist, ie. the result is a statisticalfluke D : That the data is skewed (not normally distributed) and analysis should have used non-parametric rather than parametric statistical techniques E : That the study claims that there is no difference between the treatments, when in reality the trial was just too small to detect a difference.

• E: • The null hypothesis is always that there is no difference between groups under study. A type 1 error occurs when ‘the null hypothesis is falsely rejected’. In practice this means that the study claims to find a difference that does not really exist,. A type 2 error occurs when the null hypothesis is falsely accepted’. This means that it is claimed that there is no difference between two groups, when in reality the study is simply too small to detect a difference. This type of error can be avoided by making explicit power calculations before embarking on any study. This will answer the question ‘if I am studying an outcome that occurs in (say) 20% of a conventionally treated group and want to show a (say) halving in the rate of this outcome, then how many patients do I need to study?’

A type 1 statistical error in a clinical trial means that: A : patients were not allocated into groups with an appropriate randomisation method B : the null hypothesis is falsely accepted C : the null hypothesis is falsely rejected D : the statistical analysis was incomplete or incorrect E : the statement of the hypothesis to be tested was incomplete or flawed.

• C: • Comment : A type 1 error is formally defined as being where the null hypothesis (which is that there is no difference between the groups) was falsely rejected. In practice this means that the study claims to find a difference that does not really exist.

Molecular medicine

•

Genome= complete complement of coding genes. • Transcriptome= complete complement of expressed m RNA. • Proteome= protein translated from m RNA. • 2 organism may have the same n of genes but diff proteins dt; 1. Variation in gene expression (temporal, spatial). 2. Post transcription (diff. exons, splicing). 3. Post translation (glycosylation, sialydation).

• Human genome = 30.000 gene. • Each cell express 16.000 gene. • Housekeeping genes =genes expressed in all cells to provide basic function for cell survival (constitutive). • Microarray analysis of transcriptome  identify the expressed genes.e.g.

Gene 3’

5’ RNA polymerase binding site

Transforming factor binding sites

TATA box

Promotor elements

ex

in

ATG Translation Starting site

ex

in

Translation termination code

• • • • •

•

•

Exons= segment of the gene transcripted into m RNA then translated into proteins. Introns= segment of the gene transcripted then removed by splicing (not translated). Promotor elements = binding sites for initiation of transcription complex at 5’. TF can activate any gene that has a TATA box. TATA box= - a promotor element. - at 25-30 base pairs from the start of transcription. - anchor to RNA polymerase II. Enhancers= - present at 5’ or 3’. - not obligatory for initiation. - but ↑ gene expression. TF; - basal = constitutive - Housekeeping genes. - inducible = temporal, spatial expression of genes for tissue phenotype. Application of TF; 1- many cong malformation are dt inherited mutation of TF. 2- can be oncogenic e.g. CMyC, P53. 3- steroids affect TF.

• cyclins= are proteins key regulators of cell cycles. • telomere = DNA sequence at the end of each chromosome become progressively shorter with each cell division when it is reduced to a critical length, the cell is not capable of dividing. The enzyme telomerase lengthen it.

• Haplotype patterns= group of genes or alleles carried on the same chr, closely linked, travel together during meiosis, inherited as a unit. • Gene mutations; - mismatch = change in the nucleotide. - inversion= nucleotide base removed, reverse directed & reinserted. - point mutation; single base pair substitution.

• Analysis of the proteome is better as it detects changes at the protein level, not reflected at transcriptome level dt Post translation processing.(bioinformatics).

• Direct DNA testing = identify abn within specific gene. - PCR. - restrictive enzyme digestion. - southern blot. - sequencing. • Indirect DNA testing = unknown gene by tracking DNA markers in different members of the family (linkage analysis).

• southern blot (lab procedure); electrophoresis of DNA fragment through gel  solid memb as nitrocellulose+ labelled probe  visualised under x ray film. • Northern blot is a mean to detect RNA (uracil instead of thymine in m RNA). • Somatic cell hybridization; - method for gene maping. - using 2 diff species, chr from 1 species is selectively lost resulting in clones of certain chr of the another species. • FISH; fluorescence in situ hybridization, labeled probes are hybridized to chromosomes, and the hybridized probes are detected with fluorochromes.  visualised under florescent microscope, This technique is a rapid and sensitive means of detecting recurring numerical and structural abnormalities. for microdeletions & trisomy. • SSCP (single strand conformation polymorphism analysis); is a technique for detecting variation in DNA sequence by running single stranded DNA fragments through a non denaturating gel.

• • • 1. 2. • 1. 2. 3. 4. • • •

PCR Def; it is an amplification reaction in which a small amount of target DNA (template) is amplified to produce enough amount to perform analysis. PCR is powerful (need only one copy). Uses= Detect viral or bact DNA. Detect mutations. Stages; Mix the specimen with 2 primers & Taq polymerase (thermostable DNA polymerase). Heat & cool primer anneal to template. Heat ( 72 c) polymerization. Repeat & analyse. Multiplex PCR; the use of more than 2 primers if more than one gene is to be identified. Nested PCR; when the sequence to be amplified need special definition e.g. resemble others. rt PCR (reverse transcriptase ); instead of DNA template, we take the m RNA (expressed genes) & transform it into DNA by reverse transcriptase enzyme (retroviral) as the m RNA is unstable. uses; - detection of expressed genes in tumor cells. - research; function of certain dis gene in diff tissues.

Preparation of monoclonal Ab; • For specific protein detection. 1. Inject Ag into an animal. 2. Hybridize its splenic cells + Myeloma cells (no longer produce its Ab) Ab to this Ag. 3. Select most specific Ab  tissue culture. • Uses; - diagnosis (scan) & TTT of cancer (drugs as majic bullet & radiotherapy). - Transplantation & immunomodulation (OKT3).

Receptors A) Cell membrane surface receptors; 1- ligand gated Ion channel; e.g. neurotransmitter open ion channel - Nicotinic  Na. - GABA, Glycine  Cl. 2- receptors with protein tyrosine kinase (phosphorylation of tyrosine residue of receptors cascade of cytoplasmic prot). e.g. insulin, PDGF, prolactin, IGF1, MQ CSF, NGF, EGF. 3- G protein coupled ( is a protein that bind to guanine nucleotide). e.g. muscarinic, adrenergic. Dis associated with G protein abn e.g. cholera, Albright HOD, MeCune Albright S, pit adenoma. NB; prot kinases  add phosphate group to serine, threonine, tyrosine residue (# phosphatase)

B) Nuclear H; - no 2 ry mess. - intracytoplasmic receptors. - the complex travel to the nucleus & bind to hormone responsive elements.

Molecular pathogenesis of cancer 1.

Somatic evolution of Ca; escape from strictly regulated mechanism that control the growth of somatic cells. 2. Oncogenes; geneprotein cancer (=loss of growth control) protoncogene=Oncogene that is normally present in human cells i.e. C-onc e.g. C-Myc. Mutations resulting in tumors; • RAS = G protein cell growth  1/3 of tumours if mutated. • Mutations of protein kinases↑TF (Fos & Jun)+ Myc tumor. • In Burkitt lymphoma  C Myc is transposed to Ig heavy chain locus on chr 14 in lymphocytes ↑ its expression & ↑ cellular mitosis. • Philadelphia chr bcr + abl (9;22) fusion protein  tumor growth. 3. Tumor suppressor gene; • P53= normally function to inhibit cell cycle & abn growth, + apoptosis, if mutated tumor (most common cause of tumours). • Le- Fraumeni S; AD dis, ccc by cancer breast, sarcoma, brain dt inactivation of P53. • P27  Tumor suppressor gene through down regulation of cell cycle (cyclin dependent kinase inhibitor), if downregulated  sporadic Cancer colon.

Apoptosis • Def; is the morphological changes that accompagny the programmed cell death e.g. cell shrinkage, compaction of chromatin, nuclear & cytoplasmic apoptotic bodies phagocytosed by MQ, laddering of DNA on electrophoresis gel by activation of intracellular nucleases. • programmed cell death= naturally occurring cell death dt activation of a set of genes in response to ext signals e.g. from neighbour or extracellular matrix.

• Apoptosis; - non-inflammatory process. - no proteolytic enzymes. - no free radicals. - no damage of neighbouring cells. • E.g. – apopt of finger web, selection of neurons ( normal apopt in embrio). - apopt of excess or autoreactive T lymphocytes ( normal apopt in adult). - neurodegenerative dis, HIV (dis). - insufficient apoptosis e.g. cancer, autoimmune dis, viral dis. • Factors that + apoptosis; P53, P27, Fas or CD95 (receptor for TNF), withdrawal of GF. • Factors that - apoptosis; bcl2 (survival signals), B catenin accumulation adenoma. • Apoptosis occur through proteases called caspases (e.g. ICE= IL-1B converting enzyme) that + endonuleases. • Caspases = cysteine aspartate specific proteases.

P53 Fas, CD 95

+ +

_ Signals for cell death

+ TF +

caspases +

endonucleases

bcl2

• Cancer resists apoptosis by; - Mutation of P53. - Causing apoptosis of cytotoxic T cells (TNF like + Fas). - Over-expression of Bcl2.

Nitric oxide (NO) • • • • 1. 2.

Endothelial derived relaxation factor Produced from L arginine by oxidation of Nitrogen  NO + citrulin. ↑ C GMP (2ry mess) in neighboring cells. Produced in; Constitutive……..Vascular end & Nervous system  VD, ↓ sm hyperplasia, ↓ plat agg. new memory. Inducible………….. in MQ, PNL, plat, hepatocytecytotoxic.

•

Clinical application; - So used as nitrates or inhaled NO in pulm HTN. - endothelial dysf in DM, HTN, smokers & hypercholestrolemia is dt loss of NO bioavailability. - NO ↓ in atherosclerosis, HTN dt CRF, HRS, Alzeheimer. - NO ↑ in septic shock, ARDS, acute inflammation.

Endothelin I (VC) • ET-1 (end, sm, coronary, GIT). • Related to dis; - HTN, HRS, ARF, CHF, Raynauld’s. (VC) - VC following subarachnoid Hge. • ET1 receptor blockers & CEI used as anti HTN.

Pro-inflammatory cytokines • Il-1, TNF, TGF-B, Heat shock protein, free radicals. IL-1; Involved in; - Rh arthritis  IL-1 + collagenase, phospholipase, cyclooxygenese (facilitator of damage). - Atherosclerosis;  endo uptake of LDL  IL-1  ↑ PDGF. - Septic shock  IL1  ↑NO, PG, PAF  VD. - Infection, acute graft rejection  IL1  ↑ T & B lymph.

• TNF; + GM- CSF, + PG. α  MQ, esinoph, NK. ß  T lymph . • dis associated; Rheumatoid, MS, MOF. So, neutralizing Ab = anti- TNF α are used. • not used in cancer  highly toxic, + tumor growth.

TGF-ß • action; - tissue repair. - ↑ extracellular matrix. - fibrosis. • tissue injury  + plat release of TGF-B  chemotaxis  monocytes (+ fibroblast GF, TNF, IL-1) • involved in glomerulosclerosis, hep fibrosis, pulm fibrosis, bleomycin lung. • NB;

HSPs (Heat shock proteins) • heat, chemicals, free radicals  ↑ damage of intracellular proteins  ↑ HSP  ↑ cell resistance to stress through; - prot folding & unfolding. - degrad of prot ( by ubiquitination). dis associated; if mutated cataract, motor neuron deg. bact HSP + immune syst.

Free radicals Any molecule with 1or more unpaired electron (more reactive); peroxide, super, hydroxyl, NO. NB; hydroxyl is the most reactive. action; - lysosomes. - lipid peroxidation of memb. - mutations (by attaching purines & pyrimidine). Diseases  athero, cancer, neurodeg ( MND). Free radical scavengers; - α tocopherol (Vit E). - ascorbate (Vit C). - glutathione. - Beta carotene. - Flavenoids.

Adhesion Molecules • • -

Def; Molecules that interact as receptors & ligand. 4 groups; Ig ( CD2, CD3, NCA (neural cell adh), ICAM (intercellular) bind to LFA ( lymph funct ass)to recruit lymphocytes. - integrin ( cell to matrix) Integrins are surface receptors by which cells are attached to extracellular matrix.. - Cadherins (Nerve & Muscle ). - selectins ( leukocytes to endoth in inflam, over expressed in autoimmune viral hepatitis, organ rejection). • Clinical application; 1. leuk adhesions deficiency  recc bact sepsis. 2. integrin IIb IIIa ( plat receptor to fibrinogen) deficiency Glansman thrombathenia. Ab (abciximab) antithrombotic in coronary Ht.

Stem cells • • • •

progenitor cells. present in certain tissues e.g. BM, embrionic. embryonic totipotent (any tissue). BM  Bl. cells only, can be recruited by Ag sorting with CD34 Ab & undergo transdifferentiation to non hematologic cells.

47. A 24-year-old man presented with agitation and central chest • pain. He had been taking cocaine earlier in the day. On examination, he had a pulse of 100 beats per minute and a blood pressure of 170/110 mmHg. Which complication is most likely? • A B C D E

hypercalcaemia • hyperkalaemia • hyperthermia • hyponatraemia • hypothermia • C

•

Drugs affected by acetylator status; DHIPS (Dapson, hydralazine, INH, Procainamide sulphonamides) • Slow acetylators liable to adverse effect of the drug itself e.g. drug induced lupus. INH induced PN. • Fast acetylator  liable to adverse effect of the drug metabolites e.g. INH induced hepatitis & drug resistance. • Fast acetylation is a trait which is autosomal dominant inherited.

• The difference in speed of acetylation is due to the amount (or activity) of the enzyme N-acetyltransferase available.

Drug induced lupus • -

Drug list; Anti HTN; αMD, BB, clonidine, Hydralazine antiarrhythmics; procainamide, flecainide antibiotics; sulfa, minocyclin, INH. Neuro; chlorpromazine, haloperidol, lithium, phenytoin.

• C/P; arthralgia, butterfly rash, pleurisy, equal sex. • NB;- no renal involvement - no CNS. - Drug induced lupus occur with minocyclin not oxytetracyclin. - associated with slow acetylators & HLA DR4. - subacute cut lupus can occur with thiazide. • Investigation; - ↑ESR, ↑CRP, hypergammaglob, - +ve ANA, +ve antihistone - But anti DNA & RF are –ve. • TTT; Remits slowly when drug is stopped but may need steroid treatment to settle.

Rate of drug metabolism Drugs metabilized by : • Zero order kinetics; i.e. drugs whose metabolism is constant/ unit time, so ↑dose ↑↑↑ plasma cons. (liable to drug intoxication). E.g. phenytoin, hydralazine, lithium, theophilline, alcohol, fluoxetin. • 1st order kinetic; i.e. drugs whose metabolism is proportinal to drug conc. i.e. ↑dose↑ metabolism constant serum level (linear conc).

-

Drugs which are highly bound to plasma protein ; sulphonylureas, oral anticoagulants, salicylates, propranolol, ACEI, clofibrate.

• Enzyme inducers; i.e. induce the synthesis of hepatic enzymes (cytochrome P450) responsible for drug metabolism over days Treatment failure. List; PC BRAS + griseofulvin (Phenytoin, Carbamazipine, Barbiturates, Rifampicin, chronic Alcohol, sulphonylureas, griseofulvin). NB: no antibiotics! • Enzyme inhibitors; i.e. inhibit the synthesis of hepatic enzymes List; OAAK DEVICES (Omeprazole,Allopurinol, Amiodarone , ketoconazole, Disulfiram, Erythromycin, Valproate, INH, Cimetidine, cipro, acute ethanol, Sulphonamides) + Quinupristin & dalfopristin, simvastatin, fibrates. NB: many antibiotics! Drugs that are affected; Warfarin, OCP, steroids, phenytoin, carbamazipine, theophillins, cyclosporin, azathioprine.

B lactam antibiotics Inhibit bact cell wall., bactericidal 1. Penicillins 2. Cephalosporins 3. Monobactams= Astreonam (aerobic G-ve bacilli, so used instead of garamycin for abd sepsis. 4. Carbapenems. - Imepinem + cilastatin (Tienem) - Meropenem

Penicillins • • • • •

Benzyl pen (Pen G); contain B lactam ring. Pen V (oral, acid resistant.) Ampicillin, amoxacillin (bread spectrum) Antipseudomonas; Carbinicillin, piperacillin, ticarcillin, Azlocillin. Antistaph 1- B lactamase inhibitors; - Clavulonic acid + amoxacillin (Augmentin) - Sulbactam + ampicillin (Unasyn) - Tazobactam + piperacillin 2- B lactamase resistant - Mecicillin, oxacillin, cloxacillin

Mechanism of action; bind to peptidases involved in cell wall synthesis(-) cell wall synthesis. MRSA; staph that retain peptidase activity even in the presence of mecicillin.Ttt; vancomycin, teicoplanin Side effects; diarrhea ampicillin + IMN 90% rash. co-amoxaclav  cholestatic jaundice

Cephalosporins • B lactam antibiotics • Active # G+ve & G-ve except enterococci, listeria & anaerobes. • CLASSIFICATION 1. First generation; (cefazolin) most G +ve cocci except enterococci, MRSA, or penicillin-resistant pneumococci 2. Second generation less active against G +ve cocci but are more active against certain G –ve bacilli (cefuroxime) 3. Third generation more active against G-ve bacilli, and are highly active against Enterobacteriaceae. (cefotaxime, ceftriaxone, and ceftizoxime, cefoperazone and ceftazidime (antipseudo) 4. Fourth generation (cefepime) better penetration through the outer membrane of G-ve bacteria.

NB; • All of the cephalosporins except cefoperazone and ceftriaxone require dose modification in the presence of severe renal failure. • Biliary concentrations are particularly high for cefazolin, cefoperazone, and ceftriaxone. • The third generation achieve much more reliable CSF levels in patients with meningeal irritation. Cefotaxime, ceftriaxone, and ceftazidime are approved for the treatment of bacterial meningitis. • Fatal reactions due to calcium-ceftriaxone precipitates in the lungs and kidneys of neonates have been reported. The FDA has issued an advisory that IV ceftriaxone and IV calcium-containing solutions should not be co-administered to neonates, children or adults within 48 hours of one another.

Carbapenems. - Imepenem, Meropenem - B lactam antibiotics - The most broad spectrum Ab, Antibacterial activity includes resistant G-ve bacilli (Pseudomonas aeruginosa and Enterobacter sp), G +ve (MRSA and Streptococcus sp) and anaerobes. - Inactivated by the kid, so administered in combination with cilastatin (Imepenem) seizures if given in meningitis esp in renal impairment. • Side effects; • Central nervous system: Seizure • Dermatologic: Rash • Gastrointestinal: Nausea , diarrhea , vomiting • Genitourinary: Oliguria/anuria • Local: Phlebitis/thrombophlebitis , pain at I.M. injection site.

Side effects of B lactams • • • • • • •

•

•

allergic reactions Serum sickness drug-induced lupus, Skin; morbilliform rash is the most common. Erythema multiforme , StevensJohnson syndrome. Exfoliative dermatitis. Toxic epidermal necrolysis .. Hypersensitivity angiitis - palpable purpura. photosensitivity reactions. Neurologic reactions — high-dose penicillin therapy (>20 million units per day), are the most common to cause encephalopathy. Imipenem in renal disease. Pulmonary eosinophilia, GIT; - Diarrhea, esp ampicillin or amoxicillin. Clostridium difficile colitis, esp with ampicillin . - hypersensitivity hepatitis. Ceftriaxone may cause biliary sludge. - Suppression of gut flora  vitamin K deficiency Hypoprothrombinemia Renal reactions - Glomerulonephritis with hypersensitivity angiitis or serum sickness. methicillin allergic interstitial nephritis - ticarcillin (disodium salt),  sodium overload and hypokalemic alkalosis . Hematologic reactions — immune-mediated destruction of PNL,with eosinophilia, hemolytic anemia, immune thrombocytopenia. Platelet dysfunction may be caused by high doses of ticarcillin.

Macrolides • • • • • • • •

(-) protein synthesis Spiramycin Toxoplasma Erythromycin Clarithromycin. Azithromycin. Uses; legionella, Mycoplasma, chlamidia, coxiella, Campylobacter, bordetella pertussus. Side effects; prokinetic V, D, abd pain. Cholestatic jaundice ↑QT torsade de point enzyme inhibitor, so ↑toxicity of theophillin, digoxin, carbamazepine, cyclosporin.

fluoroquinolones • MECHANISMS OF ACTION; (-) DNA gyrase , Nucleic acid synthesis bactericidal

wide spectrum of activity. • Spectrum; - against aerobic G-ve bacilli, particularly Enterobacteriaceae, Haemophilus , Pseudomonas and G-ve cocci as Neisseria spp. ,Moraxella & staphylococci - Levofloxacin and moxifloxacin, however, have greater potency against gram-positive cocci, anaerobic bacteria & TB, atypical pneumonias; • PHARMACOKINETICS — • oral bioavailability, 70 – 95%. • No dose adjustment of moxifloxacin in the presence of renal failure. • Otherwise ↓The dose in patients with creatinine clearances below 50 mL/min. • Clearance by hemodialysis is low • Should be avoided in pregnancy, lactation & children < 18 yrs old.

• Side effects; - GIT; mild ANV, less frequent diarrhea. - CNS; headache and dizziness, seizure with theophylline and NSAIDs - Rash and other allergic manifestations, photosensitivity - Arthropathy, Tendinitis and tendon rupture - QT prolongation with moxi -Hypoglycemia and hyperglycemia — levofloxacin, gatifloxacin was

withdrawn from the market in the United States and Canada in June 2006. - Hematologic — Leukopenia and eosinophilia in<1% - Drug interactions; IV ciprofloxacin, precipitates with aminophylline, amoxicillin Enzyme inhibitor esp cipro ↑theoph.

Aminoglycosides • (-) protein synthesis • Against G-ve • e.g. Amikacin, Gentamicin, Kanamycin, Neomycin, Streptomycin, Tobramycin, • Amikacin is more potent than gentamycin & Tobramycin . • Aminoglycosides should only be used for treatment of serious infections because of their potential toxicity and antimicrobial spectrum. • Adverse Effects; - irreversible, cumulative ototoxicity, the vestibular system (manifest as dizziness or vertigo). - Reversible nephrotoxicity may occur and acute renal failure has been reported, often in association with the use of other nephrotoxic drugs , - neuromuscular-blocking action and respiratory depression and muscular paralysis

Tetracyclins • • • 1. 2. 3. 4. 5. 6. 7. 8. • 1. 2. 3. 4. •

(-) protein synthesis Its efficacy ↓ by antacids, Fe therapy & dairy products. Used for; Acute bacterial exacerbations of chronic bronchitis, mycoplasma. brucellosis (with streptomycin), leptospirosis, rickettsial infections, chlamydial infections (doxycycline), granuloma inguinale, Borrelia (Lyme disease and relapsing fever; doxycycline), syphilis, Vibrio cholera , plague, Vibrio vulnificus, Mycobacterium marinum (minocycline), actinomycosis in the penicillin-allergic patient Side effects; Gastrointestinal distress. Esophageal ulceration; Doxycycline (take in A.M. with fluids) Outdated tetracyclins fanconi S. Enhance established or incipient renal failure. Doxycyclin (vibramycin) is the safest in renal failure but may cause photosensitivity.

Chloramphenicol • • •

(-) protein synthesis Potentiate the action of anticoagulant, phenytoin, hypoglycemics. Aplastic an.

sulphonamides • • 1. 2. 3. 4.

Competitively inhibit enzymes in folic acid biosynthesis  (-) cell metabolism. Uses; Nocardial infections, leprosy (dapsone, a sulfone), toxoplasmosis (sulfadiazine) Trimethoprim-sulfamethoxazole (Cotrimoxazole) is used in pneumocystis carinii, listeria, UTI.

• Side effects; 1. Allergic reactions; Rashes ; erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis. 2. Hematologic reactions; Uncommon; include agranulocytosis and granulocytopenia , hemolytic and megaloblastic anemia, thrombocytopenia. 3. Renal insufficiency, Crystalluria with sulfadiazine therapy

• • • • •

Fusidic acid Active against penicillinase producing staph aureus (narrow spectrum) Well absorbed orally Used in osteomyelitis, endocarditis, staph septicemia Safe , can be used in pregnancy Occasional hepatotoxicity.

Linezolid (Zyvox) • Bacteriostatic • (--) protein synthesis. • Active against G+ve resistant org.; - penicillin resist. Strept. - mecithillin resist. Staph (MRSA) - Vancomycin resist enterococc. (VRE). • Side effects; - GIT: ANVD, gastritis, pancreatitis. - Bl; leucopenia, pancytopenia. - CNS; dizziness, bluring, tinnitus - Skin;rashes. - drug interaction as MAOI; serotonergic & adrenergic drugs.

Glycopeptides • •

•

•

Vancomycin, Teicoplanin (Targocid). Uses; - MRSA - penicillin resist strep pneum (Meningitis) - oral in Cl difficile. Side effects; - oto/ nephrotoxicity. - if given rapidly release of histamine (red man S) - if extravasation  necrosis. NB; Teicoplanin - less nephrotoxic & once daily dose. - but many side effects as linizolid (GIT, Skin, CNS, Blood)

Quinupristin & dalfopristin (synercid) •

(-) protein synthesis

• • • •

For G +ve mainly esp resistant strept pneum. & staph aureus. Only given through central line. Enz. Inhibitors. Side effects; arthralgia, myalgia, thrombophlebitis.

Metronidazole, tinidazole (fasigyn) • Nucleic acid synthesis • Used for; - anaerobics esp bacteroids. - ameba, Giardia - trichomonas vaginalis. • Drug interaction; - disulfiram like action - ↑ anticoagulant. • Toxicity; - Metallic taste - PN after prolonged use.

Clindamycin • (-) protein synthesis • Used for anaerobic infections; e.g. type 1 necrotizing faschitis. • Side effect; diarrhea, pseudomembranous colitis by clostridium difficile.

Antimicrobials Antistaph Antibiotics; • Mecicillin, oxacillin, Amoxc/clavulonate, Unasyn. - Erythromycin, - Vancomycin - 2nd & 3rd g cephalosporins - Cotrimoxasole, quinolones - clinda, fusidic acid Antipseudomonas; - Carbinicillin, piperacillin, ticarcillin - Aminoglycoside (Tobramycin), - 3rd G ceph (ceftazidime), - quinolones, - Tienam Anaerobics; - Metronidazole, - Clindamycin - Tienam

Antifungal • • •

Mucous membrane; - clotrimazole, econazole, Nystatin (not absorbed). Skin; - terbinafin, griseofulvin. Deep; - Candida Albicans  fluconazole. - other candida, aspergillosis  amphotericin B. - CSF cryptococcal meningitisfluconazole, amphotericin B, 5 flucytosine.

Side effects; amphotericin B; nephrotoxicity, ↓K, ↓Mg, neurotoxicity. Ketoconazole; hepatotoxic, enzyme inhibitor, ↓cortisone & androgens (medical adrenalectomy). 5 flucytosine  mild side effects, BM suppression. Griseofulvin enz inducer, Stevens Johnson S, headache, neurotoxicity.

Antiviral • Nucleosides analogues (-) DNA polymerase. Acyclovir  HSV, purine analogue, so highly viral specific & very low toxicity. Gancyclovir  1st line for CMV. significant side effects; BM, gonadal toxicity (-) spermatogenesis. Foscarnet  2nd line for ttt of CMV, severe side effects esp renal damage. Cidofovir  for CMV in HIV patients, nephrotoxic. Lamivudine, Adefovir, entecavir  HBV. Zidovudin, didanosine, lamivudine, adefovir  HIV. Amantadine proph & TTT of influenza A (not B), parkinsonism (- dopamine uptake). side effects; (CNS); insomnia, dizziness & headache. • Neuraminidase inhibitors ; - Zanamivir (inhalor), - Oseltamivir (Tamiflu) in influenza A & B, less side effects, given oral. • Ribavirin ; HCV, Lassa fever, inhalation in children with RSV. • INF-α  B, C, some malignancy (RCC, Kaposi).

Migraine • Precipitating factors- chocolate, alcohol, smoking, stress, type A personality, bright light, hunger, OCP. TTT; - During the attack;(in order) - paracetamol -codeine + anti-emetic - ergotamine (# in preg, renal, PVD, CVS) - sumatriptan (5HT1 agonist) - Prophylactic (if attacks are frequent; > 2/months) - propranolol - amitriptyline (TCA) - Methysergide (retroperitoneal fibrosis)

• Sumatriptan is a 5HT1 agonist and may be useful in the treatment of acute migraine attacks. is available in injectable, intranasal, and oral formulations. Ergotamine tartrate is also effective in acute migraine. Propanolol, valproate, NSAIDs, • amitriptyline, pizotifen and gabapentin are effective as prophylactic drugs in migraine

Benign intracranial Hypertension (BIH) • -

Causes; obesity, behcet, pregnancy Addison, ↓PTH, PCO Drugs; - OCP e.g. Dianette. - steroid use or withdrawal. - systemic tetracyclin, vit A, retinoic acid - nitrofurantoin, nalidexic acid. - lithium. TTT; - wt loss, VP shunt, repeated lumbar puncture - acetazolamide. - glucocorticoids; 30-60 mg/d.

Antiepileptic drugs

Phenytoin

Valproate

Carbamazepine

uses

Tonic clonic all except absence Therap level=1020 Ug/ml

All generalized

-Partial -5th neuralgia -Diab neurop -Migraine -DI

Drug interaction

Enz inducer ↓level of; -Oral anticoag. -OCP --cyclosporine -Other antiepil

Enz inhibitor

Enz inducer If uses with phenytoin ↑dose of phenytoin

Phenytoin

Valproate

Carbamazepine

CNS depression

√

√

√

hepatotoxic

Hepatitis, granuloma

Fatty, Reye S

GIT upset

√

√, pancreatitis

√

Blood

Megaloblastic an LN, gum ↑

↓plat thrombathenia

pancytopenias

skin

Lupus, Hirsutism Serum sickness

Gynecomastia Rash, alopecia

Toxic epidermal necrolysis

endocrine

DM

Wt gain, PCO

SIADH

Bone (osteomalacia)

√

√

√

Neuro

PN, enceph Chorea, Nystag Cereb ataxia,

Ataxia tremors

Headache, diploplia

teratogenic

Neural tube defect Neural tube defect (cleft, cong ht)

Side effects

Toxic epidermal necrolysis

• Gabapentine; - used as add on drug - in partial, general. - not enz inducer. -CNS side effects. - Dose adj in renal failure. • Lamotrigine  rash TEN. • Vigabatrine irreversible constriction of visual field. • Levitiraceticam - oral - Safe, fewer side effects - used for partial seizures. - No effect on liver enz - Dose adj in renal failure. • Phenobarbitone 1st line in infants. • Paraldehyde may be given IVI or rectally or IM in extreme circumstances because it cause tissue damage & slughing.

Drug induced neurological symptoms 1. Drug induced extra Δ symptoms;e.g Dystonia e.g. antipsychotic e.g., antiemetic. ttt; stop the drug, give anticholinergic for tremors e.g. Benztropine or procyclidine.(® akeniton tab 1x1, parkinol)

2. Tardive dyskinesia; -

3. -

Antipsychotic as chlorpromazine & Haloperidol, unusual with newer agents as olanzapine, clozapine. After 6 months of the drug intake. 50 % irreversible, progressive. C/P; orofacial dyskinesia e.g. chewing, lip smacking. ttt; stop & give - tetrabenazine - reserpine, valproate. - baclofen 10, 25 mg 1x2, diazepam. Malignant neuroleptic S; C/P; altered mental state, rigidity, autonomic dysf, fever, high CPK Cause; potent neuroleptics e.g. haloperidol. ttt; dantrolene, bromocriptine. Complications; Rabdomyolysis, ARF.

•

• • • •

Neuroleptic malignant syndrome is characterized by fever, muscular rigidity, labile blood pressure, altered mental status, decreased conscious level and autonomic dysfunction. Although potent neuroleptics (eg, haloperidol, fluphenazine) are more frequently associated with NMS, all antipsychotic agents may precipitate the syndrome. For example, these agents are prochlorperazine, promethazine , clozapine , risperidone . Dystonic reactions usually subsides within 24 hours following cessation of treatment and can be treated with procyclidine 5-10 mg i.m. They are well-recognized with dopamine receptor antagonists (neuroleptics). Phenothiazines, prochloperazine, haloperidol and metclopramide are examples of drugs which can cause dystonic reactions. Oculogyric Crisis is one of the acute dystonic reactions. It is the most common of the ocular dystonic reactions (which include blepharospasm, periorbital twitches, and protracted staring episodes). Priapism as a side effect is associated with phenothiazines (chlorpromazine), haloperidol, trazodone and alpha blockers (prazosin).

• -

Drug induced peripheral neuropathy; amiodarone INH, DDI, metronidazole, nitrofurantoin Gold, cisplatin, vincristin, vinblastin.

• -

Drug induced Myopathy; statins, fibrates Corticosteroids, cocaine, colchicine, chloroquine Zidovudine

• • • • • • • •

Drugs provoking Myasthenia Aminoglycosides. B. Blocker. Quinidine. Procainamide. penicllamine. Phenytoin. Lithium.

Antidepressants

TCA overdose • • • •

•

Mech; anti-cholinergic (dilated pupil, confusion, tachycardia), α blocking hypotension. E.g. procyclidine used to treat parkinson induced by neuroleptics. ECG ↑QT TTT; - IV Bicarb reduce risk of seisure & arrhysth. - pacing - activated charcoal, emesis, gastric lavage - fluid & electrolytes - diazepam for convulsion Mortality is high; 20%

Quinidine poisoning; • As TCA (anticholenergic, α blocking, ↑QT )+ irreversible blindness.

• Common side effects of Selective Serotonin Reuptake Inhibitors (SSRIs) are nausea, vomiting, diarrhoea, appetite and weight loss, sexual dysfunction and deranged liver function tests. • Similarly, the common side effects of fluoxetine are :anxiety or nervousness; decreased appetite; diarrhoea; drowsiness; headache; increased sweating; nausea; tiredness or weakness; trembling or shaking; insomnia.

Lithium -uses;

1- prophylaxis in bipolar affective disorder 2- acute manic episode. 2- augment action of antidepressant in recurrent, resistant depression. - It has a narrow therapeutic window (0.6-1.2mmol/l).toxic > 2 mmol/l. - Take Blood sample for therapeutic monitoring 12 hr after the last dose - Toxicity increase when renal excretion decrease as with RI, ACEI, NSAIDs, thiazide, loop diuretics, tetracyclin, phenytoin, ciclosporin. - Serum level ↓ with antacids, theoph, acetazolamide.

Lithium Toxicity; - neuro; lethargy ,tremor ,confusion ,seizure. - GIT; N, diarrhea. - renal; DI, RTA, ARF, CIN. - goiter, hypothyroidism - hypercalcemia. - TTT: - gastric lavage - Replete volume/forced diuresis - HD; - level > 4 mEq/L - Level > 2.5, severe CNS symptoms

Antipsychotics

Indication of antipsychotics -Schizophrenia -Mania -Paranoid psychosis -Psychotic depression

Atypical antipsychotics

Examples

Side effects

Highly selective blockade of D2 & 5 HT2A

sulpiride

hyperprolactenimia

Olanzapine Resperidone clozapine

- Wt gain - N, dyspepsia - Bl dyscrasia; Neutropenia Agranulocytosis -Myocarditis, cardiomyopathy -Hyperglycemia, DKA

• Atypical antipsychotics are the 1st line ttt of schizo (+ve symptoms) dt less side effects. • Clozapine is used for severe tardive dyskinesia

• sexual dysfunction • Cholestatic jaundice

• Clozapine induced agranulocytosis occurs in about 1% to 10% of patient who take clozapine. Patients who have experienced agranulocytosis with prior treatment of clozapine should not receive clozapine again.

• Quetiapine is indicated for the management of the manifestations of schizophrenia. The commonest side effects (>5%) are excessive sedation, dizziness, dry mouth, postural hypotension, and elevated ALT.

• β-interferon is a long term treatment (as opposed to steroids for acute relapses) which is of benefit only in the relapsing remitting form (about 40% of MS patients have this form), and slows progression of disability and reduces demyelinating lesions.

Chemotherapy

Chemotherapy 1. 2. 3. 4. 5. 6. 7.

Alkylating agents Antimetabolites Antibiotics Plant alkaloids Hormonal therapy Molecular targeted therapy Biological therapy - immune therapy - gene therapy

Cell cycle: • G1 phase ; enzymes for the production of RNA and protein, are produced. • S phase ; DNA is synthesized by replication of the existing strand. • G2 phase ; RNA and protein are synthesized. • M phase mitosis occur: • Cell division results in 2 daughter cells, each of which can – enter its own G1 phase – become an inactive resting (G0) or – die (cell loss fraction).

Mechanism of action • phase non-specific: act at any phase or when cells are resting;

- alkylating agents: - antibiotics: actinomycin D, • phase specific: act only in a specific phase of the cell cycle & are only active when the cells are not resting. • E.g. plant product – vinca alkaloid: vincristine, vinblastine (M phase) – etoposide (G2 phase) – taxol (G2 phase)

• antibiotic: bleomycin (G2 phase) • antimetabolite:(s phase)

• Alkylating agents Mech; - bind covalently to bases of DNA  cross linkage Apoptosis. - cell cycle non-specific. - used for slowly growing cancers e.g.CML, cll, MM, lymphomas. - side effects; 2ry neoplasms as leukemia, sterility. e.g. cyclophosphamide (endoxan) hemorrhagic cystitis, sterility, BM suppression. chlorambucil (leucoran) Melphalan busulfan (myleran) lung fibrosis. cisplatinum Nausea, PN, deafness, nephrotoxic,↓Mg ↓dose in renal. procarbazine mustine

• •

• -

-

Antimetabolites Mech; - compounds that structurally simulate purine & pyrimidine precursors interfere with P & P synthesis. - S phase specific. - used for rapidly growing cancers; AML, ALL. - side effects; stomatitis, diarrhea, BM suppression, no 2nd neoplasms. E.g. methotrexate; - inhibit dihydrofolate reductase reduced folate ↓thymine. - side effects; BM & mucosa, crystalluria, ↓dose in renal, hepatic fibrosis, pneumonitis, CNS dysf. given with leucovorin formyltetrahydrofolate, Cytosine arabinoside (Arac) # pyrimidine ARDS, BM, mucositis, ataxia. 5 fluorouracil # pyrimidine. BM, mucositis, DVT. Capecitabine; in HCC, 5FU prodrug, intratumoural metabolism Hand foot s, diarrhea. Azathiprine & 6 Mercaptopurine # purine BM, liver, Nausea, metabolized by xanthine oxidase so ↓the dose with allopurinol. Mycophenolate Mofetyl Hydroxyurea (-)ribonucleotide reductase in myeloproliferative states

Azathioprine • • • •

A purine analogue , rapidly converted to 6-mercaptopurine inhibits DNA and RNA synthesis, and thus cell proliferation‘ Prevents early stages of activated T & B-cell proliferation. (Non-selective immunosuppression) • Metabolised with xanthine oxidase which is inhibited by allopurinol  give Quarter dose or Better , not to be used in combination with allopurinol. • NB; don’t begin aza during pregnancy but if pregnant was on it, continue, don’t stop. • Approximately 1 in 300 Caucasians have thiopurine methyl transferase (TPMT) deficiency. TPMT is the enzyme that metabolises 6-mercaptopurine and its deficiency results in high risk of azathioprine toxicity. • Azathioprine is used when steroid withdrawal causes recurrent relapse. Bone marrow suppression (low white cell count) and pancreatitis are side effects of azathioprine Principal side-effect is • Bone-marrow suppression (Reversible)Monitoring by CBC ,platelets, Reduce if WCC<4, stop if <3, reintroduce at a lower dose when >3 • Hepatotoxicity (Reversible) ( reduce dose if hepatic dysfunction present ) • Pancreatitis

• Antibiotics Mech; - bind directly to DNA & generate free radicals. - e.g.bleomycin; Pulm fibrosis, ↓in renal. Adriamycin ); (–) Topoisomerase ( enzymes responsible for DNA unwind for duplication). BM, cardiac, mucositis. Mitomycin  HUS, CHF, Pulm fibrosis, BM, ↓in renal.

• Plant alkaloids; Mech; - cell cycle specific (M phase). - mitotic spindle inhibitors. e.g. - vinblastine ↓plat, HTN, raynaud’s, PN. - vincristine (Oncovin) SIADH, paralytic ileus, urine retension ,↑plat, jaw pain, PN. - Docetaxel; (G2 specific) stabilize microtubules against depolymerization. The "stabilized" microtubules are not able to undergo the normal dynamic changes necessary for cell cycle completion. broad spectrum against solid tumoursPN, arrhysthmias, fluid retension, BM, alopecia, mucositis, hypersensitivity reaction so premedicate with steroids, anti H1.

• Molecular targeted therapy Mech; products of oncogenes & tumour suppressor genes, regulators of cell death pathway, mediators of cell immortality e.g. telomerase, proteases, angiogenic factors. e.g.; 1- proteozome inhibitor “bortizomib” in MM (-) proteozome which ↓P53↑ P53  apoptosis; postural hypotension, hypoNa. 2- Imatinib (Gleevec) in CML  ↓ abn. Tyrosine kinase produced by bcr-abl gene, induce phil –ve haematopoisis 3- Tretinoin teratogenic, pseudotumour cerebri.

• Hormonal therapy; - High dose steroids; - Tamoxifen, aromatase inhibitors partial Estrogen antagonists. - Prostate; DES ↓LH ↓test. LHRH analogue as leuprolide tonic ↓LH. - Adrenal ketoconazole, aminoglutithemide, mitotane. - Islet cell somatostatin - Prolactin Bromocriptine.

Tamoxifen • partial Estrogen antagonists; antagonist on breast, agonist on endometrium • Uses; breast cancer • Side effect; endometrial hyperplasia and polyp formation Endometriosis, uterine fibroids and endometrial cancers .

Aromatase inhibitors • aromatase is a cytochrome P450 enzyme, convert testosterone into estrogen in the adipose and breast tissue.

• E.g. Anastrozole (Arimidix), Letrozole (Femara), Exemestane (Aromasin). • in post-menopausal women, aromatization is responsible for the majority of circulating estrogen. • Uses; post-menopausal patients with hormonedependent breast cancer.

Antiandrogens • E.g. Cyproterone Acetate, Flutamide and hydroxyflutamide. • Uses; - Female – – – –

-

Hirsutism PCO precocious puberty acne vulgaris

Male: advanced cancer prostate.

• Enzyme Inhibitors; Finasteride (Testosterone 5α reductase inhibitor); the enzyme responsible for peripheral conversion of testosterone into DHT. Used in BPH & hirsutism.

Acute complication of Cancer chemotherapy 1) Myelosuppression; • febrile neutropenia. Def; fever > 38.5 in a neutropenic pt with neopl involving BM or receiving cytotoxic agents. Ttt; 1) imperical antibiotics acc. To C/P e.g. broad spectrum B lactam with antipseud e.g. Ceftazidime +/- vanco +/-metro or imipinem (anaerobes or abd) + antifungal if persistts > 7 days. 2) G-CSFs; 1-3 days after chemo.till wbc =10.000 3) Platelet transfusion till plat >10.000 4) Anemia Packed RBCs, epo. till Hb>8 2) Nausea; 5HT3 blocker; ondansetron (zofran) Dexamethazone Antidopaminergic phenothiazine e.g. prochlorperazine. Haloperidol Lorazepam (Ativan) Metoclopramidem(primperan) Antihistaminics; diphenhydramine.

3) Diarrhea - lopiramide - octreotide 4) Mucositis - topical anathetics – 5) Infertility Pain killers in Cancer patients; - We can replace morphin by diamorphin 1/3 dose in 24 hr (nausea, constipation but less addiction). - Breakthrough pain is treated by oromorphe 1/6 daily dose of morphin (oral morphin) - Morphin undergo extensive 1st pass metabolism.

MORPHINE EQUIVALENT DOSES • 100 mg of MST has the equivalent dose of 25 ug/hr of fentanyl over a day. • A 24 hour diamorphine dose should be 1/3 of the 24 hour morphine dose. • The equivalent dose of oral oxycodone 0.833 is to diamorphine SC 1.3 (about 2/3).

Nephrology Drugs in renal failure • Drugs causing systemic toxicity in RF (GFR<10ml/min); - Digoxin; cardiac arrhys, Ht block. - Penicillins, cephalosporins;.... encephalopathy - Lithium;... cardiac arrhys, seizures. - Tienem;..... seizures. - Ribavirin;....... hemolysis.

Nephrotoxic drugs • Prerenal ARF; - ACEI, NSAIDS esp in edematous states. - calcineurin inhibitors, amphotericin, contrast, cocaine. - diuretics

• Acute tubular necrosis radiocontrast, calcineurin inhibitors, aminoglycosides, cisplatin, amphotericin B, ethylene glycol.

• Interstitial nephritis B- lactams, sulfonamides, quinolones, rifampin, vanco, tetracyclin, NSAIDs, diuretics • Intratubular obstruction acyclovir, gancyclovir, methotrexate, indinavir • Nephrotic; Membranous; gold, peniccilamine, captopril. Minimal change; NSAIDs, INF FSGS; INF, pamidronate, heroin.

Drugs associated with retroperitoneal fibrosis include: - methysergide, - beta-adrenergic blockers, - lysergic acid diethylamide (LSD), - methyldopa - pergolide,Bromocriptine • TTT; Azathioprine is used to treat retroperitoneal fibrosis.

Drug induced SIADH • Drugs that ↑ADH release from hypothalamus; - Nicotine, pheno (chloropromaine) , TCA - Carbamazipine, Clozapine, SSRI, ecstasy. - Chlorpropamide, clofibrate,. - Cyclophosphamide, vincristine. - omeprazole.

Immunosuppressive therapy used in renal transplantation

• Glucocorticoids. • Small-molecule drugs; 1. Immunophillin- binding drugs; - CNI, cyclosporin, tacrolimus _ TOR-I; sirolimus 2. Antiproliferative - inhibitors of nucleotide synthesis; Purine; MMF. Azathioprine Pyrimidine; leflunamide, Gemcitabine. • Protein drugs 1. Depleting Ab; Polyclonal, anti CD3, anti CD52, anti CD20. 2. Non- Depleting Ab; anti CD 25, CTLA4 IG.

Agent

Mechanisms

Side Effects

Glucocorticoids

Binds heat shock proteins. Blocks transcription of IL-1,-2,3,-6, TNFα and IFN γ

Hypertension, glucose intolerance, dyslipidemia, osteoporosis

Cyclosporine CsA

CNI block IL-2 production; stimulates TGF production

PN, Nephrotoxicity, ↑K, ↓Mg, HTN, dyslipidemia, glucose int., hirsutism/ hyperplasia of gums, ↑uric acid

Tacrolimus (FK506)

CNI ; block IL-2 production; stimulate TGF production

Similar to CsA, but less HTN, dyslipidemia, no hirsutism/hyperplasia of gums, but tremors & diabetes more likely

Azathioprine

Hepatic metabolites inhibit purine synthesis

Marrow suppression (WBC > RBC > platelets)

Mycophenolate mofetil (MMF)

Inhibits purine synthesis via inosine monophosphate dehydrogenase

Diarrhea/cramps; dose-related liver and marrow suppression is uncommon

Sirolimus

blocks IL-2 receptor pathway for proliferation

Hyperlipidemia, thrombocytopenia impair wound healing.

CNI Mechanisms of action • CNIs inhibit the activity of a complex of phosphatases called calcineurin. Calcineurin.... phosphorylates a family of proteins termed nuclear factoractivating T cells (NFAT), thus allowing its entrance into the nucleus, where NFAT encodes interleukin-2 (IL-2) and other cytokines . We measure the trough (lowest therapeutic concentration) levels obtained

before the dose.

Drug interactions •

Drugs That ↑CNIs Blood Concentrations:

1. 2. 3.

enzyme inhibitors e.g. Ketoconazole, metoclopramide, omeprazole. Calcium Channel Blockers, as Diltiazem, Verapamil, but not amlodipine or nifedipine Macrolide Antibiotics.

•

Drugs That ↓CNIs Blood Concentrations:

1. 2.

enzyme inducers e.g. Anticonvulsants, rifampin, Magnesium & aluminum-hydroxide

NB; post-transplant lymphoproliferative disorder [PTLD] result from the degree of immunosuppression, not specifically from the use of CNI.

steroids Name

Glucocorticoid potency

Mineralocorticoid Duration of action potency

Hydrocortisone (cortisol)/ Cortisone acetate

1

1

8

Prednisone/ Prednisolone

4-5

0.8

16-36

Dexamethasone

30

0

36-54

steroids Corticosteroids act on cytosolic rather than cell membrane receptors. Uses; 1. suppress various allergic, inflammatory, and autoimmune disorders. 2. post-transplantion immunosuppressants NB; Prednisone is safe to use in pregnancy. Side-effects 1. Immunosuppression 2. Hyperglycemia due to increased gluconeogenesis, insulin resistance. 3. Increased skin fragility, easy bruising 4. Reduced bone density (osteoporosis, osteonecrosis) 5. central obesity 6. Muscle breakdown , weakness; 7. salt and water retention , hypertension ,potassium depletion, and metabolic alkalosis 8. Endocrine System;↓ ACTH, ↓TSH, ↓FSH, Anovulation, irregularity of menstrual periods, Growth failure, pubertal delay, Adrenal insufficiency 9. Gastrointestinal System; Increased gastric acid secretion

Depleting

Non-depleting

Definition

Antibodies that destroy T cells, B cells, or both.

monoclonal antibodies that reduce responsiveness without lymphopenia

class

1.Anti- CD3 (OKT3) 2.polyclonal anti-lymphocyte sera (ATGAM, Thymoglobulin) 3.anti- CD52.(alemtuzumab) 4. anti-CD20 (Rituximab). (B cell depleting).

-anti CD25 (Basiliximab & Daclizumab) - CTLA-4-Ig fusion protein (Abatacept & Belatacept).

Advantag es

-long-lasting immunosuppression. - lowest rates of acute rejection.

-↓ risks of infection and PTLD -Target protein are present only in immune cells less systemic toxicity. -No long-lasting effects

Disadvant - cytokine release syndrome. ages -higher rates of CMV, EBV, and other viral infections. - Recovery from immune depletion takes months to years and may never be complete in older adults.

- may not facilitate recovery from ischemic injury. - ineffective for the treatment of acute rejection.

Rheumatology TTT of rheumatoid arthritis DMARDs (Disease- modifying antirheumatoid drugs):

2 Key Points: • start DMARDs as soon as the diagnosis of RA is confirmed. • Methotrexate is the DMARD of choice in patients with severe disease with relative rapidity of action. Start therapy with 7.5mg weekly and raise the dosage at 1- or 2-month intervals until peak efficacy is achieved.

Methotrexate overdose;  C/P; NV, rash, GIT bleeding  The most common dose-related toxic effects of methotrexate are on the bone marrow and gastrointestinal tractoral ulceration . Megaloblastic anaemia, usually with marked macrocytosis  Hepatic periportal fibrosis and cirrhosis may develop without obvious signs of hepatotoxicity,  interstitial pneumonitis. This is rare but a serious complication. Chest radiography reveals a diffuse interstitial or mixed interstitial and alveolar infiltrate, with a predilection for the lower lung fields.  Neurotoxicity may be seen: leukoencephalopathy, paresis, demyelination are associated particularly with intrathecal use  Carcinogenicity ,There are reports of lymphomas associated with low-dose methotrexate therapy for rheumatic disorders  crystal formation.1 These crystals can cause intrarenal obstruction and are a factor in the development of acute renal failure • Methotrexate: Binding of methotrexate to dihydrofolate reductase reduces nucleotide synthesis. Folinic acid rescue is usually given after methotrexate within 24 hours to reduce myelosuppression effects. • TTT; Ca folinate (Leucovorin).

* DMARD Therapy for RA ("GOLD PILE SCAM") DMARD

Potential Toxicities Requiring F/U

Monitoring Studies

Gold IM and PO

Myelosouppression, proteinuria

CBC & urine dipstick for protein

Penicillamine

Myelosuppression, proteinuria

CBC & urine dipstick for protein

Infliximab (Remicade)

Flu-like sx, auto-Abs; None for patients not responding to methotrexate; given IV

Leflunomide (Avara)

Thrombocytopenia, hepatotxicity, diarrehea

CBC and AST

Etanercept (anti TNF)

Reactions at site of SQ injection, flu-like sx

None

Sulfasalzine

Myelosuppression

CBC, AST, creatinine

Cyclophosphamide

Myelosuppression, malignancy, hemorrhagic CBC, urinalysis, cystitis cytology

Cyclosporine

Renal insufficiency, anemia, HTN, hirsutism

creatinine, CBC, K+, LFTs

Azathioprine

Myelosuppression,hepatotoxicity, lymphoproliferative disorders.

CBC

Antimalarials (Hydroxycholorquine)

Macular damage

Yearly fundus exams

Methotrexate

Myelosuppression, hepatic fibrosis, cirrhosis, CBC, AST, albumin pulmonary infiltrates or fibrosis

Minocycline

Photosensitivity, skin discoloration, GI upset, None drug-induced lupus, dizziness

and

urine

• LEFLUNOMIDE (Arava).  Blocks pyrimidine synthesis in lymphocytes.  inhibits the proliferation of both T and B cell lines and non-immune cell lines  Uses; -Rh. A. - Inhibits anti—donor antibody synthesis Prevent and treat acute rejection, reverse established chronic rejection. - has antiviral activity against herpes, CMV and polyoma virus  Well Tolerated, Not nephrotoxic  Common adverse effects seen with leflunomide are  hypertension, gastrointestinal disturbances, Hepatotoxicity , pancreatitis , weight loss,  Neuro., headache, dizziness, asthenia, paraesthesia, anxiety, peripheral neuropathy.  Skin , alopecia, eczema, and dry skin , erythema multiforme ,SJS, TEN, Hypersensitivity reactions ,synovitis .  Bl. leucopenia, anaemia, mild thrombocytopenia, eosinophilia, pancytopenia & agranulocytosis.

Penicillamine;  Uses; DMARD Therapy for RA Chelate cysteine in cystinuria Chelate Cu in Wilson’s scleroderma.  Side effects; reversible loss of taste membranous GN proteinuria. thrombocytopenia, neutropenia Myasthenia, drug induced lupus, SJS, myositis. • Common side effects of gold are mouth ulceration, leucopenia, proteinuria and skin rashes. Hydroxychloroquine can cause renal toxicity. • Sulphasalazine causes nausea and vomiting, leucopenia,megaloblastic an., oligospemia and deranged liver function.

• Etanercept is a dimeric fusion protein consisting of the extracellular ligand-binding portion of the tumor necrosis factor receptor (TNFR) linked to a human IgG1. The receptor binds to TNF, it is not a monoclonal antibody. It is licensed for juvenile rheumatoid arthritis and juvenile idiopathic arthritis. Side effects are septic arthritis, demyelination, pancytopenia, aplastic anaemia and congestive heart failure. .

• Infliximab is a monoclonal anti-TNF antibody. ADVERSE REACTIONS SIGNIFICANT

• • •

Central nervous system : Headache (18%) Fatigue , fever Cardiovascular: Hypertension (7%) Gastrointestinal : Nausea (21%), diarrhea , abdominal pain, Dyspepsia • Hepatic : ALT increased (risk increased with concomitant methotrexate) • Respiratory : Upper respiratory tract infection (32%), sinusitis , pharyngitis , TB flare. Bronchitis , rhinitis, dyspnea (6%) • Miscellaneous: Development of antinuclear antibodies, infection , development of antibodies to DNA, infusion reactions. Moniliasis,Arthralgia , back pain, Rash , pruritus

symptoms modifying drugs : Important points about COX-2 Inhibitors – Lower incidence of significant GI toxicity than NSAIDs. – No effect on platelet aggregation. – Similar renal and hepatic effects as NSAIDs. – Contraindicated in patients with urticaria, asthma, or other allergic-type reactions to ASA. – Can be dosed once daily for osteoarthritis. – Can be dosed without regard to food intake. – Celecoxib (Celebrex) is contraindicated in patient with allergic-type reactions to sulfonamides.

Treatment of asymptomatic hyperuricemia; 1) Persistent s.urate >13mg/dl in men and >10 mg/dl in women 2) Excretion of U.uric acid >1100 mg/d , Dose should be adjusted to keep U.uric acid <800mg/d 3) Patient about to receive radio or chemotherapy that is likely to result in extensive tumour cytolysis

• 1. 2.

Treatment of gout; Treat acute flare with anti-inflammatory drugs. Start urate lowing drugs weeks after the acute attack & continue till the patient is attack free, no tophi & s urate < 6 mg/dl for 6 months. Urate lowering drugs include; 1. Allopurinol; - xanthine oxidase inhibitor inhibit synthesis of uric acid. - use lower dose in renal impairment. - interfere with metabolism of azathioprine, cyclophosphamide. - hypersensitivity reactions. - enzyme inhibitor. 2.

Uricosuric drugs; can lead to nephrolithiasis. not effective if serum urate is more than 2 mg/dl.

3.

Uricase (Urate oxidase) IV degrade urate into allontoin, used in tumour lysis.

HRT

Thromboembolism, breast cancer, ↑TG, ↓ risk of fracture, cancer colon, ↑ HDL  ↓ coronary. Contraindications; - Absolute; • E dependant tumours; breast, endometrium. • Thromboembolic disorder. • Abn vaginal bleeding. - Relative; • FH of br cancer, hyper TG, • CLD, GB disease.

Pharmacologic therapy of osteoporosis • • 1. 2.

3. 4. 5.

Ca, vit D Drugs that decrease bone resorption; HRT (E↑uterine cancer& breast cancer). SERM (selective Estrogen receptor modulators)= agonist on bone & antagonist on breast↓ osteoporosis, br cancer & IsHD. Side effects; flushes, DVT. - Raloxifen (Evista®)used in postmenopausal osteoporosis. - Tamoxifen used in br cancer. STEAR= selective tissue estrogenic activity regulator e.g. Tibolon (Levial ®) Bisphosphonate (oral alendronate) Calcitonin ; anabolic bone effect, Side effects; nasal congestion, rash.

• 1. 2. 3. 4.

Drugs that increase bone formation; Synthetic PTH (Teripatide). Strontium (Protelos) Na floride Others; GH, GHRH, IGF1, anabolic steroids, statins.

• Ca, vit D; - ca alone; small effect on BMD, no antifracture effect. - Vit D alone; unknown effect in pt without vit D def. - Ca + Vit D; may ↑BMD, ↓fracture. • Raloxifen (Evista ®) - used in postmenopausal osteoporosis. - adv; ↓ osteoporosis, ↓vertebral fracture,but not non vert fracture, ↓ br cancer & ↓ IsHD. - Side effects; flushes, DVT. • Calcitonin; nasal spray, SC; ↓vertebral fracture, small ↑BMD.

• Alendronate (oral daily 10 mg or weekly 70 mg) - mech; taken up by osteoclast  apoptosis. - adv; effective against all fractures, long term benefit (10 yrs). - disadv; poor upper GIT tolerance. - contraindications; hypocalcemia, osteomalacia, renal failure, bed ridden, serious oesophageal dis. - side effects; hypocalcemia, ↑PTH, skin rash oral; esophagitis, ulceration. IV; flu like, arthralgia, myalgia, fever, leukopenia, eye inflammation etidronate; ↑phosphate, osteomalacia. • Teriparatide; - daily SC, 1st anabolic, ↓ all fractures, marked & rapid ↑BMD. - disadv; daily SC, use restricted to high risk pts, osteosarcoma in toxicologic studies. - contraindication; bone dis; paget dis, Hx of bone metastasis or cancer, growing child, hypercalcemia, pregnant, lactation.

• Endocrine • -

Drug induced gynecomastia; E like action; Estrogen, digoxin, spironolactone, stilbestrol. Antiandrogen; cimetidine, cyproterone acetate, LHRH. Others; verapamil, Nifedipine

• -

Drug induced hypothyroidism; amiodarone, Antithyroiid; carbimazole, propylthiouracil Lithium Iodine.

• -

Carbimazole; Inhibit a peroxidase which catalize all phases of Th synthesis. Takes 6 wks to ↓TH level. Agranulocytosis may occur during the 1st 4 months Side effects of antithyroid drugs (carbimazole & propylthyiouracil); common= MP rash, lymphopenia. rare=agranulocytosis, aplastic anemia, hepatitis, fever, arthralgia, vasculitis, LN, goiter, cholestasis.

• Drug induced gum hyperplasia; cyclosporin, phenytoin, nefidipine. • Drugs causing galactorrhoea are: - Oral contraceptive pills - Phenothiazines such as - Metoclopramide - TTT : Bromocriptine Drugs producing hypercalcemia include: • lithium • Thiazides

Antihyperglycemic Agents Major Sites of Action -Glucosidase inhibitors –

Glitazones

Plasma glucose

Carbohydrate absorption

GI tract

Metformin

Secretagogues

+Glucose uptake Muscle/Fat

–

+

Glucose production

Liver – Insulin secretion

Pancreas

+

• Metformin a biguanide. Its mode of action is • delayed uptake of glucose from the GIT, increased peripheral glucose utilization, inhibition hepatic glucose production . • In metformin overdose, main symptoms of toxicity include gastrointestinal upset & severe lactic acidosis. Hypoglycaemia is not often seen in metformin overdose.

• Insulin glargine is a long-acting insulin analogue, there is a smooth, prolonged absorption profile with no peaks. As such, it is a long-acting agent, suitable for providing a basal level of insulin which mimics the normal physiological state. • Its smooth profile reduces the risk of hypoglycaemia, and when given at night, provides good control of the fasting blood glucose.

GIT • -

Drug induced diarrhea; Mg containing antacids, laxatives. Antibiotics. NSAIDs. Chemotherapy.

• -

constipation; Ca & Al antacids, Fe, anticholinergics, opiates. Antidepressants, antiparkinson, anticonvulsants. Anti HTN; CaCBs, diuretics.

Hepatotoxic drugs Hepatitis (↑ALT);

cholestasis (↑Alk P );

INH metabolites, Rifampicin, HMG COA reduct inhib. α MD Paracetamol overdose. Amiodarone. Phenytoin. Valproate. Pyrazinamide. Nitrofurantoin.

Chlorpromazine. Coamoxaclav. Erythromycin. Flucloxacillin. Sulphonylurea. OCP (E).

Drug induced specific liver disease Amiodarone, allopurinol

Hepatic granuloma.

OCP,

Adenomas +/- intraperitoneal rupture. Cholelithiasis, cholestasis Budd chiari. Peliosis hepatis

methotrexate, amiodarone, vit A

Cirr..or fibrosis

Cocaine

Massive ischemic necrosis

TTT of IBD depends upon both the extent of colonic involvement and the severity of the disease process at presentation. 1. for ulcerative proctitis = topical 5-aminosalicylate (5-ASA) suppositories or steroid foams. 2. Patients with left-sided colitis often respond to topical enemas. 3. Pan colitis ( extends beyond the splenic flexure). A)

mild to moderate; - oral 5-ASA or sulfasalazine + topical 5-ASA or steroid enemas . - add oral prednisone (40 to 60 mg/day) in: 1- more severe symptoms and 2- failed oral 5-ASA and topical therapy. ```

B) Severe active disease - pulse IV steroid, - IV cyclosporine • •

- surgery. These agents often require 3-6 weeks to exert their maximal benefit. Once remission is achieved, the drug dose can be tapered to maintenance levels of sulfasalazine (2 g/day), mesalasine (1.2 to 2.4 g/day), or olsalazine (1 g/day) .

Antiinflammatory drugs in CD, UC; 1. 5ASA; - e.g. - sulfasalazine (sulfapyridine + 5 ASA). Side effect; oligospermia, allergic, idiosyncrasy, agranulocytosis, rash, folate def. - Olsalazine; 2 5-ASA. - Enteric coated; mesalazine (Pentasa, Asacol)2-4g. • Mesalazine can cause neutropenia. & is given in the acute attacks in Crohn's disease. 2. Steroids; for induction only not maintenance.

Infliximab; • chimeric monoclonal antibody to TNF. • Used in; 1- refractory IBD, not fit for surgery. 2-perianal 3-RA, Psoriasis. • Dose; IV 5 mg/kg at 0, 2, 6 wks then /8 wks. • Side effects; - Ab to infliximabe resistance & reaction so given with methotrexate + hydrocortisone before the dose. - lymphoma. - allergic reactions, serum sickness - infection esp TB - demylenating disorders.

Drugs causing acute pancreatitis PD FAST VET pentamidine, didanosine, frusemide, azathioprine, steroids, sulfa, thiazide, valproate, Estrogen (OCP), tetracyclin Orlistat is an inhibitor of gastrointestinal lipases, leading to reduced fat absorption. It is licensed for patients with BMI > 28 with associated risk factors, a weight management programme should be in place. Use is not recommended for more than 2 years.

Dermatology • Drug induced photosensetivity

Thiazide, tetracyclin retinoic A. Cipro, Griseo, amiodarone.

Retinoic A • • • • •

Teratogenicity. Hepatotoxicity. hyperTG. Benign increase ICT. Dryness of mucous membrane.Alopecia.

• Common drugs which can precipitate a porphyria attack are: • Barbiturates • Sulfonamides • chloroquine • steroids

Hematology Drug induced Megaloblastic anemia; •

antifolate drugs; Alcohol, phenytoin, DHF reductase inhibitors (methotrexate, trimethoprine, pyrimethamine), sulphasalazine. • drugs ↓DNA synthesis (Arac, 6MP, hydroxyurea)‫ز‬ Drug induced hemolytic anemia; Immune mediated; Penicillin, Methyldopa ,INH Direct; Dapson, lead, benzene. Ribavirin in RF. In G6PD; 1-antimalarials; primaqine, Dapson. 2- ab, nitrofurantoin. sulfa 3- analgesic; phenazopyridine. Others; naphtalene, methylene blue. Drug induced Aplastic anemia; chemo, chloramph, phenylbutazone,, carbamazepine, benzene. Drug-induced neutropenia and agranulocytosis; the second most common cause of neutropenia, including clozapine, the thionamides (antithyroid drugs), and sulfasalazine . REACTIVE THROMBOCYTOSIS; Vincristine, Epinephrine, steroids

Drug induced thrombocytopenia • • • • • • • • • •

Heparin Valproic acid Gold salts Quinine and quinidine Trimethoprim-sulfamethoxazole &other sulfonamides Interferons Penicillin Ranitidine Glycoprotein IIb/IIIa inhibitors (eg, abciximab) Diuretics.

• Drug induced TTP; cyclosporin, ticlopedine, Mitomycin C,

PRINCIPLES OF COAGULATION

-

citrate LMWH Direct thrombin inhibitors

(Fischer, Hemodialysis international, 2007)

-

-

anti Th III + heparin & indirect thrombin inhibitors

Antithrombotic drugs

Antiplatelets

Anticoagulants

1) Aspirin Oral 2) anti ADP receptors Coumarin derivatives (clopidogril [plavix®], ticlopidine) 3) GPIIbIIIa antagonists (Abceximab, Tirofibam [Agrastat®]) 4) Anti Phosphodiesterase; Indirect Dipyridamol [Aggrenox®] thrombin inhibitors

Heparin LMWH e.g. enoxaparine Heparinoid e.g. Danaparoid Fondaparinux [Arixtra®]

(Harrison's PRINCIPLES OF INTERNAL MEDICINE, 2008)

Fibrinolytics

IV - strep., urokinase, alteplase

Direct thrombin inhibitors Lepirudin (Thrombexx®) Argatroban Binalirudin

• Ticlopidine; - blocks ADP receptorsreducing platelet aggregation. - uses; 2ry stroke prevention. unstable angina post-coronary stent insertion. - side effects; agranulocytosis, TTP, diarrhea, cholestasis, BM aplasia. • Clopidogril (Plavix); - blocks ADP receptorsreducing platelet aggregation. - less neutropenia than ticlopidine. • Abceximab; - irreversible bind GPIIb IIIa receptors (-) plat aggregation. - used in; unstable angina NSTMI post-coronary stent insertion.

Drugs which decrease mortality in MI; 1) Aspirin (not dypyridamol, does not ↓ rec in 1 yr). 2) thrombolytics/ angioplasty. 3) BB (FU with PR < 0.24, HR >45, SBP > 100)3 doses of 5 mg metoprolol IV > 2 min interval then 100 mg 1x2 forever esp compensated CHF. 4) ACEI esp. CHF, EF< 40%, cardiomegaly. 5) Statin ( ↓ mortality & recurrence) even with average

cholesterol prior to discharge. NB: - nitrate ↓ morbidity not mortality. - LV function is the prognosticator post MI. - DHP CCBs inc.CVS risk after MI. - In type II DM, must be kept on insulin infusion for 24 hs then SC for 3 months  ↓ mortality.

TTT of HT failure; 1) VD; NB; ACEI ↓ mortality & hospitalization. of no benefit in – RVF. - obstructive valve lesion. - ≠ in HCM.

2) Digoxin- ↓renin, sympathetic activity, hospitalization but not ↓ mortality. - used in Syst HF, S3, severe CHF.

- ≠ AVB, asymptomatic HF, acute MI. 3)

Diuretics e.g. spironolactone ↓ mortality & hospitalization & symptoms. used in severe CHF.

4)

BB ( Meto, Biso, Carvi)  ↓ mortality & hospitalization & symptoms. not used in volume overloaded patients.

Antiarrhysmic drugs: Class

effect

site

use

A

Quinidine Disopyramide procainamide

(- )Na channels

A V acc

WPW+ AF

B

Lignocaine Phenytoin Mexiletin

(- )Na channels

V

VT

C

Flecainide propafenone

(- )Na channels

A V acc

AF

Class II

Propranolol Atenolol

BB

nodes

Stress, thyroid, sinus, cong long QT, VT

Class III

Amiodarone Sotalol Ibutilide

(- )Na, Ca, K channels ↑ plateau

A acc V

AF, A flutter AVRT+ wpw VT

Class IV

verapamil

(- )Ca channels

AV node

SVT, MAT

Others

Adenosine digoxin

K opener, no(-) inotrop.

AV node

SVT, diag of flutter

Class I

Adenosine • Is a purine nucleotide. • Acts via adenosine receptors activate K channels • Short acting. • IV, 6-12 mg • Uses; (diag diff bet VT & SVT, therapeutic SVT) • Enhanced by dipyridamole& inhibited by theophyllin. • Side effect; chest pain, bronchospasm, flushing, hypotension. NB; no prophylactic use of lignocaine after MI ↑ mortality.

Amiodarone • Mech; prolong the refractory period ↑QT, it is the least –ve inotropic antiarrhysmic. • Uses; prolong life span in pt with recurrent VT, HOCM. • 39% of its wt is iodine, structurally related to thyroid Hormone. • Side effects. most common after oral neurotoxicity, most common after IV hypotension. Lung toxicity (1-10%) IPF, ARDS, BOOP, pl effusion, radiodense plaques, bil patchy infiltrate diagnosed by CT, ttt; stop the drug & give steroids. others; hepatitis, thyroiditis, optic neuritis, corneal opacities, photosensitivity, ↑ PR, ↑QRS, ↑QT esp with 1a. • ≠ in Torsade de points. • Drug interaction; ↑digoxin & anticoag level • Effect of Amiodarone on thyroid hormone; - initial ↓TH; * dt inhibitory effect of iodine on T4 release (wolf-Chaikoff ) * then ↑ dt; * iodine loadtype1 (jod basedow), ttt with carbimazole * thyroiditis (type2)↑CRP, ttt with steroids.

Digoxin; -

mech; (-) AVN. +ve inotropic effect. Used in; Ht failure + AF or AF only. Kinetics; 85% renal elimination, 25% bound to PP, narrow therapeutic window; Dose Contraindicated in; AVB, WPW, MAT, prior to elective cardioversion, constrictive pericarditis, acute myocarditis, HCM. Drug interaction; ↑digoxin level with amiodarone (displace for tissue binding sites) & CaCB & quinidine (interfere with renal tubular excretion). ECG; reversed stick ST depression is an indication of digitalis therapy not toxicity, but pulsus bigemini is an early sign of digitalis toxicity. 1. Arrhysmogenic; - most common is Ht block. - characteristic arrhys is non paroxismal atrial tachy. with varing block. 2. Other symptoms; anorexia, nausea, vomiting, diarrhea, yellow vision, gynecomastia, yellow vision. 3. Precipitating factors; ↓K, ↓Mg, ↑Ca, aging, hypoxia, hypothyroidism, renal failure. 4. TTT; digibind (Ab to digoxin  ↑ its clearance).

• -

Flecainide; Class 1c for ttt of Ventricular arrhys., . medical cardioversion for atrial aarhys. Avoided in ; post MI, LV dysfunction Side effects; vertigo, visual disturbance.

• -

Nicorandil; Antianginal (possesses nitrate component) K channel opener arterial & venous VD Side effects; headache, flushing, dizziness, hypotension, tachycardia, oral ulcers.

• Drugs that prolong QT; 1. antiarrhyth (Ia, III), 2. antibiotics ( macrolids, quinolones, quinine, sutrim) 3. antifungal, 4. pentamidine

Antihypertensives

Drug Class

Examples

Other Indications

Contraindications/Cautions

Diuretics Thiazides

Hydrochlorothiazide

Diabetes, dyslipidemia, hyperuricemia, gout, hypokalemia

Chlorthalidone Loop diuretics

Furosemide

CHF, renal failure

Diabetes, dyslipidemia, hyperuricemia, gout, hypokalemia

CHF, primary aldosteronism

Renal failure, hyperkalemia

Ethacrynic acid Aldosterone antagonists K +retaining

Spironolactone Eplerenone Amiloride

Renal failure, hyperkalemia

Triamterene Beta blockers Cardioselective

Atenolol Metoprolol

Nonselective

Propranolol

Angina, CHF, post-MI, sinus tachycardia, ventricular tachyarrhythmias

Propranolol LA Combined alpha/beta

Labetalol

?Post-MI, CHF

Carvedilol

Alpha antagonists Selective

Prazosin

Prostatism

Doxazosin Terazosin Nonselective

Phenoxybenzamine

Pheochromocytoma

Asthma, COPD, 2nd or 3rd degree heart block, sick-sinus syndrome

Drug Class

Examples

Other Indications

Contraindications/Cautions

Post-MI, CHF, nephropathy

Renal failure, bilateral renal artery stenosis, pregnancy, hyperkalemia

CHF, diabetic nephropathy, ACE inhibitor cough

Renal failure, bilateral renal artery stenosis, pregnancy, hyperkalemia

Sympatholytics Central

Clonidine Clonidine patch Methyldopa Reserpine Guanfacine

ACE inhibitors

Captopril Lisinopril Ramipril

Angiotensin II antagonists

Losartan Valsartan Candesartan

Calcium antagonists

Heart failure, 2d or 3d degree heart block

Dihydropyridines

Nifedipine (long acting(

Angina

Nondihydropyridin es

Verapamil (long acting(

Post-MI, supraventricular tachycardias, angina

Diltiazem(long-acting( Direct vasodilators

Hydralazine Minoxidil

Severe coronary artery disease

• Thiazides block Na+ and Cl- reabsorption in the distal tubule. The distal convoluted tubule accounts for 5% of total sodium chloride reabsorption. • Thiazides elevate LDL cholesterol, reduce urinary calcium excretion and can cause impotence,thrombocytopaenia, hypokalaemia and hyperuricaemia. • Hypercalciuria can be treated with thiazides. • Thiazides can cause

•

Frusemide acts on the thick portion of the ascending loop of Henle. It inhibits Na+ and Cl- reabsorption there via Na+, K+, -ATPasedependent pump. Owing to the large NaCl absorptive capacity of the loop of Henle, agents that act at this site produce a diuretic effect much greater than that seen with other diuretic groups.

Control of systemic hypertension.

Target = 140/90 in HTN alone 130/80 mm Hg in patients with DM or CKD & proteinuria < 1 g/24 hrs. 125/75 mm Hg in patients with CKD & proteinuria > 1 g/24 hrs. • ACE inhibitors/ARBs appear to be more protective than other antihypertensive drugs in patients excreting > 500 to 1000 mg of protein per day . • ACE inhibitors/ARBs may not be of greater benefit than other antihypertensive agents in patients without proteinuria and only mildly reduced kidney function.

ACEI & ARBs • Target; > 60 % reduction, optimally to total protein excretion < 1 g/24 hrs. • No limitations; - Even with normal BP, antiproteinuric measures should be applied guided by BP. - not limited by the initial level of GFR. • Limitations for ACEI; Hyperkalemia, pregnancy, bilateral RAS angioedema, cough. • Follow up ; with BP, S. creat., S. K; at day 4 then weekly up to 3 months then monthly if high risk or every 3 months if low risk, stable dose. • Initial rise of s. creat up to 30% that stabilize in 2 months. • Stop if rise of s. creat > 30 % or s. K > 5.5 meq/dl.

Benefit of RAAS blockade • Control BP (↓ Syst BP by 10-15 mmHg & diastolic BP by 5-10 mmHg). • Antiproteinuric effect (↓by 40%, Combination therapy with ACE inhibitors and ARBs additive antiproteinuric effect; 18 to 25 % greater reduction in proteinuria) due to; - ↓ GFR. - alter mesangial function. • Renoprotective; (reduce the progression from 1 ml/min/month to 0.3 ml/min/month) - ↑ bradykinin & other antifibrotic agents. - ↓ TGF-B. - ↓ Ang II mediated free Oxygen radicals.

• ARBs - No cough (do not inhibit bradykinin) - Less hyperkalemia. • -

Verapamil is contraindicated in; Digoxin toxicity SSS, WPW, AVB With BB Hypotension, Ht failure.

Medicati ons of Hyperli pidemia

• HMG Co A reductases (Statins) Mech; - (-) HMGCo A reductase (rate limiting enzyme in cholesterol synthesis). - ↑LDL receptors  ↓LDL - ↑HDL Side effects; - fatigue, myalgia, myopathy, rabdomyolysis. - Stop statin if CPK > 10 times, or AST >3 times.

• Ezetimibe acts by prevent cholesterol absorption from the small intestine. Typically it reduces LDL-cholesterol by approximately 20%, triglycerides by up to 5% and raises HDL-cholesterol by approximately 5%. • Ezetimibe is currently licensed for use in combination with a statin in patients who fail to reach desired lipid profiles or as monotherapy in patients intolerant to a statin.

Poisonings & Intoxications  Hemodialysis; - Alcohol (methanol,ethylene glycol, alcohol) - Lithium, - salicylate, - theophylline, - metformin - barbiturate (phenobarbital). Not dialysable; - Highly protein bound; digoxin, phenytoin - Large volume of distribution as amiodarone, organoph.

Methanol - solvents, varnish ,de-icing solutions N/V, abdominal pain (pancreatitis), CNS symptoms, seizures, coma, blurred vision (papilledema), increase osmolar gap, metabolic acidosis (increase anion gap).  Treatment: - empty stomach contents - Ethanol/fomepizole (inhibit ETOH DeH) - Hemodialysis: severe metabolic acidosis, very high osmolar gap, methanol & visual changes (disc hyperemia).

Ethylene Glycol - Antifreeze ,solvents - not protein bound - 30-60 ml is lethal - NB; Cause ↓Na & ↑osmolality & osm gap+ high AG met acidosis. - EG→ glycolic acid→ glyoxylic acid→ oxalic acid. - Stage 1 (<12 hrs): n/v, seizure, hyporeflexia, coma, high osmolar gap, hypertension, noncardiogenic pulmonary oedema, metabolic acidosis. - Stage 2 (>24 hrs): flank pain, oliguria, renal failure, ca oxalate crystals. - Treatment: - Empty stomach contents - Ethanol/fomepizole (competitive inhibition of alcohol dehydrogenase) - Thiamine 100 mg IM qid, B6 50 mg IM qid ; (glyoxalate → glycine) - Hemodialysis, (severe metabolic acidosis, very high osmolar gap)

Salicylate - C/P: headache, tinnitus, confusion, sweating, n/v, - hyperventilation, resp alkalosis then metabolic acidosis, cardiovascular collapse, hypoglycemia, ↑PT.

Treatment; - Gastric emptying , activated charcoal even 4 hr after dt delayed gastric empting. - Hemodialysis: seizure, coma severe metabolic acidosis + renal failure

    

Theophylline Toxic level > 15 mg/L C/P: GIT , N/V, abdominal pain, diarrhea, CNS , tremors, agitation, confusion, seizure, CVS , arrhythmia

 Pptating factors ,↓K dt vomiting.  Treatment: - Gastric lavage, activated charcoal - - Extracorporeal therapy:

Hemoperfusion better than HD

Ectasy (Amphetamine) • Features of acute (ecstasy) toxicity include agitation, tachycardia, hypertension, dilated pupils, sweating, hyperthermia,(↑sympathetic) • (DIC) , rhabdomyolysis and acute renal failure. • TTT; forced acid diuresis with NH4 Cl.

Paracetamol overdose • • • • •

Self poisoning 10-15 gm = 20-30 tab. Patho; In normal condition, paracetamol is conjugated with glucuronic acid in overdose it is conjugated with glutathione&bind to liver macromolecules> necrosis. C/P; NV, later hepatic (peak after 12 days) & renal failure. Lab; measure serum level after 4 hr of ingestion. ↑INR  most sensitive for liver damage. hyoglycemia> severe damage. • Poor prognostic criteria; - INR >3 - raise s creat - Ph <7.3 more than 24 hr after (lactic acidosis dt ↓hepatic lactate metabolism). • Pt at higher risk for hepatic necrosis; - taking enz inducers; phenytoin, chronic alcohol. - malnurished, HIV.

• TTT; - 1 st hr activated charcoal - 2 hr oral ipecac & gastric lavage - then wait for Bl level after 4 hrs ; if high  N acetylcysteine IV, given earlier for high risk patients

Organophosphate poisoning • mech; cholinesterase inhibitor  ↑Ach. • C/P; parasymp; miotic pupil, bradycardia, ↑ salivation ,ANVD. GI ulceration. • TTT; pralidoxime.

CO poisoning • • •

• •

•

Bind to Hb Hb O2 carrying capacity  tissue anoxia. Hx; a family found in the morning in their bed dead, pink in colour. C/O; mild headacke, NV, dyspnea. severe; hypertonia, fever, rabdomyolysis, ARF, confusion, coma. Lab; ↓PO2, normal O2 sat. Level of carboxy Hb; non smoker; <3% Smoker; 5-6% TTT; 100% O2 by mask, hyperbaric O2

• Headache is the most common symptom (90%) followed by nausea & vomitting, vertigo, alteration in consciousness and weakness. The cherry red skin colour occurs when COHb concentration exceeds 20% but it is rarely seen in life. Pulse oximetry gives falsely high oxygen saturation

Met-Hb  Causes; either by a genetic defect in red cell metabolism or acquired by Dapsone, water contaminated with nitrate, local anathetic prilocaine, antimalarials, sulphonamides, aniline dyes in dyed blankets, and cleaning solution, NO gases  C/P=cyanosis, without resp sympt, dizziness, headache, coma.  Invest; ABG shows normal PO2=n, but Standard pulse oximeters give spuriously low readings in the presence of excess methaemoglobin.  TTT= if <20% no ttt, methelene blue is indicated in any patient with (mental changes, tachycardia, dyspnoea, chest pain).

• Lead poisoning; - Anemia (↓MCV, basophilic stippling, hemolytic in acute toxicity) - Encephalopathy, demylinating PN. - Proximal RTA, abd pain, constipation - Blue line on gums.

• Chronic cocaine use can result in erectile dysfunction, ejaculatory dysfunction, excitement, emotional instability, restlessness, irritability, tremors, twitching of small muscles Severe anxiety and paranoid hallucinations, mania, and psychosis .

Specific Antidote Therapy - Acetaminophen

(N-acetyl cysteine) - Atropine (physostigmine) - Nitrites, Met Hb (methylene blue) - Digoxin (Fab) - Carbon monoxide (oxygen) - Organophosphates (atropine) - Cyanide (amyl nitrite) - Methtrexate (leucovorin) Methanol, ethylene glycol  ethanol (reduce their toxic metabolites. - B blocker glucagon

PREGNANCY • Trimethoprim is a folate antagonist and can increases the risk of neural tube defects. There is relative contraindication for ciprofloxacin in pregnancy due to the possible teratogenic effect. Augmentin, cefaclor, nitrofurantoin and metronidazole are safe in pregnancy. • Carbimazole crosses the placenta and can cause nail/finger abnormalities. • Propylthiouracil is commonly used in pregnancy instead of carbimazole due to the risks of neonatal hypothyroidism with carbimazole. • Warfarin in the first trimester can cause fetal hypoplasia of the nose and limbs. After this period warfarin is associated with neurological damage – mental retardation, microcephaly, optic atrophy and blindness. There is an option to convert from heparin to warfarin in the third trimester, but the patient will have to be re-converted back to heparin before delivery.

questions • • • • • • • • •

• • • • •

mode of action of docetaxel prevent microtuble drug causes of cholastatic picture flucloxacillin,other option was parcetamol,tramdol s/e of progesteron : option inculde:nausea,breast pain,headache nephrogenic DI asking about drug causing it and answer was:lithum drug causes constipation and option were:metformin,glagazid and other??? mention hyop glycemia and hypotension and hyponatremia,which is best to give hydrocortison pt is not controled on glgazid and has renal impairment extenide,other were metformin drug causes of gynecomastia:option amidaron,pheothiazine...?!!! excessof cortisol where will it go? bind 2 albumin bind to fat others..... mechansim of alloprinol machansim of imatinib vomiting from ca what other you add to ondansetron:dexamethone,metochropromide vt what is contra indicating:verapamil Bosentan mode of action

• • •

• • • • • •

•

dog bite: coamoxiclave pt with ethenol poisining and asking about the mechansim by which inhibation of alchol dehydrogens is done by fomepizole which drug can be givin with finsteride doxazin nitrate nicorandil ACEinhibitor drug which cause pancytopenia/aplastic an trimethoprin drug lead to LN and wt gain?? phenytoin the prognosis 26 hr after paracetamol poisoning? Inotropic support for patient with TSS (from tampons) dobutamine/noradrenaline/adrenaline Patient with SBP, treatment? - vanco/cipro/3d gen cephalosporin Pt on MTX, has been taking 40mg instead of 10mg per week. Now has ulcers, signs/symptoms of MTX overdose, treatment? - folinic acid 51) Pt had TURP done for BPH, now has urge incontinence and nocturia, treatment? - amitryptyline/can't remember options Oral treatment of S.aureus ulcer, with a list of resistance/sensitivities chlramphenical/vancomycin/ciprofloxacin (to test if you know that certain drugs do not have oral formulations) Pt with AF on amiodarone and developed hyperthyroidism, stopped amiodarone, started carbimazole to no effect, isotope scan shows low uptake, treatment? - prednisolone

• • •

• • • •

Drug induced lupus - minocycline Pt on dapsone, with methhaemoglobinemia, treatment? - methylene blue Sickle cell pt on morphine for bone infarction, overdosed, reversed with naloxone, screams in pain, treatment? - IM diclofenac/IM haloperidol/IM pethidine 8 soon starting chemo patient having agitation / suicidal thoughts ? steroids psychosis patient on lithium need to start HTN medication . patient on bendro still having high bp had side effects of fluid retention / gum bleeding /lehtargy / with other HTN medication what next ? beta blocker .inr decrease after starting tb medicine ? rifam clopigogrel adp inhibitor obese lady failed sulphonylurea low gfr what next ? exenatide high cholesterol with raised tsh what treatment ? thyroxine

•

46 . od of 80 tab thyroxine 24 hr later treatment ? beta blocker cellulitis showing MRSA what should be added along with vanco

•

73. cipro causing tendon damage withdrwal symptoms give chlordiazepoxide

• • •

124. wernicke / delerium tremens 125. phenytoin levels not decreaing in renal failure patient why

acetylar status which drug hydralazine

• •

126. patient on bendrofluthiazide having low k whats the mechanism patient agitated / mettalic taste after stopping her pshychiatric medications

• • • • • • •

raised cholestrol ,ldl,triglycerides tx ....... atrorva Subacute IE. treatment? Benpen + gent 2. litium toxicity. precipitant. 3. chronic CML, (?not candodate for imintab). a-interferon 4. Discoid lupus on steroids. next treatment. hydroxychloroquine. jaw stiffness with multiple injected sites with discharging sinus tx? metronidazole /vac Carbamazepine autoinduction 16. Respiratory depression in an overdose--Diazepam ??

Rate control in AF in a heart failure patient already on Digoxin---Amiodarone • Hypertension in Pregnancy -- Methyldopa • Beta Blocker Toxicity with very low blood sugar and bradycardia non-responsive to atropine -- Give Glucagon • Pt took cocaine, what else can be found -- Ischaemic Cardiac pain 54. Coronary Vasospam--give Calcium Channel Blocker • Patient with SIADH -- Fluoxetine 1. Lithium toxicity ---Concomittant use of ACE-Inhibitor 64. Rheumatooid Arthritis patient alread on Diclofenac Sodium,what should be started next– Methotrexate 2. Lithium toxicity ---Concomittant use of ACE-Inhibitor --/increas toxicity

3. recently had chemotherapy now has neuropathy ? cause /vincristine 4. carbamazemine autoinduction 3. valporate hair loss 4. cyclosporin excessive hair 5.patient suffered peripheral neuropathy , had chemo whic medication to stop ? vincristine

• patient on 5 Anti HTN medications develops ankle edema amlodipine/ doxazocin / minoxidil • Patient on lithium HTN medication made levels high ACE • CML treatment Imatinib

Dermatology

Scabies



Molluscum contagiosum caused by a DNA pox virus. The lesions are Discrete, solid, small, skin coloured papules -central umbilication, not surrounded by erythema & they may be spread following scratching to other sites. TTT: curetage, cryo, liquid nitrogen, trichloroacetate.



(DD chicken pox), Chickenpox lesions in the early stages may be mistaken as molluscum. However, presence of associated macules with later vesicles & pustules help to differentiate them. These lesions also affect mucus membranes, usually disappear within a few weeks, while molluscum can persist up to a year.

Sister Mary Joseph’s Nodule

Psoriasis is associated with a dermopathy & arthropathy which may be range from mild distal Interphalangeal joint involvement & nail pitting to severe Arthritis Mutilans.  A Koebner Phenomenon refers to outbreak of a skin eruption following minor trauma which is a feature of psoriasis.  Psoriatic arthropathy may be associated with an anterior uveitis.  Chloroquine may produce a severe attack of psoriasis 

Psoriasis

Psoriasis 

T cell. Prevalence 0.5-4.5%.



Types;

1.

Plaque 80% most common. Pustular Guttate. Erythrodermic. Nail psoriasis; onycholysis, pitting, subungual hyperkeratosis.



2. 3. 4. 5.

 1. 2. 3.

Associated signs; Koebner. Auspitz. Pitting.

Types; Plaque psoriasis  Guttate psoriasis  Nail psoriasis  Pustular psoriasis  Erythrodermic psoriasis 

Psoriasis   1. 2. 3.

4.

Associated; arthropathy, gout, IBD Exacerbating factors; Trauma,stress Infection; strept., HIV Endocrine; improve during pregnancy, increase during post partum period. Drugs; BB, lithium, antimalarials, steroid withdrawal , NSAIDs, INF.

Psoriasis TTT;  

  



Topical; tar, dithranol, vit D, weak steroids for face genitalia & flexures. Systemic retinoids (not monotherapy, used with UV), methotrexate, ciclosporin, aza, hydroxyurea, MMF. UV radiation; PUVA, UVB narrow band Biologic; efalizumab, Alefacept, Etanercept, infleximab.

Exacerbating factors — 

Several drugs are associated with worsening psoriasis. The most common offenders are beta blockers, lithium, and antimalarial drugs;ACEI , NSAIDs, and terbinafine .



Infections, both bacterial and viral, also may be associated with worsening of psoriasis. poststreptococcal flares of guttate psoriasis and the onset or worsening of psoriasis in association with HIV infection are well recognized.



The prevalence of psoriasis is increased among patients who abuse alcohol .

  

Urticaria is a common & usually responds very well to systemic antihistamines as first line ttt. Oral steroids .... in severe cases . topical steroids/ topical antihistamines have no effect.

Type

Description

Mechanism

Clinical features

I

Anaphylactic, immediate-type hypersensitivity

Antigen exposure causes release of vasoactive substances such as histamine, prostaglandins, and leukotrienes from mast cells or basophils. This response is usually but not always IgE-dependent.

Anaphylaxis Angioedema Bronchospasm Urticaria (hives)

II

Antibody-dependent cytotoxicity

An antigen or hapten that is intimately associated with a cell binds to antibody, leading to cell or tissue injury

Hemolytic anemia Interstitial nephritis

III

Immune complex disease

Damage is caused by formation or deposition of antigen-antibody complexes in vessels or tissue

Serum sickness

IV

Cell-mediated or delayed hypersensitivity

Antigen exposure sensitizes T cells, which then mediate tissue injury

Contact dermatitis

Immediate reaction (30-60 min) Accelerated reaction (1-72 hrs



A patient an allergy bee stings likely develop a type I reaction a bee sting therefore anaphylactic shock.

Bullous disease DIFFERENTIAL DIAGNOSIS Cong; epidermolysis bullosa.  Immune; pemphigus V, pemphigoid, dermatitis herpitiform, herpes gestationis.  Drugs; barbiturate.  Others; SSSS, TEN, diabetic bullae. 



Nicolesky sign

Pemphigus

Autoimmune bullous diseases Bullous pemphigoid

Pemphigous vulgaris

benign

May be life threatening

IgG at BM Tense bullae

IgG at intercellular substance Flaccid bullae

subepidermal

intraepidermal

TTT; less immunosuppressive

more

Potential causes of erythema multiforme include: 

INFECTIONS:   



NEOPLASIA:  



leukaemia lymphoma.

ANTIBIOTICS: 



viruses: herpes simplex 1 2, EBV, enteroviruses. bacteria: Group A Streptococcus , mycoplasma pneumoniae. other: TB , histoplasma, coccidioides.

penicillins, sulphonamides, isoniazid, tetracycline.

ANTICONVULSANTS: 

Phenytoin , phenobarbitone, carbamazepine , NSAIDs.

Steven Johnson S 

  

SJS & TEN mucocut. drug induced or idiopathic erythema then desquamation with prominent bullae but no target lesion. Erythema multiformSJS (<10% BSA epidermal detachment)  TEN (>30%). Drugs; sulfa, allopurinol, carbamazepine, phenylbutazone , piroxicam. Mortality 5% in SJS.

TEN







TEN is a severe mucocutaneous exfoliative disease of an uncertain pathogenesis & a high mortality rate. It is difficult to say whether it is another variant of Stevens-Johnson Syndrome. treatment of both are similar. It is often idiopathic but may be associated with viral infections, leukaemia, lymphoma & drugs in particular Sulphonamides , anticonvulsants & allopurinol. Usually caused by drugs, toxic epidermal necrolysis begins with widespread erythema; confluent vesicular and necrotic areas of the arm and trunk then lead to peeling away of the skin. TTT ; IVIG ,antibiotics , mortality 30%.

Contact dermatitis

asteatotic eczema



asteatotic eczema which a common problem improve just by plain emollients. dry, pruritic rash affecting upper back shins.

Seborrheic Dermatitis and Otitis Externa

Hereditary angioneurotic edema. 2 ry to C1 esterase deficiency.  Non painfull, nonpruritic, non erythematous.  No urticaria.  Inherited FH , adolescent , AD.  Symptoms: Mococutaneous .:lips, eyes, penis,Glottal& laryngeal oedema. Abd pain ( intestinal wall). mild trauma flare.  TTT: attenuated androgens or danazol  hepatic synthesis of C1-INH & C4.  Acquired; excessive utilization in malignancy or anti C1INH Ab or drugs; ACEI, opiates, NSAIDS. 

Pytriasis Rosea Begin as a herald patch,on the trunk, after 1-2 wks generalized exanthematous eruption, resolve spontaneous after 6 wks.  Spring & fall.  May be due to papova virus.  Most patients do not require therapy. For patients with mild itching treatment with moderate potency topical corticosteroids. 

Acne rosacea A chronic acneform disorder due to increased reactivity to heat flushing & telangectasia. It begins as erythema (flushing and redness) & telangiectasia, red domed papule and pustules on the central face mainly the forehead, the chin and the lower half of the nose & progress to a red lobulated nose (rhinophyma) .

Rosacea      

Ppt factors; alcohol, caffeine, spicy, hot. No comedones. 40-50 years old. F>M except rhinophyma. TTT: topical metronidazole or topical antibiotics, oral TCN, PO isotretinoin.(steroid contraindicated worse) Complication in males; rhinophyma=bullous red nose.

e.g. Rhinophyma "end stage" of sebaceous overgrowth and scarring from poorly controlled acne rosacea . Older age.

Differential diagnosis of flushing 

Autonomic-mediated



Thermoregulatory flushing



Fever Exercise Heat exposure (environmental or ingestion) Menopause

  

 

Emotional flushing Neurologic



CNS tumor. Cluster headache, Migraine. Multiple sclerosis Trigeminal neuralgia .



Vasodilator-mediated



Rosacea . Medications (ie, calcium channel blockers, nicotinic acid) Food ingestion . Alcohol . Serotonin syndrome . Anaphylaxis . Carcinoid syndrome . Systemic mastocytosis . Pheochromocytoma . Medullary thyroid carcinoma . Hyperthyroidism..

  

         

Osler-Weber-Rendu syndrome= hereditary hemorrhagic telangiectasia     

  

AD triad of; telangiectasia, recurrent epistaxis, and a positive family history for the disorder. presenting at any age. multiorgan arteriovenous malformations (AVMs). C/P; asymptomatic or have multiple organ involvement, - left-to-right shunting, high-output cardiac failure, CV stroke. - Most commonly, telangiectases involve the mucous membranes, skin, conjunctiva, retina, GI tract, lungs & brain. MRI scanning is the best noninvasive test to delineate the extent of pulmonary and CNS AVMs. Angiography is used to map the exact extent of the vascular lesions. Treatment controlling the bleeding.

Drug eruptions Urticaria.  Morbilliform .  Fixed drug eruption.  Erythema multiforme.  Stevens-Johnson Syndrome.  Toxic epidermal necrolysis .  Angioedema/anaphylaxis.  Hypersensitivity syndrome . 

Fixed drug eruption

SCC

Actinic keratosis Actinic keratosis (also called solar keratosis) is a premalignant condition of thick, scaly, or crusty patches of skin.

Basal cell carcinoma The most common type of skin cancer.  Rolled in borders.  Nodular or superficial type.  Locally malignant. Risk factors:  Sun exposure.  Arsenic exposure. 

BCC

Malignant melanoma Most important prognostic factor is tumour thickness.  5 signs of malignant melanoma: Asymmetry. Border is irregular. Color mottled. Diameter > 6 mm Enlargement.  Risk factors; FH of melanoma. cong. Melanocytic nevi. white skin, red hair, freckling, severe sunburns.  Superficial spreading.  Nodular.  Lentigo. 



Kaposi sarcoma

Kaposi Sarcoma Vascular neoplasia any organ, mc. Violaceous .  HHV-8 in HIV  TTT radiotherapy+/-chemo + antiretroviral ttt.

Cutaneous T call lymphoma         

= Mycosis fungoids. Malignant helper cell (CD4). HTLV 1. Severe pruritis, sun exposed areas, plaques, nodules, LN, large ant. Mediastinal mass. Mimic psoriasis (SCALY). EXTENSIVE INFILTRATION OF THE FACE  LEONINE. Esinophilia, high LDH. Male: female 27:1. Ttt; Puva, topical nitrogen mustard, total body irradiation, topical & systemic retinoid.

Internal malignancy Acanthosis nigricans. Tripe palm  Pruritis.  Dermatomyositis.  Erythema gyratum repens.  Acquired hypertrichosis lanuginosa.  Necrolytic migratory erythema.  Migratory thrombophlebitis.  Acquired ichthyosis.  Pyoderma gangrenosa. 

Migratory thrombophlebitis (underlying malignancy)

Tripe palms cutaneous paraneoplastic AN, (90%) of the cases are associated with internal neoplasm. (gastric adenocarcinoma, bladder, bronchus, rectum).  release of epidermal growth factors (EGF) by the tumor. 

velvety thickening of palms, with accentuation of the normal dermatoglyphic ridges and sulci (exaggerated finger prints) .

ICHTHYOSIS

Non Hodgkin lymphoma

Erythema gyratum repens Associated with cancer in 80% of cases Most commonly associated with Lung Cancer & breast  Onset may precedes cancer diagnosis by 9 months  Resolves within 1 week of cancer treatment





Erythema nodosum characterised by painful, indurated, shiny, red, hot, elevated nodules 1-3cm diameter particularly on shins. There may be associated fever, malaise, arthralgia. Over days become violaceous, then dull purple then fade like a large bruise without residual ulceration or scar.

Causes include: 

INFECTIONS: 



OTHER: 



TB, histoplasmosis, coccidiodomycosis.

DRUGS: 



bacteria: strep pharyngitis ,Streptococci, leptospirosis, psittacosis, yersinia. viruses: EBV.

sulphonamides, oral contraceptive pill.

SYSTEMIC DISEASES: 

SLE, vasculitis, regional enteritis, ulcerative colitis, Behçet Syndrome. Lofgren’s S. sarcoidosis. Hodgkin. Pregnancy



Idiopathic 25%.

Dermatologic manifestations of HCV infection Lichen planus . Acral necrolytic erythema. sicca syndrome (Sjogren Syndrome). Leukocytoclastic reactions . Cryoglobulinemia . Antiphospholipid syndrome. Vitiligo . Porphyria cutanea tarda. Pruritus .

Acral necrolytic erythema

PCT Porphyria cutanea tarda (PCT) is the most common of the porphyrias in North America and Europe. Exposure of patients with PCT to sunlight results in increased skin fragility, vesicles, bullae, hypertrichosis, hyperpigmentation and scarring in a photodistribution.  Adult  c/o fragile skin,bullae, vesicle on dorsum of hand.  Hyperpigmentation, hypertrichosis, bullae, crusts, scars on face &hand.  Confirmed by orange red fluoresence under wood’s lamp.  Cause: ethanol, estrogen, Fe, HCV, HIV.  Gradual onset.  Increase plasma Fe in 50%.  TTT; stop offending agent, phlebotomy, chloroquine .

Porphyria cutanea tarda

sicca syndrome (Sjogren Syndrome)

vitiligo     

vitiligo is associated with numerous autoimmune conditions including in order of frequency, autoimmune hypothyroidism, pernicious anemia, alopecia areata. Addison's disease.

Gastrointestinal 

Liver cirrhosis: White nails, Terry’s nail, Muehrcke's lines, palmar erythema.



Underlying cause; Dupuytren’s contracture------ Alcoholic L. C. PCT------HCV Clubbing: primary biliary cirrhosis Inflammatory B.D Clubbing. Pyoderma gangrenosum. Celiac disease--------- Dermatitis herpetiform Migratory thrombophlebitis------- Malignancy Malabsorption: Acrodermatitis Enteropathica (Zinc deficiency) koilonychia, Long. striation, brittle----Fe def. Colonic Bilh. polyposis-------- Clubbing.

   



palmar erythema     

Idiopathic Cirrhosis alcohol Pregnancy Connective tissue disorders: 

 

Particularly rheumatoid arthritis ,SLE.

Thyrotoxicosis Polycythaemia.

Dupuytren's contracture 



Dupuytren's contracture is thickening of the palmar fascia which may eventually pull the fingers into the palm . Dupuytren's disease is alcoholic liver cirrhosis familial, vascular disease, diabetes .

Hypoalbuminemia

Dermatitis herpetiformis occurring in up to 24 % of patients with celiac d.  characterized by an itchy papular vesicular eruption usually located symmetrically on the extensor surfaces of the elbows, knees, buttocks, and occasionally within the mouth. The predominant symptoms are itching and burning .  Similar to celiac disease, anti-tTG antibodies are elevated in patients with dermatitis herpetiformis .  TTT : medications such as dapsone, complete resolution of the skin lesions occur with gluten withdrawal. . 

Dermatitis herpitiformis



dermatitis herpetiformis. DH is one of the immunobullous conditions characteristically by very intensely pruritic vesicles. It is not usually responsive to topical steroids, but would respond well to dapsone. It associated with gluten sensitivity coeliac disease .

pyoderma gangrenosum.

Peutz-Jeghers S AD.  GI hamartomatous polyp , (low malignant ptential 2%).  MC pigmentation (blue/black macules mouth, lips, buccal mucosa. 

New onset DM, Diarrhea ,DVT of lt Lower limb.  Deep vein thrombosis .  N N anemia , Weight loss. (WARD)  glossitis, angular cheilitis, stomatitis, and blepharitis. 

Necrolytic migratory erythema — NME , characteristically begins as erythematous papules or plaques involving the face, perineum, and extremities . the lesions enlarge and coalesce. The affected areas are often pruritic and painful.  NME, the characteristic skin lesion of the glucagonoma syndrome, is often the clue which leads to the correct diagnosis. 

Black hairy tongue. Black tongue

In rheumatological diseases   



   

Nails: Pitting / Oncholysis (Psoriasis) splinter Hge------------Vasculitis Nail fold erythema & telangectasia----- DM infarcts-------------vasculitis Joint swelling (DIP, PIP, MCP, Wrist) : Heberden's nodes/ Bouchard's nodes------OA rheumatoid nodules. Gouty tophi Deformity : Ulnar deviation, Z-thumb, Swan-neck, Boutonnière (RA,PA); squaring of hand (OA) Wasting of small muscles of hand. Skin lesions: Gottron's papules-----------Dermato M Pyoderma gangrenosum-----Behset Palm: Dupytrens, palmar erythema, DeQuervain tenosynovitis, vasculitis, keratoderma blennorragica (Reiter) elbows psoriatic plaques, rheumatoid nodules, gouty tophi.

lupus vasculitis

Palpable purpura 1.    

Vasculitis Hypersensitivity (HSP) Septic Cryo. Wegner, PAN, Kawasaki.

Discoid Lupus plaque on nose with follicular pluggingscarring





red scaly plaques on her cheeks, forehead sides of neck. On close inspection of lesions there was plugging of some hair follicles . Lesions are discrete plaques, often erythematous, covered by scale & These lesions are typically occur on face, scalp, behind ears on neck. They can exist in areas exposed to sun. Central atrophic scarring is characteristic.

Scleroderma

Systemic sclerosis (finger plup ulcer & scars) Systemic sclerosis - Calcinosis

Finger tips & pulp Raynaud's phenomenon

Acrogangrene - Raynaud's

Rheumatoid deformities

Swan-neck Boutonnièr e Rheumatoid nodules.

Elbow 

Rheumatoi d nodule overlying the olecranon of the right arm

Livedo reticularis a web-like pattern of reddish-blue discoloration, mostly involving the legs, occurs in autoimmune vasculitis, especially in SLE and antiphospholipid syndrome, & cholesterol emboli.

•

mechanics hand mechanic's hand seems to be a distinctive feature of the Polymysitis. The anti-synthetase antibodies e.g. anti-Jo-1 (-tRNA synthetases ) predicts interstitial lung pathology, which is its most relevant internal manifestation. & are specific for a distinctive syndrome characterized by  myositis  non-erosive arthritis,  interstitial lung disease,  skin changes (Mechanic's hand in 70% of patients, Raynaud's phenomenon)  fever.

characterized by scaling and hyperkeratosis of the distal skin pad and lateral aspect of the fingers. PM-SCL autoantibody positive scleroderma with dermatomyositis (scleromyositis)

Dermatomyositis

Nail fold erythema & telangectasia 1. 2. 3. 4.



rheumatoid arthritis, SLE, dermatomyositis, scleroderma, irregular, twisted, and dilated vessels giving an injected, erythematous appearance

Strawberry tongue Kawasaki disease

Signs of inflammation e.g. Relapsing polychondritis

Pseudoxanthoma elasticum -Multiple, discrete as well as coalescent, skin colored to yellowish, indurated, papular lesions ("plucked chicken skin") -occur in flexural regions , most commonly the neck and axillae. --characterized by  dermal,  ocular (angioid streaks )and  vascular lesions (gastrointestinal bleeding , premature atherosclerosis and hypertension).

Gouty tophi

Gouty tophi of the index finger

•Suspicious skin lesions on the pinna e.g. Gouty tophi

Nodal osteoarthritis (Heberden's nodes).

Nodules

rheumatoid nodules

Gouty tophi

1.

Keratoderma blenorrhagicum: vesicles & crust in palm & soles in Reiter S + conjunctivitis, urethritis, arthritis, circinate balanitis.

Diabetes Mellitus

Acanthosis nigricans   1. 2.

3. 4. 5.

Diffuse velvety thickening & hyperpigmentation of the flexural skin. 5 types; Hereditary benign. Benign; insulin resistant states (DM, acromegaly, cushing, Addison. Pseudo; obesity. Drug induced; OCP, nicotinic acid. Malignant; Gastric adenocarcinomas.

Diabetic dermopathy

Granuloma annulare 

pale, shiny rings and nodules usually seen on the hands in DM.

Granuloma annulare

Granuloma annulare.

Diabetes: Fungal nail infections

granuloma annulare

Diabetic cheiroarthropathy

Dupuytren's contracture

Necrobiosis L D

familial partial lipodystrophy



The lipodystrophic syndromes are a heterogeneous group of congenital or acquired disorders characterized by either complete or partial lack of adipose tissue (lipoatrophy) . The extent of fat loss correlates with the severity of the metabolic abnormalities. Clinically, patients with severe lipodystrophy have severe insulin resistance and a group of unique features, such as MPGN type 2, severe hyperlipidemia, progressive liver disease, and increased metabolic rate .

Endocrinal disorders       

 

Acromegaly --------------Spade hand, Carpal tunnel S Graves' disease: finger-clubbing (thyroid acropachy), thyrotoxicosis of any cause: Palmar erythema, fine tremor, warm, sweaty. hypothyroidism Dryness & thickness & yellow pig. due to carotenemia. Addison's Palmar pigmentation, brown nails -------increased ACTH with ; vitiligo. Cushing: cigarette paper like shining of the skin, ecchymosis. diabetes: Fungal nail infections, Diabetic cheiroarthropathy, Dupuytren's contracture, carpal tunnel syndrome, granuloma annulare, Vitiligo with type 1 diabetes, Acanthosis nigricans in type II . tendon xanthomata in familial hypercholesterolaemia. eruptive xanthomata in hypertriglyceridaemia.

Pretibial Myxedema 

Pretibial myxedema is characteristically associated with Graves’ disease.Patients with pretibial myxedema may be hypothyroid , hyperthyroid or euthyroid when this skin disorder occurs. Pretibial myxedema occurs in about 3-5% of patients with Graves’ disease .The majority of patients have associated exophthalmos. Clinically.sharply demarcated,edematous,indurated plaques over the pretibial areas .

How is pretibial myxedema treated? -. Treatment of the thyroid disease doesnot affect the cutaneous findings -some cases may resolve spontaneously -many cases respond to potent topical corticosteroids or better to intralesional corticosteroids -More extensive cases may be treated with oral systemic corticosteroids





These are the shins of a 73 year old female who is admitted as a consequence of increasing confusion and inability to look after herself.

Erythema Abe Igni The diagnosis is erythema ab igne and  this is due to sitting too close to a fire. It frequently occurs on the front of the shins or lower back, the latter especially associated with the use of a hot water bottle. In this patient case the confusion and coldness with erythema ab igne suggest a diagnosis of hypothyroidism.

Albright Hereditary Osteodystrophy Albright Hereditary Osteodystrophy is characterised by short stature, round face, short neck, short 4th & 5 th ,metacarbals and obesity. May be associated with pseudohypoparathyroidism

Brittle nails, Alopecia Dry skin Coarse hair

What is the diagnosis of the patient whose hand on the right and suffers hyponatremia Slide no 10

Normal hand

DD of Hyperpigmentation

Addison's disease

Cigarette paper like skin (Cushing syndrome)

Xanthomas 

Xanthomas are firm, raised waxyappearing papules (bumps) which may occur on the trunk, arms, and legs. The lesions may be skin-colored, pink or even yellow. The presence of this type of skin lesion may be associated with abnormal levels of lipids (fats) in the blood.

Xanthomas xanthomas may be the first sign of one of the hyperlipoproteinemias. 1. xanthelasma are xanthomas of eyelids that may or may not be associated with hyperlipidemia (Familial hypercholestrolemia=type 2a). 

2.

tendon xanthomas extensor tendons of fingers, patella, elbows, Achilles tendon (one of the most common sites); diffuse infiltration of tendon by lipid 

3.

hypercholesterolemia; Types II and III

tuberous xanthomas lipid deposits in the dermis and subcutis; papuler, nodular or plaques; extensor surfaces of large joints, heels (type III)

Eruptive—small yellow papules; buttocks, posterior thighs , usuallyincrease in serum triglyceride levels (type 1) 5. Plane xanthomas--flat yellow plaques on palms, face, seen in biliary cirrhosis, familial type III. NB: xanthelasma may not be associated with hyperlipidemia but eruptive xanthomas, tendon xanthomas, and tuberous 4.

xanthomas are signs of significant hyperlipidemia; these patients require careful evaluation and prompt treatment

1ry hyperlipidemia

combined

hypertrigliceridemia

Type IIb

Type 4

Type III (tuberous, palmar)

Type I Eruptive, pancreatitis, lipemia retinal

hypercholestrolemia

Type IIa (xanthelasma & tendon)

IHD

xanthelasma

Swellings Tendon xanthoma 





familial hypercholesterolae mia Achilles tendon, tibial tuberosities and the extensor tendons of the hands, over the knuckles ,. felt as hard nodules along the length of the tendon and quite easy to miss.

Tendon xanthoma

Tendon xanthoma

tuberous xanthomas

Eruptiv e

Plane xanthomas-

Cutaneous manifestations in infectious diseases

2 Toxic shock syndrome Staph aureus toxin mediated (TSST-1, enterotoxin).  Fever, hypotension, generalized skin & mm erythema, diarrhea, MOF.  In menstrual & non menstrual patterns, barrier contraception, puerpurium, septic abortion, surgery, burns, insect bite.  TTT; staph IV nafcillin or oxacillin. strept pen. G + clinda IV 

Toxic shock syndrome (streptococcal toxins ----- injury to the skin).

3 Ampicillin + EBV or CMV 

Morbilliform rash, viral like exanthematous drug eruption , mimic measles.

5- erysipelas Cellulitis + raised sharp demarcated borders, group A strept (more commonly), & staph. Less commonly  Shin of tibia & face. 

7- Scarlet fever Desquamation & stawberry tongue.  Group A strep.  DD; Kawasaki. 

Norwegian scabies

Scabies is a highly contagious disease caused by mite, Sarcoptes Scabiei. Infestation is common, found worldwide, affects people of all races & low social classes  . Infestation is easily spread with sexual partners , household members. Infestation may also occur by sharing clothing, towels, bedding. Scabies is characterised by papularlike irritations, burrows rash of skin, especially webbing between fingers; skin folds on wrist, elbow.  treatment includes Permethrin cream , topical Benzyl Benzoate & malathion, oral ivermectin in resistant cases. Antihistamines , calamine lotion may be used to alleviate itching. 

Tinea capitus  is a dermatophyte infection of the scalp  caused by trichophyton tonsurans, occasionally by microsporum canis.  scaly circular plaque (ringworm) with broken infected hairs (exclamation mark hairs).  pruritis.  a severe inflammatory response produces an elevated boggy granulomatous mass (kerion), studded with sterile pustules.  Fever, regional LN, scarring alopecia.  The crusted patches fluoresce dull green under Wood's light. Microscopic examination of a KOH preparation shows tiny spores of fungi .  Oral griseofulvin 2-3 months is required, Ketoconazole in resistant cases.

Pytriasis versicolor  

  

Chronic asymtomatic scaling rash. Pityriasis versicolor (also called tinea versicolor) a skin lesion cause by a fungus called Malassezia furfur. Well demarcated scaling patch with variable hyperpigmentation on the trunk. Diagnosis; KOH prep. Hyfal form of pytriosporum oval. TTT; antifungal as ketoconazole or Oral Itraconazol or topical azole creams, topical selenium sulfide.

Hypopigmented areas Vitiligo (hypo, hyper thyroidism, addisson or, SLE, Alopecia areata)  Pityriasis versicolor.  Tuberculoid leprosy.  Ash leaf of tuberous sclerosis.  Morphea. 

Occupational infectious diseases Human ORF (virus)-------sheep handlers  fish tank granuloma (MB marinum)------fishing  Sporotrichosis (fungal)------------gardener 

Human ORF

fish tank granuloma

fish tank granuloma

Sporotrichosis Ulceronodular dermatosis.  Sporotrhrix schenckii (soil fungus)  Gardner, farmer, florist.  + chronic nodular lymphangitis & LN. 

Sporotrichosis

4- Impetigo Crusted golden yellow erosions.  On nose & cheek, lips, chin.  Staph aureus, group A strept. 

ECM

Erythema chronicum migrans Rapid expanding ring with clearing middle in trunk & axilla.  Lyme disease.  Borrelia burgdorferi transmitted by tick bite.  Prodome; malaise, stiff neck, arthralgia. 

Coxsackie (Hand, Foot and Mouth disease)

Cat scratch disease

Cat scratch disease Bartonella henselae, as bacillary angiomatosis.  Benign self limiting.  1ry skin then tender LN 



Bacillary angiomatosis; vascular papules or nodules, bartonella henselae& quantana, transmitted by cats & ticks, TTT: erythromycin or Doxycycline.

Scrofuloderma

Extension into the skin from underlying mycobacterial infection, most commonly of cervical lymph nodes . firm, painless, subcutaneous nodules that gradually enlarge and suppurate and then form ulcers and sinus tracts in overlying skin. Typical ulcers have undermined edges and a floor of granulation tissue.

GVHD

Desquamation Causes • Kawasaki •Contact dermatitis • Toxic epidermal necrolysis • GVHD • Streptococcal infection /pharyngitis /Scarlet fever/ Toxic shock syndrome (streptococcal toxins ----- injury to the skin).

AIDS dermatology Kaposi sarcoma.  Herpes Zoster.  Oral hairy leukoplakia; EBV in advanced AIDS. DD; Oral leukoplakia; HPV, smoking, smokless tobaco, alcohol, syphilis, can be invaded by candida, premalignant.  Molluscum contagiosum  Bacillary angiomatosis. 

Renal

Slide no 6

This female patient sufferred convuslions in childhood. She experienced several attacks of hematuria recenly. Proteinuria was less thn 1gm/24hrs and her RFTs were normal. 1. What is her condition. 2. What is the most likely lesion of her CT scan

Tuberous sclerosis

Periungual fibroma

Angiokeratoma

This is a patient with end stage renal disease, with severe uncontrolled hyperparathyroidism. What is the skin lesion

Slide no 9

Image quiz

NSF 







Nephrogenic systemic fibrosis (NSF) or Nephrogenic fibrosing dermopathy is a rare and serious syndrome that involves fibrosis of skin, joints, eyes, and internal organs. Its cause is not fully understood, but it seems to be associated with exposure to gadolinium (which is frequently used as a contrast substance for MRIs) in patients with severe kidney failure. Four of the five FDA-approved gadolinium contrast agents have been principally implicated in NSF, including Omniscan, Multihance , Magnevist, and OptiMARK. No cases were reported by use of ProHance (the fifth one).

What is this disease in a patient with abdominal pain, hematuria, and renal impairment and a palpable rash on thighs

Slide no 11

What is the most common glomerular lesion on light microscopy of this patient when a biopsy is taken

Chest disease  

   

Respiratory failure: cyanosis, Flapping tremors, warm. Clubbing------non small cell lung cancer, Mesothelioma, Interstitial lung disease, Suppurative lung disease, Pulmonary hypertension COPD: Brown nails due to nicotine staining. Sarcoidosis--- dactylitis, digital cysts, nodules Wegner’s granulomatosis---nodules Yellow nails ------bronckiectasis, pleural effusion

Tar staining

Sarcoidosis Sarcoidosis affecting the ear lobule , with a prominent purple color. Lymphomas can produce very similar lesions at this site.

Lupus pernio

Lupus pernio Lupus pernio, a chronic variant of sarcoidosis which typically affects the nose and central face, is usually very purple, and may be destructive locally. This type of lesion may also become verrucous, but can respond well to lowdose methotrexate.

Cardiovascular cases       

Clubbing---- Congenital cyanotic heart disease, SBE, Atrial myxoma Signs of infective endocarditis: Osler’s nodes, Janeway spots, splinter hemorrhage. CHF -------- Red lunnula, Pitting oedema, cold, cyanosed or pale. AI ----- Capillary pulsations & WHP , arachnodactyly in Marfan IsHD ---------Beau lines, Mee’s lines, tendon xanthomas. Vascular diseases; Burger's dis, Raynauld’s Cholesterol emboli; livedo reticularis

Signs of infective endocarditis

Splinter hemorrhages 

1. 2. 3.

longitudinal red or brown thin lines, beneath the nail plate. when capillaries within the epidermal ridges leak. local trauma, fungal infection, endocarditis.

Janeway lesion in infective endocarditis

Osler’s nodes

Burger's dis



venous ulcerations are the most common type of ulcer affecting lower extremities. The probable underlying cause of venous congestion, which may promote ulceration, venous insufficiency. The treatment of venous ulceration are control of oedema, treating any infection, compression. However, compressive dressings should be applied if arterial circulation is impaired. It is thus important to identify any arterial disease, ankle-brachial pressure index is a simple way of doing this. One may then progress to lower limb arteriogram if indicated.

Acrodermatitis Enteropathica



Zinc deficiency can lead to acrodermatitis which presents with perioral dermatitis with acral involvement & sometimes alopecia.



The diarrhea bowel resection suggest zinc deficiency

1ry systemic amyloidosis Pink ,Pinch ,purpura, in upper eye lid following straining due to deposition of amyloid in bl vs.  Papules 

RACCON”S EYES

NF NF1; lish nodules; pigmented hamartomas of Iris. chr 17, AD.  NF2; bilateral acoustic neuromas , chr 22, AD.  Both; >6 café au lait patches & neurofibromas. 



individual must have at least two of following features. Some people NF1 have only two, while others can have several of these features:



Six more cafe-au-lait spots, coffee-colored birthmarks, each measuring over an inch in adults (1/4 inch in children). Two of more neurofibromas or a plexiform neurofibroma. Freckles under arm & in groin region. A tumor of nerve the eye called an optic glioma. Two or more spots on iris of eye called Lisch nodules. A problem of one of bones such as bowing of a leg, without a fracture. A parent, brother, sister, child with NF1( FH).

     

Bone metastasis Paget disease of bone

Pulmonary osteodystrophy

Non scaring alopecia  

Androgenic baldness. A. areata.



Endocrine; hypopituitarism, hypo & hyper thyroidism, hypo para., pregnancy.



Drugs; retinoids, anticoagulants,antimitotics,OCP,



carbimazole, thiouracil, Lithium, valproate. Fe def. Chronic illness.



Scaring alopecia Bacterial;TB, S.  Physical injury; burns, radiotherapy.  Fungal (favus, kerion).  Discoid lupus.  Licken planus.  Scleroderma; morphea.  Cicatricial pemphigoid. 

DD of pruritis

Nail examination

• distal matrix ------- deeper layers of the nail plate-----ridging or splitting. • proximal matrix ---------- superficial layers---- superficial nail problems (e.g., pitting).

Hypoplasia (Nail-Patella Syndrome)

brittle nails • • • •

Low levels of zinc iron deficiency thyroid problems aging.

Pitting

punctate depressions in the nail plate. caused by defective layering of the superficial nail plate by the proximal nail matrix. Psoriasis(10-50 %), Reiter's syndrome, alopecia areata

Longitudinal Linear Lesions Longitudinal striations

• accentuated ridges in the nail surface as a normal part of the aging process. • If nails become thin and lusterless , the condition may be referred to as trachyonychia; in patients with vitiligo.

Koilonychia

Clubbing • CLUBBING is a thickening of the soft tissue beneath the proximal nail plate that results in sponginess of the proximal plate. • caused by hypervascularity and the opening of anastomotic channels in the nailbed. • may result from megakaryocytes and platelet clumps that have escaped filtration in the pulmonary bed and have entered the systemic circulation. Platelets then may release platelet-derived growth factor at the nail bed, causing periosteal changes.

Degrees of Clubbing • 1st degree: obliteration of the normal diamondshaped space at the proximal end of the nail when the distal phalanges are opposed (Schamroth window sign). • 2nd degree: Parrot peak • 3rd degree: drum stick • 4th degree: HOA (X ray finding)

Causes of clubbing • •

familial . secondary : Lung disease: – Suppurative lung disease: lung abscess, empyema, bronchiectasis, cystic fibrosis – Interstitial lung disease esp. cryptogenic fibrosing alveolitis, asbestosis. – non small cell bronkogenic carcinoma, Mesothelioma (HOA ) – Pulmonary hypertension Heart disease: – Congenital cyanotic heart disease – Subacute bacterial endocarditis – Atrial myxoma Gastrointestinal and hepatobiliary: – Crohn's disease and ulcerative colitis – Cirrhosis, especially in primary biliary cirrhosis Skin disease - Pachydermoperiostosis, palmoplantar keratoderma. Malignancies - Thyroid, thymus, Hodgkin, CML, POEMS syndrome with plasma cell dyscrasia Endocrinal - Acromegaly, thyroid acropachy, pregnancy, severe secondary hyperparathyroidism Others: Vascular anomalies of the affected arm (unilateral clubbing)

Transverse Linear Lesions

Beau’s line They develop in response to many diseases, such as • chronic paronychia • zinc deficiency,

• syphilis, • uncontrolled DM, • myocarditis, • PVD, • chemotherapy.

Mees’ lines

• In patients with Mees' lines, the nail bed is normal, but the nail itself is microscopically fragmented, probably because of the disruption of normal growth at the nail matrix during the insult. The width of the lines varies and, because the defect is in the nail itself, the line moves distally with time.

Onycolysis – Systemic diseases • Anemia (iron deficient) , • Bronchiectasis , Pleural effusion , • Hyperthyroidism , Pellagra , • peripheral ischemia , Neuritis • Leprosy , Syphilis , • SLE , Scleroderma , Psoriatic arthritis – Dermatologic diseases • Psoriasis , Lichen planus , PCT, Pemphigus, _ • Mechanical • Chemical – Drug induced • Microbial: Dermatophytosis, Candida, Bacteria (Pseudomonas),Virus (HS)

Color changes • Leukonychia Totalis, Partialis; Terry’s nails, Muehrcke's lines , True' Leukonychia.

• • • •

Half-and-half nails Yellow nail syndrome brown nails Blue nails; cyanosis

Leukonychia Totalis

Terry’s nails

• 80% of patients severe liver disease, usually cirrhosis. • 25 % of hospitalized patients with varied diseases • The condition is thought to be caused by a decrease in vascularity and an increase in connective tissue in the nail bed .

• Pairs of transverse white lines that extend all the way across the nail.

•hypoalbuminemic states ( less than 2 g per dL) and disappear when the protein level normalizes. •abnormality of the vascular nail bed •disappear while the nail is depressed •does not move with nail growth. These characteristics distinguish Muehrcke's lines from Mees' lines.

'True' Leukonychia. Children and active adults commonly have one or more white lines or spots on one or more nails; this condition is known as leukonychia . These lines and spots are nonuniform, appear in different places on different nails, do not span the nail, and are of no significance. They are thought to result from random minor trauma to the proximal nail bed. They should not be confused with Mees' and Muehrcke's lines, which parallel the lunula across the entire nail bed and occur in more than one nail.

Half-and-half nails • in patients with chronic renal failure, increased melanin production may cause the distal part of the nail bed to turn brown. In patients with severe renal disease, the proximal portion of the nail bed can turn white, obliterating the lunula and giving a half-brown, half-white appearance, also called half-and-half nails

Yellow nail syndrome

• Patients note that nail growth slows and appears to stop. The nail plate may become excessively curved

Changes in the color of the lunula • Wilson's disease------- blue (azure lunula). • Silver poisoning will turn the nail itself a bluegray color. • Heart failure ---------- red, • tetracycline ------------ yellow. • Excessive fluoride ingestion can turn nails brown or black.

Diabetes Mellitus

Diagnosis of DM Fasting

normal

IFG

<110 mg/dL <6 m mol/ L

110-125 mg/dL 6-7 m mol/ L

IGT

DM

Goal of ttt in DM

>126 mg/dL 80-120 >7 mmol/ L

RBS <140 or 2h PP <7.8 after a 75-g OGTT

140-199

Bed time

7.8-11.1

>200 >11.1

<180

100-140

IGT Predicts increased risk of diabetes and cardiovascular disease)

Classification of DM Type 1 (10%)

-cell destruction—complete lack of insulin

Type 2 (85%)

-cell dysfunction and insulin resistance

Gestational

-cell dysfunction and insulin resistance during pregnancy, 50 %DM in 10yrs.

Other specific types

American Diabetes Association: Position Statement, Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 32:S62-S67, 2009

VI. Other specific types C. Diseases of the exocrine A. Genetic defects of b-cell function pancreas 1. Chromosome 12, HNF-1 (MODY3) 1. Pancreatitis 2. Chromosome 7, glucokinase (MODY2)2. Trauma/pancreatectomy 3. Cystic fibrosis 3. Chromosome 20, HNF-4 (MODY1) 5. Hemochromatosis 4. Chromosome 13, insulin promoter factor-1 (IPF-1; MODY4) D. Endocrinopathies 5. Chromosome 17, HNF-1 (MODY5) 1. Acromegaly 6. Chromosome 2, NeuroD1 (MODY6) 2. Cushing’s syndrome 3. Glucagonoma 7. Mitochondrial DNA.

B. Genetic defects in insulin action 1. Type A insulin resistance 2. Lipodystrophy S

4. Pheochromocytoma 5. Hyperthyroidism 6. Somatostatinoma 8. Others

VI. Other specific types E. Drug- or chemical-induced 1.Calcinurin inhibitors ( cyclo, Tac) 2. Glucocorticoids 3. Nicotinic acid 4. Pentamidine 6. Diazoxide 7. β-blocker 8. Thiazides 9.α –Interferon 10.phenytoin, clozapine 13. somatostanin F. Infections 1. Congenital rubella 2. Cytomegalovirus 3. coxsakie

G. Uncommon forms of immune-mediated diabetes 1. Anti–insulin receptor antibodies H. Other genetic syndromes sometimes associated with diabetes 1. Down’s syndrome 2. Klinefelter’s syndrome 3. Turner’s syndrome 4. Friedreich’s ataxia 6. Myotonic dystrophy 7. Laurence moon beadle 8. Prader willi.

Maturity onset diabetes of youth (MODY)    

Type 2 DM in patients under the age of 25 ys. AD & strong family history. Single gene defect defect insulin secretion. Treated by oral hypoglycemics.

Latent autoimmune DM of the adult (adult, not obese, autoimmune, require insulin). NB; so diagnosis of new onset DM may require assessment of; - C peptide, if low need insulin, - & auto Ab (ICA, GAD) need insulin.

Type 1

type2

genetics

Both parents=10-20% Identical twins 30-50% Father DM=6% Mother DM 3%

70-100% 90%

↑risk

On chr 6, HLA DR3/4, DQ8

No HLA, K channel subunit KCNJ11

protective

HLA DR 2

autoab

60-90 % ICA, GAD

----

prevalence

1/1000

1/100

age

<30 yrs

> 30 yrs

Associated

Other autoimmune, wt loss, ketosis, insulin def

Metabolic S, obesity, acanthosis, amyloid deposit in Islet cells

ttt

Insulin

all

Gestational Diabetes

Hyperglycemia during pregnancy usually resolves after birth  Complicates ~4% of all pregnancies.  High risk of perinatal morbidity and mortality  High risk of later type 2 diabetes in both mother and baby  Diabetic mother  high risk of fetal malformation.  Screening for GDM at 24-28 wks if >35 yrs, obese, FH.  Oral HypoGlycemics are #.  Glucose cross the placenta macrosomia, but insulin does not cross. 

Who Should Be Tested for Diabetes? Consider if One or More of the Following Apply 1. 2. 3. 4. 5.

Symptoms suggesting diabetes: weight loss, hunger, urinary frequency, blurred vision Age >45 (>30 if patient has other risk factors) family history of diabetes Prior gestational diabetes Women with polycystic ovarian syndrome (PCOS)

Management of DM 1- patient education; self monitoring, insulin administration, hypos, foot care. 2-nutrition 3-glycemic control

glycemic control Assessment of glycemic control; 1- serial measurement of Blood glucose (SMBG)( 3 times preprandial, 1 at bedtime) 2- Hb A1C (assess nocturnal & postprandial), reflects BG in the last 3 months. A1C  6% = mean BG 135 mg/dl, 7.8 mmol/l . ↑ 1% ↑ 35 mg/dl 7% 170 mg/dl, 9.5 mmol/l 8% 205 mg/dl. 11.5mmol/l. 3-fructosamine (glycated Alb); used in hemoglobinopathies, reflects BG in the last 2-3 weeks. NB; ↑ Hb A1C, normal SMBG ↑ nocturnal & postprandial, ↑ SMBG, normal Hb A1C  intercurrent infection or illness, hemolysis.

α-Glucosidase inhibitor

(Acarbose) Repaglinide nateglinide

Pioglitazone, rosiglitazone

Antihyperglycemic Agents Major Sites of Action -Glucosidase inhibitors –

Glitazones

Plasma glucose

Carbohydrate absorption

GI tract

Metformin

Secretagogues

+Glucose uptake Muscle/Fat

–

+

Glucose production

Liver – Insulin secretion

Pancreas

+

Insulin Secretagogues Sulfonylureas Mechanism of action

Increase basal and/or postprandial insulin secretion

Efficacy depends upon

Functioning -cells

Dosing

Sulfonylureas: 1 or 2 times daily

Side effects

Hypoglycemia, Weight gain, allergy (rare) ↑CVS mortality, cholestasis, agranulocytosis, drug interaction ( Hajat wehsha).

Contraindications;

Renal, hepatic, old

Selected Sufonylureas Dosing Information Generic Name Effect

Dose Strengths

Recommended Dose Range

Glimepiride (Amaryl)

1, 2,3 or 4 mg

1–8 mg

Glibenclamide (Doanil)

1.25, 2.5, or 5 mg

1.25–20 mg

5 or 10 mg bid

Gliclazide MR

30 mg

30–120 mg

60 or 120 mg

Gliclazide

40 or 80 mg

40–360 mg

80 or 160 mg bid

(Diamicron MR & Diamicron)

Usual Maximal 4 mg qd

Insulin Secretagogues Repaglinide (Novonorm 0.5, 1, 2 mg) repaglide 1 mg Mechanism of action Increase postprandial insulin secretion ( fast phase of insulin release)

Efficacy depends upon Functioning -cells Dosing

Repaglinide:

(Novonorm 0.5, 1, 2 mg)

3 or 4 times daily with meals Side effects

Weight gain, allergy (rare)

Main risk

Hypoglycemia

Biguanides Metformin (Glucophage, Cidophage, 500, 850, 1000mg) Primary mechanism of action

Decreases hepatic glucose production (↓insulin resistance at the liver)

Efficacy depends upon Dosing adv;

Presence of insulin 2 or 3 times daily wt loss

Side effects

Diarrhea, nausea

Main risk

Lactic acidosis

Contraindications;

s creat >1.5♂, 1.4 ♀, radiocontrast, serious illness, acidosis, CHF. 1-2 days after surgery.

Glitazones (TZDs) Pioglitazone (Glusitin, Actos 15, 30, 45 mg) Rosiglitazone (Avandia 2, 4, 8 mg) Mechanism of action

Enhance tissue response to insulin, + PPAR-γ ↑Glut 4 (↓insulin resistance at ms & adipose tissue

Efficacy depends upon

Presence of insulin and resistance to its action

Dosing

Once daily

Side effects

Edema, weight gain, anemia, macular edema, fractures, resumption of ovulation

Main risk

Congestive heart failure

Contraindications;

CHF, hepatic

α-Glucosidase Inhibitors Acarbose (Glucobay 50, 100mg) Mechanism of action Efficacy depends upon Dosing

slow glucose absorption. Postprandial hyperglycemia

Acarbose (Glucobay 50, 100mg) 3 times daily, with meals

Side effects

Flatulence

Main risk

Liver enzyme elevation (rare)

GLP-1-based therapies 

1.

1.

↑ GLP-1 ↑insulin release, ↓glucagon ↓glycogenolysis & gluconeogenesis, ↓gastric empting (↓ postprandial hyperglycemia but GIT upset). GLP-1 agonist (Incretin analogues)(SC). Dipeptidyl peptidase IV inhibitors (DPP-IV I ) ↓catabolism of endogenous GLP-1 (Incretin enhancers ) (oral).

GLP-1 agonist (Exenatide, Liraglutide) Mechanism of action GLP-1analogue ↑insulin release, ↓glucagon, ↓gastric empting, ↓appetite, ↑ B cell mass, as adjuvant in combination in type2. Efficacy depends upon

Functioning -cells

Power

Decrease A1C 0.5%–1%

Dosing

Exenatide sc injection twice daily, Liraglutide once daily.

Adv;

wt loss, ↓ CVS risk, ↓HTN

Disadv; injection, not used with insulin, hypoglycemia with secretagogues. Side effects

Contraindications;

GIT upset renal, agents which ↓GI motility.

DPP-IV INHIBITORS (Sitagliptin, Vildagliptin) Mechanism of action ↑endogenous GLP-1 ↑insulin release, ↓glucagon, ↓gastric empting. as monotherapy or in combination in type2. Efficacy depends upon Dosing

Functioning -cells

Sitagliptin (Januvia) 25 mg, 50 mg, 100 mg once daily

Adv;

no hypoglycemia

Disadv; no ↓appetite, no wt loss, no ↓ CVS risk, ↓dose in CKD. Side effects

GIT upset

Amylin agonist (pramlintide) Mechanism of action Amylin is a 37-amino acid peptide co-secreted with insulin ↓glucagon, ↓gastric empting, ↓appetite. Amylin is deficient in type 1 diabetes and relatively deficient in type 2 diabetes. Adv; wt loss, ↓ postprandial hyperglycemia,decrease insulin dose by 20% used in CKD, moderate dose if GFR<20ml/min Disadv; injection, only as adjuvant with insulin in type 1 & 2. cannot be mixed in a syringe with insulin. Mild to moderate nausea is the most commonly reported side effect and generally dissipates by four weeks. Dosing it requires injections with each meal in the setting of type 1 diabetes, and at least twice daily in type 2 diabetes. Side effect Contraindications; agents which ↓GI motility.

Reasons for insulin use in type 2 diabetes 1.

2. 3.

6.

7. 8. 9. 10.

Hyperglycemia despite maximum dose of oral agents; A1c levels >7%, FPG > 7 mmol/l) FPG > 11.1 mmol/l from the start Decompensation due to inter current events: Infection, acute injury . Perioperative Pregnancy Renal or hepatic diseases. Allergy to oral agents Latent autoimmune diabetes in adult.

Current Insulin Preparations Onset Short acting Lispro/aspart <15 min Regular 0.5-1 hr Long acting NPH 2-4 hr Insulin glargine 1-2 hr Insulin detemir 1-2 hr Combinations NPH/ Regular 0.5-1 hr (70/30, 50/50) Protamine Lispro/Lispro <15 min (75/25, 50/50)

Peak

Duration

1 hr 2-3 hr

3 hr 3-6 hr

7-8 hr Flat Flat

10-12 hr 24 hr 12-20 hr

dual; 2-3

10-12

7-8 dual; 1 hr several hrs

12

Lispro as Apidra , aspart as novorapid , glargine =lantos, not mixed.

Twice-daily regimen of insulin or Multiple daily injections.

(0.5 -1.0 IU / Kg /d)

Twice-daily Insulin Regimen (SplitMixed and Pre-Mixed Regimens) 

Total insulin dose

• 2/3 Morning dose : 2/3 NPH 1/3 Regular (or insulin lispro/aspart)

• 1/3 Evening dose: 1/2 NPH 1/2 Regular (or insulin lispro/aspart)

Physiologic Insulin Replacement Insulin therapy should closely mimic normal insulin physiology Ideally, insulin therapy should address: Basal needs: Intermediate-/long-acting insulins (NPH, detemir, glargine) Bolus needs: Rapid-/short-acting insulins given with meals (lispro, aspart, glulisine, regular insulin)

Meal

Meal

Meal

Expected insulin changes during the day for individuals without diabetes

• Normal insulin physiology is matched by multiple insulin injections

This image cannot currently be display ed.

Humulin R, Mixtard

Onset 0.5-1 hr

Peak 2-3 hr

Duration 3-6 hr

Humalog, Novorapid, Apidra

Onset <15 min

Peak 1 hr

Duration 3 hr

 Insulin Lispro Insulin lispro is an insulin analog that The (proline), (lysine) amino acid sequence of the insulin molecule is reversed to be lysine-proline resulting in a rapid absorption, within 15 minutes. Because insulin lispro can be injected just before (or after) the meal versus waiting 30 minutes with regular insulin, patients may find it provides them with more flexibility and convenience & has a reduced risk of hypoglycemia compared to regular insulin.

Insulin Aspart 

Insulin aspart is a human insulin analog approved 2000. The amino acid proline is substituted with aspartic acid resulting in a rapid onset of activity. Insulin aspart should be injected 5-10 minutes before the meal.

Onset Humulin N, Insulatard 2-4 hr

Peak 6-8 hr

Duration 10-12 hr

Lantus

Onset 1-2 hr

Peak Flat/Predictable

Duration 24 hr

 1.

2. 3. 4. 5.

Insulin therapy perioperatively; Continuous basal insulin is given (either IVI 1 unit /h or 0.02 U/kg or SC long lasting insulin (25-50%) of the usual dose . +/- IVI glucose. Oral HypoG # as insulin & Glucose requirement are changing rapidly, dangerous specially in fasting. Sliding scale upon rise of BG should be avoided. TPN ↑insulin need even in non-DM IVI of insulin.

Diabetes: Fungal nail infections

granuloma annulare

Diabetic cheiroarthropathy

Dupuytren's contracture

Granuloma annulare 

pale, shiny rings and nodules usually seen on the hands in DM.

Granuloma annulare.

Ketoacidosis

Hyperglycemic Hyperosmolar Coma

Clinical Impact of Diabetes Mellitus Diabetes

A 2- to 4fold increase in cardiovascular mortality

The leading cause of new cases of end stage renal disease

The leading cause of new cases of blindness in workingaged adults

The leading cause of nontraumatic lower extremity amputations

Lessons from UKPDS: Better control means fewer EVERY 1% complications REDUCED

reduction in HBA1C

RISK*

Deaths from diabetes

Heart attacks

1% Microvascular complications

Peripheral vascular disorders UKPDS 35. BMJ 2000; 321: 405-12

*p<0.0001

Hypoglycemia is a serum glucose < 60 mg/dL (3.3 mmol/L)



Hypoglycemia

Hypoglycemia: Etiology: Liver disease Alcohol intake Adrenal failure, hypopituatarism,. Factitious hypoglycemia. Insulin producing tumours & B-cell hyperplasia( insulinoma & others)

Hypoglycemias in diabetics : Risk Factors Drug related: Patient related: o o o o o o o o

Elderly Poly-pharmacy. Initiation of treatment. Tight BG control. Neuropathy. Non compliance. Infection. Irregular/missed meals or exercise

o o o o

Insulin treatment Pattern of insulin release Type of SU and presence of active metabolites. Drug interaction e.g. ACEI and BB

CAUSES OF HYPOGLYCEMIA IN DIABETICS Management related  Overdosages  Insufficient caloric intake.  Site of injection, local massage, hot baths or sauna.  Sudden exercise.  Alcohol intake with SU.  Severe renal & hepatic dysfunction.  Adrenal failure, hypothyroidism. Hypopituitarism.  Factitious hypoglycemia. 

Nocturnal hypoglycemia 

Often identified by the patient’s partner, or family members by : Restlessness ,Sweating ,Convulsions. The patients may have :  Morning headache. Chronic fatigue.  Poor sleep quality. Nightmares. 

More common with long-acting insulins that have a distinct peak four to eight hours after injection (such as NPH insulin, 70/30 insulin ) More likely when the evening dose of long-acting insulin is taken before the evening meal rather than at bedtime

Always Carry Rapid-Acting Carbs

Hypoglycemia Treatment

Severe Low  Unconscious / Unresponsive



Seizure



Uncooperative



• A 25-year-old female presented with six months history of depression, irritability and painful sensory symptoms in her legs. Over the last four weeks she presents a broad base ataxic gait. • An MRI brain showed bilateral posterior thalamic nuclei (pulvinar region) high signals. • Which of the following is the most likely diagnosis? • Herpes simplex encephalitis. • Multiple system atrophy. • New variant CJD. • Sporadic CJD . • Wilson disease

• New variant Creutzfeldt-Jakob disease (CJD) usually presents in a young person, in their twenties or thirties. • In the majority of the cases the first symptoms are psychiatric and painful sensory symptoms in the lower limbs. • Ataxia and involuntary movements (for example, myoclonus) usually appear at an interval of about six months after the initial symptoms. • MRI brain shows bilateral pulvinar (posterior thalamic nuclei) high signals. • EEG is usually normal in new variant CJD.

• A 35 year old woman has been admitted to hospital for investigation of progressive weakness in her legs. For the past 5 years. The patient's mother has similar difficulties with weakness and sensory problems. Examination revealed power of 3/5 distally in the upper and lower limbs with a glove and stocking pattern sensory loss to pain and touch. • What is the most likely diagnosis? • A. subacute combined degeneration of spinal cord. • B. Friedrich's ataxia • C. Chronic inflammatory demyelinating polyneuropathy . • D. Multiple sclerosis . • E. Hereditary sensory & motor neuropathy.

•

•

•

Answer: e) hereditary sensori motor neuropathy. In view of the family history, this patient is most likely to have hereditary sensori motor neuropathy type I (Charcot Marie Tooth disease). HMSN 1 is the most common form of hereditary neuropathy. Severely and uniformly slowed nerve conduction velocities (NCVs) and primary hypertrophic myelin pathology with prominent onion bulbs and secondary axonal changes are the hallmarks of the disease. Motor symptoms predominate over sensory symptoms. Often, patients report loss of balance, muscle weakness, and foot deformities. Onset in the first decade of life is typical, but disease develops in some patients in young or mid adulthood. HMSN 2, on the other hand, represents the nondemyelinating neuronal type with relatively normal NCVs and primary axonal pathology. Although nerves are not enlarged in the neuronal form, weakness often is less marked and onset of this neuropathy is delayed. Peripheral nerves are not enlarged clinically, and weakness of feet and leg muscles predominates; hands are less severely affected than the legs. Patients experience sensory loss in the distal extremities, and foot deformities (ie, pes cavus) tend to be less marked than those of HMSN 1.

• A 40 year old man presents with an uncomfortable sensation in his face, comes to the casualty department. He is unable to lift his eyebrows and also has bilateral facial weakness. Which one of the following is most likely to cause bilateral lower motor neuron weakness? A. Cerebrovascular disease. B. Pontine haemorrhage. C. Lyme disease. D. Multiple sclerosis. E. Motor neuron disease

Answer: c) lyme disease. Causes of Upper Motor Neuron facial weakness are: CVA pontine haemorrhage Multiple Sclerosis motor neuron disease Lyme disease usually causes lower motor neuron facial weakness.

A 47-year-old personal assistant attends the outpatient clinic with a six-month history of malaise and joint pains. She has had to quit her job. She is also complaining of difficulty sleeping at night and urinary frequency. The investigations show: full blood count normal, U&E normal, LFTs normal, ESR normal, CRP normal, Thyroid function normal Autoimmune screen normal What is the most likely diagnosis? 1. fibromyalgia 2. Depression 3. rheumatoid arthritis 4. Vasculitis 5. systemic lupus erythematosus

True 1. Fibromyalgia is said to occur in between 1 and 2% of the general population and has a female to male ratio of 9:1, presenting most often in the 30–50 year age group. It presents with musculoskeletal pain that often has multiple trigger points and may be poorly defined. Self-management strategies, reassurance and tricyclic anti– depressants for sleep disturbance are the mainstays of therapy. Aerobic exercises such as swimming are recommended. Symptoms wax and wane for many years.

33- A teenage girl presents with Guillain-Barre syndrome. Her weakness continues to worsen after admission to hospital. Which of the following should be used to monitor her? 1) arterial blood gases 2) chest expansion size 3) FEV1/FVC ratio 4) PEFR 5) vital capacity

• A 46-year-old male presents passing 4-5 litres of urine per day, after commencing a new drug. S.sodium 142 mmol/l, Plasma osmolality 295 mosmol/l (275-290), Urine osmolality 280 mosmol/l (350-1000).What drug was prescribed? 1 )Carbamazepine 2 )Chlorpropamide. 3 )Fluoxetine . 4 )Furosemide . 5 )Lithium.

A 21-year-old Nigerian woman was referred by her general practitioner with a progressive history of polydipsia and polyuria of 6 months duration. She has a history of sickle cell disease and had been admitted on two previous occasions to hospital with chest pain precipitated by crisis. Fasting blood glucose is 4.5 mmol/l. She is not on any medication. A water deprivation test was performed. Water deprivation phase plasma osmolality298 mosm/kg (278–300 mosm/kg) urine osmolality300 mosm/kg DDAVP Phase plasma osmolality295 mosm/kg,urine osmolality325 mosm/kg. What diagnosis would best fit the clinical picture and investigation result? 1. Sickle cell nephropathy 2. Cranial diabetes insipidus 3. Psychogenic polydipsia 4. Nephrogenic diabetes insipidus 5. Lithium-induced nephrotoxicity

True 4. The disease is characterised by the inability to concentrate urine due to the lack of response of renal tubules to antidiuretic hormone (ADH). Normally the kidneys concentrate urine by increasing water resorption by the collecting duct in the presence of ADH; this mechanism helps to maintain plasma osmolality and extracellular volume. Without ADH, a large amount of dilute urine is excreted. The water deprivation test after an overnight fast assesses the kidneys’ urine-concentrating ability and response to ADH. The result shows abnormally low (< 750 mosm/kg) urine osmolality, which increases only slightly after exogenous ADH (1-deamino-8-D-argininevasopressin (DDAVP), vasopressin). Nephrogenic diabetes insipidus (NDI) is X-linked recessive. Homozygous affected people (all males) are completely unresponsive to ADH while heterozygous females show normal or slight impairment. Acquired NDI occurs in disorders that disrupt the medulla or distal nephron and impair concentrating ability. Causes are: sickle cell nephropathy, polycystic kidney disease, pyelonephritis, amyloidosis, certain nephrotoxins such as lithium and demeclocycline.

27- In Psoriatic arthropathy all true except A is usually associated with psoriatic nail change. B may cause sacro-iliitis . C can occurs in the absence of psoriasis of the skin. D is associated with uveitis. E responds to chloroquine, which is the treatment of choice.

A 25 year-old lady recently diagnosed with rheumatoid arthritis. She has developed weakness, double vision and tiredness. Examination reveals bilateral weakness of eye abduction, bilateral ptosis, slightly reduced proximal motor power in the limbs, normal reflexes and sensation. What is the diagnosis? 1) Chronic progressive external opthalmoplegia. 2) Guillain-Barre syndrome. 3) Multiple sclerosis. 4) Myasthenia gravis. 5) Polymyositis

The answer is 4 Myasthenia gravis is well known to be associated with other autoimmune diseases such as pernicious anaemia, thyroid disease and rheumatoid arthritis. In Guillain-Barre syndrome you will expect absent reflexes. Polymyositis does not usually cause ptosis or ophthalmoplegia.

A 70 year man has been short of breath for 1 year. An electrocardiogram shows T wave inversion and q waves in the anterolateral leads at rest. He has cardiomegaly on the chest X ray. Clinical examination shows a third heart sound, a soft systolic murmur in the mitral area and also bilateral inspiratory crepitations in his lungs. • Which of the following is he at risk of? • A. Deep vein thrombosis • B. Pulmonary embolus • C. Systemic arterial embolus from mural thrombus • D. Venous thrombosis due to mural thrombus • E. Coronary artery thrombus due to mural thrombus

• Answer: c) systemic arterial embolus from mural thrombus. This man has features indicating that he has an enlarged left ventricle from previous anterior myocardial infarction in the LAD artery territory. Poor LV function also causes his symptoms of heart failure. He is at risk of developing mural thrombus with embolus to the arterial circulation.

A 12 year old girl has a diagnosis of the 21 hydroxylase deficiency form of congenital adrenal hyperplasia. Which one of these features is likely to be present? • A. High cortisol . • B. Ambiguous genitalia . • C. Alopecia . • D. Precocious puberty. • E. Hypertension.

• Answer: b) ambiguous genitalia. In congenital adrenal hyperplasia, hirsutism, ambiguous genitalia and normal puberty (precocious puberty in boys) are seen in girls. There is also cortisol deficiency and replacement with dexamethasone is appropriate. Hypertension typically occurs in the rarer forms but not 21 hydroxylase deficiency which is the commonest form of CAH. • • 21 Hydroxylase deficiency

A 63 year old male is admitted with acute onset unsteadiness of gait, dizziness and dysphagia. Examination revealed a right-sided Horner's syndrome, nystagmus, loss of pain and temperature sensation on the left side of the trunk and in the left arm and leg, and gait ataxia. What is the most likely diagnosis? 1) leaking posterior communicating artery aneurysm 2) left sided acoustic neuroma 3) posterior inferior cerebellar artery occlusion 4) right sided pontine infarct 5) spontaneous left sided cerebellar haemorrhage

The answer is 3 This is Wallenberg's syndrome/ lateral medullary syndrome and is due to occlusion of the posterior inferior cerebellar artery.

• A 50 year old lady has polyuria. Her serum calcium is 2.85 mmol/l and phosphate is 0.9 mmol/l. Which of the following could cause this? • A. Vitamin D deficiency • B. Loop diuretics • C. Lithium • D. Diltiazem • E. Bisphosphonates

• Answer: c) lithium. Lithium, thiazides (not loop) diuretics and vitamin A or D intoxication can cause hypercalcaemia.

.A 45 year old patient presents with proximal muscle weakness, particularly in the lower limbs. She has a heliotropic rash around the eyes and also Gottron’s papules. Which one of the following antibodies is most strongly associated? A.La B. Ro C. Jo-1 A.D. SCL-70 E. Anti DsDNA

• Answer: C) Jo-1. The diagnosis is dermatomyositis. Anti Jo-1 antibody is associated with acute onset myositis, particularly dermatomyositis. The limb girdle or proximal muscles are most severely affected in both polymyositis and dermatomyositis. • • Gottron's papules

A 35 year old lady has grey pigmentation of her skin and hypotension. Her early morning cortisol is 45 μmol/l and her sodium is 127 mmol/l. Which of the following is the best replacement regimen? A. Hydrocortisone 10mg mane, 5mg mid day and 5 mg evening and also fludrocortisone 100 μg mane B. Hydrocortisone 10mg mane, fludrocortisone 100 μg mane C. Prednisolone 20 mg mane D. Hydrocortisone 40mg mane and fludrocortisone 300 μg mane E. Hydrocortisone 20mg mane, 10 mg mid day

• Answer: a) hydrocortisone 10mg mane, 5mg mid day and 5 mg evening and also fludrocortisone 100 μg mane. She has Addison's disease and needs both glucocorticoid (hydrocortisone) and mineralocorticoid (fludrocortisone) replacement. Steroid replacement is usually given 10/5/5 mg or 10/5 mg, although this is adjusted with cortisol day curves. Fludrocortisone 100 μg mane should be adequate.

A patient has been in atrial fibrillation for at least several months. He is brought in for DC cardioversion because of troublesome palpitations and breathlessness. His current medications are digoxin and warfarin. Following successful cardioversion, which changes should be made? A. Discontinue warfarin and digoxin B. Continue warfarin but not digoxin till outpatient review C. Continue digoxin but not warfarin D. Continue both digoxin and warfarin E. Continue warfarin for life

• Answer: b) continue warfarin but not digoxin till outpatient review. For at least 4 weeks following DC cardioversion, the patient is still at risk of thromboembolism. If the patient remains in sinus rhythm after 6-8 weeks then warfarin can be discontinued unless there is evidence of paroxysmal AF. Digoxin should be stopped once sinus rhythm is achieved since its role is only for rate control. It does not help in maintenance of sinus rhythm.

A 20-year-old man presents with a history of intermittent fever for 1 month, accompanied by chest pain, which is worse on lying down. He has recently also noticed pain in the joints of his hands and feet. He is febrile, with a temperature of 39oC. His pulse is 98/min and his blood pressure is 110/70 mmHg. The positive findings on examination are enlarged anterior cervical lymph nodes, pericardial rub, mild hepatomegaly and synovitis of the proximal interphalangeal (PIP) and wrist joints. Investigations show the following:Hb 10.5 g/dl, WBC 20 x 10 9/l, P82%, PLT540 x 109/l, ESR110 mm/1st hr, CRP 246 mg/l, ALT69 IU/l, ALK-P 246 IU/l, Ferritin 4567 μg/l (normal range 14 – 200 μ/l), CXR cardiomegaly, 2D echocardiogram pericardial effusion MSU and blood culture negative, ANA, RF, ANCA all negative, CT abdomen hepatosplenomegaly. Which of the following is most likely diagnosis? 1. SLE 2. Mixed connective tissue disease (MCTD) 3. Undifferentiated connective tissue disease (UCTD) 4. RA 5. Adult-onset Still’s disease

True 5. Clinical features of adult-onset Still’s disease include arthralgia or arthritis; a high fever (> 39oC), especially in the afternoon and evening; fleeting salmon-pink maculopapular rash which is most prominent with fever; serositis; anaemia; elevated acute phase reactants; and evidence of reticuloendothelial activation. In between the febrile episodes the patient feels rather well. The laboratory investigations commonly reveal leucocytosis, thrombocytosis, raised serum ferritin and an elevated erythrocyte sedimentation rate and C-reactive protein. Autoantibodies are negative.

• A 70-year-old woman referred by a a breast lump. She was asymptomatic but her investigations reveal:Corrected calcium2.72 (2.2 2.6)Phosphate0.80 (0.8-1.4)Alkaline phosphatase110 U/L (20 - 95)PTH concentration5.1 pmol/L (0.9-5.4) • What is likely diagnosis? 1 )bony metastases 2 )chronic vitamin D excess 3 )ectopic PTH related peptide (PTHrp) secretion 4 )multiple myeloma 5 )primary hyperparathyroidism

• A 19-year-old male presents with concerns regarding his pubertal development. On examination he 1.8 m tall, thin little pubic & axillary hair. Both testes are approximately 5 mls in volume (Normal 15mls). No other abnormalities are encountered. Investigations reveal: LH 3.3 mu/l (3-10) FSH 5.5 mu/l (3-10) Testosterone 5.5 nmol/l (9-30) Which of following is the most likely diagnosis? 1 )Anorexia nervosa . 2 )Craniopharyngioma . 3 )Kallmann syndrome . 4 )Klinefelter’s syndrome . 5 )Primary testicular failure.

A 74-year-old man has had increasingly severe, throbbing headaches for several months, centered on the right. There is a palpable tender cord-like area over his right temple. His heart rate is regular with no murmurs, gallops, or rubs. Pulses are equal and full in all extremities, BP is 110/85 mmHg. A biopsy of this lesion is obtained, and histologic examination reveals a muscular artery with lumenal narrowing and medial inflammation with lymphocytes, macrophages, and occasional giant cells. He improves with a course of high-dose corticosteroid therapy. Which of the following laboratory test findings is most likely to be present with this disease? 1) Anti-double stranded DNA titer of 1:1024 2) Erythrocyte sedimentation rate of 110 mm/hr 3) HDL cholesterol of 0.6 mmol/L 4) pANCA titer of 1:160 5) Rheumatoid factor titer of 80 IU/mL

A 21-year-old man has recently returned from a holiday in the Far East. He gives a history of symmetrical joint pain in his knees and ankles and feet and also complains of sore eyes. His ESR is raised. A synovial fluid aspirate is sterile but with a high neutrophil count.What is the most likely diagnosis? 1. Ankylosing spondylitis 2. Septic arthritis 3. Reactive arthropathy 4. Rheumatoid arthritis 5. Still’s disease

True 3. The history of recent travel to the Far East raises the possibility of venereal disease. The lower limb symmetrical arthropathy is characteristic of reactive arthropathy. A history should be taken of urethritis/dysuria and conjunctivitis to complete the Reiter’s syndrome triad.

• A 32-year-old woman presents a four month history of amenorrhoea. She takes no specific therapy. She has two children her husband has a vasectomy. Examination reveals an obese individual but no other abnormality. • Investigations reveal:Serum oestradiol 100 pmol/L(NR 130 - 500) S. LH 2.1 mU/L(NR 3.0 - 6.6) S. FSH 2.2 mU/L(NR 3.3 – 10) S. prolactin 800 mU/L(NR 50 - 300)Serum testosterone2.1 pmol/L(NR < 3.0) Which investigation 1 )Insulin tolerance test 2 )Pregnancy test 3 )17 hydroxy-progesterone 4 )Urine free cortisol concentration 5 )Magnetic resonance imaging (MRI) of pituitary .

A 75-year-old man presents with 12 months history of cognitive impairment, parkinsonism, intermittent confusion and generalised myoclonus. He was started on 62.5 tds of sinemet. In the following 2 months he was started experiencing visual hallucinations. The most likely diagnosis is: 1) Idiopathic Parkinson's disease 2) Alzheimer's disease 3) Diffuse Lewy body disease 4) Multiple system atrophy 5) Progressive supranuclear palsy

A 70-year-old man from Lancashire has noted increasing back & leg pain over several years. X-rays reveal bony sclerosis of the sacroiliac, lower vertebral, & upper tibial regions with cortical thickening, but without mass effect or significant bony destruction. He also says his hat does not fit him anymore. He has greater difficulty hearing on the left. He has orthopnea & pedal edema. Blood tests reveal an elevated serum alkaline phosphatase. The most likely pathologic process that explains these findings is? 1 )Decreased bone mass 2 )Metastatic adenocarcinoma 3 )Paget's disease of bone 4 )Renal failure & renal osteodystrophy 5 )Vitamin D deficiency

Comments: true 3. This man has Paget's disease with high output cardiac failure & sensorineural deafness. Renal osteodystrophy leads to lesions of osteitis fibrosa cystica admixed with osteomalacia, which are focal in nature. Metastatic disease in bone produces focal lesions.

• A 17 year presents tingling & muscle cramps. There is no other past history of note. Investigations reveal Creatinine68 micromol/L (50-100)calcium1.76 (2.22.6)albumin38 g/L (37-49) • Which one of following investigations is likely to confirm diagnosis? 1 )Alkaline phosphatase concentration 2 )CT brain scanning 3 )PTH concentration 4 )Urine calcium concentration 5 )Vitamin D concentration

An otherwise healthy middle-aged man without prior medical history has had increasing back pain & right hip pain over the past 10 years. The pain is worse at the end of the day. He has bony enlargement of the distal interphalangeal joints. A radiograph of the spine reveals the presence of prominent osteophytes involving vertebral bodies. There is sclerosis & narrowing of the joint space at the right acetabulum seen on a radiograph of the pelvis. Which of the following pathologic processes is likely to be taking place in this patient? 1 )Gout 2 )Lyme disease 3 )Osteoarthritis 4 )Osteomyelitis 5 )Rheumatoid arthritis

Comments: true 3. Degenerative osteoarthritis is a common & progressive condition that becomes more frequent symptomatic with aging. There is erosion & loss of articular cartilage. Rheumatoid arthritis typically involves small joints of the hands & feet, there is a destructive pannus that leads to marked joint deformity. A gouty arthritis is more likely to be accompanied by swelling, deformity & joint destruction. The pain is related to usage. Osteomyelitis represents an ongoing infection that produces marked bone deformity, not just joint narrowing. Lyme disease produces a chronic arthritis, but it is typically preceded by a deer tick bite & a skin lesion. It is much less common than osteoarthritis.

A 62-year-old man attends for review. He has evidence of arthritis affecting the shoulder, elbow, radiocarpal, and knee joints bilaterally, with pain also in the left first metatarso-phalangeal joint. Xray of the left knee reveals calcification within the hyaline cartilage. Aspiration of the left knee reveals calcium pyrophosphate crystals. Serum uric acid is slightly above the upper limit of normal. Other medical history of note is ulcerative colitis. What is the most likely diagnosis in this case? 1. Gout 2. Pseudogout 3. Primary osteoarthritis 4. Rheumatoid arthritis 5. Sero-negative arthritis

True 2. The clinical picture of joint involvement, coupled with evidence of chondrocalcinosis and pyrophosphate crystals is strongly suggestive of a diagnosis of pseudogout. The slightly elevated uric acid and history of ulcerative colitis are ‘redherrings’ in this case. Management involves use of simple painkillers and non-steroidal anti-inflammatory agents coupled with physiotherapy where appropriate. Associated conditions include haemochromatosis and Wilson’s disease, where there are other symptoms and signs it may be worth screening for these concomitant illnesses. Pseudogout has an equal male:female ratio, with frequency increasing with increasing age; it is said to affect around 5% of subjects above the age of 30 years.

35- A 35-year-old man returned from a two-week holiday complaining of pain in the loins and painful swollen knees. On examination he was afebrile and had significant bilateral knee effusions. Mild penile erythema was also noted. Laboratory investigations showed. • Hb 15.6 g/dL • WBC 16.2 x 109/l • Neutrophils 14.1 x 109/l • ESR 65 mm/h • Rheumatoid factor 10 IU/L • Urinalysis No cells, casts or bacteria seen

• What is the most likely diagnosis? 1) Arthritis due to Neisseria gonorrhoeae infection. 2) Lymphogranuloma venereum. 3) Reactive arthritis. 4) Reitter's syndrome. 5) Rheumatoid arthritis.

A 70-year-old man presents with weight loss, lower limb weakness and dry mouth. He has been a heavy smoker. On examination, he looks cachectic; he has proximal lower limb weakness, areflexia (reflexes normalise with repetitive muscle contraction). There is no wasting or fasciculations. Sensory examination is normal. Which of the following blood test is the most likely to confirm the diagnosis? 1) Acetylcholine receptors 2) Voltage gated calcium channels antibodies 3) Anti GM1 antibody 4) Antinuclear antibody 5) Anti Ro/La antibodies

The answer is 2 The most likely diagnosis is Lambert-Eaton syndrome. It results when IgG autoantibodies blockade the voltagegated calcium channels of peripheral cholinergic nerve territory. 50% of the cases are associated with small cell lung carcinoma. Proximal lower limb weakness is the most consistent neurological feature. Ptosis and ophthalmoplegia are rare. Autonomic dysfunction is common (e.g. dry mouth). The reflexes are depressed or absent but normalise with repetitive muscle contraction.

A 42-year-old man reviewed in outpatients has a 6month history of increasing shortness of breath on exertion and feelings of lightheadedness when digging in his garden. His general practitioner organised an open access echocardiogram which showed a septal thickness of 26mm and a left ventricular outflow gradient of 85mmHg. Which of the following is NOT a risk factor for sudden death in patients with hypertrophic cardiomyopathy? • A : Unexplained syncope • B : Sudden death from HOCM in 2 or more first degree relatives <40years of age • C : Family history of sudden death • D : left ventricular wall thickness of >30mm • E : Hypertension.

• Major risk factors for hypertrophic cardiomyopathy are: • · Cardiac arrest (ventricular fibrillation) • · Spontaneous sustained ventricular tachycardia • · Family history of sudden death. • · Unexplained syncope • · Left ventricualr wall thickness>30mm • · Abnormal blood pressure on exercise(failure to rise from baseline by 25mmHg) • · Non sustained Ventricular tachycardia

61- 54 year old female is admitted with progressive weakness following a trivial flulike illness. Which of the following would exclude Guillain-Barre Syndrome as the diagnosis? 1) Autonomic dysfunction. 2) Elevated protein on CSF examination. 3) Areflexia. 4) Ophthalmoplegia. 5) Sensory level below D1.

The answer is 5 GBS is a post-infectious acute polyneuritis typified by elevated CSF protein with few cells and often normal glucose. There is a profound weakness associated with areflexia and peripheral sensory neuropathy. Ophthalmoplegia is associated in particular with the Miller-Fisher variant. However, a sensory level is NOT a feature and would suggest cervical myelopathy. Muscle wasting is typical with prolonged illness. Autonomic disease may also feature.

• A 68 year-old presents with a 4 month history of weight loss, headaches & had recently developed double vision. 6 years previously she underwent a right mastectomy for breast carcinoma & remains on treatment with Tamoxifen. • Examination shows tenderness over the temporal region & a left sixth nerve palsy. • Her chest X-ray was reported as normal, but she had an ESR of 100 mm/hr , her Hb was 10.8 g/dl. Which of following statements correct? 1 )An isotope bone scan should be performed 2 )An urgent CT brain scan required 3 )She should be treated prednisolone immediately 4 )She should have a lumbar puncture 5 )She should be given Diamorphine

An 18 year old man presented with a history of a sudden onset of a frontal headache and photophobia. He had neck stiffness and a temperature of 38°C. Which one of the following findings would suggest a diagnosis of subarachnoid haemorrhage rather than bacterial meningitis? 1) a blood neutrophil leucocytosis 2) a family history of polycystic renal disease 3) a fluctuating conscious level 4) a history of diabetes mellitus 5) a history of opiate abuse

The answer is 2 Fluctuating level of consiousness can occur in both meningitis and subarachnoid haemorrhage (SAH). Hypertension is a risk factor for SAH, but not diabetes. Opiate abuse does not increase the risk for SAH. Cerebral aneurysm are associated with polystic kidney disease.

An 80-year-old woman has a three month history of progressive numbness and unsteadiness of her gait. On examination, there is a mild spastic paraparesis, with brisk knee reflexes, ankle reflexes are present with reinforcement, extensor plantars, sensory loss in the legs with a sensory level at T10, impaired joint position sense in the toes, and loss of vibration sense below the iliac crests. Investigations were as follows:haemoglobin 12.0 g/dl MCV 99 fl What is the most likely diagnosis? 1) anterior spinal artery occlusion 2) dorsal meningioma 3) multiple sclerosis 4) subacute combined degeneration of the cord 5) tabes dorsalis

• A 46-year-old male presents passing 4-5 litres of urine per day, after commencing a new drug. S.sodium 142 mmol/l, Plasma osmolality 295 mosmol/l (275-290), Urine osmolality 280 mosmol/l (350-1000).What drug was prescribed? 1 )Carbamazepine 2 )Chlorpropamide. 3 )Fluoxetine . 4 )Furosemide . 5 )Lithium.

• A 50-year-old man presented with a six-week history of general malaise and a 2 day history of a right foot drop, a left ulnar nerve palsy and a widespread purpuric rash. He complained of arthralgia but had no clinical evidence of inflammatory joint disease. Investigations revealed: ESR100 mm/hr, ANCA negative, ANA negative, Rheumatoid factor strongly positive, C3 0.8 g/L (NR 0.75 - 1.6), C4 0.02 g/L (NR 0.14 - 0.5), Urine dipstick Blood ++, no protein. An echocardiogram was normal and two sets of blood cultures were negative.What is the most likely diagnosis? 1 )ANA negative SLE 2 )Cryoglobulinaemia 3 )Infective endocarditis 4 )Polyarteritis nodosa 5 )Rheumatoid arthritis

The answer is 2 The presence of a sensory loss at T10 indicates a thoracic mylopathy. Subacute combined degeneration of the cord is unlikely as Hb and MCV are normal. Anterior spinal artery occlusion is unlikely as the history is progessive.

63- A 45-year-old man has a history of progressive weakness for 5 weeks. He had particular difficulty getting out of the bath. On examination there was severe truncal and proximal limb weakness, without wasting or fasciculation. Tendon reflexes, plantar and sensation were all normal. The vital capacity was 1.8L. What is the most likely diagnosis? 1) cervical myelitis 2) Guillain-Barre syndrome 3) polio 4) polymyositis 5) syringiobulbia

The answer is 4 The presentation of myopathy is characterised by priximal weakness with normal reflexes and sensation and the absence of fasciculations. Polymyositis is the commonest cause of inflammatory muscle disease in < 50 years old (inclusion body myositis is the commonest in >50 years old).

A 17-year-old male is investigated for short stature. He has a previous diagnosis of slipped femoral epiphysis diagnosed at the age of 11. He presented with this disorder at this age with pain in the hip and limp. This was treated by the orthopaedic surgeons with nonsurgical containment of the femoral head in the acetabulum using casts. On examination he is on the 12th centile for height, a BMI of 30 and has normal pubertal development. His blood pressure is 108/70 mmHg and he has a pulse of 90 beats per minute. No abnormalities are noted on examination of the chest, heart and abdomen. • Investigations reveal: • Haemoglobin 12.8 g/dL (13.0-18.0) White cell count 5.4 x109/L (4-11 x109) Platelets 143 x109/L (150-400 x109) Serum Na 133 mmol/L (137144)Serum K 4.2 mmol/L (3.5-4.9) Serum Creatinine 96 µmol/L (60-110) Serum Calcium 2.02 mmol/L (2.2-2.6) Serum Phosphate 1.8 mmol/L (0.81.4) PTH 15.8 pmol/L (0.9-5.4). Which of the following is the most likely explanation of this boy's presentation? • Coeliac disease. • Primary hypoadrenalism . • Pseudohypoparathyroidism. • Renal osteodystrophy. • Vitamin D resistant osteomalacia.

• This young boy has short stature and previous history of slipped femoral epiphysis. • The investigations reveal a hypocalcaemia and a hyperphosphataemia suggesting a hypoparathyroidism (both calcium and phosphate would be expected to be low in vitamin D deficiency and hypophosphataemia in vitamin D resistant rickets) yet the raised parathyroid hormone (PTH) concentration is elevated indicating pseudohypoparathyroidism.

A 55-year-old man who had received haemodialysis for many years presents with deteriorating discomfort in both shoulders. Past medical history included bilateral carpal tunnel decompression. His Investigations reveal: haemoglobin10 g/dl, ESR 30 mm/1st hr (1-10), C-reactive protein 12mg/L (1-10), Urate 0.58 (less than 0.45)What is the most likely diagnosis? 1 )B2 microglobulin amyloidosis 2 )Gout 3 )Pseudogout 4 )Polymyalgia rheumatica 5 )Osteoarthritis

Comments: true 1. The features of shoulder pain associated with a past history of carpal tunnel syndrome in a patient receiving haemodialysis suggests a diagnosis of b2 microglobulin amyloidosis. Amyloid deposits composed of b2-microglobulin as a major constituent protein are mainly localized in joints with periarticular bone that lead to destructive arthropathy which tends to develop 5- 10 years after the initiation of dialysis. Death from amyloidosis of gut & heart may occur after 20 years of dialysis.

The dual X-ray bone absorptiometry (DXA) scan results of a 60-year-old man with RA being treated with prednisolone 7.5 mg per day and methotrexate 10 mg per week show T scores of -1.6 at spine and - 1.8 at hips. Which of the following would you add? 1.Calcium and vitamin D 2.Parathyroid hormone 3.Alendronate 4.Strontium 5.No change in therapy

True 3. A T score of less than -2.5 at hip or spine is indicative of osteoporosis. However, in patients on steroid therapy, a score of -1.5 is taken as a cut-off value to start osteoporosis therapy. Use of bisphosphonates (alendronate and risedronate) has been shown to be associated with a reduced risk of fractures. Bisphosphonates are most commonly used first-line agents for the treatment of osteoporosis. Calcium and vitamin D alone are not sufficient in reducing the risk of fractures, although they do offer some benefit. They may be given concomitantly with bisphosphonates. Strontium and parathyroid hormone are used in case of intolerance or lack of response to bisphosphonates.

A 16 year old girl presented with a three week history of headache and horizontal diplopia on far right lateral gaze. On two separate occasions she noted dimmed vision whilst bending forwards. Over the last year she had gained 12 kilograms in weight. On examination, her weight was 95 kg, and height 162cms. Neurological examination revealed bilateral papilloedema and a partial right sixth cranial nerve palsy. What is the most likely diagnosis? 1) Benign intracranial hypertension. 2) Multiple sclerosis. 3) Pituitary tumour 4) Superior sagittal vein thrombosis. 5) Thyroid eye disease.

The answer is 1 This patient is markedly obese with a BMI of 36 and the history suggestive of BIH. Vision may be affected with enlargement of the blind spot and the visual obscuration with movements that provoke a rise in ICP (eg bending) is typical of BIH. Dysthyroid eye disease would not present like this and is more commonly associated with Hyperthyroidism. The papilloedema would argue against MS. A bitemporal hemianopia or a visual field defect would be expected with a pituitary tumour. Venous sinus thrombosis is a possibility but would be expected to produce deteriorating symptoms.

5.A 30-year-old lady with a history of intravenous drug use is admitted feeling generally unwell. She has a fever and is complaining of arthralgia and a photosensitive rash. On examination she has a soft systolic murmur at the lower left sternal edge. Investigations reveal: Electrocardiogram Sinus tachycardia, Haemoglobin10.2 g/dl,White cell count 12.2 × 109/l, Platelets,474 × 109/ l , Sodium 132 mmol/l, Potassium 4.6 mmol/l , Urea15.2 mmol/l,Creatinine 145 µmol/l,Urine microscopy=Red cell casts,Erythrocyte sedimentation rate 32 mm/h (0–20),C-reactive protein 64 mg/l (<10), Complement C3--- 20 mg/dl (65–190), Complement C4 --- 3 mg/dl (15–50), Renal biopsy=Focal segmental proliferative glomerulonephritis What are the next appropriate investigations? 1. Antinuclear antibodies. 2. Rheumatoid factor. 3. Echocardiography. 4. Anticardiolipin antibodies. 5. Chest x-ray.

6. One of the following features is consistent with a diagnosis of polymyalgia rheumatica: A B C D E

proximal muscle pain & stiffness. an increased creatine kinase activity . proximal muscle weakness. an abnormal EMG. a macrocytic anaemia .

Which is true of herpes simplex encephalitis? 1) brain MRI is characteristically normal 2) fits are uncommon 3) genital herpes is usually present 4) temporal lobe involvement is common 5) viral identification using polymerase chain reaction on CSF is non-specific

The answer is 4 Herpes simplex encephalitis (HSE) is associated with high signal in one or both temporal lobes (limbic encephalitis). Seizures are commonly present in HSE. Herpes Simplex Virus type 1 is the causative virus (Not type 2 which is associated with genital herpes). PCR for herpes simplex virus on CSF is highly specific test.

• A patient who has rheumatic mitral stenosis is considered for percutaneous mitral valvuloplasty. Which of the following would contraindicate this procedure? • A. Dilated left atrium • B. Atrial fibrillation • C. Aortic regurgitation • D. Heavy calcification of the mitral valve • E. Long history of mitral stenosis

• Answer: d) heavy calcification of the mitral valve. The contraindications towards valvuloplasty are heavy MV calcification, thrombus in the left atrial appendage on transoesophageal echocardiography and severe mitral regurgitation. These patients are indicated for mitral valve surgery instead.

• A 35 year old woman is admitted with a blood pressure of 230/120. She has a sinus tachycardia of HR 160 with intermittent runs of non sustained ventricular tachycardia. 24 hour urine shows increased Adrenaline of 720 (<80 nmol/24 hours) and Noradrenaline 2300 (<780 nmol/24 hours). • Which one of the following medications would be most useful? • A. Intravenous labetalol. • B. Intravenous amiodarone. • C. Intravenous phentolamine. • D. Intravenous diltiazem . • E. Oral flecainide.

• Answer: c) intravenous phentolamine. In the management of acute hypertensive crisis of phaeochromocytoma as in this case, IV administration of sodium nitroprusside, nitroglycerine, or phentolamine can be used. Preoperatively, phenoxybenzamine preoperative adrenergic-blockade of a1 and a2 receptors with phenoxybenzamine (10-30 mg twice daily), or a1 receptors with prazosin (starting with 1 to 2 mg three times daily. Beta blockers can be useful for arrhythmias, but should not be commenced before alpha blockers because b-blockade alone can cause marked hypertension.

• A 50 year old man presents with breathlessness. His chest XR shows cardiomegaly. Which of the following in the history might elucidate a cause of cardiomyopathy? • A. Inferior T wave inversion • B. Systolic murmur in the mitral area • C. History of diabetes and a tanned complexion • D. Family history of hyperlipidaemia • E. Family history of myocardial infarction

• Answer: c) history of diabetes and a tanned complexion. A history of diabetes and bronze / tanned pigmentation suggest haemochromatosis. Liver function tests and iron studies would help to confirm the diagnosis.

• A 68 year old man with bone pain has the following blood results: • calcium 2.27 (2.25-2.7) mmol/l phosphate 1.3 (0.8-1.45) mmol/L ALP 335 (20-120) U/l • What is the likely diagnosis? A. Multiple myeloma B. Paget’s disease C. Osteoporosis D. Osteomalacia E. Primary hyperparathyroidism

• Answer: B) Paget’s disease In paget’s disease, increased plasma alkaline phosphatase reflects osteoblastic activity. . Parathyroid hormone secretion usually maintains a normal level of calcium ions in the serum. Concentration of phosphate in the serum may be normal or slightly elevated.

A 21 year old female with epilepsy is well controlled on sodium valproate 600mg bd and had been taking oral contraceptives for three years. She presented to her general practitioner 12 weeks pregnant. Which of the following is correct? 1) An alternative anticonvulsant should be used in place of sodium valproate 2) Interaction of sodium valproate with the oral contraceptive increased the risk of pregnancy 3) The dose of sodium valproate should be increased 4) There is an increased risk of a neural tube defect in her fetus 5) She is at increased risk of anaemia in pregnancy

The answer is 4 There is an increased risk of neural tube defects associated with anti-convulsants during pregnancy. However, the risks associated with treatment are outweighed by the benefits in preventing seizures, so the drug should be continued. The risks may be minimised through use of folate supplements. Sodium valproate is not an enzyme inducer and would not speed up metabolism of the pill.

• A 35 year old woman is suspected of having systemic sclerosis following presentation with Raynaud's phenomenon. Which one of the following is an associated feature? • A. Lax skin on the hands. • B. Non blanching purpura . • C. Perioral puckering. • D. Liver nodules. • E. Mesothelioma .

• Answer: c) perioral tethering. Systemic sclerosis is usually associated with dry mouth and dry eyes, raynaud's phenomenon, telangiectasia and perioral tethering. • • Perioral tethering in systemic sclerosis

• A 60 year old woman has had difficulty walking due to unsteadiness. She has lost 5 kg in weight over the past 6 months. On examination, she has horizontal nystagmus. Her speech is slurred. There is incoordination of the upper limbs evident on past pointing. Her gait is ataxic. General examination reveals a palpable breast lump. Which of the following is most likely to yield the diagnosis? • A. Anti Yo antibodies • B. Anti Hu antibodies • C. Anti GAD antibodies • D. MRI of the brain • E. CT of the head

• Answer: a) Anti Yo antibodies. This lady has a cerebellar syndrome which may be related to a breast malignancy. Anti Yo antibodies are associated with a cerebellar syndrome due to either lung, breast or ovarian carcinoma.

Regarding pseudotumours cerebri (benign hypercranial hypertension) which is true? 1) A mildly increased CSF cell count is typical. 2) May be caused by prolonged steriod therapy. 3) Is occasionally associated with focal neurological signs. 4) Frequently presents with ataxia. 5) Is distinguished from hydrocephalus by the absence of suture separation.

The answer is 2 Pseudotumour cerebri is a clinical syndrome that mimics brain tumours, and is characterised by raised intracranial pressure with normal CSF cell count and protein content, normal ventricular size, anatomy and position. Causes: Metabolic disorders: galactosaemia, hypoparathyroidism, pseudohyperparathyroidism, hypophosphatasia, steroid therapy, hypervitaminosis A, vitamin A deficiency, Addison's Disease, obesity, menarche, oral contraceptives, pregnancy. Infections: Roseola infantum, chronic otitis media, mastoiditis, Guillain Barré Syndrome. · Drugs: Nalidixic acid, tetracycline. Haematological disorders: Polycythemia, haemolytic and iron deficiency anaemia, Wiskott Aldrich Syndrome. Destruction of intracranial drainage by venous thrombosis: Lateral sinus or posterior saggital sinus thrombosis, head injury, obstruction of the superior vena cava. It usually presents with headache and vomiting, though this is rarely as bad as that associated with posterior fossa tumour. Diplopia is common due to 6th nerve palsy. Children are alert with no systemic upset. A bulging fontanelle, cracked pot sounds, or separation of the cranial sutures may be present. Papilloedema with an enlarged blind spot is the most consistent sign beyond infancy. Focal and neurological signs indicate a process other than pseudotumour cerebri. It may be complicated by optic atrophy and blindness. Most can be treated conservatively with monitoring of visual acuity. For others, multiple lumbar punctures may be necessary to reduce intracranial pressure. Very rarely are shunts required.

Which of the following features is characteristic of myasthenia gravis? 1) Diplopia 2) Equal sex incidence 3) Fasciculation 4) Lid lag 5) Loss of pupillary reflexes

The answer is 1 Myasthenia gravis is commoner in females (it is an autoimmune disease). The commonest features include ptosis, diplopia and ophthalmoplegia. It is a neuromuscular disorder and therefore does not cause any lower motor neuron signs such as fasciculations, wasting, and loss of reflexes. Pupils are always normal. Lid lag is a feature of thyroid eye disease.

A 68-year-old man presents with progressive visual impairment. On examination there is an incongruous homonymous hemianopia. The most likely anatomical site of the neurological lesion is at: 1) optic nerve 2) optic tract 3) chiasma 4) optic radiation 5) occipital lobe

The answer is 2 Optic neuropathy causes a central scotoma, an optic tract lesion an incongruous homonymous hemianopia, a chiasmal lesion a bitemporal hemianopia, an optic radiation and occipital lobe lesion a congruous homonymous hemianopia.

A 25-year-old female presents with 2 days history of diplopia and unsteadiness. 2 weeks ago she suffered an upper respiratory tract infection. On examination there is complete opthalmoplegia, areflexia and gait ataxia. Which of the following blood tests is the most likely to confirm the underlying diagnosis? 1) Acetylcholine receptors antibodies 2) Anti GM1 antibodies 3) Anti GQib antibodies 4) Anti Hu antibodies 5) Anti purkinje cell antibodies

The answer is 3 The most likely diagnosis is Miller Fisher syndrome (variant of Guillain Barre syndrome). It consists of complete or partial ophthalmoplegia, areflexia and ataxia. It usually follows antecedent infections. Serum IgG antibody to the ganglioside GQib is present in more than 95% of patients. It is highly specific for the syndrome. Elevated levels of antibodies to the glycolipid ganglioside-monosialic acid (GM1 antibodies) have been shown, in some instances, to be associated with certain neurological disorders: lower motor neuron syndromes, amyotrophic lateral sclerosis, multiple sclerosis, other multifocal neuropathies, and systemic lupus erythematosus (SLE) with central nervous system involvement. Neuronal Nuclear (Hu) Antibodies (NNA) are found in a number of paraneoplastic syndromes, including subacute sensory neuronopathy, paraneoplastic encephalomyelitis and paraneoplastic cerebellar degeneration and are associated with small cell lung carcinoma. Purkinje cell cytoplasmic antibodies are useful for identifying individuals with subacute cerebellar degeneration or peripheral neuropathy due to a remote (autoimmune) effect of gynecologic or breast carcinoma.

A 17-year-old man has been diagnosed with schizophrenia 4 weeks ago. He was started on haloperidol. Two weeks later he was found confused and drowsy. On examination he was pyrexial (40.7 C), rigid with blood pressure of 200/100. Which of the following treatment will you initiate? 1) phenytoin 2) diazepam 3) cefuroxime 4) acyclovir 5) dantrolene

The answer is 5 Neuroleptic malignant syndrome is the most likely diagnosis. Its major features are: rigidity, altered mental state, autonomic dysfunction, fever, and high creatinine kinase. It is usually caused by potent neuroleptics. The treatment of choice is dantrolene and bromocriptine. Withdrawal of neuroleptic treatment is mandatory. Rhabdomyolysis and acute renal failure are potential complications.

A 60-year-old woman presents with a short history of sinus congestion, epistaxis and joint pains in her hands. She becomes increasingly short of breath and develops haemoptysis precipitating admission to hospital. On direct questioning she admits to passing less urine in the preceding few days. On examination, Heart sounds are normal with no murmurs. She has bibasilar fine crackles on auscultation of the lungs but her JVP is not elevated and she has no pedal oedema. A chest X-ray (CXR) shows bilateral air space shadowing throughout both lung fields. Urinalysis demonstrates red blood cells and red blood cell casts. Her haemoglobin (Hb) is 6 g/dl and her urea is 45 mmol/l, with a creatinine of 800 μmol/. What is the most likely diagnosis? 1. IgA nephropathy 2. Goodpasture's syndrome 3. Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis 4. Cryoglobulinemia 5. Uric acid nephropathy

True 3. This is a classic history for Wegener's granulomatosis. She would need treatment with dialysis; immunosuppression and most centres would advocate plasma exchange with a creatinine above 400 μmol/l. None of the other diagnoses would classically cause sinus or joint involvement, and pulmonary haemorrhage is typically seen only in Goodpasture's syndrome and ANCA-positive vasculitis. Note (LVF) can lead to pink sputum and may be confused for pulmonary haemorrhage. To confirm the diagnosis of pulmonary haemorrhage, a raised potassium channel opening (K+-CO) would be seen on lung function tests. The low haemoglobin (Hb) in the setting of acute renal failure and the disproportionate degree of abnormality seen on chest X-ray (CXR) compared to clinical findings suggest pulmonary haemorrhage rather than infection or fluid to explain the CXR findings.

26-A 25-year-old man presents with right-sided facial weakness and swelling. There is a right LMN facial nerve palsy but no other abnormalities on examination. Lumbar puncture findings are: Opening pressure18 cm, CSF Protein 0.9 g/l Glucose3.5 mmol/l, Microscopy 85 lymphocytes. What is the most likely diagnosis? A. Lyme disease B. Multiple sclerosis (MS) C. Guillain Barre syndrome (GBS) D. Neurosarcoidosis E. Ramsey Hunt syndrome

An 81-year-old female presents with bilaterally painful knees. There was no history of gastrointestinal diseases. On examination she had crepitus but had a full range of movement of both knees. Which one of the following is an appropriate initial treatment for her painful knees? 1 )Dihydrocodeine 2 )Naproxen 3 )Paracetamol 4 )Celecoxib 5 )Topical Diclofenac

Comments: true 3. This woman has osteoarthritis (OA) of both knees. The principle goal of systemic therapy is to provide an effective pain relief with the least associated toxicity. Paracetamol is the initial therapy recommended for the treatment of OA of the hip & knee. Studies have shown that short-term & long-term efficacy of paracetamol is comparable to that of ibuprofen & naproxen in people with knee osteoarthritis. Specific COX-2 inhibitors such as celecoxib have clinical benefit similar to that of traditional NSAIDS, but less GI toxicity although issues remain regarding their cardiovascualr risk. They may be used in patients with GI intolerance of traditional NSAIDs.

A 50 year-old male epileptic presents with paraesthesia of hands and feet. He also has unsteadiness when walking. On examination he has a peripheral sensory neuropathy and palpable lymph nodes in his neck and axillae. Which of the following drugs is the most likely cause of these features? 1) Carbamazepine. 2) Clonazepam 3) Lamotrigine. 4) Phenytoin. 5) Sodium valproate.

The answer is 4 Phenytoin is well known to cause neurological side effects such as peripheral sensory neuropathy and cerebellar ataxia. Other side effects include gingival hypertrophy, lymphadenopathy hypocalcaemia, hirsutism.

18. A 45-year-old male attends for an insurance & is in good health. Examination was normal but investigations reveal that he has a serum urate concentration of 0.55 mmol/l (NR 0.25-0.45). Which of the following is the most appropriate management of this patient? 1 )Lifestyle advice. 2 )Start Allopurinol . 3 )Start Colchicine. 4 )Start Diclofenac. 5 )Start Prednisolone.

.

A 30-year-old woman presented with a deep vein thrombosis. Her previous history included investigation for infertility. Investigations revealed: Haemoglobin 12.8 g/dl (12.5-16.5), White cell count 3.6 x 109/L (4-11), Platelet count 35 x 109/L (150-400). Select one of following investigations which are most likely to be abnormal? 1 )Antiphospholipid antibodies. 2 )Homocystine concentration 3 )Platelet function test 4 )Protein C concentration. 5 )Indium-labelled white cell scan.

• A 30 year old of average height and weight presents with polyuria and thirst. He has a blood glucose of 15 mmol/l. There is no ketonuria and his older sister is diabetic How should he be treated? • A. Start metformin • B. A fasting blood glucose should be sent before treatment • C. Subcutaneous insulin should be started • D. Commence on gliclazide and reassessment with BM monitoring at home • E. Dietary advice, review in a month with repeat glucose without any treatment

• Answer: d) commence on gliclazide and reassessment with BM monitoring at home. He is a type 1 diabetic but there are no features of ketonuria or acidosis. He may have some residual β islet cell function and hence sulphonylureas may help to stimulate insulin production.

A 62-year-old man presented with difficult walking. He had a past history of diabetes mellitus and cervical spondylosis, which had required surgical decompression eight years previously. He drank 40 units of alcohol weekly. On examination there was fasciculation, wasting and weakness in the left deltoid and biceps, with weakness in the shoulder girdle muscles bilaterally. There was fasciculation in the glutei and quadriceps bilaterally, weakness of hip flexion and foot dorsiflexion, brisk reflexes in upper and lower limbs, and extensor plantar responses. There was no sensory impairment. What is the diagnosis? 1) alcoholic myopathy 2) diabetic amyotrophy 3) motor neurone disease 4) recurrent cervical cord compression 5) syringomyelia

The answer is 3 There are signs of lower (wasting, fasciculations) and upper (brisk reflexes, extensor plantar response) motor neuron involvement in the presence of normal sensation. Motor neuron disease is the commonest cause of such presentation. Alcoholic myopathy and diabetic amyotrophy do not share upper motor neuron signs. Syringomyelia presents with sensory symptoms and signs (spinothalamic). You expect sensory involvement with cervical cord compression.

• 78 years old man presents with an acute onset of severe pain & swelling of the left wrist which had developed since she had a chest infection two weeks previously. On examination, he had a temperature of 38 °C,left wrist was red, swollen & painful. • What is the appropriate investigation for this pt? • 1)Erythrocyte sedimentation rate. • 2 )Full bl. count . • 3 )Joint aspiration. • 4 )Serum urate concentration. • 5 )X ray of joint.

• A 30-year-old woman is evaluated in the endocrinology clinic for increased urine output. She weighs 60 kg and has a 24-hour urine output of 3500 ml. Her basal urine osmolality is 210 mOsm/kg. She undergoes a fluid deprivation test and her urine osmolality after fluid deprivation (loss of weight 3 kg) is 350 mOsm/kg. A subsequent injection of subcutaneous DDAVP (desmopressin acetate) did not result in a further significant rise of urine osmolality after 2 hours (355 mOsm/kg). Which of the following is the likely diagnosis? A. Normal B. Primary polydipsia C. Osmotic diuresis D. Pituitary diabetes insipidus E. Nephrogenic diabetes insipidus

• A 60 years old woman diagnosed with giant cell arteritis was commenced on high dose prednisolone therapy. What is the best appropriate treatment for prevention of steroid- induced osteoporosis? 1 )Bisphosphonate therapy 2 )Calcium vitamin D 3 )Hormone replacement therapy 4 )Raloxifene. 5 )Salmon Calcitonin.

A 19 year old girl presents at the antenatal clinic. She is approximately six weeks pregnant and the pregnancy was unplanned. She has a two year history of grand mal epilepsy for which she takes carbamazepine. She has had no fits for approximately six months. She wants to continue with her pregnancy if it is safe to do so. She is worried about her anticonvulsant therapy and the effects on the baby and enquires how she should be managed? 1) Advise termination due to drug teratogenicity 2) Continue with carbamazepine 3) Stop carbamazepine until the second trimester 4) Switch therapy to phenytoin 5) Switch therapy to sodium valproate

The answer is 2 The patient and fetus are at far more risk from uncontrolled seizures than from any potential teratogenic effect of the therapy. In pregnancy total plasma concentrations of anticonvulsants fall and so the dose may need to be increased. The potential teratogenic effects (particularly neural tube defects) of carbamazepine do need to be explained and in an effort to reduce this risk she should receive folate supplements. Screening with AFP and second trimester ultrasound are required. Vitamin K should be given to the mother prior to delivery. There is no point in switching therapies as this could precipitate seizures in an otherwise stable patient. Similarly, both phenytoin and valproate are again associated with teratogenic effects.

Which of the following investigations best supports a diagnosis of new variant CJD: 1) CSF analysis 2) CT brain 3) EEG 4) EMG 5) MRI brain

The answer is 5 MRI brain typically shows bilateral posterior thalamic high signal abnormalities in patient with new variant CJD. EEG , CSF analysis only shows non-specific changes. EMG and CT brain are normal. Sporadic CJD (and not new variant CJD) is associated with specific EEG changes.

A 65 year old lady has ischaemic cardiomyopathy and symptoms of breathlessness walking up one flight of steps. Her breath sounds are clear. Chest X ray shows cardiomegaly and clear lung fields. She is currently on frusemide 40mg bd and perindopril 4 mg at night. What medication should be added? A. Spironolactone B. Carvedilol C. Digoxin D. Amiodarone E. Diltiazem

Answer: b) carvedilol. The two best options are carvedilol and spironolactone. Both B blocker trials (CIBIS II, Merit HF, Copernicus) and spironolactone trials (RALES) have shown symptomatic improvement and decreased mortality. In this patient with little signs of fluid overload, a beta blocker can be started first, and then spironolactone added as well.

A 33 year old epileptic female presents with visual problems. Examination reveals a constriction of visual fields to confrontation. Which of the following may be responsible for her visual deterioration? 1) Vigabatrin 2) Lamotrigine 3) Gabapentin 4) Phenytoin 5) Sodium Valproate

The answer is 1 Vigabatrin is associated with constricted visual fields and when detected therapy should be stopped.

• A 45-year-old attends clinic complaining of tiredness. She is hypothyroid & takes thyroxine 150 micrograms daily. Which of following useful test assessing appropriateness of thyroid hormone replacement in primary hypothyroidism? 1)Free T3 & T4 concentrations 2 )Skin biopsy 3 )Thyroid binding globulin 4 )Total T3 T4 5 )TSH

• A 52 year old lady has palpitations. Her ECG shows a broad complex tachycardia. Which of these features suggests that the tachycardia is more likely to be of ventricular origin? • A. QRS of 150 ms • B. Left bundle branch block and left axis deviation • C. P wave for every QRS complex • D. History of atrial fibrillation • E. Heart rate of 150

• Answer: a) QRS of 150ms. Features that favour VT are : QRS of > 140ms, dissociated p waves, history of ischaemic heart disease, right bundle branch block with left axis deviation, HR >170 beats per minute.

A 59 year lady has a history of hypertension and has recently been prescribed a new antihypertensive agent. She now has fevers and joint pains in the arms, shoulders, knees and ankles. Which of the following drugs could cause this? A. Bendrofluazide B. B. deltiazem C. C. Methyldopa D. D. Amlodipine E. E. Lisinopril

Answer: c) methyldopa. The history would be consistent with drug induced SLE. In druginduced lupus erythematosus, the features of arthritis, systemic symptoms, and cardiac and pulmonary (lung) symptoms may be present. Other symptoms associated with SLE, such as lupus nephritis and neurological disease, are rare. The drugs which may cause this are procainamide, isoniazid, chlorpromazine, penicillamine, sulfasalazine, hydralazine, methyldopa, and quinidine.

• A 55 year old man has bitemporal hemianopia. He also has elevated IGF-1 levels in the serum and an enlarged pituitary seen on MRI. Which one of the following is an associated feature? • A. Hypolipidemia • B. Hypoglycaemia • C. Rheumatoid arthritis • D. Myocarditis • E. Hypertension

• Answer: e) hypertension. The diagnosis is acromegaly. Carpal tunnel syndrome, impaired glucose tolerance, carpal tunnel syndrome and high cardiac output cardiac failure are associated. • • MRI showing a pituitary tumour in acromegaly

An 18 year-old girl receives radioactive iodine as treatment of thyrotoxicosis. Which of following is likely long-term complication of this treatment? 1)hypoparathyroidism. 2 )hypothyroidism. 3 )increased risk of developing cancer. 4 )recurrent laryngeal nerve damage. 5 )osteoporosis.

• Which of following percentages accurately reflects mortality associated with modern management of diabetic ketoacidosis? • 1 )0.5% • 2 )1% • 3 )2-3% • 4 )5-6% • 5 )8-10%

A 30 year old lady has recurrent attacks of dizziness and blackouts. A 72 hour fast reveals periods where her plasma glucose is 2.5 mmol/l with elevated insulin and C peptide levels. What is the next best investigation? A. Repeat 72 hour fast B. B. Glucagon stimulation test C. C. Glucose tolerance test D. D. MRI of abdomen E. E. Insulin antibodies

• Answer: d) MRI of abdomen. The tests so far suggest an insulinoma. Localisation of the insulinoma can be done with MRI, CT, superior mesenteric angiography or pancreatic venous catheterisation. • • Insulinoma

• A 35 year old lady has a history of diarrhoea, profuse sweating and irritability. Her parents had similar symptoms and passed away in their fourties after doing radical surgery . • Which one of the following is the most likely diagnosis? • A. Phaeochromocytoma • B. Acromegaly • C. Diabetes • D. Ovarian carcinoma • E. Medullary thyroid carcinoma

• Answer: e) medullary thyroid carcinoma. Medullary thyroid carcinoma produces peptides and neurohormones which lead to symptoms of irritability, diarrhoea and sweating. It can be inherited in association with MEN type II.

A young woman has acne and is taking oral medication. She develops polyarthritis and raised liver enzyme tests. Investigations show AST 95 ALT 170 bilirubin 16 antinuclear antibodies strongly positive at 1/640, Which of the following drugs is she most likely to have been prescribed? 1) erythromycin 2) isotretinoin 3) minocycline 4) oxytetracycline 5) trimethoprim

The answer is 3 Except trimethoprim all other drugs are used in the treatment of acne. And all of these can cause hepatotoxicity. Erythromycin usually causes cholestasis. Minocycline can cause drug induced SLE.

Which of the following features is characteristic of early Alzheimer's disease? 1) ataxic gait 2) impaired short term memory 3) myoclonic jerks 4) urinary incontinence 5) visual hallucinations

The answer is 2 Alzheimer's disease is characterised early in the disease by short term memory loss. The other features listed here would suggest an alternative diagnosis such as normal pressure hydrocephalus (gait ataxia and urinary incontinence), Creutzfeld-Jacob disease (myoclonic jerks) and delirium or vascular dementia (visual hallucinations).

A 45-year-old man presents with an insidious onset of binocular horizontal diplopia and left sided facial pain. On examination ha has a left abducens nerve palsy and numbness over the maxillary division of the left trigeminal nerve. The most likely anatomical site of his neurological lesion is: 1) Cavernous sinus 2) Petrous apex 3) Superior orbital fissure 4) Cerebellopontine angle 5) Midbrain

The answer is 2 In the pre-antibiotic era an abducens nerve palsy with ipsilateral pain and numbness was due to petrous osteitis (Gradenigo syndrome) but is now more likely the result of a meningioma or nasopharyngeal carcinoma of the petrous apex. The cavernous sinus syndrome consists of variable involvement of: oculomotor, trochlear, abducens, trigeminal (ophthalmic and maxillary division) and oculo-sympathetic nerves. The superior orbital fissure syndrome is similar to the cavernous sinus syndrome except for the presence of proptosis.

2. A 75-year-old male was admitted with chest pain & dyspnoea. His pain subsides, he is generally well, although dyspnoea restricts his mobilisation. He is unable manage the stairs, but can mobilise solely around the ward. Whilst being monitored his telemetry demonstrates short runs of non sustained ventricular tacchycardia, associated lightheadedness. What is the next appropriate investigation for this patient? 1 )24hr tape 2 )Coronary angiography 3 )Echocardiography 4 )Electrophysiological studies 5 )Outpatient Cardiology referral

• Comments: 3 )Echocardiography patients with reduced LV function or asymptomatic VT may benefit from implantation of an implantable cardiac defibrillator . You need to know the patients cardiac function, so we feel that an ECHO would be the next appropriate study in this patient, followed by coronary angiography & inpatient cardiology referral.

A 55-year-old female receiving 10 mg of Methotrexate & 5mg of folate* weekly presents with a sore right finger after cutting herself in the garden. On examination, she has a swollen, erythematosus right ring finger up to the proximal interphalangeal joint & you diagnose a cellulitis. You give her a prescription of erythromycin as she is allergic to penicillins. She has being receiving the Methotrexate over just one year with no problems in all routine bl monitoring which are normal. Whilst monitoring the response of the infection to treatment, what appropriate strategy regarding her Methotrexate therapy? 1 )Continue Methotrexate unchanged & increase folate supplements to 10mg daily. 2 )Continue Methotrexate & folate unchanged. 3 )Reduce dose of Methotrexate to 5mg weekly 4 )Stop Methorexate until the infection is resolved. 5 )Stop Methotrexate only if full bl. count reveals a neutropaenia.

Comments: true 4. In the circumstances of infection, one should consider temporarily stopping methotrexate as it is an immunosuppressant. Any infection should be treated as usual to response to treatment monitored. Once the infection is successfully treated methotrexate can be reinstated. However, if the patient has recurrent serious infections while taking methotrexate, its continued long term use should be discussed with the patient's rheumatologist. *some local variations may exist regarding dose & frequency of folate therapy.

14.A 26-year-old man with a history of alcohol & drug abuse was admitted with a 14 day history of fever, cough & fatigue. He was emaciated. His temperature was 39.4°C. Cervical & axillary lymphadenopathy were present. Chest X-ray showed bilateral areas of pulmonary shadowing. Which of the following is the likely diagnosis? 1 )alcoholic cardiomyopathy 2 )pneumococcal pneumonia 3 )pneumocystis pneumonia 4 )pulmonary tuberculosis 5 )tricuspid endocarditis

A 45 year old woman with breathlessness presents for further investigation. She has a known history of rheumatoid arthritis and is on methotrexate and folate. She has a CXR and lung function tests. Which one of the following is a recognized respiratory manifestation of rheumatoid arthritis? A. Mesothelioma B. B. Asthma C. C. Bronchiolitis obliterans D. D. Pulmonary eosinophilia E. E. Pulmonary embolus

• Answer: c) bronchiolitis obliterans. In rheumatoid arthritis, exudative pleural effusions, fibrotic lung disease, Caplan’s syndrome (pneumoconiosis, pulmonary nodules), and obstructive lung disease in the form of bronchiolitis obliterans (obstruction of bronchiolar lumen with inflammatory exudate) may occur. Pulmonary eosinophilia may be found in Churg Strauss or Wegener’s vasculitis.

• A 55 year old female has been on long-term steroids for chronic obstructive pulmonary disease. She complains of pain in her right groin radiating down the anteromedial thigh. On examination of the hip, there is decreased range of movement especially flexion, abduction and internal rotation. What is the likely diagnosis? • A. Osteoarthritis • B. Rheumatoid arthritis • C. Metastatic hip lesion • D. Avascular necrosis of the femoral head • E. Hairline fracture

• Answer: d) avascular necrosis of the femoral head. • In a patient on long term steroids presenting with groin pains radiating to the thigh associated with an antalgic gait and decreased range of movement of the hip, the most likely diagnosis is avascular necrosis of the femoral head. • In this condition, MRI is the most sensitive and specific technique and is useful for early diagnosis before collapse of bone occurs. CT scan and x-ray are useful to rule out advanced disease if duration is not clear. Bone scanning is more sensitive than x-ray but is non-specific. • • MRI showing avascular necrosis of the femoral head

• A patient who is 8 months pregnant has a thyroid function test because she has a smooth palpable goitre. Her Free T4 is 20 pmol/l and TSH is 5 mU/l. Which of these diagnoses is most likely? • A. Medullary thyroid carcinoma • B. Multinodular goitre • C. Grave's disease • D. Thyroid adenoma • E. Colloid goitre

• Answer: e) colloid goitre. A colloid goitre is most likely. Presentation is with mildly elevated TSH (0.3-4.0 mU/l) and normal free T4. Mild iodine deficiency or a pregnancy can cause the goitre to become more noticeable. • • Colloid Goitre -increased size of follicles and flattening of follicular epithelial cells

A 55 year old patient with type 2 diabetes is reviewed in the diabetic clinic. Which of the following is a feature of diabetic neuropathy to watch out for? A. Cervical myelopathy B. B. Brisk reflexes C. C. Muscle hypertrophy D. D. Loss of vibration sense E. E. Myotonia

• Answer: d) loss of vibration sense. Autonomic neuropathy to the gut, bladder and sexual organs (impotence) can occur. A 3rd nerve mononeuropathy can occur. Motor neuropathy can cause muscle wasting, and sensory neuropathy causes vibration sensory loss. With myotonia, prolonged contraction of muscle fibres associated with muscle dystrophy is due to genetic causes of muscle protein abnormality and is not neurologically dependent.

• A 40 year old lady has a pulmonary systolic murmur which is louder on inspiration. She also has a right ventricular heave. The second heart sound is wide and fixed with splitting. What is the likely diagnosis? • A. Mitral stenosis • B. Aortic stenosis • C. Atrial septal defect • D. Dilated cardiomyopathy • E. Hypertrophic cardiomyopathy

• Answer: c) atrial septal defect. • In Atrial Septal Defect (ASD), a Primum defect causes RBBB and LAD, whilst Secundum causes RBBB and RAD on the ECG. A systolic murmur is heard in the pulmonary area because of increased pulmonary valve flow due to pulmonary hypertension. Similarly, a left parasternal heave is present due to RVH. • ECG showing RBBB and LAD

A 75 year old man with known moderate to severe aortic stenosis presents to hospital with breathlessness. Which of the following features would indicate poor prognosis without urgent treatment? A.Early diastolic murmur B. Displaced apex beat C. Pulmonary oedema D. Aortic valve calcification seen on X ray E. Breathlessness

Answer: c) pulmonary oedema. Pulmonary oedema and angina can occur with aortic stenosis, these are symptoms which indicate urgent assessment should be made with a view towards surgery.

• A 45 year old man has polyuria and abdominal pains. His calcium is 2.9 mmol/l, phosphate 0.8 mmol/l and PTH 12 pmol/l. Which one of the following would suggest that he has primary hyperparathyroidism? • A. Serum alkaline phosphatase is increased • B. Normal skull • C. Arthritis • D. Low urinary phosphate excretion • E. Low urinary cAMP

Answer: a) serum alkaline phosphatase is increased. Serum alkaline phosphatase is usually increased in primary hyperparathyroidism. • Primary hyperparathyroidism does not respond to steroids. • Salt and pepper changes on the skull can be a hallmark. • Gout, rather than arthritis, is worsened by hyperparathyroidism. • High urinary phosphate excretion leads to serum phosphate and a high cAMP in the urine suggests active excretion.

• A 40 year old lady has increasing hirsutism. She is embarassed about having to shave her chin and also her chest. Her voice is becoming deeper. What is the most likely diagnosis? • A. Drug induced hirsutism . • B. Polycystic ovarian syndrome. • C. Adrenal tumour. • D. Congenital adrenal hyperplasia. • E. Ovarian carcinoma .

• Answer: c) adrenal tumour. Rapid development of hirsutism is usually caused by an adrenal tumour. There are high testosterone or DHEA levels in the plasma. • • MRI showing an adrenal tumour

• A 60 year old man has worsening joint stiffness, hip and back pains. He has spinal and hip X rays for assessment. Which one of the following is a recognised X ray change of osteoarthritis? A. Osteitis fibrosaB. B.Lytic lesions C. Fibrosis D. Subchondral cysts E. Hairline fracture

• Answer: d) subchondral cysts. Osteophytes, loss of joint space, subchondral sclerosis and subchondral cysts are common in osteoarthritis.

• A 55 year old lady has abdominal pains. She has polyuria and polydipsia. Her free T4 is 16 pmol/l and TSH is 3.0 mU/l. Which of the following is most likely? A. Subclinical hypothyroidism B. Renal tubular acidosis C. MEN 1 D. Diabetes E. Primary hyperparathyroidism

• Answer: e) primary hyperparathyroidism. Hypercalcaemia can cause abdominal pain, polyuria and polydipsia. There are no features suggestive of pituitary tumour, phaeochromocytoma or medullary thyroid involvement, hence MEN is unlikely.

A 10 year old child with joint pains is suspected of having juvenile chronic arthritis. A full rheumatological history is taken. Which of the following is a recognised presenting feature of juvenile chronic arthritis? A. Low grade fever B. Transient purpuric rash C. Haematuria D. Involvement of one or two large joints only E. Ulcerative colitis

• Answer: d) involvement of one or two large joints only. Juvenile chronic arthritis is rheumatoid factor negative. Commonest type is Still’s disease. Peaks of disease are about 5 years and 15 years of age. A high swinging fever is typical. An erythematous rash can occur, but it is non purpuric. Haematuria is not typical. Certain forms can involve only one or two large joints only. Different classifications are systemic, pauciarticular and polyarticular. There is no relation with ulcerative colitis.

La boratory evaluation of a 19-year-old male who is being worked up for polyuria and polydipsia yields the following results: • S. Na+ 144, K+ 4.0, Cl– 107, HCO3– 25 BUN: 6.4 mmol/L. Bl. gl: 5.7 mmol/L , Urine electrolytes (mmol/L): Na+ 28, K+ 32 Urine osmolality: 195 mosmol/kg water After 12 h of fluid deprivation, body weight has fallen by 5%. Laboratory testing now reveals the following: Serum electrolytes (meq/L): Na+ 150, K+ 4.1, Cl– 109, HCO3 – 25 BUN: 7.1 mmol/L (20 mg/dL) (98 mg/dL) Urine electrolyte : Na+ 24, K+ 35 Urine osmolality: 200 mosmol/kg water One hour after the subcutaneous administration of 5 units of arginine vasopressin urine values are as follows: Urine electrolytes (meq/L): Na+ 30, K+ 30 Urine osmolality: 199 mosm The likely diagnosis is • A. nephrogenic diabetes insipidus • B. osmotic diuresis • C. salt-losing nephropathy • D. psychogenic polydipsia • E. none of the above

Slide no 6

This female patient sufferred convuslions in childhood. She experienced several attacks of hematuria recenly. Proteinuria was less thn 1gm/24hrs and her RFTs were normal. 1. What is her condition. 2. What is the most likely lesion of her CT scan

A 50 year man presents with lightheadness. He has frequent nonsustained ventricular tachycardia on the ECG and cardiac monitor. His bloods show a Hb 13.0 g/dl, WCC 7 x 10^9/l, platelets 230 x 10^9/l, urea 11mol/l, creatinine 80μmol/l, sodium 134 mmol/l, potassium 3.2 mmol/l, serum magnesium of 0.6 mmol/l (0.75). Which one of following is likely to be responsible for his arrhythmias? A. Poor diet B. Alcoholism C. Frusemide D. Diarrhoea E. Hyperphosphataemia

• Answer: c) frusemide. The likely cause of the arrhythmias is hypomagnesaemia and hypokalaemia, which is most commonly associated with diuretic use.

A 38 year old lady presents with myalgia and lethargy. Her blood tests show a positive ANA with a titre of 1:1024 and rheumatoid factor is negative. The CK is raised at 360 U/l. Extranuclear antigen tests show a negative Ro and negative La, negative Scl70 and positive ribonuclear protein antibody at 160 units. What is the likely diagnosis? A.Polymyalgia rheumatica. B. Polymyositis. C. Scleroderma. D. Systemic lupus erythematosus . E. Mixed connective tissue disease.

• Answer: e) mixed connective tissue disease. A positive ANA (speckled pattern), raised CK and positive anti RNP antibody suggests mixed connective tissue disease.

• A 29-year-old banker is said to have gone camping three weeks ago. He reports having developed a skin rash around the groin area. It began as a papule but went on to become a macule with a bright outer border and a clear centre. It was warm but not painful. The macule is disappearing, but he has since developed severe headache, mild neck stiffness, fever chills, pains which were once in the knees but are now in the ankles and elbows. He also has malaise and fatigue. • What is the most probable diagnosis? • Infective endocarditis • Lyme disease • Meningococcal meningitis • Q fever • Rheumatic fever

A 40 year old man has genital ulceration and uveitis. his GP suspects Behcet's syndrome and is referred to the rheumatologist. Which one of the following is a feature of Behcet’s syndrome? A. Facial asymmetry B. Receding hair line C. Hirsutism D. Malignant melanoma E. Arterial thrombosis

• Answer: e) arterial thrombosis. Behcet's syndrome is an inflammatory disorder (associated with certain HLA B and DR types) causing mouth ulceration, arthritis, eyes (anterior uveitis, retinal vein occlusion), vasculitis (thrombophlebitis) and thrombosis. CNS vasculitis involvement may lead to TIA, meningoencephalitis, parkinson’s and dementia.

• A 42-year-old male a 15 year history of type 1 diabetes presents a two month history of deteriorating pain & stiffness of the right shoulder. On examination he has painful limitation of internal rotation but can abduct right arm only 90 degrees. Flexion is relatively unimpaired. There some weakness of movement of shoulder slight wasting of shoulder muscles. He has some reduced vibration sensation in both hands. • Which of following is likely diagnosis? 1 )Adhesive capsulitis 2 )Brachial plexopathy 3 )Calcium pyrophosphate arthropathy 4 )Diabetic arthropathy 5 )Rheumatoid arthritis

A 70 year old lady presents with bilateral shoulder and neck pains which have been present for several years. She also feels constantly lethargic. Her ESR is 105 mm/hour. What is the likely diagnosis? • A. Fibromyalgia • B. Supraspinatus tendinitis • C. Polymyalgia rheumatica • D. Temporal arteritis • E. Cushing's syndrome

• Answer: c) Polymyalgia rheumatica. With a raised ESR, polymyalgia rheumatica is far more likely than fibromyalgia. Temporal arteritis should always be considered especially if a headache is present.

A 50-year-old male is admitted to the hospital with pneumonia. He does well after the administration of antibiotics,but his sodium is noted to rise from 140 to 154 meq/L over 2 days. He reports thirst and has had a urine output of approximately 5 L per day. Which of the following is the most appropriate next step to evaluate the patient’s disorder? • A. Measurement of serum osmolality • B. Measurement of serum vasopressin level • C. 24-h measurement of urinary sodium • D. Trial of arginine vasopressin • E. Trial of free water restriction

A 55 year old patient presented with breathlessness and ankle oedema. The blood pressure is 135/80 mmHg. On examination, her JVP rises with inspiration. She has a soft systolic murmur and a third heart sound. Blood tests reveal Hb 10.5 g/dl WCC 7.5 x 10^9/l Platelets 150x 10^9/l sodium 136 mmol/l potassium 3.5 mmol/l creatinine 140 µmol/l urea 6 µmol/l ECG shows poor R wave progression. An echocardiogram shows no pericardial effusion, the ventricles are stiff and systolic function is mildly impaired. Which of the following is the likely diagnosis? A.Restrictive cardiomyopathy B. Dilated cardiomyopathy C. Constrictive pericarditis D. Ischaemic cardiomyopathy E. Pulmonary embolus

• Answer: a) restrictive cardiomyopathy. In this scenario, there symptoms can be caused by any form of cardiomyopathy. The rise in JVP with inspiration suggests either constrictive or restrictive cardiomyopathy. Echocardiography showing no pericardial effusion and stiffness suggests restrictive rather than constrictive cardiomyopathy. The transmitral dopplers on the echo may show E/A wave reversal and high velocities which may suggest restrictive picture. This may be due to infiltration due to haemochromatosis, endomyocardial fibrosis, sarcoidosis, myeloma, lymphoma or connective tissue disease.

A 35 year old female presents with sweatiness, tremors and palpitations. Examination reveals a exopthalmos and a goitre. Her GP requests TFT’s which show a TSH of 0.01mU/l, FT4 35 pmol/l, FT3 3.1 nmol/l. She has positive antithyroid antibodies. What is the likely diagnosis? A. Hashimoto's thyroiditis B. Grave's disease C. Iodine deficiency D. Post radioiodine treatment E. Papillary thyroid carcinoma

• Answer: b) Grave's disease. • Graves disease is the diagnosis - thyroid autoantibodies are increased. Almost 80% of patients have exopthalmos. Medical treatment such as carbimazole or radioiodine treatment are recommended rather than surgery. There will be increased uptake on the thyroid radioisotope scan. • • Exopthalmos in Grave's disease

A 68-year-old female is referred to outpatients with a three-month history of dyspnoea and significant peripheral oedema. Clinical findings are solely of the oedema. Echocardiography demonstrates thickened myocardium with impaired relaxation and a bright speckled appearance. What is the likely diagnosis? • A : Hypertrophic cardiomyopathy. • B : Cor pulmonale. • C : Sarcoidosis. • D : Amyloidosis. • E : Secondary neoplastic myocardial deposition.

A 44-year-old woman presents to her GP for review. She has attended the GP on a number of occasions during the past year for sinusitis and is now concerned that the bridge of her nose has collapsed and that she may require cosmetic surgery. Chest X-ray is abnormal and reveals multiple nodules. Routine blood testing reveals a creatinine of 205 μmol/l. Renal biopsy reveals a necrotising microvascular glomerulonephritis. Which of the following is the best initial treatment for this condition? 1. Corticosteroids 2. Cyclophosphamide 3. Corticosteroids and cyclophosphamide. 4. Azathioprine 5. Methotrexate

True 3. The clinical history is highly suggestive of Wegener’s Granulomatosis. Often patients present with severe rhinorrhoea, complicated by nasal ulceration and later cough with haemoptysis. Chest X-ray reveals nodular changes +/– pneumonic features. Renal involvement is characterised by microvascular glomerulonephritis. Treatment is with cyclophosphamide in combination with corticosteroids in patients with severe disease.

A 45-year-old woman presented with a 1-year history of intermittent swelling and pain in the small joints of her hands. Maximal stiffness occurs on waking and eases after an hour. On examination rheumatoid nodules on the elbows and symmetrical soft tissue swelling over the PIP and MCP joints were noted. Effusions of both wrists were also noted. She is rheumatoid factor positive. Radiological examination of the wrist and hands showed erosions and bony decalcification. Her GP has commenced her on NSAIDs and she been referred to a rheumatologist for consideration of DMARD. She has a past history of TB. Which of the following is best avoided if possible? 1. Methotrexate 2. Chloroquine 3. Sulfasalazine 4. Infliximab 5. leflunomide

True 4. Anti-TNF-a is an effective treatment for rheumatoid arthritis (RA). It has been shown to give a sustained clinical response over 2 years. However, it can reactivate old TB and should be used with caution in these patients.

A patient with a history of Sj ِ◌gren’s syndrome has the following laboratory findings: plasma sodium 139 meq/L, chloride 112 meq/L, bicarbonate 15 meq/L, and potassium 3.0 meq/L; urine studies show a pH of 6.0, sodium of 15 meq/L, potassium of 10 meq/L, and chloride of 12 meq/L. The most likely diagnosis is • A. type I renal tubular acidosis (RTA) • B. type II RTA • C. type III RTA • D. type IV RTA • E. chronic diarrhea

• 72-year-old male presents a 2 month history of weight loss & weakness. Examination reveals a BMI of 24.5 kg/m2 a pressure of 186/100 mmHg. Examination of lower limbs reveals a bilateral weakness of knee extension. He is unable to rise from squatting position. There absence of knee reflex but ankle reflexes are preserved both plantars are flexor. There are no abnormalities on sensory examination. • Which of following tests may be diagnostic? 1 )Vitamin B12 concentration 2 )Thyroid function test 3 )Oral glucose tolerance test 4 )Urine free cortisol concentration 5 )Vitamin D concentration

• Which of the following would be correct in keeping with a diagnosis of ploymyalgia rheumatica? 1 )raised creatinine kinase 2 )increased alkaline phosphatase 3 )sudden loss of vision in one eye 4 )shoulder & pelvic girdle pain in 35-yearold man 5 )erythema nodosum

• Correct answer 2

• A 45-year-old woman admitted a spiking temperature sweats. She unwell last 3 weeks flitting arthralgia lethargy. There a rash over her trunk which prevalent in mornings. Blood cultures are sterile. Her recent transthoracic echocardiogram normal. ESR 56mm/hour. Her ferritin elevated at 6000(g/l. Autoimmune screen negative. 1 )bacterial endocarditis. 2 )systemic lupus erythematosus . 3 )rheumatoid arthritis 4 )adult onset Stills disease . 5 )meningitis .

• A 52-year-old schoolteacher attends for weight loss & sweats. Subsequent investigations show: Free T4 of 40 pmol/L (9-23) Free T3 ofs 9.8 nmol/L (3.5-6) TSH of 7.0 mU/L (0.5-5) She is clinically thyrotoxic a diffuse goitre & commenced on Propranolol & Carbimazole. What is appropriate test this patient? 1 )FNA of thyroid gland ]2 )MRI scan pituitary gland 3 )Radio-isotope uptake scan of thyroid gland 4 )Repeat TFT 5 )Thyroid auto antibodies

A 75-year-old man presents with 12 months history of cognitive impairment, parkinsonism, intermittent confusion and generalised myoclonus. He was started on 62.5 tds of sinemet. In the following 2 months he was started experiencing visual hallucinations. The most likely diagnosis is: 1) Idiopathic Parkinson's disease 2) Alzheimer's disease 3) Diffuse Lewy body disease 4) Multiple system atrophy 5) Progressive supranuclear palsy

The answer is 3 Diffuse lewy body disease presents with cognitive impairment, visual hallucinations, intermittent confusion, parkinsonism, myoclonus and marked sensitivity to neuroleptic treatment. Visual hallucinations in parkinson's disease treated with L-dopa usually appear late (>2 years after initiation of treatment). Visual hallucinations are not features of multiple system atrophy or progressive supranuclear palsy.

A female patient aged 30 has a 5 years history of difficulty getting upstairs and out of a low chair and mild upper limb weakness but no pain. There is no family history. She presented with severe type 2 respiratory failure. EMG showed evidence of myopathy. The most likely diagnosis is: 1) Polymyositis 2) Inclusion body myositis 3) Acid Maltase Deficiency 4) Miller-Fisher Syndrome 5) Lambert-Eaton Myasthenic Syndrome

The answer is 3 Acid maltase deficiency typically presents with insidious onset of proximal myopathy and early respiratory muscle weakness. Respiratory failure in inflammatory myopathies (polymyositis, dermatomyositis, inclusion body myositis) and limb girdle muscular dystrophy is rare. Muscle biopsy shows vacuolation in muscle fibres. Miller-Fisher Syndrome, a variant of GBS, is characterised by ophthalmoplegia, ataxia and areflexia. Lambert-Eaton Myasthenic Syndrome, often a paraneoplastic phenomenon, is associated with hyporeflexia which returns after exercise, autonomic symptoms and fatiguability.

Which statement is true regarding Gabapentin? 1) is a potent hepatic enzyme inducer 2) side effects typically include visual field defects with long-term use 3) therapy is best monitored through measuring plasma concentrations 4) is of particular value as monotherapy in absence attacks (petit mal) 5) requires dose adjustment in renal disease

The answer is 5 Gabapentin does not induce cytochrome P450 unlike other anticonvulsants such as phenytoin and phenobarbitone. Vigabatrin may cause visual field defects, which may be irreversible. Rarely have visual disturbances been associated with gabapentin. No use in Petit Mal and is used for add-on therapy in partial or generalised seizures.

Which of the following clinical manifestations suggests Guillain Barré Syndrome? 1) Weakness beginning in the arms 2) Asymmetrical involvement of distal muscles 3) Bulbar involvement in about 50% of cases 4) Brisk tendon reflexes 5) Normal CSF protein

The answer is 3 GB is a post-infectious polyneuropathy causing demyelination in mainly motor but also sensory nerves. It usually follows a non-specific viral infection. Campylobacter and mycoplasma are recognised causes. Weakness begins in the legs and progressively ascends to involve the trunk, upper limbs and finally the bulbar muscles (Landry's ascending paralysis). Asymmetry is present in only 9% of patients, with symmetrical involvement being typical. Usually there is painless progression over days or weeks, but in cases of abrupt onset, there may be tenderness or muscle pain. Bulbar involvement occurs in 50%, with a risk of aspiration and respiratory insufficiency can be problematic. In the Miller Fisher Syndrome there is external ophthalmoplegia, ataxia and areflexia. In 20% of cases there is urinary incontinence of retention. Clinical symptoms usually improve within 2-3 weeks, though a chronic relapsing form is recognised. CSF protein is elevated to more than twice the upper limit of normal, with normal glucose and no pleocytosis. Bacterial cultures are negative and viral cultures rarely isolate anything. The dissociation between a high CSF protein and a lack of cellular response in a person with an acute or subacute polyneuropathy is diagnostic of Guillain Barré Syndrome

A 72-year-old lady has 4 months of memory loss, urinary incontinence and falls. On examination she has mild memory loss and a broad-based, slow gait. Muscle tone is normal and both plantar reflexes are downgoing. What is the likely diagnosis? 1) Alzheimer's disease 2) Frontal lobe dementia 3) Mulit-infarct dementia 4) Normal-pressure hydrocephalus 5) Parkinson's disease

The answer is 4 Normal pressure hydrocephalus characterized by abnormal gait, urinary incontinence, and dementia. It is an important clinical diagnosis, because it is a potentially reversible cause of dementia. It is important to distinguish it from Parkinson's Disease. The onset of gait disturbance and urinary symptoms is unusual so early in dementia. Frontal lobe dementia is characterised by loss of 'executive' functions and multi-infarct state usually has a step-wise history.

• A patient has, on examination, weakness in plantar flexion and foot inversion on the left. He also is unable to tiptoe on the same foot. Ankle jerk is absent. Which of the following nerve lesion is most likely? • A. Common peroneal nerve • B. L4 nerve root • C. Tibial nerve • D. Sciatic nerve • E. Femoral nerve

• Answer: c) tibial nerve. Tibial nerve supplies the gastrocnemius muscle and leads to the above findings. The common peroneal nerve causes weakness of eversion and dorsiflexion.

• A 25 year old secretary has had several episodes of brief jerking of the right arm over the past few weeks. There is no loss of consciousness. A CT scan of the head is unremarkable. Which is the best medication to commence? A. Carbamazepine B. Phenytoin C. Lorazepam D. Diazepam E. Levodopa •

• Answer: a) carbamazepine. Brief episodes of jerking suggests simple partial seizures. Carbamazepine is first line therapy for this.

• A 40 year old patient has a transthoracic echocardiogram as a follow up. He has a diagnosis of hypertrophic obstructive cardiomyopathy. Clinically he has a systolic murmur heard loudest in the right upper sternal edge. His ECG shows grossly large QRS complexes with LVH strain pattern. Which of the following suggests highest risk for sudden death? • A left ventricular outflow tract gradient of 20 mmHg • B. Tricuspid regurgitation • C. Systolic anterior motion of mitral valve • D. ECG showing ventricular ectopics • E. Interventricular septal thickness of 4 cm

• Answer: e) interventricular septal thickness of 4 cm. The LV outflow tract gradient is not significantly high in this patient, however, this may vary with exercise. The large interventricular septal thickness of 4 cm (normal <1.3 cm) suggests very hypertrophic myocardium and high risk of outflow tract obstruction with exertion.

A 18 year old man is referred for an echocardiogram for further investigation of a systolic murmur. This reveals a bicuspid aortic valve. Which of the following is an association? • A. Mitral stenosis • B. Mitral valve prolapse • C. Marfan's syndrome • D. Down's syndrome • E. Coarctation of aorta

• Answer: e) coarctation of aorta. Bicuspic aortic valve can be congenital. 5% of cases demonstrate significant association with coarctation of the aorta. • • Coarctation of Aorta

• A 50 year old woman with rheumatoid arthritis has hand and spine X rays due to worsening joint and back pains. Which of the following is a recognised X ray change of rheumatoid arthritis? • A. Juxta-articular osteosclerosis • B. Sacroilitis • C. Tendon swelling • D. Marginal erosions • E. Calcification of entheses

• Answer: d) marginal erosions. Juxta-articular osteoporosis or osteosclerosis occurs in OA. Sacroilitis is seen in seronegative arthritis. Marginal erosions are seen at the articular cartilage and attachment of synovium. There is associated loss of joint space. Calcification of entheses also occurs in seronegative arthritis. • • Marginal Erosions of the first MTP joint

• A 35 year old lady has positive ANA, and has a butterfly shaped rash on her face. Her physician makes a diagnosis of SLE. She has flare ups of joint swellings and pains requiring several months treatment with prednisolone. 1 year later she presents with hip pain limiting her mobility. Which one of the following is the likely cause? • A. Rheumatoid arthritis • B. Septic arthritis • C. Juvenile chronic arthritis • D. Avascular necrosis • E. Perthe's disease

• Answer: d) avascular necrosis. 15% of patients with SLE develop avascular necrosis of the bone. Nephritis, vasculitis and long term steroid use predispose to avascular necrosis. Collapse of the femoral head due to avascular necrosis

A 65 year old man has impaired hearing in his left ear, an enlarged skull vault, bowing of the left tibia which is warm to touch. In this patient, one of the complications of immobilisation would be: • A. Osteoarthritis • B. Hypercalcaemia • C. Peripheral vascular disease • D. Venous varicosities • E. Disseminated intravascular coagulation

• Answer: b) hypercalcaemia. The patient has the clinical features of Paget’s disease of bone. In this condition immobilisation is likely to cause hypercalcaemia. Other complications are gout, high output cardiac failure and coincidental hyperparathyroidism. • • Bowed tibia in Paget's disease

A 60 year old lady has an autosomal dominant condition. She small red lesions on her face and mouth. She has been on ferrous sulphate tablets for chronic iron deficiency anaemia. In view of the likely diagnosis, which feature may be associated? • A. Oesophageal dysmotility • B. Pulmonary AV malformation • C. Pulmonary fibrosis • D. Hiatus hernia • E. Aortic aneurysm

• Answer: b) pulmonary AV malformation. She has hereditary haemorrhagic telangiectasia (OslerRendu-Weber syndrome). Patients have a chronic problem with recurrent GI bleeding and require multiple transfusions and iron supplementation. 10% of patients have pulmonary AV malformation. Oesophageal dysmotility is seen in scleroderma. • • Telangiectatic lesions in HHT

• A cardiothoracic surgeon is planning for surgery in a 60 year old man with coronary artery disease. In coronary artery bypass grafting, which of the following vessels should be considered for grafting to the Left anterior descending artery? • A. Saphenous vein graft • B. Left internal mammary • C. Right internal mammary • D. Radial artery • E. Brachial artery

• Answer: b) left internal mammary. The left internal mammary artery supplies the anterior chest wall. It has been shown to be superior to saphenous vein grafts (from aorta to LAD) in staying patent and hence is now the choice artery (LIMA to LAD) graft. Although circumflex and right coronary arteries are usually grafted with veins, RIMA arteries are sometimes used to graft the RCA.

A 45 year old man has developed pains and swelling over his wrist joints bilaterally over 3 months. He has limited wrist movements and clubbing. X rays show periosteal reaction at the ends of the radius and ulnar bones suggestive of periostitis. Which medical condition predisposes to this? Behcet's disease B. Crohn's disease C. Amyloidosis D. Diabetes E. Hyperthyroidism

• Answer: b) Crohn's disease. Hypertrophic osteoarthropathy (or hypertrophic pulmonary osteoarthropathy when there is mesothelioma or bronchogenic carcinoma associated) is associated with conditions such as liver cirrhosis, ulcerative colitis, whipple's disease and crohn's disease. • • Hypertrophic osteoarthropathy

A 30-year-old woman complains of severe headache, mainly in the occipital region, as well as irritability, low mood and lack of energy. Her husband informs you that he has noted her to be withdrawn and short tempered. She also gives a history of a recent increase in hair loss, and joint pains, predominantly in the wrist and knees. She has had amenorrhoea for the last 3 months. She works as a secretary, and is now finding it extremely difficult to cope with her work and household activities. She and her husband are requesting sick leave. On examination, she looks unwell. Her temperature is 38oC, she is pale and there is an erythematous rash on her face. Joint examination is remarkable for tenderness in the wrists and knees, but no swelling. Cardiovascular, Respiratory and abdominal examination are unrevealing. Neurological examination does not show focal neurologic signs or neck stiffness. Laboratory results were returned as follows: Hb 9.7 g/dl WBC3.8 x 10 9/l, N2.1 x 10 9/l,L0.8 x 10 9/l, PLT88 x 10 9/l, ESR 88 mm/1st hr, CRP8 mg/l, AST 44 IU/l, ALK-P156 IU/l, ALT 50 IU/l, ANA positive, DNA and ENA awaited, Urine dipstick protein+ What is the most likely clinical problem that may explain the above? 1. Neuropsychiatric lupus 2. Viral meningitis 3. Lupus glomerulonephritis 4. Antiphospholipid antibody syndrome 5. Cranial angitis

True 1. The above clinical findings and investigation results are suggestive of systemic lupus erythematosus (SLE). However, the symptoms of headache and mood changes point towards the possibility of neuropsychiatric lupus. Features of neurological disease in lupus range from the common, relatively harmless migraine headache, to major psychotic episodes and grand mal seizures, recognised in some lupus patients. Lupus glomerulonephritis cannot be completely excluded but active urinary sediment with proteinuria of ++ on dipstick will be more suggestive. Antiphospholipid antibody syndrome (APS) is unlikely even though the patient has thrombocytopenia; lymphocytosis rather than lymphopenia would be more consistent with APS.

• A 65 year old man is assessed on the ward for weakness in his legs. He is an ex smoker and drinks 15 units of alcohol in a week. His wife mentions that he is confused. On examination, his MMSE score is 20/30. He has an ataxic gait. There is bilateral pyramidal weakness and coordination is impaired. Routine blood tests are normal. An MRI scan of the head shows diffuse white matter changes, more in the cerebellar region than the cerebrum. Which of these tests would help most in confirming the diagnosis? • A. CSF for oligoclonal bands • B. CSF for anti Hu and anti Yo antibodies • C. CSF for TB culture • D. EEG E. EMG

• Answer: b) CSF for Anti Hu and anti Yo antibodies. Anti Hu and anti Yo antibodies would help confirm a diagnosis of paraneoplastic syndrome. Multiple sclerosis is unlikely in view of late presentation and is not commonly associated with dementia.

A 36 year old female gave a recent history of sensory impairment and imbalance in left half of the body. She also complained of tingling .She had recurrent episodes of ataxia in last year – each episode resolved spontaneously. What is the likely diagnosis of this episode? A. Transient ischaemic attack B. Intracranial space occupying lesion C. Multiple sclerosis D. Cerebellar haemorrhage

• Answer: C) Multiple sclerosis. • History of patchy sensory loss, and ataxia which improves on occasion is suggestive of an inflammatory disorder, in this case most likely multiple sclerosis.

Which of the following diseases is associated with an increased frequency of HLA -DR4 on the cell membranes? A. Ankylosing spondylitis B. B. Rheumatoid arthritis C. C. Porphyria D. D. Congenital adrenal hyperplasia E. E. Narcolepsy

• Answer: b) rheumatoid arthritis. Lack of HLA DR2 is associated with narcolepsy, and increased HLA DR4 is associated with rheumatoid arthritis.

11.Anti-neutrophilic cytoplasmic autoantibodies: A positive only in Wegener’s syndrome associated with renal disease . B cause neutropenia in SLE . C present in inflammatory bowel disease . D is invariably associated with Polyarteritis Nodosa. E ANCA positive glomerulonephritis characteristically causes nephrotic syndrome.

25 year old lady complains of unilateral throbbing headache for 10 months. Each time she has headaches, she also complains of unilateral weakness in the arm which resolve spontaneously when the headaches improve. CT head was normal. What is the diagnosis? A. Cluster headache B. Migraine C. Tension headache D. Somatoform disorder E. Cavernous sinus thrombosis

• Answer: B) migraine. Hemiplegic migraine is a term used to describe the migraine syndrome that is associated with a weakness or sensory loss of the limbs on one side of the body. The headache usually precedes the weakness by a day or more. The limbs gradually return to normal over several days.

• 31 yrs old female coming for infertility. PCO by US , BMI 35. what is the most appropriate drug? • A. Testosterone • B. clomiphene • C. Finasteride • D. Rosiglitazone • E. Metformin

• Answer: clomiphene Both metformin and clomiphene has been shown to be effective in stimulating ovulation in patients with PCOS (clomiphene is more effective, but not in the options). The reduction of hormonal imbalance and treating insulin resistance helps to restore the ovulatory cycles and fertility.

• A 65 year old lady is seen in the rhematology clinic with the results of a DEXA scan. The T score of the hip is -2.8 SD and in the spine is 2.5 SD. Which of the following medications does NOT improve bone mineral density? • A. Calcium and vitamin D • B. Oestrogen replacement • C. Selective oestrogen receptor modulator (SERM) • D. Bisphosphonates • E. Phosphate replacement

59- 50-year-old old man is admitted to hospital unconsious, and smelling of alcohol. One hour after admission, he becomes suddenly sweaty with a regular tachycardia of 110 bpm and a BP of 100/50. What is the diagnosis? 1) Alcohol withdrawal. 2) Hepatic encephalopathy. 3) Hypoglycaemia. 4) Subdural haematoma. 5) Wernicke's encephalopathy.

The answer is 3 This is a bit early for alcohol withdrawal particularly as the patient is admitted smelling of alcohol. The most likely diagnosis is hypoglycaemia. We do not have any clinical findings to suggest any of the other alternativies.

A 45 year old lady has had long standing arthritis of her hands and feet. Which of the following X ray changes suggests rheumatoid arthritis instead of a seronegative arthropathy? • A. Osteosclerosis • B. Osteophytes • C. Osteoporotic changes • D. Periarticular erosions • E. Loss of joint space

• Answer: d) periarticular erosions. Osteophytes and loss of joint space are commonly found in osteoarthritis, and can also be found in rheumatoid arthritis. Periarticular erosions are suggestive of rheumatoid arthritis. • • Periarticular Erosions

• A 60 year old man is brought to hospital having collapsed to the ground suddenly and was unable to move his left leg or arm. There was no loss of consciousness. He has a past medical history of hypertension only. The episode lasted a few seconds and he has been relatively well. Examination reveals a mild hemiparesis of the left arm and leg. Which is the likely diagnosis? • A. Pontine haemorrhage • B. Primary epilepsy • C. Medullary haemorrhage • D. Right internal capsule infarct • E. Left internal capsule infarct

• Answer: d) right internal capsule infarct. This patient is likely to have a lacunar infarct involving the internal capsule, causing transient contralateral hemiparesis.

A 35 year old man presents acutely with urethritis, conjunctivitis and arthritis. Rheumatoid factor is negative and he has raised inflammatory markers. In view of the likely diagnosis, which one of the following features is associated? A. Myocardial infarction B. B. Pulmonary embolus C. C. Circinate balanitis D. D. nail dystrophyE. Calcinosis

• Answer: c) circinate balanitis. The diagnosis is Reiter's syndrome. Reiter’s syndrome is urethritis, conjunctivitis, seronegative arthritis (cannot see, cannot pee, cannot climb a tree). The typical patient is a young man with recent urethritis or dysentery. The seronegative arthritis is usually a mono or oligoarthritis. • Other features are anterior uveitis, keratoderma blenorrhagica (brown abscesses on palms and soles), mouth ulcers, plantar fasciitis and archilles tendinitis (enthesopathy), circinate balanitis (painless rash) and aortic incompetence. The arthritis may relapse or remain chronic. Management is usually with rest and NSAIDs.

A demyelinating polyneuropathy is typically caused by: 1) Diabetes 2) Excessive alcohol 3) Hereditary motor-sensory neuropathy 4) Renal failure 5) Vitamin B12 deficiency

The answer is 3 The differential diagnosis of demyelinating neuropathy includes: hereditary motor-sensory neuropathy (Charcot-Marie Tooth disease), Refsum's Disease, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), paraprotein-related disorder, leukodystrophies. Amiodarone, Diabetes, alcohol, Vitamin deficiencies and renal failure cause an axonal polyneuropathy.

• A 35 year old lady has skin pigmentation, hypotension, hyponatraemia. A short synacthen test shows a rise in cortisol from 100 to 140 μg/ml. Which one of the following conditions is associated? • A. Papillary thyroid carcinoma • B. Ovarian fibroids • C. Phaeochromocytoma • D. Hepatocellular carcinoma • E. Pernicious anaemia

• Answer: e) pernicious anaemia. Addison's disease is described. Many autoimmune diseases are associated e.g. vitiligo, diabetes, primary ovarian failure and pernicious anaemia.

A 70-year-old woman presented with episodic impairment of consciousness. Which of the following is the most likely cause? 1) Alzheimer type dementia 2) chronic sub-dural haematoma 3) Creutzfeldt-Jacob disease 4) depressive stupor 5) normal pressure hydrocephalus

The answer is 2 This is quite a grey question. The clinical scenario is very brief with no mention of any neurological signs so a logical deduction must be made. Alzheimer's disease would be expected to have a continous impairment of consciousness in its advanced stages but could be episodic if there were variation in drugs therapy or concurrent illnesses. Similarly Normal Pressure Hydrocephalus, Creutzfeld-Jacob and depression would present with dementia (or apparent dementia) but not fluctuant. Of all those listed subdural haematoma is classically associated with fluctuating level of consciousness. This would make it the most likely.

Temporal lobe lesions cause: 1) Apraxia 2) 2) Astereogenesis 3) Primitive reflexes 4) Visuospatial neglect 5) Wernike's (receptive) aphasia

The answer is 5 Lesions of the frontal lobe include difficulties with task sequencing and executive skills. Expressive aphasia (receptive aphasias a temporal lobe lesion), primitive reflexes, perseveration (repeatedly asking the same question or performing the same task), anosmia and changes in personality. Lesions of the parietal lobe include apraxias, neglect, astereognosis (unable to recognise an object by feeling it) and visual field defects (typically homonymous inferior quadrantanopia). They may also cause alcalculia (inability to perform mental arithmetic). Lesions of the temporal lobe cause visual field defects (typically homonymous superior quadrantanopia), Wernike's (receptive) aphasia, auditory agnosia, and memory impairment. Occipital lobe lesions include cortical blindness (blindness due to damage to the visual cortex and may present as Anton syndrome where there is blindness but the patient is unaware or denies blindness), homonymous hemianopia, and visual agnosia (seeing but not percieving objects - it is different to neglect since in agnosia the objects are seen and followed but cannot be named).

A 72-year-old lady has 4 months of memory loss, urinary incontinence and falls. On examination she has mild memory loss and a broad-based, slow gait. Muscle tone is normal and both plantar reflexes are downgoing. What is the likely diagnosis? 1) Alzheimer's disease 2) Frontal lobe dementia 3) Mulit-infarct dementia 4) Normal-pressure hydrocephalus 5) Parkinson's disease

The answer is 4 Normal pressure hydrocephalus characterized by abnormal gait, urinary incontinence, and dementia. It is an important clinical diagnosis, because it is a potentially reversible cause of dementia. It is important to distinguish it from Parkinson's Disease. The onset of gait disturbance and urinary symptoms is unusual so early in dementia. Frontal lobe dementia is characterised by loss of 'executive' functions and multi-infarct state usually has a step-wise history.

What is the diagnosis of the patient whose hand on the right and suffers hyponatremia Slide no 10

Normal hand

•

A 2 year old girl with unrepaired tetralogy of Fallot presents to the emergency department with increased cyanosis. Physical examination shows a small, very cyanotic child lying on a stretcher with her knees drawn up against her chest. Pulse oximetry shows an oxygen saturation of 58% in room air. Her respirations are rapid and deep. Auscultation of the heart discloses tachycardia but no murmur. Which of the following is the most appropriate general treatment strategy for this patient?

• • • • •

Decrease systemic vascular resistance to increase right-to-left shunting Decrease pulmonary vascular resistance to decrease left-to-right shunting Decrease systemic vascular resistance to decrease right-to-left shunting Increase pulmonary vascular resistance to increase left-to-right shunting Increase systemic vascular resistance to decrease right-to-left shunting

•

Explanation

• •

The correct answer is Choice E. Understanding the anatomy of patients with congenital heart disease is crucial for understanding their care. Often, the best way to think about the anatomy for a patient with congenital heart disease is to imagine the path of blood flow. For example, imagine a single red blood cell in a normal patient. The red blood cell returns to the heart via lesion: the pulmonary outflowthe tract obstruction thethe VSD. the vena cava, deoxygenated. It then enters right atrium,and then right ventricle, then goes to the lungs via the pulmonary artery. After getting oxygenated in the pulmonary capillaries, it returns to the left atrium via a pulmonary vein, then enters the left ventricle, then moves out to the body to deliver its oxygen to the tissues. Patients with Tetralogy of Fallot have four distinct lesions ("PROVe": pulmonary outflow tract obstruction, right ventricular hypertrophy, an overriding aorta, and a large VSD) but only two of them are necessary for understanding the pathophysiology of the lesion: the pulmonary outflow tract obstruction and the VSD. Imagine now a single red blood cell returning to the heart in a patient with Tetralogy of Fallot. After leaving the vena cava and the right atrium, the RBC enters the right ventricle. Here, the cell must make a "choice" - to pass through the stenotic pulmonary valve and enter the lungs, or to pass through the VSD and into the left ventricle (and on to the systemic circulation) without ever getting oxygenated? Remember, blood flows to the path of least resistance, and thus how much blood goes to the lungs versus how much goes to the body without being oxygenated depends on the balance between the pulmonary vascular resistance and the systemic vascular resistance. When the pulmonary vascular resistance is high and the systemic vascular resistance is low, it is much more difficult for blood to get into the lungs than it is for it to pass through the VSD and out to the circulation without being oxygenated. This leads to severe right-to-left shunting, called a "Tet spell," and is what is happening to the patient in the vignette. Alternately, if the systemic vascular resistance is high and the pulmonary vascular resistance is low, it is easier for blood to pass through the pulmonary outflow tract obstruction and into the lungs, where it can be oxygenated. This is the goal of treatment for a Tet spell. Thus, the correct answer is choice E - if the systemic vascular resistance increases, then the right-to-left shunt should decrease - which will reduce the patient's cyanosis. Decreasing the systemic vascular resistance would lead to increased right-to-left shunting (choice A), but this will cause more cyanosis and would not be the goal of treatment. Decreasing pulmonary vascular resistance (as in choice B) is a good idea, as it would allow more blood to enter the lungs - but the goal is to decrease the right-to-left shunt, not the left-to-right. Decreasing systemic vascular resistance (choice C) will lead to more right-to-left shunting, which is not what this patient needs. Increasing pulmonary vascular resistance (choice D) would cause increased right-to-left shunting, which as described previously, would be very bad in this situation.

• •

•

•

• • • • •

• A 67-year-old woman was referred with a 3-month history of painful legs, malaise and weight loss. She had had type 2 diabetes mellitus and hypertension for 18 years. Her medication was gliclazide 160 mg twice daily, ramipril 2.5 mg daily and atorvastatin 20 mg daily. On examination, her blood pressure was 145/90 mmHg. There was some tenderness over her spine and lower legs. • Investigations: • serum sodium 138 mmol/L (137–144) • serum potassium 5.5 mmol/L (3.5–4.9) • serum creatinine 240 µmol/L (60–110) • serum corrected calcium 1.80 mmol/L (2.20–2.60) • serum phosphate 1.6 mmol/L (0.8–1.4) • plasma parathyroid hormone 22.2 pmol/L (0.9–5.4) • • What therapy is most likely to correct the calcium and parathyroid hormone concentrations? • • A alendronic acid • B alfacalcidol • C calcitonin • D cinacalcet • E ergocalciferol

• Answer Key: B

• A 53-year-old man presented with a 2-week history of diarrhoea associated with cramping abdominal pain. He was passing up to 15 very loose and watery stools per day. There was no blood in stools. He had had a heart transplant 2 years previously, and his medication comprised ciclosporin, prednisolone, aspirin and ramipril. Investigations: • haemoglobin 110 g/L (130–180) • white cell count 12.5 109 /L (4.0–11.0) • serum urea 14.4 mmol/L (2.5–7.0) • serum creatinine 135 µmol/L (60–110) • serum C-reactive protein 35 mg/L (<10) • stool culture negative • stool microscopy cysts identified on modified acid-fast stain • What is the most likely pathogen? • A Cryptosporidium parvum • B Entamoeba histolytica • C Giardia lamblia • D Pneumocystis jirovecii • E Toxoplasma gondii

• Answer Key: A

•

•

A 56-year-old man was referred to the medical clinic from the psychiatric unit because of weight gain of 20 kg over 4 months. He had a 6-month history of severe depression with psychosis, which had required inpatient treatment. He was taking olanzapine 20 mg daily and fluoxetine 40 mg daily. On examination, he appeared Cushingoid, with centripetal obesity and a few abdominal striae. He had reasonable proximal muscle strength. His blood pressure was 170/100 mmHg.

Investigations: • fasting plasma glucose 8.5 mmol/L (3–6) • serum cholesterol 6.4 mmol/L (<5.2) • serum LDL cholesterol 5.01 mmol/L (<3.36) • serum HDL cholesterol 0.75 mmol/L (>1.55) • fasting serum triglycerides 2.42 mmol/L (0.45–1.69) • overnight dexamethasone suppression test (after 1 mg dexamethasone) • serum cortisol 55 nmol/L (<50) 24-h urinary cortisol 310 nmol (55–250)

What is the most likely diagnosis? • A adrenal Cushing‟s syndrome • B ectopic ACTH syndrome • C metabolic syndrome • D pituitary-dependent Cushing‟s disease • E pseudo-Cushing‟s syndrome

• E

• An 82-year-old woman with hypertension presented with tiredness, ankle swelling and arthralgia. On examination, her pulse was 92 beats per minute and her blood pressure was 150/90 mmHg. She had bilateral ankle oedema. Her serum creatinine concentration had been normal 6 months previously. Urinalysis showed protein 2+, blood 2+. Investigations: • haemoglobin 103 g/L (115–165) white cell count 10.5 109/L (4.0–11.0) platelet count 410 109/L (150–400) • serum creatinine 252 µmol/L (60–110) • What is the most likely cause of her renal impairment? • A amyloidosis • B crescentic glomerulonephritis • C IgA nephropathy • D membranoproliferative glomerulonephritis • E membranous nephropathy

• Answer Key: B

A 72-year-old man presented with a 4-year history of acute intermittent pain and swelling of the knees. The problem affected one knee at a time and each episode lasted about a week. He took naproxen for the pain. His serum urate was measured during one of the attacks and was found to be normal. He had drunk 24–28 units of alcohol per week for 30 years. There was no family history of diabetes mellitus. On examination, his body mass index was 34 kg/m2 (94–99). His pulse was 64 beats per minute and his blood pressure was 110/70 mmHg. His liver was enlarged to 5 cm below the costal margin and his spleen to 3 cm. The metacarpophalangeal joints of the index and middle fingers in both hands were swollen. Urinalysis showed glucose 3+. Investigations: • haemoglobin 165 g/L (130–180) • white cell count 9.5 109/L (4.0–11.0) • platelet count 135 109/L (150–400) • serum sodium 128 mmol/L (137–144) • serum potassium 3.1 mmol/L (3.5–4.9) • serum urea 3.5 mmol/L (2.5–7.0) • serum creatinine 56 µmol/L (60–110) • serum albumin 31 g/L (37–49) • serum total bilirubin 32 µmol/L (1–22) • serum alanine aminotransferase 133 U/L (5–35) • serum aspartate aminotransferase 110 U/L (1–31) • fasting plasma glucose 13.4 mmol/L (3.0–6.0) What is the most likely diagnosis? • A alcoholic cirrhosis • B haemochromatosis • C palindromic rheumatism • D rheumatoid arthritis • E sarcoidosis

• Answer Key: B

• • • • •

A 26-year-old woman was admitted as an emergency. She complained of right upper quadrant pain, fever and shaking. She was 30 weeks pregnant with her first child. On examination, her temperature was 39.5°C, her pulse was 120 beats per minute and her blood pressure was 105/80 mmHg. She was jaundiced and tender over her liver. The uterine fundus was palpable above the umbilicus.

Investigations: haemoglobin 107 g/L (115–165) • white cell count 14.9 109/L (4.0–11.0) • neutrophil count 12.1 109/L (1.5–7.0) • platelet count 257 109/L (150–400) prothrombin time 15.5 s (11.5–15.5) • serum sodium 138 mmol/L (137–144) • serum potassium 3.4 mmol/L (3.5–4.9) • serum urea 8.7 mmol/L (2.5–7.0) • serum creatinine 130 μmol/L (60–110) • serum albumin 34 g/L (37–49) • serum total bilirubin 118 μmol/L (1–22) • serum alanine aminotransferase 204 U/L (5–35) • serum alkaline phosphatase 609 U/L (45–105) • serum gamma glutamyl transferase 748 U/L (4–35) • • What is the most likely diagnosis? • A autoimmune hepatitis • B common bile duct stone • C HELLP syndrome • D hepatitis A infection • E primary sclerosing cholangitis

• Answer Key: B

• A 73-year-old retired man was admitted after he had been found to have renal impairment by his general practitioner. He gave a 3-month history of lethargy and back pain, with thirst and constipation over the past 4 weeks. He had noticed that he had passed less urine than normal in the past 3 days. Abdominal examination was normal. • Investigations: haemoglobin 98 g/L (130–180) • white cell count 5.6 109 /L (4.0–11.0) • platelet count 380 109 /L (150–400) • erythrocyte sedimentation rate 115 mm/1st h (<20) • serum urea 36.3 mmol/L (2.5–7.0) • serum creatinine 651 μmol/L (60–110) • serum corrected calcium 2.92 mmol/L (2.20–2.60) • serum total protein 85 g/L (61–76) • serum albumin 34 g/L (37–49) • serum alkaline phosphatase 99 U/L (45–105) • What is the most likely diagnosis? • A carcinoma of prostate • B myeloma • C primary hyperparathyroidism • D sarcoidosis • E tuberculosis

• Answer Key: B

• A 60-year-old woman was admitted with a 2-day history of dysuria, loin pain and rigors. On admission, she was unwell and confused. She was also febrile and tachycardic. She was transferred to the medical high-dependency unit for invasive monitoring. • Which set of haemodynamic values is most likely to be present? M Arterial pr normal

A B C D E

85 80 110 85 66 60

M Right atrial pr M.PAP

3 8 18 6 20 2

15 22 20 16 22 15

PA wedge Pr .

9 20 11 8 20 8

COP

5.0 3.0 4.0 2.5 2.0 4.5

• A 34-year-old woman was admitted with shortness of breath, and found to have a pulmonary embolus. On systemic enquiry, she admitted to cold intolerance. She was taking no medication. On examination, she had a livedo reticularis rash on the thighs. Blood tests showed marked thrombocytopenia and a prolonged activated partial thromboplastin time. Antinuclear antibodies were negative and complement C3 and C4 levels were normal. The blood film was normal, with no evidence of haemolysis. • • • • • • •

What is the most likely diagnosis? A antiphospholipid antibody syndrome B cryoglobulinaemia C mixed connective tissue disease D systemic lupus erythematosus E thrombotic thrombocytopenic purpura

• Answer Key: A

• A 19-year-old woman presented with a widespread eruption 2 weeks after a sorethroat. • On examination, there were multiple 5-mm diameter, scaly, erythematous papules over her trunk and limbs. • What is the most likely diagnosis? • A atopic eczema • B dermatitis artefacta • C guttate psoriasis • D lichen planus • E pityriasis versicolor

• Answer Key: C

A 27-year-old woman attended the emergency department with a 1-week history of progressive dyspnoea and cough, and a 2-day history of left basal thoracic pain on inspiration and haemoptysis. She had a history of bronchiectasis. She was a nonsmoker. She had recently returned from a holiday in New Zealand, and was taking co-amoxiclav and prednisolone prescribed by her general practitioner for an exacerbation of her bronchiectasis. On examination, she was thin. Her temperature was 37.3°C, her pulse was 115 beats per minute and regular, her blood pressure was 128/78 mmHg and her respiratory rate was 22 breaths per minute. Further examination was normal. Investigations: haemoglobin 157 g/L (115–165) white cell count 18.0 109/L (4.0–11.0) serum C-reactive protein 68 mg/L (<10) arterial blood gases, breathing air: • PO2 8.9 kPa (11.3–12.6) PCO2 4.9 kPa (4.7–6.0) • pH 7.40 (7.35–7.45) • H+ 40 nmol/L (35–45) • bicarbonate 22 mmol/L (21–29) • ECG sinus tachycardia • chest X-ray cystic changes at left base What is the most appropriate next investigation? • A CT pulmonary angiography • B D-dimer • C echocardiography • D ultrasound scan of legs and pelvis • E ventilation/perfusion isotope lung scan.

• Answer Key: A

• A 30-year-old woman had a 3-year history of Crohn‟s disease, which had required the formation of an ileostomy. She presented with a sore area around the stoma . This was causing problems with adhesion of the stoma pouch. What is the most appropriate treatment? • A oral flucloxacillin • B oral prednisolone • C radiotherapy • D surgical debridement • E topical terbinafine

• Answer Key: B

• A 60-year-old man was admitted with a 3-day history of diarrhoea. A diagnosis of lung and peritoneal metastases from an unknown primary carcinoma had been made 4 months previously and he had been receiving platinum-based combination chemotherapy. He had been discharged from hospital 5 days earlier after an episode of neutropenic sepsis following his second cycle of chemotherapy. On examination, he was apyrexial, his pulse was 98 beats per minute and his lying blood pressure was 110/65 mmHg. He looked dehydrated. His abdomen was soft but tender over the left iliac fossa. Investigations: haemoglobin 113 g/L (130–180) white cell count 6.5 109/L (4.0–11.0) neutrophil count 5.4 109/L (1.5–7.0) platelet count 170 109/L (150–400) CT scan of abdomen thickened sigmoid colon • What is the most likely diagnosis? • A cryptosporidiosis • B flare-up of diverticular disease • C ischaemic colitis • D pseudomembranous colitis • E tumour progression

• Answer Key: D

• A 79-year-old woman was referred to the medical outpatient clinic with a 3month history of low back pain. She was taking regular paracetamol and occasional ibuprofen. She was normally fit and active, with no other complaints. Examination was normal. Investigations: • full blood count normal • serum urea and electrolytes normal • Serum calcium normal • serum immunoglobulin (Ig) G 15.2 g/L (6.0–13.0) • serum IgA 2.5 g/L (0.8–3.0) • serum IgM 1.0 g/L (0.4–2.5) • serum protein electrophoresis IgG kappa paraprotein: 4.3 g/L X-ray of lumbar spine generalised osteopenia; no focal collapse; mild degenerative change • What is the most likely diagnosis? • A amyloidosis • B low-grade lymphoma • C monoclonal gammopathy of undetermined significance • D myeloma • E solitary plasmacytoma • •

• Answer Key: C

• A 52-year-old man presented with the sudden onset of severe anterior chest pain. An acute myocardial infarction was suspected and subsequently confirmed by serum troponin concentration and ECG. Following admission, he was noted to be hypotensive with oliguria. A Swan–Ganz catheter was inserted. The right atrial pressure was found to be 20 mmHg (4–8) and the indirect left atrial mean pressure (wedge) was 2 mmHg (5–10). What is the most likely explanation for these pressure measurements? • A acute left ventricular failure • B acute mitral regurgitation • C hypovolaemia • D pericardial tamponade • E right ventricular failure

• Answer Key: E

• A 50-year-old woman presented with a 24-hour history of palpitations. An ECG revealed atrial fibrillation with a ventricular rate of 130 beats per minute. • Which drug is most likely to restore sinus rhythm? • A adenosine • B bisoprolol • C digoxin • D flecainide • E verapamil

• 2. Answer Key: D

• A 48-year-old woman complained of leg weakness and tenderness, which was worse on exercise. Her serum creatine kinase was elevated, but a muscle biopsy was inconclusive. • Antinuclear antibodies were negative, but antibodies to gastric parietal cells and thyroid peroxidase were both detected. There was no anaemia but the MCV was raised. • • What is the most likely diagnosis? • A alcohol abuse • B folate deficiency • C hypothyroidism • D pernicious anaemia • E polymyositis

• Answer Key: C

• A 25-year-old woman was reviewed 6 weeks after stopping anticoagulant therapy. She had received anticoagulants for 3 months following a right iliofemoral vein thrombosis that had developed 7 days post partum. Investigations: • protein C 85 IU/dL (80–135) • protein S 110 IU/dL (80–120) • antithrombin 95 IU/dL (80–120) • prothrombin 20210A allele negative • factor V Leiden mutation heterozygous What is the most appropriate further management? A anticoagulation for an indefinite period with target international normalised ratio (INR) 2.5 B anticoagulation for an indefinite period with target INR 3.5 C anticoagulation for another 3 months with target INR 2.5 D long-term aspirin E no further anticoagulation

• Answer Key: E • Long-term anticoagulant therapy is not recommended in patients with VTE provoked by surgery (1B) Long-term anticoagulant therapy is not recommended in • patients with VTE provoked by non-surgical transient trigger factors (1B). • Patients with unprovoked proximal DVT or PE should be considered for long-term anticoagulation, taking intoaccount information that may help predict risk of recurrence and risk of bleeding in the individual patient(2B). • Long-term anticoagulant therapy is not recommended in patients with VTE confined to the calf (i.e. not extending into the popliteal vein)(1A).

• A 21-year-old man was admitted to hospital with a 5-day history of fevers and vomiting. He also complained of knee and ankle pains. He was homosexual, and had last had receptive anal intercourse 6 weeks previously. On examination, he had a widespread erythematous macular rash. His temperature was 37.5°C, his pulse was 85 beats per minute and his blood pressure was 115/60 mmHg. There was no joint swelling. Investigations: • haemoglobin 147 g/L (130–180) • white cell count 6.5 109 /L (4.0–11.0) • serum urea 4.3 mmol/L (2.5–7.0) • serum total bilirubin 50 µmol/L (1–22) • serum alanine aminotransferase 687 U/L (5–35) • serum alkaline phosphatase 110 U/L (45–105) • serum gamma glutamyl transferase 89 U/L (<50) What is the most likely diagnosis? • A acute hepatitis B • B acute hepatitis C • C acute HIV infection • D gonococcal bacteraemia • E secondary syphilis

• A

• A 24-year-old man presented with a 2-day history of fever and a generalised blistering rash. He was taking prednisolone 10 mg daily for asthma. His son had had chickenpox 2 weeks previously. • On examination, he was low in mood. His temperature was 38.5°C, his blood pressure was 118/76 mmHg and his respiratory rate was 14 breaths per minute. His oxygen saturation was 96%, breathing air (94–99). He had a widespread eruption consisting of vesicles and pustules. Examination of his chest revealed a few wheezes but no crackles.

Investigations: • haemoglobin 128 g/L (130–180) platelet count 189 109/L(150–400) • white cell count 15.2 109/L (4.0–11.0) neutrophil count 13.8 109/L (1.5–7.0) lymphocyte count 1.0 109/L (1.5–4.0) chest X-ray normal What is the most appropriate next management step? • A antipyretic • B intravenous aciclovir • C intravenous flucloxacillin • D oral valaciclovir • E varicella zoster hyperimmune globulin

• B

• A 72-year-old woman presented with weakness of her right leg and numbness in her right hand. She had a 20-year history of rheumatoid arthritis and also had long-standing type 2 diabetes mellitus and hypertension. Her medication comprised gliclazide, amlodipine, simvastatin and sodium aurothiomalate. • On examination, she had chronic rheumatoid changes in her hands and feet, and subcutaneous nodules at her elbows. She had bruises in the nailfolds, and her right index fingertip was cold and discoloured. Neurological examination revealed altered sensation in all of the fingers of her right hand. She was unable to dorsiflex her right ankle. Investigations: • erythrocyte sedimentation rate 110 mm/1st h (<30) • antinuclear antibodies positive at 1:80 dilution • c-ANCA negative • p-ANCA positive What is the most likely cause of her symptoms? • A amyloidosis • B diabetes mellitus • C rheumatoid vasculitis • D systemic lupus erythematosus • E Wegener‟s granulomatosis •

• Answer Key: C

• A 42-year-old man was admitted to hospital with severe abdominal pain. His alcohol intake was 18 units per week. His serum amylase level was raised at 1346 U/L (60–180) and a diagnosis of acute pancreatitis was made. There was no evidence of gallstones. He made an uncomplicated recovery. Investigations (after recovery): • fasting plasma glucose 5.7 mmol/L (3.0–6.0) • serum cholesterol 5.8 mmol/L (<5.2) • serum LDL cholesterol 3.41 mmol/L (<3.36) • serum HDL cholesterol 0.96 mmol/L (>1.55) • fasting serum triglycerides 22.63 mmol/L (0.45–1.69) What is the most appropriate treatment to reduce his risk of recurrent pancreatit • A atorvastatin • B ciprofibrate • C ezetimibe • D nicotinic acid • E omega-3-marine triglycerides

• Answer Key: B

• A 65-year-old man had a 10-year history of dialysis-dependent renal failure caused by renovascular disease. He began taking warfarin because of recurrent arteriovenous fistula thrombosis. One month later, he presented with livedo reticularis on his trunk, and areas of painful ulceration on his shins. Investigations: • haemoglobin 102 g/L (130–180) white cell count 5.4 109 /L (4.0–11.0) eosinophil count 0.78 109 /L (0.04–0.40) • platelet count 478 109 /L (150–400) • international normalised ratio 1.9 (<1.4) serum corrected calcium 2.58 mmol/L (2.20–2.60) serum phosphate 1.9 mmol/L (0.8–1.4) • plasma parathyroid hormone 18.5 pmol/L (0.9–5.4) • anticardiolipin antibodies: • immunoglobulin G 32 U/mL (<23) • immunoglobulin M 24 U/mL (<11) What is the most likely diagnosis? • A antiphospholipid antibody syndrome • B calciphylaxis • C cholesterol embolisation • D coumarin necrosis • E thromboembolism from arteriovenous fistula •

• Answer key C

• A 35-year-old woman with early stage IV chronic kidney disease (glomerular filtration rate 15–29 mL/min) was being considered for erythropoietin therapy. • On examination, her blood pressure was 140/90 mmHg and she had an arteriovenous fistula in situ for planned haemodialysis. Investigations: haemoglobin 95 g/L (115–165) MCV 84 fL (80–96) What is the most likely outcome of erythropoit. therapy? • A improved blood pressure control • B improved exercise tolerance • C increased ventricular hypertrophy • D reduced likelihood of red cell aplasia • E stabilisation of renal function

• 3. Answer Key: B

A 51-year-old woman presented with a 2-year history of intermittent episodes of arthralgia, rash and fevers. She complained of increasing fatigue, breathlessness and swollen ankles over the previous 6 months. On examination, she had a purpuric rash on the lower extremities and a right-sided pleural effusion. Urinalysis showed protein 3+, blood 1+. • Investigations: • erythrocyte sedimentation rate 140 mm/1st h (<30) • serum creatinine 140 µmol/L (60–110) • serum complement C4 <5 mg/dL (15–50) • antinuclear antibodies positive at 1:600 dilution (negative at 1:20 dilution) rheumatoid factor 90 kIU/L (<30) • What is the most likely diagnosis? • A Henoch–Schönlein purpura • B microscopic polyangiitis • C mixed cryoglobulinaemia • D systemic lupus erythematosus • E systemic rheumatoid disease

• 4. Answer Key: D

• 5. A 27-year-old woman presented with a rightsided thyroid swelling with associated cervical lymphadenopathy. • What is the most likely cause? • A anaplastic carcinoma • B follicular adenoma • C follicular carcinoma • D Hashimoto’s thyroiditis • E papillary carcinoma

• 5. Answer Key: E

A previously well 64-year-old woman presented with haemoptysis. Biopsy of a right upper-lobe endobronchial lesion confirmed the diagnosis of non-small cell bronchogenic carcinoma. • Investigations: • forced expiratory volume in 1 s 61% of predicted • forced vital capacity 78% of predicted • CT scan of chest and abdomen 3.5-cm mass in right upper lobe with ipsilateral hilar lymph node enlargement; no disease below the diaphragm • PET scan increased uptake in right upper lobe and ipsilateral hilar nodes • What is the most appropriate management? • A chemotherapy • B palliative radiotherapy • C pneumonectomy • D radical radiotherapy • E radiofrequency ablation

• Answer Key: C

• 6. A 77-year-old man presented with anaemia and diarrhoea. He had undergone emergency partial gastrectomy for a bleeding ulcer 9 months previously. He was having maintenance proton pump inhibitor therapy. • Investigations: endoscopy active, benign-looking stomal ulceration • What is the most appropriate next investigation? • A barium follow-through • B endoscopic ultrasound of gastric remnant • C fasting serum gastrin concentration • D Helicobacter pylori serology • E prolonged glucose tolerance test

• 6. Answer Key: C

• A clinical trial compared medical versus surgical treatment for stable angina. A large number of patients withdrew from the study. Which type of analysis should be used to estimate the likely benefits in similar groups of patients in future? • A intention-to-treat • B meta-analysis • C on-treatment • D post-hoc • E sensitivity

• A

A 62-year-old man presented with a 2-day history of pleuritic right lower chest pain associated with a cough productive of red–brown sputum. He had a 1-year history of microscopic polyangiitis which had initially presented with pulmonary haemorrhage and rapidly progressive glomerulonephritis. He had responded well to plasma exchange, methylprednisolone and cyclophosphamide before being switched to azathioprine at 3 months. At his clinic visit 3 weeks previously, his serum C-reactive protein had been 5 mg/L (<10) and his eGFR 28 mL/min (>60). His current medication was prednisolone 7.5 mg daily and azathioprine 100 mg daily. On examination, he was comfortable at rest. His temperature was 37.8°C, his blood pressure was 106/78 mmHg and his respiratory rate was 18 breaths per minute. There was bronchial breathing and a pleural rub at the right lung base but no crackles. Investigations: • haemoglobin 120 g/L (130–180) white cell count 9.4 109 /L (4.0–11.0) platelet count 256 109 /L (150–400) serum C-reactive protein 56 mg/L (<10) estimated glomerular filtration rate (eGFR) 26 mL/min (>60) arterial blood gases, breathing air: • PO2 10.6 kPa (11.3–12.6) • PCO2 4.2 kPa (4.7–6.0) • pH 7.44 (7.35–7.45) • H+ 36 nmol/L (35–45) • bicarbonate 18 mmol/L (21–29) • chest X-ray patchy shadowing at right base What is the most appropriate treatment? • A intravenous cefotaxime and clarithromycin • B intravenous cefotaxime, clarithromycin and co-trimoxazole • C intravenous clarithromycin, amoxicillin and co-trimoxazole • D oral amoxicillin and clarithromycin • E oral amoxicillin, clarithromycin and co-trimoxazole

• Answer key: D

• 7. A 70-year-old man presented with a 2-week history of persistent fever. Some weeks previously, he had undergone colonoscopy and biopsy for a suspected carcinoma of the colon, and was awaiting surgery. He had a history of moderate mitral regurgitation caused by mitral valve prolapse. •

Investigations: echocardiogram a vegetation on the anterior leaflet of the mitral valve.

What is the most likely causative organism? • A Bartonella henselae • B Staphylococcus aureus • C Streptococcus bovis • D Streptococcus viridans • E Yersinia enterocolitica

• 7. Answer Key: C

• 8. A 37-year-old woman with a history of depression was brought to hospital having been found in a state of collapse. She had written a suicide note, and had an empty bottle of amitriptyline in her jacket. On examination, her pulse was 135 beats per minute and her blood pressure was 105/50 mmHg. Investigations: • serum potassium 4.5 mmol/L (3.5–4.9) • serum bicarbonate 18 mmol/L (20–28) • serum urea 8.5 mmol/L (2.5–7.0) • serum creatinine 110 µmol/L (60–110) • ECG sinus tachycardia; QRS duration of 135 ms; bursts of non-sustained ventricular tachycardia What is the most appropriate initial intravenous treatment? • A amiodarone • B esmolol • C magnesium • D sodium bicarbonate • E sodium chloride 0.9%

• 8. Answer Key: D

• 9. A 21-year-old man presented after he had injured his back, resulting in hemisection of his spinal cord at T10 level. What is most likely to be present below the level of the lesion 2 months after the injury? • • A contralateral gross wasting • B contralateral loss of pain and temperature sensation • C contralateral loss of proprioception • D contralateral upper motor neurone weakness • E ipsilateral gross wasting

• 9.

Answer Key: B

• • • • • • • • • • • • • • • • • • • • • • •

A 46-year-old man with profuse diarrhoea was admitted to measure his daily stool weight for 3 days, with a further measurement on day 4 when fasting. He had previously had a normal colonoscopy and small bowel meal. Investigations: serum sodium 135 mmol/L (137–144) serum potassium 2.4 mmol/L (3.5–4.9) serum urea 5.8 mmol/L (2.5–7.0) serum creatinine 78 µmol/L (60–110) daily stool weight: day 1 1450 g (<200) day 2 1200 g day 3 1560 g day 4 (fasting) 1400 g What is the most likely diagnosis? A coeliac disease B irritable bowel syndrome C lactose intolerance D pancreatic insufficiency E VIPoma

• Answer Key: E

• 11. A 79-year-old woman was admitted for elective hip replacement surgery. On examination, she was pale. There was a 2-cm splenomegaly and there were small discrete axillary lymph nodes. • Investigations: • haemoglobin 107 g/L (115–165) white cell count 34.5 109/L (4.0–11.0) platelet count 183 109/L. • What is the most likely diagnosis? • A acute myeloid leukaemia • B chronic lymphocytic leukaemia • C chronic myeloid leukaemia • D myelodysplasia • E myelofibrosis

• 11. Answer Key: B

• A 60-year-old man with diet-controlled type 2 diabetes mellitus gave a 3-month history of numbness and “pins and needles” sensations in his feet. He also felt unsteady. Two years previously, he had undergone surgery for carcinoma of the stomach. • On examination, he had mild weakness of hip flexion. His ankle reflexes were absent and all of his other limb reflexes were diminished. His plantar responses were extensor. There was diminished sensation to pinprick and light touch below the knees, vibration sense was impaired at the ankles, but joint position sense was normal. Romberg‟s test was positive. • • • • • •

What is the most likely diagnosis? A diabetic amyotrophy B paraneoplastic sensory ataxic neuropathy C spinal arteriovenous malformation D subacute combined degeneration of the cord E syringomyelia

• Answer Key: D

• A 23-year-old man presented to the emergency department with acute severe asthma. His regular medication was inhaled salbutamol and beclometasone, and oral theophylline. • On examination, he was dyspnoeic and in distress. His pulse was 104 beats per minute, his blood pressure was 108/64 mmHg and his respiratory rate was 40 breaths per minute. Auscultation of his lungs revealed expiratory wheezes throughout. He was unable to perform a peak expiratory flow reading and he failed to respond to initial therapy with oxygen, nebulised salbutamol and ipratropium bromide, and oral prednisolone 40 mg. • What is the most appropriate next step in treatment? • A intravenous aminophylline • B intravenous hydrocortisone • C intravenous magnesium sulphate • D non-invasive ventilation • E subcutaneous terbutaline

• Answer Key: C

•

A 20-year-old Chinese woman presented with a 2-week history of ankle swelling. She had suffered from asthma since childhood and was taking paracetamol regularly for pains in her wrists and knees. She was also taking an oral contraceptive. Examination showed bilateral pitting oedema to mid-shin level. Her blood pressure was 148/92 mmHg and her heart sounds were normal. Chest, abdominal and neurological examinations were normal. Urinalysis showed blood 1+ and protein 4+, but was negative for glucose. • • • • • • • • •

Investigations: haemoglobin 118 g/L (115–165) MCV 79 fL (80–96) white cell count 3.3 109 /L (4.0–11.0) serum sodium 136 mmol/L (137–144) serum potassium 4.1 mmol/L (3.5–4.9) serum urea 5.7 mmol/L (2.5–7.0) serum creatinine 73 µmol/L (60–110) 24-h urinary protein 7.8 g (<0.2)

• • • • • •

What is the most important diagnostic investigation? A anti-glomerular basement membrane antibodies B anti-neutrophil cytoplasmic antibodies C antinuclear antibodies D antistreptolysin O titre E serum complement levels

• Answer Key: C

• 12. A 74-year-old woman presented with distressing restlessness in her legs, particularly at night. She usually had to get out of bed several times every night to reduce her symptoms, and her sleep was being disturbed. • What is the most appropriate treatment? A clonazepam. B co-beneldopa . C propranolol . D quinine. E ropinirole.

• 12. Answer Key: E • is a non-ergoline dopamine agonist. It is used in the treatment of Parkinson's disease. Ropinirole is one of three medications approved by the FDA to treat Restless Legs Syndrome, the other two being pramipexole and gabapentin. • Ropinirole can cause nausea, dizziness, hallucinations, orthostatic hypotension, and sudden sleep attacks during the daytime

• 13. A 34-year-old woman with a 6-year history of Sjögren’s syndrome found that she was 14 weeks pregnant. Which autoantibody in this condition is associated with an increased risk of congenital heart block in the fetus? • A anticardiolipin • B anticentromere • C anti-La . • D anti-neutrophil cytoplasmic (ANCA) • E anti-Ro

• 13. Answer Key: E

• 14. A 40-year-old woman presented for review of her asthma. Her current treatment was inhaled beclometasone 800 micrograms per day and inhaled salbutamol as required via a metered-dose inhaler. She used the salbutamol two or three times a day and woke at night wheezing once or twice a week. What is the most appropriate management? • A add montelukast • B add salmeterol • C change to a powder inhaler • D double the dose of beclometasone • E maintain current treatment

• 14. Answer Key: B

• 15. A 21-year-old woman presented with watery diarrhoea and cramping abdominal pain 5 days after arriving in Mexico. On examination, her temperature was 37.8°C and there was mild abdominal tenderness. There was some mucus in the stools, but no blood. What is the most likely pathogen? • A Aeromonas hydrophila • B Entamoeba histolytica • C Escherichia coli • D Giardia lamblia • E rotavirus

• 15. Answer Key: C

• 16. A 27-year-old man was referred with an acute hepatic illness. Which laboratory finding would indicate the need for inpatient management? • A aspartate aminotransferase:alanine aminotransferase ratio >1.0 • B prothrombin time 24 s (11.5–15.5) • C serum alanine aminotransferase 1400 U/L (5–35) • D serum alkaline phosphatase 1800 U/L (45–105) • E serum conjugated bilirubin 110 µmol/L (<3.4)

• 16. Answer Key: B

• 17. A 75-year-old woman presented with a 6-month history of an ulcer over the right ankle. She had a history of right deep venous thrombosis 5 years previously. On examination, she had a superficial sloughing ulcer 6 cm in diameter over the medial malleolus. What is the most appropriate investigation? • A ankle–brachial pressure index • B bacteriological swab of the ulcer • C bilateral lower limb arteriography • D right leg venography • E venous duplex ultrasound scan

• 17. Answer Key: A

• 18. A 66-year-old woman presented with a 4week history of cough and haemoptysis. She was a lifelong non-smoker. Investigations: chest X-ray right upper lobe tumour and an enlarged right hilum, bronchoscopy normal What is the most likely histological diagnosis? • A adenocarcinoma • B carcinoid tumour • C large cell carcinoma • D small cell carcinoma • E squamous cell carcinoma

• 18. Answer Key: A

• A 75-year-old man presented to his general practitioner with worsening palpitations and dyspnoea on exercise. He had lost about 3 kg in weight during the past 2 months. He had developed a coarse tremor in both hands. His past medical history included ischaemic heart disease and recurrent supraventricular tachycardia. He was taking aspirin 75 mg daily, simvastatin 40 mg daily, bisoprolol 5 mg daily, ramipril 10 mg daily, amiodarone 200 mg daily, glyceryl trinitrate spray as required, and warfarin. • On examination, there was a small palpable goitre. He had a tremor, warm hands, bilateral upper eyelid retraction and proptosis. • • Investigations: • plasma thyroid-stimulating hormone <0.1 mU/L (0.4–5.0) • plasma free T4 95.0 pmol/L (10.0–22.0) • plasma free T3 35.2 pmol/L (5.0–10.0) • ECG sinus tachycardia • • What is the most likely cause of this patient‟s thyroid dysfunction? • A amiodarone-induced thyrotoxicosis • B Graves‟ disease • C Reidel‟s thyroiditis • D solitary toxic nodule • E toxic multi-nodular goitre

• Answer Key: B

• 19. A 65-year-old man presented with an acute coronary syndrome. He was advised to take clopidogrel in addition to aspirin, atenolol, glyceryl trinitrate and low-molecularweight heparin. What is the predominant mechanism through which clopidogrel inhibits platelet aggregation? • A it enhances the effect of circulating antithrombin • B it inhibits binding of adenosine diphosphate • C it inhibits cyclooxygenase-1 • D it irreversibly binds glycoprotein IIb/IIIa receptor sites • E it prevents production of thromboxane A2

• 19. Answer Key: B

• 20. In a clinical trial to assess the effectiveness of a new antihypertensive drug, subjects were randomised to be treated with either the new drug or an existing standard antihypertensive one. The main outcome criterion was the blood pressure after 2 months of treatment. What is the most appropriate statistical technique to compare mean blood pressure between the groups? • A chi-squared test • B Mann Whitney U test • C Pearson’s correlation coefficient • D regression analysis • E two-sample t-test

• 20. Answer Key: E

• 21. A 21-year-old woman, undergoing chemotherapy for non-Hodgkin’s lymphoma, was in contact with her nephew for 2 hours on the day that he developed a chickenpox rash. Investigations: varicella serology negative What is the most appropriate management? • A advise her to seek treatment if she develops a chickenpox rash • B interrupt chemotherapy for 2 weeks • C oral aciclovir 800 mg five times daily for 1 week • D varicella immunisation • E varicella zoster immunoglobulin

• 21. Answer Key: E

• 23. A 65-year-old woman presented with generalised arthralgia for the previous 2 weeks. She had a past medical history of urinary tract infections. She was advised to take a non-steroidal anti-inflammatory drug. On examination, her blood pressure was 139/98 mmHg and she had pitting oedema below the knees. Investigations: serum creatinine 458 µmol/L (60–110), 24-h urinary total protein 2.3 g (<0.2) What is the most likely cause of the renal impairment? • A acute tubular necrosis • B immunoglobulin A (IgA) nephropathy • C interstitial nephritis • D membranous glomerulonephropathy • E papillary necrosis

• 23. Answer Key: C

• 25. A 25-year-old woman presented with increasingly severe headache and two generalised fits 36 hours after the normal vaginal delivery of her first baby at 40 weeks’ gestation. She had been treated with epidural analgesia during labour. On examination, her temperature was 37.6°C, she was drowsy, there was a mild left hemiparesis and both plantar responses were extensor. What is the most likely diagnosis? • • • • •

A B C D E

bacterial meningitis cortical thrombophlebitis pre-eclamptic toxaemia subarachnoid haemorrhage viral encephalitis

• 25. Answer Key: B

• 26. A 37-year-old woman with breast cancer had a family history of breast and ovarian cancer. Molecular genetic testing revealed a BRCA1 mutation. What is the normal function of BRCA1? • A angiogenesis • B apoptosis • C cell adhesion • D promotion of mitosis • E tumour suppression

• 26. Answer Key: E

• 27. A 66-year-old man, who was undergoing maintenance haemodialysis through a subcutaneous tunnelled catheter, presented with fever, chills and rigors during haemodialysis. On examination, his temperature was 38.6°C, his pulse was 105 beats per minute and his blood pressure was 100/60 mmHg. Examination of his respiratory and cardiovascular systems was normal. • What is the most likely cause of his infection? • A Escherichia coli • B Pseudomonas aeruginosa • C Staphylococcus epidermidis • D Streptococcus pneumoniae • E Streptococcus viridans

• 27. Answer Key: C

• 28. A 35-year-old woman presented with a 6-month history of episodes of sweating, joint pain and headaches. On examination, her blood pressure was 160/90 mmHg. A clinical diagnosis of acromegaly was suspected. Investigations: fasting plasma glucose 8.1 mmol/L (3.0–6.0) Which additional investigation would confirm the diagnosis? • A fasting growth hormone • B growth hormone suppression test • C insulin-like growth factor 1 • D insulin tolerance test • E MR scan of pituitary

• 28. Answer Key: B

• 29. A 54-year-old right-handed woman presented with the sudden onset of reading difficulties. Investigations: CT scan of head a recent left parietal lobe infarct. Which additional feature is most likely to be present? • A acalculia • B confabulation • C cortical deafness • D expressive dysphasia • E homonymous hemianopia

• 29. Answer Key: A

• 30. A 75-year-old man presented with a 2-day history of recurrent fever and a cough productive of purulent sputum. Investigations: chest X-ray right lower lobe pneumonia • What additional finding would most indicate a poor prognosis? • A respiratory rate of 25 breaths per minute • B serum sodium concentration of 130 mmol/L (137–144) • C serum urea concentration of 9.0 mmol/L (2.5–7.0) • D systolic blood pressure of 95 mmHg • E temperature of 38.5°C

• 30. Answer Key: C

• 31. A 30-year-old woman presented with a 6-month history of tremor and difficulty in speaking. On examination, she was found to have increased muscle tone in all four limbs, bradykinesia and 4-cm hepatomegaly. Which laboratory finding would best support a diagnosis of Wilson’s disease? • A increased incorporation of radioactive copper into caeruloplasmin • B low hepatic copper content • C low serum caeruloplasmin concentration • D low serum copper concentration • E low urine copper concentration

• 31. Answer Key: C

• A 65-year-old man presented with a 1-week history of increasing drowsiness and confusion. He rapidly deteriorated and was intubated, ventilated and transferred to the intensive care unit. He had a history of recurrent chest infections in the previous year, treated with several courses of oral antibiotics. He had developed progressive difficulty in climbing the stairs over the previous 5 years. His father had died of „respiratory failure‟ in his mid-fifties. On examination, he had bilateral ptosis and facial weakness. His eye movements were normal. His neck flexors were weak. He had predominantly distal weakness affecting his arms and legs. The deep tendon reflexes were absent. The plantar responses were flexor. Sensory examination was normal. • What is the most likely underlying diagnosis? • A Becker‟s muscular dystrophy • B Guillain–Barré syndrome • C motor neurone disease • D myasthenia gravis • E myotonic dystrophy

• Answer Key: E

• 33. A 72-year-old man presented with a 2-day history of pain and swelling of the right knee. Analysis of synovial fluid from the right knee confirmed the presence of calcium pyrophosphate crystals. What is the microscopic appearance of these crystals? • A needle-shaped with negative birefringence • B needle-shaped with no birefringence • C needle-shaped with positive birefringence • D rhomboid with negative birefringence • E rhomboid with positive birefringence

• 33. Answer Key: E

• 34. The half-life of a novel anti-obesity drug exhibiting first-order kinetics was calculated to be 4 hours. What percentage of the drug will be eliminated 20 hours after ingestion? • A 75% • B 80% • C 90% • D 97% • E 100%

• 34. Answer Key: D

• 35. A 16-year-old girl presented with non-scaly, discrete areas of hair loss on the scalp. She had a past history of atopic eczema and had a number of depigmented areas on her hands and around her eyes. What is the most likely diagnosis? • A alopecia areata • B hypothyroidism • C lupus erythematosus • D seborrhoeic dermatitis • E trichotillomania

• 35. Answer Key: A

• 37. A 38-year-old woman required extraction of her wisdom teeth. She gave a history of haemorrhage after a dental extraction 10 years previously, when she had required suturing. There had been no history of excessive bleeding before this. What is the most likely diagnosis? • A factor V Leiden • B factor IX deficiency • C factor XII deficiency • D primary antiphospholipid syndrome • E von Willebrand’s disease

• 37. Answer Key: E

• 38. A 25-year-old intravenous drug user presented with an injection site abscess. On examination, his temperature was 38.5°C and there was a pansystolic murmur. Which organism is most likely to be cultured from both the abscess and the blood? • A Clostridium novyi • B Klebsiella pneumoniae • C Staphylococcus aureus • D Staphylococcus epidermidis • E Streptococcus viridans

• 38. Answer Key: C

A 72-year-old man presented following an episode of collapse. There had been two similar episodes recently, each lasting about 1 minute. He had experienced an anterior myocardial infarction 4 years previously. On examination, he was orientated and symptom-free with a regular pulse of 80 beats per minute. His blood pressure was 140/80 mmHg and the apex beat was displaced to the left. There was an apical systolic murmur. There were no signs of trauma. ECG showed sinus rhythm, anterior Q waves and anterior ST segment elevation without reciprocal depression. • What is the most likely diagnosis? • A acute anterior myocardial infarction • B cerebral embolism • C epilepsy • D pulmonary embolism • E ventricular tachycardia

• 39. Answer Key: E

• 41. A 33-year-old man presented with a 6-month history of cough and breathlessness that tended to worsen as the week progressed and improve when he went on holiday. He was a lifelong non-smoker and worked as a paint sprayer in a car factory.Investigations: chest X-ray normal. Which further investigation would be most useful in establishing a diagnosis? • A cardiorespiratory exercise test • B histamine challenge • C immunoglobulin E antibody to isocyanate • D serial peak expiratory flow rate measurements • E transfer factor

• D

• 43. A 30-year-old man presented with increasing breathlessness and wheeze. He smoked five cigarettes per day. Investigations: • serum α1-antitrypsin 0.12 g/L (1.1–2.1) • forced expiratory volume in 1 s 0.85 L (3.4–5.1) • forced vital capacity 4.75 L (4.2–6.5) • transfer factor for CO (TLCO) 4.1 mmol/min/kPa (7.1–12.7) • • • • • •

Which protease inhibitor genotype is present? A MM B MZ C SS D SZ E ZZ

• E

• 44. A 25-year-old man presented with a 3-month history of hearing two people commenting on his actions. For the past 2 years, he had become increasingly withdrawn and had neglected his self-care. He had graduated from university at 21 years of age, but had never been employed and had few friends. He had taken an overdose of paracetamol 2 months previously. He had smoked cannabis regularly for 5 years. He drank 60 units of alcohol weekly. On examination, he made poor eye contact and his speech was disjointed. • • • • • •

What is the most likely diagnosis? A alcoholic hallucinosis B borderline personality disorder C cannabis-induced psychosis D paranoid schizophrenia E psychotic depression

• D

• 45. A 42-year-old man with a 20-year history of ulcerative colitis was advised that he was at increased risk of developing cancer of the colon. He was taking sulfasalazine with intermittent courses of corticosteroids for acute exacerbations. He had also tried various diets in the past, including a lactosefree diet and a low-fibre diet. Which factor is most likely to increase his risk of developing cancer of the colon? • A chronic colonic inflammation • B he is likely to be a carrier for the caspase recruitment domain-containing protein 15(CARD 15) gene mutation • C he is likely to have the APC (adenomatous polyposis coli) gene • D long-term immunosuppression • E reduced intake of dietary fibre

• A

• 46. A 75-year-old woman presented with a 2-month history of generalised malaise and headaches that had disturbed her sleep. For the past 24 hours, she had been unable to see with her right eye. She had a past medical history of glaucoma and was using regular timolol eye drops. Fundoscopic examination revealed a swollen, pale right optic disc and a normal left optic disc. • What is the most likely diagnosis? • A central retinal vein occlusion • B closed-angle glaucoma • C giant cell arteritis • D optic neuritis • E raised intracranial pressure

• C

• 48. A 78-year-old man presented after several falls. He had a 20-year history of rheumatoid arthritis and his only medication was sulfasalazine. On examination, he had been incontinent of urine and had difficulty in recalling recent events. He had chronic rheumatoid hand deformities, a right-sided grasp reflex and bilateral extensor plantar responses. He had difficulty in rising from a chair, walked with small paces and was unsteady on turning, having to hold on to his wife. • What is the most likely diagnosis? • A Alzheimer’s disease • B cervical myelopathy • C multi-infarct dementia • D normal pressure hydrocephalus • E Parkinson’s disease

• D

• 51. A 28-year-old man presented with weight loss, abdominal distension, flatulence and foul-smelling diarrhoea for 1 month following a visit to India. • Investigations: • endomysial antibodies negative • stool cultures and microscopy negative • What is the most likely diagnosis? A acute HIV seroconversion illness B coeliac disease C giardiasis D hookworm infection (ancylostomiasis) E viral gastroenteritis

• c

• 52. A 45-year-old man presented with recurrent epistaxis. Examination revealed telangiectasia on his lips and in the mouth. A diagnosis of hereditary haemorrhagic telangiectasia was made. • A B C D E

What is the most likely mode of inheritance? autosomal dominant autosomal recessive mitochondrial inheritance sporadic mutation X-linked recessive

• A

• 53. A 37-year-old man with hypertension attended for outpatient review. He had previously been treated with several drugs that he could not name. He had been obliged to stop taking each of these because of unacceptable adverse effects, which included lethargy, ankle swelling and severe gum swelling and bleeding. He was currently taking bendroflumethiazide. On examination, his blood pressure remained elevated at 168/96 mmHg. In view of his previous history of adverse drug effects, what is the most appropriate additional therapy? A B C D E

amlodipine bisoprolol diltiazem minoxidil perindopril

• E

• 54. A 17-year-old boy presented with a non-blanching rash over his legs, a swollen knee and painless frank haematuria. Urine dipstick analysis showed blood 3+, protein 1+. • Investigations: serum creatinine 210 µmol/L (60–110) • urine culture negative • ultrasound scan of kidneys normal Which glomerular abnormality is most likely to be present at renal biopsy? A focal and segmental sclerosis B foot process fusion C linear deposition of IgG on the basement membrane D mesangial deposition of IgA E thickening of basement membranes

• D

• 55. A 77-year-old man presented with increasing pains around the low back and lower limb girdle. He had recently presented with symptoms of hesitancy and postmicturition dribbling. Investigations: • erythrocyte sedimentation rate 28 mm/1st h (<20) • serum corrected calcium 2.34 mmol/L (2.20–2.60) • serum phosphate 0.8 mmol/L (0.8–1.4) • serum alkaline phosphatase 2985 U/L (45–105) • serum prostate-specific antigen 6 μg/L (<4) • A B C D E

What is the most likely cause of this man’s pain? insufficiency fracture of the pelvis osteomalacia Paget’s disease of the pelvis polymyalgia rheumatica prostatic carcinoma with metastases

• C

• 56. A healthy 19-year-old medical student was asked to perform a Valsalva manoeuvre (forced expiration against a closed glottis) for demonstration purposes in a physiology class. • What is the most likely initial haemodynamic response? A decreased jugular venous pressure B decreased pulse C decreased systolic blood pressure D decreased venous return to the heart E increased cardiac output

• D

• 57. A 16-year-old boy with type 1 diabetes mellitus was treated with a biphasic insulin preparation but achievement of good blood glucose control proved difficult. He was offered treatment with the insulin analogue, insulin lispro. Which characteristic of insulin lispro might improve his glycaemic control? A low incidence of hypoglycaemia B low incidence of lipoatrophy at the injection site C low risk of immunogenic reaction D rapid onset of action E small injection volume

• D

• 58. A 16-year-old boy presented within half an hour of falling. His parents reported that he had fallen and hit the right side of his head on the ground. He had lost consciousness for a few seconds and then made a full recovery. On examination, he was fully cooperative and had no focal neurological signs. Two hours later, his conscious level deteriorated. • What is the most likely diagnosis? A cerebral oedema B diffuse axonal injury C extradural haematoma D subarachnoid haemorrhage E subdural haematoma

• C

• 59. A 17-year-old girl presented with a single, painless, enlarged cervical lymph node. She was asymptomatic. Investigations: • chest X-ray enlarged mediastinal lymph nodes • What is the most likely diagnosis? A angioimmunoblastic T-cell lymphoma B extramedullary plasmacytoma C follicular B-cell non-Hodgkin’s lymphoma D Hodgkin’s lymphoma E mantle cell lymphoma

• D

• 60. A 55-year-old man was found to have an abnormal chest X-ray at an employment medical check. He was well and had no respiratory symptoms or signs. He smoked 10 cigarettes per day and had been heavily exposed to asbestos when working in a shipyard 30 years previously. Which abnormality is most likely to be seen on his chest X-ray? • A asbestosis • B bronchial carcinoma • C calcified pleural plaques • D diffuse pleural thickening • E mesothelioma

• C

On removal of the renal arterial clamp following a donor kidney transplantation, the surgeon noted changes suggestive of hyperacute rejection. • Which immunoglobulin is likely to be responsible? A IgA B IgD C IgE D IgG E IgM

• D

A 46-year-old man presented within 1 hour of ingesting 40 tablets of slow-release theophylline. What is the most appropriate initial management? • A activated charcoal • B alkaline diuresis • C gastric lavage • D observation only • E whole bowel irrigation

• A

A 17-year-old boy presented with breathlessness and night sweats. Investigations; confirmed a diagnosis of Burkitt’s lymphoma. What is the most likely underlying abnormality of gene expression? A expression of BCR-ABL B loss of p53 C over-expression of BCL-2 D over-expression of c-MYC E over-expression of JAK2

• D

A 50-year-old man was admitted to the coronary care unit. In which circumstance would it be most appropriate to use a glycoprotein IIb/IIIa receptor inhibitor? A acute life-threatening pulmonary embolism B acute myocardial infarction with ST segment elevation C continuing pain following thrombolytic therapy D continuing pain with positive troponin and awaiting coronary angiography E left ventricular thrombus post myocardial infarction

• D

• 66. A 45-year-old man had recurrent nephrolithiasis. Renal function tests and serum calcium measurements were normal. • Investigations: • 24-h urinary calcium 15.0 mmol (2.5–7.5) • 24-h urinary urate 3.0 mmol (<3.6) • 24-h urinary oxalate 0.20 mmol (0.14–0.46) • 24-h urinary citrate 2.0 mmol (0.3–3.4) • What is the most useful therapy to reduce stone formation? A allopurinol B dietary calcium restriction C penicillamine D potassium citrate E thiazide diuretic

• E

• A 29-year-old woman was admitted to hospital with a 12-hour history of severe throbbing headache and right-sided weakness. She was otherwise well with no significant past medical history and was taking no medication apart from the oral combined contraceptive. She denied any regular illicit drug use but admitted to taking an „ecstasy‟ tablet 2 days previously. Examination confirmed decreased power on the right, with brisk tendon reflexes and an extensor plantar response. Her pupils were equal and reactive to light. Fundoscopy was normal. Investigations: • CT scan of head (18 h after symptom onset) no evidence of haemorrhage • cerebrospinal fluid: • opening pressure 200 mmH2O (50–180) • total protein 0.41 g/L (0.15–0.45) • • • • • •

What is the most likely diagnosis? A cerebral infarction B cerebral venous thrombosis C hemiplegic migraine D idiopathic intracranial hypertension E subarachnoid haemorrhage

• Answer Key: B

• 67. A 42-year-old man was found to have abnormal liver function tests. He had had ulcerative colitis for 15 years. He had been treated initially with mesalazine but this had been stopped 8 years previously when his disease had gone into remission. Investigations: • serum albumin 40 g/L (37–49) • serum total bilirubin 15 µmol/L (1–22) • serum alanine aminotransferase 63 U/L (5–35) • serum aspartate aminotransferase 41 U/L (1–31) • serum alkaline phosphatase 741 U/L (45–105) • serum gamma glutamyl transferase 221 U/L (<50) • What is the most likely cause of these blood results? A autoimmune hepatitis B fatty liver C liver metastases D primary biliary cirrhosis E primary sclerosing cholangitis

• E

• 68. A 32-year-old woman returned from a holiday in the Mediterranean with a suntan and numerous hypopigmented, slightly scaly lesions on the neck and upper trunk.What is the most likely diagnosis? • A chronic plaque psoriasis • B discoid eczema • C pityriasis rosea • D pityriasis versicolor • E seborrhoeic dermatitis

• D

• 69. A 72-year-old woman with rheumatoid arthritis presented with dysuria of 2 days’ duration. Her regular medication comprised methotrexate, prednisolone and paracetamol. On examination, she had a body mass index of 34 kg/m2 (18–25). Investigations: urine culture coliforms, sensitive to ciprofloxacin. Which condition is most likely to be precipitated by the use of ciprofloxacin? • A gastric ulceration • B glucose intolerance • C hepatitis • D pneumonitis • E tendinopathy

• E

• 70. A 50-year-old man presented with a 24-hour history of agitation, confusion and suicidal thoughts. He had started VADchemotherapy (vincristine 0.4 mg daily, doxorubicin 9 mg/m2 daily and dexamethasone 40 mg daily) 4 days previously, following a diagnosis of multiple myeloma. What is the most likely cause of his symptoms? • A adjustment disorder • B confusion secondary to sepsis • C corticosteroid psychosis • D reactive depression • E vincristine encephalopathy

• C

A 30-year-old doctor presented following a needlestick injury sustained while treating a patient with recently diagnosed HIV infection. The patient was hepatitis C negative and had been vaccinated against hepatitis B virus, and was taking no antiretroviral treatment. What is the most appropriate post-exposure prophylaxis for the doctor? • A single-drug antiretroviral treatment for 1 month • B single-drug antiretroviral treatment for 3 months • C three-drug antiretroviral treatment for 1 month • D three-drug antiretroviral treatment for 3 months • E two-drug antiretroviral treatment for 1 month

• C

A 65-year-old woman presented with a 12-hour history of the sudden onset of gait unsteadiness, vomiting and headache, followed by increasing drowsiness. What is the most likely diagnosis? • A acute cerebellar haemorrhage • B acute subdural haemorrhage • C frontal subdural empyema • D herpes simplex encephalitis • E pituitary apoplexy

• A

A 75-year-old woman with hypertension had been treated with bendroflumethiazide for the past 5 years. On examination, her blood pressure was 125/78 mmHg. Investigations: • serum sodium 140 mmol/L (137–144) • serum potassium 3.2 mmol/L (3.5–4.9) • serum creatinine 67 µmol/L (60–110) • What is the most likely mechanism for the hypokalaemia? A increased flow in the distal tubule B increased potassium secretion in the proximal tubule C opening of potassium channels in the principal cells D reduced aldosterone secretion E reduced potassium reabsorption in the loop of Henle

• A

• 74. A 47-year-old man presented with a 6-month history of episodic sweating and hunger. He had gained 10 kg in weight and drank 10 units of alcohol per week. • Investigations: • full blood count normal • fasting plasma glucose 4.0 mmol/L (3.0–6.0) • liver function tests normal • What is the most appropriate next investigation? A B C D E

CT scan of pancreas electroencephalography home blood glucose monitoring plasma glucose concentration following a prolonged (72-h) fast serum C-peptide concentration

• D

A 27-year-old woman had a history of repeated attendances for acute exacerbations of asthma. On current presentation, she had been short of breath for 4 hours and had features of acute severe asthma. Which finding would indicate that this exacerbation of her asthma should be regarded as life-threatening? • A PaCO2 of 5.5 kPa • B PaO2 of 8.4 kPa • C peak flow 35% predicted • D pulse 114 beats per minute • E respiratory rate 30 breaths per minute

• A

A 37-year-old woman with immune thrombocytopenia failed to respond to corticosteroid therapy. Splenectomy was planned. • What is the optimum time for pneumococcal vaccination? • A 1 month after surgery • B 1 month before surgery • C 1 week after surgery • D 1 week before surgery • E perioperatively

• A

A 32-year-old woman presented with feverishness and myalgia for 2 days followed by headache, photophobia and neck stiffness for the past 6 hours. Investigations: white cell count 10.4 109/L (4.0–11.0) random plasma glucose 5.2 mmol/L cerebrospinal fluid: opening pressure 180mm (50–180) total protein 0.60 g/L (0.15–0.45), glucose 3.5 mmol/L cell count 76/µL ( 5) Lymphocyte count 46/μL (≤3.5) neutrophil count 30/μL What is the most likely causative organism? A enterovirus B Listeria monocytogenes C Mycobacterium tuberculosis D Neisseria meningitidis E Streptococcus pneumoniae

• A

• 78. A 25-year-old woman presented complaining of loose stools five to six times a day. One year previously, she had undergone resection of her terminal ileum for Crohn’s disease. Her only drug therapy was mesalazine. On examination, there was no abdominal tenderness. Investigations: • haemoglobin 126 g/L (115–165) • serum albumin 38 g/L (37–49) • serum C-reactive protein 4 mg/L (<10) • What is the most likely diagnosis? A active Crohn’s disease B adverse effect of mesalazine C bile salt-induced diarrhoea D enteric infection E irritable bowel syndrome

• C

• 79. A 71-year-old woman presented with a 2hour history of severe pain and loss of vision in her right eye. She had noticed halos around lights during the previous 24 hours. On examination, there was ciliary vessel hyperaemia and a dilated unreactive pupil on the affected side. • What is the most likely diagnosis? • A anterior uveitis • B closed-angle glaucoma • C diffuse scleritis • D orbital cellulitis • E retinal artery occlusion

• B

A 65-year-old man presented with chest discomfort consistent with stable angina pectoris after climbing two flights of stairs. Investigations: serum cholesterol 4.8 mmol/L (<5.2). echocardiogram good left ventricular systolic function Bruce protocol exercise test 3mm ST segment depression in stage 3. Which treatment has been shown to improve the prognosis in this situation? A aspirin B diltiazem C isosorbide mononitrate D ivabradine E nicardipine

• A

Which dietary substrate is broken down into glucose and galactose by the action of intestinal enzymes? A fructose B lactose C maltose D mannose E sucrose

• A

A 47-year-old woman was being treated with lithium for bipolar affective disorder. On examination, her blood pressure was 168/104 mmHg. What drug is the most appropriate antihypertensive? • A amlodipine • B bendroflumethiazide • C doxazosin • D losartan • E ramipril

• A

A 50-year-old man with tophaceous gout presented with painful joints 2 days after starting treatment with allopurinol. His only other medication was paracetamol. He had a history of alcohol abuse. On examination, his temperature was 38.5°C and there was acute inflammation of the finger joints, wrists, knees and ankles. • Investigations: • serum gamma glutamyl transferase 90 U/L (<50) • serum urate 0.65 mmol/L (0.23–0.46) • serum C-reactive protein 180 mg/L (<10) • What is the most likely cause of his symptoms? A acute pseudogout B alcoholic binge C allergic reaction to allopurinol D allopurinol therapy E joint sepsis

• D

A 45-year-old woman presented with right flank pain. She had a 4-year history of hypertension and progressive cognitive impairment. On examination, she had livedo reticularis and tenderness in the right flank. Her blood pressure was 185/105 mmHg. Urinalysis showed blood 3+, protein 1+. Investigations: • haemoglobin 129 g/L (115–165) • white cell count 8.7 109/L (4.0–11.0) • platelet count 83 109/L (150–400) • serum creatinine 106 µmol/L (60–110) • Which antibody test is most likely to be positive? A anticardiolipin B anticentromere C anti-glomerular basement membrane D antimitochondrial E anti-neutrophil cytoplasmic

• A

A 20-year-old man presented with a 7-day history of bloody diarrhoea, abdominal pain and fevers. He had recently returned from a backpacking holiday in South America. On examination, his temperature was 38.5°C and the abdomen was tender on palpation. • Investigations: • stool microscopy pus cells and red blood cells • What is the most likely causative organism? A Cryptosporidium parvum B rotavirus C Salmonella typhi D Schistosoma mansoni E Vibrio cholerae

• C

A 65-year-old woman with a 40-year history of rheumatoid arthritis presented with a 4-month history of lower leg oedema. She was taking methotrexate weekly and prednisolone daily. Urinalysis showed protein 3+. • Investigations: • haemoglobin 94 g/L (115–165) • white cell count 10.6 109/L (4.0–11.0) • erythrocyte sedimentation rate 105 mm/1st h (<30) • serum albumin 24 g/L (37–49) • Which investigation is most likely to be of diagnostic value? A lower leg venography B rectal biopsy C renal angiography D serum protein electrophoresis E ultrasound scan of kidneys

• B

A 71-year-old woman required a transfusion of 2 units of blood after a hip replacement. One week later, her haemoglobin concentration had fallen by 42 g/L. Which associated finding is most likely to indicate a delayed transfusion reaction? • A conjugated hyperbilirubinaemia • B elevated D-dimer • C haemoglobinuria • D haemosiderinuria • E positive direct antiglobulin test

• E

75-year-old man presented with weight loss, lethargy and repeated haemoptysis. He had been treated for pulmonary tuberculosis 10 years previously. Investigations: • Aspergillus fumigatus precipitins positive • chest X-ray a solid lesion at the left lung apex • What is the most likely diagnosis? A allergic bronchopulmonary aspergillosis B aspergilloma C bronchial carcinoma D invasive aspergillosis E reactivation of tuberculosis

• B

A 36-year-old HIV-positive man presented with a 1-week history of generalised pruritus. He had taken part in unprotected anal sex 2 months previously while on holiday in Spain. He had previously been vaccinated against hepatitis B virus, with an adequate antibody response. On examination, his temperature was 37.8°C and he was jaundiced. Examination was otherwise normal. • Investigations: • CD4 count 550 106/L (430–1690) • serum total bilirubin 99 µmol/L (1–22) • serum aspartate aminotransferase 754 U/L (1–31) • serum alkaline phosphatase 173 U/L (45–105) • hepatitis A immunoglobulin M negative • What is the most likely diagnosis? • A acute hepatitis C • B acute hepatitis D • C cytomegalovirus infection • D syphilis • E toxoplasmosis

• A

• 92. A post-marketing observational study of a new drug was conducted on 5000 patients following clinical trials. • What best describes the data generated from this type of study? • A comparative efficacy • B cost–benefit • C cost effectiveness • D potency • E profile of adverse effects

To help protect y our priv acy , PowerPoint has block ed automatic download of this picture.

• • • • •

• •

•

E Clinical trials involving new drugs are commonly classified into four phases. Each phase of the drug approval process is treated as a separate clinical trial. The drugdevelopment process will normally proceed through all four phases over many years. Preclinical trial .It involves in vitro (test tube or cell culture) and in vivo (animal) experiments using wide-ranging doses Phase 0 trials are also known as human microdosing studies . Phase I trials are the first stage of testing in human subjects. Normally, a small group of 20-100 healthy volunteers will be recruited. This phase is designed to assess the safety (pharmacovigilance), tolerability, pharmacokinetics, and pharmacodynamics of a drug. Phase II trials are performed on larger groups (100-300) and are designed to assess how well the drug works, as well as to continue Phase I safety assessments in a larger group of volunteers and patients. Phase III studies are randomized controlled multicenter trials on large patient groups (300–3,000 or more depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is, in comparison with current 'gold standard' treatment. Because of their size and comparatively long duration, Phase III trials are the most expensive, time-consuming and difficult trials to design and run, especially in therapies for chronic medical conditions. Phase IV trial is also known as Postmarketing surveillance Trial. Phase IV trials involve the safety surveillance The safety surveillance is designed to detect any rare or long-term adverse effects over a much larger patient population and longer time period than was possible during the Phase I-III clinical trials.

• 93. A 20-year-old woman presented with a 2-month history of an intensely pruritic rash on her trunk and limbs. She was otherwise well. On examination, she had multiple, violaceous, flat-topped papules over the flexor surfaces of the wrists, and on the ankles and lower back. The papules were aggregated in a linear fashion at one site on her left forearm. • Which clinical feature is most likely to be present? • A asymmetric oligoarthritis • B burrows in finger webs • C conjunctival scarring • D involvement of the buccal mucosa • E non-scarring alopecia

• D

•

• •

95. In a large prospective trial of a statin in patients with angina, 1000 patients were treated with a statin and 1000 with a placebo. A total of 150 patients taking the placebo experienced a cardiovascular event, compared with 100 taking the active drug. placebo cardiovascular event 150 no cardiovascular event 850

statin total 100 250 900 1750

•

What is the number-needed-to-treat (NNT) to prevent one cardiovascular event?

A B C D E

2.5 (250/100) 5 (250/50) 10 (1000/100) 20 (1000/50) 40 (2000/50)

• D

A 58-year-old man with congestive heart failure remained oedematous despite treatment with furosemide 120 mg daily. Investigations: • serum sodium 134 mmol/L (137–144) • serum potassium 3.4 mmol/L (3.5–4.9) • serum urea 10.6 mmol/L (2.5–7.0) • serum creatinine 156 µmol/L (60–110) What is most likely to be present? A high plasma aldosterone concentration B high serum cortisol concentration C low plasma angiotensin II concentration D low plasma atrial natriuretic peptide concentration E low plasma renin concentration

• A

A 43-year-old woman presented with a 1-week history of polyuria and nocturia without weight loss. Clinical examination was normal. Investigations: • serum sodium 142 mmol/L (137–144) • serum potassium 3.5 mmol/L (3.5–4.9) • serum corrected calcium 2.60 mmol/L (2.20–2.60) • random plasma glucose 7.0 mmol/L • plasma osmolality 310 mosmol/kg (278–300) • urinary osmolality 200 mosmol/kg (350–1000) • A B C D E

What is the most likely diagnosis? compulsive polydipsia diabetes insipidus diabetes mellitus hyperparathyroidism syndrome of inappropriate antidiuretic hormone secretion

• B

A 55-year-old woman presented with a 2-day history of diplopia and progressive unsteadiness while walking. On examination, she had limited eye movement in all directions although her pupils were normal. Muscle power in the limbs was normal but tendon reflexes were absent. There was prominent bilateral finger nose ataxia. Plantar responses were flexor. Sensation was normal. What is the most likely diagnosis? A brainstem stroke B Miller Fisher syndrome C multiple sclerosis D myasthenia gravis E Wernicke’s encephalopathy

• B

A 60-year-old woman with rheumatoid arthritis presented with an acutely inflamed right knee. The joint was aspirated and methylprednisolone 80 mg was injected after the removal of 20 mL of non-purulent synovial fluid. The knee improved following this procedure but her symptoms recurred and became much worse a week later. Investigations: • haemoglobin 105 g/L (115–165) • white cell count 15.5 109/L (4.0–11.0) • neutrophil count 13.5 109/L (1.5–7.0) • erythrocyte sedimentation rate 55 mm/1st h (<30) • What is the most appropriate immediate management? A arthroscopic washout of right knee B re-aspirate right knee C re-inject right knee with corticosteroid D rest right knee in a splint E start intravenous flucloxacillin

• B

• A 52-year-old man presented with a 4-month history of altered bowel habit with occasional bright-red blood per rectum. Colonoscopy revealed an annular sigmoid tumour and histology confirmed an adenocarcinoma. A staging CT scan of abdomen revealed two 1-cm adjacent lesions in the right lobe of the liver, highly suspicious for liver metastases. • • What is the most appropriate next management step? • • A biopsy of liver lesions • B palliative chemotherapy • C palliative radiotherapy • D stenting of colorectal carcinoma • E surgical resection of carcinoma and liver lesions

• Answer Key: E

• 42. A 26-year-old woman presented with unequal pupils. On examination, the right pupil was larger than the left and did not react to light, directly or consensually. On convergence, the right pupil reacted very slowly, but eventually became smaller than the left pupil. What type of pupillary abnormality does this woman have? • A Adie’s tonic pupil • B afferent pupillary defect • C Argyll Robertson pupil • D Horner’s syndrome • E third cranial nerve palsy

• A