Embryology CVS Embryonic Structure Gives RISE TO: Truncus arteriosus Ascending aorta and pulmonary trunk. Bulbus cordis Primitive atrium
Smooth parts (outflow tract) of left and right ventricles. Trabeculated part of left and right atria
Primitive ventricle Trabeculated part of left and right ventricles Primitive pulmonary vein Left horn of sinus venosus
Smooth part of left atrium
Right horn of sinus venosus
Coronary sinus
Smooth part of right atrium (sinus venarum)
Right common cardinal vein and right anterior cardinal vein: Superior vena cava (SVC)
Heart morphogenesis:
First functional organ in vertebrate embryos; beats spontaneously by week 4 of development.
Cardiac looping: Primary heart tube loops to establish left-right polarity; begins in week 4 of gestation. Defect in left-right dynein (involved in L/R asymmetry) can lead to dextrocardia, as seen in Kartagener syndrome (primary ciliary dyskinesia).
Septation of the chambers: Atria 1-Septum primum grows toward endocardial cushions, narrowing foramen primum.
2-Foramen secundum forms in septum primum (foramen primum disappears). 3-Septum secundum develops as foramen secundum maintains right-to-left shunt. 4-Septum secundum expands and covers most of the foramen secundum. The residual foramen is the foramen ovale. 5-Remaining portion of septum primum forms valve of foramen ovale. 6-Septum secundum and septum primum fuse to form the atrial septum. 7-Foramen ovale usually closes soon after birth because of •LA pressure. Patent foramen ovale—caused by failure of septum primum and septum secundum tofuse after birth; most are left
untreated. Can lead to paradoxical emboli(venous thromboemboli that enter systemic arterial circulation), similar to those resulting from an ASD. RX: most common cardiac defect in down is ASD defect in primitive atrium.
Ventricles 1-Muscular ventricular septum forms. Opening is called interventricular foramen. 2-Aorticopulmonary septum rotates and fuses with muscular ventricular septum to form membranous interventricular septum, closing interventricular foramen. 3-Growth of endocardial cushions separates atria from ventricles and contributes to both atrial Septation and membranous portion of the interventricular septum. Ventricular septal defect (VSD)—most commonly occurs in the membranous septum.
Outflow tract formation:
Truncus arteriosus rotates; neural crest and endocardial cell migrations truncal and bulbar ridges that spiral and fuse to form aorticopulmonary septumascending aorta and pulmonary trunk.
Conotruncal abnormalities: 1. Transposition of great vessels. 2. Tetralogy of Fallot. 3. Persistent truncus arteriosus.
UW: T4 abnormal neural crest cell migration
UW: transposition of great vessels failure of septation. ”failure of AP septum to spiral normally during septation of truncus arteriosus”
anterosuperior displacement of conal
UW: endocardial cushion defect failure of fusion ostium primum ASD
septum.
Valve development: Aortic/pulmonary: derived from endocardial cushions of outflow tract. Mitral/tricuspid: derived from fused endocardial cushions of the AV canal.
Valvular anomalies may be stenotic, regurgitant, atretic (e.g., tricuspid atresia), or displaced (e.g., Ebstein anomaly).
Fetal erythropoiesis Fetal erythropoiesis occurs in:
Yolk sac (3–8 weeks) Liver (6 weeks–birth) Spleen (10–28 weeks) Bone marrow (18 weeks to adult) Young Liver Synthesizes Blood.
Hemoglobin development
Embryonic globins: ζ and ε.
Fetal hemoglobin (HbF) = α2γ2.
Adult hemoglobin (HbA) = α2β2.
NB: HbF has higher affinity for O2 due to less avid binding of 2, 3-BPG, allowing HbF to extract O2 from maternal Hemoglobin HbA1 and HbA2) across the placenta.
UW: the highest value of O2 saturation is recorded in IVC in fetal circulation. As it carries oxygenated blood from umbilical veins.
UW: venous system of the developing embryo: Vitelline veins of the portal system,Umbilical degenerate, Cardinal veins veins of the systemic circulation e.g. SVC
Surface anatomy of the heart: 2*3=6 + apex
P= pulmonary trunk 2nd intercostal, left sternal border. UW: stab wound at left sternal border 4th intercostal (at the level of the nipple) RV injury. UW: stab wound in theleft 5th intercostal MCL lung injury as it should pass through the bulk of the lung before it reach the LV. UW: Anterior surface of the heart mostly by RV, Inferior surface of the heart (diaphragmatic) RV, LV post. Surface LA. K: stab in the back immediately RT to the vertebral bodies IVC injury.
UW: Aortic valve 2nd IC RT sternal border. Pulmonic valve 2nd IC LT sternal border. Tricuspid valve 4th IC LT at the lower LT sternal border. Mitral valve 5th LT IC MCL.
UW: which chamber is closest to the probe of transeosophegeal ECHO Left atrium. *if the probe is faced post descending aorta.
UW: blood supply of the diaphragmatic surface of the heart posterior descending artery (PDA).“The idea is from which this artery is coming” UW: AV nodal artery arises from PDA (if rt dominant) or from LCX (if left dominant). Rx: patient e post MI then developed mitral regurge, why? Due to occlusion of the PDA rupture of the post. Papillary muscle MR. Papillary muscles of the mitral valve: *post. Papillary muscle: supplied only by PDA. *Ant papillary muscle: has dual blood supply by LAD&PDA less likely to rupture after MI. UW: venous drainage of the heart is through coronary sinus “opens in the RA and normally not seen by ECHO” so, coronary sinus dilatation
is d2 increase in the RT side pressure because of pulmonary HTN.
UW: Aortic rupture: -cause: Mostly d2 motor accident d2 acceleration deceleration injury -site: at the aortic isthmus “connection between ascending and descending aorta distal to the srcin of Lt Subclavian.” -C/P: chest pain, back pain, dyspnea, low BP, CXR wide mediastinum.
UW: perfusion of the heart is mainly during diastole. The systolic reduction of the coronary flow is greatest in the subendocardial myocardium of the LV. UW: exercise stimulate sympathetic causing: -increase HR increase CO (to meet the metabolic needs of the body). -venous constriction increase preload. -shunt blood to the exercising muscle.
As the exercising ms release Although MAP remains slightly constant during exercise (only increase 20-40) why?
vasodilatory factors e.g. lactate, adenosine
decrease in systemic vascular resistance.
KQB: exercise increase symp. Constriction to veins & venules increase mean circulatory filling (MCFP) increase capillary filtration pressure increase lymph flow. KQB: exercise has 2 types *dynamic: increase blood flow d2 metabolic VD of arterioles. *static (weight lifting): skeletal ms compress BV increase vascular resistance decrease blood flow. KQB: old patient with wide pulse pressure HTN, why? Aortic stiffness, as atherosclerosis ↓ compliance ↑ pulse pressure.
UW: Diastolic HF:
Systolic HF:
normal EF. ↑ LV end-diastolic pressure. Normal LV EDV. ↓EF ↑ LV end-diastolic pressure ↑ LV EDV.
UW: diastolic HF Caused by ↓ compliance d2
↓relaxation e.g. ischemia. Wall stiffness e.g. amyloidosis restrictive cardiomyopathy. Hypertrophy e.g. HTN & HCM.
Dilated cardiomyopathy systolic dysfunction Hypertrophic cardiomyopathy diastolic dysfunction
UW: patient e shock then infused 2L saline ↑ preload ↑ end diastolic sarcomere length. UW:
UW:
UW: total circulation parallel… UW: Flow Q = (
P
circulation in individual organ Series.
4
r ) / ηL
“blood flow is directly proportional to the vessel radius to the fourth power” blood flow per minute. UW: in Exercise, what is the same in pulmonary and systemic circulation? As pulmonary circulationis low pressure and high flow system if the flow ↓ in pulmonary LV will soon empty completely if the flow ↑ in pulmonary LV overloaded.
UW: total flow = A1*V1 = A2V2 = constant. UW: removal of kidney or any other organ: -↑ TPR (as organs are arranged in parallel) -↓ CO -normal arterial blood pressure (MAP= CO*TPR) -↓ total renal blood flow (there is only one kidney) UW: Which anatomical site would normally have a blood O2 content that differs mostly from O2 in Aorta?? Coronary sinus “myocardial O2 extraction exceeds that of any other tissue; resting myocardium extracts 75% of O2 in the blood while at work extract 90%”.
UW: which ↑CO & ↑VR with the same MSFP? ↓TPR (exercise & acute AV shunt) ↑contractility, Which ↑CO & ↑VR with ↑MSFP? Chronic AV fistula d2 sympathetic and renal compensation ↑vascular tone and ↑blood volume.
K: spinal anesthesia ↓ venous tone and has no rule with TPR.
UW:
↑ESV more volume remaining in the ventricle after contraction.
UW: AV shunt blood shunts from arterioles (↓afterload) to veins (↑preload)
UW: Na nitruprusside: balanced dilator venodilator (↓preload) & arteriodilator (↓afterload) so, SV remain constant.
UW: UW: furosemide (diuresis) ↓ preload ↓ EDV. Rx: ↓afterload ↑ SV ↑ width of the curve. AR volume overload synthesis of new sarcomeresin series eccentric hypertrophy. AS pressure overload synthesis of new sarcomeresin parallel concentric hypertrophy.
UW: S3 d2 rushing of blood into a partially filled ventricle or very stiff ventricle. Best heard with: -bell of the stethoscope pressed lightly over the apex (the bell detects low frequency voices) -left lateral decubitus. -at the end of expiration. S3 if young normal adult LV systolic failure or restrictive cardiomyopathy UW: In AR, what maintains CO?? 1- ↑ LV preload 2- eccentric LVH not ↑ HR as the HR increases acutely then returns to normal. UW: in MS normal LV diastolic pressure. But if MS + ↑ LVEDP suspect presence of additional lesion e.g. 1- rheumatic involvement of aortic valve (typically cause combined AR & AS) 2- Infective endocarditis superimposed aortic valve deformity. * MS + stroke d2 RA dilatation atrial mural thrombus. d2 ↑ LA pressure ↑ PCWP pulmonary HTN pulmonary vascular sclerosis ↓ compliance * MS + TR RV dilatation functional TR.
UW: diacritic notch represents the elasticity of the aorta; lost in AR, Marfan and syphilis. UW: rapid deep descentin y-descent in constrictive pericarditis. Rx: in aortic stenosis ↑ isovolumetric contraction phase d2 need to ↑ pressure to open the stenotic valve. “Normally aortic valve opens when the ventricular pressure exceeds the pressure in the aorta” Rx: post-radiation therapy constrictive pericarditis ↓ EDV. KQB: how to calculate the diastolic BP from the aortic pressure curve? DBP= pressure at the point of aortic valve opening. UW: how to diagnose AR on aortic pressure curve? 1- Absence of diacritic notch. 2- Steep diastolic decline on the curve. UW: in MR, which ↑ forward-to-regurgitant volume ratio ↓LV afterload. “In MR, some blood is pumped forward through the aortic valve (forward stroke volume), while some blood is forced backwards through incompetent valve (regurgitant SV).
UW: pt with MS (↑LA pressure on the curve) where is the site of the opening snap?
Answer: C OS is early diastolic shortly after the aortic component of the second heart sound (A2)
UW: Aortic stenosis curve: which point corresponds to the maximum point of murmur?
Answer B *normally pressure in aorta = pressure in LV during systole.
UW: AR curve.
*loss of diacritic notch + high peak of aortic pressure + wide pulse pressure. *murmur intensity is best heard at point C (aortic valve closure) UW: Mitral regurge curve:
*V-wave
LA pressure d2 passive filling during systole.
UW: patient with AS then developed AF sudden onset of acute HF (pulmonary edema & hypotension) Cause: sudden loss of LV preload. Explanation: acute AF most likely precipitated sudden HF in chronic AS as AF loss of atrial systolic kick ↓LV preload ↓LVEDV ↓CO with AS that caused concentric LV hypertrophy which worsen the case.
*pulmonary & aortic murmurs systolic at their sites but diastolic at left sternal border. * ASD systolic & VSD diastolic. UW: left lateral decubitus ↑ intensity of which murmurs? * MS * MR * left sided S3 & S4 UW: murmur best heard when patient sits up and leans forward? AR.
KQB: inspiration ↑ -ve intrathoracic pressure ↑ venous return ↑ blood in RV pooling of blood of blood in lungs *↓ systolic arterial pressure. *↑ HR. * ↓ LV EDP & ↑ RV EDP. NB: inspiration ↑ tricuspid murmurs. Expiration ↑ mitral murmurs.
UW: holosystolic murmurs MR & TR & VSD. UW: water hammer pulse + head bobbing AR. UW: in MS the opening snap is best heard at mitral opening in pressure volume curve.
UW: UW: late diastolic murmur eliminated by atrial fibrillation MS & TS. UW: How to differentiate betweenOS of MS & splitting of S2? * splitting ↑ with inspiration & *OS ↑ with expiration UW: In MR, what is the best indicator forseverity of the problem? The presence of audible S3 NOT the holosystolic murmur intensity as the later doesn’t correlate well with the regurgitant volume but correlate with the effective regurgitant orifice. NOT S4 asMR+S4 end stage decompensation of severe MR LV failure; however many patients with severe MR may not have developed LV failure. UW: The best indicator of MS severity A2 – OS interval the shorter the interval the more severe the stenosis. NOT the rumble as it depends on the patient anatomy. NOT the presystolic accentuation as it indicates LA contraction. UW: Case: HTN + S3 + holosystolic murmur over the apex but the murmur and the S3 disappeared after diuretics and vasodilators Dx: Functional MRwhich caused by either 1- transient hemodynamic factor causing LV dilatation OR papillary ms ischemia. “Acute LV dilatation can separate otherwise normal mitral valve”.
UW:
K: plateau
↓ with CCBs. ↑ with K channel antagonists.
K: Execution by K infusion ↑ K in ECF no K efflux no repolarization arrest. UW: the resting potential of cardiac ms (phase 4) is -90 not -70, why? to reduce the risk for arrhythmia, as larger stimulus is needed to excite the cells. UW: verapamil is a CCB but doesn’t affect skeletal ms? As Sk. ms doesn’t depend on extracellular calcium. “Skeletal ms doesn’t require extracellular calcium influx for excitation contraction coupling whereas cardiac and smooth ms depends on extracellular calcium entering by voltage gated L-type calcium channels for excitation contraction coupling”. In SK ms, Ca comes from SR not from outside.
UW: verapamil slows diastolic depolarization by ↓ Ca influx during phase 0 and the later part of phase 4 ↓ rate of SA node firing and slows AV node conduction. increased by class 1 Threshold potential: is the amount of depolarization required to initiate the action potential antiarrhythmic (Na channel blockers) and class 4 (CCBs). UW: Norepinephrine opens L-type Ca channel and Na channels in phase 4 prolongs time taken to reach the threshold. K: Effect of the sympathetic on pacemaker action potential: *↑ funny Na ch annels threshold reached sooner ↑slope. * ↑ Ca current
UW:
*Used in chronic HF with ↓EF and persistent symptoms despite approprtiate ttt.
UW:
K: the fast fibers in the heart (purkinje, atria, and ventricles) can be converted into slow fibers by ischemia. Ischemia ↑ k in ECF ↓ -ve resting membrane potential. UW: QRS ventricular depolarization = phase 0 in ventricular contraction (in myocardial action potential curve). Rx: Inotropic ↑ contractility by ↑ inward Ca current. Chronotropic ↑ HR by ↑ inward Na current ↑ SA node firing. Dromotropic ↑ conduction velocity through AV node by ↑ inward Ca current.
WPW syndrome. *recurrent temporary arrhythmia in otherwise normal person *Don’t slow AV with (digoxin, CCBs, BBs or adenosine) but block the accessory pathway with (antiarrhythmic 1a & 3).
UW: Normal axis of the heartis 60 “The axis of the heart tends to move toward the hypertrophied tissue and away from the infarcted tissue” Rt Axis Deviation RVH, MI on the Lt and conduction deficit on the Rt. Lt Axis Deviation LVH, MI on the RT and conduction deficit on the Lt.
UW: in AF, which factor determines the ventricular rate? AV node refractory period. “ AF occurs d2 irregular electrical activity in the atrium; while some of the atrial impulses are transmitted to the ventricles, most are not d2 AV nodal refractory period” UW: Case scenario: irregular HR and party in the previous day AF “holiday heart syndrome”
UW: in complete heart block, the ventricular pacing is coming from AV node which becomes the pacemaker. UW: Mobitz type 2 is d2 defect in His-Purkinje system. For this reason the PR interval is constant as the AV node is normal.
UW: ANP
kidney *dilate afferent *↓Na reabsorption *↓renin. Adrenal gland ↓aldosterone. Blood vessels *VD *↑ capillary permeability.
UW: paroxysmal SVT(patient with no other heart disease) cause: reentrant circuit in the AV node. TTT: carotid sinus massage ↑ parasympathetic prolong AV node refractory period.
K: why patient e meningitis hyperventilate? D2 CSF infection ↑H ions ↓ PH of the CSF stimulate the central chemoreceptors in the medulla hyperventilate. K: “the main drive for alveolar ventilation is central chemoreceptorswhich is affected by PCO2 except when (PO2<80 or FiO2< 17) in this 2 cases the peripheral receptors take over the alveolar ventilation. ↓PO2 + peripheral receptors. Case: Morphine overdose chronic hypoventilation ↑PCO2 + central chemoreceptors BUT it is already suppressed by morphine. SO, giving 100% O2 inhibits peripheral receptors↑PCO2 SO, the peripheral receptors are the main drive for resp. NB: ↑↑PO2 isn’t inhibitory to peripheral receptors but ↓PO2 is stimulatory. *normal ventilation *central R are the main drive Q: What will happen when subject moves from room air to 100% O2 hyperventilate d2 ↓O2 Q: mask with 3% CO2 and 15 % O2 (NB: normal air contains 1% CO2 and 21% O2) peripheral R ↑ventilation but not d2 ↑CO2 as whatever the CO2, the peripheral R take the drive d2 ↓O2. UW: Case scenario: patient e COPD + cyanosis then treated by supplemental O2 ↓RR Pt then confused. WHY? D2 ↓ stimulation of carotid bodies. EXPLANAION: prolonged hypercapnia in COPD causes that high PCO2 no longer stimulate the respiratory drive. In such patients, respiration is stimulated by hypoxia sensed by peripheral chemoreceptors. Rapid ↑ of the fraction of inspired O2 respiratory failure. KQB: Cutting glossopharyngeal nerve baroreceptor reflex HTN & tachycardia. KQB: Carotid occlusion ↓ blood flow to carotid sinus ↓ stretch ↑HR & ↑MAP stimulate aortic arch baroreceptors ↓HR & ↓MAP to normal BUT in vagotomy ↑BP & ↑HR.
UW: PCWP= LA EDP = LV EDP UW: RV infarction in the setting of inferior MI hemodynamics:
UW: Nitric Oxide released also in response to pulsatile stretch and flow shear forces in coronary arteries.
NB: Nervous input has very little role on coronary blood flow. UW: During exercise ↑HR ↓duration of diastole ↓coronary flow. BUT in times of stress ↑adenosine VD of coronary. UW: Case scenario: pregnant>20 wks + hypotension e supine position supine hypotension syndrome: d2 compression of the gravid uterus on the IVC ↓VR ↓CO hypotension & syncope. *orthostatic hypotension autonomic neuropathy (DM isthe most common cause). *hypotension in early pregnancy d2 ↓ systemic vascular resistance.
UW: Venous thrombosis like CHF causes edema by ↑ capillary hydrostatic pressure. UW: patient e CHF and ↑ CVP but there isno edema! Why? D2 ↑ tissue lymphatic drainage which can compensate for moderate CVP elevation to prevent development of clinically apparent edema. RT to left shunt e.g. VSD “A significant UW: O2 saturation in RT atrium 75% and in RV 85%.what does it mean? els indicate the presence of RT to LT shunt.” increase in blood O2 saturation between 2 RT sided vess
UW: Case scenario: “cyanosis in neonate + Echo (apical displacement of tricuspid valve + ↓RV volume + atrialization of the RV) Dx: Ebstein anomaly: Cause: lithium exposed in utero (the mother had bipolar disorder) C/P: wide fixed splitting (80% have PFO with RT to LT shunt) + TR Dilated RA ↑risk of SVT and WPW syndrome.
UW: Patent foramen ovale: *considered normal variant in adults (20-30%) *Remains closed as pressure in LA > RA so, ↑RA pressure RT to LT shunt hypoxemia & paradoxical embolization (DVT + stroke).
UW: Case scenario: “the baby turns blue when cries and when the episode lasts a long time he gets agitated and gasps for air.” Dx: T4 (Tet spells) cyanosis that worsens with feeding, crying or exercise d2 spasm in pulmonary trunk. Boot-shaped heart
adult RVH infant T4
*Failure of fusion PFO *septal defect ASD
UW: patient with adult type of Coarctation dies from hypertensive associated complications rupture intracranial aneurism (↑ incidence of congenit al berry aneurism with Coarctation). NB: Coarctation + murmur AR d2 bicuspid aortic valve UW: Bicuspid aortic valve: *the most common associated anomaly with turner. *early systolic + high-frequency th click over the apex. Can be present also with AR murmur. *premature calcification at the 6 decade (normally aortic valve calcification occurs at 8th to 9th decades). *Most common cause of congenital aortic stenosis is calcification of bicuspid aortic valve. UW: MVP: *Cause: defect in connective tissue proteins e.g. Marfan & Ehler Danlos syndromes. *C/P: midsystolic click, short late systolic murmur which disappears with squatting.
*Renal artery stenosis if
male caused by atherosclerosis. Female fibromuscular dysplasia.
*lipid laden histiocytes: dermal accumulation of macrophages containing cholesterol and triglycerides. UW: Case scenario: Pancreatitis in childhood + hyperlipidemia. Lipoprotein lipase deficiency. C/P: child with hyperlipidemia + pancreatitis + lipemia retinalis + eruptive skin xanthoma + hepatosplenomegaly. * Usually not at risk of accelerated coronary artery disease.
UW: Familial hypercholesterolemia: *one of the most common autosomal dominant disorders. accelerated *cause: mutation in the LDL receptor gene in the liver which clears 70% of the LDL in the blood atherosclerosis early onset coronary artery disease.
UW: Myxamatous changes in the media of the arteries is referred to cystic medial degeneration in Marfan causing aortic dissection and aneurism. Cystic medial necrosis aortic dissection in Marfan syndrome.
UW: Case Scenario:12y + flat yellow spots on the inner surface of the aorta Fatty streaks: not raised, don’t disturb blood flow and shows intracellular lipid accumulation *can be seen in the aorta of children less than 1 year. *presents in all aortas of all children > 10 years normal finding. UW: Which cell does provide the major proliferative stimuli for the cellular component of the atherosclerotic plaques? PLATELETS. Endothelial injury platelet adhesion PDGF smooth ms migration from media to intima and proliferation. TGF interstitial collagen production.
UW: Vascular reaction to intimal injury migrate from the media to the intima.
intimal hyperplasia and fibrosis mediated by smooth ms cells that
Fibrous plaque = intimal plaque = necrotic lipid core + fibromuscular cap.
UW: characters of unstable atheromatous plaque: *thin fibrous cap ulcerate rupture thrombosis MI. *rich lipid core rupture … *activated macrophages in atheroma metalloproteinase collagen degradation intimal inflammation ulceration ….. (NB: STATINS decrease this inflammation and are useful in acute coronary syndrome to stabilize the plaque). UW: Fixed plaque + obstruction > 75 % stable angina. MI transmural. Rupture plaque Ulcerated plaque MI subendocardial or unstable angina.
Rupture AAA hypotension + pulsatile abdominal mass + flank pain. UW: isolated systolic hypertension in old age d2
which is predisposed by atherosclerosis.
UW: The cause of the abdominal aortic aneurismis chronic transmural inflamation proteases that defrade elastin and collagen loss of elastin & abnormal collgen remodelling and cross linking aneurism formation. NOT fatty streaks “Atherosclerosis is commonly associated with AAA but the histopathological changes are limited to the intima and subendothelium don’t significantly contribute to aortic wall weakening.
UW: The likelihood of MI is increased with the action of which enzyme Metalloproteinase degrade collagen ↓ plaque stability plaque rupture. UW:
is the single most important risk factor for
UW: Dx of prinzmetal’s Angina by
from intimal tear.
Ergonavine provocative test.
UW: Reversible injuries in cardiac muscle: 1- myofibril relaxation early sign < 30 min, d2 anaerobic glycolysis. 2- Disaggregation of polysomes dissociation of rRNA from mRNA ↓ protein synthesis. 3- Disaggregation of nucleus. 4- Clumping of nuclear chromatin d2 ↓PH. 5- Triglyceride droplet accumulation d2 ↓ lipoproteins. 6- Glycogen loss early d2 ↓ATP. UW: Mitochondrial vacuolization: irreversible cell injury which indicates that the mitochondria is permanently unable to reduce ATP. Mitochondrial swelling reversible BUT Mitochondrial vacuolization irreversible. UW: Mitochondrial swelling or cell swelling is d2 ↓ATP
↓pumps ↑ intracellular Na & Ca.
UW: Reperfusion injury: apoptosis or necrosis of the cells after resumption of the blood supply. Leading to *O2 free radicals *severe irreversible mitochondrial damage *inflammation which attracts neutrophils which cause additional injury.
*neutrophils fibrinous pericarditis: Sharp pain increase with coughing, swallowing (d2 irritation of the posterior pericardium), radiating to the neck (d2 irritation of the inferior pericardium to the phrenic nerve). temponade. *macrophages rupture of free wall Interventricular septum VSD or shunt. Papillary muscle mitral regurge. UW: Case scenario: Holosystolic murmur at the apex radiating to the axilla 3-10 days post MI acute MR d2 rupture of the papillary muscle. UW: Case scenario: holosystolic murmur at the left sternal border rupture of the interventricular septum VSD. Rx: Contraction bands located at the margins of the necrotic area. D2 reperfusion of the irreversibly damaged cells Ca influx hypercontraction of the myofibrils. UW: Case: angina+hypokinesia of the anterior wall of LV + EF=35% then CABG was done no hypokinesia + EF=50% this phenomenon is called *Def.: chronic, reversible loss of contractile function. *cause: repetitive ischaemia or persistent hypoperfusion. *mechanism: ↓energy metabolism but there is sufficient ATP to prevent contracture ↑gene expression of TNF-alpha and nitric oxide synthase inhibitors of contracture. Reversed by revascularization (CABG or balloon angioplasty). less severe form of ischaemia-induced reversible loss of contractile function. *cause: brief ischaemic episode (<30 min) followed by reperfusion. *repetitive stunning can lead to hibernation. UW: How much time does it take for 1 min. If restoration of blood <30 min reversible contractile dysfunction (myocardial stunning) contractility gradually returning to normal over hours to days. IF restoration >30 min total ischemia becomes irreversible.
UW:
one of the earliest signs of coagulative necrosis of myocytes.
RX: *area of infarction expansion, thinning and regional dysfunction. *the rest hypertrophy to compensate. *net result dilated ventricular hypertrophy with enlarged LV cavity. cause hypotension and bradycardia, why? D2 ischemia to SA node which is supplied by UW: RCA which supplies also inferior wall of the myocardium.
UW:
UW:
increases the risk of
by 3 times.
UW: 1-bacterial endocarditis (the most common cause). 2-MI within 10 days. 3-connective tissue disease.
UW: Case scenario: Acute onset of MI + recent viral infection DCM caused by viral myocarditis diagnosed by exclusion and characterized by dilatation of all chambers & biventricular failure. UW: Doxorubicin DCM: *cumulative dose dependent presents many months after discontinuation of the drug. *prevented by DEXRAZOXANE: iron chelating agent that ↓ O2 free radicals produced by doxorubicin.
UW: *B-myosin heavy chain mutation HCM *cardiac cell cytoskeleton mutation + mitochondrial enzyme mutation DCM (third of the cases are AD)
UW: HCM is the most common cause of ventricular fibrillation in individuals < 30 years. Dystrophin mutation DCM & Duchene myopathy & Becker myopathy. UW: HOCM + harsh systolic murmur d2 systolic anterior motion of the anterior leaflet of the mitral valve to the interventricular septum which is bulged by asymmetrical enlargement outflow obstruction. UW: Cardiac amyloidosis
localized atrial natriuretic peptide (ANO) diffuse Ig light chains.
UW: ↑mRNA of natriuretic peptides in the atria indicates hypertrophy & dilatation. UW: Lipofuscin: yellow brown pigment in the myocyte of myocytes in old age d2 product of free radical injury and lipid peroxidation. UW: Carcinoid heart: RT sided endocardial fibrosis (endocardial thickening) restrictive cardiomyopathy & pulmonary stenosis. Dx: plasma serotonin, urinary 5-hydroxy indol acetic acid. UW: Mitral stenosis left recurrent laryngeal nerve impingement (neuropraxia) hoarseness of voice. UW: Constrictive pericarditis: CT scan thickening and calcification of the pericardium.
JVP rapid and steep y descent.
DIT
(the severe form of HF): NO LIP (better than loop diuretics as 50% of patients are euvolumic or hypovolemic. oxygen, loop diuretics, inotropes, positioning.
nitrates
UW: pulmonary congestion ↑hydrostatic pressure capillary leak pulmonary edema alveolar collapse ↓ventilation hypoxemia reactive VC to shunt blood to area with better ventilation pulmonary artery HTN. dysregulation of vascular smooth muscle tone & structural remodeling of pulmonary vasculature.
UW: Aortic stenosis early can cause diastolic dysfunction and hypertrophy then late can cause systolic dysfunction and LVF.
*Osler nodes is d2 immune complex deposition. *Janeway lesions is d2 septic emboli. UW: Progressive
may be the presenting symptom of IE.
UW: cancer + NVBE d2 hypercoagulable state caused by circulating products of cancer which is procoagulable e.g. in Trousseau’s Syndrome (migratory thrombophlebitis) d2 visceral malignancy. UW: Effect of IE on kidney:
*if microemboli hematuria *if immune complex deposition acute diffuse proliferative GN red cell casts and increase in serum creatinine.
nephritic syndromehematuria, proteinuria,
UW: Native valve bacterial endocarditis (NVBE) MVP is the most common cause then RHD. UW: Tricuspid endocarditis + pleuritic chest pain
septic pulmonary emboli.
UW: the least organ to be affected by thromboembolism of IE is LIVER d2 dual blood supply.
for rheumatic fever: (2 major OR 1 major + 2 minors) with evidence 1-evidence of group A beta hemolytic str. ASO titer or anti-DNAase B titer. 2-Minor: fever, ↑ESR, arthralgia and prolonged PR interval. 3-Major: migratory polyarthritis, pancarditis, SC nodules, erythema marginatum and chorea.
UW: Chorea * latency 2-3 months after sore throat * Dx by antineural Abs binding to caudate and subthalamic nuclei. UW: RHD combined AR & AS acute IE AR cong. AS supravalvular + mental retardation + peculiar facies. Accelerated calcific AS with bicuspid aortic valve at 6 th decade. Dystrophic aortic calcification proceeding cell injury and necrosis. UW: Myocarditis cardiac dilatation functional MR HF. Rx: Aschoff body focal areas of interstitial inflammation characterized by 1-fragmented collagen 2mononuclear (antischkow’s cells) 3-multinucleated giant cells (aschoff cells).
UW: Case: mild respiratory illness one week ago, hypotension, tachycardia, JVD, pulse undetected during inspiration, lungs are clear on auscultation. Dx cardiac temponade d2 serous viral pericarditis. NB: (acute JVD + hypotension + tachycardia) cardiac temponade clear lung on auscultation. Tension pneumothorax diminished air entry. *why not fibrinous pericarditis pleuritic chest pain + friction rub. *why not constrictive pericarditis requires month to years to produce cardiac temponade.
UW: chronic constrictive pericarditis: *takes long time *RT sided HF resistant to ttt *tuberous caseaus pericarditis isthe most common cause. *pericardial knock in early diastole after S2.*Kausmel sign, pulsus paradoxicus.
UW: segmental vasculitisthat extend into contiguous veins and nerves buerger disease. Hypersensitivity to intradermal tobacco injection buerger disease. *transmural fibrinoid necrosis PAN. *palpable purpura HSP OR microscopic polyangiitis OR Churg Straus syndrome.
UW: intranasal ulcer + oliguria
Wagner.
UW: pedunculated mass + scattered cell in mucopolysaccharide stroma + abnormal BVs, hmge
Myxoma.
UW: lightening related complications: *Cardiac arrest & arrhythmias (most common cause of death). *Neurological peripheral nerve damage, seizures, confusion, respiratory arrest, autonomic dysfunction. *Dermatological Lichtenberg figures (pathognomonic for lightning strikes) erythema in a fern like pattern. *MSK rhabdomyolysis, bone fracture, compartmental syndrome. *Other cataract (late sequel) rupture tympanic membrane, curling ulcers. UW: Alveolar cells containing golden cytoplasmic granules that turn dark blue with Prussian blue staining? “hemosiderin-laden macrophages” NB: Prussian blue detects iron (hemosiderin) NB: golden yellow cytoplasmic granules or brown pigment is one of two options 1-hemosiderin detected by Prussian blue pigment. 2-lipofuscin NOT detected by Prussian blue.
they inhibit myocardial remodeling and the UW: the most effective long term ttt option of HF + HTN associated deterioration of ventricular contraction function. Also BB.
UW: ttt of isolated systolic htn in old patientif
diabetic ACEIs. Non-diabetic CCBs (amlodipine) or thiazide.
UW: nitrates causes myosin light chain dephosphorylation. K: Theophylline is adenosine receptor blocker by preventing the bronchospastic effect of adenosine.
UW: the most frequent side effect of verapamil is *constipation *gingival hyperplasia *heart block. UW: subacharanoid hmge generates substances from blood clots that cerebral vasospasm altered mental status and -focal neurological deficit 7-10 days after SAH. * .
UW: ttt of postoperative HTN esmolol short acting & easily reversible. *ttt of HTN + renal insufficiency the only available IV agent that improves renal perfusion while it lowers BP.
K: nitruprusside ↓TPR in arteries and veins so used in htn emergency (the DOC used IV). *side effect cyanide poisoning which is treated by: -nitrites produce methaemoglobin which binds the cyanide cyanomethemoglobin. -thiosulfate convert cyanomethemoglobin to methemoglobin.
UW: nitrates venodilator ↓preload which is the main effect in stable angina. NB: nitrates are venodilator in low dose, but in high dose arteriolodilator ↓ afterload but it also ↓coronary flow. UW: which nitrate has the highest bioavailability if given oral? Isosorbide mononitrate. K: tackyphylaxis of nitrates (receptor downregulation): people who use the patch should remove it at night to prevent tackyphylaxis. Due to depleted glutathione stores.
K: K: minoxidil & diazoxide. *Mechanism: ↑ K efflux hyperpolarization of smooth muscle arteriolodilator. *uses: HTN emergency diazoxide (↓insulin release, so used also in ttt of insulinoma) severe HTN minoxidil (hypertrichiosis, so used also in baldness) UW: Energy for myocardium is coming from 3 sources: 1-glycolysis. 2-glucose oxidationless O2 consumption. 3-produce more ATP but requires more O2 * newer drugs for ttt of aiming to shift from FA oxidation to glucose oxidation.
UW: : *stop if ALT > 3 upper normal limit. *Liver function tests are recommended before starting attain therapy; BUT routine monitoring isn’t recommended unless signs of liver dysfunction develop (fatigue, malaise, anorexia) *most hepatotoxicity is within 3 months. UW: Case: patient with angina taking the following medications metoprolol, atorvastatin, aspirin coming to the ER with muscle pain, fatigue, dark urine and acute renal failure. What medication did he take? Enzyme inhibitor that enhance the action of atorvastatin causing these manifestations of rhabdomyolysis. NB: Statins are metabolized by CYP 450 3A4 except pravastatin. UW: Case: H/O MI + low HDL ! “Patients with ↓HDL have high risk CVS events. Non-pharmacological measures such as exercise and weight loss and smoking cessation have significant CVS benefits”
d2 ↓mevalonic acid ↓farnesyl ppi K: Why ↓ATP ↓Na & K pumps cell swelling rupture.
↓electron transport chain
UW: All statins are metabolized by P450 except pravastatin. UW:
is treated by (
+ niacin + omega 3 fatty a cids in fish oil).
UW ↓enterohepatic circulation ↑bile acid synthesis from cholesterol d2 ↑HMG CoA reductase ↑ gallbladder stones. This effect can be blocked by adding statins to cholestyramine. BUT cholestyramine ↓absorption of statins, so administered 4 hours apart. UW: The antilipid drug that ↑TG is cholestyramine. UW: : 5 H: 1-Hot flush use aspirin. 2-hyperglycemiaacanthosis nigricans 3-hyperuricemiaprecipitate gout. 4-hepatitis. 5-Harsh (pruritis). UW:
has a vasodilatory effect and can potentiate the antihypertensive therapy, so adjust the dose.
UW 1-Statins + fibrates ↑myopathy. 2-Cholestyramine + fibrates gallstones. UW: HTN + Dyslipidemia DON’T USE BB or Thiazides ↑lipids.
UW
UW: the dose of digoxin must be reduced in elderly patients even if normal creatinine as digoxin is cleared by the kidney and elderly exhibit age-related renal insufficiency. UW: The initial cellular event triggering digoxin response UW: K:
delayed after repolarization via ↑Ca ventricular tachycardia death.
is used in all
syndrome as it ↑ conduction in the accessory pathway.
UW: The best BB in HF is Carvedilol. UW:
1-BB, CCBs 2-Digoxin 3-amiodarone and sotalol 3-cholinergic agonists pilocarpine & rivastigmine.
:
K: has also: *Muscarinic receptor antagonist↑HR, ↑AV conductionso need initial digitalization before use in AF. &↑QRS&↑QT. *Alpha blocking activity Vasodilatation reflex tachycardia. K:
hematotoxic thrombocytopenia & agranulocytosis.
I II III
Intermediate binding to Na channels but also blocks K. Rate of binding and release is so rapid no change in Vmax. Since they block Na window current ↓APD. Very tight binding & slow release.
↓V max & ↑APD No V max & ↓APD ↓↓↓V max & no effect on APD
UW: Drug with QRS prolongation + little effect on QT class Ic *QRS prolongation means in phase 0 Na blocking activity *little effect on QT minimal effect on APD.
class I
UW: Drug that without the risk of torsade de point Amiodarone. NB: Drugs that prolongs QT interval class Ia & III NB: BB has no effect on QT. UW: drug that prolong QT & prolong PR intervals Sotalol. UW: *verapamil *metoprolol *sotalol *lidocaine *digoxin. UW: ttt of WPW Syndrome Amiodarone & procainamide. UW: class Ic exhibit strong use dependence prolongs QRS at high HR “normally, QRS decrease when HR increase”. Class III exhibit reverse-use dependent prolongs QT at slow HR.
UW: Drug that ↓HR but has no effect on myocardial contractility or relaxation Ivabradine. Ivabradine inhibit Naf channels prolonging phase IV (slow depolarization phase) ↓HR. Ivabradine is a –ve chronotropic with no effect on contractility or relaxation. Uses: used in chronic HF with ↓EF + persistent symptoms despite appropriate ttt.
UW:
