Derm In psoriasis: Neutrophils may form spongiotic clusters in the supercial dermis and the parakeratotic stratum corneum (munro microabscesses) Melanoma commonly mets to the brain, GI tract, bone, liver and lungs !he most common metastatic tumors to the brain are are lung cancer, cancer, renal cancer, cancer, and melanoma melanoma "isinfectants:
#gent #lcohols (isopropanol, ethanol) &hlorhe'idine ydrogen pero'ide
Iodine
Mechanism "isruption of cell membranes% denaturation of proteins "isruption of cell membranes% coagulation of cytoplasm roduces destructive free radicals that o'idi*e cellular components alogenation of proteins and nucleic acids
$poricidal No N +es +es
+es +es
eroderma pigmentosum is #- It is "N# e'cision repair . can/t repair "N# follo0ing 12 light damage #n Ig3 independent urticarial can develop after e'posure to substances that directly stimulate mast cell degranulation (opiates, #4, radiographic contrast media) 3rythema migrans is the classic skin lesion of lyme disease Mycobacterium scrofulaceum is commonly found in and around around environmental 0ater sources It is the etiologic agents of scrofula, a disease characteri*ed by lymphadenitis (cervical) that occurs most often in children -ocky mountain spotted fever risk factors include fre5uent contact 0ith dogs and e'posure to 0ooded areas or grassy elds Most common organisms that cause otitis media are: strep pneumo, h in6uen*a, and mora'ella -ecurrent infections 0ith these organisms suggests humoral immunodeciency neumocystitis and chronic candidiasis suggests !7cell deciency deciency !he key cells involved involved in cell mediated immunity immunity are macrophag macrophages, es, &"89 helper helper ! cells, &" &" cytoto'ic cytoto'ic t cells and N; cells
el) &ommon medical conditions in6uenced by multiple genes: 7 #ndrogen #ndrogenetic etic alopeci alopecia, a, epilepsy, epilepsy, ischemic ischemic heart heart disease, disease, schi*op schi*ophre hrenia, nia, glaucom glaucoma, a, !N, malignan malignancy, cy, type II "M ;oplik spots are grains of sand on an erythematous base ne't to the ? nd molar !ubercu !uberculoid loid leprosy leprosy spots are are hypopigmented hypopigmented and anestheti*ed anestheti*ed due due to superical nerve involvement involvement $kin test for tuberculoid leprosy is the lepromin skin test It 0ill be positive because of the strong &"8 !h@ cell7mediated cell7mediat ed immune response Aepromatous leprosy is is characteri*ed by a 0eak cell mediated response response !he lepromin lepromin skin test test is usually nonreact nonreactive ive in these pts pts -emember: -emember: tuberculosis tuberculosis itself itself involves involves a strong strong cell7 mediated response (resulting in caseating necrosis) !his should help remember it
lane 'anthomas are linear lesions in skin folds that are strongly associated 0ith primary biliary cirrhosis anthelasma is a cutaneous lesion (commonly found on th eyelid) that contains lipid7laden histiocytes (foam cells) &lassically, these are are associated 0ith primary or secondary hyperlipidemia &hronic cholestatic processes including obstructive biliary lesions and primary biliary cirrhosis result in subse5uent hypercholesterolemia, leading to the formation of 'anthelasmas 2=2 mainfests 0ith a burning sensation andBor pain unilaterally in a dermatomal distribution In ?7C days, an erythematous maculopapular maculopa pular rash develops in the aDected dermatome !he papules transform into the vesicles that later coalesce -upture of the vesicles produces produces ulcers that crust in a fe0 0eeks !he pt is contagious until the lesions are dry !*anck . intranuclear intranuclear invlsuion invlsuions s in keratinocytes keratinocytes and and multinucleated multinucleated giant cells cells are seen seen In bacterial vaginosis, alterations in the normal vaginal 6ora (specically loss of lactobacilli and overgro0th of mi'ed anaerobic organisms) produce a gray discharge and a shy odor that becomes more prominent 0ith addition of ;E (the 0hiD test)
&lass #nti7pseudomonal pe pencillins &ephalosporins #minoglycosides
"rugs !icarcillin, pi piperacillin &efta*idime (C rd generation), cefepime (8th generation) #mikacin, gentamycin, tobramycin &ipro6o'acin, levo6o'acin #*teronam Imipenem, meropenem
Aymphangiosarcoma (pg ?F) is also called $te0art7!reves syndrome In breast carcinoma, nipple inversion is observed 0hen the tumor invades the central region of the breast, and skin retraction is identied 0hen the cancer inltrates the suspensory &ooper ligaments Granulomas associat ed 0ith !4 develop a central *one of necrosis due to hypo'ia hypo'ia and free7radical in>ury in>ury !his appears grossly as a granular and cheesy material 4acillary angiomatosis is from bartonella henselae (cat scratch disease, 0hich can also cause culture7negative endocarditis) &at scratch disease is characteri*ed characteri* ed by lo0 fever, lymphadenopathy, and self limited course 4# can be fatal if left untreated though #4# esters are sunscreens for 124 only (?FH7C?H) 12# is C?H78HH # number of topical and systemic therapies are available for treating psoriasis !opical vitamin " analogs are fre5uently used and include calcipotriene, calcitriol, calcitrio l, tacalcitol !hese medications bind to and activate the vit " receptor, a nuclear transcription factor that causes inhibition of keratinocyte proliferation and stimulation of keratinocyte diDerentiation diDerentiatio n !reatment 0ith vit " analogs has also been sho0n to inhibit ! cell proliferation and other in6ammatory mediators Nafcillin is often used to treat skin and soft tissue infectinos for 0hich $ aureus is a common cause (folliculitis, abscess) #cyclovir, its prodrug valacyclovir, famiciclovir, and ganciclovir are all nucleoside analogues that re5uire both herpes viral and cellular kinases for conversion to their active nucleoside triphosphate form &idofovir is a nucleoside monophosphate that re5uires only cellular kinases for activation Aocal cutaneous adverse eDects of chronic topical corticosteroid administration including atrophyBthinning of the dermis that is assoacited 0ith loss of dermal collagen, drying, cracking, andBor tightening of the skin, telangiectasias, and ecchymoses
Musculoskeletal &audal regression syndrome is a rare condition atients are born 0ith agenesis of the sacrum and occasionally lumbar spine and e'perience resultant 6accid paralysis of the legs, dorsi6e'ed contractures of the feet, and urinary incontinence &audal regression syndrome can range in severity from isolated anal atresia to sirenomelia It is fre5uently related related to poorly controlled maternal diabetes, though this is certainly not the only etiologic factor considering the fre5uency of diabetes and the relative rarity of caudal regression syndrome
lane 'anthomas are linear lesions in skin folds that are strongly associated 0ith primary biliary cirrhosis anthelasma is a cutaneous lesion (commonly found on th eyelid) that contains lipid7laden histiocytes (foam cells) &lassically, these are are associated 0ith primary or secondary hyperlipidemia &hronic cholestatic processes including obstructive biliary lesions and primary biliary cirrhosis result in subse5uent hypercholesterolemia, leading to the formation of 'anthelasmas 2=2 mainfests 0ith a burning sensation andBor pain unilaterally in a dermatomal distribution In ?7C days, an erythematous maculopapular maculopa pular rash develops in the aDected dermatome !he papules transform into the vesicles that later coalesce -upture of the vesicles produces produces ulcers that crust in a fe0 0eeks !he pt is contagious until the lesions are dry !*anck . intranuclear intranuclear invlsuion invlsuions s in keratinocytes keratinocytes and and multinucleated multinucleated giant cells cells are seen seen In bacterial vaginosis, alterations in the normal vaginal 6ora (specically loss of lactobacilli and overgro0th of mi'ed anaerobic organisms) produce a gray discharge and a shy odor that becomes more prominent 0ith addition of ;E (the 0hiD test)
&lass #nti7pseudomonal pe pencillins &ephalosporins #minoglycosides
"rugs !icarcillin, pi piperacillin &efta*idime (C rd generation), cefepime (8th generation) #mikacin, gentamycin, tobramycin &ipro6o'acin, levo6o'acin #*teronam Imipenem, meropenem
Aymphangiosarcoma (pg ?F) is also called $te0art7!reves syndrome In breast carcinoma, nipple inversion is observed 0hen the tumor invades the central region of the breast, and skin retraction is identied 0hen the cancer inltrates the suspensory &ooper ligaments Granulomas associat ed 0ith !4 develop a central *one of necrosis due to hypo'ia hypo'ia and free7radical in>ury in>ury !his appears grossly as a granular and cheesy material 4acillary angiomatosis is from bartonella henselae (cat scratch disease, 0hich can also cause culture7negative endocarditis) &at scratch disease is characteri*ed characteri* ed by lo0 fever, lymphadenopathy, and self limited course 4# can be fatal if left untreated though #4# esters are sunscreens for 124 only (?FH7C?H) 12# is C?H78HH # number of topical and systemic therapies are available for treating psoriasis !opical vitamin " analogs are fre5uently used and include calcipotriene, calcitriol, calcitrio l, tacalcitol !hese medications bind to and activate the vit " receptor, a nuclear transcription factor that causes inhibition of keratinocyte proliferation and stimulation of keratinocyte diDerentiation diDerentiatio n !reatment 0ith vit " analogs has also been sho0n to inhibit ! cell proliferation and other in6ammatory mediators Nafcillin is often used to treat skin and soft tissue infectinos for 0hich $ aureus is a common cause (folliculitis, abscess) #cyclovir, its prodrug valacyclovir, famiciclovir, and ganciclovir are all nucleoside analogues that re5uire both herpes viral and cellular kinases for conversion to their active nucleoside triphosphate form &idofovir is a nucleoside monophosphate that re5uires only cellular kinases for activation Aocal cutaneous adverse eDects of chronic topical corticosteroid administration including atrophyBthinning of the dermis that is assoacited 0ith loss of dermal collagen, drying, cracking, andBor tightening of the skin, telangiectasias, and ecchymoses
Musculoskeletal &audal regression syndrome is a rare condition atients are born 0ith agenesis of the sacrum and occasionally lumbar spine and e'perience resultant 6accid paralysis of the legs, dorsi6e'ed contractures of the feet, and urinary incontinence &audal regression syndrome can range in severity from isolated anal atresia to sirenomelia It is fre5uently related related to poorly controlled maternal diabetes, though this is certainly not the only etiologic factor considering the fre5uency of diabetes and the relative rarity of caudal regression syndrome
Glenohumeral >oint is the most commonly dislocated >oint int eh body o0ing to the shallo0 articulation bet0een the humeral head and the glenoid fossa of the scapula In rotator cuD syndrome, the most commonly in>ured tendon is the supraspinatous because this tendon is prone to repeated impingement trauma bet0een the humeral head and the acromion ections into the gluteal region should target the superloateral 5uadrant, to avoid damage to the gluteal nerves and sciatic nerve !his pt is e'hibiting e'hibiting the classic gluteus medius gaitJ . hip dips do0n0ards 0hen the ipsilateral foot is lefted oD of the ground !his is observed 0hen there is in>ury to the superior gluteal nerve or to the gluteus medius muscle itself itself !he superior gluteal nerve leaves the pelvis through the greater sciatic foramen above the level of the piriformis In>ection in the superomedial 5uandrant of the buttock is liekyl to in>ure this nerve $ciatic nerve is in the inferomedial 5uadrant of the buttock Aarge 6uid collection in the retroperitoneum laying anterior to the psoas muscle 0ith isodense 6uid is consistent 0ith a spontaneous retroperitoneal hematoma, likely secondary to 0arfarin use !he femoral nerve descends through the bers of the psoas muscle, and then runs beneath the inguinal ligament into the thigh ury, or ischemia ury . knee buckles, patellar re6e' is diminished, sensory loss over the anterior thigh $everal muscles insert of the clavicle including the pectoralis ma>or on the inferior medial aspect, the deltoid on the inferior lateral aspect, the subclavius on the interior lateral aspect, the trape*ius on the superior lateral aspect, and the $&M on the superior medial aspect $&M is innervated by &N I -adial head sublu'ation (nursemaid/s elbo0) is the M& elbo0 in>ury in children children It occurs most fre5uently bet0een the ages of @78 yo !he in>ury often results from a sarp pull on the hand 0hile the forarm is pronated pronated and the elbo0 is e'tended !his traction causes the annular ligament to tear form its periosteal attachement at the neck of the radius It then becomes trapped in the radiohumeral >oint ;ids 0ith this in>ury present 0ith the in>ured arm held close to the body 0ith the elbo0 e'tended (or slightly 6e'ed) and the forearm pronated !he child is is typically in little distress distress until until attempts are made to move the elbo0 elbo0 !he inferior inferior gluteal nerve nerve e'its the the pelvis through through the greater greater sciatic foramen foramen belo0 the the piriformis piriformis ousemaid/s knee . prepatellar bursitis . chornic trauma from repeated kneeling #lso common in roofers, plumbers,a nd carpet layers "ysthymic disorder is a chronic, lo07intensity mood disorder (at least ? years) that responds 0ell to antidepressant medications Ma>or depression is diagnosed 0hen at least of the follo0ing symptoms are present for at least ? 0eeks: depressed mood, sleep disorder, anhedonia, guilt (0orthless, hopelessness, regret), energy decit, concentration decit, appetite disorder, psychomotor retardation or agitation, suicidality ($#G3&#) !he median nerve nerve courses courses 0ith the brachial brachial artery in the groove groove be0te0een be0te0een the biceps brachii brachii and the brachialis brachialis muscles It gains access to the forearm in the medial aspect of the antecubital antecubital fossa and immediately immediatel y courses bet0een the humeral and ulnar heads of the pronator teres muscle It then courses bet0een the 6e'or digitorum supercialis and the 6e'or digitorum profundus muscles before netering the 0rist and hand 0ithin the 6e'or retinaculum !he musculocutaneous musculocutaneous nerve nerve courses courses directly bet0een the biceps biceps brachii brachii and the coracobrach coracobrachialis ialis muscles muscles In>ury to this nerve leads to paralysis of the biceps and the brachialis, 0hich results in an inability to 6e' the forearm !reatment !reatment for for paro'ysmal paro'ysmal supraventricu supraventricular lar tachycardia tachycardia can be 0ith 0ith vagal stimulation, stimulation, such such as carotid carotid sinus massage or the valsalva maneuver Maneuvers that increase vagal tone increase the refractory refractory period in the #2 node and help prevent a reentrant circuit from conducting If valsalva fails, the I2 adenosine is used $erum sickness is a type III $ reaction 0hich generally produces fever, urticarial, arthralgias, glomerulonephritis, glomerulonephrit is, and lymphadenopathy 7@H days after e'posure e'posure to an antigen It can have vasculitis 0ith vessel 0all brinoid necrosis and neutrophil inltration can be features of systemic despotition of circulating
immune comple'es in arteries and arterioles $ulfonamides can provoke this condition !here is often hypocomplimentemia, including a decreased serum &C level $erum sickness is a type III $ reaction characteri*ed by desposition of circulating, complement 'ing immune comple'es and resulting vasculitis #ssociated ndings include fever, urticarial, arthralgias, glomerulonephritis, lymphadenopathy, and a lo0 serum &C level 7@H days after intravascular e'posure to antigen Neuromuslcular lesions, ragged red skeletal muscle bers, and lactic acidosis suggest mitochondrial encephalomyopathy Mitochondria make #! via o'idative phsophorylation, 0hich is 0hy mitochondrial problems often lead to lactic acidosis and primarily aDect tissues 0ith the highest metabolic rates (neural tissue, muscular tissue) eteroplasmy describes the condition of having diDerent organellar genomes (mutated and 0ild type) 0ithin a single cell aundice, poor feeding, and congenital heart defects $trep pneumo, in6uen*a, Neisseria, and salmonella are encapsulated (increased risk in asplenics and $$ pts) Give pneumova' for $ pneumo, hib for h in6uen*a type 4, and the meningitis polysaccharide capsular vaccine for N meningitidis $almonella possesses a special capsule called the vi antigen (2i stands for virulence) 0hich protects the bacterium from opsoni*ation and phagocytosis 3 coli is second M&& of osteomyelitis after salmonella in $$K $acroiliitis occurs in ?HL of reactive arthritis cases #lso assoacited is synovitis, enthesitis, con>unctivitis, mouth ulcerations, balanitis circinata, and keratoderma blennorrhagicum !etanospasmin is a protein to'in produces by & tetani that can travel by retrograde a'onal transport into the &N$ !he tetanospasmin heavy chain binds ganlioside receptors on the neuronal membranes and the light chain inhibits release of glycine and G#4# from inhibitor interneurons #bsence of these inhibitor N!s causes sutained muscle contraction, or tetanus rominent signs and symptoms include: masseter muscle spasm (lock>a0), opisthotonos, dysphagia, and facial muscle spasm (risus sardonicus) !etanus is inhibited by tetanus to'oid (inactived tetanus to'in) vaccination !his vasccination elecitis humoral immunity for tetanus to'in (antito'in antibodies . active immunity) In goodpastures, autoantibodies are formed against the noncollagenous domain of the alpha7C chain of collagen I2 (anti7G4M antibodies) Esteocytes in bone communicate via gap >unctions to send signals and e'change nutreints and 0aste products Esteocytes can stress mechanical stresses and send signals to modulate the activity of surface osteoblasts, thereby helping to regulate bony remodeling Myelopero'idase deciency is an immune deciency not unlike the caused by &G" In &G" the absence of N#" o'idase causes an inability to form hydrogen pero'ide, and therefore the en*yme ME has no susbtrate (hydrogen pero'ide) to metaboli*e into reactive o'ygen species (o'ygen free radicals) used to kill microorganisms !he diDerence bet0een these ? illnesses lies in the fact that in &G" some phagocytosed organisms can be killed because these organisms produce their o0n ?E? 0hich ME then uses to produce free radicals In ME deencicy, the en*yme ME is absent, so both catalase positive and catalase negative organisms 0ill survive 0ith pahgocytes #n Interesting =oo Must ave Mammals (#ctin in the I7band attaches at the =7line, Myosine in the 7band attaches at the M line) Many infections of aeruginosa often begin 0ith e'posure to a 0ater course of creation of a moist environment (s0immers ear, hot tub folliculitis, burn 0ound) ot tub folliculitis is a supercial and self7limited aeruginosa infection of the hair follicles $trep pyogenes is pyrrolidonyl arylamidase (+-) positive #ll medically important fungi may be divided into a fe0 groups according to the area of involvement:
7 7 7 7
&utaneous mycoses (dermatophytoses and tinea versicolor) $ubcutnaeous mycoses (sporotrichosis) Mycoses 0ith systemic involvement (most often lungs, are histoplasmosis, coccioidoses, blastomycoses) Epportunistic mycoses (candida, aspergillus, mucor, rhi*opus)
& perngens makes gas gangrene by rapidly metaboli*ing carbohydrates & perfrigens causes late onset food poisoning 4 anthracis produces an antiphagocytic capsule that is re5uired for pathogenicity !he capsule is uni5ue in that it contains "7glutamate instead of polysaccharide !here are ? diDerent types of bones in the body !he cortical or compact bone makes up the shafts of long bones and outer envelopes of all bones ostmenopausal osteoporosisi typically involves cancellous bone, 0hich is preodiminantly present in the vertebral column, distal radius, hip, and neck of femur !he interaction of -#Nk 0ith its ligand is decreased by another protein secreted by the osteoblast . osteoprotegerin (EG), and it acts as a decoy receptor 4one turnover increases 0hen -#N;7A is high and EG is lo0 ! stimulates the secretion of monocyte colony stimulating factor and -#N;7A by osteobalsts, thus stimulating osteoclastic precursor to become mature osteoclasts Evere'pression of -#N; receptors in hypoestrogenic states causes increased bone resorption due to increased osteoclastic activity 4lack females have high bone density than 0hites 3ven at same bone density, blacks fracture less often 4one density increases 0ith increasing 4MI hen a specic ion channel opens, the respective ions 0ill 6o0 across the membrane in a direction that brings the resting membrane potential closer to that ion/s e5uilibrium potential (5uestion I": @C@) 4one specic alkaline phosphatase is easily denatured by heat (bone 0ill boil) yridinoline covalently corss7links collagen bers% these cross7links are the most commonly used method in assessing osteoclastic activity ydro'yproline is also released into blood 0hen osteoclasts resorb bone, but meat products also increase hydro'yproline !artrate resistant acid phosphatase, urinary hydro'yproline, and urinary deo'ypyridinoline re6ect osteoclastic activity% urinary deo'ypyridinoline is the most reliable !' of MG involves cholinesterase inhibitors, animmunosuppresive agent, or thymectomy $keletal muscle is nicotinic cholinergic receptors% gut is muscarinic &lubbing: lung cancer (large cell carcinoma especially), !4, &<, bronchiectasis, pulmonary !N, empyema, other chronic lung d* assoacited 0ith hypo'ia% cyanotic congenital heart d* (especially tet) and bacterial endocarditis% I4" (crohns, 1&), hyperthyroidism, malaborption 3levated levels of G3? and "G< and 23G< causing brovascular proliferation is associated 0ith clubbing Iron deciency: spoon shaped nails $ubperiosteal thinning: hyperparathyroid (from <#: renal osetodystrophy) Esteoclasts in aget/s d* are typically very large and can have up to @HH nuclei In skeletal muscle, one !7tubule contacts ? terminal cisterns forming a triad at the >unction of the #7band and the I7band Genetic factors are responsible for up to HL of the variation in peak bone mass among invididvuals 1274 light is necessary for activation of pro7vit "C into pre7vit"C 0hich then, 0ith heat, converts to "C (must still be activated in kidney though) rolyl and lysyl hydro'ylase hydrolate proline and lysine residues of pro7collagen 2it & is re5uired ithout the hydro'ylation, cross linking is greatly reduced and strength is 0orse
$igns and symptoms of psoas abscess include fever, back or 6ank pain, inguinal mass, and diOculty 0oalking ain is e'acerbated by movements that cause the psoas to be stretched or e'tended (such as e'tension fo the hip . this is the psoas sign) !hese pts have hip 6e'ion and lumbar lordosis to inhibit hip 6e'ion Esteopetrosis is characteri*ed by the peristance of primary, unmineralie**d spongiosa in the medullary canalsJ oints $ymptoms generally resolve spontaneously $pasmodic torticollis: focal dystonia 0here the neck is stuck in @ position 4lephorospasm is second most common focal dystonia sriter/s cramp is another common dystonia MMs are important in 0ound healing !hey degrade collagen and remodel !hey also encourage myobroblast accumulation at the 0ound edges and scar tissue remodeling Myobroblasts initiate 0ound contraction during healing by second inteitn &ontracture may occur 0hen unusually pronounced MM activity results in e'cessive 0ound contraction (are actin containing brobalsts myobroblastsQQ) A3M$ R pro'imal uscle 0eakness $ubdural hematoma and bilateral retinal hemorrhages R shaken baby syndrome $piral fractures R child abuse In ankylosing spondylitis there are enthesitis (in6ammation 0here tendons insert into bone) If it happens at the costovertebral and costosternal >unctions there 0ill be pain limiting chest 0all e'pansion leading to hypoventilation !ype I muscles R postural muscles (lo07level sustained force) If a leg is immobili*ed for a 0hile, skeletal muscle bers in his leg 0ill decrease in si*e If it is more prolonged, it can start decreasing in number as 0ell +ou can also get osteoporosis of disuse (0ith bone resorption) 3ye stuD (I" S?) emolysis causes haptoglobin levels to decrease by binding to free haptoglobin and the comple' is cleared hepatically Esteomyelitis aDects young boys Iti usually aDects the metaphysis because this region contains slo0 6o0ing, sinusoidal vasculature that is conducive to microbial passage ithout treatment, it can progress to chronic suppurative osteomyelitis Golgi tendon organs are sensory receptors located at the >unction of the muscle and tendon that are innervated by group Ib sensory a'ons G!Es are connected in series 0ith the contracting e'trafusal skeletal muscle bers hen a muscle actively contracts against resistance, the increase in tension is transitted through the tendon activated the G!E in the process IN contrast, G!Es are relatively insensitive to changes in muscle length because the lengthening that occurs 0hen a muscle is passively stretched takes place primarily in the muscle bers and not in the tendon !he Ib bers then synapse on inhibitory interneurons in the spinal cord that stop the alpha motor bers !his 0ay, !he golgi tendon circuit is a negative feedback system that regulates and maintains muscle tension hen a muscle e'erts too much force, the G!Es inhibit contraction of the muscle, causing sudden muscle rela'ation (I" ?SS) Ia and II muscle bers from the intrafusal muscle bers from muscle psindles are responsible for the stretch re6e'
Biochemistry
Erotic aciduria en*ymes messed up are orotate phosphoribosyl transferase and EM decarbo'ylase !hese turn orotic acid into 1M It orotic aciduria, give uridine, 0hich is coverted to 1M by the action of nucleoside kinases and then 1M inhibits carbamoyl phosphate synthetase ?, thus attenuating orotic acid production !his is a problem in pyramidine base synthesis only (not purines) 4S (pyrido'ine) is a coafactor in transamination, deamination, decarbo'ylation, and condensation r'ns
#mino groups are funneled into glutamate during protein catabolism (I" @CSF) &atabolims of isoleucine, valine, threonine, methionine, cholesterol, and odd chian <#s leads to the formation of propionic acid, 0hich is then converted to methylmalonic acid by biotin dependent carbo'ylation Isomeri*ation of methylmalonyl &o# forms succinyl co#, 0hich then enters the !&# cycle # congenital deciency of propianyl &o# carbo'ylase, the en*yme responsible for the conversion of propionyl co# to methylmalonyl co#, leasd to a development of propionic academia, as propionyl &o# accumulates ropionic academia is clinically characteri*ed by poor feeding, vomiting, hypotonia, lethargy, dehydration, and an anion gap acidosis ropionic acid is the intermediate in the catabolism of branched chain ##s, such as valine, and is not produced during the catabolism of other amino acids listed (@C8H) "N# polymerase synthesi*e ne0 N"# strands in / to C/ direction and re5uire a free C/7E group upon 0hich to begin polymeri*ation !his C/7E group is provided by the en*yme primase, a "N#7dependent -N# polymerase 0hich forms -N# primers 3'posure to radiation, including therapeutic and palliative radiation therapy, induced "N# damage through "N# ds fractures and the formation of o'ygen free radicals "N# damage from e'posure to 12 radiation leads to the formation of pyrimidine7pyrimidien dimers (thymine dimers) rimary structure: ## linked by peptide bonds $econdary structure: alpha7eli' and beta pleated hseet heald together by hydrogen bonds (every 8 in alpha heli', bet0een all residues of antiparallel strands in beta pleated sheets) !ertiary structure: comple' folding (many forces icnludign ionic bonds, hydrophobic interactions, 7bonds, disulde bonds) 4eta pleated sheets are less soluble than alpha heli' and therefore aggregate (al*heimers) - is a substrate used by G-! during purine salvage and it accumulates 0hen there is deciency of the en*yme - is created by - synthetase in the rst step of de novo purine synthesis hen - is high, it 0ill be shuttled into more IM formation and ultimately more GM and #M (purine) formation !his makes sense, because 0ithout purine salvage, 0e 0ill have to make more, 0hich re5uires - #n en*yme in converting - to IM is - amidotransferase, so this enyme 0ill be up also GM re5uires #! and #M re5uires G! so that purine synthesis favors the nucleotide that is decient ropionyl co# to to methylmelanyl co#, and then methylmelanyl co# becomes succinyl co# !his last step is an isomeri*ation using methylmalonyl &o# mutase and vit 4@? ith a vit 4@? defcieincy, the pt 0ill have an isomeri*ation problem at this step !his is called methylmalonic aciduria (I" @C8@, pg F) #rginase deciency R spasticity !hymine (pyrimidine) dimers can be removed by the action of 12 specic endonucleases !his en*yme causes nicks at damaged sites that are later e'cised yb the / to C/ e'onuclease activity of "N# polymerase, 0hich also synthesis ne0 "N# in the place of the damaged "N# Most common &< mutation is a deletion of the phenylalanine at position H in the &
from disorders of the urea cycle is increased blood concentration of ammonia, leading to &N$ system dysfunction !reatment of urea cycle disorders is balancing protein intake to output Neuroaminidase (sialidase) deciency is the cause of human sialidosis
2ery long chain and some branched chain <#s cannot undergo mitochondrial beta o'idation !hese undergo special o'idation (beta for 2A&<# or alpha for branched cahin <#) in pero'isomes =ell0eger syndrome can/t form myelin properly -efsum d* build up of phytanic acid (branched chain <#) in the body $trict avoidance of chlorophyll in the diet is re5uired
seudotumor cerebri
cerebral edema in the setting of benign intracranial !N
arkin, IN;@, "T7@ are assoacited 0ith #- forms of parkinsons d* (UH) and all promote the degradation of misfolded proteins via the 1b7proteosome system
Gluconeogenesis is thus impaired due to lack of energy 0hile glucose consumption is markedly increased, resulting in severe hypoglycemia Glycine is the smallest ## and it ts into the space 0hen three alpha collagen chain come together to form heli' Neutrophils are the primary cell responsible for the intense in6ammatory response in pts 0ith gout due to the phagocytosis of M$1 crystals &olchincine stops the chemota'is of neutrophils romoters: !#!# is ? nuc upstream &##! bo' is PH nucleotides upstream Marfan/s syndrome is a defect in brillin, an e'tracellular glycoprotein that is abundant in the *onular bers of the lens, the periosteum, and the aortic media ompe d* presents not 0ith hypoglycemia, but 0ith hepatomegaly and icnresed risk of cirrhosis (also cardiomegaly, macroglossia, hypotonia, M-) athology sho0s abnormal accumulation in the lysosomes !he @S$ r-N# strand is the only piece of r-N# found in the prokaryotic CH$ ribosomal subunit !his r-N# 0ithin the CH$ subunit e'presses a se5uence complementary to the $ine7"elgarno se5uence in all prokaryotic m-N# !he $hine7"elgarno se5uence is located @H bases upstream from the #1G start codon on prokaryotic m-N# !hese ? complementary se5uences allo0 the m-N# and the CHs ribosomal subunit to bind in preparation for protein translation Ence the m-N# is bound to the CH$ subunit, an initator t-N# binds to the #1G start codon, the H$ ribosomal subunit >oins the comple', and the protein synthesis begins 4 (&o#) is important in o'aloacetate to citrate and then succinyl7&o#, but also synthesis of vit #, ", cholesterol, steroids, heme #, <#s, ##s, proteins "eciency of pantothenic acid is rare, though it has been observed in severely malnourished people 0ho complain of paresthesias and dysesthesias (burning feet syndrome) and GI distress $plicing is performed by spliceosomes, 0hich consist of sn-Ns plus proteins $ynthesis of sn-N occurs in the nucleus, cataly*ed by -N# pol II "ebranching en*yme deciency can be diDerentiated from other glycogen storage d* by demonstrating the accumulation of abnormally short outer de'trin7like structures in the cytosol of hepatocytes 0ith an absence of histopathological fatty inltration of the liver !Gs stored in adipose tissue is metaboli*ed to free <#s and glycerol by hormone sensitive lipase Glycerol is then transported to the liver 0here it is phosphorylated to GC via liver specic glyercol kinase GC is then converted to "# "# can then be used for glycolysis (#!) or gluconeogenesis (glucose) Glycerol in the liver can also be used for !G synthesis oly# tail protects m-N# from degradation 0ithin the cytoplasm after it e'its the nucleus &holesterol and <# synthesis use N#" as an electorn donor 3'amples of proteins that are able to bind "N# include transcription factors, steroids, thyroid proteins, vit " receptors, retinoic acid receptors, "N# transcription and replication proteins, and others N7myc can bind "N# &7myc is up in burkitt lymphoma omobo' genes typically code for "N#7binding transcription factors 0hich alter the e'pression of genes involved in morphogenesis !he insulin receptor is a tetrameric structure consisting of ? alpha and ? beta subunits !he alpha subunits are e'tracellular and they provide the binding site for insulin !he beta subunits are intracellular and contain tyrosin kinase domains that are activated 0hen insulin attaches to the alpha subunits # series of do0nstream signaling is then triggered, starting 0ith the autophosphorylation of the I- !hen the I-$ gets involved !N<7 alpha is a proin6ammatory cytokine that induces insulin resistance through the activation of serine kinases, 0hich then result in phosphorylation of the I-$7@ serine residues !his inhibits I-$ tyrosine phosphorylation by insulin osphorylation of serine residues in the beta subunit of the I- also hinders do0nstream signaling, resulting in resistance to the normal actions of insulin &atecholamines, glucocorticoids, and glucagon can also induce insulin resistance by this same mechanism, and intracellular <<#s are suspected of increasing serine kinase activity as 0ell !ransmembrane domain . P alpha helical segments each containing ?H ##s 0ith hydrophobic, nonpolar groups Nonpolar hydrophobic ##: valine, alanine, isoleucine, methionine, phenylalanine
&ortisol is a cytoplasmic receptor that is bound to $s hen cortisol binds to the carbo'yl terminal, the $s liberate, the receptors dimeri*e, and go to the nucleus !hey control gene e'pression by binding to t"N# at the hromoen7responsive elements in the promoter region of target genes &ortisol increases NM! If delta G is negative, ;e5 0ill be greater than @, and the concentration of products at e5uilibrium 0ill e'ceed that of the substrates If delta G is positive, ;e5 0ill be less than @, and the formation of substrates 0ill be favored # ;e5 of H is not mathematically possible # ;e5 of @ 0ould occur in a state 0here G is H # ;e5 of @ 0ould occur in a state 0here G is negative Gluconeogenesis: alanine
glucose 0hich begins 0ith the transamination of alanine to pyruvate
-3- is the site of secretory, lysosomal, and integral membrane proteins #! is generated from the !&# cycle via o'idative phosphorylation #! can also be generated by substrate level phosphorylation, a process 0hich involves the direct transfer of a phosphate group to #" from a reactive intermediate $ubstrate level phosphorylation can occur in botht he cytoplasm and the mitochondrial matri' IN the citric acid cycl, G! by succinyl co# synthetase during the conversion of succinyl co# to succinate Mitochondrial G! can undergo transphosphorylation 0hereby G! donates a high energy phosphate to #" to form #! IN gluconeogenesis, the hydrolysis of G! is re5uired for the phosphorylation and decarbo'ylation of o'aloacetate to 3 by 3 carbo'ykinase ##s 0ith C titratable protons: histidine, arginine, lysine, aspartic acid, glutamic acid, cysteine, tyrosine istidinemia e'ists: speech defects, psychomotor and retardation, emotional disturbance 4ig in Tapan Aack of histidase
shock
Aactic acidosis is an angion7gap metabolic acidosis that results from overproduction andBor impaired clearance of lactic acid In septic shock, impaired tissue o'ygenation decreases o'idative phosphorylation, leading to the shunting of pyruvate to lactate after glycolysis ence, there is an increase in lactic acid formation epatic hypoperfusion also contributes to buildup of lactic acid, as the liver is the primary site of lactate clearance #spiration pneumonia: superior lo0er lobe or posterior upper lobe #naerobic cause this: peptostreptococcus, bacteroides, fusobacterium, prevotella rotons dissociate from ##s 0hen the p e'ceeds the p;a associated 0ith each given proteon
!he alpha subunit of the inactivated G7protein is bound to G" 1pon activation of the receptor, the alpha subunit undergoes a conformation change and G" is released $ubse5uent binding of G! then allo0s for the dissociation of the alpha subunit from the remainder of the G protein comple' !here are multiple subtypes of alpha G proteins, each 0ith diDerent secdonary eDects Gs is c#M then activates ;# ;# phosphorylates the serine tor threonine residues in some en*ymes, leading to actiation or deactivation
"iabeics get hyperosomolar hyperglycemia, a metabolic derangement often precipitated by infection &haaracteri*ed by dehydration, hyperglycemia, hyperosomoalrty 0ithout ketoacidosis Glucose into beta cell 4eta cell enters glycolysis !&# cycle happens #! is made igh #!%#" ratios 0ithin the beta cells results in the closure of ;#! channel, 0hich causes insulin secretion by opening the voltage dependent calcium channels GAucokinase is a ma>or glucose sensor in the beta cell !his is a rate limiting step in the beta cell !his is ME"+ Nuclear receptors% #-, <#s, retinoids, thyroid mt"N# has ?? t-N#s and ? r-N#s erpsensitivity pneumitis lo0 &"8:&"% #I"$ lo0 &"8:&"% sarcoidosis high &"8:&" &yanide poisoning is bitter, almond breath
ithin the brain, astrocytes and neurons interact to regulate the metabolism of glutamate, glutamine, and ammonia in a process kno0n as the glutamate7glutamine cycle Glutamate released by neurons during neurtotranmission is taken up by astrocytes and converted to glutamine, a non7neuroactive compound Glutamine is then released by astrocytes and taken up by neurons, 0here it is either converted back to glutamate for use as a N! or transaminated into a7;G for use in the ;rebs cycle yperammonemia in hepatic encephalopathy results in depletion of a7;G, caushing inhibition of the ;rebs cycle 3'cess ammonia also depletes glutamate, an e'citatory N!, and causes accumulation of glutamine, resulting in astrocyte s0elling and dysfunction &alcium in6u' into endothelial cells causes eNE$ activation and ultimately arginine NE and citrulline !he NE then goes into the smooth muscle cells and activates guanylyl cyclas e to make cGM !his then casues vasodilation by decreasing calcium levelsin the smooth muscle cytoplasm via ;G
t-N# is the only -N# species that contains the nucleoside thymidine Aeptin is produced by adipocytes, and large fat cells produce more leptin than small ones $erum leptin concentrations are highly correlated 0ith body fat content Aeptin decreases food intake int eh follo0ing important 0ays: 7 Aeptin decreases the production of Neuropeptide +, a potent apetite stimulatnt, in the arcuate nuc of the hypothalamus 7 Aeptin stimulates the produdciton of EM& in the arcuate nucleus a7M$ is produced by cleavage of EM& and inhibits food intake 4acterial m-N# can be polycistronic, meaning that one m-N# codes for several proteins #n e'ample is the bacterial lac operon, 0hich codes for proteins necessary for lactose metabolism by 3 coli% the transcription and translation of these bacterial proteins is regulated by a single promoter, operator, and set of regulatory elements &lutluring 3 coli in lactose containing media results in the binding of lactose to the repressor protein !his bidnign causes a conformational change 0hich prevents the attachment of the repressor protein to the operator region, 0hich, in turn, increses transcription of the lac operon structural genes and, subse5uently increases utili*ation of lactose for energy &ulturing 3 coli in glucose7containing media 0ith or 0ithout lactose represses the e'pression of the lac operon Glucose decreses the activity of #denylyl cyclase and leads to a reduction of intracellular c#M "epletion of c#M by the presence of glucose decreases the e'pression of the lac operon structural genes igh c#M levels activate a protein called catabolite activator protein (&#), 0hich binds c#M to form a c#M7&# comple' 0hich then binds to a region upstream from the promoter region and acts as positive regulator of the lac operon 3nteropeptidase is produced in the duodenum and cleaves tryspinogen to trypsin $E$ activates -#$ 0hich then actiaves -#< to activate M# ;inase kinase after G< ligand binds to an autophosphorylating tyroskine kinase !elomeres add to C/ end of "N# $yndromes of premature aging, such as 4lood syndrome, are assoacited 0ith shortened telomeres 4itots spots are seen in 2it # deciency !hey are abnormal s5uamous cell proliferation and keratini*ation of the con>unctiva Aeishmaniasis in histiocytes . in Ira5, desert
Neurology !rigem nerve arises from the lateral aspect of the mid7pons at the level of the middle cerebellar peduncle Infarcts of anterior pons: &$! (contralateral hemiparesis and 4abinski) and corticobulbar tract (&A facial palsy and dysarthria) &an also cause &A dysmetria and dysdiadochokinesia, resulting ina syndreom kno0n as ata'ic hemiparesis !hese are &A cerebellar decitis (cerebellar lesions are ipisilateral decits) !umor ad>acent to the fal' cerebri and compressing the medial surface of the hemisphere !ypical meningioma location &ommonly located in the parasagittal region, but can also be found ad>acent to the lateral conve'ity of the hemisphere, in the region of the sphenoid 0ing and olfactory groove (0ould present 0ith # and anosmia) !innitus and unilateral hearing loss R &# angle tumor such as an acoustic neuroma
rogressive neurologic d* 0ith cystic degeneration of putamen R ilsons It is lateral to G and internal capsule $ciatica can result from herniations, spinal canal stenosis, irritation by bone spurs, and irritation by the piriformis osterior e'ternal auditory canal . vagus nerve !he rest of the e'ternal auditory canal (including the e'ternal portion of the tympanic membrane is the mandibular division fo the trigem% the inner portion fo the tympanic membrane is the I) 2asovagal syncope is parasympathetic out6o0 via the vagus nerve leads to decreased heart rate and blood pressure
&N2II and &N2 can also be aDected by sch0annomas yperacusis of from paralysis of the stapedius . &N 2II Ipsilateral hyperacusis is a common nding in 4ell/s palsy &hronic loss of upper e'tremity pain and temperature sensation, upper e'tremity 0eakness and hypore6e'ia, lo0er e'tremity 0eakness and hyperre6e'ia, and kyphoscoliosis R syringomelia C important "# path0ays: 7 Mesolimbic7mesocortical o -egulates behavior schi*ophrenia 7 Nigrostriatal &oordination of voluntary movements parkinsons o 7 !uberoinfundibular o &ontrols -A secretion hyperprolactinemia
Myeres loop is pie in the ski seudotumor cerebri . hydrocephalus . a condition that classically occurs in over0eight young females and is related to decreased &$< out6o0 at the arachnoid villi 3levated intracranial pressure 0ith normal &$< content and normal neuro imaging Manifests as # and papilledema Eptic nerve atrophy and blindness are the concern E'aloacetate forms aspartate 0hile reacting 0ith glutamate !his is transamination 0ith 4S necessary
!he concept of a latent period can be applied to both d* pathogenesis and e'posure to risk modiers !he initial steps in pathogenesis andBor e'posure to a risk factor sometimes occur years before clinical manifestations of a d* are evident #dditionally, e'posure to risk modiers may need to be continuous over a certain period of time before in6uencing the outcome #ta'ia telangeiectasia is an #- disorder resulting from a defect in "N#7repair genes !he "N# of these pts is hypersensitive to ioni*ing radiation Manifestations include cerebellar ata'ia, oculocutaneous telangiectasias, repeated sinopulmonary infections, and an increased incidence of malignancy # number of inherited disorders are caused by deciency "N#7repair en*ymes: 7 #ta'ia telangiectasia is characteri*ed by "N# $ to ioni*ing radiation 7 In 'erdoerma pigemntosia, "N# is hypersensitive to 12 radiation, causing premature skin agin and increased risk of skin cancer (melanoma, s5cc) 7
Meningococcal sepsis may be associated 0ith "I& and hemorrhagic destruction of the bilateral adrenal glands !his constellation of ndings is kno0n as the 0aterhouse7friedrichson syndrome N meningitis sepsis does NE! necessarily include meningitis !etanus vaccine is a to'oid e start it ? months after birth WFSX ainful spasms 0ith s0allo0ing or inspiration are the reason for dysphagia in rabies -abies travels retrograde to the "-G and then back to brain It gets into the peripheral nerve a'ons by binding to #&h receptors #t this point, post e'posure prophyla'is is no longer eDective Neisseria is in the nasopharyn' Neisser meningitiidis gains access to the &N$ by rst coloni*ing the nasopharyn' and subse5uently invading the mucosal epithelium and gaining access to the bloodstream !hrough the blood, it spreads to the choroid ple'us, gains access to the &N$ through the 444 and intiiates an in6ammatory process 3nteroviruses are the most common cause of aseptic meningitis $trep pneumo is the most common cuase of bacterial meningitis in adults of all ages It often follo0s a pulmonary infection or mild upper respiratory infection #lcoholics, sickle cell pts, aslepnic individuals, and those in generally poor health are at greater risk for $ pneumonia meningitis $taph is common cause of meningitis in neurosurgical pts $trep pneumo is leading cause of community ac5uired pneumonia, otitis media, and meningitis in adults rimary &N$ lymphoma occurs in immunocomprosmised pts and is of 4 lymphocyte origin Aatent 342 infection is strongly assoacited 0ith #I"$ related primary &N$ lymphoma !he three "s of botulinum to'in: diplopia, dysphagia, dysphonia Aisteriosis occurs e'clusively in immunocomrpoised pts 3at contaminated food, then into bloodstream Gro0s in macrophages Aisteria can resemble corneybacterium but tumbiling motility is uni5ue to listeria &ryptococcus: 7 +east only 7 !hick polysaccharide capsule (virulence factor) ydrocephalus, intracranial calcications, and chorioretinitis are classic triad of to'oplasmosis !o'oplasmosis is ac5uired in utero . it is transplacental $taph epidermidis is assoacited 0ith foreign bodies (2 shunts included) It forms biolms It is an e'crecelluar polysaccharide matri' &$< culture sho0ing gro0th on Mac&onkey agar implies &N$ infection 0ith enteric bacteria . specically, 3 &oli 3 coli is a fre5uent cause of neonatal meningitis, second only to G4$ !he capsule synthesi*ed by some 3 coli (;@ antigen) is a virulence factor that allo0s the bacteria to survive hematogenous spread and to establish meningeal infection Most strains of 3 coli causing neonatal meningitis do possess this ;@ antigen Most important mechanism of the development of diabetic neuropathy is non en*ymatic glycosylation of proteins leads to increased thickness, hyalini*ation, and narro0ing of the 0alls of the arteries !hese changes lead to diabetic microangiopathy of endoneural arterioles Ischemic nerve damage follo0s Er intracellular hypergcymia occurs in peripheral nerves #ccumulating glucose is converted into sorbitol and fructose by aldose reductase $orbitol increases cell osmolarity and facilitates 0ater in6u' into the cell !he result is osmotic damage to a'ons and sch0ann cells Menieres d* is characteri*ed by the triad of tinnitus, vertigo, and sensorineural hearing loss Its pathogenesis is related to an increased volume and pressure of endolymph in the vestibular apparatus Medullobalstoma symptoms: increased intracranial pressure (morning as, vomiting, lethargy) &erebellar dysfunction occurs as the tumor compresses ad>acent strucutrs Microglia move to the area of ischemic infarct in appor'iamtely C7 days after the onset of ischemia and phagocyti*e the fragments of neurons, myelin, and necrotic debris # cystic space replaces the necrosis, and astrocytes form a glial scal along the peripheray
Erientation &omprehension &oncentration $hort term ememory Aong term memeory Aanguage
Name location and current date
2isual spacial
ermanent memory loss and confabulation don/t come back from ernicke korsakoDs !remulousness is commonly the rst symptom of alcohol 0Bd Ether symptoms are GI distress, agitation, an'iety, and other autonomic disturbances "elerium tremens is the most severe manifestation of alcohol 0ithdra0al and typically begins bet0een ?7C days after the last drink Germinomas are the most common tumor of the pineal gland leading to obstructive hydrocephalus, parinaud syndrome
precocious puberty, a5ueductal compression
Eligoclonal bands of antibodies to the measles virus are found in the &$< of patients 0ith $$3 #ntibodies to the M component of the measles virus are absent Epsoclonus7myoclonus is a paraneoplastic syndrome associated 0ith neuroblastoma !his tumor, associated 0ith increased number of copies of the N7myc gene, is the most common e'tracranial neoplasm in children It is non rhythmic con>ugate eye movements assoacited 0ith myoclonus !he hippocampus is the area of the brain demonstrating the greatest degree of atrophy in #l*heimers d* $ynaptophysin is a protein found in the presynaptic vesicles of neurons, neuroendocrine and neuroectodermal cells &N$ tumors of neuronal origin fre5uently stain positively for synaptophysin on immunohistology Neoplasms of glial origin (astrocytomas, ependymomas, and oligodendrogliomas) stain for G<# Aoss of oligodendrocytes in M$ 3pidural . bet0een bone and dura $ubdural . bet0een dura and arachnoid $ubarachnoid . bet0een arachnoid and pia !abes dorsalis get severe stabbing pains as 0ell as loss of proprioception and vibration sense araneoplastic syndromes occur due to the tumor cells producing substances that fre5uently induce an autoimmune r'n and cause damage and degeneration of healyhy organs and tissues Neurologic paraneoplastic syndromes such as paraneoplsatic cerebellar degeneration are #I 4en*odia*epines% 7 !ria*olam (alpra*olam) short duration of action (US hr) 7 Aora*epam intermediate duration of action (S7?8 hr) 7 "ia*epam long duration of action (K?8 hr) 7
# temporary course of ben*odia*epines are sometimes used during $$-I intiation if thre is a signicant increase in an'iety7related problems, since it takes $$-Is 8 0eeks to kick in $chi*oaDective disorder: 7 Multiple psychotic episodes 0ith concurrent ma>or depressive or manic symptoms 7 K? 0eeks of delusions of hallucination in absence of mood ysmptoms 7 Mood symptoms present for ma>ority of total illness Ma>or depressive or bipolar disorder 0ith psychotic features are psychotic symptoms occur e'clusively during mood episodes "iDerentiating schi*oaDective disorder form bipolar disorder or ma>or depression 0ith psychotic features re5uires determing the temporal relationship of psychotic s' to mood s' In bipolar disorder and ma>or depression 0ith psychotic features, the psychotic s' occur e'clusively during manic or depressive episodes hen the pts mood is euthymic, there are no psychotic symptoms !o d' schi*oaDective disorder, psychosis must occur in the absence of ma>or episdoes, but mood symptoms have to be present for most of the illness
ection $erum sickness is a type III $ reaction characteri*ed by deposition of circulating, complement 'ing immune comple'es and resulting vasculitis #ssociated ndings include fever, urticarial, arthralgias, glomerulonephritis, lymphadenopathy, and lo0 serum &C level 7@H days after intravascular e'posure to antigen 4ody temperature over 8H& is called hyperpyre'ia and may lead to permanent brain damage if left untreated 3mergent treatment of hyperpyre'ia should consist of increased body heat loss (cooling) and decreasing the hypothalamic set point (antipyretics) e system) is thought to be the ma>or underlying cellular event ection sensitivity, increased sleep and appetite M#Eis are used in atypical depression ralido'ime is the only medication that reverses both muscarinic and nicotinic eDects of organophosphates by restoringJ cholinesterase from its bond 0ith these substances #ntidepressants can induce mania in susceptible pts, especially those 0ith unrecogni*ed bipolar disorder ts treated 0ith antidepressants should be monitored for mood elevation and symptoms suggestive of mania that re5uire emergency treatment rimidone is metaboli*ed to phenobarbital and phenylehtylmalonamide (3M#) #ll C compounds are active anticonvulsants G#4#a and G#4#c are ion channels 0hile G#4#b receptor is linked to a G&- 4en*odia*epines, barbiturates, and alcohol all bind to G#4#a and facilitate the inhibitor action of G#4# in the &N$ ts must 0ait ? 0eeks after discontinuing M#Eis before starting $$-I therapy allo0ing suOcient time for M#E regeneration !he most common side eDect of dia*epam is sedation so don/t give it 0ith other &N$ depressants "on/t use 0ith alcohol, barbs, neuroleptics, or @ st generation antihistamines
"antrolene blocks ryanodine receptors and prevents release of &a into the cytoplasm of skeletal muscle bers 2alproic acid is the drug of choice for myoclonic sei*ures !his drug suppresses abnormal electric activity in the corte' by aDecting G#4# and NM"# receptors, as 0ell as Na and ; channels Nalo'one mostly binds mu, so it is best for opioid into'ication It is an antagonist !&#s have anticholinergic aDects and 0ill cause urinary retention &EM! inhibitors stop peripheral breakdo0n of A7"E# and increase the A7"E# reaching the brain "rugs that cause ! syndrome: antidepressants, tramadol, ondansetron, line*olid, triptans ! syndrome: hyperre6e'ia, myoclonus, clonus, rigidity% hyperthermia, tachycardia, diaphoresis, tremor% agitation, confusion #tropine is indicated for the treatment of rbadycardia as it decreases vagal in6uence on the $# and #2 node # common side eDect is increased intraocular pressure It may precipitate acute closed7angle glaucoma in susceptible individuals 2itamin 4S increases the pierphal metabolism of A7"E#, 0hich decreases its eDectiveness eople 0ith MG that get an e'acerbation get it for ? reasons: myasthenic crisis in 0hich they are undertreated and they don/t have enough #&h in the synaptic cleft to compete 0ith the autoantibodies IIn this case, give edrophonium (tensilon test), 0hich increases NM transmission and provides temporary improvement of symptoms !hey can also get e'acerbation from a cholinergic crisis !his is if the pt has too high dose of cholinesterase inhibitor and e'cessive #&h in the synaptic cleft !he increased #&h causes e'cessive stimulation of the skeletal muscles and results in muscle refractory to future impulses &holinergic crises also present 0ith muscle 0eakness $ince the NMT becomes insensitive to #&h, an infusion of edrophonium produces no improvement Aora*epam and o'a*epam are short acting ben*odia*epines preferred in pts 0ith advanced liver dysfunction Aong acting ben*os (chlordia*epo'ide, dia*epam) are generally preferred though to treat "! in alcohol 0Bd !ryptophan is a precuroser to ! . so that is the ## responsible for ! syndrome "epressed pt 0ith hyperre6e'ia and ankle clonus (0ith tremulesness, diarrhea, cramping too) R ! syndrome # chronically progressive pre7senile dementia 0ith cortical atrophy but no other radiological or laboratory abnormalities permits a d' of #l*heimers "rugs 0ith high bloodBgas partition coeOcients are most soluble in the blood, demonstate slo0er e5uilibrium 0ith the brain, and have longer onset times &lo*apine . agranulocytosis . check blood regularly Nicotinic receptor . Na into the cell (and &a), ; out of the cell Aithium is e'clusively e'creted by the kidneys, 0ith ltration and resorption in the ! follo0ing sodium reabsorption -enal in>ury, to'ins and drugs that lead to increased ! absorption of Na (N$#I"s, thia*ide diuretics, #&3 inhibitors) also increase Ai levels and elevate the risk of Ai to'icity emodialysis is the most eDective 0ay of acutely reducing the blood Ai level #dding carbidopa can reduce most of the peripheral side eDects of levodopa o0ever, behavioral changes from levodopa can actually 0orsen 0ith addition of carbidopa because more "# becomes available to the brain !he on7oDJ phenomenon is an unpredictable and dose7independent characteristic of advanced arkinson disease . there is no clear etiology of this phenomemom EN the other hand, the 0earing oDJ phenomenon of arkinson disease is due to progressive destruction of straitoniagral "# neurons over a period of time !he on oD phenomenon is not temporary and 0ill not self resolve spontaneously Massive hepatic necrosis is a rare but severe complication of halothane e'posure It occurs due to direct liver in>ury by halothane metabolites and formation of autoantibodies against liver proteins Aight microscopy sho0s massive centrilobular hepatic necrosis &holinergics bind muscarinics and endothelial cells and cause vasodilation
Hematology/Oncology 2aline . non polar Glutamic acid . charged $ickling occurs under conditions of ano'ia, including lo0 p and high ?,C "G $ignal 7 7 7 7 7
transduction systems: M#7kinase path0ay IC;B#kt (;4)Bm!E- path0ay Inositol phospholipid path0ay c#M path0ay T#;B$!#! path0ay
igh o'ygen aOnity hemoglobins have a decreased H that is represented by a left0ard shift of the o'ygen7 dissociation curve igh o'ygen aOnity hemoglobins have reduced ability to release o'ygen 0ithin the peripheral tissues, leading to renal hypo'ia, increased 3E synthesis, and compensatory erythrocytosis ury Aysis of erythrocytes in hematomas causes release of hemoglobin intot he soft tissue, and the heme molecule is ultaimtely degraded to bilirubin !o see hemoglobin type, use electrophoresis T#;? mutations in chornic myeloproliferative disorders is a constitutively active form, and conse5uently, cytokine independent activation of $!#! transcription factors If a hemoglobin molecule is dissociated, the individual subunits 0ill have a hyperbolic o'ygen7dissociation curve Methhemoglobinemia cuases dusky discoloration to the skin (similar to cyanosis), and because methemoglobin is unable to carry o'ygen, a state of functional anemia is induced !he blood partial pressure of E? is a measure of E? dissolved in the plasma and is not realted to hemoglobin function In &E poisoning, anemia (lo0 b) or olycythemia (high b) E? is al0ays normal o0ever, percent saturation is 0orse in &E posinoing and E? ceontent is decreased in both &E posinoing and anemia 0ith lo0 b Nitrites induce methemoglobinemia Nitrites are o'idi*ing agetns that are eDective in the treatment of cyanide poisoning due to their ability to cause methemoglobinemia Methemoglobinemia contains ferric rather than ferrous iron &yanide binds to
ferric iron more avidly than to mitochondrial cytochrome en*ymes, 0hich saves these mitochondrial en*ymes from cyanides to'ic eDects In the lungs, the binding of o'ygen to hemoglobin drives the release of and &E? from hemoglobin (aldane eDect) In the peripheral tissues, high concentrations of &E? and facilitate o'ygen unloading from hemoglobin (bohr eDect) W@CSX "ysphagia and spoon nails are specic for iron deciency anemia Aiver takes up uncon>ugated bilirubin through a passive organic anion transporting polypeptide (E#!) It secretes direct (con>ugated) con>ugated bilirubin into the biliary system through active transport form an #4& protein kno0n as M-? (an organic anion transporter) If you block M-? you 0ill get an isolated con>ugated hyperbilirubinemia !he con>ugated bilirubin is 0ater soluble and 0ill then be e'creted in urine W@8PX !umor lysis syndrome can develop during chemotherapy for cancers 0ith rapid cell turnover (poorly diDerentiated lymphomas and leukemias), substanti al tumor burden, or high sensitivity to chemotherapy It is characteri*ed by hyperphosphatemia, hypocalcemia, hyperkalemia, and hyperuricemia revention of tumor lysis syndrome involves hydration and the use of hypouricemic agents such as allopurinol or rasburicase &E binds to hemoglobin 0ith much higher aOnity than E?, thus preventing o'ygen binding to hemoglobin It also reduces o'ygen unloading from hemoglobin in the tissues &E poisoning does not aDect the aE? and does not precipitate methemoglobiemia #MA M? is t(%?@) MC . acute promyelocytic leukemia ol gene mutations are responsible for ac5uired resistance to I2 reverse transcriptase inhibitors and I2 protease inhibitors 3nv gene mutations enable espae from host neutrali*ing antibodies !he @%@P translocation in #MA MC is the MAB-#-alpha retinoic acid fusion gene epcidin is an acute phase reactant synthesi*ed in the liver hepatocytes It binds ferroportin, causing it to be internali*ed and degraded !his decreases absoalteral iron transport in the intestine and also inhibits the release of iron by macrophages igh iron levels and in6ammatory conditions increase the synthesis of hepcidin, 0hile diminished iron levels and hypo'ia decrease hepcidin levels +easts and pseudohyphae and a positive germ tube test are diagnostic of candida infection arvovirus is highly tropic for erythroid precursor cells and replicates in the bone marro0 eparin and drugs that directly inhibit thrombin formation can prolong !hrombin !ime (!!) &"8 and I2 gp@?H% &"?@ and 342 gpCH% erythrocyte antigen and parvovirus 4@F !ype E mothers have antibodies that are predominately IgG and can cross the pplacenta . # and 4 are IGM Neutropenia 0ith ticlopidine presents 0ith fever and mouth ulcers +ou should monitor &4& for C months on ticlopidine reventing intracellular dehydration is a treatment modality for sickle cell anemia using Gardos channel blockers !he calcium7dependent (Gardos) ;7channel regulates the transport of ; and 0ater throught he red blood cell membrane . 0hen blocked, ; and 0ater eVu' is reduced, preventing dehydration of erythrocytes and reducing the polymeri*ation of b$ !N
in6u' of drugs into the cytosol and can increase eVu' from the cytosol, thereby preventing the action of chemotherapeutic agents N7fomryl7tetrahydrogolate R folinic acid, leucovorin (can overcome M! 0ith these) !umor invasiveness is the biggest prognostic factor in bladder cancer !his is stage !umor penetration of the 0all is the ma>or determinant of prognosis !his is true for colon cancer too !he laminin in basement membranes may post a physical barrier to the sproudting of ne0 42s in angiogenesis in neoplastic and granulation tissue induced by 23G< and
!he schilling test helps to diDereneitate bet0een dietary deciency of 4@?, pernicious anemia, and malabsorption syndromes Ao0 absorption of cobalamin not correctable by intrinsic factor is indicative of a malabsorption syndrome such as ileal d*, pancreatic insuOciency, or bacterial overgro0th GS" deeicny e'acerbation: dark urine, anemia, high reticulocyte count "' of #MA re5uires K?HL myeloblasts 4last cells in the peripheral blood are strongly suggestive of leukemia #AA is the most common malignancy in childhood ! cell #AA is less common (?HL of all #AA) and presents as a medistinal mass that can cause respiratory symptoms, dysphagia, or $2& syndrome $ickle trait patients usually have normal peripheral smears and indices, reticulate counts, and M&& values $ickle cell trait -4&s 0ill sickle 0hen $E"I1M M3!#4I$1A
Respiratory
1mbilical vein
ductus venosus
I2&
hosphatdiylcholine (Aecithin) and phosphotidylglycerol are ma>or constituents of surfactant $phingomyelin stays about constant os the A:$ ratio at the end should be ?:@ In the respiratory tract, the nose, paranasal sinuses, nasopharyn', and tracheobronchial tree are lined 0ith pseudostratied columnar, mucus7secreting epithelium $tratied s5uamous epithelium is found only in the oropharyn', laryngopharyn', anterior epiglottis, upper half of the posterior epiglottis, and vocal folds (true cords) 3lastase is a neutral protease contained in macrophage lysosomes and in the large, a*urphil granules of neutrophils Normally, elastase release from inltrating neutrophils and macrophages is balanced by the antielastase activity of serum #@#! 3'cess elastase activity in lung acini is thought to be a ma>or factor in the development of centriacinar and panacinar emphysema !he ape' of each lung e'tends into the neck appro'imately C78 cm above the rst rib !he ape' of the heart lies behind the th left intercostal space at the left midclavicular line (A2) !he steroncostal (anterior) surface of the heart is formed by the -2 !he diaphagmantic (inferior) surface is formed by the left and right ventricles, and is in contact 0ith the central tendon of the diaphgram !he posterior surface of the ehart is formed mainly by the A# !he -# makes up the ma>ority of the right border of the heart on # chest lms !he -2 forms the anterior 0all of the heart and is best seen on lateral &- !he $2& and I2& compose the superior and inferior borders of the cardiac silhouette on the right side Ao0er border of the pleura -ight Aeft YAo0er border of lung is ?
Midclavicular line
Mida'illary line
Pth rib 1pper border of @H th rib Pth rib Ao0er border of @Hth rib spaces above the end of the pleura
aravertebral line @?th rib @?th rib
!he process of bicarb diDusing out of a -4& and chloride diDusing in to maintain electroneutrality is called chloride shift It is the reason 0hy high -4& chloride content in venous blood ypo'ic vasoconstriction . increase arteriolar resistance increases as the blood o'ygen decreases . occurs in the pulmonary circulation so that blood 6o0 is diverted a0ay from underventilated regions of the lung and to0ards more 0ell7ventilated areas 3osinophils release ma>or basic protein, a protent anti7helminthic to'in capable of causing damage to epithelial and endothelial cells "elayed type hypersensitivity reactions are !h@ lymphocytes that release I
;ussmaul breathing is in ";# #spergillus does not invade lung tissue, but gro0s inside the cavity forming a fungus ballJ or aspergilloma !his condition may be asymptomatic or it may cause hemoptysis It 0ill appear as a radiopa5ue structure that shifts 0hen the pt changes position !he center of the air0ay pressure volume curve is the <-& of the lungs% it identies the resting state 0here the air0ay pressure e5uals *ero #t the <-&, the intrapleural pressure is 7 cm ?H It gets to 7P in inspiration Medium si*ed bronchi are responsible for the most air0ay resistance, terminal bronchioles is the least !he tissue destruction caused yb M!4 infection is the direct result of host immune activation and in6ammation through a type I2 $ reaction !he characteristic pathologic lesion consists of granulomatous ifnlmmation and caseous necrosis Mycolic acid is a long branched chain saturated <# used in the mycobacterial cell 0all and in the formation of virulence factors It is responsible for the acid fast7ness of M!4 IN inhibits mycolic acid synthesis
"ust particles smaller than ? microns in si*e reach the alveoli !hey are taken up by macrophages and sitmulate &! gro0th !he pneumoconiosis are diseases that result from the inhalation of ne dust particles -ifampin is used as monotherapy prophyla'is for i4 and N meningitidis . it is used in combination therapy for M!4 and leprosy &romolyn and nedocromil are mast cell stbali*ing agents $0eat is initially isotonic !hen &ection is a ma>or problem in lung transplant recipients It aDects small air0ays, causing bronchiolitis obliterans Aymphocytic in6ammation, necrosis, and brosis of the bronchiolar 0all occur 1ltimately, there is occlusion fo the bronchiolar lumen 3osinophils are recruited and activated yb IA7 secreted by !h? helper ! cells in asthma eptidoglycan cell 0all protects form osmotic forces If a gram 9 bug treated 0ith an antibiotic is then placed in a hypotonic solution and lyses, you kno0 the peptidoglycan cell 0all must have been disrupted byt eh #4 so that the osmotic forces destroyed the bacteria I29 0omen should be given *idovudine (#=!, ="2) during pregnancy and then I2 at brith and then the baby should get it for S months post7brith as 0ell !he 0ork done against the elastic resistance of the lung is increased 0hen tidal volume is increased, 0hile the 0orkd one aginst air6o0 resistance is increased 0hen the breathing fre5uency is increased If the ? components are summated and the total 0ork is plotted against respiratory fre5uency, there 0ill be an optimal breathing rate at 0hich the total 0ork of breathing is minimi*ed
Mycoplasma pneumonia is the causative agent of 0alking pneumonia and many cases of tracheobronchitis It is an organism 0ith no peptidoglycan cell 0all% it only has a phospholipid bilayer cell membrane It shares antigens 0ith human erythrocytes, and 0hen the body mounts a response against these antigens, it also lyses red blood cells leading to anemia !he #4s cauisn this -4& destruction re referred to as cold agglutinins #fter the immune system is not longer activated (0hen the bacteria is cleared) the concentration of the antibodies decreases and the anemia resolves spontaneously M pneumo also causes $T$ and >oint poins Aegionella sho0s neutrophils but no organisms !hink legionella of pneumonia, fever, and GI symptoms (maybe confusion and &N$ too)
"imorphic fungi: sporothri', coccidio, histo, blasto, paracoccidio $aE?UF?L (aE?US) can cause secondary polycythemia p&E? is the most potent cerebral vasodilator It decreases cerebral vascular resistance leading to increased cerebral perfusion and increase I& ts 0ith &E" usually have a lo0 E? (hypo'ia) and high &E? (hypercapnea) !hus, their cerebral circulation is most likely to be increased a&E? is the ma>or stimulator of respiration in healhy people 3ven a lsight increase in a&E? results in increased pulmonary ventilation In prolonged hypercapnea, h0oever, high a&E? ceases to sitmulate the respiratory drive In such pts, respiration is stimulated by hypo'ia (lo0 aE?) sensed by peripheral chemoreceptors -apid increases in the fraction of inspired o'ygen may lead to respiratory failure in these pts &entral cehmoreceptors in the medulla are indirectly sensitive to changes in a&o? and direcyl sensitive to changes in p !hese receptors are not sensitive to aE? Nocardia is also catalase positive ost op R 3 (not sedative for pain) !he most common side eDect of inhaled glucocorticoids is oropharyngeal candidiasis 1se a spacer and learn to rinse the mouth 3chinocandins are a ne0er group of antifungal mediations that inhibit synthesis of the polysaccharide glucan, an essential component of the fungal cell 0all Aobar pneumonia is in 8 stage: 7 &ongestion (day @) o -ed, heavy and boggy lobe o 2ascular dilatation, alveolar e'udate contains mostly bacteria 7 -ed hepati*ation (day ?7C) o -ed, rm lobe (liver like consistency) #lveolar e'udate contains erythrocytes, neutrophils, and brin o 7 Gray hepati*ation (day 87S) Gray bro0n rm lobe o -4&s disintegrate, alveolar e'udate contains neturophils and brin o 7 -esolution o 3n*ymatic digestion of the e'udate !he normal #E? is @H8 Incoming systemic venous blood as a E? of 8H 4lood E? nromally reaches the #E? by the time it passes through the rst third of the alveolar capillaries due to high rate of E? diDusion through the respiratory membrane aE? belo0 H is called hypo'emia !hen you have to look at the #7a gradient to see the reason Normal #7a gradient 0ill be: high altitude (lo0 air E?) or hypoventilation igh #7a gradient 0ill be: 2BZ mismatch, - to A shunt, "iDusion barrier (brosis) ulmonary alveolar proteinosis present 0ith gradual 0orsening of dyspnea and productive cough En histologic e'amination there is bilateral patchy pulmonary opacication due to intraalveolar accumulation of amorphous protein and phospholipid material (constituents of surfactant) M& benign lung tumor is a hamartoma In6uen*a vaccine is thought to prevent serious cases of the 6u by increasing the host circulating antibodies against the hemagglutinin of the selected viral strains 1pon subse5uent e'posure to live virus, these #4s interfere 0ith the bidnign fo the # to the sialic acid conitaining oligosaccharides of hose cell plasma membrane glycoprotein receptors !he live virus is prevented from entering cells via receptor mediated endocytosis !he a*oles (not >ust ketocona*ole) inhibit the &+s 2arenciline is a partial agonist of nicotinic #&h receptors It can assist pts 0ith cessation of tobacco use by reducing 0ithdra0al cravings and attenuating the re0arding eDects of nicotine #n accentuated pulmonary component of the second heart sound suggests an increase in pulmonary artery pressure and #, in turn, causes cor pulmonale and symptoms of right heart failure (dyspnea on e'ertion, A3 edema, $M) 4ronchoalviolar carincoma is a subtype of lung adenocarcinoma !his uncommon tumor occurs in nonsmokers and arises form alveolar epithelium It is located in the peripheral parts of the lung and is often multifocal En
microscopic e'amination it is composed of tall, columnar cells that line the alveolar septa 0ithout evidence of vascular or stromal invasion Neuroendocrine cancers are positive for neuroendocrine markers such as neuron specic enolase, chromogranin, and synaptophysin !his is small cell carcinoma and bronchial carcinoid In noncardiogenic pulmonary edema (#-"$), the pulmonary capillary 0edge pressure is normal Nontypable strains of in6uen*a are strains of in6uen*a that do not form an antiphagocytic capsule !hey are part of the normal 6ora of the upper respiratory tract, but can cause otitis media, sinusitis, and bronchitis Immunity to nontypable strains, as 0ell as capsular strains other than type 4, is not conDered by vaccination 0ith the ib vaccine anic attacks are assoacited 0ith hyperventilation and decreased &E? ypocapnia causes cerebral vasocontrsitction and decreased cerebral blood 6o0 yra*iniamide is not active against e'tracellular M!4 because it needs the acid in the macrophage phagolysosome &E" can cause hypo'ia suOcient to stimulate increased 3E production by the cortical cells of the kidney Metabolic alkalosis is most commonly caused yb vomiting, NG suction, diuretic use, hyperaldosteronism Measuring the urinary chloride concentration and determining the pts volume status helps to identify the cause of metabolic alkalosis Aung ape' R superior sulcus !he three cytokines IA@, IA7S, !N< alpha (and I
!he late distal and cortical collecting tubules are the primary sites for regulation of ; concentration in the urine ; depletion stimulates alpha interacalated cells to reabsorb e'tra ;% principal cells secrete ; under conditions of normal or increased ; load L of urea is normally absorbed @@th and @?th ribs are 6oating ribs !he distal tip of the @?th rib can be displaced into the retroperitoneum 0hen fractured, lacterating the left kidney Minimal change is a selective proteinuria . you >ust lose albumin and transferrin (the lo0 molecular 0eight) proteins Metbaolic acidosis is normally partially compensated for by a respiratoyr alkalsosis hen the steady state a&E? persists above the range given by 0inter/s formula, the patient has superimposed degree of respiratory acidosis and failure (@FPF) 2asopressin produces a 2? receptor mediated increase in permability to 0ater and urea at the luminal membrane of the inner medullary collecting duct !he increase in urea reabsorption corresponds to a decrease in the frational e'cretion of urea and a decrease in renal clearance of urea from plasma N$#I" assoacited chornic renal in>ury is morphologically characteri*ed by papillary necrosis and chronic interstitial nephritis Glomerular and vascular abnormalities, if present, are usually mild or may be seen only in advanced stages N$#I"s7assoacited nephropathy is common, especially in patients suDering from chronic pain $pironolactone reduces mortaility in heart failure pts ossibly from decreased ventricular remodeling "igo'in is renally e'creted and must be reduced dosage in the elderly #nti G4M antibodies react 0ith the alphaC chain of collagen type I2, found in the glomerular 4M !his is goodpasture syndrome $evere hypokalemia and hypomagnesemia are commonly seen during therapy 0ith amphoterrible 4 !his is from nephroto'icity "ecreases G<- and direct to'ic eDects on the tubular epithelium #lso increased membrane permeability &onsider MM 0hen an elderly pt present 0ith the follo0ing ndings: 7 3asy fatigability 7 &onstipation (due to hypercalcemia) 7 4one pain . most commonly in the back and ribs 7 -enal failure 4ence >ones proteins are ltered by the glomerulus in small amounts and then are reabsorbed in the tubules hen levels e'ceed the reabsorptive capacity of the tubules, these light chains precipitate 0ith !amm orsfall protein and form eosinophilic casts !hese casts impede renal function (obstruct lumens, compress epithelium) !hey also cause atrophy -enal vein thrombosis is a complication of nephrotic syndrome and presents 0ith 6ank pain, hematuria, and left sided varicoclele Murobonab (E;!C) is an #nti7&"C anitbody that inhibits ! lymphocytes, 0hich is useful in the treatment of acute re>ection in pts 0ith kidney, heart, and liver transplants !he ltration of # is not a process that can be saturated #t any given blood concentration, a constant portion of # 0ill be ltered from the glomerular capillaries into 4$ $ecretion of # is a carrier en*yme mediated process and therefore is able to be saturated #s the blood concentration of # increases, the secretion of # by pro'imal tubular epithelial cells increases . but only up to a ma'imum value of HmgBmin !his ma'imum secretion corresponds 0ith the transport ma'imum of the secretion en*ymes, and at this level, secretion plateaus and any increase in the urine # concentration are due to increased ltration $ is a leukocytoclastic vasculitis, IG# mediated $
M&" can be from an atopic problem, immuni*ations, or recent repiratory infection I": P I": @H? Gastrointestinal !he liver has glycerol kinase to make glycerol into "# Aiver is only organ 0ith glycerol kinase It uses it for triglyceride synthesis, glycolysis, gluconeogenesis e don/t have an &2 virus because it the envelope proteins keep mutating #poptosis in hepatitis is around councilman bodies ects into the lumen of the stomach% diDuse carcinoma fo the stomach is 0ithin the stomach 0all e e'crete old ceruloplasmin (alpha ? microglobulin made form copper) and e'cess copper in the bile and stool 3'cess ammonia combines 0ith alpha7;G to make glutamate Glutamate then is released at the synapse 3'cess is reabsorbed by the astrocyte and converted to glutamine !his accumulation of glutamine in the astrocyte leads to cellular s0elling and dysfunction erson 0ith history of generali*ed atherosclerosis and epigastric pain post prandially that does not respond to antacids R chronic mesenteric ischemia It is post prandial pain out of proportion to e'am ndings #6ato'in messes up pC Glucose decreases adenylate cyclase, 0hich decreases c#M Ao0 c#M leads to lo0 "N# binding, 0hich upltimately results in lo0 gene e'pression of the structural genes of the lac operon 1& associated &-& is early pC mutations and late #& mutations !hey are multifocal in nature !he e'tendend and duration of colitis is the biggest determinant 4lack stones from hemolysis are from uncon>ugated bilirubin increases pylori is found in greatest amounts in the prepyloric area of the gastric antrum &rohns gets gallstones because the terminal ileium is aDected, they can/t reabsorb their bile salts, and the cholesterol precipitates &rohns get o'alate stones because: they can/t reabsorb their bile, 0hich leads to malabsorption of fat !he unreabsorbed fat then binds calcium in the GI tract &alcium is normally bound to o'alate No0 it isn/t, and o'alate is freely absorbed (it suually is unabsorbale bound to calcium) !he reabsorbed o'alate leads to stones &o'7? increases risk of adenomatous polyp formation int eh colon #spirin can help decrease risk Epioid analgesics can cause sphincter of Edi contraction and spasm leading to biliary colic and -1Z pain I": @P@S !he $abin live attenuated polio virus is good at making Ig# in the oral mucosa 2I increases intestinal chloride loss in the stool !hen 0ater, Na, and ; follo0 & dif diagnosis by detecting to'in genes in stool via &- pylori leads to ulcers because it reduces the number of antral somatostatin releasing cells, so gastrin is left unchekd
#ppendicitis is caused by an obstruction of the lumen Mucus then can/t 6o0 out of the appendi' and there is a dilation of the appendi' !his restricts venous out6o0, resulting in hypo'ia 0hich causing ischemia and associated bacterial invasion I": 8H? &holera is very acid labile, and any drug that decreases acidity 0ill increase chance of cholera infection (omepra*ole) !he b$#g of hep 4 must coat the "#g of hep " before it can infect hepatocytes and multiply regnant 0omen or on oral contraceptives get cholesterol gallstones because estrogen increases cholesterol secretion and progesterone reduces gallbladder motility In all cases of acute viral hepatitis, ballooning degeneration, mononuclear cell inltrates, and &ouncilman bodies are seen ury It is 0here the left subclavian comes oD I": @S? Aiver can tolerate arterial occlusion better than other organs because it has dual blood supply In order it goes: brain, myocardium, kidney, spleen, liver In a pt 0ith severe aortic stenosis and subse5uent A2, A2 lling is dependent signicantly on atrial contraction to get the blood into the hypertrophied ventricle If there is a7b, and the A# is no longer contracting properly to ll the A2, then the A2 0ill have reduced preload to the point 0here systemic hypotension occurs !his can also lead to increased A# pressure leading to acute pulmonary edema "ystrophic calcication is a hallmark of preceding cell in>ury and necrosis (even in heart valves) !here is rst an intiaiton phase (0hich transpires 0ithin the mitochondria of dead or dying cells) and propagation (0hich can eventually perforate the cell membrane from 0ithin) &"C@ is 3&#M@ 0hich is an endothelial cell marker &"C8 is also an endothelial cell marker as is v factor #fter the age of H, isolated systolic !N becomes common $ystolic blood pressure greater than @SH 0ith a diastolic 4 belo0 FH is found in ?HL of pts over H Isolated systolic !N is caused by age7realted decreases in the compliance of the aorta and its pro'imal ma>or branches Numerous alterations in vessel 0all structure and function, including atherosclerotic changes, have been porposed to e'plain this stiDening # & higher than the A2 3" means that there is something impeding 6o0 (M$) bet0een the A# and A2 &E7? has a M of P?k" It is usually undetectable in tissues unless in6ammation induces it !hird degree #2 block, impulses are coming from the #2 node Z-$ is still narro0 since ventricular depoarli*ation proceeds normally It beats at 87 beats per minute If heart sounds are only heard at rst during e'piration, think about pulsus perido'us ulsus pero'us can happen in severe obstructive pulmonary disease such as asthma 4eta drenergic agonists control acute asthma e'acerrbations by causing bronchial smooth muscle rela'ation via increased incracellular c#M !he [a/ 0ave on >ugular venous tracing is absent in pts 0ith a7b !he adaptation to volume overload is eccentric hypertrophy (chamber dilation due to increased end diastolic volume) 0ith predominantly [in series/ synthesis of ne0 mycocardial sarcomeres &oncentric hypertrophy, the response to pressure overload, involves [in parallel/ dposition of ne0 sarcomeres, 0hich produces net ventricular 0all thciking and a reduction in ventricular chamber si*e (decreased 3"2) ressure overload may occur to stenosis or systemic !N !he ma>or long term hemodynamic compensatory response to the volume overload of #- includes an increase in left ventricular preload (A2 3"2) in associated 0ith eccentric A2
!reatment 0ith statins causes hepatocytes to increase their A"A receptor density as a means of increasing their uptake of circulating A"A #miodarone does not predispose to !orsades like the other @#s and IIIs !he &a#!ase pump uses active transport to se5uester calcium 0ithin the $- and ressstablish the ion gradient !he sarcolemmal NaB&a transmembrane protein does not re5uire #! and accepts C e'tracellular Na ions in e'change for one intracellular &a ion !his calcium eVu' is necessary for rela'ation 4eurgers d* is usually seen among heavy cigarette smokers 0ith onset before age C It is associated 0ith $ to intradermal in>ections of tobacco e'tracts !his segmental thrombosing vasculitis often e'tends into contiguous veins and enrves, encasing them in brous tissue ain of pericarditis is sharp and pleuritic It is e'acertbated by s0allo0ing% relieved by leaning for0ards 2aricose veins are dilated, tortuous veins resulting from impairment of the venous valves and re6u' of venous blood !his leads to venous stasisBcongestion, edema, and increased incidence of supercial venous thrombosis !hromboembolism is a very infre5uent complication of varicose veins, 0hile venous stasis ulcers are very common and often occur over the medial malleolus !he resulting chronic venous insuOciency causes stasis dermatitis, 0hich manifests as erythema and scaling 0ith progressive dermal brosis and hyperpigmentation N3 is greater in6uence on alpha and beta @ Aess on beta ? !reatment of coagulase7negative staph infection involves initial empric treatment 0ith vancomycin 0ith or 0ithout rifampin or gentamicin due to the 0idespread antibiotic resistance of $ epidermidis, especially in nosocomial infections "ilation of the A2 in response to increased preload can result in functional M-, 0hich can be eliminated by preload reduction and reduced by afterload reduction A2 dysfunction can lead to increased pulmonary arterial pressure due to reactive vasoconstriction secondary to pulmonary venous congestion -eactive changes in the pulmonary vasculature (endothelial dysfunction resulting in further vasoconstriction) also contribute to pulmonary !N In a crossover study, sub>ects are randomly allocated to a se5uence of ? or more treatments given consecutively # 0ashout (no treatment) period is often added bet0een treatment intervals to limit the confounding eDects of prior treatment !he I- is a tetrameric structure consisting of ? alpha and ? beta subunits !he alpha subunits are e'tracellular and provide the bidning site for snsulin !he beta subunits contain !; domains "o0nstream signaling is initiated, started by the autophosphorylation fo the insulin receptor !N< alpha is a proin6ammatory that induces insulin resistance through the activation of serine kianses, 0hich then result in phosphorylation of the I-$7@ serine residues !his inhibits I-$7@ tyrosine phosphorylation by insulin hosphorylation of serine residues in the beta subunit of insulin receptors also hinders do0nstream signaling, resulting in resistance to the normal actions of insulin hosphorylation of threonine residues has similar eDects &atecholamines, gulcocorticoids, and glucagon can also induce insulin resistance by this same mechanism, and intracellular <<#s are suspected of increasing serine kinase activity as 0ell -omano70ard and Tervell and Aange7Nielsen syndrome are thought to result from mutations in a ; channel protein that contributes to the delayed rectier current (I k) of the cardiac action potential More than a @HL increase in urine osmolality follo0ing administration of vasopressin during a 0ater deprivation test suggests &"I # urine osmolality increase above HL suggests complete central "I 1nlike epinephrine, glucagon has an insignicant eDect on skeletal muscle cells and adipocytes Glucagon does gluconeogenesis in the liver ";# presents as volume depletion (hypotension and tachycardia) 0ith ketones and glucose in the urine It occurs most commonly in type I "M -egular insulin is preferred for the acute treatment of ";# Nitroglycerine causes venous pooling, leading to re6e' tachycardia Nitroglycerine reduces myocardial o'ygen consumption, and is used for treating angina pectoris 3'opthalmous does not improve 0ith beta blocker therapy
&arotid sinus is acutally part of the internal carotid ydrophobic R valine, alanine, methionine, pheynalanine, isoleucine $ubperiosteal thinning is a characteristic feature of hyperparathyroidism -adiologically, this thinning appears as subperiosteal erosions in the medial sides of the second and third phalances of the head, and as a granular, salt and pepper appearance of the calvarium Nitrates acut primarily as venodilators causing a decrease in cardiac 0ork by decreasing left ventricular lling volume or preload 2isceral obesity as measured by 0asit7to7hop ratio is important determinant of insulin resistance !he pathogenesis of nonbacterial thrombotic endocarditis (N4!3) often involves a hypercoagulable state hen the hypercoagulability is the result of the procoagulant eDects of circulating products of cancer,s, the resulting cardiac valve vegetations may also be called amrantic endocarditis !he pathophysiology of N4!3 is similar to that of !rousseau/s syndrome . 0hich may also by induced by disseminated cancers &ortisol has several permissive eDects . cortisol increases vascular and bronchial smooth muscle reactivity to catecholamines #ngioedema most commonly involves s0elling of the tongue, lips, and eyelids and patients can also e'perience laryngeial edema and diOculty breathing &ombineduse of non dihydropyridine calcium cahnnel blockers and beta blockers can have additive chronotopic eDects yielding severe bradycardia and hypotension &pasaicin reduces pain by decreasing the level of substance in the N$ G increases gro0th through production of IG<7@ from the liver IG<7@ causes bone gro0th by stimulating the proliferation of cartilage in bone cells igh G levels but lo0 IG<7@ is laron/s d0arsm . a defective G receptor $2- decreases during e'ercise because of massive vasodilation so 4 doesn/t increase much #&! is the ma>or trophic hormone of the fasciulata and reticularis, 0hereas the glomerulosa is primarily regulated by #!II rolonged #&!stimulation casues hyperplasia of the fasciculate and reticularis, resulting in e'cessive cortisol production (cushing syndrome) !he vascular reaction to endothelial and intimal in>ury is intimal hyperplasia and brosis, predominantly mediated by reactive smooth muscle cells that migrate from the media to the intima #denosine and dipyridamole are selective vasodilators of coronary vessels that can cause coronary steal Immuni*ation 0ith diphtheria to'oid induces production of circulating IgG against the e'oto'in 4 subunit, eDectively preventing disease Nuclear receptors: thyroid, retinoids, #-, <#s !reatment of &# involves lo0 dose e'ogenous corticosteroids to suppress e'cessive #&! secretion and reduce stimulation of the adrenal corte'
Reproductive IAioinguinal, pudendal, and genitofemoral blockade 0ould provide complete perineal and genital anesthesia Iliohypogastric nerve is derived from !@?BA@ and courses in that dermatome to innervate the ksin overlying the iliac crests
IN the absence of ovulation, the ovarian follicle does not degenerate and becomes a &A #s a result, no progesterone is produced and estrogen levels remain persistently high, causing the endometrium to remain in the proliferative phase &hronically proliferative endometrium becomes disorgani*ed and fragile 0ith unstable venous capillaries, resulting in irregiular preiods of stromal breakdo0n 0ith variable, but often heavy, bleeding Aoss to follo0 up R selection bias rimary amenorrhea in a pt 0ith fully developed secondary se'ual characteristics suggests the presence of an anatomic defect in the gential tract, most commonly an imperforate hymen or a mullerian duct anomly #dolescent girls 0ith undiagnosed imperforate hymen commonly present 0ith cyclic abdominal or pelvic pain and physical e'amination ndings suggestive of hematocolpos omologous chromosomes separate in meiosis @ or a failure of sister chromatids to separate during meiosis II or mitosis (C?) uman placental lactogen increases insulin resistance, simtulated proteolysis and lipolysis, and inhibits gluconeogenesis Maternal insulin resistance results from increased secretion of hA, placental gro0th hormone, estrogens, progesterone, and glucocorticoids 1nbalanced translocations and mosaicism cause do0ns if it isn/t non7dis>unction 3ntrococci produce aminoglycose modifying en*ymes that transfer diDerent chemical groups (acetyl, adenyl, or phosphate) to the aminoglycoside and therefore impair antibiotic binding to ribosomal subunits "o0ns has e'cess skin on the nape of the neck Mucor d' needs b' &ongenital torticollis is typically noted by ?78 0eeks of age, after 0hich the child prefers to hold the ehad tilted to one side It is most commonly the result of malposition of the ehad in utero or birth trauma Most cases resolve 0ith conservative therapy and stretching e'ercises !here can be a palpable s0elling int eh childs neck 0hich might be the bulging of the $&M contracted &hin points a0ay from contracted muscle Ior adaptive immune mechanisms that prevent reinfection 0ith the in6uen*a virus include anti7 hemagglutinin IgG antibodies in circulation and mucosal anti7hemagglutinin Ig# antibodies in the nasopharyn' Erbital fractures usually involve the medial or inferor 0alls because the bone bordering the ethmoid and ma'illary sinuses is thin -ight brachiocephalic vein drains the right lymphatic duct, 0hich drains lymph from the right upper e'tremity, the right face and neck, the right hemithroa', and the right upper 5uadrant of the abdomen &M2 only causes mono in the immunocompetent host "irect hernias is caused by 0eakness of the transversalis fascia in esselbach/s triangle !hey are covered by the e'ternal spermatic fascia !he ureters cross over the commonBe'ternal iliac vessels and under the gonadal vessels (and ovarian vessles in the female) !hey pass lateral to the internal iliac vessels and medial to the gonadal vessels as they enter the true pelvis I": @H8 $eptic arthritis is N gonnarhea in a se'ually active young adult It is $ auerus in a non7se'ually active child or adult &ricothyrotomy incision passes through the supercial cervical fascia, pretracheal fascia, and the cricothyroid membrane &ardiomyoapthy is the most common cause of death (myocarditis) in diphtheria !reatment includes diphtheria antito'in (passive immuni*ation), antibiotics, and active immuni*ation Ef these, passive immuni*ation 0ith antito'in is the most important and has the greatest eDect on prognosis of a pt 0ith cornybacterium diphtheria #ntimuscarin drugs: atropic, !&#s (amitryptaline), @ antagonists (diphenhydramine), neuroleptics, antiparkinsonian drugs
ypetrophic cardiomyopathy R #" GA1!7C . placenta IN pts 0ith heart failure, compensatory activation of the -## path0ay and sympathetic nervous system results in increased afterload (from e'cessive vasoconstriction), e'cess 6uid retention, and deleterious cardiac remodeling Neurophysins are proteins involved in the posttranslational processing of o'ytocin and vasopressin !hese hormones and their resepective neurophysins are produced 0ithin the neuronal cell bodies of the paraventricular and suproptic neucli, and they are released into the circulation from a'on terminals in the post pit gland A2 and prior MI protect against A2 rupture (C7P days out from MI) rotease inhibitors cause cushings -ecurrences of genital herpes can be reduced through daily treatment 0ith oral valacyclovir, acyclovir, or famciclovir% these drugs suppress reactivation of latent $2 infections -heumatic fever and post7strep glomerulonephritis are the late se5uelae of strep pyogenes (G#$) ost strep glomerulonephritis can follo0 either a skin infection (impetigo) or an episode of pharyngitis -heumatic fever is associated only 0ith strep throat infection 1rge incontinence is uninhibited bladder contraction by the detrusor 3osinophils play a role in host defense during parasitic infection hen stimulated by Ig3 bound to a parasitic cell, they destroy the parasite via antibody dependent cellular cytoto'icity 0ith en*ymes from their cytoplasmic granules #nother function of eosinophils is regulation of type @ $ rections "epression of the entire # a'is by glucocorticoid therapy is the most common cause of adrenal insuOciency #drenal crises can be precipitated in these pts under stressful situations (infections, surgery) if their glucocorticoid dose is not appropriately increased A2 heart failure R kurly b lines
3arly antibiotic t' (penciling) of G#$ is important for prevention of acute rheumati c fever If you have -< you need surgery 3rgonovine can provoke coronary vasospasm, and can aid in the d' of prin*metals !his condition is treated 0ith vasodilating nitrates and calcium channel blockers h&G can be given in a large dose to simulate the A surge $C can be accentuated by having the pt lie in the left lateral decubitis position and fully e'hale $C is associated 0ith mitral regurg and &< . increased lling pressures It is the sound of blood lling into a partially lled or stiD A2 ($8 is also from atrial contraction into a stiD ventricle) In N"I and &"I the serum Na concentration is K@8? In primary polydipsia it is U@CP !="s increase adiponectin levels in type II "M, 0hich are actually normally lo0 in these pts yperaldosteronism produces renal Na retention and e'cess ; secretion, resulting in hypertension and hypokalemia #dditionally, pts 0ith &onns syndrome commonly e'perience a metabolic alkalsosis !he hypokalemia may cause muscle 0eakness ypokalemic alkalosis may promote paresthesias &lass I&s antiarrhythmics are potent Na channel blockers that e'hibit strong use7dependence by prolonging the Z-$ duration to a greater e'tent at higher heart rates &lass III antiarrhythmics block the repolari*ing ; current and demonstrate reverse use7dependence (the slo0er the heart rate, the more the Z!c interval is prolonged) Ishcemic preconditioning is the development of resistance to infarction by cardiac myocytes preveiously e'posed to repetitive non7lethal ischemia &ardiac hibernation #&3 inhibitors can cause rst dose hypotension if the pt is on diuretics before hand
!C cannot be conveted to r!C or to !8 3'ogenous !C administriation causes decreased !$ levels, 0hich act upon the thyroid gland to reduce endogenous !8 production (and thus reduce peripheral conversion to r!C) Tervell lange neilseon . decreased out0ard ; current during the repolari*ation phase of the cardiac action potential Z! prolongation
2alvular in6ammation and damage and scarring predispose to infective endocarditis Glomus R thermoregulation Aoss of cardiac myocyte contractility occurs 0ithin SH seconds after the onset of total ischemia hen ischemia lasts less than CH minuts, restoration of blood 6o0 leads to reversible contractile dysfunction (myocardial stunning), 0ith contractility gradually returning to normal over the ne't hours7days o0ever, after CH minutes of total ischemia, ischemic in>ury becomes irreversible Aactic acidosis occurs in pts 0ith septic shock because of tissue hypo'ia, 0hich results in impaired o'idative phosphorylation and the shunting of lactate follo0ing glycolysis epatic hypoperfusion also contributes to the buildup of lactic acid, as the liver is the primary site of lactate clearance In a pt 0ith M-, the most reliable auscultatory nding indicating a high regurgitant volume (severe M-) and A2 volume overload is a left sided $C gallop !he intensity of the holosystolic murmur does not correlate 0ell 0ith regurgitant volume as larger regurgitant orices often present 0ith softer murmurs !he classic presentation of pernicious anemia is an older, mentally slo0 0oman of northern 3uropean descent 0ho is lemon coloredJ (anemic and icteric), has a smooth shiny tongue (atrophic glossitis), and demonstrats a shuVing, broad based gait #nion inhibitor (perchlorate, pertechnetate) block iodide absorption by the thyroid gland via competitive inhibition !hionamides (methima*ole, !1) decrease the formation of thyroid hormones by inhibiting thyroid pero'idase Iodide salts inhibit synthesis as 0ell as release of thyroid hormone I" @FPC Isolated diastolic <: A2 end diastolic pressure is increased, but A2 end diastolic volume and e>ection fraction are normal !rousseaus syndrome . migratory supercial thrombophlebitis . is an indication of visceral cancer It is a paraneoplastic syndrome of hypercoagulability may be seen $upercial venous thrombosis may appear in one site and then resolve, only to recur in another site Ene of the most common reasons for elevated #< in pregnancy screening is underestimation of gestational age $enile calcic aortic valve degeneration becomes clinically apparent in the P th decade of life (the guy in the 5uestion 0as P) #$ assoacited 0ith congentially bicuspid aortic valves tends to present by the S th decade #ortic valve infective endocarditis causes aortic regurg Glucokinase is a glucose sensor 0ithin the pancreatic beta cells Inactivating mutations of the en*yme result in mild hyperglycemia that can be e'acerbated by pregnancy ts 0ho overdose on beta blockers should be treated 0ith glucagon, 0hich increases - and contractility indepdnent of adrenergic receptors Glucagon activates G&-s on cardiac myocytes, causing activation of adenylate cyclase and raising intracellular c#M !he result is calcium release from intracellular stores and icnresed $# node ring !opical preparations of alpha adrenergic agonists cause vasoconstriction of the nasal mucosa vessels and are used as decongestants Everuse of these drugs cuases negative feedback, resulting in decreased N3 synthesis and release from nerve endings, 0hich diminishes their eDect (tachyphyla'is) Nitroprusside is the agent of choice in treating hypertensive emergency It has a 5uick onset of action and short duration of action Nitroprusside is intiitally metaboli*ed to cyanide, 0ith subse5uent conversion to thiocyanate by liver rhodanase !hus, one ma>or disadvantage of its use involves the risk for developing cyanide to'icity Na thiosulfate is used to treat cyanide to'icity and 0orks by donating sulfur to liver rhodanase to enhance conversion of cyanide to thiocyanate
$A3 can cause acute coronary syndrome at a young age even 0ith angiographically normal coronary arteries Glucocorticoids are predominantly catabolic, causing muscle 0eakness, skin thinning, impaired 0ound healing, osteoporosis, and immunosuppression o0ever, they increase liver protein synthesis, specically en*ymes involve din gluconeogenesis and glycogenesis !his, along 0ith peripheral antagonism of the eDects of insulin, contributes to the development of hyperglycemia ropranolol decreases the rate of !8 !C conversion (0hich is 0hy 0e use it along 0ith !1 and prednisone for thyro'icosis #nd because beta blockers stop sympathetic adrenergic impulses)
#7b occurs due to irregular, chaotic electrical activity 0ithin the atria hile some of the atrial impulses are transmitted to the ventricles, most are not due to the #2 nodal refractory period
Massaging the carotid prolonges the #2 node refractory period to help $2! &an also use adenosine #menorrhea from anore'ia is due to loss of pulsatile secretion of Gn- from the hypothalamus !he defect is in the hypothalamus, not the ovaries or pituitary !he initital commited step of gluconeogenesis is the conversion of pyruvate to o'aloacetate, and o'aloacetate to phosphoenolpyruvate Ion pump failure due to #! deciency during cardiac ischemia causes intracellular accumulation of Na and &a !he increased intracellular solute concentration dra0s free 0ater into the cell, causing the cellular and mitochondrial s0elling that is observed histologically Ne0 onset murmur in a young adult R bacterial endocarditis Glomerulonephritis secondary to circulating immune compel'es can be complicate bacterial endocarditis and result in acute renal insuOciency #2 shunts increase preload and decrease afterload by routing blood directly from arterial to venous system, bypassing the arterioles igh volume #2 shunts can eventually result in high7output cardiac failure ericardial knock is sounds that occurs earlier in diastole than the $C heart sound It is from constrictive pericarditis reducing ventricular compliance via an e'ternal force -educed IN!-IN$I& ventricular 0all compliance is a cause of $C Aoss of consciousness brought about by severe hypoglycemia is typically treated 0ith intramuscular glucagon in the non7medical setting and 0ith I2 de'trose in the medical setting #bdominal pain due to acute pancreatitis is the most likely presentation for hyperchylomicronemia Niacin can potentiate the eDects of some anti7hypertensive medications because of its vasodilatory eDects "ecrease the dose Niacin also increases insulin resistance and oftentimes necessitates an increase in diabetes medications #myloid specic organ: &ardiac atria: #N !hyroid gland: calcitonin ancreatic islets: amylin &erebrumBcerebral blood vessels: beta amyloid ituitary gland: prolactin rednisone is used for Graves opathalmopathy ts 0ith adult type coarctation of the aorta commonly die of !N associated complications, including A2 failure, ruptured dissecting aortic aneurysm, and intracranial hemorrhage !hese pts are at increased risk for ruptured intracranial aneurysms because of the increased incidence of congenital berry aneurysms of the circle of 0illis as 0ell as aortic arch !N 3Dect modication is present 0hen the eDect of the main e'posure on the outcome is modied by the presence of another variable 3Dect modication is not bias !he murmur of #- is best heard at the left sternal border, 0ith the pt leaning for0ard at end e'piration "amage to the posterior pituitary produces only transient central "I ermanent central "I usually rsults form dmage to hypothalamic nuclei or the pituitary stalk Glucagonoma R "M, necrolytic erythema, and anemia ericarditis pain radiates to the neck and shoulders and is relieved by sitting up retibial my'edema (lo0er leg skin thickening and induration . it manifests as nonpitting edema that is sometimes scaly in appearance resembling an orange peel) and e'opathlamos are $3&I
