Goljan 5 Days (125 PGS)

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GOLJAN PATHOLOGY LECTURE NOTES

(125 PAGES)
Day 1 Audio file 1: Cellular Injury 1 CHAPTER 1: CELLULAR REACTION TO INJURY Key issues hypoxia, cyanide poisoning, free radicals, apoptosis, growth alternations (i.e. hypertrophy, atrophy, hyperplasia, etc ! I. Hypoxia " inade#uate oxygenation of tissue (sa$e definition of as shoc%!. &eed '( for oxidation phosphorylation pathway where you get A)* fro$ inner +ito $e$,rane (electron transport syste$, called oxidati-e phosphorylation!. )he last rxn is ' ( to recei-e the electrons. *rotons are ,eing %ic%ed off, go ,ac% into the $e$,rane, and for$ A)*, and A)* in for$ed in the $itochondria A. Terms: 1. Oxygen on!en! " ., x '( satn / partial pressure of arterial oxygen (these are the 0 $ain things that carry '( in our ,lood! In .,, the '( attaches to he$e group ('( sat1n! *artial pressure of arterial '( is '( dissol-ed in plas$a In 23C, four he$e groups (4e $ust ,e /(5 if 4e/ is /0, it cannot carry '(! )herefore, when all four he$e groups ha-e an '( on it, the '( sat1n is 1667. ". O" sa!#n is the '( I& the 23C is attached )' the he$e group " ($easured ,y a pulse oxi$eter! $. Par!ia% press&re o' O" is '( dissol-ed in *8A9+A '( flow: fro$ al-eoli through the interphase, then dissol-es in plas$a, and increases the partial pressure of ' (, diffuses through the 23C $e$,rane and attaches to the he$e groups on the 23C on the .,, which is the '( sat1n )herefore if partial pressure of '( is decreased, '( sat1n .A9 to ,e decreased (3:c '( ca$e fro$ a$ount that was dissol-ed in plas$a! (. Ca&ses o' !iss&e )ypoxia: 1. Is )emia (decrease in A2);2IA8 ,lood flow &') -enous!
+CC Ische$ia is thro$,us in $uscular artery (,:c this is the $cc death in <9A " +I, therefore +I is good exa$ple of ische$ia ,:c thro$,us is ,loc%ing arterial ,lood flow, producing tissue hypoxia! 'ther causes of tissue ische$ia: decrease in Cardiac 'utput (leads to hypo-ole$ia and cardiogenic shoc%! ,:c there is a decrease in arterial ,lood flow. ". "n* +CC o' !iss&e )ypoxia , )ypoxemia Hypoxia " =,ig1 ter$ Hypoxemia " cause of hypoxia (they are not the sa$e!5 deals with the partial pressure of arterial '( ('( dissol-ed in arterial plas$a, therefore, when the particle pressure of '( is decreased, this is called hypoxe$ia!. .ere are > causes of hypoxe$ia: a. Resp a i*osis (in ter$s of hypoxe$ia! in ter$s of ?alton1s law, the su$ of the partial pressure of gas $ust " @A6 at at$ospheric pressure (ha-e '(, C'(, and nitrogen5 nitrogen re$ains constant therefore, when you retain C'(, this is resp acidosis5 when C'( goes up, p'( .A9 to go down ,:c $ust ha-e to e#ual @A65 )herefore, e-ery ti$e you ha-e resp acidosis, fro$ A&B cause, you ha-e hypoxe$ia ,:c low arterial p' (5 increase C'(" decrease p'(, and -ice -ersa in resp al%alosis!. -. .en!i%a!ion *e'e !s ,est exa$ple is resp distress syndro$e (a%a hyaline $e$,rane dC in children!. In adults, this is called Adult 2?9, and has a -entilation defect. 8ost -entilation to the al-eoli, ,ut still ha-e perfusion5 therefore ha-e created an intrapul$onary shunt. ;xa$ #uestion: pt with hypoxe$ia, gi-en 1667 of '( for (6 $inutes, and p'( did not increase, therefore indicates a 9.<&), $assi-e -entilation defect. . Per'&sion *e'e !s %noc% off ,lood flow +CC perfusion defect " pul$onary e$,olus, especially in prolonged flights, with sitting down and not getting up. 9tasis in -eins of the deep -eins, leads to propagation of a clot and 0DE days later an e$,olus de-elops and e$,oliCes. In this case, you ha-e -entilation, ,ut no perfusion5 therefore there is an increase in dead space. If you gi-e 1667 ' ( for a perfusion defect, p'( will go <* (way to distinguish -ent fro$ perfusion defect!, ,:c not e-ery single -essel in the lung is not perfused. )herefore, perfusion defects ,ecause an increase in dead space, while -entilation defects cause intrapul$onary shunts. )o tell the difference, gi-e 1667 '( and see whether the p'( stays the sa$e, ie does not go up (shunt! or increases (increase in dead space!.
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*. Di''&sion *e'e ! so$ething in the interphase that ' ( cannot get through ie fi,rosis. 3est exa$ple9arcoidosis (a restricti-e lung disease!5 '( already ha-e trou,le getting through the $e$,rane5 with fi,rosis it is worse. Another exa$ple*ul$onary ede$a5 '( cannot cross5 therefore there is a diffusion defect. Another exa$ple is plain old fluid fro$ heart failure leads to dyspnea, ,:c acti-ated the F reflex is initiated (inner-ated ,y C&16!5 acti-ation of C&16, leads to dyspnea (can1t ta%e a full ,reath! ,:c fluid in interstiu$ of the lung, and the F receptor is irritated. )hese are the four things that cause hypoxe$ia (resp acidosis, -entilation defects, perfusion defects, and diffusion defects!. $. Hemog%o-in re%a!e* )ypoxia In the case of ane$ia, the classic $isconception is a hypoxe$ia (decrease in p' (!. )here is &' hypoxe$ia in ane$ia, there is nor$al gas exchange (nor$al respiration!, therefore nor$al p'( and '( saturation, ,ut there is a decrease in .,. )hat is what ane$ia is: decrease in .,. If you ha-e E g$ of .,, there is not a whole lot of ' ( that gets to tissue, therefore get tissue hypoxia and the patient has exertional dyspnea with ane$ia, exercise intolerance. a. Car-on monoxi*e /CO0: classic heater in winter5 in a closed space with a heater (heater ha-e $any co$,usta,le $aterials5 auto$o,ile exhaust and house fire. In the house fire scenario, two things cause tissue hypoxia: 1! C' poisoning and (! Cyanide poisoning ,:c upholstery is $ade of polyurethrane products. Ghen theres heat, cyanide gas is gi-en off5 therefore pts fro$ house fires co$$only ha-e C' and cyanide poisoning. C' is -ery diffusi,le and has a high affinity for .,, therefore the ' ( 9A)1& will ,e decreased ,:c its sitting on the he$e group, instead of '( (re$e$,er that C' has a (66H affinity for .,!. (., is nor$al its &') ane$ia, p' ( ('( dissol-ed in plas$a! is nor$al, too!5 when ' ( diffuses into the 23C, C' already sitting there, and C' has a higher affinity for he$e. )o treat, gi-e 1667 ' (. ?ecrease of '( sat1n " clinical e-idence is cyanosis &ot seen in C' poisoning ,:c cherry red pig$ent +A9K9 it, therefore $a%es the diagnosis hard to $a%e. +C sy$pto$ of C' poisoning " headache -. +e!)emog%o-in: +ethe$oglo,in is 4e0/ on he$e group, therefore ' ( CA&&') ,ind. )herefore, in $ethe$oglo,in poisoning, the only thing screwed up is '( saturation (,:c the iron is /0, instead of /(!. ;xa$ple: pt that has drawn ,lood, which is chocolate colored ,:c there is no '( on he$e groups (nor$al p'(, ., concentration is nor$al, ,ut the '( saturation is not nor$al!5 Iseat is e$pty, ,ut cannot sit in it, ,:c it1s /0J. 23C1s ha-e a $ethe$oglo,in reductase syste$ in glycolytic cycle (reduction can reduce /0 to /(!. ;xa$ple: *t fro$ roc%y $ountains was cyanotic5 they ga-e hi$ 1667 '(, and he was still cyanotic (was drin%ing water in $tns water has nitrites and nitrates, which are oxidiCing agents that oxidiCe ., so the iron ,eco$e /0 instead of /(!. Clue was that ' ( did not correct the cyanosis. 2x: IK $ethaline ,lue (?'C!5 ancillary 2x " -ita$in C (a reducing agent!. +ost recent drug, ?apsone (used to 2x leprosy! is a sulfa and nitryl drug. )herefore does two things: 1! produce $ethe$oglo,in and (! ha-e potential in producing he$olytic ane$ia in glucose A phosphate dehydrogenase deficiencies. )herefore, he$olysis in LA*? def is referring to oxidiCing agents, causing an increase in peroxide, which destroys the 23C5 the sa$e drugs that produce he$olysis in LA*? def are sulfa and nitryl drugs. )hese drugs also produce $ethe$oglo,in. )herefore, exposure to dapsone, pri$a#uine, and )+*D9+H, or nitryl drugs (nitroglycerin:nitroprusside!, there can ,e a co$,o of he$olytic ane$ia, LA*? def, and $ethe$oglo,ine$ia ,:c they are oxidiCing agents. Co$$on to see $ethe$oglo,ine$ia in .IK ,:c pt is on )+*D9+H for 2x of *C*. )herefore, potential co$plication of that therapy is $ethe$oglo,ine$ia. . C&r1es: %e'! an* rig)! s)i'!s Gant a right shifted cur-e want ., with a decreased affinity for ' (, so it can release '( to tissues. Causes: (,0 ,isphosphoglycerate (3*L!, fe-er, low p. (acidosis!, high altitude (ha-e a resp al%alosis, therefore ha-e to hyper-entilate ,:c you will decrease the C'(, leading to an increase in p'(, leading to a right shift ,:c there is an increase in synthesis of (,0 3*L!. 8eft shift C', $ethe$oglo,in, .,4 (fetal .,!, decrease in (,0D3*L, al%alosis )herefore, with C', there is a decrease in '( sat1n (hypoxia! and left shift. 2. Pro-%ems re%a!e* !o pro-%ems re%a!e* !o oxi*a!i1e pa!)3ay a. +os! imp: y!o )rome oxi*ase (last enCy$e ,efore it transfers the electrons to '(. 2e$e$,er the 0 C1s cytochro$e oxidase, cyanide, C' all inhi,it cytochro$e oxidase. )herefore 0 things for C' (1! decrease in ' ( sat (hypoxia!, ((! left shifts (so, what little you carry, you can1t release!, and (0! if you were a,le to release it, it ,loc%s cytochro$e oxidase, so the entire syste$ shuts down -. Un o&p%ing a,ility for inner $ito $e$,rane to synthesiCe A)*. Inner $ito $e$,rane is per$ea,le to protons. Bou only want protons to go through a certain pore, where A)* synthase is the ,ase, leading to production of A)*5 you don1t want rando$ influx of protons and that is what uncoupling agents do. ;xa$ples: dinitrylphenol (che$ical for preser-ing wood!, alcohol, salicylates. <ncoupling agents causes protons to go right through the $e$,rane5 therefore you are draining all the protons, and -ery little A)* ,eing $ade. 3:c our ,ody is in total e#uili,riu$ with each other, rxns that produce protons increase (rxns that $a%e &A?. and 4A?., these were the protons that were deli-ered to the electron transport syste$!. )herefore any rxn that $a%es &A?. and 4A?. that leads to proton production will re- up
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rxns $a%ing &A?. and 4A?. to $a%e $ore protons. Gith increased rate of rxns, leads to an increase in te$perature5 therefore, will also see .B*;2).;2+IA. Co$plication of salicylate toxic " hyperther$ia (,:c it is an uncoupling agent!. Another exa$ple: alcoholic on hot day will lead to heat stro%e ,:c already ha-e uncoupling of oxidati-e phosphorylation (,:c $ito are already $essed up!. )hese are all the causes of tissue hypoxia (ische$ia, ., related, cyto oxidase ,loc%, uncoupling agents!. A,solute %ey thingsM 4. 5)a! )appens 3)en !)ere is: a. resp acidosis ., stays sa$e, '( sat1n decreased, partial pressure of '( decreased ('( sat decreased ,:c p'( is decreased! ,. ane$ia only ., is affected (nor$al '( sat1n and p'(! c. C':$ethe$oglo,in ., nor$al, '( sat1n decreased, p'( nor$al 2x C' 1667 '(5 $ethe$o IK $ethaline ,lue (?'C! or -it C (ascor,ic acid! C. De rease* o' ATP /as a res&%! o' !iss&e )ypoxia0 1. +os! imp: )a1e !o go in!o anaero-i g%y o%ysis5 end product is lactic acid (pyru-ate is con-erted to lactate ,:c of increased &A?.!5 need to $a%e &A?, so that the &A? can feed,ac% into the glycolytic cycle to $a%e ( $ore A)*. Ghy do we ha-e to use anaero,ic glycolysis with tissue hypoxiaN +itochondria are the one that $a%es A)*5 howe-er, with anaero,ic glycolysis, you $a%e ( A)* without going into the $itochondria. ;-ery cell (including 23C1s! in the ,ody is capa,le of perfor$ing anaero,ic glycolysis, therefore sur-i-ing on ( A)* per glucose if you ha-e tissue hypoxia. +itochondrial syste$ is totally shut down (no '( at the end of the electron transport syste$ can only get ( A)* with anaero,ic glycolysis!. Lood news get ( A)* 3ad news ,uild up of lactic acid in the cell and outside the cell (increased anionDgap $eta,olic acidosis with tissue hypoxia! due to lactic acidosis fro$ anaero,ic glycolysis. .owe-er, causes ha-oc inside the cell ,:c increase of acid within a cell will denature proteins (with structural proteins $essed up, the configuration will ,e altered!5 enCy$es will ,e denatured, too. As a result, cells cannot autodigest any$ore ,:c enCy$es are destroyed ,:c ,uildup of acid. )issue hypoxia will therefore lead to C'AL<8A)I'& necrosis (a%a infarction!. )herefore, ,uildup of lactic acid within the cell will lead to Coagulation necrosis. ". "n* pro-%em o' %a 6ing ATP: a%% ATP p&mps are s re3e* &p ,:c they run on A)*. A)* is the power, used ,y $uscles, the pu$p, anything that needs energy needs A)*. Na78 p&mp ,loc%ed ,y digitalis to allow &a to go into cardiac $uscle, so Ca channels open to increase force of contraction (therefore, so$eti$es you want the pu$p ,loc%ed!, and so$eti$es you want to enhance it. Gith no A)*, &a into the cell and it ,rings .(6, which leads to cellular swelling (which is re-ersi,le!. )herefore, with tissue hypoxia there will ,e swelling of the cell due to decreased A)* (therefore will get '( ,ac%, and will pu$p it out therefore it is 2;K;29A38;!. In true 23C, anaero,ic glycolysis is the $ain energy source ,:c they do not ha-e $itochondria5 not nor$al in other tissues (want to utiliCe 4A1s, )CA, etc!. $. Ce%% 3i!)o&! O" %ea*s !o irre1ersi-%e )anges. Ca )anges 3i!) irre1ersi-%e *amage Ca:A)*ase pu$p. Gith decrease in A)*, Ca has easy access into the cell. Githin the cell, it acti-ates $any enCy$es (ie phospholipases in the cell $e$,ranes, enCy$es in the nucleus, leading to nuclear py%nosis (so the chro$atin disappears!, into goes into the $ito and destroys it!. Ca acti-ates enCy$es5 hypercalce$ia leads to acute pancreatitis ,:c enCy$es in the pancreas ha-e ,een acti-ated. )herefore, with irre-ersi,le changes, Ca has a $ajor role. 'f the two that get da$aged ($ito and cell $e$,rane!, cell $e$,rane is da$aged a lot worse, resulting in ,ad things fro$ the outside to get into the cell. .owe-er, to add insult to injury, %noc% off $itochondria (energy producing factory!, it is a -ery ,ad situation (cell dies! CKD+3 for +I, transa$inases for hepatitis (9L') and A9):A8)!, a$ylase in pancreatitis. II. 9ree Ra*i a%s 8i-er with ,rownish pig$ent lipofuscin (seen on gross pic5 can also ,e he$osiderin, ,iliru,in, etc5 therefore need to ha-e a case with the gross pic!5 end products of free radical da$age are lipofuscin ,:c certain things are not digesti,le (include lipids!. A. De'ini!ion o' 'ree ra*i a% co$pound with unpaired electron that is out of or,it, therefore it1s -ery unsta,le and it will da$age things. (. Types o' 9ree Ra*i a%s: 1. 'xygen: Ge are ,reathing '(, and '( can gi-e free radicals. If gi-e a person E67 '( for a period of ti$e, will get superoxide free radicals, which lead to reperfusion injury, esp after gi-ing t*A when trying to rid a da$aged thro$,us. 'xygentated ,lood goes ,ac% into the da$aged cardiac $uscle"reperfusion injury. Kids with resp distress syndro$e can get free radical injury and go ,lind ,:c they destroy the retina called retinopathy pre$aturity5 also leads to ,ronchopul$onary dysplasia, which leads to da$age in the lungs and a crippling lung disease.
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(. Gater in tissues con-erted to hydroxyl free radicals, leading to $utations in tissues. Co$plication of radiation therapy is CA&C;2 (+C cancer fro$ radiation is leu%e$ia, due to hydroxyl free radicals!. 4e(/ produces hydroxyl free radicals ,:c of the fenton rxn. )his is what $a%es 4e o-erload diseases so dangerous, ,:c where-er 4e is o-erloaded, leads to hydroxyl free radicals which will da$age that tissue (therefore, in li-er leads to cirrhosis, in heart leads to restricti-e cardio$yopathy, in pancreas leads to failure, and $ala,sorption, along with dia,etes!. Audio file (: Cell Injury ( 0. )ylenol (a%a aceta$inophen!: +CC drug induced ful$inant hepatitis ,:c free radicals (esp targets the li-er, ,ut also targets the %idneys!. Cytochro$e *>E6 in li-er $eta,oliCes drugs, and can change drugs into free radicals. ?rugs are often changed in the li-er to the acti-e $eta,olite ie phenytoin. Ghere in the li-er does aceta$inophen toxicity $anifest itselfN right around central -ein. )reat$ent: nDacetylcysteine5 howN Gell, the free radicals can ,e neutraliCed. 9uperoxide free radicals can ,e neutraliCed with supraoxide dis$utase (9'?!. Llutathione is the end product of the hexose:pentose phosphate shunt and this shunt also generates &A?*.. +ain function is to neutraliCe free radicals (esp drug free radicals, and free radicals deri-ed fro$ peroxide!. Llutathione gets used up in neutraliCing the aceta$inophen free radicals. )herefore, when gi-e nDacetylcysteine (a%a $uca$ist!5 you are replenishing glutathione, therefore gi-ing su,strate to $a%e $ore glutathione, so you can %eep up with neutraliCing aceta$inophen free radicals. (li%e $ethotrexate, and leu%o-erin rescue using up too $uch folate, leu%o-erin supplies the su,strate to $a%e ?&A, folate reductase!. >. Car,on tetrachloride: CCl> can ,e con-erted to a free radical in the li-er (CCl0! in the li-er, and a free radical can ,e for$ed out of that (seen in dry cleaning industry!. E. Aspirin / )ylenol " -ery ,ad for %idney (ta%es a long ti$e for da$age to ,e seen!. 4ree radicals fro$ aceta$inophen are destroying the renal $edulla Oonly recei-es 167 of the ,lood supplyDrelati-ely hypoxic! and renal tu,ules. Aspirin is %noc%ing off the -asodilator *L;(, which is $ade in the afferent arteriole. )herefore AL II (a -asoconstrictor! is left in charge of renal ,lood flow at the efferent arteriole. ;ither sloughing of $edulla or destroyed a,ility to concentrate:dilute your urine, which is called analgesic nephropathy (due $ainly to aceta$inophen!. III. Apop!osis *rogra$$ed cell death. Apoptotic genes Iprogra$$ed to dieJ (theory!. &or$al functions: (1! e$,ryo s$all ,owel got lu$ens fro$ apoptosis. ((! King of the ,ody B c1so$e (for $en!5 +I4 -ery i$p ,:c all $ullarian structures (uterus, cer-ix, upper 1:0 of -agina! are gone, therefore, no $ullarian structures. +I4 is a signal wor%ing with apoptosis, -ia caspasases. )hey destroy e-erything, then wrap e-erything in apoptotic ,odies to ,e destroyed, and lipofuscin is left o-er. (0! 4or wo$an H c1so$e5 only ha-e one functioning one ,:c the other is a ,arr ,ody. A,sence of y c1so$e caused ger$inal ridge to go the o-arian route, therefore apoptosis %noc%ed off the wolfian structures (epidydy$is, se$inal -esicles, and -as deferens!. (>! )hy$us in anterior $ediastinu$ large in %ids5 if a,sent, it is ?iLeorge syndro$e (a,sent thy$ic shadow!, and would also ha-e tetany5 cause of thy$us to in-olute is apoptosis. (E! Apoptosis is the $ajor cancer %illing $echanis$. (A! *rocess of atrophy and reduced cell or tissue $ass is due to apoptosis. ;x. .epatitis council$an ,ody (loo%s li%e eosinophilic cell without apoptosis! of apoptosis (indi-idual cell death with infla$$ation around it!. Fust needs a signal (hor$one or che$ical! which acti-ate the caspases, and no infla$$ation is around it. Apoptosis of neurons loss ,rain $ass and ,rain atrophy, and leads to ische$ia. 2ed cytoplas$, and pynotic nucleas. Atherosclerotic pla#ue. )herefore, apoptosis is in-ol-ed in e$,ryo, pathology, and %noc%ing off cancer cells. I.. Types o' ne rosis $anifestations of tissue da$age. A. Coag&%a!ion Ne rosis: 2esults often fro$ a sudden cutoff of ,lood supply to an organ i.e. Ische$ia (definition of ische$ia " decrease in arterial ,lood flow!. In ische$ia, there is no oxygen therefore lactic acid ,uilds up, and leads to coagulation necrosis. Lross $anifestation of coagulation necrosis is infarction. <nder $icroscope, loo%s li%e cardiac $uscle ,ut there are no striations, no nuclei, ,right red, no infla$$atory infiltrate, all due to lactic acid that has denatured and destroyed all the enCy$es (cannot ,e ,ro%en down neutrophils need to co$e in fro$ the outside to ,rea%down!. )herefore, -ague outlines " coagulation necrosis (see color change in heart!. 1. *ale -s he$orrhagic infarctions: loo% at consistency of tissue. (a! Lood consistency " grossly loo% pale: infarct: heart, %idney, spleen, li-er (rarest of the organ to infarct ,:c dual ,lood supply!5 ie coagulation necrosis. ;xa$ple of a pale infarction of the spleen, $ost li%ely due to e$,oli fro$ left side of heart5 causes of e$,oli: -egetations (rarely e$,oliCe in acute rheu$atic endocarditis!5 infecti-e endocarditis5 $itral stenosis (heart is repeatedly attac%ed ,y group A ,eta he$olytic streptococcus!5 and clots:thro$,i. )he worst arrhyth$ia associated with e$,oliCation in the syste$ic circulation is atrial fi, ,:c there is stasis in the atria, clot for$ation, then it -i,rates (lil pieces of clot e$,oliCe!. :angreno&s Ne rosis: *ry an* 3e! gangrene: *icture of a dry gangrene not wet gangrene ,:c there1s no pus. 'ccurs in dia,etic1s with atherosclerosis of popliteal artery and possi,le thro$,osis5 (dry gangrene related to coagulation necrosis related with ische$ia (definition of ische$ia " decrease in arterial ,lood flow!, which is due to atherosclerosis of the popliteal artery. *athogenesis of +I: coronary thro$,osis o-erlying the athero$atous pla#ue, leading to ische$ia, and lu$en is ,loc%ed due to thro$,osis. +CC nontrau$atic a$putation " dia,etes ,:c enhanced atherosclerosis (popliteal artery " dangerous artery!. Coronary is also dangerous ,:c s$all lu$en. In wet gangrene, it1s co$plicated ,y infecti-e heterolysis and conse#uent li#uefacti-e necrosis.
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(,! 8oose consistency of tissue" he$orrhagic infarct: ,owel, testes (torsion of the testes!, especially the lungs ,:c is has a loose consistency and when the ,lood -essels rupture, the 23C1s will tric%le out, leading to a he$orrhagic appearance. ;xa$ple: he$orrhagic infarction of s$all ,owel due to indirect hernia. (nd +CC of ,owel infarction is getting a piece of s$all ,owel trapped in indirect hernial sac. +CC of ,owel infarction is adhesions fro$ pre-ious surgery. ;xa$ple: In the 8ung he$orrhagic infarction, wedge shaped, went to pleural surface, therefore ha-e effusion and exudates5 neutrophils in it5 ha-e pleuritic chest pain (%nifeDli%e pain on inspiration!. *ul$onary e$,olus leads to he$orrhagic infarction. (. Li;&e'a !i1e Ne rosis: ;xception to rule of Coagulation necrosis seen with infarctions: ,rain. +C site of infarction fro$ carotid artery why we listen for a ,ruit (hearing for a noise that is going thru a -essel that has a narrow lu$en place with thro$,us de-elops o-er atherosclerotic pla#ue and leads to stro%e!5 leads to transient ische$ic attac%s is little atherosclerotic pla#ues going to little -essels of the ,rain, producing $otor and sensory a,nor$alities, that go away in (> hrs. 3rain with =$eshwor%1 in ,rain, astrocytes is analogous to the fi,ro,lasts ,:c of protoplas$ic processes. )herefore, acting li%e fi,ro,last (can1t $a%e collagen!, ,ut its protoplas$ic processes gi-es so$e structure to the ,rain. )herefore, infarction of the ,rain ,asically li#uefies it (has no struct!, and you see a cyst space %i;&e'a !i1e ne rosis. )herefore, exception to the rule of infarctions not ,eing coagulati-e necrosis is the ,rain and it undergoes li#uefacti-e necrosis (no struc, therefore lea-es a hole!. Cere,ral a,scess and old atherosclerotic stro%e D,oth are li#uefacti-e necrosis. 8i#uefacti-e li#uefies5 thin% neutrophil, ,:c their jo, is to phagocytosis with their enCy$es (to =li#uefy1!5 li#uefacti-e necrosis relates to an infection with neutrophils in-ol-ed (usually acute infection producing an a,scess or an infla$$atory condition, which li#uefies tissue!. )herefore, li#uefacti-e necrosis usually applies to acute infla$$ation, related to neutrophils da$aging the tissue. ;xception to the rule: li#uefacti-e necrosis related to infarct (not an infla$$atory condition, it just li#uefies! (slide shows li#uefacti-e necrosis due to infection in the ,rain!. 9o, if you infarct the ,rain, or ha-e an infection, or ha-e an a,scess it is the sa$e process li#uefacti-e necrosis. ;xa$ple: A,scess gra$ I/J cocci in clusters. Ghy are they in clustersN Coagulase, which leads to a,scesses with staph aur. Coagulase con-erts fi,rinogen into fi,rin, so it localiCes the infection, fi,rin strands get out, resulting in an a,scess. 9trep: releases hyaluronidase, which ,rea%s down LAL1s in tissue, and infection spreads through the tissue (cellulitis!. 4ro$ point of -iew of necrosis, neutrophils are in-ol-ed, therefore it is li#uefacti-e necrosis. ;xa$ple: A39C;99: 8ung yellowish areas, high fe-er and producti-e cough5 gra$ stain showed gra$ I/J diplococcus, which is strep pneu$oniae. (+CC of ,ronchopneu$onia.!. &ot he$orrhagic ,:c its pale, and wedged shaped necrosis at the periphery, which leads to pleuritic chest pain. ;xa$ple: pt with fe-er, night sweats, wt loss + t,, which has granulo$atous (caseous! necrosis. granulo$a (in-ol-es I8D1( and su,set of helper ) cells and I/J **?!. *athogenesis of
C. Caseo&s / )eesy onsis!en y0 Ne rosis: either ha-e $yco,acterial infection (any infections, including atypicals, or syste$ic fungal infection!5 these are the '&8B things that will produce caseation in a granulo$a. It is the lipid in the cell wall of the organis$1s leads to cheesy appearance. 9arcoidosis get granulo$as, ,ut they are not caseous ,:c they are not $y,acteriu$ or syste$ic fungi (hence =noncaseating1 granulo$as! Crohn1s dC get granulo$as, ,ut not caseous ,:c not related to $yco,acteriu$ or syste$ic fungi. D. 9a! Ne rosis: 1. ;nCy$atic 4at &ecrosis: uni#ue to pancreas ;xa$ple: pt with epigastric distress with pain radiating to the ,ac% pancreatitis (cannot ,e *eptic <lcer ?C ,:c pancreas is retroperitoneal!, therefore just ha-e epigastric pain radiating to the ,ac%. A type of enCy$atic 4A) necrosis (therefore necrosis related to enCy$es!. ;nCy$atic fat necrosis is uni#ue to the pancreas ,:c enCy$es are ,rea%ing down fats into 4A1s, which co$,ine with Ca salts, for$ing chal%y white areas of enCy$atic fat necrosis (chal%y white areas due to calciu$ ,ound to 4A1s saponification (soap:li%e salt for$ation!!5 these can ,e seen on xrays ,:c ha-e calciu$ in the$. ;xa$ple: A pt with pain constently penetrating into the ,ac%, show xDray of 2<P. ?x is pancreatitis and esp seen in alcoholics. .isto slide on enCy$atic fat necrosis ,luish discoloration, which is calcification (a type of dystrophic calcificationDcalcification of da$aged tissue!. Ghat enCy$e would ,e ele-atedN A$ylase and lipase (lipase is $ore specific ,:c a$ylase is also in the parotid gland, s$all ,owel, and fallopian tu,es!. Ghat type of necrosisN Another exa$ple: ;nCy$atic fat necrosis. <nderlying causeN Alcohol produces a thic% secretion that will lead to acti-ation of enCy$es5 which leads to pancreatitis. )herefore, whene-er you see ,lue discoloration and atherosclerotic pla#ue in a pancreas, it will ,e calciu$. (. )rau$atic 4at &ecrosis: ;xa$ple: wo$an with da$age to ,reasts is )2A<+A)IC 4A) necrosis (not enCy$atic!5 it can calcify, can loo% li%e cancer on $a$$ogra$. ?iff ,twn that and calcification in ,reast cancer is that it is pain4<8. (cancer " painless!. )rau$atic fat tissue usually occurs in ,reast tissue or other adipose tissue E. 9i-rinoi* ne rosis: (the Doid $eans: loo%s li%e, ,ut isn1t! )herefore, loo%s li%e fi,rin, ,ut is not fi,rin .it is the necrosis of i$$unologic dC: ;xa$ples of i$$unologic dC: *alpa,le purpura " s$all -essel -asculitis (i$$une co$plex type III!.
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4i,rinoid necrosis has i$$une co$plex deposition of s$all -essel. *athogenesis of i$$une co$plex: da$age of type III .*B (an i$$une co$plex is an AgDA, circulating in the circulation5 it deposits where-er circulation ta%es it ie glo$erulus, s$all -essel, where-er!. It acti-ates the co$ple$ent syste$ (the alt syste$!, which produces CEa, which is che$otactic to neutrophils. )herefore, da$age done as a result of type III .*B is done ,y neutrophils. And they are there ,:c the i$$une co$plex acti-ated the alternati-e co$ple$ent syste$. )he co$plex has little to do with the da$age, it1s the neutrophils do e-entual da$age! .enochD9cholein purpura feel person1s legs, and see palpa,le purpura (due to type III .*B!. 2he$atic fe-er (-egetations off the $itral -al-e! ha-e fi,rin li%e (fi,rinoid necrosis! $aterials (necrosis of i$$unologic dC!. +orning stiffness " rheu$atoid arthritis, see fi,rnoid necrosis ,:c i$$unologic da$age. )herefore, fi,rinoid necrosis is necrosis of i$$unologic da$age (in -essel it1s a -asculitis, in %idney it1s a glo$erulonephritis, and in lupus glo$erulonephritis in-ol-ing i$$une co$plexes!. 9. Li1er: )riad area: portal -ein, hepatic artery, ,ile duct. 8i-er is uni#ue ,:c it has dual ,lood supply and so hepatic artery and and portal -ein will du$p ,lood into sinusoids. 'ther exa$ples of sinusoid organs are 3+ and spleen. Characteristic of sinusoids: gaps ,etween endothelial cells, with nothing there so things can fit through (things li%e 23C1s and infla$$atory cells!. L3+ is fenestrated, ha-e little tiny pores within the cells, for filtration. 9inusoids ha-e gaps so large cells can get through the$ (not true with L3+ ,:c it is intact, and lil pores allow filtration!. *ortal -ein ,lood and hepatic artery ,lood go through sinusoids, and e-entually ta%en up ,y central -ein, which ,eco$es the hepatic -ein. )he hepatic -ein du$ps into the inf -ena ca-a, which goes to the right side of the heart. )herefore, there is a co$$unication ,etween right heart and li-er. 2ight .4 (,lood fills ,ehind failed heart!, therefore the li-er ,eco$es congested with ,lood, leading to nut$eg li-er (a%a congesti-e hepato$egaly!. If you ,loc% the portal -ein, nothing happens to the li-er, ,:c it is 3;4'2; the li-er. 3loc%age of hepatic -ein leads to ,udd chiari and li-er ,eco$es congested. Ghich part of li-er is $ost suscepti,le to injury nor$allyN Around central -ein, ,:c it gets first di,,ies on '( co$ing out of the sinusoids (Cone 1!. Qone ( is where yellow fe-er will hit ($idCone necrosis! due to ides egypti. Qone 0, around portal -ein, which will ha-e least ' ( (analogous to renal $edulla, which only recei-es 167 of the ,lood supply, and the cortex recei-es R67!. 4atty change is around Cone 0 (part around central -ein!. )herefore, when as%ing a,out aceta$inophen toxicity, which part is $ost suscepti,leN Around the central -ein ,:c it gets the least a$ount ' (, and therefore cannot co$,at free radical injury.
1.
Alcohol related li-er da$age: (a! +CC fatty change: alcohol. (,! +eta,olis$ of alcohol: &A?. and acetyl CoA (acetate is a 4A, and acetyl CoA can ,e con-erted to 4A1s in the cytosol!. &A?. is part of the $eta,olis$ of alcohol, therefore, for ,ioche$ical rxns: Ghat causes pyru-ate to for$ lactate in anaero,ic glycolysisN &A?. dro-e it in that direction, therefore always see lactic acidosis (a for$ of $eta,olic acidosis! in alcoholic1s ,:c increased &A?. dri-es it in that direction. Also, in fasting state, alcoholic will ha-e trou,le $a%ing glucose ,y gluconeogenesis ,:c need pyru-ate to start it off. .owe-er, you ha-e lactate (and not pyru-ate! therefore alcoholics will ha-e fasting hypoglyce$ia. Acetyl CoA can also $a%e %etone ,odies (acetoacetyl CoA, .+L CoA, and ,eta hydroxy,utyric acid!. 9ee ,eta hydroxy,utyric %etone ,odies in alcoholic1s ,:c it1s a &A?. dri-en reaction. )herefore, two types of $eta,olic acidosis seen in alcoholics are lactic acidosis (,:c dri-ing pyru-ate into lactate! and increased synthesis of %etone ,odies ,:c excess acetyl CoA5 $ain %etoacid " ,eta hydroxy,utyric acid. Ghy does it produce fatty changeN In glycolysis, around rxn >, get inter$ediates dihydroxyacetone phoshphate (&A?. rxn! and is forced to ,eco$e glycerol 0Dphosphate. 3ig ti$e ,oard #uestionM Gith glycerol 0 phosphate shuttle, get A)*. Also i$p to car,ohydrate ,ac%,one for $a%ing tryglycerides (add 0 4A1s to glycerol 0 phosphate, and you get )L1s!. In li-er, the lipid fraction if K8?8 (endogenous )L is synthesiCed in the li-er fro$ glycerol 0 phosphate deri-ed fro$ glycolysis!. 2estricting fat will &') decrease the synthesis of K8?8. 2estricting car,s GI88 decrease the K8?8 synthesis ,:c it is glucose inter$ediate it is $ade fro$. Llycerol 0 phosphate is a product of glycolysis which is why fatty li-er is +C1ly due to alcoholis$ (this rxn!M Audio file 0: Infla$$ation 1 (. Kwashior%er %id with fatty change. )he $echanis$: when you $a%e K8?8, and to ,e a,le to get it out of the li-er, the K8?8 $ust ,e surrounded ,y apoproteins. In %washior%or, there is decreased protein inta%e5 they ha-e ade#uate nu$,er of calories, ,ut its all car,s. )herefore, they cannot get K8?8 that they $ade in the li-er out ,:c there are no apolipoproteins to co-er it and put it out in the ,loodstrea$ and solu,iliCe it in water. 8ipid and water do not $ix5 therefore it is necessary to put proteins around the lipid to dissol-e it in water. )herefore, the protu,erant a,do$en in these pts is there for two reasons: 1! decreased protein inta%e which decreases oncotic pressure, leading to ascites. (! )he ,iggest reason is that they ha-e huge li-ers related to fatty change. )he $echanis$ for fatty change is different fro$ alcohol ,:c in alcohol5 the $ech is due to increased synthesis of K8?8. In this case, there is a lac% of protein to put around the K8?8 and export it out of the li-er. 0. .e$osiderin and 4errtin: ,rief discussion: 4erritin " solu,le for$ of circulating 4e, and is a good $ar%er for 4e in 3+. It is the test of choice in dx1ing any 4e related pro,le$ 4e def ane$ia, or Ane$ia of Chronic ?C or 4e o-erload dC1s such as he$ochro$atosis and he$osiderosis (would ,e ele-ated!. 4erritin is a solu,le for$ of 4e, while he$osiderin is an insolu,le for$ of 4e storage, and is stored in $acrophages and 3+. 9tain it with *russian ,lue.
.. Types o' a% i'i a!ion: dystrophic and $etastatic A. Dys!rop)i a% i'i a!ion: $eans a,nor$al calcification. )he da$aged tissue gets calcified. 1. ;xa$ple: 9een in enCy$atic fat necrosis (chal%y white areas on xDray are a result of dystrophic calcification!.
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(. ;xa$ple: foot,all player with he$ato$a in foot, that ,eco$es calcified dsystrophically (Ca ,inds and coDproduces dystrophic Ca deposits!. 9eru$ Ca is nor$al, ,ut da$aged tissue ,eco$es calcified. 'ccurs in athero$atous pla#ues (causes serious tissue da$age!, therefore they are difficult to dissol-e (need to ,e on the ornish diet a -egan diet!. 0. +CC aortic stenosis (+CC: congenital ,icuspid aortic -al-e! " dystrophic calcification (also leads to a he$olytic ane$ia!. 9lide: the aorta has only ( -al-es doing the jo, of three, and gets da$aged, leading to dystrophic calcification which narrows orifice of -al-e, leading to aortic stenosis. (. +e!as!a!i a% i'i a!ion: In cases of .ypercalce$ia or hyperphosphate$ia, Calciu$ is actually $ade to deposit in nor$al tissues, nonDda$aged tissues. +CC hypercalce$ia (outside of hospital! " pri$ary hyperparathyroidis$ +CC hypercalce$ia (inside the hospital! " $alignancy induced hypercalce$ia. Gith hypercalce$ia, can put Ca in &'2+A8 tissues5 this is called $etastatic calcification. In dystrophic calcification there is da$aged tissue with nor$al seru$ Ca le-els. +etastatic calcification is when there is high Ca or phosphorus seru$ le-els (actually when Ca is deposited into ,one, it is the phosphorus part of solu,ility product that dri-es Ca into ,one!. .igh phosphate le-els (-ery dangerous! will ta%e Ca and dri-e it into nor$al tissue. )his is why ha-e to put a pt with renal failure on dialysis (ha-e high phosphorus seru$ le-els! therefore need to dialyCe the phosphate ,:c the phosphate will dri-e Ca into nor$al tissue ie heart, conduction syste$, renal tu,ules, ,ase$ent $e$,rane (nephrocalcinosis! all lead to da$age. .I. Ce%% +em-rane De'e !s A. R(C mem-rane *e'e !: 9pherocytosis is a defect in spectrin within 23C cell $e$,rane5 if you can1t see a central area of pallor (if you don1t see a donut! then it1s a spherocyte. A,sence of spectrin with in the 23C does not allow the 23C to for$ a ,iconca-e dis%5 it is defecti-e, and therefore for$s a sphere. (. U-i;&i!in stress protein. .igh u,i#uitin le-els are associated with high le-els of stress. 9o$e of the inter$ediate fila$ents (%eratin, des$in, -i$entin! are part of the superstructure of our cells (Ifra$e of the cellJ, upon which things are ,uilt!. Ghen these inter$ediate fila$ents get da$aged, the u,i#uitin $ar%s then for destruction. )he inter$ediate fila$ents ha-e ,een tagged (u,i#uinated! and $ar%ed for destruction. 9o$e of these products ha-e na$es, for exa$ple: there are open spaces within the li-er tisse, these spaces are fat and they are pro,a,ly due to alcohol. )he u,i#uinited products of the li-er are called +allory ,odies. )hese are the result of u,i#uinated fila$ents called %eratin and these are seen in alcoholic hepatitis. Another exa$ple: 9il-er stain of neurofi,ilary tangles Faco, crutCfelt and alChei$ers dC. )au protein is associated with neurofi, tangles5 this is an exa$ple of a u,i#uinated neurofila$ent. ;xa$ple: 9u,stantia nigra in *ar%inson1s ?C include inclusions called 8ewy ,odies, neurotrans$itter deficiency is dopa$ine. 8ewy ,odies are u,i#uinated neurofila$ents. )herefore, +allory ,odies, 8ewy ,odies, and neurofi, tangles are all exa$ples of u,i#uintation. .II. Ce%% Cy %eD -ery -ery i$portant: ,ig ,ig ,ig ti$e A. Di''eren! !ypes o' e%%s: 1. 8a,ile cells cell where the di-ision is -ia a ste$ cell. )hree tissues that has ste$ cells: ,one $arrow, ,ase$ent $e$,rane of s%in, and the ,ase of crypts in the intestine. )hese cells ha-e the tendency of ,eing in the cell cycle a lot. In phar$: there are cell cycle specific and cell cycle nonspecific drugs. )he cells that are $ost affected ,y these drugs are the la,ile cells ,:c they are in the cell cycle. Co$plications of these drugs are 3+ suppression, diarrhea, $ucocidis, and rashes on the s%in (there are ste$ cells in all these tissuesM!. (. 9ta,le cells in resting phase, Lo phase. +ost of perenchy$al organs (li-er, spleen, and %idney! and s$ooth $uscle are sta,le cells. 9ta,le cells can ungo di-ision, ,ut $ost of the ti$e they are resting, and so$ething $ust sti$ulate the$ to get into the cell cycle and di-ide ie a hor$one or a growth factor. 4or exa$ple: estrogen in wo$an will help in the proliferati-e phase of the $enstrual cycle. )he endo$etrial cells are initially in the L o phase and then the estrogen sti$ulated the cells to go into the the cell cycle. )herefore, they can di-ide, ,ut they ha-e to ,e in-ited ,y a hor$one or a growth factor. 0. *er$anent cells can no longer get into the cell cycle, and ha-e ,een per$anently differentiated. )he other types of $uscle cells: striated, cardiac and neuronal cells. 'nly $uscle that is &') a per$anent tissue " s$ooth $uscle5 hyperplasia " increase in S, while hypertrophy " increase in siCe. Gould a per$anent cell ,e a,le to under hyperplasiaN &', ,:c that $eans $ore copies of it. Can it go under hypertrophyN Bes. A s$ooth $uscle cell can undergo hyperplasia A&? hypertrophy. (. Di''eren! p)ases o' e%% y %e: 1. L1 phase: )he $ost -aria,le phase of cell cycle is the L1 phase. Co$pare with $enstrual cycle: )he $ost -aria,le phase is the proliferati-e phase (not the secretory phase!. )he proliferti-e phase -aries with stress5 howe-er, once o-ulation has occurred, it is 1> days. )herefore, proliferati-e phase is analogous to L1 phase of the cell cycle ,:c it can ,e shorter or lengthened5 none of the other phases (9, L (, and + phase! changes, they stay the sa$e. )herefore, in cancer cells, ones with a longer cell cycle will ha-e a longer L1 phase, and cancer cells with a shorter cell cycle will ha-e a shorter L1 phase. L1 phase is the $aster$ind of e-erything. Cyclin dependent %inase (%inase " phosphorylation " acti-ation!. *hosphorylation usually in-ol-es sending a $essage to acti-ate so$ething. Llucagon is a phosphorylator, while insulin is a dephosphorylator. Llucagon will phosphorylate protein %inase and acti-ate it, while Insulin would dephosphorylate protein %inase and inacti-ate it. L1 to 9 phase: Inacti-e Cyclin d dependent %inase: Cyclin d acti-ates it, and L1 phase $a%es cyclin ?. 'nce cyclin ? is $ade in the L1 phase, it then acti-ates the enCy$e: cyclin dep. %inase (therefore it is now acti-e!. Key area to control in
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cell cycle: transition fro$ L1 to 9 phase. 3ecause if you ha-e a $utation and it goes into 9 phase, it then ,eco$es duplicated, then you ha-e the potential for cancer. )wo suppressor genes that control the transition: (1! 2, suppressor gene: located on chro$oso$e 10, which $a%es the 2, protein, which pre-ents the cell fro$ going fro$ the L1 to the 9 phase. In general, to go fro$ L1 to 9, the acti-e cyclin dep %inase phosphorylates the 2, protein5 when it is phosphorylated"acti-ation, it can go fro$ the L1 phase to the 9 phase. A pro,le$ occurs if there is a $utation. )herefore the enCy$e is chec%ed ,y ((! pE0 suppressor gene: located on chro$oso$e 1@, which $a%es a protein product that inhi,its the cyclin d dep %inase. )herefore, it cannot go into the 9 phase5 pE0 is the nu$,er 1, $ost i$p gene that regulates hu$an cancer. ;xa$ple: .*K inacti-ates 2, suppressor gene and pE0 suppressor gene. .*K $a%es two genes products ;A (which %noc%s off the pE0! and ;@ (which %noc%s of the 2, suppressor gene!. If you ha-e a point $utation the 2, suppressor gene, the 2, suppressor gene is %noc%ed off, there will ,e no 2, protein, and the cell will progress to the 9 phase ,:c it is uncontrolled. )his $utation in the 2, suppressor gene predisposing to $any cancers, such as retino,lasto$a, osteogenic sarco$a (ie %id with pain around %nees, Cod$an1s triangle sun,urst appearance on xDrays!, and ,reast cancer (2, suppressor can ,e in-ol-ed!. ?epending on the age ,rac%et, it hits in different areas. If you %noc% of pE0 suppressor gene: the %inase will ,e always acti-e, it will always phosphorylate the 2, protein, and that $eans that it will always go into the 9 phase, and this is ,ad. If you %noc% off any of those genes, the cell will go into the 9 phase. )he pE0 suppressor gene is the guardian of the geno$e, ,:c it gi-es the cell ti$e to detect if there are any defects:a,nor$alities in the ?&A (splicing defects, codon thing, whate-er, etc!. ?&A repair enCy$es can splice out the a,nor$ality, correct it, and the cell is ready to go to the 9 phase. If the cell has too $uch da$aged ?&A, then it is re$o-ed ,y apoptosis. )herefore this gene is i$p ,:c it gi-es the cell an opportunity to clean its ?&A ,efore going into the 9 phase. (. 9 phase " synthesis phase, where e-erything is dou,led, includes ?&A and chro$oso$es (fro$ (& to >&!. 4or exa$ple: if it1s in $uscle, it will ha-e dou,le the nu$,er of contractile ele$ents. 0. L( phase " where tu,ulin is $ade (i$p to $icrotu,ule of the $itotic spindle!5 it is ,loc%ed ,y etoposide and ,leo$ycin. >. + phase " $itosis5 where the cell di-ides into two (& cells. )he cell can either go into the L o resting phase, or can continue di-iding in the cycle, or can ,e per$anently differentiated. pE0 gene $a%es a protein to inhi,it the %inase, therefore pre-ents the 2, protein fro$ ,eing phosphorylated, therefore stays in the L1 phase. )herefore, when you %noc% it off, no one is inacti-ating the %inase, and the cell is constantly phosphorylated and that %eeps the cell di-iding, and then has the potential to lead to cancer. C. Dr&gs !)a! a ! on !)e e%% y %e: 1. ?rugs acting on 9 phase: a! ;rgot al%aloids wor% on the $itotic spindle in 9 phase ,! +ethotrexate wor%s in 9 phase: ;xa$ple: pt with rheu$atoid arthiritis has $acrocytic ane$ia. ?rug responsi,le for this is in what phase of the cell cycleN 9 phase ,:c it is $ethotrexate ,loc%ing dihydrofolate reductase (. ?rugs acting on L( phase: a! ;toposide ,! 3leo$ycin 0. ?rugs acting on + phase: a! Lresioful-in in + phase ,! *aclitaxel specifically wor%s in the + phase: Clinical scenario: this drug is a che$otherapy agent $ade fro$ a yew treeN *aclitaxel ($ phase! c! Kincristine and Kin,lastine d! )his drug used to ,e used for the treat$ent of acute gouty arthritis ,ut ,:c of all the side effects is no longer used. Ghat drug and where does it actN Colchicine ($ phase! >. Clinical scenario that does not wor% on the cell cycle: .IK I/J person with dyspnea and white out of the lung, on a drug5 ends up with cyanosis5 which drugN ?apsone .II. A*ap!a!ions !o en1ironmen!a% s!ress: :ro3!) a%!era!ions A. A!rop)y: ?iagnosis: the decrease in tissue $ass and the cell decreases in siCe. )he cell has just enough organelles to sur-i-e, ie less $itochondria then nor$al cells, therefore, just trying to =ee%1 it out until whate-er it needs to sti$ulate can co$e ,ac%. 1. ;xa$ple: hydronephrosis, the co$pression atrophy is causing thinning of cortex and $edulla, +CC hydronephrosis is stone in the ureter (the pel-is is dilated!. Puestion can ,e as%ed what %ind of growth alteration can occur here. Answer is atrophy ,:c of the increased pressure on the cortex and the $edulla and produces to ische$ia, ,lood flow decreases and can produce atrophy of renal tu,ules. (. ;xa$ple: Atrophied ,rain due to atherosclerosis (+C! or degeneration of neurons (alChei$ers, related to ,eta a$yloid protein, which is toxic to neurons!.
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0. ;xa$ple: In $uscle, $any causes of atrophy ie 8ou Lehrig1s ?C (a$ylateral sclerosis! %noc% off neurons to the $uscle, so it is not sti$ulated, leading to atrophy. >. ;xa$ple: ;ndocrine related: a! .ypopituitaris$ will lead to atrophy of adrenal cortex: the Cona fasiculata and retiucularis layers of the adrenal cortex5 &') the glo$erulosa ,:c AC). has nothing to with sti$ulating aldosterone release. )he fasiculata is where glucocorticoids (cortisol! are $ade, while reticularis is where sex hor$ones are $ade (1@ %etosteroids and testosterone!. AC). is responsi,le for sti$ulating these, therefore Cona fasiculata and Cona reticularis are atrophied. ,! )a%ing thyroid hor$one will lead to atrophy of thyroid gland. )his is due to a decrease of )9. and therefore nothing is sti$ulating the thyroid gland which leads to atrophy. E. ;xa$ple: 9lide showing a ,iopsy of a pancreas in a patient with cystic fi,rosis. Ghat is growth alterationN Atrophy, ,:c the C4)2 regulator on c1so$e @ is defecti-e and has pro,le$s with secretions. )he secretions ,eco$e thic%er and as a result, it ,loc%s the ducts and so that $eans that the glands that were $a%ing the fluids (the exocrine part of the gland! cannot $a%e fluids ,:c of the ,ac% pressure ,loc%ing the lu$en of the duct, which leads to atrophy of the glands, which then leads to $ala,sorption in all children with cystic fi,rosis. A. ;xa$ple: 9lide of an aorta, with atherosclerotic pla#ue, which leads to atrophy of the %idney and secondary .)& (reno-asuclar .*, leading to high renin le-el co$ing out of the %idney!. In the other %idney, it is o-erwor%ed, therefore there is hypertrophy (renin le-el co$ing out of this -ein is decreased and suppressed!. (. Hyper!rop)y increase of the 9IQ; of cell, not nu$,er 9cenario: A cell ,iology #uestion: what is the & of thisN .ypertrophy of a cardiac $uscle (per$anent $uscle!, suppose there is a ,loc% just ,efore the L( phase. Ghat is the nu$,er of chro$oso$esN Answer: S of c1so$es is >&, ,:c it already underwent synthesis: already dou,led. 1 & " sper$ ((0 c1so$es! ( & " nor$al (diploid cell! 0 & " triso$y > & " dou,le the nu$,er C. Hyperp%asia increase in the S of cells In nor$al proliferati-e gland, there are thousands of $itoses, therefore see $ore glands with hyperplasia. 1. ;xa$ple leading to cancer: Gith unopposed estrogen, you $ay end up with cancer, ,:c if you didn1t ha-e progesterone (undoes what estrogen didDcounteracts the estrogen!, you will get cancer. )he cells will go fro$ hyperplasia, to atypical hyperplasia to endo$etrial cancer. )herefore hyperplasia left unchec%ed there is an increased ris% of cancer. 'ne exception: ,enign prostatic hyperplasia5 hyperplasia of the prostate does &') lead to cancer5 just urinary incontinence. (. ;xa$ple: gra-id uterus (wo$an1s uterus after deli-ery!. )his is an exa$ple of E6:E6: E67 hypertrophy of the s$ooth $uscle cells in the wall of the uterus, and E67 related to hyperplasia. 0. ;xa$ple: 3one $arrow: nor$ally should ha-e 0H as $any G3C1s as 23C1s. 9lide shows few G3C1s, and increased 23C1s. )herefore, ha-e 23C hyperplasia. )his is not expected to ,e seen in Iron def ane$ia nor in thalasse$ias ,:c in those, there a defect in ., production. It is expected to ,e seen in chronic o,structi-e pul$onary dC (C'*?! ,:c the hypoxe$ia causes the release of hor$one ;*' (erythropoietin!5 which is $ade in the endothelial cells of the peritu,ular capillaries. 9o in the slide this is an exa$ple of ;*' sti$ulated $arrow. >. ;xa$ple: psoriasis on el,ow an exa$ple of hyperplasia (unregulated proliferation of s#ua$ous cells in the s%in!, leading to red s%in, and raised red pla#ue, ,:c excessi-e stratu$ corneu$. )his is why $ethotrexate wor%s here, ,:c it1s a cell cycle specific for the 9 phase, and pre-ents the ,asal cells fro$ proliferating. E. ;xa$ple: prostate gland and ,ladder hyperplasia of prostate glands, it a hor$one related hyperplasia5 all hor$one sti$ulated glands undergo hyperplasia, not hypertrophy. )he wall of the ,ladder is too thic%5 ,:c urine has to go out thru a narrow opening in the urethra, therefore the $uscle has to wor% harder which leads to hypertrophy of s$ooth $uscle cells of the ,ladder wall ($ore urine $ust go out against a greater force ,:c of an increase in after load!. D. +e!ap%asia replace$ent of one adult cell type ,y another 1. ;xa$ple: 9lide of an esophagus, part of if is all ulcerated away. 'n a section surrounding the ulcer (right at the edge of the $uscosa! there are $ucous secreting cells and go,let cells (these are grandular cells!. )hese cells are not supposed to ,e present in lower esophagus5 s#ua$ous cells should ,e there (not glandular cells!. +etastatic grandular: 3arrets esophagus is a precursor for adenocarcino$a. Adenocarcino$a has surpassed s#ua$ous cell carcino$a of $idDesophagus as the +C cancer of the esophagus. )herefore, L;2? is the nu$,er one precursor to esophageal cancer (adenocarcino$a!. Audio file >: Infla$$ation ( (. ;xa$ple: 8ining of $ainste$ ,ronchus ciliated colu$nar, pseudostatified colu$nar. exa$ple of $etaplasia would ,e s#ua$ous. In s$o%ers, this would ,e an
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0. ;xa$ple: )here are increased go,let cells within $ainste$ ,ronchus of an old s$o%er, also see go,let cells in the ter$inal ,ronchial. &or$ally there are go,let cells in the $ainste$ ,ronchus ,ut there are no go,let cells in the ter$inal ,ronchus, therefore this is an exa$ple of hyperplasia. >. ;xa$ple: Lo,let cells in the sto$ach are a,nor$al (should ,e in the intestines, only!. )his is a glandular $etaplasia, which is a precursor for adenocarcino$a of the sto$ach. .. pylori are a precursor for adenocarcino$a in the sto$ach. 3:c .. pylori causes da$age to pylorus and antral $ucosa ,:c it is a chronic gastritis which intestinal glandular $etaplasia, which is a precursor for adenocarcino$a. +CC adenocarcino$a of the sto$ach " .. pylori. E. ;xa$ple: Cases where $etaplasia causes an increased ris% to caner: a! 2e$e$,er that if hyperplasia is left unchec%ed, could potentially lead to cancer. 4or exa$ple: in endo$etrial hyperplasia the +C precursor lesion to endo$etrial carcino$a due to unopposed estrogen. )he exception is prostatic hyperplasia, which doesn1t ,eco$e cancer. ,! +etaplasia can also go through a process leading to cancer: (1! In lung, ciliated colu$nar epitheliu$ 3;C'+;9 s#ua$ous, therefore, this is called 9P<A+'<9 $etaplasia5 this will lead to s#ua$ous dysplasia, which then proceeds to cancer (s#ua$ous carcino$a!5 ((! In distal esophagus, went fro$ s#ua$ous to glandular epitheliu$ ,:c s#ua$ous epitheliu$ cannot handle the acid, therefore it needs $ucous secreting epitheliu$ as a defense against cellular injury. .owe-er, the glandular $etaplasia can go on to an atypical $etaplasia, predisposing to adenocarcino$a of the distal esophagus. (0! *arasites: ( parasites produce cancer: clonesis sinesis leads to cholangiocarcino$a (Chinese li-er flu%e!5 and shistoso$a he$atoa,ia. )he schistoso$ias he$ato,ia causes ,ladder cancer ,y causing the transitional epitheliu$ to undergo s#ua$ous $etaplasia. )his leads to s#ua$ous dysplasia, and then on to s#ua$ous cancer. )ransitional epitheliu$ leads to s#ua$ous epitheliu$ (called $etaplasia!, then dysplasia, then on to cancer. E. Dysp%asia is really an atypical hyperplasia. 1. ;xa$ple: 9lide of a s#ua$ous epitheliu$ is disorganiCed, with nuclei that are larger near the surface and the ,asal cell layer is responsi,le for the di-iding5 cells at top are ,igger than the ones that are di-iding, it has lac% orientation. If it was found during a cer-ical ,iopsy in pt with .*K infection, or if it was found in the $ainste$ ,ronchus ,iopsy, you should ,e a,le to tell that it is dysplastic. )herefore dysplasia, whether glandular or s#ua$ous, is a precursor for cancer. (. ;xa$ple: )here was a far$er with lesion on the ,ac% of his nec% (can grow on any part of the ,ody, due to sun exposure!, which could ,e scraped off and grew ,ac% actinic %eratosis (a%a solar %eratosis! is a precursor for s#. cell carcino$a of the s%in. <KD, light da$ages the s%in. Actinic %eratosis does not predispose to ,asal cell carcino$a, e-en though ,asal cell carcino$a is the $ost co$$on s%in cancer. CHAPTER T5O: IN9LA++ATION I. A &!e In'%amma!ion A. Car*ina% signs o' in'%amma!ion In the scenario with a ,ee sting: you will see redness (T&-or!. )he %ing of -asodilators is hista$ine and it -asodilates the arterioles. )herefore, hista$ine is responsi,le for the redness of acute infla$$ation (ie ,ee sting!, and is wor%ing on arterioles. &ow if we felt the area, it will ,e war$ ( Ca%or " heat!, this is due to -asodilating the arterioles, which is caused ,y hista$ine. 4or exa$ple in endotoxic and septic shoc%, the s%in is war$ ,:c you are -asodilated. T&mor is a raised structure caused ,y hista$ine. .ista$ine can lead to increased -essel per$ea,ility in the -enules5 is arterial thic%er than -enulesN Bes. )he -enules are -ery thin5 they ,asically ha-e an endothelial cell with a ,ase$ent $e$,rane, all you ha-e to is drill a hole through the 3+ and you are out. )herefore, increased -essel per$ea,ility occurs at the -enule le-el, not the arterial le-el. .ista$ine contracts the endothelial cells, and lea-es the 3+ ,are, leading to increased -essel per$ea,ility, producing an exudate, and swelling of tissue, hence !&mor of acute infla$$ation. )he area $ay hurt ( Do%or " pain! ,ut hita$ine does not ha-e anything to do with this. 3rady%inin is part of the %ininogen syste$ ,etween factor 11 and .age$an factor 1(. 9o when you acti-ate the intrinsic pathway, you auto$atically acti-ate the %ininogen syste$. Ghen you acti-ate factor 1( (.age$an factor!, it will acti-ate 11 and the whole %ininogen syste$. )he end product is ,rady%inin. AC; degrades ,rady%inin. Co$plication of AC; inhi,itor is angioede$a. Also inhi,it $eta,olis$ of ,rady%inin, which increases -essel per$ea,ility, producing the angioede$a (swelling of the tissues!. .ow ,rady%inin produces cough is not really understood. 3rady%inin and *L;( cause pain (*o%or! and is the only one out of the four 8atin ter$s of acute infla$$ation that is not due to hista$ine release. (. <!eps in1o%1e* in A &!e in'%amma!ion (this the nor$al se#uence in acute infla$$ation!: 1. ;$igration: includes $argination, pa-eenting, rolling, adhesion, and trans$igration &eutrophils in circulation start to ,eco$e stic%y ,:c of adhesion $olecule synthesis. ;ndothelial cells ,egin to synthesiCe adhesion $olecules. ;-entatually, neutrophils will stic% to endothelial cells, these steps are called pa-$enting or $argination. )hen neutrophils loo% for ,are ,ase$ent $e$,rane on the -enules and then they drill a hole through it -ia type > collagenase. Cancer cells also ha-e type > collagenase, that1s how they $etastasiCe. Cancer
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cells attach to endothelial -ia adhesion $olecules, usually against la$inin in 3+, and they ha-e collagensae to get through the 3+, therefore, cancer cells are pretty $uch li%e a neutrophil when in-ading tissue. (. Che$otaxis: Ghen they pass 3+ of s$all -enules, they e$igrate ,ut they ha-e to %now what direction to go. )hey get directions in a process called directed che$otaxis. CEa and 8)D3> (leu%otriene 3>! are the che$otactic agents. )hese che$otactic agents are also in-ol-ed in $a%ing adhesion $olecules on neutrophils!. )herefore, they $a%e adhesion $olecules A&? gi-e direction ,y acting li%e che$otactic agents. 0. *hagocytosis -ia opsoniCation: a! ;xa$ple: in an acute infla$$ation with staph aureus, the ,acteria are ,eing processed ,y opsonins, which i$$o,iliCe the particles on the surface of the phagocyte. )he two $ain opsonins are IgL and C0,. )hey help with phagocytosis. ,! ;xa$ple of an opsoniCation defect: 3rutons aga$$aglo,ine$ia: an xDlin%ed recessi-e dC, where all the i$$unoglo,ulins are $issing, including IgL. )herefore, +CC death in these pts is due to infection ,:c cannot opsoniCe things. It produces hypoga$$aDglo,ine$ia, ,ut the $echanis$ of infection is due to not ha-ing IgL to opsoniCe ,acteria, therefore cannot phagocytose it. 3acteria are opsoniCed ,y IgL and C0,, which $eans that neutrophils $ust ha-e receptors for those. In acute infla$$ation the $ain cell is neutrophil and in chronic infla$$ation the $ain cell is $acrophage:$onocyte ($onocytes ,eco$e $acrophages!. )hese cells ha-e to ha-e receptors for these opsonins (IgL and C0,!. )hen they ,eco$e phagocytosed or ,eco$e phagolyso$es. Ghen they are phagocytosed, the lysoso$es go to $icrotu,ules and e$pty their enCy$e into this. c! ;xa$ple: In IDcell disease: in this dC, $annose residues cannot ,e phosphorylate in golgi apparatus therefore the enCy$es are not $ar%ed with phosphorus, and the lysoso$e are e$pty. >. Intracellular $icro,ial %illing: a! ;xa$ples: (1! 9taph aureus in hottu, surrounded ,y enCy$es ((!Chla$ydia can get out of phagolysoso$e, $echanis$ un%nown, ,ut so$eti$es they ha-e $ucous and all %inds of things around the$. ,! O" *epen*en! mye%operoxi*ase sys!em is the ,oardsMM +olecular '( is con-erted ,y &A?*. oxidase, which is in the cell $e$,rane of neutrophils and $onocytes, ,ut not $acrophages. )he $ost i$portant cofactor is &A?*., which is synthesiCed in the pentose phosphate shunt. )he enCy$e responsi,le is glucose A phosphate dehydrogenase, which con-erts LA* into ADphosphogluconate, generating &A?*. and a neutraliCing factor for free radicals (glutathione!. It is con-erting '( into a free radical, superoxide. 9uperoxide has an unpaired electron gi-ing off energy, which is called a resp ,urst, which can ,e $easured ,y radiation detectors5 and ,y a negati-e &3) dye test. In the &3) test, you ha-e a test tu,e, add the colorless &3) dye5 and if neutrophils and $onocytes are wor%ing nor$ally, they will phagocytose it, will ha-e a respiratory ,urst, and the free radical ' ( will cause the color to change to ,lue, indicating that the resp ,urst is wor%ing. If there is no color change, there is not a resp ,urst, therefore the pt has chronic granulo$atous dC of childhood. 4ree radical '( is con-erted ,y 9'? (it1s neutraliCer! into peroxide. *eroxide itself could %ill ,ugs, ,ut it is used for another reason. Githin the neutrophils and $onocytes are reddish granules which are lysoso$es, and are seen in the peripheral ,lood. +yeloperoxidase (one of the $any enCy$es in the granules! will catalyCe the rxn. It will co$,ine peroxide with chloride to fro$ ,leach. )his is !)e mos! po!en! -a !eri i*a% me )anism = O " *ep mye%operoxi*ase sys!em, which is in &;<)2'*.I89 and +'&'CB);9 ,ut &') in $acrophages, ,:c $acrophages lose the syste$ when they con-ert fro$ $onocytes to $acrophages and they use lysoso$es to %ill. +acrophages of the C&9 are $icroglial cells, so the reser-oir cell for C&9:AI?9 is the $icro,ial cell. 'utside the C&9, it is the dendritic cell5 it is a $acrophage located in the ly$ph nodes. c! In LA*? deficiency, infection is the +C precipitation of he$olysis ,:c there is no &A?*., therefore there is no functioning '( dependent $yeloperoxidase syste$, and therefore you are suscepti,le to infection, which will set of he$olysis of 23C19. d! Chronic granulo$atous dC of childhood " H lin%ed recessi-e dC where the $o$ gi-es the dC to the ,oy, and is an asy$pto$atic carrier, and they will trans$it the dC to E67 of their son1s. In this dC, there is a deficient acti-ity of &A?*. oxidase, and the &3) dye test is negati-e (doesn1t show color of die!, therefore no resp ,urst. ?o they ha-e superoxideN &o. *eroxideN &o. +yeloperoxidaseN Bes. ChlorideN Bes. )herefore, if they phagocytosed a ,acteria that could $a%e peroxide, and add it inside the phagolysoso$e, this is what the %id would need to %ill the ,acteria. )hese %ids are $issing *;2'HI?; ,:c there is no &A?*. oxidase. A88 li-ing organis$s $a%e peroxide (including A88 ,acteria!. .owe-er, not all ,acteria contain catalase, which is an enCy$e that ,rea%s down peroxide. 9o, in chronic granulo$atous dC, what can they and can1t they %illN Cannot %ill staph, ,ut can %ill strep. GhyN 3:c staph is Coagulase and CA)alase I/J5 so, ie, if it1s staph. aureus and when it $a%es peroxide, it will also $a%e catalase and neutraliCe it, therefore the child cannot %ill staph, and will %ill the %id. If it was a streptococcus organis$ that $a%es peroxide (does
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not ha-e catalase therefore peroxide can ,e used ,y the child!, it adds what %id really needed to $a%e ,leach, and the ,acteria is then wiped out. )herefore, can %ill strep and not staphM e! +yeloperoxidase deficiency: ?o they ha-e a resp ,urstN Bes ,:c they ha-e &A?*. oxidase. ?o they ha-e peroxideN Bes. ?o they ha-e superoxide free radicalsN Bes. ?o they ha-e chlorideN Bes. ?o they ha-e $yeloperoxidaseN &o. )hey ha-e a nor$al resp ,urst and a nor$al &3) dye test, ,ut they can1t %ill the ,acteria ,:c they cannot $a%e ,leach. )his is called a $yeloperoxidase defect. 'ther types of defects: (1! opsoniCation defects with ,rutons ($issing IgL!, C0 def1s5 ((! che$otactic defects where cells do not respond to che$otaxis5 (0! $icro,iocidal defects, the defect in the a,lility to %ill ,acteria, exa$ple: chronic granul$atous dC of childhood and $yeloperoxidase deficiency are ,oth $icro,iocidal dC, in that they cannot %ill ,acteria, ,ut for different reasons. In $yeloperoxidase def the pro,le$ is that they cannot $a%e ,leach (,:c of the $issing enCy$e!, ,ut do ha-e resp ,urst, and is Autoso$al recessi-e dC. In CL?C the pro,le$ is that they cannot $a%e ,leach either, ,ut they ha-e an A39;&) resp ,urst, and is a HD8I&K;? recessi-e dC. f! Child has an u$,ilical cord that doesn1t fall off when it should. Ghen it was re$o-ed and loo%ed at histologically, they did not see neutrophils in the tissue or neutrophils lining the s$all -essels. )his is an adhesion $olecule defect or ,eta ( integrin defect. <$,lilcal cord needs to ha-e an infla$$atory rxn in-ol-ing neutrophils5 they ha-e to stic% in order to get out. )herefore, if the neutrophils can1t stic%, they can1t get out, and then they can1t get rid of your u$,ilical cord this is a classic adhesion $olecule defect. C. C)emi a% me*ia!ors: 1. .ista$ine: the %ing of che$ical $ediators of acute infla$$ation a! Ghat does it do to arteriolesN Kasodilates ,! KenulesN Increased -essel per$ea,ility (. 9erotonin: a! Ghat a$ino acid $a%es serotoninN )ryptophan ,! Is serotonin a neurotrans$itterN Bes c! In a deficiency, you get depression (also decreased &;! d! a -asodilator and increases -ascular per$ea,ility 0. Co$ple$ent syste$: Anaphylatoxins C0a, CEa. 4unction: sti$ulate $ast cells to release hista$ine, leading to -asodilation and increased -essel per$ea,lility. )hey also play a role in shoc%, ,:c when there is infla$$ation the co$pli$ent syste$ is acti-ated, therefore there will ,e $ast cells and hista$ine, therefore C0a, and CEa will ,oth ,e there. >. &itric oxide $ade $ainly in endothelial cells, and is a potent -asodilator. hypertension. It has a ,ig ti$e role in septic shoc%. It is used for treating pul$onary
E. I8D1 associated with a fe-er, it is a pyrogen, therefore sti$ulates the hypothala$us to $a%e *L1s, which sti$ulate ther$oregulatory syste$ to produce fe-er. Aspirin wor%s ,y inhi,iting the synthesis of prostaglandins there,y reducing the fe-er. A. Arachidonic acid $eta,olites: a! Corticosteroids inhi,its *hospholipase A(, therefore do not release arachidonic acid fro$ phospholipids, therefore not $a%ing *L1s or leu%otrienes. )his is the supre$e antifla$$atory agent ,:c 3'). *L1s and leu%otrienes are ,loc%ed ,y ,loc%ing phospholipase A(. Arachidonic acids $a%e linoleic acid (o$ega 0!, which is found in fish oils and walnuts. It is -ery good for you ,:c it acts li%e aspirin, and ,loc%s platelet aggregation, and that1s how o$ega 0 protects your heart. ,! 8ipoxygenase pathway: Qileutin ,loc%s EDlipoxgenase, other drugs act ,y ,loc%ing the receptors, exa$ple: Cir%ufulast, etc. 8eu%otriene (8)! C>, ?>, ;> (the slow reactor su,stances of anaphylaxis! seen in ,ronchial asth$a. )hey are potent ,ronchoconstrictors5 therefore it can ,e seen why Cileutin wor%s well in asth$a ,:c it ,loc%s the leu%otrienes, including these (8)DC>, ?>, and ;>!. 8) 3> is an adhesion $olecule in che$otaxis. c! Cyclooxygenase pathway: Aspirin ,loc%s cycoloxygenase, irre-ersi,ly in platelets. *L.(: where e-erything see$s to ,e deri-ed fro$. *LI(: deri-es fro$ endothelial cells, it1s also called prostacyclin synthase5 is a -asodilator and inhi,its platelet aggregation (exact the opposite of )xA(!. )hro$,axane A( (the ene$y of *LI(! is $ade in the platelet5 it1s a -asoconstrictor, a ,ronchoconstrictor, and pro$otes platelet aggregation. Ghat drug ,loc%s thro$,axane synthase and is used to stress testing for CA?N ?ipyrra$idal ,loc%s the enCy$e, )xA( synthase, therefore does not ha-e to perfor$ a tread$ill stress test, all you ha-e to do is use the drug dipyrra$idal. *L;(: -asodilator in %idney5 %eeps patent ductus patent in ,a,y heart5 $a%es the $ucous ,arrier in LI (sto$ach! there,y pre-enting ulcers5 can cause dys$enorrhea wo$an and increased uterine contractility, and it an a,ortifactant, to get rid of fetal $aterial. d! C'H (D$a%e sure you %now how this wor%sM e! Corticosteroids ,loc%s phospholipase A(, and it also decreases adhesion $olecule synthesis, along with other steroids li%e epinephrine and &;. ?ecreased adhesion $olecule synthesis, will lead to increased neutrophils on C3C5 in i$$uno, E67 neutrophils are stuc% to the endothelial -essels, and the other E67 are circulating, therefore, decreasing adhesion $olecule synthesis will lead to dou,led G3C (,:c the E67 of neutrophils that were stuc% are now circulating!. Corticosteroids destroy 3Dcells ,:c they are ly$phocytotoxic. +echanis$: decrease G3C1s (3 and ) cells! -ia apoptosis5 therefore, corticosteroids are the signal to acti-ate the caspasases. ;osinophils, $ainly seen in type one
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.*B rxn, corticosteroids decrease the$. Ghen on corticosteroids, the only thing that is increased is neutrophils, -ia decreased adhesion $olecule synthesis. 8y$phocytes and eosinophils are decreased. ;xa$ple: If ha-e Addisons, do not ha-e cortisol, therefore the neutrophil ct decreases and the eosinophil count will increase. ;xa$ple: a person with +I with an 1T,666 C3C $ost of which are neutrophils. +echanis$: ;pinephrine decreases adhesion $olecule sythesis and neutrophil count goes up. D. E%e !ron mi ros opy o' in'%amma!ory e%%s: 1. In lung, type II pneo$ocyte (,lac% dots are lysoso$es!. 8a$ellar ,odies structures where lecithin and phosphotidyl choline is located5 if as% where $acrophage, is, will as% which $a%es surfactant. (. +onocyte: single nucleus with a grayish cytoplas$ has sca-aged5 can for$ foa$ cell in atherosclerotic pla#ue ,:c it has phagocytiCed oxidiCed 8?81s (which is a free radical!5 Kit ; neutraliCes oxidiCed 8?8. 0. 8y$phocyte all nucleus and scant cyptoplas$, pro, a ) cell (A67 of peripheral ,lood ly$phocytes are ) cells!5 ratio of helper to suppressor: C?>:C?T is ((:1!, therefore, $ore li%ely to ,e a .elper ) cell, then a suppressor )Dcell, and 3 cells ((67! are least li%ely. >. 2;2 loo%s li%e a thu$,print, ha-e ri,o1s on it, and li%es to $a%e proteins, li%e Ig1s (therefore it is a plas$a cell!. +ultiple $yelo$a has eccentrically located nucleus, cytoplas$ is always s%y ,lue, $a%ing plas$a cells eC to recogniCe. *las$a cells are deri-ed fro$ 3 cells, and located in the ger$inal follicle. E. Lranules eosinophil (ha-e a red color si$ilar to color of 23C1s! ha-e crystals in the granules. ;osinophils are the only infla$$atory cell that has crystals in the granules. )hey are called CharcotD8eiden crystals when it1s seen in the sputu$ of asth$atic patient. )hey are degenerated eosinophils in sputu$ of asth$atic, and ha-e for$ed crystals that loo% li%e spear heads. 3asophils ha-e granules that are $ore purplish and dar%er, while ,asophils ha-e dar%er colors. A. +ech for %illing in-asi-e hel$inthes)ype II .*B$ajor ,asic protein is in-ol-ed. 2e$e$,er that shistotoso$e eggs are coated ,y Ig; A,1s. ;osinophils ha-e Ig; receptors5 therefore, eosinophils hoo% into the Ig; receptor and release che$icals5 the $ain one released is $ajor ,asic protein, which destroys the hel$inth, which is type II .*B, ,:c it is a cell hoo%ing into an A, on the target cell. )he effector cell is )ype II .*B rxn is the eosinophils5 don1t get confused with )ype I .*B rxn where the effector cell is the +A9) C;88, and they release hista$ine (an eosinophil che$otactic factor!, therefore they are in-ited to area of type I .*B ,:c they ha-e hista$inase and arylsulfatase, which neutraliCes leu%otrienes. )he purpose of eosinophils in type I .*B is to %noc% off che$ical $ediators produced in rxn5 howe-er, when an eosinophil %ills an in-asi-e hel$inth, it does so -ia type II .*B. E. C%&s!er *esigna!ions: .elper t cell " C?> Cytotoxic ) cell " C?T +ar%er for Ag recognition site for all ) cells is C?0 +ar%er for histiocytes (including langerhan1s cells! is C?1 +ar%er for +C leu%e$ia in children " C?16 (calla Ag!5 positi-e 3Dcell ly$pho$a C?1E and 06 " 29 cell C?(1, 'nly on 3 cells ;pstein ,arr -irus5 hoo%s into C?(1 on 3 cells, and actually the atypical ly$phocytes are not 3Dcells ,ut )Dcells reacting to the infected 3Dcells. 3ur%itts is a 3 cell ly$pho$a C?>E is found on all leu%ocytes, is a co$$on antigen on e-erything 9. 9e1er I8D1 is responsi,le and *L;( (this is what the hypothala$us is $a%ing! which sti$ulates the ther$oregulatory center. 4e-er is goodM It right shifts the '( dissoc cur-e. Ghy do we want $ore '( in the tissues with an infectionN 3:c of '( dependent $yeloperoxidase syste$. )herefore, with antipyretics it1s ,ad ,:c thwarting the $echanis$ of getting '( to neutrophils and $onocytes to do what they do ,est. Also, hot te$ps in the ,ody are not good for reproduction of ,acteria:-iruses. II. Types o' in'%amma!ion /s enarios0 A. post partu$ wo$an, with pus co$ing out of lactiferous duct this is staph aureus supplerati-e infla$$ation 3. 3one of child with sepsis, on top of the ,one, was a yellowish area, and it was an a,scess osteo$yelitis staph. aureus5 if the %id had sic%le cell, it is sal$onella5 why at $etaphysis of ,oneN 3:c $ost of ,lood supply goes here, therefore, $echanis$ of spread is he$atogenous (therefore co$es fro$ another source, and then it gets to ,one!. C. .ot, spread o-er face cellulitis due to strep (play oddsM! group A pyogenes (called erysipilis, another na$e for cellulitis! ?. ?iphtheria " psuedo$e$,rane (coryne,acteriu$ diphtheria!, a gra$ / rod, that $a%es an exotoxin, $essing up ri,osylation of protiens -ia elongation factor (, the toxin da$ages $ucosa:su,$ucosa, producing a pseudo$e$,rane5 when ,acteria doesn1t in-ade, produces a toxin that da$ages the $e$,rane5 clostridiu$ difficile also does this. It also produeces a pseudo$e$,rane and a toxin, which we $easure in stool to $a%e the dx. )herefore, the answer is C. difficle.
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;. 4i,rinouis pericarditis, usually with increased -essel per$ea,ility5 seen in (1!lupus, leading to friction ru,5 also seen in ((! the first wee% of +I, and then again A wee%s later in dresslers1s syndro$e, (0! seen in Coxsac%ie 4. +C organis$ producing infection in third degree ,urns " pseudo$onas auriginosa. Color of pus: green due to pyocyanin. L. 3asal cell layer on ,oth sides of clot, proliferate, and go underneath it to clot. In a pri$ary wound it1s usually sealed off in >T hrs (ie appendecto$y!. Key to wound healing is prescence of granulation tissue. 4i,ronectin is a -ery i$portant proteoglycan and is in-ol-ed in the healing of the wound. 4i,ronectin is an i$portant adhesion agent and che$otactic agent, in-iting fi,ro,last in helping healing process. )he granulation tissue starts at day 0 and is on its pri$e ,y day E. If you e-er pic%ed at a scar and it ,leed li%e $ad and you try to stop it ,ut it still ,leed li%e $ad, that1s granulation tissue. &o granulation tissue $eans no healing of a wound. )ype of collagen in initial stage of wound repair " type 05 type > collagen seen in 3+5 type 1 -ery strong tensile strength5 seen in ,one, s%in, tendons, liga$ents. After a few $onths, after $onths, the collagen type 0 is ,ro%en down ,y collagenases, and a $etallic enCy$e con-erts type 0 into type 1. Qinc is part of the $etallic enCy$e, this is why in a pt with Cinc deficiency has poor wound healing ,:c it screws up the collagenase ($ust replace type 0 with type 1!. +ax tensile strength after 0 $onths " T67. +CC poor wound healing " infection .. ;hlers ?anlos defect in collagen due to syn:,rea%ing down5 ha-e poor wound healing. I. $arfan defect in fi,rilin5 also ha-e poor wound healing F. *t with scur-y defect in hydroxylation of two aa1s proline and lysine -ia ascor,ic acid. 2e$e$,er it1s a triple helix5 what $a%es the triple helix stic% together and increase tensile strengthN Cross,ridges. Ghen you cross,ridge things, they anchor into areas where you ha-e hydroxylated proline and lysine. )herefore ha-e wea% a,nor$al collagen in scur-y ,:c there are no cross,ridges to attach, leading to not ,eing a,le to heal wounds, he$orrhaging, he$arthroses .collagen has wea% tensile strength ,:c cannot cross,ridge. Audio file E: 4luid and .e$odyn1 K. Lranulation tissue with a lot of ,lood -essels due to lot of fi,ro,last L, with infla$$atory cells fro$ plas$a cells and ly$phocytes, necessary for wound healing (rich -ascular tissue, which is a,solutely essential for nor$al wound healing!. 8. Keloid (hypertrophic scar! " excess in type 0 collagen deposition5 which causes a tu$or loo%ing lesions, esp in ,lac%s. In a white %id %eloid to due to third degree ,urns. In another exa$ple: in a chronically draining sinus tract of the s%in, they tried to put anti,iotics on it (didn1t wor%!, there was an ulceration lesion at the orifice of this chronically draining tract, and nothing wor%ed. Ghat is itN )he answer is s#ua$ous cell carcino$a due to a lot of turno-er5 type 0 con-erted to type 1, and fi,ro,lasts are in-ol-ed. A lot of cell di-ision occurring, which can presdispose to $utations and cancer, esp s#ua$ous cell cancer. 9#ua$ous cancer is i$p ,:c chronically draining sinus tracts, and predisposes to s#a$ous cell carcino$a. .yperplasia predisposes to s#ua$ous cell carcino$a. III. C)roni in'%amma!ion A. ?ifference in I$$unoglo,ulins: 1. Acute Infla$$ation: Ig+ " $ain Ig first, and then IgL Ig+ " $ain Ig5 need a lot of co$ple$ent co$ponents in healing process5 Ig+ is the $ost potent acti-ator, and ha-e acti-ation of co$ple$ent pathway (all the way for 1DR!5 Ig+ has 16 acti-ating sites (penta$er!. IgL can acti-ate the classical syste$, ,ut does &') go passed C0 and stops and does not go onto CEDR. After 16 days, there is isotype switching, and the $u hea-y chain is spliced out ($u chain defies specificity of an Ig!5 it splices in a ga$$a hea-y chain, and IgL is $ade -ia isotype switching (. Chronic infla$$ation: IgL (as $ain Ig Ig+ is co-erted to IgL i$$ediately! 3. ?ifference in Cell )ypes: 1. Acute infla$$tions " neutrophil (. Acute allergic reactions" eosinophils ($ast cells are in tissues! 0. Kiral infections " ly$phocytes are the $ain infla$$atory cells >. Chronic infla$$ations " $onocytes:$acrophages are i$p. And see a lot of plas$a cells and ly$phocytes5 do not see pusDexudati-e (this is in acute infla$$ increased -essel per$ea,ility, and increased e$igration of neutrophils into interstitial tissue, a protein rich fluid with U0 gra$s:d8, with a protein rich fluid " pus!. ;xa$ple: Cholecystis. C. )ype IK .ypersensiti-ity 2eaction: Another exa$ple: Lranulo$a " chronic infla$$ation (ne-er acute!5 ie caseious necrosis in so$eone with )35 roundish, pin%, $ultinucleated giant cells " granulo$as5 pathogenesis " type IK hypersentisti-ity reaction delayed .*B. )he $ain actors are cytoxic ) cells5 when they %ill neoplastic, -irally infected cells, these are also type IK .*B (no A,1s in-ol-ed!. *oison i-y " type IK .*B. 3ac% to )3 infection, aleo-lar $acrophage phagocytoses it, and there is ly$phohe$otogenous spread5 $eanwhile the $acrophage is processing the Ag. )hen after wee%s, it presents it to helper ) cells. )herefore, the %ey players in )ype IK hypersensiti-ity rxn are $acrophages which process that Ag and presents that Ag -ia class II +.C sites to the helper ) cells. )hese helper )Dcells release cyto%ines: ga$$a I4& and $acrophage inhi,itory factor. La$$a I4& will acti-ate the $acrophage to %ill the )3, Cryptococcus, histoplas$osis, etc. )herefore the ga$$a I4& is the trigger to acti-e the $acrophage5 $acrophage cannot %ill without the acti-ation fro$ ga$$a I4&5 ,:c syst$e$ic fungi and )3
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ha-e lipid in the cell wall, this leads to caseous necrosis. All the pin% staining cells are =epthiloid1, which are acti-ated $acrophages (which ha-e ,een acti-ated ,y ga$$a I4&!5 when they die, they die in style they fuse together and for$ $ultinucleated giant cells (li%e their =gra-estone1!. )herefore, epitheloid cells are fused $acrophages5 ,lac% dots are helper ) cells. )here are two types of helper )Dcell: a. 9u,set 1: in-ol-ed in )ype IK (delayed type! .*B5 $acrophages ha-e I8D1(5 when it is secreted, the su,set 1 helper ) cells are presented with the antigen5 then, su,set 1 ,eco$e +;+'2B ) cells. I8D1( is in-ol-ed in acti-ating the $e$ory of su,set 1 helper t cells. +ost people in their pri$ary dC usually reco-er with no pro,le$s, ,ut the granulo$as can calcify, as seen on xDray. A calcified granulo$a is not dead ,:c they are resistant to dying. )herefore, $ost cases of secondary )3 are due to reacti-ation )3. Lranulo$as necrosis is due to reacti-ation. I/J **? (purified protein deri-ati-e! injected into the s%in5 the $acrophage of the s%in is a langerhan1s cell (histiocyte! ($ar%er: C? 1! which ha-e ,ir,ec% granulesDloo% li%e tennis rac%ets on ;+. )hey phagocyotose the Ag (the **?!, and process it -ery #uic%ly5 they present it to helper su,set 1, which has $e$ory of pre-ious exposure. )herefore, it hoo%s in the +.C class II Ag sites (as all i$$une cells do!, and once the Ag (**? processed ,y the langerhan1s cell! is presented, the helper ) cell releases the cyto%ines producing the infla$$atory rxn with induration called the I/J **?. Correlation: older people usually don1t host a -ery good )ype IK hypersensitity rxn: they ha-e a less response to I/J **?5 therefore ha-e to do a dou,le test on the$. In pt with AI?s, $ay not get any rxn. )hey don1t ha-e enough helper )Dcells therefore don1t ha-e granulo$a for$ation. +acrophage inhi,itory factor %eeps $acrophages in that area5 therefore, with .IK, ,:c the helper t cell ct is decreased, you don1t for$ granulo$as at all. )herefore, they will ha-e +AI (organis$s! all o-er the ,ody without granulo$as ,:c helper ) cells are decreased. Ghen you do I/J **?, E $$ induration is enough to say it1s positi-e. . I.. Tiss&e Repair 9car tissue (,:c its per$anent tissue!5 scar tissue (fi,rous tissue! does not contract5 therefore, if you ha-e $ore scar tissue to free wall of left -etricle will lead to decreased ejection fraction (which is stro%e -olu$e di-ided ,y ;?K!. A. 2esponse of Kidneys to Injury: Kidney will for$ scar tissue5 $edulla is $ost suscepti,le to ische$ia (,:c least a$ount of ,lood supply!. Ghat part of nephron $ost suscepti,le to tissue hypoxiaN ( places: 1. 9traight portion of prox tu,ule ,:c $ost of oxidati-e $eta,olis$ is located there, with ,rush ,orders this is where $ost of rea,sorption of &a, and reclai$ing of ,icar, is there. (. +edullary seg$ent of thic% ascending li$, where the &a:KD(Cl pu$p is which is where loop diuretics ,loc%. )he &a:KD(Cl pu$p generates free water. )he two type of water in urine: o,ligated and free. If the water is o,ligated, then the water is o,ligated to go out with e-ery &a, K, and Cl (concentrated urea!. 3asically (6 $l1s of o,ligated water for e-ery &a, K, Cl (it1s o,ligated! -ia &a:K:(Cl pu$p. )he A?. hor$one a,sor,s free water ,:c the pu$p generates free water. 8et1s say you a,sor, one &a, how $uch free water is left ,ehind in the urineN (6 $ls5 then rea,sor,ed another K, that is another (6, so its up to >65 another ( Cl1s are rea,sor,ed which is another >65 therefore, for a,sor,ing one &a, one K, and ( Cl1s, you ha-e ta%en T6 $ls of free water fro$ the urine this is free water that is generated5 its is this pu$p that loop diuretics ,loc%, which is in the thic% ascending li$, of the $edullary seg$ent. 3. 8ung repair cell is type II pneu$ocyte (can also repair type I pneu$ocytes!5 it also synthesiCes surfactant. C. C&9 repair cell is the astrocyte5 the astrocyte proliferates (,:c it1s a sta,le cell, not a neuron!, that can proliferate and produces protoplas$ic processes called gliosis (rxn to injury in the ,rain, which is due to astrocyte proliferation!5 this is analogous to fi,ro,lasts laying collagen type 0 in the wound. ?. *&9 wallarian degeneration is the $ech of axonal regeneration In *&9, ha-e 9chwann cells, while in the C&9, ha-e oligodendrocytes (,oth $a%e $yelin!. )u$or 9chwann cell " schwanno$a5 if it in-ol-es C& KIII it is called acoustic neuro$a. Ghat genetic dC that is auto do$inant has associationN &eurofi,ro$atous. (9ide note: $yasthenia gra-is tensilon injection will increase Ach in synapses in eyelids, and $yasthenic crisis will end! .. Ex!ra <i*e no!es an* Re1ie3 o' In'%amma!ion: A. ;92 putting whole ,lood into cylinder and see when it settles. )he higher the density, or weight, therefore settle pretty #uic% and therefore ha-e a increase sedi$entation rate. Ghen stuc% together and loo%s li%e coins " roulouex. Ghen aggregated together " increased sed rate, which is increased IgL and fi,rinogen (includes e-ery acute and chronic infla$$ation there is. Ghat causes 23C1s to clu$p Ig+, ,:c the neg charge nor$ally %eeps 23C1s fro$ stic% to e:o. Ig+ is a lot ,igger5 cold agglutinins are associated with Ig+ a,, leading to agglutinin. )his is why in cold whether, you get 2aynaud1s pheno$enon (lips, nose, ears, toes, fingers turn ,lue!. )he Ig+ a, can cause cold agglutinins, leading to ische$ia. Another type of clu$ping of Ig+ are Cryoglo,ulins Ig1s congeal in cold weather5 Ig+ a,1s do the sa$e thing. .igh assoc of hep C with cryoglo,ulins. +ult $yleo$a " increased esr ,:c increased IgL5 with waldenstro$s, will see increased Ig+ (Galdenstro$1s +acroglo,e$ia!. 3. Acute appendicitis get C3C, and want to see a,solute neutrophilic leu%ocytosis, $eaning that you ha-e an increase of neutrophils in the peripheral ,lood5 also loo%ing for toxic granulation, and a 8;4) 9.I4). Assu$ing you start fro$ $yelo,last on
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the left, and e-entually for$ a seg$ented neutrophil on the right5 nor$ally go left to right on $aturation5 therefore, with a left shift, its $eans that we go ,ac% to i$$ature neutrophils5 the definitions is greater than 167 ,and neutrophils is considered a 8;4) 9.I4) (all the neutrophils are ,ands!5 if you ha-e just one $eta$yelocyte or one $yelocyte, its is auto$atically considered a 8;4) 9.I4). In acute appendicitis, there is an a,solute increase in neutrophils, with toxic granulation and a left shift. C. +ost potent syste$ for %illing ,ugs " '( dependent $yeloperoxidase syste$5 +yeloperoxidase is located in aCurophilic granules, which are lysoso$es. Gant a lot of lysoso$e in an acute infla$$atory rxn, ,:c therefore there is $ore $yeloperoxidase around for %illing ,ugs this is what toxic granulation. )herefore, toxic granulation ensures that there is enough $yeloperoxidase to wor% that potent syste$ to %ill ,ugs ('( dep $yeloperoxidase syste$!. CHAPTER $: 9LUID AND HE+ODYNA+IC< I. E*ema excess fluid in the interstitial space, which is extracellular fluid (;C4!5 this is outside the -essel A. Types o' E*ema 1. &onD*itting ede$a increased -essel per$ea,ility with pus in the interstial space (pus"exudates!. 8y$phatic fluid is another type of nonDpitting ede$a. 3loc%age of ly$phatics leads to ly$phatic fluid in the interstial space. *its early, ,ut e-entually ,eco$es nonpitting. ;xudates and ly$phatic fluid does not pit. (. *itting ede$a transudate with right heart failure, swelling of the lower extre$ities, fluid in the interstial space. )ransudate does pit. 0. 9o there are three things that cause ede$a: exudates, ly$phede$a, and transudate, and transudates are the only one that has pitting ede$a. (. Trans&*a!e7Pi!!ing E*ema )ransudate deals with starling forces: 1. Ghat %eeps fluid in our ,lood -esselsN Al,u$in, and this is called oncotic pressure. T67 of our oncotic pressure is related to the seru$ al,u$in le-els. Anyti$e there is hypoal,u$ine$ia then we will ha-e a lea%ing of a transudate (protein of less than 0 g:d8! lea%ing into interstial space -ia capillaries and -enules (pitting ede$a!5 (. &or$ally, hydrostatic pressure is trying to push fluid out. )herefore, in a nor$al person, oncotic pressure is winning. )herefore, a decrease in oncotic pressure and an increase in hydrostatic pressure will lead to transudate (pitting ede$a!. 0. Al,u$in is $ade in the li-er. Gith chronic li-er dC (cirrhosis!, ha-e a decreased al,u$in le-el. Can you -o$it it outN &o. Can crap it out ($ala,sorption syndro$e!, or can pee it out (nephrotic syndro$e!, can co$e off our s%in (0 rd degree ,urn ,:c losing plas$a!, another possi,ility of low protein ct (lowDinta%e! is seen in %ids Kwashior%or %id has fatty li-er and decreased protein inta%e, leading to low al,u$in le-el. >. ;xa$ples: a. *erson with +I (> hrs ago and he died and he has fluid co$ing out transudate ,:c increased hydrostatic pressure and left .4 due to +I so things ,ac%ed up into the lungs. 3:c the C' decreased, the ;?K increases and pressure on left -entricle increases, and the pressure is trans$itted into the left atriu$, to the pul -ein, %eeps ,ac%ing up, and the hydrostatic pressure in the lung approaches the oncotic pressure, and a transudate starts lea%ing into the interstitial space, which leads to acti-ation of the F receptor, which will cause dyspnea. 8eads to full ,lown in al-eoli and pul$onary ede$a, which is what this is. ,. -eno$ fro$ ,ee sting on ar$ leads to exudate due to anaphylactic rxn (face swelled!, with hista$ine ,eing the propagator, and type one .*B, causing tissue swelling. 2x airway, 1:1666 a#ueous epinephrine su,cutaneously c. cirrhosis of li-er, with swelling of the legs: transudate, $echanis$: decreased oncotic pressure ,:c cannot syn al,u$in, and increased hydrostatic pressure ,:c portal .)&5 there is cirrhosis of the li-er, and the portal -ein e$pties into the li-er5 in this case, it cannot, and there is an increase in hydrostatic pressure, pushing the fluid out into the peripheral ca-ities (so there are ( $ech for acites!. *itting ede$a in legs: decreased in oncotic pressure d. *t with dependent pitting ede$a: pt has right heart failure, and therefore an increase in hydrostatic pressure5 with right heart failure, the ,lood ,ehind the failed right heart is in the -enous syste$5 cirrhosis of li-er is due to decrease in oncotic pressure. e. $odified radical $astecto$y of that ,reast, with nonpitting ede$a: ly$phede$a. 'ther causes w. ,ancrofti, ly$phogranulo$on -enariu$ (su,type of chyla$dia tracho$ata scarring tissure and ly$phatics, leading to ly$phede$a of scrotu$ ly$phatic!. Infla$$ation carcino$a of ,reast (p1eau de orange of the ,reast! deals with der$al ly$phatics plug with tu$or5 excess leads to di$pling, and loo%s li%e the surface of an orange. +CC ly$phede$a " postradical $astecto$y5 can also run ris% of ly$phangiosarco$a.
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II. Rena% P)ysio A. EC97IC9 ;C4 (1:0! " extracellular fluid of two co$part$ents -ascular (1:0! and interstitial ((:0! IC4 ((:0! " intracellular fluid co$part$ent
17
;xa$ple: how $any liters of isotonic saline do you ha-e to infuse to get 1 liter into the plas$aN 0 8iters ((:0:1:0 relationship!5 ( liters in interstial space, and 1 8 would go to the -ascular space5 it e#uili,rates with interstial:-ascular co$part$ents. (. Osmo%a%i!y " $easure of solutes in a fluid5 due to three things: &a, glucose, and ,lood urea nitrogen (3<&! urea cycle is located in the li-er, partly in the cytosol and partly in the $itochondria5 usually $ultiply &a ti$es ( (,:c one &a and one Cl!. Audio file A: 4luid and .e$odyn ( &or$al &a is 10ED1>6 range, ti$es that ,y ( that (T6. 4or glucose, nor$al is 166 di-ide that ,y 1T, let1s say it1s roughly E, so that1s not contri,uting $uch. 3<&: located in the li-er, part of the cycle is in the cytosol and part of it is in $itochondria. )he urea co$es fro$ a$$onia, that1s a$$onia is gotten rid of, ,y urea. 3:c the end product of the urea cycle is urea. )he nor$al is a,out 1(5 di-ide that ,y 0, so we ha-e >. )herefore, in a nor$al person &a is controlling the plas$a os$olality. )o $easure seru$ os$olality: dou,le the seru$ &a and add 16. C. Osmosis ( of these 0 are li$ited to the ;C4 co$part$ent5 one can e#uili,rate ,etween ;C4 and IC4 across the cell $e$,ranes urea5 therefore, with an increased urea, it can e#uili,rate e#ually on ,oth sides to it will ,e e#ual on ,oth sides5 this is due to os$osis. 3:c &a and glucose are li$ited to the ;C4 co$part$ent, then changes in its concentration will result in the $o-e$ent of GA);2 fro$ low to high concentration (opposite of diffusion ie in lungs, 166 $$.g in al-eoli of ' (, and returning fro$ the tissue is >6 $$.g p'(5 166 -s. >6, which is ,igger, 166 is ,igger, so -ia diffusion, ' ( $o-es through the interspace into the plas$a to increase '( to a,out RE$$.,!. )herefore, in diffusion, it goes fro$ high to low, while in os$osis, it goes fro$ low to high concentration. 1. ;xa$ple: In the case with hyponatre$ia water goes fro$ ;C4 into the IC4, ,:c the lower part is in the ;C4 (hence .B*'natre$ia!5 water goes into the IC4, and therefore is expanded ,y os$osis. &ow $a%e ,elie-e that the ,rain is a single cell, what will we seeN cere,ral ede$a and $ental status a,nor$alities -ia law of os$osis (the intracellular co$part$ent of all the cells in the ,rain would ,e expanded! (. ;xa$ple: hypernatre$ia water goes out of the IC4 into the ;C4, therefore the IC4 will ,e contracted. 9o in the ,rain, it will lead to contracted cells, therefore $ental status a,nor$alities5 therefore, with hypo and hypernatre$ia, will get $ental status a,nor$alities of the ,rain.
2.
;xa$ple: ?KA ha-e (1666$g! large a$ount ,lood sugar. 2e$e$,er that ,oth &a and glucose are li$ited to the ;C4 co$part$ent. Bou would thin% that glucose is in the IC4 ,ut it1s not. Bou thin% that since glycolysis occurs in the cytosol therefore glucose in the IC4 (again its not! ,:c to order to get into the cell (intracellular!, glucose $ust ,ind to phosphorus, generating LA*, which is $eta,oliCed (it1s the sa$e with fructose and galactose, which are also $eta,oliCed i$$ediately, therefore, there is no glucose, fructose, or galactose, per se, intracellularly!. 9o, with hyperglyce$ia, there is high glucose in the ;C4, so water will $o-e fro$ IC4 to ;C4. )herefore, the seru$ &a concentration will go down this is called dilutional hyponatre$ia (which is what happens to the seru$ sodiu$ with hyperglyce$ia!.
)herefore the two things that control water in the ;C4 are &a and glucose5 ,ut a nor$al situation, &a controls. <rea does not control water $o-e$ents ,:c its per$ea,le, and can get through ,oth co$part$ents to ha-e e#ual concentrations on ,oth sides. D. Toni i!y isotonic state, hypotonic state, and hypertonic state Ge ha-e all different types of saline: Isotonic saline, hypotonic saline (1:( nor$al saline, V nor$al saline, E7 dextrose in water!, and hypertonic saline (07, E7!5 nor$al saline is 6.R7. Ge are referring to nor$al tonicity of the plas$a, which is controlled ,y the seru$ &a. )hese are the three types of tonicity (iso, hypo, and hyper!. 9eru$ &a is a reflection of total ,ody &a di-ided ,y total ,ody .(6. 4or exa$ple: hypernatre$ia is not just caused ,y increased total ,ody &a5 it can also ,e caused ,y decreasing total ,ody water with a nor$al total ,ody &a, therefore there is an increase in seru$ &a concentration. It is really a ratio of total ,ody &a to total ,ody .(6. )o deter$ine seru$ &a, just loo% at seru$ le-els. Gith different fluid a,nor$alities, can lose or gain a certain tonicity of fluid. 1. Iso!oni %oss o' '%&i* loo% at ratio of total ,ody &a and water5 in this case, you are losing e#ual a$ounts of water and &a, hence I9'tonic. )his fluid is $ainly lost fro$ the ;C4. )he seru$ &a concentration is nor$al when losing isotonic fluid. ;C4 would loo% contracted. )here would ,e no os$otic gradient $o-ing into or out of the ;C4. Clinical conditions where there is an isotonic loss of fluid: he$orrhage, diarrhea. If we ha-e an iso!oni gain, we ha-e in e#ual increase in salt and water5 ie so$eone getting too $uch isotonic saline5 nor$al seru$ &a, excess isotonic &a would ,e in the ;C4, and there would ,e no os$otic gradient for water $o-e$ent. (. Hypo!oni so%&!ions ,y definition, it $eans hyponatre$ia. .ypoglyce$ia will not produce a hypotonic condition. +CC of low os$olality in plas$a is hyponatre$ia. .owN 8ose $ore salt than water, therefore, seru$ &a would ,e decreased. If losing $ore salt than water, %idney is pro,a,ly the location of where:why it is happening. +ain place to deal
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with sodiu$ (either to get rid of it or to get it ,ac%! is in %idney, esp when dealing with diuretics (furose$ides and .C)Q!. )he tonicity of solution you lose in your urine is .B*;2tonic, so that1s how you end up with hyponatre$ia with a hypotonic condition. ;C4 concentration is low with hyponatre$ia, therefore the water will $o-e into the IC4 co$part$ent. ('s$osisD re$e$,er low to high! ;xa$ple: If you gained pure water, and no salt, you ha-e really lowered your seru$ &a: +CC " 9IA?. in s$all cell carcino$a of the lung5 you gain pure water ,:c A?. renders the distal and the collecting tu,ule per$ea,le to free water. Gith A?. present, will ,e rea,sor,ing water ,ac% into the ;C4 co$part$ent, diluting the seru$ &a, and the ;C4 and IC4 will ,e expanded. )he ;C4 is expanded due to water rea,sorption, and the IC4 is expanded ,:c it has a high concentration le-els (its le-els are not diluted!. )his can lead to $ental status a,nor$alities. )herefore, the $ore water you drin%, the lower your seru$ &a le-els would ,e. )he treat$ent is ,y restricting water. ?on1t want to restrict &a ,:c the &a le-els are nor$al. Ghen A?. is present, you will C'&C;&)2A); your urine ,:c ta%ing free water out of urine5 with a,sent A?., lose free water and the urine is diluted. )herefore, for with 9IA?., water stays in the ,ody, goes into the ;C4 co$part$ent, and then $o-e into the IC4 co$part$ent -ia os$osis. )he lowest seru$ sodiu$ will ,e in 9IA?.. 'n the ,oards, when seru$ &a is less than 1(6, the answer is always 9IA?.. ;xa$ple: pt with 9IA?., not a s$o%er (therefore not a s$all cell carcino$a!, therefore, loo% at drugs she was on chlorpropra$ide, oral sulfylureas produce 9IA?.. ;xa$ple: Lain ,oth water and salt, ,ut $ore water than salt, leading to hyponatre$ia these are the pitting ede$a states ie 2.4, cirrhosis of the li-er. Ghen total ,ody &a is increased, it always produces pitting ede$a. Ghat co$part$ent is the total ,ody &a inN ;C4 Ghat is the ,iggest ;C4 co$part$entN Interstial co$part$ent. )herefore, increase in total ,ody &a will lead to expansion of interstial co$part$ent of the ;C4, water will follow the &a, therefore you get expansion -ia transudate and pitting ede$a5 seen in right .4 and cirrhosis. ;xa$ple: hypertonic loss of salt (fro$ diuretic! leads to hyponatre$ia ;xa$ple: 9IA?. (gaining a lot of water! leads to hyponatre$ia ;xa$ple: gaining $ore water than salt will lead to hyponatre$ia: pitting ede$a 0. Hyper!oni s!a!e ,y definition, ha-e too $uch &a (hypernatre$ia! or ha-e hyperglyce$ia (ie pt with ?KA has a hypertonic condition, which is $ore co$$on than hypernatre$ia!. Gith hypernatre$ia, what does IC4 loo% li%eN It will always ,e contracted or shrun%en. *ri$ary aldosteronsi$ gain $ore salt and water. ?ia,etes insipidus 8ose pure water (-s. gaining pure salt in 9IA?.!. If you lose $ore water than salt in the urine, you ha-e os$otic diuresis $ixture. Ghen there is glucose and $annitol in the urine, you1re losing hypotonic salt solution in urine. ;xa$ple: 3a,y diarrhea " hypotonic salt solution (adult diarrhea is isotonic!, therefore, if ,a,y has no access to water and has a rota-irus infection, seru$ sodiu$ should ,e high ,ecause losing $ore water than salt, leading to hypernatre$ia. .owe-er, $ost $o$s gi-e the ,a,y water to correct the diarrhea5 therefore the ,a,y will co$e in with nor$al seru$ &a or e-en hyponatre$ia ,:c the deno$inator (.('! is increased. )reat$ent is pedialyte and Latorade these are hypotonic salt solution (just gi-e the$ ,ac% what they lost!. Ghat has to ,e in pedialyte and what has to ,e in Latorade to order to rea,sor, the &a in the LI tractN Llucose ,:c of the coDtransport. Gith the coDtransport, the &a .A9 to ,e rea,sor,ed with glucose or galactose. ;xa$ple: cholera, in oral replace$ent, need glucose to rea,sor, &a ,:c coDtransport pu$p located in the s$all intestine. Latorade has glucose and sucrose (which is con-erted to fructose and glucose!. 9weat " hypotonic salt solution5 if you are sweating in a $arathon, you will ha-e hypernatre$ia E. .o%&me Compar!men!s Arterial ,lood -olu$e is sa$e as stro%e -olu$e and C' (cardiac output!. Ghen C' decreases, all physiologic processes occur to restore -olu$e. Gith decrease C' (ie hypo-ole$ia!, oxygenated ,lood will not get to tissues, and we can die. )herefore, -olu$e is essential to our ,odies. Ge ha-e ,aroreceptors (low and high pressure ones!. )he low pressure ones are on the -enous side, while the high pressure ones are on the arterial side (ie the carotids and arch of aorta!. )hey are usually inner-ated ,y C& R and 16 (the high pressure ones!. Ghen there is a decrease in arterial ,lood -olu$e (decreased 9K or C'!, it will under fill the arch -essels and the carotid5 instead of Rth or 16th ner-e response, you ha-e a sy$pathetic &9 response, therefore catechola$ines are released. )his is good ,:c they will constrict the -enous syste$, which will increase ,lood returning to the right side of the heart (do not want -enodilation ,:c it will pool in your legs!. Catechola$ines will act on the ,eta adrenergic receptors on the heart, which will increase the force of contraction, there will ,e an increase in stro%e -olu$e (slight! and it will increase heart rate (I/J chronotropic effect on the heart, increase in systolic 3*!. Arterioles on the syste$ic side: sti$ulate ,eta receptors in s$ooth $uscle. ?iastolic pressure is really due to the a$ount of ,lood in the arterial syste$, while you heart is filling with ,lood. Gho controls the a$ount of ,lood in arteriole syste$, while your heart is filling in diastoleN Bour peripheral resistance arterioles that $aintains your diastolic ,lood pressure. 9o, when they are constricted, -ery little ,lood is going to the tissues (,ad news!5 good news: %eep up diastolic pressure this is i$portant ,:c the coronary arteries fill in diastoles. )his is all done with catechola$ines. 2enin syste$ is acti-ated ,y catechola$ines, too5 angiotensin II can -asoconstrictor the peripheral arterioles (therefore it helps the catechola$ines!. AL II sti$ulates 1T hydroxylase, which con-erts corticosterone into aldosterone, and sti$ulates aldosterone release, which leads to rea,sorption of salt and water to get cardiac output up.
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Gith decreased 9K, renal ,lood flow to the %idney is decreased, and the 2AA can ,e sti$ulated ,y this $echanis$, too. Ghere exactly are the receptors for the juxtaglo$erlur apparatusN Afferent arteriole. )here are sensors, which are $odified s$ooth $uscle cells that sense ,lood flow. A?. will ,e released fro$ a ner-e response, and pure water will increase ,ut that does not help with increasing the cardiac output. &eed salt to increase C'. ;xa$ple: ,leeding to death and there is a loss of 0 81s of fluid how can you %eep 3* upN Li-e nor$al saline is isotonic therefore the saline will stay in the ;C4 co$part$ent. &or$al saline is plas$a without the protein. Any ti$e you ha-e hypo-ole$ic shoc%, gi-e nor$al saline to increase 3* ,:c it stays in the ;C4 co$part$ent. Cannot raise 3* with W nor$al saline or E7 dextrose5 ha-e to gi-e so$ething that rese$,les plas$a and has the sa$e tonicity of plas$a. &or$al saline is 6.R7. *eritu,ular capillary pressures: you rea,sor, $ost of the sodiu$ in the proxi$al tu,ule (A6DT67!. Ghere is the rest a,sor,edN5 in the distal and collecting tu,ule ,y aldosterone. )he &a is rea,sor,ed into the peritu,ular capillaries. 9tarling forces in the capillaries $ust ,e a$ena,le to it. )wo starling forces: oncotic pressure (%eeps fluids in the -essel! and hydrostatic (pushes fluids out of -essel!. ;xa$ple: Ghen renal ,lood flow is decreased (with a decreased 9K and C'!, what happens to the peritu,ular capillary hydrostatic pressureN It decreases. )herefore, the peritu,ular oncotic pressure is increasing (ie the force that %eeps fluids in the -essel!, and that is responsi,le for rea,sorption of anything into the ,lood strea$ fro$ the %idney. )his is why *' (peritu,ular oncotic pressure! U *. (hydrostatic pressure of peritu,ular capillary!, allows a,sorption of salt containing fluid ,ac% into ,lood strea$ into the %idney. )onicity of fluid rea,sor,ing out of proxi$al tu,ule is isotonic (li%e gi-ing nor$al saline!. A?. is rea,sor,ing isotonic salt solution, ,ut not as $uch as the proxi$al tu,ule. A?. contri,utes pure water, therefore, with all this rea,sorption you ha-e an isotonic sol1n add the A?. effect and the pt ,eco$es slightly hyponatre$ic and hypotonic, therefore a,sor,s into the ;C4 co$part$ent when there is a decreased C'. 'pposite ;xa$ple: increased 9K, and increase arterial -olu$e, will lead to stretch of ,aroreceptors (inner-ated ,y R th and 16th ner-e!, and a parasy$pathetic response will ,e elicited, instead of a sy$pathetic response. )here will not ,e any -enuloconstriction nor any increase in the force of contraction of the heart. )his is fluid o-erload5 therefore we need to get rid of all the -olu$e. )here is increased renal ,lood flow, so the 2AA will not ,e acti-ated. 4luid o-erload does not A?. ,e released. )he peritu,ular hydrostatic pressure is greater than the oncotic. ;-en of the pt a,sor,ed salt, it wouldn1t go into the ,lood strea$, and it would ,e pee1d out. )herefore pt is losing hypotonic salt solution with increased in arterial ,lood -olu$e. &eed to %now what happens if there is decreased C', what happens when A&* is released fro$ the atria, and gi-e off diuretic effect5 it wants to get rid salt. A&* is only released in -olu$e o-erloaded states. ;xa$ple: pt gi-en 07 hypertonic saline: what will happen to os$olalityN Increase. Ghat will that do to seru$ A?.N Increase increase of os$olality causes a release of A?.. ;xa$ple: Ghat happens in a pt with 9IA?.N decreased plas$a os$olality, high A?. le-els. ;xa$ple: Ghat happens in a pt with ?IN no A?., therefore, seru$ &a increases, and A?. is low .ow to tell total ,ody &a in the pt: )wo pics: pt with dry tongue " there is a decrease in total ,ody &a, and the pt with indentation of the s%in, there is an increase in total ,ody &a. ?ehydration: 9%in turgur is prefor$ed ,y pinching the s%in, and when the s%in goes down, this tells you that total ,ody &a is nor$al in interstial space. Also loo% in $outh and at $ucous $e$,ranes. If you ha-e dependent pitting ede$a that $eans that there is an increase in total ,ody &a. 9IA?. gaining pure water, total ,ody sodiu$ is nor$al, ,ut seru$ &a is low5 ha-e to restrict water. 2ight .4 and dependent pitting ede$a fluid %idney rea,sor,s is hypotonic salt solution with a decreased C' (little $ore water than salt!, therefore seru$ &a will low. &u$erator is increased for total ,ody sodiu$, ,ut deno$inator has larger increase with water. Ghat is nonphar$alogical 2x of any ede$a statesN (ie 2.4:li-er dC! restrict salt and water Ghat is the 2x for 9IA?. " restrict .(' Ghat is the 2x for any pitting ede$a stateN 2estrict salt and water *har$acological 2x for pitting water diuretics (also get rid of so$e salt!. III. <)o 6 A. Ca&ses o' )ypo1o%emi s)o 6 diarrhea, ,lood loss, cholera, sweating, not ?I (,:c losing pure water, and not losing &a, total ,ody &a is &'2+A8M 8osing water fro$ IC45 no signs of dehydration5 when you lose salt, show signs of dehydration!. ;xa$ple: lady with hypo-ole$ic shoc% when she was lying down, her 3* and pulse were nor$al5 when they sat her up, the 3* decreased and pulse went up. Ghat does this indicateN )hat she is -olu$e depleted. )his is called the )I8) test. &or$al 3* when lying down ,:c there is no effecti-e gra-ity, therefore nor$al ,lood returning to the right side of the heart,
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and nor$al C'. .owe-er, when you sit the patient up, and i$pose gra-ity, you decrease the -enous return to right heart. 9o, if you are hypo-ole$ic, it will show up ,y a decrease in 3* and an increase in pulse. Cardiac output is decreased, and the catechola$ine effect causes this scenario. .ow would you 2xN &or$al saline. Audio file @: 4luid and he$odyn 0 ;xa$ple: pt collapses, and you do a tilt test: 166:T6 and pulse of 1(6 while lying down. 9itting up, it was @6:A6 and pulse of 1E6. )he pt is se-erely hypo-ole$ic, therefore 2x is nor$al saline. )reat$ent: 'ne liter in, showed no signs, put another liter and the 3* ,eco$es nor$al, and is feeling ,etter, ,ut still signs of -olu$e depletion (dry $outh!. Ge ha-e the 3* sta,iliCed, ,ut the pt lost hypotonic salt solution, therefore we need to replace this. 9o on IK, gi-e hypotonic salt sol1n (,:c was losing hypotonic salt solution!. Ge do not gi-e E7 dextrose and water ,:c there1s not any salt in it. )herefore, we will gi-e W nor$al saline. )he treat$ent protocol is: when a pt loses so$ething, you replace what they lost. And when pt is hypo-ole$ic, always gi-e isotonic saline. ;xa$ple: ?KA, ha-e os$otic diuresis5 tonicity of fluid in the urine that has excess glucose is hypotonic. .ypotonic fluid has a little $ore fluid than salt. 9o the pt is se-erely hypo-ole$ic5 therefore the first step in $anage$ent is correction of -olu$e depletion. 9o$e people are in hypo-ole$ic shoc% fro$ all that salt and water loss. )herefore need to correct hypo-ole$ia and then correct the ,lood sugar le-els (?KA pts lose hypotonic solution!. )herefore, first step for ?KA pt is to gi-e nor$al saline ,:c you want to $a%e the$ nor$oDtensi-e. ?o not put the pt on insulin ,:c it1s worthless unless you correct the hypo-ole$ia. It can ta%e ADT liters of isotonic saline ,efore the ,lood pressure starts to sta,iliCe. After pt is feeling ,etter and the pt is fine -olu$e wise. &ow what are we going to doN )he pt is still losing $ore water than salt in urine, therefore still losing a hypotonic salt solution, therefore need to hang up an IK with W nor$al saline (ie the ratio of solutes to water! and insulin (,:c the pt is loosing glucose!. 9o, first thing to do always in a pt with hypo-ole$ic shoc% is nor$al saline, to get the 3* nor$al. )hen to correct the pro,le$ that caused the hypo-ole$ia. It depends on what is causing the hypo-ole$ia (ie if pt is sweating, gi-e hypotonic salt solution, if diarrhea in an adult gi-e isotonic salt sol1n (ie nor$al saline!, if pt with ?I (ie sta,le 3*, pt is lucid! gi-e water (they are losing water, therefore gi-e E7 dextrose (ie E67 glucose! and water!. (. 9o&r 6in*s o' s)o 6: 1. .ypo-ole$ic shoc%: ,lood loss, diarrhea (adult or child!, ,asically whene-er you are lose salt, you could end up with hypo-ole$ic shoc% (. Cardiogenic shoc%: +C due to +I 0. &eurogenic shoc%: assoc. with spinal cord injuries >. 9eptic shoc%: +C due to ;. coli5 also +CC sepsis in hospital and is due to an indwelling of the urinary catheter. 9taph aureus is not the +C cause of IK related septice$ia in the hospital, ;.Coli wins hands down. ;ndotoxin in cell wall is a lipopolysacharide, which are seen in gra$ negati-e ,acteria. )he lipids are endotoxins. )herefore, gra$ negati-es ha-e lipids (endotoxins! in their cell wall, gra$ positi-e do not. 9' if you ha-e ;.Coli sepsis, you will ha-e ,ig ti$e pro,le$s, and is called septic shoc%. E. Classical clinical presentations: a! .ypo-ole$ic and cardiogenic shoc%: you would see cold and cla$$y s%in, ,:c of -asoconstriction of the peripheral -essels ,y catechola$ines (release is due to the decrease in 9K and C'! and AL II. )hese will -asoconstrict the s%in and redirect the ,lood flow to other i$portant organs in the ,ody li%e ,rain and %idneys, leading to a cold cla$$y s%in. 3* is decreased, pulse is increased. ,! *ouseau1s laws: is a concept that teaches you a,out peripheral resistance of arterioles which control the diastolic ,lood pressure. )*2 " )otal peripheral resistance of the arterioles K " Kiscosity r " radius of the -essel to the >th power
!PR " #$r4
)he $ain factor controlling )*2 is radius to the >th power Ghat controls the -iscosity in the ,loodN .,. 9o if you are ane$ic, -iscosity of ,lood is decreased (ie low he$oglo,in!, and if you ha-e polycythe$ia (high he$oglo,in!, -iscosity will ,e increased. )herefore, )*2 in ane$ia will decrease, and in polycythe$ia will increase. c! 9eptic shoc% )here is a release of endotoxins which acti-ates the alternati-e co$ple$ent syste$. )he co$ple$ent will e-entually release C0a and CEa which are anaphylatoxins, which will sti$ulate the $ast cells to release hista$ine. )he hista$ine causes -asodilation of arterioles (the sa$e ones of the peripheral resistance arterioles!. )herefore ,lood flow is increased throughout the peripheral resistance arterioles and the s%in feels war$. )he endotoxins also da$age the endothelial cells5 as a result, two potent -asodilators (&' and *LI (! are released. )herefore, ( or 0 -asodilators are released, and affect the )*2 to the fourth power. )herefore, the )*2 will decrease (due to -asodilation!. )*2 arterioles control your diastolic 3* ,:c when they are constricted5 they control the a$ount of ,lood that re$ains in the arterial syste$ while your heart is filling up in diastole. )herefore, when the )*2 arterioles are dilated, the diastolic 3* will pan out. )hin% of a da$ (with gates!: if all the gates are wide open all that water will co$e gushing through. )his is what happens to the arterioles when they are dilated. )he ,lood gushes out and goes to the capillary tissues, supposedly
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feeding all the tissues with '(. )hin% in the context of fishing: when the da$ wall opens, all the water rushes thru causing tur,ulent waters, therefore this would ,e a ,ad ti$e to go fishing. )he fishes would ,e trying to sa-e the$sel-es. )hat is what the '( is doing. )herefore, with all this ,lood going ,y, the tissues cannot extract '( ,:c it is going too fast and ,:c it isn1t a controlled release of ,lood. )herefore, the ,lood is co$ing ,ac% to the right side of the heart faster than usual, ,:c all the arterioles are widely dilated. ?ue to the ,lood going ,ac% to the heart faster, the cardiac output is increased. )his is seen in septic shoc% and the s%in feels war$ ,:c the -essels are dilated. )herefore, with septic shoc%, there is a .IL. output failure, with war$ s%in. .owe-er, in hypo-ole$ic and cardiogenic shoc%, the cardiac output is decreased (,:c the -essels are constricted ,y catechola$ines and angiotensin II!, and the s%in feels cold and cla$$y. C. <3an gan> a!)e!er is inserted in the right side of the heart and it $easures all para$eter that is taught in physiology. All of these things are $easured in a swan ganC catheter. 1. Cardiac 'utput: $easured ,y swan ganC (. 9yste$ic -ascular resistance: this is a calculation. )he ,asically $easures the )*2, ie $easures what arterioles are doing 0. +ixed -enous '( content. Bou %now nor$ally that the '( content is e#ual to " 1.0> x ., x ' ( sat1n / p'(. +easured in 2A with swan ganC catheter5 this is the 3;9) );9) for e-aluating tissue hypoxia. Cardiac output in cardiogenic and hypo-ole$ic shoc% is low, therefore, ,lood not ,eing pushed ahead with a great deal of force. 9o, tissue will ha-e a lot of ti$e to extract ' ( fro$ what little ,lood that is ,eing deli-ered. As a result, $ixed -enous '( content in hypo-ole$ic and cardiogenic shoc% will ,e decreased ie -ery low ,:c the ,lood going through the -essels is -ery slow (no force is helping to push it through!. )herefore, it extracts $ore ' ( than nor$al. +ixed -enous '( content in septic shoc% (when ,lood is passing through -essels at a -ery fast rate! will lead to a .IL. $ixed -enous content (,:c tissues una,le to extract '(!. >. *ul$onary capillary wedge pressure $easures 8eft -entricular end diastolic -olu$e and pressure (;?K and ;?*!. Catheter in right heart will tell you what the pressure is in the left -entricle. E. ?ifferences ,etween .ypo-ole$ic, Cardiogenic, and 9eptic 9hoc% using swan ganC catheter: C' in hypo-ole$ic and cardiogenicN ,oth decreased C' in septic shoc%N Increased 9yste$ic -asc resistance ()*2! is a $easure of what the A2);2I'8;9 are doing. Ghat is )*2 in hypo-ole$ic and cardiogenic shoc%N Increased due to -asoconstriction )*2 in septic shoc%N ?ecreased due to -asodilation. +ixed -enous in hypo-ole$ic and cardiogenicN 8ow. +ixed -enous in septic shoc%N .igh. .ow do we separate hypo-ole$ic and cardiogenicN *ul$onary capillary wedge pressure ($easures left -entricular ;?K! In .ypo-ole$ic, what is 8K;?KN 8ow. In Cardiogenic, what is 8K;?KN .igh. In ;ndotoxin shoc% it1s decreased. D. Examp%es: 1. ;xa$ple: 'f all organs in the ,ody, which suffers the greatest due to decreased 3*N Kidneys. Ghat partN +edulla. &ot the ,rain ,:c with decreased C', the circle of willis will distri,ute ,lood flow to certain areas in the ,rain, especially the areas where there are neurons. 9o$eone with hypo-ole$ic, or cardiogenic, or septic shoc%: oliguria, and an increased in 3<&:Creatine causes sugars in the ,ody. )his occurs ,:c the patient is going into acute tu,ular necrosis. &ephrologists want to correct the renal ,lood flow, so that you can pre-ent A)& ,:c a pt can die. Ghat type of necrosisN Coagulation necrosis. )he dead renal tu,ules will slough off and produce renal tu,ular casts in the urine which will ,loc% urine flow, there,y producing oliguria. )here is also a decrease in L42, leading to A)& (chances of sur-i-al are Cero!. 9o it is the %idneys that are the $ost affected when the cardiac output is decreased, ie decreased ,lood flow. 3rain would ,e a close second to necrosis. )he heart has a ,it of a collateral circulation as well. (. ;xa$ple: *t with the sic%le cell trait can get %idney dC5 ,:c the renal $edulla1s ' ( tension is low enough to induce sic%ling. )herefore if you ha-e a young ,lac% wo$an with $icroscopic he$aturia co$ing to the office, what is first test you should doN 9ic%le cell screen, ,:c she pro,a,ly has the sic%le cell trait. )herefore, sic%le cell trait has pro,le$s, ,:c ' ( tension in renal $edulla is low enough to induce sic%ling in peritu,ular capillaries, which produces $icroinfarctions in the %idneys. )herefore, don1t want to produce Coagulation necrosis (a%a A)&! I.. A i*?-ase an* (%oo* :as Acidosis increase in ./ ions, therefore decrease in p. Al%alosis decrease in ./ ions, therefore increase in p.
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A. Ne3 e;&a!ion for acid:,ase physio ,y Loljan:
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*+,rease i+ bi,arb " i+,rease p% " -etaboli, al.alosis /e,rease i+ bi,arb " de,rease p% " -etaboli, a,idosis *+,rease pC'2 " de,rease p% " respiratory a,idosis /e,rease pC'2 " i+,rease p% " respiratory al.alosis
(. Compensa!ion " ,odies atte$pt to try to $aintain a nor$al p. (which it ne-er does!. 9o if you want to %eep p. roughly nor$al (assu$ing you could!. 1. ;xa$ple: if you ha-e $eta,olic al%alosis (increase in ,icar,: which is in the nu$erator!, then ha-e to increase deno$inator (pC'(! to %eep it nor$al, therefore, co$pensation is due to respiratory (pC'(! acidosis. A nice way of $e$oriCing it is what is the opposite of $eta,olicN 2espiratory and what is the opposite of acidosisN Al%alosis, and -ice -ersa. (. ;xa$ple: if you ha-e $eta,olic acidosis (decrease ,icar,! what do we ha-e to do with the pC' (N Ge ha-e to get rid of it. If we decrease the no$inator, we ha-e to decrease the do$inator in order for the e#uation to stay the sa$e. )herefore, we ha-e to ,low off the C'( (hyper-entilation!. 0. Kentilation is a C'( ter$M .yper-entilation " Increase in respiratory rate allows for the ,lowing off of C'(, therefore results in respiratory al%alosis. 4or the treat$ent of respiratory al%alosis is to gi-e the pt a paper ,ag and as% to ,reath in it, ,:c then they are reD,reathing their own C'(. .ypo-entilation " ?ecrease in respiratory rate allows for the retention of C'(, therefore results in respiratory acidosis. 4ull co$pensation does not exist5 you ne-er ,ring ,ac% the p. to the nor$al range. )here is one exception: chronic respiratory al%alosis in high altitude5 ie $ountain sic%ness (ie peru!. C. Respira!ory on*i!ions: a i*osis an* a%6a%osis 1. )hings that deal with C'(: a! 2espiratory center is in $edulla o,longata, which controls the ,reathing rate ,! <pper airways if o,structed, there will ,e a pro,le$ getting rid of C'(. c! Chest ,ellows $ost i$p $uscle of respiration is diaphrag$. 'n inspiration: the diaphrag$ goes down, the negati-e intrathroacic pressure increases, and air is suc%ed into the lungs and ,lood is suc%ed into the right side of the heart (this is why nec% -eins collapse on inspiration!. &egati-e -acuu$ suc%s ,lood and air into your chest. 'n expiration, there is a I/J intrathrocic pressure, pushing things out. It helps the left heart to push ,lood out and it also helps the lungs ,y pushing out air. (. ;xa$ples: (a! 3ar,iturates or any drug that depresses the respiratory center will leads to respiratory acidosis (,! C&9 injury to $edulla o,longata resp acidosis (c! Anxiety " +CC resp al%alosis. Ghen you ta%e a test, so$eti$es you feel strange, and get nu$, and tingly, especially around $outh and on the tips of fingers, and ,eco$e twitchy (,:c you are in tetany! its all caused ,y ,eing al%alotic and ioniCing calciu$ le-el gets lower and you really are getting tetany. )herefore you ,eco$e twitchy and paresthesias (ie carpal pedal sign or trousseau1s sign are ,oth signs of tetany!. All due to tetany ,:c of ,reathing too fast fro$ anxiety. (d! *regnant wo$an ha-e resp al%alosis ,:c estrogen and progesterone o-er sti$ulate the respiratory center. 8ocated in the lungs are spider angio$as due to AK fistulas related to high estrogen, therefore clear $ore C'( per ,reath than a nor$al wo$an. A lot of shunting occurring within lungs. )hese spider angio$as go away after deli-ery of the ,a,y. (e! ;ndotoxins o-er sti$ulate the syste$. All pts in endotoxic shoc% ha-e resp al%alosis. )hey are also in anaero,ic $eta,olis$, producing lactic acid, therefore are also in $eta,olic acidosis. )herefore, endotoxic resp al%alosis due to o-ersti$ulation, and $eta,olic acidosis due with nor$al p.. (f! 9alicylate o-erdose o-ersti$ulate resp center, leading to resp al%alosis. 9alicylic acid is an acid, hence $eta,olic acidosis, and p. will ,e nor$al ,:c they ,alance e:o out. ()innitus in salicylate '? also a +IH;? disorderM! (g! A y:o child with inspiratory strider do a lateral xDray, and see thu$,print sign, with a swollen epiglottis. )he diagnosis is acute epiglottitis, due to .. influenCa5 -accination has decreased incidence, hence you don1t see any ids with .. $eningitis ,:c of the -accination. )he +C of $eningitis in 1 $onth 1T yrs " &. $eningitis.
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(h! 0 $onth old croup, a larygiotracheo,ronchitis dC due to parainfluenCa -irus. Gant to do a lateral xDray and see a steeple sign. Ghere is the o,struction in croupN )rachea (i! *t sho-ing food in their $outh (cafX coronary! .ei$lich $aneu-er5 if they can tal%, lea-e alone and let the$ cough it out. (j! ?iaphrag$ inner-ated ,y the phrenic ner-e ie er, ?uchene palsy, with ,rachial plexus injury, and child has resp difficulty, and diaphrag$ on right side is ele-ated. *aralysis of the diaphrag$ will lead to increased C'(. (%!8ou Lehrig1s dC a$yotrophic lateral sclerosis dC, a 8+&1s and <+&1s gone therefore cannot ,reath ,:c no inner-ation to the diaphrag$ (ie diaphrag$ and intercostals are paralyCed! (l!LuillainD3arre ascending paralysis in a patient who a wee% ago had a respiratory infection. )he spinal fluid shows increased protein, slight increase in ly$phocytes, and a gra$ stain negati-e. ?C: LuillainD3arre, de$yelinating dC (o! *olio destroys 8+&1s and e-entually <+&1s. )herefore, anything that paralyCes $uscle of resp will lead to resp acidosis. (p! 8<&L9: o,structi-e and restricti-e lung dC1s ',structi-e lung dC pro,le$ getting air out, co$pliance increased and elasticity is decreased, therefore, ha-e a resp acidosis. In restricti-e lung dC, ie 9arcoidosis and pneu$onocionioses, there is a pro,le$ in getting air in therefore has a resp al%alosis (N! Day " Caisson1s ?isease <nderwater: for e-ery 06 ft, increase 1 at$, (ie @A6 at le-el, ,ut 06 ft lower it will ,e ( at$!5 the re-erse is true when you go to high altitudes ie at top of $t e-erst, the at$ospheric pressure is (66 at$5 still ,reathing (17 ' (5 ,reathing the sa$e, ,ut at$ospheric pressure is different, depending on where you are. 4or$ula for calculating: al-eolar '( " (6.(1 x at$ospheric pressure! *C'( : .T .igh Altitude: (.(1 x (66! >6$$.,:.T " ($$.g of air in al-eoli, therefore will ha-e to hyper-entilate at high altitudes, ,:c lower pC'(" increased *'( (you .AK; to hyp-er-entilate otherwise you die!. .owe-er, when you go under, the at$ pressure increases, and the nitrogen gases are dissol-ed in your tissues, leading to an increase in pressure. Ie A6 ft ,elow, want to get up fast5 li%e sha%ing a soda ,ottle5 as you ascend, the gas co$es out of fat in ,u,,les5 the ,u,,les get into tissues and 3K1s5 this is called the ,ends5 leads to pain, and #uadriplegia, loss of ,ladder control. 2x " hyper,aric '( cha$,er. CHAPTER 2: NUTRITION I. Ea!ing *isor*ers = in %&*es o-esi!y@ anorexia@ -&%imia ?ifference ,etween anorexia and ,uli$iaN A. Anorexia ?istorted ,ody i$age5 wo$en with anorexia can ha-e distorted i$age5 control issue5 they ha-e lost control of e-erything in their life, and the only thing that they can control o-er is what they put in their $outh. Gith a decrease of ,ody fat and wt, Ln2. decreases, therefore 49. and 8. also decrease, leading to low estrogen5 as a result, a$enorrhea occurs, A&? predisposes to osteoporosis, as if pt is post$enopausal. Anorexic people will e-entually de-elop osteoporosis. 2x con-ince person to gain enough wt to ,ring period ,ac%5 not ,irth control. (ie first step in $anage$ent of .*:dia,etes " wt loss5 as you lose adipose, you upregulate insulin resistance!. In anorexia, usually die to cardiac dC (heart failure: heart just stops!. (. (&%imia Ner1osa 1. +eta,olic Al%alosis: It1s not a ,ody i$age pro,le$ they can ,e o,ese, nor$al or thin (no weight issue!5 howe-er, they ,inge (eat a lot!, then force the$sel-es to -o$it. *ic on ,oards: fro$ -o$iting, wear down ena$el on teeth5 so, ,rownish stuff seen on teeth is just dentine (erosions seen on teeth!. +eta,olic al%alosis fro$ forced -o$iting will ,e seen. +eta,olic al%alois is ,ad ,.c there is a left shift cur-e, and the co$pensation is resp acidosis, which drops p' (, therefore will get hypoxia with $eta,olic al%alosis, and the heart do not li%e that. )he heart already with low '( will get *KC1s (preD $ature -entricular contractions!, 22) pheno$, then KDfi,, then death. )herefore, $et al%alosis is -ery dangerous in inducing cardiac arryth$ias, and this co$$only occurs in ,uli$ics due to forced -o$iting. *t can also -o$it out ,lood +allory Geiss 9yndro$e tear in distal esophagus or proxi$al sto$ach. (. 3orha-e syndro$e, which is worse. In the syndro$e, there is a rupture and air and secretions fro$ the esophagus get into the pleural ca-ity5 the air will dissect through su,cutaneous tissue, co$e around the anterior $ediastinu$, which leads to .e$i$ans crunch o,ser-ed when dr loo%s at pt1s chest, puts a stethoscope down, and you hear a =crunch1. )he IcrunchJ is air that has dissected through interstial tissue up into the $ediastinu$, indicating that a rupture occurred in the esophagus5 this is another co$$on thing in ,uli$ics. 9o, there are ( things i$p in ,uli$ics: 1! +eta,olic al%alosis fro$ -o$iting (which can induce arrthy$ias (! 3orha-e1s syndro$e C. O-esi!y: Gith o,esity, using a diff $ethod: 3+I: %g1s in ,ody wt:$eters in ,ody
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ht1(. If your 3+I is 06 or greater, you are o,ese5 if your ,$i is >6 or greater, you are $or,idly o,ese. +ain co$plication of o,esity " .)&5 with .)&, leads to 8K., and potentially heart failure. +CC death in .)& " cardiac dC. 'ther co$plications of o,esity include: gall,ladder dC, cancers with a lot of adipose, you aro$atiCe $any 1@D%etosteroids li%e androstenedione into estrogens. )herefore, will hyperestrinis$ (all o,ese wo$en ha-e hyperestrinis$!, you are at ris% for estrogen related cancers ie ,reast cancer, endo$etrial carcino$a, colon cancer. II. +a%n&!ri!ion *roteinDcalorie $alnutrition: 1. +aras$us total calorie deposition, and wasting away of $uscle5 howe-er, high chance of sur-i-al if they get food (. Kwashior%or pro, gonna die5 ha-e car,s, ,ut no protein5 also ha-e ane$ias, cellular i$$unity pro,s (ie no rxn to ags!, low al,u$in le-els, ascites, fatty li-ers. )hese %ids are apathetic and need to ,e forceDfed5 therefore, %id with %washior%or is $ore li%ely to die than child with +aras$us. ;xa$ple: %id with ede$a, fla%y der$atitis, reddish hair (Cu def! %washior%or III. .i!amins A. Di''eren e -e!3een 'a! an* 3a!er so%&-%e 1i!amins: 1. 4at solu,le -ita$ins dissol-e in fats, indicating that they are ta%en up ,y chy$lo$icrons. )he chy$lo$icron will ha-e A, ?, ;, and, K ,:c these are the fat solu,le -ita$ins. 4at solu,le are $ore li%ely to ,e stored in fat, so the toxicity is $uch greater, ,:c if it is water solu,le, we just pee it out. +CC ,right yellow urine " -ita$ins (. Gater solu,le -ita$ins are all cofactors for ,ioche$ical rxn1s. (. 9a! so%&-%e 1i!amins: 1. .i!amin A a. 4unction: Is -ery i$p in children for growth and can ha-e failure to thri-e in -it A def. Kery i$portant in iodopsin:rhodopsin within the eye and the first sign of -it A def is night ,lindness which is called nictolopia. Kit A also pre-ents s# $etaplasia. ,. ;xa$ple of Kit A def: eye with s# $etaplasia, goose ,u$ps on ,ac% of ar$ called follicular hyper%eratois. ;ye is lined with cu,oidal epitheliu$5 when you get s# $etaplasia, will get white spots on the eye. If ,eco$e extensi-e, grow o-er eye, and can lead to softening of the cornea (%erato$alacia!, and leads to ,lindness. (nd +CC ,lindness glo,ally " -it A def. +CC ,lindness glo,ally " tracho$a5 +CC ,lindness in <9A " dia,etes. )herefore, -it A will pre-ent s# $etaplasia, if you are Kit A deficient and a nons$o%er, a person can end up with s# $etaplasia in $ainste$ ,ronchus and ,ronchogenic carcino$a. c. )oxicity: .yper-ita$inosis A ex. ,ig ga$e hunter that eats ,ear li-er and has headaches. Increased -it A causes cere,ral ede$a, also get papilloede$a (which causes the headache!, can alsp lead to herniation and death. )here is also an increase of retinoic acid (used fro$ treating acne and acute progranulocytic ane$ia!. )he retinoic acid toxicity can lead to se-ere li-er toxicity. )herefore, hyper-ita$inosis of -it A affects ( areas: 1! cere,ral ede$a (,rain! (! li-er. ;xa$ple: if ha-e young lady pt on retinoic acid for acne, need to chec% li-er enCy$es and as% for headaches (can ,e de-eloping papilloede$a or cere,ral ede$a related to -it A toxicity!. +assi-e a$ount of -it A in ,ear li-ers, and hunter dies with $assi-e headaches or li-er failure ". .i!amin D " K;2B i$p on the ,oards5 +C source of -it ? is fro$ sunlight. a. Cholesterol is the 1. +ain co$ponent of our cell $e$,ranes (. 9tarting point for $a%ing ,ile salts and ,ile acids 0. 4irst co$pound that starts the synthesis of steroid hor$ones in the adrenal cortex >. And the @Ddehydrocholesterol in the s%in is photocon-erted to -ita$in ?. )herefore we need cholesterolM ($a%es ,ile salts, hor$ones, cell $e$,ranes, and -it ?!. ,. 9ource: 9un is the $ost i$p source of -it ?. ta%e ,a,y out to expose to sunlight (no -it ? or -it K in ,reast $il%, therefore $ust ,e supple$ented expose to sun for -it ?!. c. 9ynthesis of Kita$in ?: 2ea,sor,ed in the jejunu$. <ndergoes ( hydroxylation steps5 first is in the li-er, where it is (E hydroxylated and the (nd is in the %idney and its 1 alpha hydroxylase. Ghat hor$one puts 1Dalpha hydroxylase in the proxi$al tu,uleN *).. *). is responsi,le for synthesis of 1DaDhydroxylase and is synthesiCed in the proxi$al tu,ule. (AC; is fro$ the endothelial cells of the pul$onary capillary, ;*' is fro$ the endothelial cells of the peritu,ular capillary!. 1DaDhydroxylase is the (nd hydroxylation step, and now it is acti-e (the first was in the %idney!. d. Kit ? function: rea,sor, Ca and phosphorus fro$ the jejunu$. It .A9 to rea,sor, ,oth of these, ,:c its $ain jo, is $ineraliCing ,one and cartilage. .a-e to ha-e appropriate solu,ility product to ,e a,le to do that5 Ca and phosphorus are necessary to $ineraliCe cartilage and ,one (li%e the osteoid $a%ing ,one!. )herefore, it $a%es sense to rea,sor, Ca and phosphorus ,:c it needs to $a%e sure that ,oth of the$ are present in ade#uate a$ounts to ha-e an ade#uate solu,ility product to $ineraliCe ,one. e. *arathyroid .or$one (*).! 4unctions: (1!is so$ewhat related to Kita$in ? $eta,olis$, it helps last step for hydroxylation of -it ? syn. ((! *). will lead to rea,sorption of Ca in the early distal tu,ule (this is also where &a is rea,sor,ed, and thiaCides ,loc% this channel!. At that location, there is a Ca channel5 *). helps rea,sorption of the Ca
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in this location. Ca has to =ta%e turns1 with &a, usually $ore &a, rea,sor,ed5 therefore Ca has to snea% through channel, with help of *).. )herefore, with thiaCides, &a is ,loc%ed, lea-ing the Ca channel co$pletely open, and the thiaCides will lead to hypercalce$ia. )herefore, use in Ca stone for$ers $ost of stone for$ers ha-e hypercalciurea5 these pts ha-e too $uch Ca in their urine5 when they are on thiaCides, the drug ta%es Ca '<) of the urine, so they do not for$ stones. (0! *). will decrease rea,sorption of phosphorus in the prox tu,ule, and (>! decrease the reaccu$ulation of ,icar,, too. f. Kita$in ? and *). and how they wor% together: .i! D#s $ain function is $ineraliCing ,one, and osteo,lasts (,one ,uilders! are in-ol-ed with this process, therefore the receptor for Kit ? is located on the osteo,last. Ghen -it ? hoo%s into the receptor, it causes the release of al%aline phosphatase. 9o, when you are growing ,one or rehealing of a fracture, you expect to see an increase in al%aline phosphatase, which $a%es the appropriate solu,ility product to $ineraliCed cartilage and ,one. Knowing that PTH ,rea%s down ,one ($aintains Ca le-els in the ,lood strea$! you would thin% that its receptor would ,e on the osteoclast (cell nor$ally ,rea%s ,one down!. .owe-er, only one hor$one has a receptor on ostoeclasts and that is a% i!onin. Ghen calcitonin hoo%s into the osteoclast receptor, it inhi,its the osteoclast, and therefore is used to treat hypercalce$ia. Calcitonin also used in treating osteoporosis. )he receptor for *). is on the osteo,last, ,ut not sharing the sa$e one as -it ?. Ghen *). hoo%s on the osteo,last, it releases I8D1. Another na$e for I8D1 is osteoclast acti-ating factor (other functions of I8D1 are also in-ol-ed in fe-er, sti$ulates A, synthesis, and 3 cell sti$ulation!. 9o, I8D1 (released fro$ the osteo,last! acti-ates osteoclasts -ia I8D1 release fro$ osteo,last, and osteoclast is signaled to ,rea% down ,one to $aintain Ca le-els in our ,loodstrea$. 9ex hor$ones %eep I8D1 in chec%5 in wo$en, estrogen le-els %eep a chec% on I8D1 (do not want too $uch osteoclast acti-ation!5 in $en, it is testosterone that %eeps I8D1 in chec% (puts inhi,itory effect on I8D1 release fro$ the osteo,last after *). hoo%s in!. )herefore, in wo$en, can see why they get osteoporosis lac% of estrogen " I8D1 not in chec% and ,rea%ing $ore ,one down than $a%ing (this is the $echanis$ of post$enopausal osteoporosis!. *). is $ore in-ol-ed in $aintaining Ca le-els in our ,lood, while Kit ? is $ore in-ol-ed in $ineraliCing our ,ones and cartilage. g. Kita$in ? deficiency: +any reasons: lac% of sun, poor diet, li-er dC, renal dC. ;xa$ple: *t on phenytoin and pt has hypocalce$ia, whyN *henytoin, alcohol, ,ar,1s, rifa$pin all induce the cyt p>E6 syste$ located in the 9;2. )herefore, get 9;2 hyperplasia5 therefore, you $eta,oliCe drugs and other things $ade in the li-er, including (EDhydroxy-ita$in ?. )herefore, anything that re-1s up the p>E6 enCy$es will cause a decrease in -it ?, and any other drugs ,eing ta%en. ;xa$ple: wo$an on ,irth control pills and ta%ing phenytoin, and she got pregnant, whyN )he phenytoin re-1ed up the p>E6 syste$, which increased the $eta,olis$ of estrogen and progesterone in the ,irth control pills, therefore not enough le-els to pre-ent pregnancy. ;xa$ple: what is the enCy$e in the 9;2 that increases when the p>E6 is re-1d upN La$$a gluta$yl transferase (LL)! enCy$e of 9;2M (loo% at in alcoholics! ;xa$ple: +CC chronic renal dC in <9A: dia,etes $ellitus tu,ular da$age, so no 1DaDhydroxylase, therefore inacti-e -it ?. )herefore, pts with chronic renal failure are put on 1D(ED-it ?. ;xa$ple: if so$eone gets ')C -it ?, what steps does it go through to ,eco$e $eta,olically acti-eN (E hydroxylated in li-er, and 1DaDhydroxylated in your %idney (it is &') 1, (E -it ? this is a prescription drug, and extre$ely dangerous!. +any people ha-e the $isconception that the -ita$in ? is already wor%ing. )his is not the case5 pt $ust ha-e a functioning li-er and %idney. Gith -it ? def in %ids " ric%ets5 -it ? def in adults " osteo$alacia (soft ,ones!. If you can1t $ineraliCe ,one, you cannot $ineraliCe cartilage, and they will ,oth ,e soft, therefore pathologic fractures are co$$on. Kids ha-e different a few things that are different in ric%ets ie craniotopies, soft s%ulls (can actually press in and it will recoil!. )hey can also get ric%etic rosaries, ,:c the osteoid is located in the costochondral junc, and ,:c they are -it ? def, there is a lot of nor$al osteoid waiting to ,e $ineraliCed, ,ut not an appropriate Calciu$:phosphorus solu,ility product5 will ha-e excess osteoid with little ,u$ps, which is called ric%etic rosary. &ot seen in adults1 ,:c they are getting fused. 9o, ( things you see in %ids and not adults: 1! craniotopies (! ric%etic rosaries5 rhe rest is the sa$e, with pathologic fractures ,eing the $ain pro,le$. h. )oxicity:.yper-ita$inosis of -it ?: hypercalce$ia, therefore ris% of ha-ing too $any stones in the urine, and stones is a +CC co$plication. )ype 1 ric%ets $issing the 1DaDhydroxylase )ype ( ric%ets $issing the receptor for -it ? $. .i!amin E a. +ain function: $aintain cell $e$,ranes and pre-ent lipid peroxidation of the cell $e$,ranes5 in other words, it protects the cell $e$,ranes fro$ ,eing ,ro%en down ,y phospholipase A (lipid peroxidation, which is free radical da$age on the cell $e$,rane, and is pre-ented with -it ;!. 'ther function: neutraliCed oxidiCed 8?8, which is far $ore atherogenic than 8?8 ,y itself. Ghen 8?8 is oxidiCed, it is way $ore injurious to the cell then when it is not
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oxidiCed. Kit ; will neutraliCe oxidiCed 8?8, therefore is a cardioprotectant (-it ; and C ,oth neutraliCe oxidiCed 8?8!. In su$$ary: -it ; func " 1! protects cell $e$ fro$ free radical da$age. (! 'xidiCes free 8?8 (this is the 8?8 that $acrophages phagocytose to produce foa$ cells, and leads to atherosclerotic pla#ues!. ,. ?eficiency of -ita$in ;: Is seen ,ut is -ery unco$$on, and if seen if would ,e in %ids with cystic fi,rosis5 fro$ ,irth, %ids ha-e resp pro,s and pancreas pro,le$s. (loo% at in ro,,ins, too!. A %id that has cystic fi,rosis will ha-e $ala,sorption pro,le$s5 therefore what four -ita$ins should you gi-e hi$N Cystic fi,rosis pt has a $ala,sorption of fat5 therefore they will ha-e $ala,sorption of fat solu,le -ita$ins A, ?, ;, and K. Kit ; def in <9A is usually seen in cystic fi,rosis patients. c. Clinical presentations: 'ne of the features of -it ; def is he$olytic ane$ia (-it ; nor$ally $aintains the integrity of the $e$,rane!5 this pt is now suscepti,le to free radical da$age, da$aged $e$ of 23C leads to he$olysis of 23C and he$olytic ane$ia. Another feature of -it ; are things related to $yelin: posterior colu$n dC, spinal cere,ellar pro,s. )herefore, with -it ; def, ha-e neurological pro,le$s and he$olytic ane$ia. d. Kita$in ; toxicity: anything $ore than 1166 units (a-erage capsule is >66 units, therefore, if ta%e 0 pills, already toxic!. Kita$in ; toxicity will inhi,it synthesis of Kit K dependent Coagulation factors ((, @, R, 16, protein C, protein 9!5 in other words, you are antiCoagulated. ;xa$ple: pt with +I ta%e antioxidants, and aspirin5 with anterior +I, they antiCoagulate the pt, and pt goes ho$e on three $onths of warfarin. &or$al I&2 ratio, and ta%es lots and lots of -it ; and other -ita$ins. )a%e a lot of -it ; and will help warfarin, leading to o-er antiCoagulated state, (re$e$,er that warfarin ,loc%s ga$$a car,oxylation of -ita$in K dep factors!. Kit ; will pre-ent the 9B&).;9I9 of these factors. )herefore, -it ; toxicity is synergistic in acti-ity with warfarin. ;xa$ple: pt on warfarin, ca$e ho$e fro$ +I, I&2 ratio is huge5 whyN )a%ing -it ;. 2. .i!amin 8 a. 9ources: Can co$e fro$ what we eat, ,ut $ost is synthesiCed ,y our colonic ,acteria (our anaero,es in our gut! this is why we gi-e -it K injections to our ,a,y when they are ,orn5 they only ha-e 0 days worth of -it K fro$ $o$, ,ut after that, they won1t ha-e any ,:c its not in ,reast $il%5 therefore, a -ery low le-el of -it K ,etween days 0DE5 also, they don1t ha-e ,acteria to $a%e the -it K. )herefore, can get he$orrhagic dC of the new,orn (this is why we gi-e -it % when they are ,orn!5 after E days, the ,acteria coloniCe, and -it is $ade ,y the ,a,y. ,. +eta,olis$: 3acteria $a%e -it K in an inacti-e for$ K(. K( (inacti-e for$ $ust ,e con-erted ,y epoxide reductase to K1 (K1 is the acti-e for$ of -ita$in K!. K1 will ga$$a car,oxylates the -it K dependent factors ((, @, R, 16, protein C and 9!. La$$a car,oxylates re#uires the sa$e understanding as Kita$in C, in -it C If you don1t hydroxylate pro and lys then the crosslin%s are wea%er (anchor pt!. La$$a car,oxylation of -it K dep factors actually acti-ates the$ to ,eco$e functional. Kit K dep factors all ha-e so$ething in co$$on: (1!ha-e to ,e acti-ated ,y -it K1 and ((! they are the only Coagulation factors that are ,ound to a clot ,y Calciu$ (Ca!5 so they ha-e to ,e ,ound ,y Ca in order to wor% and for$ a clot5 if you can1t ,ind, then you are antiCoagulated. )hat is what ga$$a car,oxylation: gluta$ic acid residues are ga$$a car,oxylated on the -it K dep factors (which is done with K1!, and allows Ca to ,ind the factors5 therefore, it %eeps the$ together and you are a,le to for$ a clot5 therefore, if they are not ga$$acar,oxylated, they are useless ,:c Ca can1t gra, the$ to for$ a clot (so, ga$$acar,oxylation is the anchor pt, so Ca can ,ind to for$ a clot, si$ilar to hydroxylation of proline and lysine in collagen synthesis!. Garfarin ,loc%s epoxide reductase, so all the -it K pt has is K( and no ga$$acar,oxylation will occur. )herefore, the patient is anticoagulated. c. Kita$in K deficiency: +CC -it K def (in hospital! " ,road spectru$ A,1s. ( nd +CC " poor diet, ,eing a new,orn, $ala,sorption. ?ef -it K " he$orrhagic diathesis (,leeding into s%in or ,rain!. Know why new,orn has -it K def: ;xa$ple: %id with rat poison rat poison is warfarin5 when rats eat it, they get antiCoagulated and die. )reat with intra$uscular Kita$in K. ;xa$ple: %id li-ed with grandparents and de-eloped he$orrhagic diathesis: whyN 3:c the elderly were on warfarin, and %id ate the warfarin, and led to toxic le-els. C. 5a!er <o%&-%e .i!amins: all are cofactors in $ajor ,ioche$ical pathway 1. .i!amin C: a! Classic exa$ple of Kita$in C deficiency: older person on tea and toast diet indicating that they are $alnourished5 pt gets ,leeding of the gu$s " scur-y, due to -it C def. Kit C is responsi,le for hydroxylation of proline and lysine, and this occurs in the Lolgi apparatus ,:c that1s where postDtranslational $odification occurs. *ts ha-e wea% )ype I collagen ,:c cannot cross,ridge it5 therefore, 3K1s are unsta,le and gu$s ,leed. Let ,leeding of the gu$s, infla$$ation, and $ay loose teeth. ,! Associated #uestion: what co$plication is associated with se-ere he$ophilia AN .e$earthroses, and caused ,y Kit C deficiency (,:c the 3K1s are unsta,le and they rupture!. c! *hysical diagnosis of Kita$in C deficiency: Along with the tea and toast diet, there is also perifollicular he$orrhage (he$orrhage around the hair follicles!. 9ee ring sidero,last (nucleated 23C, and has too $uch iron in the $itochondria!, ring around the hair follicle and also see cor% screw hairs due to -it C def. )he tongue loo%s li%e it hurts and patients with -it C ha-e a s$ooth tongue glossitis, with %elosis around an%les, plus a he$orrhagic diathesis " scur-y. d! ;xcess -ita$in C: -ery co$$on ,:c pts ta%e way too $uch -it C (ADTg$!, $ain co$plication is 2enal stones (increased uric acid stones, and other %inds of stones!. Kita$in C and ? ,oth ha-e toxicity stones.
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e! Kita$in C is used in ancillary 2x for $ethe$oglo,inuria5 it is a reducing agent and a great sca-enger hunter for free radicals (%noc%s the$ off!. f! Cofactor in ,ioche$ical pathway: Kit C is a cofactor for con-erting the catechola$ine &; into ;pi.
". .i!amin (1 /T)iamine0: a! In-ol-ed in $any ,ioche$ical reactions: trans%etolase rxn1s in the pentose phosphate shunt5 and pyru-ate dehydrogenase5 alpha %eto glutarate dehydrogenase5 and alpha %eto acid dehydrogenase. All the dehydrogenase rxns re#uire thia$ine as a cofactor. *yru-ate dehydrogenase is the $ain rxn that con-erts pyru-ate into acetyl CoA. *yru-ate can also ,e con-erted to 'AA with a car,oxylase enCy$e. Ghen you co$,ine acetyl CoA with 'AA, you $a%e citrate, and you are in the )CA cycle. ,! 9o, if thia$ine def, ,:c it is in-ol-ed in the pyru-ate dehydrogenase rxn (which con-erts pyru-ate to acetyl CoA!, you will not ha-e a lot of acetyl CoA around, therefore, won1t ha-e $uch citrate around, therefore, you won1t ha-e the )CA cycle wor%ing efficiently, and 8;99 A)*. )herefore, the pro,le$ with thia$ine def is A)* depletion. Ghen you go fro$ pyru-ate to acetyl CoA, you generate ( &A?.1s and since this is in the $ito, you get A A)* (so, just fro$ going fro$ pyru-ate to acetylDCoa, gi-es A A)*!5 and then with )CA, get (> A)*1s. A / (> " 06 A)*5 the total you can get fro$ co$pletely $eta,oliCing glucose is 0T A)*5 so, if you are thia$ine def, you are out 06 A)*1s5 so, the $ain pro, of thia$ine def is A)* depletion. c! In thia$ine def you1ll see foot drop (dry ,eri,eri!, and pitting ede$a (wet ,eri,eri!. .ow does this explain wet:dry ,eri,eriN 1! ?ry ,eri,eri " peripheral neuropathy, and refers to Gernic%e1s %orsa%off psychosis (can1t re$e$,er old and new things li%e an exa$ ie Iused to %now that, ,ut can1t re$e$,er nowJ5 a $e$ory pro,le$!. It ta%es a lot of A)* for synthesis of $yelin5 without $yelin, you will get peripheral neuropathy and foot drop (due to co$$on peroneal palsy!, can get wrist drop (radial ner-e palsy!, and claw hand (ulnar ner-e palsy!. Gernic%e1s encephalopathy is confusion, ataxia, and nystag$us. All of these are due to de$yeliCation. (! Get ,eri,eri " heart failure5 +CC thia$ine def " alcohol (not polished rice!. Alcoholics are the +C people with thia$ine def. Get ,eri,eri is referring to cardio$yopathy cause: 8.4 went into 2.4 which lead to pitting ede$a. .eart needs A)* to function, therefore, the pt with ha-e congesti-e cardio$yopathy5 their heart will ha-e ,i-entricular enlarge$ent (the whole chest will ,e heart!, with left and right .4 (pitting ede$a is a sign of right .4 due to increased hydrostatic pressure ,ehind the failed heart!. If you gi-e IK thia$ine, can re-erse5 and in so$e cases it1s related to toxicity of alcohol, and cannot wor%. d! ;xa$ple: pt in ;2 gi-en IK of E7 dextrose and nor$al saline5 all of sudden, pt de-elops confusion, nystag$us, and ataxia, and opthal$aplegia. ?iagnosis: su,clinical thia$ine deficiency. As soon as the glucose was hung up, the pyru-ate went to acetyl CoA and used the rest of thia$ine...then went into acute Gernic%e1s encephalopathy. )herefore, $oral of the story: gi-e IK thia$ine ,efore hanging up IK glucose, especially in ;2. f! Ghen people co$e in co$atose or se$ico$atose, se-eral things you always do: 1! E67 glucose if a hypoglyce$ia pro,le$ (! naloxone ('?! 0! IK thia$ine $. .i!amin ($ /Nia in0: 9lide: 2ash in sun exposed area " pellagra (a%a der$atitis!, due to niacin def (also diarrhea, der$atitis, de$entia!5 hyperpig$entation in sunDexposed areas " Cassel1s nec%lace (der$atitis:pellagra!5 &A?:&A?* rxns (& stands for nicotina$ide, and the nicotina$ide was deri-ed fro$ niacin!. )herefore, all the oxidation rxns rxn1s are niacin dependent. ;xa$ple: pyru-ate to acetyl CoA " went fro$ &A? to &A?. and niacin is in-ol-ed here. )ryptophan can used in synthesiCing niacin and serotonin (why it1s an essential aa!5 ,ut it1s not the $ain source of niacin, ,ut a good source. &icotinic acid " least expensi-e lipid lowering drug5 see the flushing assoc with it5 supposed to ta%e aspirin with it to re$o-e the flushing related to nicotinic acid (used in treating fa$ilial hyperlipide$ia!, it is the ?'C for ele-ated hyper)Le$ia. 2. .i!amin (" /Ri-o'%a1in0: 4A?:4+& rxns are ri,ofla-in cofactor rxns (therefore, whene-er you ha-e 4A? and 4+& rxns, these are ri,ofla-in cofactor rxns!. (&iacin for &A?:&A?* rxns, and ri,ofla-in for 4A?:4+& rxns!. Also, the first rxn: glutathione reductase con-erts oxidiCed glutathione into glutathione which ri,ofla-in is a cofactor for. 4. .i!amin (A /Pyri*oxine0: Ge1re tal%ing a,out $icrocytic ane$ia. 4irst rxn in the synthesis of he$e in-ol-es succinyl Coa, plus glycine. )he enCy$e is A8A synthase, and the cofactor is 3A. )herefore, it is i$p to the synthesis of he$oglo,in and he$e proteins. )he cytochro$e syste$ is the he$e syste$, too. +yoglo,in is different fro$ ., (has one he$e group!, while ., has
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four he$e groups. )here is also he$e in the li-er, in the cytochro$e syste$. *yridoxine is in-ol-ed in the synthesis of he$e, which is in porphyrin. *yridoxine is in the transa$inases rxn. +ost a,undant su,strate fro$ $a%ing glucose in the fasting state " alanine (aa fro$ $uscle aa1s ,ro%en down fro$ $uscle to get glucose, -ia gluconeogenesis!. .ow can an aa ,e used to $a%e glucoseN )ransa$ination. )ransa$inations (9L'), 9L*)! fro$ the li-er can ta%e transa$inases5 they ta%e a$ino groups out and put the$ into other things5 if you ta%e the a$ino group out of alanine, this produces pyru-ate (an alpha %eto acid!. If you ta%e aspartate and ta%e the aa out, you ha-e 'AA, which is a su,strate for gluconeogenesis. If you ta%e pyru-ate, and add an a$ino group, can synthesiCe alanine. If you ta%e 'AA, and add an a$ino group, you can $a%e aspartate. )his is what the transa$inases do, with 3 A as a cofactor. 3A is also in-ol-ed in the synthesis of neurotrans$itters. )herefore, a child that is 3 A deficient, they end up with se-ere neurological pro,le$s ,:c no neurotrans$itters (3A i$p to synthesiCing the neurotrans$itters!. I$portant in transa$ination, neurotrans$itter, and he$e synthesis. +CC def 3A def " isoniaCid5 without 3A, will de-elop neurologic pro,le$s and sidero,lastic ane$ia related to he$e pro,le$. D. O!)er impor!an! o?'a !ors 1. Pan!o!)eni a i* is related to 4A synthase5 not the rate li$iting rxn, ,ut i$p in $a%ing pal$itic acid (a 1A C 4A!, and helps in $a%ing CoA (ie acetyl CoA, .+L CoA!5 pantothenic acid is the cofactor for these rxns. ". (io!in Cofactor for other rxn of pyru-ate to acetyl Coa -ia pyru-ate dehydrogenase " thia$ine is the cofactor, while ,iotin is the cofactor for *yru-ate decar,oxylase to 'AA. )herefore, thia$ine helps for$ acetyl CoA fro$ pyru-ate, while ,iotin helps for$ 'AA fro$ pyru-ate. If you are def, need to eat (6 raw eggs:day ?eficiency: get a rash and go ,ald (alopecia!. If ,iotin def, cannot for$ 'AA, and cannot fro$ citrate either (this is the first step in gluconeogenesis, therefore you can end up with fasting hypoglyce$ia!. If you ,uild pyru-ate, it will ,e forced to go to lactic acid. $. Tra e e%emen!s a! Chro$iu$ " glucose tolerance factor, and helps insulin do its jo,. 'at$eal can also decrease glucose with all the fi,er5 good for a type II dia,etic to ,e on chro$iu$. ,! Copper lysl oxidase puts cross,ridge ,etween collagen fi,rils and elastic tissue. )herefore, if Cu def, ha-e wea% collagen and wea% elastic tissue, predisposing to dissecting aortic aneurys$. 2ed hair in %washior%or also due to Cu def. c! 4luorine needed to pre-ent dental carries5 too $uch fluorine leads to white, chal%y teeth, also in Colorado ,:c water has too $uch fluorine. It will also get calcification of the liga$ents, where liga$ents go into ,one5 the calcified liga$ents are su,ject to rupture5 any good radiologist can detect fluorine toxicity. d! 9eleniu$ in pentose phosphate shunt, for$ glutathione, and ha-e ri,ofla-in helping that enCy$e. Llutathione can neutraliCe peroxide, and this re#uires glutathione peroxidase5 seleniu$ is the cofactor for this reaction. )herefore, in other words, it is an antioxidant ,:c if you are def in it5 the glutathione cannot ,rea%down the peroxide. (Kit ; usually co$es with seleniu$ so one wor%s on glutathione, while the other protects the lipid $e$,rane fro$ free radical da$age and sca-enges oxidiCed 8?8!. e! Qinc ;xa$ple: older person with dysgusia (a,nor$al taste! and anos$ia (lac% of sell!5 s$ell and taste are ,oth def in Cinc def. Qinc is a $etalloenCy$e5 therefore it has a trace $etal as a cofactor. Collagenase is a $etalloenCy$e ,:c it has Cinc in it, and it ,rea%s down the type 0 collagen, so you can for$ type 1 collagen. )herefore, if deficient in it, will ha-e poor wound healing, and you get a rash on the face. 9o, rash on face, dysgusia, anos$ia, poor wound healing " Cinc deficiencyMMM ?ia,etics are Cinc def, unless ta%ing supple$ents. 2. Die!ary 'i-er /inso%&-%e an* so%&-%e0 solu,le fi,er can lower cholesterol (not the insolu,le fi,er!. .ow it wor%s (ie oat$eal!: oat$eal has insolu,le fi,er, when it1s in the gut, it will suc% up water into it fro$ the colon, and also suc% up ,ad things lipopolic acid. RE7 of ,ile acids and ,ile salts are rea,sor,ed in the ter$inal ileu$. )he E7 are lipopolic acids, which are carcinogenic (produces colon cancer!. 9o, fi,er (insolu,le and solu,le!, it suc%s the lipopolic acid up, into the interior of the stool, so it has no contact with the ,owel $ucosa. *lus, defecate $ore often and therefore lipopolic acids ha-e e-en less contact with the stool. Go$en are luc%y ,:c they recycle estrogens5 $ain way of excreting estrogens is in ,ile and out of your stool, ,ut a s$all 7 of estrogens are recycled ,ac% into the syste$. Bou $ay not necessarily need that, so, when on fi,er, increased estrogen is passed out, therefore, decreasing chance of ,reast cancer, o-arian cancer, and uterine cancer ,:c fi,er in the diet. I.. <pe ia% *ie!s = pro!ein res!ri !ion Ghat ( dC1s would you restrict protein inN 1! 2enal failure ,:c excess protein ,ro%en down to a$$onia and other things the a$$onia is $eta,oliCed in the urea cycle, will ha-e increase urea and the %idney will ha-e to get rid of $ore urea. (! Cirrhosis of the li-er defecti-e urea cycle therefore cannot $eta,oliCe a$$onia5 $ost of the a$$onia that we ha-e in our ,odies co$es fro$ ,acteria in our colon that ha-e urease in the$ (.. pylori!5 and they ,rea%down urea to a$$onia in our
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colon. A$$onia is rea,sor,ed, and supposed to go ,ac% to our li-er and go into the urea cycle, ,eco$e urea and get rid of it. 3ut with cirrhosis, no urea cycle, so the a$$onia le-els increase in the ,lood, leading to hepatic encephalopathy, $ental status a,nor$alities, asterixis5 also caused ,y octpane$e, ,enCoic acid, neurotrans$itters. 9o, two situations to restrict protein: cirrhosis and chronic renal failure. CHAPTER 4. NEOPLA<IA I. Nomen %a!&re: (B 1s. ma%ignan! A. +ain *i''eren e 3R usually does not $etastasiCe, $alignant has the capacity to $etastasiCe. $etastasiCe: in-asi-e $ole ($etastasiCe to lungs, ,ut goes away!. ;xception: 3R tu$or that
(. <%i*es: a! +C s%in cancer I&KA?;9 ,ut does not $etastasiCe: ,asal cell carcino$a. ,! <terus: leio$yo$a5 +C 3R tu$or in wo$an is +C located in which organN <terus it1s a leio$yo$a5 tu$or of s$ooth $uscleM c! 4i,roids s$ooth $uscle5 ,eco$e -ery hard d! +C 3R tu$or in $ale (yellow! " lipo$a e! 3R tu$or of glands " adeno$as (ie adrenal adeno$a thin adrenal cortex ,:c it is functional5 it could ,e $a%ing cortisol, therefore suppressing AC)., and the fasiculata and reticularis would undergo A)2'*.B leads to Cushing1s. If tu$or secreting $ineralocorticoids it is Conn1s syndro$e, causing atrophy of the Cone glo$erulosa (L42 salty sweet sex! f! )u,ular adeno$a " +C precursor lesion for colon cancer (loo%s li%e straw,erry on a stic%! C. Car inoma 1s. sar oma 1. Carcino$a $alignancy of epithelial tissue (0 epithelial tissues s#ua$ous, glandular, and transitional! a! 9#ua$ous carcino$a how to recogniCeN 8ittle swirls of increased redness (,right red! called s#ua$ous pearls5 ,! Llandular carcino$a 2ound glands, with so$ething in the $iddle " adenocarcino$a c! )ransitional cell carcino$a fro$ ,ladder, ureter, renal pel-is (fro$ genital urinary tract! all with transitional epitheliu$ )herefore 0 carcino$as " s#ua$ous, adenocarcino$a, and transitional cell carcino$as. d! ;xa$ple: +alignant $elano$a first step in $anage$entN ;xcision (,R -ersion " ne-us!, ,oth are deri-ed fro$ $elanocytes. )his is the $ost rapidly increasing cancer in the <9A, not +C. )hey are 9D166 Ag I/J tu$ors aput tu$ors e! Aput )u$ors: 9D166 Ag I/J tu$ors aput tu$ors5 aput is precursor upta%e decar,oxylation, $eaning that they are of neurosecretory or neural crest origin. )herefore, on ;+, ha-e neurosecretory granules. 9D166 Ag is used to stain things of aput origin or neural crest origin ($ost, not all, will ta%e up that Ag!. ;xa$ples of aput tu$ors: $elano$a5 s$all cell carcino$a of the lung5 ,ronchial carcinoid5 carcinoid tu$or at the tip of the appendix5 neuro,lasto$a (secretory tu$or!, ie ( y:o with tu$ors all o-er s%in, and on ,iopsy, it is 9D166 I/J, tu$or was fro$ adrenal $edulla, $etastasiCe to s%in. (. 9arco$as are $alignancy of +;9;&C.B+A8 tissue (not epithelial!. 9arco$a of s$ooth $uscle " leioy$yosarco$a5 9triated $uscle " rha,do$yosarco$a5 4at " liposarco$a5 (these are $alignancies of $esenchy$al tissue, while carcino$a1s are of epithelial tissue!. ;xa$ples: a! 3one, see $etaphysis, see Cod$an1s triangle, and sun,urst appearance on xDray ,:c this tu$or actually $a%es ,one. ?x " osteogenic sarco$a (,one $a%ing sarco$a!. ,! 3iopsy fro$ girl ha-ing necrotic $ass co$ing out of her -agina, Ki$entin and %eratin IDI, and des$in I/J, dxN ;$,ryonal rha,do$yosarco$a (see striation of $uscle!. )his is the +C sarco$a of children (-agina in little girls and penis in little ,oys! c! +o-a,le $ass at angle of jaw " $ixed tu$or (in parotid!5 =$ixed1 ,:c two histologically ha-e two different types of tissue ,ut deri-ed fro$ 9A+; cell layer (not a terato$a, which is fro$ three cell layers!,. +C o-erall sali-ary gland tu$or (usually ,R! " $ixed tu$or d! )erato$a " tooth, hair, deri-ed fro$ all three cell layers (ectoder$, $esoder$, and endoder$! A%a ger$ cell tu$ors ,:c they are totipotential, and stay $idline. ;x. anterior $ediastinu$, or pineal gland5 therefore, terato$as are ger$ cell, $idline tu$ors. e! Cystic terato$a of the o-aries: 1A y:o girl with sudden onset of 28P pain (don1t confuse with appendicitis, Crohn1s dC, ectopic pregnancy, follicular cyst!. 'n xDray, see calcifications of the pel-ic areaM Cystic terato$a (the calcifications can ,e ,one or teeth!. <sually de-elop in $idline ger$ cell tu$or.
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II. Nomen %a!&re: Le&6emia an* %ymp)oma +C on the ,oards: Auer rod fro$ $yelo,last, and hyperseg$ented neutrophil fro$ 31( and folate deficiency. A. Le&6emia " $alignancy of ste$ cells in the (+, and they can $etastasiCe (li%e all cancer! and to ly$ph nodes, leading to generaliCed ly$phadenopathy and hepatospleno$egaly. ?eri-ed fro$ ste$ cells in the $arrow and $etastasiCe. (. +a%ignan! %ymp)oma: arise fro$ LY+PH no*es, and can $etastasiCe anywhere, include 3+. )he +C site in ,ody for ly$pho$a &') de-eloping in ly$ph node: s!oma ) +ost extranodal (outside ly$ph node! pri$ary ly$pho$as occur in the sto$ach5 .. pylori can produce these. (nd +CC location (ly$phoid organ in the LI tract! " Payer#s pa! )es (located in the ter$inal ileu$!. +C ly$pho$a " follicular 3 cell ly$pho$a. )his is an exa$ple of %noc%ing off apoptosis gene D1>:1T translocation of a hea-y chain5 when you get the translocation, 3 cells will $a%e ,clD(, which inacti-ates apoptotic gene in the 3 cell, therefore, the apoptotic gene is i$$ortal, leads to cancer. III. Nomen %a!&re o' Trop)o-%as!i T&mors A. Hy*a!i*i'orm mo%e, presents with cluster of grapes. It $anifests in the first tri$ester with signs of preecla$psia (.*, proteinuria, ede$a in the first tri$ester!. 'n ultrasound, will see uterus too large for its gestational age, with a snowstor$ appearance " classic co$plete $ole5 and can progress to choriocarcino$a. (. C)orio ar inoma mo%e is a ,enign tu$or of the chorionic -illus5 chorionic -illi are lined with tropho,lastic cells, including synctiotropho,last on the outside (has contact with the ,lood, fro$ which ' ( is extracted!5 under the synctiotropho,last is the cytotropho,last, then ha-e warten1s jelly in the chorionic -illus, then ha-e -essel that ,eco$es the u$,ilical -ein, which has the $ost '( in the -essels of the fetus. 9o, hydatidifor$ $ole is a 3R tu$or of the G.'8; chorionic -illus, and it loo%s li%e grapes ,:c it1s dilated up. Choriocarcino$a is a $alignancy of the lining of the chorionic -illus: the synctiotropho,last and the cytotropho,last (not the actual chorionic -illus!. Ghich $a%es hor$onesN )he syncytiotropho,last synthesiCes 3D.CL and hu$an placental lactogen (growth hor$one of pregnancy it gi-es aa1s and glucose fro$ $o$ to ,a,y!. 9o, when gestationally deri-ed, and e-en when they $etastasiCe to the lungs, they respond well to che$otherapy ($ethotrexate, chla,ucil!. )herefore, these are highly $alignant tu$ors, ,ut go away with che$otherapy. I.. T)ings !)a! en* in C=omaD: ;-erything that end in o$a is not necessarily ,R ie $elano$a ($alignant tu$or of $elanocytes!, ly$pho$a ($alignant tu$or of ly$ph nodes! Also, all that ends in o$a is not necessarily a neoplas$ ie he$arto$a " o-ergrowth of tissue that is nor$ally present in that area. ;xa$ple: A ,ronchial he$arto$a seen lung which is ,R cartilage and a solitary coin lesion is seen in lung (also wonder if it1s a granulo$a!. )he polyp in *eutC Feghers syndro$e is a he$arto$a (not e-en a neoplas$!, that1s why there is no increase in ris% of poly cancer. .yperplastic polyp (+C polyp in LI! is a he$arto$a, it1s a 3R tissue in place it is not suppose to ,e (ie pancreatic tissue in the sto$ach! this is called a choristo$a, or heterotopic ret. +ec%el1s ?i-erticulu$ +C co$plication of +ec%el1s ?i-erticulu$ " ,leeding fro$ a gastric $ucosa that is ulcerated, or pancreatic tissue that is ulcerated. 9hould gastric $ucosa ,e in the $ec%el1s di-erticulu$N &o, ,:c it is in the s$all ,owel (a,out ( ft fro$ the ileocecal -al-e!. .e$arto$as are nonDneoplastic, and therefore do not ha-e cancer producing potential. .. +a%ignan! Ce%%s Increased $itotic rate does not $ean cancer. Ghat $a%es $itosis $alignant is ha-ing an atypical $itotic spindle (they are aneuploid and ha-e $ore than the nor$al >A c1so$es0. 8ey !)ing !)a! *e!ermines i' i! is ma%ignan! is i!s a-i%i!y !o me!as!asi>e. +alignant cells usually ha-e a longer cell cycle than the cells they deri-ed fro$. Ho3 many *o&-%ing !imes *oes i! !a6e !o ge! a !&mor !)a! an -e *e!e !e* %ini a%%yE $F *o&-%ing !imes $eans that the tu$or goes through the cell cycle 06 ti$es, and a tu$or of one sono$eter in siCe is produced5 16 R in $ass. +alignant cells are i$$ortal they don1t li%e each other and lac% adhesion5 if they were stuc% to each other, they would ha-e pro,le$s infiltrating tissue. +alignant cells ha-e si$ple ,ioche$ical syste$s, typically anaero,ic $eta,olis$, and ha-e $any enCy$es such as proteases (used to ,rea% through tissue!, collagenases (used to ,rea% through 3+!. )his is what $a%es a $alignant cell $alignant. .I. +e )anisms o' +e!as!asis: %ymp)a!i @ )ema!ogeno&s@ see*ing A. Lymp)a!i me!as!asi>es: .ow do ar inomas usually $etastasiCeN 8y$ph nodes they drain to their regional ly$ph nodes5 ie ,reast cancer goes to axillary nodes or internal $a$$ary nodes. 4or colon cancer, go to nodes around the$ (the local ly$ph nodes!5 sa$e with carcino$a of the esophagus. Ghat part of the ly$ph node do $etastases go toN 9u,capsular sinus. If they can get through the ly$ph node, they go to the efferent ly$phatics which drains into the thoracic duct, and then into the su,cla-ian, and then they ,eco$e he$atogenous. )herefore, carcino$a can ,eco$e he$atogenous, this $eans that they 1st went through the ly$ph nodes 5 now, they can spread to other organs (ie ,one, li-er, etc!. )his is ,etter than sarco$a ,:c can feel the ly$ph nodes ,y clinical exa$ and pic% up ,efore it spreads.
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(. Hema!ogeno&s me!as!asi>es: 'n the other hand, sar omas do not li%e to go to ly$ph nodes. )hey go right through 3K1s and are characteriCed ,y he$atogenous spread, and that1s why lungs and ,ones are co$$on sites of sarco$as. )hey don1t li%e to go to ly$ph nodes. )herefore, they are a little worse ,:c they i$$ediately go he$atogenous, and do not gi-e a clue that they are spreading. ;xa$ple: ha-e angiosarco$a of the ,reast5 would you do a radical dissection of the axillaN &o, ,:c angiosarco$a does not go to the ly$ph nodes, therefore, do a si$ple $astecto$y. If it is ,reast carcino$a, ta%e ,reast and lu$pecto$y and local axillary ly$ph nodes and co$plete the dissection. ;xceptions: 4ollicular carcino$a of the thyroid (thin%s it1s a sarco$a! s%ips ly$ph nodes and goes straight to 3K1s, and ta%es the he$atogenous route. 2enal adenocarcino$a goes to renal -eins (also deter$ines prognosis! .epatocellular carcino$a li%e to attac% the -essels In general, carcino$as 1st li%e to go to ly$ph nodes, and the ha-e the potential to ,eco$e he$atogenous. 9arco$as go he$atogenous, $a%ing the$ dangerous. C. <ee*ing: Classical ;xa$ple: cancers that are in ca-ities and ha-e a potential of seeding, li%e little $alignant i$plants. +ost o-arian cancers are surface deri-ed cancers, therefore deri-ed fro$ lining around the o-ary, and they seed li%e little i$plants. )herefore, easy to throw out these i$plants and for it to $etastasiCe to the o$entu$, and into the pouch of ?ouglas. )he pouch of ?ouglas is posterior to the uterus and anterior to the rectu$ and is felt ,y digital rectal exa$. )he pouch of ?ouglas is to a wo$an, as the prostate gland is to the $an. If you do a rectal on a $an, and push forward, you will feel the prostate. If you do a rectal on a wo$an and push forward, this is the pouch of ?ouglas. )his is an i$p area ,:c it1s the $ost dependent area of a wo$an1s pel-is and $any things go here clotted ,lood in a rupture ectopic pregnancy, where endo$etrial i$plants go in endo$etriosis, and where seeding goes in o-arian cancers (pouch of ?ouglas!. 9o, seeding of o-arian cancer to the o$entu$ and can actually in-ade. Can also seed in the pleural ca-ity, for exa$ple: peripherally located lung cancer that can seed into the pleural ca-ity. L3+ (+C pri$ary $alignancy of the ,rain in adults! can seed into the spinal fluid and i$plant into the entire spinal cord, as can a $edullo,lasto$a in a child. 9o, the 0 $echanis$s for $etastasis are ly$phatic, he$atogenous, and seeding. .II. +os! Common /+C0 an ers )he first #uestion is to as%: IIs the $etastasis $ore co$$on than pri$ary cancerNJ In $ost cases, $etastasis is the +C cancer in an organ (not a pri$ary cancer!. ;xception: renal adenocarcino$a (which is $ore co$$on than $etastasis to it!. L&ng: +C cancer is $etastasis fro$ the ,reast cancer. )herefore, +C cancer in the lung is ,reast cancer. )herefore, wo$en are $ore li%ely to get lung cancer. (one: +C cancer in ,one is $etastasis (not $ultiple $yelo$a or osteogenic sarco$a!. +C cancer that $etastasis to ,one is ,reast cancer ,:c the ,atso$ syste$5 it is a -enous co$plex going fro$ ,ase of the s%ull down to the sacru$, and has no -al-es in it. )he little tri,utaries co$$unicate with the -ena ca-a and also go right into the -erte,ral ,odies. )hen they collect around the spinal cord and go up. 4or exa$ple: a lady has a little plug of tu$or in the intercostal -ein, and ,ends down to pic% up so$ething off the ground, which causes the cancer to ,e dislodged fro$ the -ein to the -ena ca-a to the ,atson plexus in the -erte,ral ,odies, and 0 $onths later she is co$plaining of lower ,ac% pain. All of a sudden, she is stage four cancer. +C ,one $etastasis )' the -erte,ral colu$n. (nd +C is the head of the fe$ur (in a wo$an, this is due to ,reast cancer ie ,reast cancer in head of fe$ur, when they thought it was degenerati-e arthritis!. +C organ me!as!asis !o , %ymp) no*es (carcino$as are $ore co$$on than sarco$as, and carcino$as li%e to go to ly$ph nodes, $eaning it is the +C $etastasis to! Li1er: +C cancer of li-er " $etastasis fro$ lung into li-er (not colon colon is (nd ,:c portal -ein drainage!. Tes!i &%ar Can er: Ghere would testicular cancer $etastasiCe firstN *araortic ly$ph nodes5 &') the inguinal ly$ph nodes ,:c it deri-ed fro$ the a,do$en, and then descended. ;xa$ple: se$ino$a ($alignant! will $etastasiCe to paraortic nodes ,:c that is where it ca$e fro$ Le'! s&pra %a1i &%ar no*e@ a6a .ir )o3#s no*e. )he +C pri$ary $etastasiCe to Kirchow1s nodes " sto$ach cancerM )here is a $ass in the left supracla-icular nodes along with wt loss and epigastric distress. (one: 3est test loo%ing for ,one $etsN 2adionucleide scan. ;xa$ple: e-erywhere that is ,lac% in a wo$an is $ets fro$ ,reast cancer. +C ,one $etastasis to " -erte,ral colu$nM +ets that are %y!i (,rea% ,one down! and $ets that are -%as!i ($ets go into ,one and induce osteo,lastic response!. A. 8ytic +etastasis: 4or lytic $ets, they can lead to pathologic fractures and hypercalce$ia. +&%!ip%e mye%oma with punched out lesions ,:c all $alignant plas$a cells ha-e I8D1 in the$ (a%a osteoclast acti-ating factor!
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3. 3lastic $etastasis: 4or ,lastic $ets, a%6a%ine p)osp)a!ase will ,e ele-ated. ;xa$ple: this is a $ale with prostate cancer (prostate cancer is ,lasticM!5 it is $a%ing ,one and will release al%aline phosphatase +C %o a!ion 'or me!s , %&m-ar 1er!e-rae ;xa$ple: T6 y:o $an with lower lu$,ar pain with pt tenderness5 what is first step in $anage$entN ?igital rectal exa$ would ,e the first thing to do ,:c this would ,e stage four dC, and the prostate is palpa,le5 so, this is the easiest and cheapest test (not *9A, or radionucleide ,one scan to $a%e sure its not $ets!. 8ytic $ets ha-e lucency (a,sence of ,one! ie -erte,rae collapse 3lastic $ets ha-e entity on x ray I' yo& see any spe imen 3i!) m&%!ip%e %esions in i!@ i! is +ET< /primary organ0. +C +C +C +C cancer ,rain " $ets cancer %iller in $en and wo$en " lung cancer pri$ary site for cancer in ,rain " lung cancer in lung " $ets fro$ ,reast an ers are on'ine* !o one area o' !)e
+C $ets to adrenal " lung therefore they always do a C) of the hilar ly$ph nodes, and adrenal glands in the staging of all lung cancers. 3one " ,lastic, therefore the $ost li%ely cause is prostate cancer. .III. <!ains an* E+ &se* !o )e%p *x *>: <!ains: des$in good stain for $uscle ie used for rha,do$yosarco$a 9tain for %eratin ($ost carcino$as ha-e %eratin in it, therefore stain for that! 9tains help I? diff types of tu$ors Ki$entinD $esenchy$al cells E+: <sed when nothing else helps Auput tu$or see neurosecretory granules. .istiocyte tu$or (ie histiocytosis H! see ,ir,ec% granules, with C? 1 +uscle see actin and $yosin fila$ents Kascular $alignancy Gi,,le palad ,odies (ha-e -G4 in the$!5 they are of endothelial origin Know gap junc (which co$$unicate, which don1t! IG. On ogenesis: A. (ig pi !&re o' on ogenesis 1! Initiation ($utation ie within the cell cycle! (! *ro$otion (where $ultiple copies of the $utation are $ade! 0! *rogression (su,DspecialiCing! diff types of cancer cells ha-e diff func $alignant cells with one purpose to %ill you. ?iff cells with diff func: so$e stay where they are5 so$e in-ade (and are gi-en special things for it to ,e a,le to in-ade!5 so$e ha-e special receptors to ho$e in to specific organs5 so$e resist che$o, so$e spread, so$e $a%e enCy$es to penetrate tissues. ( sets of genes in-ol-ed with cancer: 1! In-ol-ed in growth process (cell cycle related! (! Lenes that suppress things (suppressor genes! (. T)ings !)a! are in1o%1e* in !rying !o ge! a e%% !o *i1i*e: L41s (epider$al deri-ed L4!5 protooncogenes nor$al genes, which ha-en1t ,een acti-ated, and ha-e nor$al function. Ghen they ha-e ,een acti-ated, they ,eco$e oncogenes, which are ,ad and ,eco$e cancerous. Certain protooncogenes code for growth factors ie sis, whose func is to $a%e L41s. All L41s ha-e to hoo% into a receptor5 therefore certain protooncogenes whose $ain jo, is to $a%e receptors ie er,D( " ,reast cancer, which codes for a receptor and ret " seen in +;& syndro$e (+;& I and IIa and II,!. Ge ha-e to send a $essage to the nucleus, so ha-e another set of genes, whose jo, is to send the $essage5 so$e located in the cell $e$,rane. ;xa$ple: ras protooncogene sends a L)* (a phosphorylated protein $essage!, therefore it1s a cell $e$,rane located $essenger syste$. Another exa$ple: a,l protooncogene which li-es in the cytosol, -ery close to the nuclear $e$,rane and also is in-ol-ed in $essages. Gho is the $essenger sent toN )he $essage is sent to a group of protooncogenes in the nucleus. 'nce that $essage is sent to the$, there is sti$ulation of nuclear transcription of that $essage5 in other words, the cell di-ides and $a%es whate-er it is supposed to $a%e. C%assi pro!oon ogenes !)ere are = my pro!oon ogenes , n?my an* ?my /n?my is 'or ne&ro-%as!oma@ an* ?my is 'or (&r6i!!s %ymp)oma0. 9o, the protooncogenes in-ol-ed $a%e L41s, growth factor receptors5 send $essages (which are often phosphorylated proteins!. ;xa$ple ie insulin hoo%s into receptor on adipose and acti-ated tyrosine %inase (located right on the receptor!, which $a%es a
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phosphorylated product, goes to the nucleus (to di-ide!, and also goes to LA and attaches to L8<)D>, which is $ade fro$ golgi apparatus, goes to the cell $e$,rane and there1s the receptor for glucose. )herefore the $essages go to nuclear transcri,ers in the nucleus and these are $yc oncogenes. T)e s&ppressor genes are on!ro%%ing !)e e%% y %e. T)e " mos! imp are R- s&ppressor gene an* p4$ s&ppressor gene. &or$ally, they control the cell cycle and do not let cell cycle progress to 9 phase. If unregulated, cells go to 9 phase and ,eco$e =initiated1. .ow do we initiate a cellN +utations$echanis$s: usually a point $utation ie su,stitutes aa for e:o. )he pE0 suppressor gene and the ras oncogenes is a pt $ut1n. All suppressor genes are due to pt $ut1n. 'ther $utations include: A$plification $a%e $ultiple copies (er,D( is an a$plification syste$! and )ranslocation (putting in another place and can1t go ,ac%! classic: C+8 translocation of a,l (non receptor tyrosine %inase acti-ity fro$ c1so$e R to ((. 'n c1so$e ((, it fuses on a cluster region of the fusion gene, and ,:c of the tyrosine %inase acti-ity, it sends a $essage and ste$ cells %eep di-iding5 a%a *hilly c1so$e. Another exa$ple: Cancer assoc with ;pstein 3arr -irus translocation of $yc nuclear transcri,er gene fro$ c1so$e T and puts it on c1so$e 1>5 it doesn1t li%e it there, so it leads to 3ur%itts ly$pho$a. 2eceptor for ;pstein ,arr -irus on all 3 cells C? (15 when it hoo%s on to receptor, it causes 3 cells to ,eco$e plas$a cells and $a%e A, (therefore, this -irus is an a$aCing sti$ulating of A, synthesis, as is the C+K -irus.! )he $ore a cell di-ides, the worse it is if so$ething happens to it5 ie ;3K -irus , T,1> translocation of $yc oncogenes fro$ T to 1> and all of a sudden you are $a%ing $ultiple copies, and leads to ly$pho$a (greater chance that you do so$ething, the greater chance that you will screw up!. 4ollicular 3 cell ly$pho$a translocation of 1>:1T5 inacti-ation of suppressor gene. Trans%o a!ion 14:1H , a &!e progran&%o y!i !)ere'ore !)e ma%ignan! e%% -e omes (B. %e&6emiaI Rx = .i! A /re!inoi a i*0 -7 i! ma!&res !)e -%as!s@
C. <&ppressor genes 9uppressor genes suppress, therefore if %noc%ed off, whate-er they were suppressing %eeps on going . 8ey s&ppressor genes: p4$@ R- gene@ a*enoma!os po%yposis o%i /'ami%ia% po%yposis0@ ne&ro'i-roma!osis@ 3i%m#s !&mor gene@ -r a1 an* " (,oth in-ol-ed in ?&A repair, and one is on c1so$e 10 while the other is on c1so$e 1@!5 ,rca1 can ,e ,reast cancer, o-arian cancer, or others5 -r a" is TOTALLY re%a!e* !o -reas! an er. 'nly 1E7 of ,reast cancers ha-e genetic assoc with these genes, therefore, $ost cases are sporadic. G. Common !)ings !)a! pre*ispose m&!a!ions: *rotooncogenes are acti-ated, while suppressor genes are inacti-ated 0 $ain ways this occurs: che$icals, -iruses, radiation A. C)emi a%s: Ghich of the three is $ost co$$on in initiating a cell producing a $utationN C)emi a%s = smo6ing , +CC *ea!) in U<A *&e !o po%y y %i )y*ro ar-ons. 3y itself, s$o%ing is +C than -irally induced or radiation induced cancers. 9$o%ing causes lung cancer, s#ua$ous cancer of the $outh, larynx, lung, pancreas, ,ladder, and if it1s not the S1 cause, it1s often S(, such leu%e$ias, cer-ical ca, and colon. +CC papillary tu$or of the ,ladder " transitional cancer (s$o%ing! Ghat if you wor%ed in a dye industryN Aniline 5)a! i' yo& )a* 5egener#s gran&%oma!osis@ p&! on a *r&g an* go! )ema!&ria@ *i* y!o%ogy an* sa3 e%%s@ 3)a! *r&g is p! onE Cy %op)osp)ami*e /)emorr)agi ys!i!is0I pre1en! 3i!) mesna@ an* an a&se !ransi!iona% e%% ar inoma /!)ere'ore a !s as a ar inogenJ0 8ung cancer +CC " polycyclic hydrocar,ons fro$ s$o%e5 $ost often assoc with s$o%ing is s$all cell and s#ua$ous5 (. .ir&ses: Kirus assoc cancer: a -irus with nonpruritic raised red lesions. ?xN Kaposi1s sarco$a (due to ..K T! (&r6i!!sI *&e !o Eps!ein -arr 1aries 3)i ) a%so a&ses nasop)aryngea% ar inoma@ esp. in C)inese %i1er = Hepa!o e%%&%ar ar inoma *&e !o )epa!i!is ( 'rom AsiaI a%so *&e !o a mo%* = aflatoxin B; om-o o' )ep (@ irr)osis@ p%&s a'%a!oxin ma6es is ommon in AsiaI an a%so -e a&se* -y )ep C .IK is assoc with pri$ary C&9 ly$pho$a. )hey will as%: the rapidly increasing incidence of pri$ary C&9 ly$pho$a can ,e directly attri,uted to whatN .IK .*K causes s#ua$ous cancer of cer-ix, -agina, and -ul-a, and anus of ho$osexuals due to unprotected intercourse5 due to .*K 1A, 1T, 01. )his -irus causes anal s#ua$ous cell carcino$a in ho$osexuals. )he -irus wor%s ,y $a%ing two proteins, EA 3)i ) 6no 6s o'' p4$@ 3)i%e EH 6no 6s o' R-. C. Ra*ia!ion +C an er asso 3i!) ra*ia!ion , %e&6emia
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*apillary carcino$a of thyroid is also co$$only seen as a result of radiation. ;xa$ple: pt had radiation in head and nec%, and has nontender nodular $asses in cer-ical region " $etastatic papillary carcino$a of the thyroid related to ioniCing radiation. ;xa$ple: osteogenic sarco$a ;xa$ple: which $edical profession is $ost su,ject to leu%e$iaN 2adiologist, leu%e$ias are co$$only caused ,y radiation and it1s the radiologist that are co$$only in-ol-ed with this. ;xa$ple: if you ha-e Faco, CrutCfelt dC, what dr are youN &euroD*athologist (,c wor% with ,rains and prions! ;xa$ple: ,asal cell carcino$a (pic!, $ultifocal5 this is non ioniCing radiation (ioniCing radiation is the ,ad stuff!. )his is <K 3 light (, is ,ad!5 <K A light is for fluorescing superficial der$atophytes (wood1s light! or green1s patches in tu,erous sclerosis (therefore used ,y der$atologists!, a%a ,lac% light. <K 3 light is what you protect yourself fro$ to pre-ent getting s%in cancers (,asal cell " +C, then s#ua$ous cell, then $elano$a!. <K ? " thy$idine di$$ers ;xa$ple: lesion in sun exposed areas that is scraped off and grows ,ac% a%a solar (actinc! %eratosis5 it predisposes to s#ua$ous dysplasia. Arsenic is a $etal that is associated with s%in cancer. (ang%a*es) )as -a* 3a!er s&pp%y 3)i ) on!ains arseni @ !)ere'ore !)ey )a1e a )ig) n&m-er o' s;&amo&s s6in an ers@ an* 3i!) !ime i! an %ea* !o an er o' !)e %&ng@ an* angiosar oma o' !)e %i1er. ;xa$ple: %id with white eye reflex retino,lasto$a c1so$e 10. )his dC is sporadic and fa$ilial. It ta%es the sporadic dC ( separate $ut1n to ,eco$e retino,lasto$a (%noc% off on each c1so$e 10!. If it is fa$ilial, which is Autoso$al do$inant it ta%es just one $ut1n, ,:c you are ,orn with one already inacti-ated, therefore only need one $ore $utation on the other chro$oso$e in order to de-elop retino,lasto$a. 5)i!e eye re'%ex is no! +C *&e !o re!ino-%as!oma = !)e +CC is ongeni!a% a!ara ! /3)i ) an -e *&e !o C+.@ r&-e%%a@ or any ongeni!a% in'e !ions0. 5)i ) *r&g pre*isposes !o a!ara !sE Cor!i os!eroi*sI !)ere'ore a person 3i!) C&s)ing#s *> may *e1e%op a!ara !s. GI. :ene!i *> Gero*erma pigmen!osa sun exposed areas, auto recessi-e, can cause all s%in cancers (3CC, 9CC, and $elano$as!, and !)e *e'e ! is in DNA repair en>ymes. 'ther ?&A repair defects are associated with 32CA1 and 32CA(, pE0, they splice out the defects, this group is called the chro$oso$al insta,ility syndro$es wis%ott Aldrich, 3loo$s, Ataxia )elangiectasias, and 4anconi1s, all ha-e pro,s with ?&A repair. (asi r&%e o' !)&m- 'or (CC an* <CC: Upper %ip an* &p is -asa% e%% ar inomaI %o3er %ip an* *o3n is s;&amo&s e%% /!)ere'ore@ %esion on %o3er %ip , s; e%%I %esion on &pper %ip , -asa% e%%0 ;xa$ple: inside nose is 3CC, ,:c a,o-e the upper lip ;xa$ple: %eloid s# cell carcino$as and 0rd degree ,urns and s# cell carcino$a de-eloping in areas of drainage fro$ the sinus and ulcer that doesn1t heal fro$ anti,iotics. 9o, where-er there is constant irritation, and di-ision of cells related to irritation, there is an increase suscepti,ility to cancer. )his does not hold true for scar cancer tissue related cancers of the lungs or adenocarcino$a (just applies to things on the s%in ie ,urns and draining of sinus tracts!. 'nly ,acteria assoc with cancerN .. pylori adenocarcino$a and low grade $alignant ly$pho$as. GII. :ra*e 1s <!age A. :ra*e " 3)a! *oes i! %oo6 %i6eE )he ter$ well differentiated $eans that the tu$or is $a%ing so$ething li%e %eratin or glands, and if it1s identifia,le it1s called low grade. Ghen the cells are anaplastic, poorly differentiated under the $icroscope, and if you cannot tell what it is, then it1s called high grade. ;xa$ple: s# cell carcino$a can see %eratin pearls5 can I? it, so it1s a low grade cancer. ;xa$ple: see gland li%e spaces, can I? so its low grade (. <!age , /TN+0 +C staging syste$5 goes fro$ least i$p to $ost i$p ()&+! ;xa$ple: ,reast cancer with axillary node in-ol-e$ent5 therefore, the &"1, ,ut the I+J is worse, ,:c it indicates that cancer has spread to other organs li%e ,one, etc. Fust ,:c it goes to ly$ph nodes doesn1t $ean it is the $ost i$p prognostic factor. T"siCe of tu$or5 if tu$or is o-er ( sono$eters, it has a chance of $ets N"nodes (next $ost i$p for prognosis! +"$ets outside of nodes ($ost i$p prognostic factor! 9tage is $ore i$portant than grade for prognosis5 and within staging, + is the $ost i$p factor for prognosis ;xa$ple: pt with prostate cancer, which of following has it the worstN )he answer choices were cancer li$ited to prostate, it went into se$inal -esicles, it in-ol-ed the wall of ,ladder, went to ly$ph nodes, or ,oneN Answer " ,one (,one represents the I+J of the )&+ syste$ this ie is stage > ,y definition"$ets!
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;xa$ple: a slide of a colon cancer and a ly$ph node: what is $ost i$portant siCe of tu$or or ly$ph node in-ol-e$entN 8y$ph node. If it was also in the li-er, what is $ost i$pN 8i-er speci$en is the $ost i$p prognostic factor. GIII. Hos! *e'enses $ost i$portant is Cytotoxic C?T ) cell 'thers &K cells, A,1s, $acrophages, type ( .*B In hospital, they loo% for altered +.C class I Ag1s in the cancer pt, ,:c cancer wants to %ill ) cells5 they do this ,y putting in perforins, which acti-ate caspasases, and this leads to apoptosis (the signal, fro$ the perforins, acti-ate the caspasases, which ha-e proteases, which ,rea% down the nucleus and $itochondria, and cell dies, without any infla$$atory infiltrate!. GI.. O!)er *iseases seen in ma%ignan y: A. Ca )exia cause is )&4 alpha5 it is irre-ersi,le 'nce you see a pt with disse$inated cancer a,out to go into cata,olic state, can gi-e then total nutrition, ,ut still won1t help. (Gill not get $uscle $ass ,ac%, and this is due to )&4Dalpha! (. +any )ema!o%ogi a&ses o' anemia seen in ma%ignan y
+C ane$ia in $alignancy is Ane$ia of chronic disease (this is the o-erall $ost co$$on! Co%on an er: %e'! si*e o-s!r& !s 37 rig)! si*e -%ee*sI i' yo& )a1e RT si*e -%ee* in 1ery ommon. +ets to 3+ and replace 3+ 'r, use che$otherapy drugs that are cell cycle specific or cell cycle nonspecific they wipe out the $arrow Can ha-e autoi$$une $echanis$ with certain $alignant dC. C. Asso ia!ions 3i!) *issemina!e* an ers: 1. +ost pts with disse$inated cancers are )yper oag&%a-%e, $eaning that they ha-e a tendency for for$ing clots. Classic ;xa$ple: a pt with painless jaundice, left supracla-icular node (this is a distracter!, had light color stools, lesions that ju$p fro$ one part of ,ody to next trousseau1s sign: a superficial $igratory thro$,ophle,itis due to carcino$a of the head of the pancreas!. *ancreatic cancers can A89' $ets to left supracla-icular node (-irchow1s node!, and often descri,e trousseau1s sign, which is a -ascular pro,le$ in the -eins that ju$ps fro$ one place to the next. (. Another co$$on thing seen is disse$inated cancers is !)rom-o y!osis an ele-ated platelet count. 'ther causes of thro$,ocytosis: 4e def, splenecto$y (ie see scar on a,do$en!, )3, ane$ias. If you cannot find any o,-ious cause of thro$,ocytosis then the cause is cancer. >67 of disse$inated cancers are thro$,ocytosis 'r a do a stool guaic for colon cancer D. +CC 'e1er in ma%ignan y , gram neg. in'e !ion. An ;. coli if you ha-e an indwelling catheter5 *seudo$onas if you ha-e a respirator, staph aureus can also ,e the cause fro$ an indwelling catheter, ,ut this is gra$ I/J. +CC death in cancer " infection G.. Paraneop%as!i syn*romes )hese are signs and so$eti$es sy$pto$s saying that you $ay ha-e an underlying cancer present. Its i$portant ,:c when you recogniCe the signs and sy$pto$s, then you can catch the cancer ,efore it $etastasiCe. +C Paraneop%as!i syn*rome , )yper a% emia ( $echanis$ for hypercalce$ia in $alignancy: 1! $ets to ,one, produce a che$ical (I8D1, *L; (, ,oth of which acti-ate osteoclasts! that produces lytic lesions in ,one, and you get hypercalce$ia (! renal adenocarcino$a or s#ua$ous carcino$a of $ainste$ ,ronchus that sits there and $a%es *).Dli%e peptide and causes hypercalce$ia ,:c it acts li%e *). and ,rea%s down ,one. )his is *araneoplastic, ,ut it1s not the $ost co$$on one. ;xa$ple: ( ,lac% lesions ,oth are $ar%ers for gastric adenocarcino$a5 usually under the ar$ called acanthosis nigricans, and other is called se,orrheic %eratosis (these are not neoplas$s!5 howe-er, when these suddenly de-elop o-ernight, you get $ultiple outcroppings (lesserr treeDar sign!, and the outcroppings is a phenotypic $ar%er for gas!roa*eno ar inoma5 this is easy to re$e$,er ,:c ( ,lac% lesions are $ar%ers fro$ gastroadenocarcino$a. ;xa$ple: %&--ing infla$$ation ,eneath on the ,one called periostitis5 infla$$ of underlying ,one causes proliferation of the soft tissue around it, which leads to clu,,ing (called hypertrophic osteoarthropathy!. Clu,,ing is not always assoc with cancer5 also assoc with ,ronchiectasis, I39. 3ut, if it1s a $alignancy, it is due to pri$ary lung dC. ;xa$ple: least co$$on collagen -ascular dC, ,ut the $ost often assoc with a certain cancer. )hey ha-e an ele-ation of seru$ CK5 this is der$ato$yositis5 raccoon eyes, so you see infla$$ation of s%in and $uscle5 high assoc with leu%e$ias, ly$pho$as and lung cancer. patches of %nuc%les goltrin1s patches (seen in der$ato$yositis!. o%on an er@ 9e *e' anemia is
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;xa$ple: -egetations (sterile! on the $itral -al-e assoc with $ucous producing cancers such as colon cancer5 this is called $arantic endocarditisDa%a non,acterial thro$,otic endocarditis5 they are not infections and these $arantic -egetations are assoc with $ucous secreting colon cancers. Can they e$,oliCeN Bes. Bou will need history to separate fro$ rheu$atic fe-er, ,ut history will relate $ore to colon cancer (ie polyarthritis! ;xa$ple: hyponatre$ia or Cushing1s cancer in the lung " s$all cell carcino$a, which is secreting either A?. or AC).5 also, for s$all cell, they are aput tu$ors, 9D166 Ag positi-e, neural crest origin, neural secretory granules. ;xa$ple: .ypercalce$ia or secondary polycythe$ia: renal adenocarcino$a (can $a%e *). li%e peptide and:or ;*'!. Examp%e: Hypog%y emia or se on*ary po%y y!)emia: Hepa!o e%%&%ar 'a !or0. ar inoma /!)ey an ma6e EPO or ins&%in?%i6e
;xa$ple: .ypocalce$ia or Cushing1s: auto do$inant, and the rare tu$or $ar%er that can ,e con-erted to a$yloid (calcitonin! $edullary carcino$a of the thyroid. G.I. T&mor mar6ers A. ( $ar%ers associated with )esticular cancer alpha feto protein (A4*! (which is really the al,u$in of a fetus! and .CL. A4* is a $a%er foryol% sac tu$or (endoder$al sinus tu$or!. 9o the tu$ors in %ids are yol% sac tu$ors (alpha feto protein! A4* is also assoc with .epatocellular carcino$a, increased in neural tu,e defects ($ust ,e on folate while pregnant to pre-ent neural tu,e defects!. In ?own1s syndro$e A4* is decreased. +ar%er for $alignancy in ,one, assoc with $onoclonal spi%e: 3ence Fones *roteins (light chain Ig!, assoc with +ultiple +yelo$a. )u$or $ar%er for prostate cancer: *9A5 not sp for cancer ,:c it can ,e also increased in hyperplasia5 it is sensiti-e ,ut not specific. If you do a rectal exa$, it is not increased. *9A is &') an enCy$e5 it is an Ag and is within the actual cell. It will not increase with a rectal exa$. 3reast cancer (surface deri-ed! 1E, 0. C;A1(E: '-arian cancer C;A Ag for colon cancer5 and so$eti$es used for s$all cell, and ,reast ca. C;A can ,e a part of an i$$une co$plex, and will get C;A: antiDC;A i$$une co$plexes which deposit in the %idney, and lead to nephrotic syndro$e this is diffuse $e$,ranous glo$erulonephritis " +C o-erall cause of nephrotic syndro$e. +any of these are related to $alignancy ,:c C;A can ,e the Ag that is deposits in the glo$eruli. wo$an with a tropho,lastic $ole, what would you getN 3eta .CL Ghat is +C pri$ary tu$or of the ,rain in %idsN Cere,ellar cystic astrocyto$a (3R!. It1s not $edullo,lasto$a. All astrocyto$as are 3R (if as%ed what is the $ost co$$on $alignant pri$ary tu$or, and then the answer is $edullo,lasto$a, which deri-es fro$ cere,ellu$!. +C actual tu$or of the ,rain cere,ellar tu$or deri-ed fro$ astrocytes5 +C )i%*)oo* an er " A88 leu%e$ia (other childhood tu$ors include C&9 tu$ors, neuro,lasto$as (in the adrenal $edulla!, 3ur%itts, ;wing1s (tu$or of ,one with onion s%inning!, e$,ryonal rha,do$yosarco$a.! A*&%!s: incidence: in wo$an: ,reast, lung, colon In $en: prostate, lung, and colon Killers: lung is S1 in ,oth (followed ,y prostate:,reast and colon! (nd +C cancer and cancer %iller in $en and wo$en co$,ined " colon )herefore, fro$ age E6 and on, you should get a rectal exa$ and a stool guaic. After E6, +CC cancer of I/J stool guaic is colon cancer. +C gyn an er: endo$etrial (S( is o-arian, and S0 is cer-ix! Cer-ix is least co$$on ,:c *ap s$ear. Ghen you do a cer-ical pap, pic%ing up cer-ical dysplasia, not cer-ical cancer (therefore the =incidence1 isn1t the highest!. 3:c cer-ical pap s$ears5 the incidence of cer-ical cancer has gone down significantly ,:c the detection of the precursor lesion, cer-ical dysplasia. 9o, ,:c cer-ical *ap s$ear, incidence of cer-ical cancer has gone down dra$atically (pic%ing up the precursor lesion!5 with $a$$ography, the incidence of ,reast cancer decreases, sa$e with *9A. +C :yn an er 6i%%er: o-arian (S( " cer-ical, S0 " endo$etrial!5 therefore to re$e$,er, the +C has the ,est prognosis endo$etrial is +C and has the ,est prognosis. Ghat is the only %nown existing tu$or -accineN .3K whyN +C infection trans$itted ,y accidental needle stic% in the hospital " .epatitis 3 3:c -iral ,urden of .epatitis 3 is greater than any infection, e-en $ore so than .IK.
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9o, with the .epatitis 3 -accine, you won1t get three things (1! .epatitis 3, ((! .epatitis ? (re#uires .ep 3!, and (0! hepatocellular carcino$a (related to .epatitis 3 related cirrhosis!. .ow do you eradicate hepatocellular carcino$aN Kaccination (ie in the 4ar ;ast!. CHAPTER A. HE+ATOLO:Y: R(C I. T)in6 -ig pi !&re. A. (. C. ct: +C. K LF: +i ro y!i anemia#s: 4e def " +C and Ane$ia of chronic dC, thalasse$ias, sidero,lastic ane$ias +C. M 1FF: +a ro y!i anemia#s: 31(:4olate def " +C5 usually folate def in an alcoholic +C. LF?1FF: Normo y!i anemia#s: low reticulocyte ct corrected: aplastic ane$ia, renal dC5 high corrected reticulocyte he$olytic ane$ias hereditary spherocytosis, sic%le cell, LA*? def, autoi$$une he$olytic ane$ia, $icroangiopathic
II. Re!i &%o y!e o&n!: 2eticulocyte count next to C3C is the first step in the wor% up of any ane$ias. Ghat is reticulocyteN Boung 23C. In (> hrs, a reticulocyte will ,eco$e a $ature 23C with a ,iconca-e dis%. If you ha-e an ane$ia, the reticulocyte count is i$p ,:c it tells you where the pro,le$ is: is the pro, in the 3+ in $a%ing the 23C, or is it a pro, outside the 3+ causing the pro,le$N )o deter$ine this, loo% at reticulocyte ct. If the 3+ was the pro,, then the reticulocyte ct would not ha-e an appropriate response. Ghat is an appropriate responseN Bou would ha-e a 3+ with hyperplasia, that has re-1d itself up, and $a%ing 23C1s and should ,e putting reticulocytes out pre$aturely, therefore wor%ing correctly to correct the ane$ia. )herefore, it tells whether the 3+ is responding appropriately or not. If you ha-e ,lood loss right now, do not expect reticulocyte ct to ,e ele-ated in (> hrs5 it ta%es at least ED@ days to get the response of $a%ing $ore reticulocytes (li%e the %idney $a%ing ,icar,, which ta%es a few days (0D>! to $a%e!. If nothing is wrong with the 3+, then it should host a nor$al reticulocyte response5 if there is so$ething wrong, will not ha-e a nor$al response (i$p ,:c $ight decide whether you ha-e to do a 3+ exa$ or not!. )herefore, if you ha-e a nor$al reticulocyte ct, do not do a 3+ exa$. .a-e to correct the reticulocyte count for the degree of ane$ia. Corre !e* re!i &%o y!e ! , H ! o' !)e p! N 24 O re!i &%o y!e ! that you are gi-en ;xa$ple: pt1s .ct is 1E7 (which is -ery se-ere ane$ia!, and the reticulocyte ct that was initially $easured is R7 (which is increased anything o-er 07 is increased!. )his =loo%s1 li%e the 3+ is responding correctly ,:c the ret ct is R7 (,ut ha-e to correct for the degree of ane$ia!. 1E:>E H R is 05 so, when we correct for the ane$ia, we ha-e 075 that1s what the corrected is therefore, 07 or greater " good response5 07 or less " ,ad response5 so, this figure is saying that it is a reasona,le response occurring in the pt. 9lide of a reticulocyte (%now what it loo%s li%e! need to do a special gie$sa stain to see the ,lac% fila$ents (which are 2&A fila$ents!5 ,:c they are 2&A fila$ents, the reticulocyte is still synthesiCing .,. 9o, in a,out (> hrs, (E7 the nor$al ., is ,eing synthesiCed and need 2&A fila$ents5 cannot see these without doing a special stain (loo% li%e little ,lac% wor$s in the 23C do not confuse with .einC ,ody!. Another slide using right gie$sa stain of reticulocyte with ,luish stain polychro$asia. )hese are younger ,lood cells than the (> hr old reticulocytes. )hey still ha-e the ,asophilia, which is not nor$ally present in the peripheral ,lood5 so, when we see the$, it $eans that the 3+ is really responding, and pushing e-en the younger ones out. )herefore, whene-er the ,oards say1s =polychro$asia1, they are tal%ing a,out these cells and these cells ta%e (D0 days ,efore they ,eco$e a $ature 23C. Ghy is this i$pN 3:c we ha-e to $a%e an additional correction whyN Ghen we are wor%ing up an ane$ia, we do a corrected ret ct and want to %now how the 3+ is responding right now at this day. &ot interested a,out what will happen in (D0 days, ,ut what will happen right now. .ere1s the pro,: when they do a reticulocyte stain, these guys will also ha-e 2&A fila$ents and will ,e counted in the ret ct and it will show a falsely ele-ated ret ct (we don1t want these ,:c they ta%e (D0 days ,> they ,eco$e a $ature 23C! instead we want the nor$al guys there. 9o, how do we factor the$ outN ?i-ide ,y (. 9o, $a%e the first correction for the degree of ane$ia (did it with 07 in this case!, loo% at C3C and see nothing that says polychro$asia. 8et1s say the C3C ct says =polychro$asia present1 then ha-e to $a%e an additional correction ,y di-iding ,y (. All of a sudden, it is now 1.E7 and this is not a good reticulocyte responseM <o@ 3)en yo& see !)e !erm Cpo%y )romasiaD@ !)en yo& )a1e !o ma6e an a**i!iona% orre !ion -y *i1i*ing -y ". ;xa$ple: reticulocyte cannot see with right gie$sa stain5 use special gie$sa stain to see 2&A fila$ents, and ri,oso$es (loo% li%e dots 3A9'*.I8IC 9)I**8I&L, seen in lead poisoning!. III. <i*e no!es: Ghen loo%ing at C3C you can $a%e $any dx1s. 2ule of 0 is good: ., x 0 should roughly e#ual the .ct ;xa$ple: for pre-ious ie, had 1E7 .ct, therefore the ., was a E )ransfusion of pac%ed 23C1s for e-ery unit transfused increase the ., ,y 1 and the .ct ,y 07. ;xa$ple: pt with E gra$ .,, and gi-en 0 units of pac%ed 23C1s. )he following day the ., is A and the .ct is 1T, is that an appropriate responseN &', it should1-e ,een T, with .ct of (>. It wasn1t T ,:c the pt has a LI ,leed (pt was ,leeding!. +CC anemia 3or%*3i*e , 9e *e' anemia +CC a&se o' 9e *e' /o1era%%0 , :I -%ee* T)ere'ore@ !)e +C reason 3)y H- an* H ! *on#! go &p a'!er !rans'&sion is -7 -%oo* %oss@ +C *&e !o :I !ra ! -%ee*.
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I.. R(C in*i es = +C. how ,ig is the cellN 3est way to classify is with +CK ($ean corpuscular -olu$e! 9$all, nor$al or ,igN )he $achine has the 23C1s pass through an aperture and siCes it. And then ta%es an a-erage5 this is the ,est way for classifying an ane$ia +CK: Y T6, it is $icrocytic (if you play odds, its 4e def! +CK (nor$al!: T6 D166 "5 ha-e &or$ocytic ane$ia5 +CK a,o-e 166 " $acrocytic (,1( or folate! If you ha-e s$all and large cells (di$orphic popcorn of 23C1s! it will ,e &or$ocytic (8i%e the $et acidosis, and resp al%, ,ut nor$al p.!. 9o, how could you ha-e a 4e def ane$ia and a folate def ane$ia at the sa$e ti$eN Know where these things are rea,sor,ed 4e rea,sor,ed in the duodenu$, 4olate is rea,sor,ed in the jejunu$, and 31( is rea,sor,ed in the ter$inal ileu$. 9o if you ha-e all these, you ha-e sma%% -o3e% *> /ie e%ia *>05 pt has $ala,sorption that affects diff areas of the ,owel. ;xa$ple: celiac sprue (+CC $ala,sorption! in-ol-es duodenu$ and jejunu$, therefore will ha-e def of 4e and folate, and will ha-e s$all cells and large cells. ;xa$ple: if it in-ol-es the jejunu$ and ter$inal ileu$, you will ha-e folate and 31( def. .. RD5 = R(C Dis!ri-&!ion 5i*!) )his $achine loo%s at the 23C1s and tells if the 23C1s co$ing out of the aperture are all unifor$ly s$all, nor$al, $acrocytic, or different in siCe. 9o, the 2?G detects a change in siCe of the 23C1s and it reports it as a nu$,er. ;xa$ple: $icrocytic ane$ia, with an increased 2?G5 this tells us that is $icrocytic, and there are different siCed $icrocytic cells. ;xa$ple: if you de-elop $icrocytic ane$ia o-ernight and all the cells are 4e def, the cells don1t ,eco$e $icrocytic i$$ediately5 they are nor$ocytic first ,efore they ,eco$e $icrocytic, and there will ,e a siCe -ariation pic%ed up ,y the 2?G. .ere1s the tric%: when you loo% at the C3C, and it shows *e rease* +C. 3i!) an in rease* RD5@ !)is is 9e *e' anemia (not thalasse$ias ,:c that is genetic and A88 the cells are $icrocytic!. 9lide with high 2?G has large and s$all cells. Another slide with spherocyte (ha-e too little $e$,rane, and therefore cannot hold a ,iconca-e dis% D an anorexic cell!, and target cell (has too $uch $e$,rane and too $uch ., collects in there and loo%s li%e a ,ull1sDeye an o,ese cell!. )arget cells are i$p $ar%ers for alcoholics ,:c they ha-e altered cell $e$,rane due to an altered cholesterol concentration of the $e$,rane and $ar%ers for he$oglo,inopathies (ie thalasse$ias, 9C?, .,C!. +ature 23C loo%s li%e ,iconca-e dis% and is thin in the $iddle ,:c there is less ., there, and $ore is concentrated at the edges5 this is why there is a central area of pallor in a nor$al 23C when it lying flat. All $icrocytic ane$ias ha-e one thing in co$$on: decreased ., synthesis5 with less .,, the redness of the cell with decrease and see greater area of pallor will increase (and if you play odd it1s I?A!. 9pherocyte too lil $e$, therefore it1s a sphere5 &' central area of pallorM (All red, no central area of pallor!. +icrocytic ane$ias all ha-e a *A8;, ,lan% color to the$5 therefore, it is -ery easy to I? spherocyte and $icrocytic cells with hypochro$ia and I?A of chronic dC. Audio ?ay 0: .e$atology 4ile ( .I. Normo y!i Anemia: 4or nor$ocytic ane$ia, you need to loo% at the reticulocyte count. 4irst, you ha-e to correct for the degree of ane$ia (.ct:>E H ret ct!. )hen loo% to see if there is polychro$asia, if there is polychro$asia (then di-ide ,y (!5 07 or higher " 3+ responding nor$ally, and (7 or lower " not responding properly. P)ysi a% signs o' anemia: spoon nails " 4e def (a%a %elosis!, ri,ofla-in def *allor of conjuncti-a " ha-e A gra$s or less of ., *al$er crease wor%s for white people if don1t see red, pt is ane$ic Ie wo$en, often due to 4e def 8ead line discoloration in gu$s due to lead poisoning &eurologic exa$ -ery i$p in 31( def ,:c the posterior colu$ns are %noc%ed off and lateral corticospinal tract, therefore ha-e propioception a,nor$alities and decreased -i,ration sensation and ,a,ins%i (lateral cortical!. .II. +i ro y!i anemias A. 9e s!&*ies = 'o&r 9e s!&*ies: 1. 9eru$ 4e (nor$al " 166, li%e the al-eolar '(!, (. 9eru$ ferritin. ,est test this is a solu,le, circulating for$ of 4e storage5 it rep the a$ount of 4e stored in the 3+, so, if you had to pic% one test for dx of 4e def, ane$ia of a chronic dC, or 4e o-erload, you would pic% seru$ ferritin ,:c this is the ,est screening test. 0. )I3C (total 4e ,inding capacity!5 the carrying protein for 4e is transferrin (trans " =carrys1! and it is $ade in the 8IK;2. >. 7 saturation" seru$ 4e di-ided ,y )I3C (. $ r&%es: 1. )ransferrin and the )I3C is the 9A+;M (2e$e$,er transferrin is what carries 4e!. (. )here is a relationship of 4e stores in 3+ with the transferrin synthesiCed in the li-er. Ghen the 4e stores in the 3+ are deficient (ie 4e def ane$ia!, that is the signal for the li-er to $a%e $ore transferrin, so it1s increased5 therefore, )I3C will also ,e increased in 4e def. )herefore, low 4e stores " increased transferrin synthesis and increased )I3C (an in-erse relationship!5 also, if 4e stores increase, transferrin and )I3C will decrease (ie 4e o-erload he$ochro$atosis, transfusions!
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0. 7 saturation is a calculation " seru$ 4e:)I3C (nor$al seru$ 4e is 166 and nor$al )I3C is 066, therefore, the 7 sat1n is nor$ally 166:066 " 007 D therefore, 1:0 of the ,inding sites are occupied with 4e. )hese are the ter$s and 4e studies we use, esp for $icrocytic ane$ias (related to 4e pro,le$s!. C. Pa!)ogenesis o' mi ro y!i anemias All $icrocytic ane$ias are $icrocytic (,:c they ha-e a pro,le$ $a%ing .,!. Ghen the 23C is de-eloping in the $arrow, it1s the ., concentration within the 23C that deter$ines the nu$,er of cell di-isions. )herefore, if the ., synthesis is decreased, it is a signal in the $arrow to increase the nu$,er of $itoses. Ghen cells $itoses, they go fro$ so$ething originally ,ig to so$ething s$all. 9o ,:c of the decrease in ., syn, there are extra di-isions and therefore the cell is s$aller. All four groups of $icrocytic ane$ias ha-e a decrease in .,. ., " he$e / glo,in5 .e$e " 4e / protoporphyrin5 Llo,in is $ade ,y the ,ody alpha ( !, ,eta01 2, delta ( !, ga$$a ( !5 .,A ( ( 5 .,A(( ( 5 .,4 ( ( Ge can dispense ( of the > $icrocytic ane$ias i$$ediately: 9e *e' " don1t ha-e 4e, therefore there is no 4e to for$ with protoporphyrin to for$ he$e5 so, no 9e , no )eme , no HD. Pa!)ogenesis o' Anemia o' )roni *> Ghen we ha-e infla$$ation, our ,odies respond to infla$$ation as if it is an infection. In $icro, ,ugs increase their reproduction with 4e, therefore, the $ore 4e they ha-e, the $ore they reproduce. 9a$e concept: with ane$ia of chronic infla$$ation and ,ody assu$es it is su,ject to a ,acterial infection, the o,ject is to %eep 4e away fro$ the ,acteria. .ow does it do thatN Its li%e a safety deposit ,ox, and you ha-e the %ey 4e is nor$ally stored in $acrophages in the 3+ this is where transferrin goes (to the $acrophage! to pic% up the 4e and ta%e it to the 23C. If you don1t want ,acteria to ha-e access to the 4e, it will ,e loc%ed away in the $acrophages in the 3+ and the =%ey1 to the $acrophages will ,e lost5 therefore, there is lots of 4e in the $acrophages of the 3+, ,ut cannot get it out. .owe-er, the good news is that you are %eeping it away fro$ the ,ugs so they don1t reproduce. 3ad news %eeping it away fro$ the 23C1s, and therefore ha-e an decrease in ., synthesis. .owe-er, unli%e 4e deficiency, where there is no 4e in the $acrophages of the 3+, there is *I8;9 of 4e, ,ut the =%ey1 ha-e ,een lost and you cannot get it out. 9o, irrespecti-e of that, your seru$ 4e is decreased ,:c it is all loc%ed in the $acrophages, and you don1t ha-e enough 4e to $a%e he$e. 9o, it1s the sa$e $echanis$ as 4e def, ,ut for different reasons: (1! you ha-e no 4e (I?A! and ((! you ha-e lots of it, ,ut its loc%ed in the safety deposit ,ox and you cannot get it so, either way, you cannot $a%e he$e and therefore you cannot $a%e he$oglo,in. To *is!ing&is) -e!3een IDA an* ACD>@ !)ere are )ig) 'erri!in %e1e%s in ACD>@ 3)ereas !)ere is a )ig) TI(C in 9e *e' anemia E. Heme syn!)esis Certain rxns in ,ioche$ occur in the cytosol, the inner $ito $e$,rane (ox phos!, $ito $atrix (,eta ox of 4A1s, )CA!, and in the cytosol A&? the $itochondria (gluconeogenesis, which starts in the $ito and ends up in the cytosol, urea synthesis, which starts in the $ito and goes to the cytosol and ,ac% into the $ito, and he$e syn in $ito, then cytosol, and then again in the $ito!. 9o, there are 0 ,ioche$ical rxns in the $ito and cytosol. 4irst part of he$e syn (a%a porphyrin syn! ,egins in the $ito. 4irst rxn is succinyl coA (su,strate in )CA cycle and su,strate for gluconeogenesis!, which can ,e put together with glycine (which is an inhi,itory neurotrans$itter of $uscle, ,loc%ed ,y tetanus toxin rhesus sardonicus and tetanic contraction so when glycine is inhi,ited, the $uscles are in a tonic state of contraction!. Know all 2A); 8I+I)I&L ;nCy$e1s (28;! for e-ery ,ioche$ical rxn. (28; in cholesterol syn " .+L CoA reductase!. 28; in he$e synthesis " A8A synthase, cofactor " pyridoxine. 9o, protoporphyrin is $ade and goes ,ac% to the $ito. 9o you ha-e protoporphyrin plus 4e, so you ha-e a $etal plus protoporphyrin. Chelatase puts these together5 so, it is called ferrochelatase, with co$,ines 4e with protoporphyrin and for$s he$e. .e$e has a feed,ac% $echanis$ with A8A synthase (all 28;1s ha-e a feed,ac% $ech!. 9o, with increased he$e, it will decrease syn of A8A synthase, and when he$e is decreased, it will increase A8A synthase syn. 9. Pa!)ogenesis o' <i*ero-%as!i anemias (least co$$on of the $icrocytic ane$ias!. IsideroJ " 4e. 2arest of $icrocytic ane$ias " si*ero-%as!i anemias5 they ha-e 0 causes: 1. Alcohol (sidero,lastic ane$ia is &') the +C ane$ia in alcohol, +CC of sidero,lastic ane$ia is alcohol5 +C ane$ia o-erall " AC?C, followed ,y folate def!. Alcohol is a $itochondrial poison and uncouples ox phos, and da$ages inner $ito $e$,rane, allowing protons to go in and drain the$ off. 'n ;+ of the $ito of an alcoholic is huge ,:c they are da$aged (called $ega$itochondria!. )herefore, any process that occurs in the $ito is screwed up. )his, therefore, includes he$e synthesis. 9o, 4e is deli-ered to the 23C ,y transferrin and doesn1t %now where to go. 9o$e is stored as ferritin, while $ost of it goes to the $ito, which is 3A? newsM GhyN 3:c it can get in, ,ut CA&&') get out. 9o, there is da$aged $itochondria that were da$aged ,y alcohol, 4e goes in and now cannot go out. 9o, there will lots of 4e caught and 4e ,uilds up within the $ito. +ito is located around the nucleus of an 23C in the 3+, leading to a ringed sidero,last. )his is the $ar%er cell for sidero,lastic ane$ia5 also in 4e o-erload dC will excess iron, and will not get he$e ,:c $ito destroyed (so alcohol is the +CC!. (! LA*? def pyridoxine def5 ie not ta%ing Kit 3A during 2x of )3. 9o, no Kit 3A " no he$e, and the first rxn will not happen. 3ut 4e doesn1t %now that5 again, 4e goes to the $ito, waiting for porphyrin, leading to ringed sidero,last. 0! lead poisoning so lead leads to sidero,lastic ane$ia. 8ead is a denaturer. All hea-y $etals denature proteins (enCy$es are proteins!. 8ead1s fa-orite enCy$e to denature is ferrochelatase, so it won1t wor%, and no he$e " no .,, leading to $icrocytic ane$ia. 8ess of inhi,itory effect, ,ut does ha-e a little one on a$inole-ulinic acid dehydratase. 3ut is
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+'9) co$$only %noc%s off ferrochelatase. 9o, when 4e co$es into $ito, it cannot ,ind to protoporphyrin to for$ he$e. No )eme , *e rease* H- , mi ro y!i anemia. ;xa$ple: if ferrochelatase is decreased:inhi,ited, he$e decreases, ,ut what happens to protoporphyrin ,efore the ,loc%N It increases (used to ,e screening test of choice for lead poisoning!. &ot used any$ore. GhyN 3:c if you don1t ha-e 4e ,:c AC?C:4e def, what will happen to the protoporphyrin in the $itoN It will increase. 9o, they found out that $any people had an increase in 23C protoporphyrin, and got IDI test for lead poisoning, and then %new that the pts had either 4e def or AC?C, and concluded that it was not a good screening test. 9o, now ,lood lead le-el is the screening and confir$atory test for lead poisoning, not 23C protoporphyrin (too $any false I/J1s! :. Pa!)ogenesis o' T)a%assemias: Auto rec dC1s 1. A%p)a !)a%assemias who do we see alpha thalasse$ias inN Asians (4ar eastern! and ,lac%s (all genetic he$atologic dC1s are seen in the ,lac% pop1n alpha:,eta thal, LA*? def, 9C?C!. 1. ., electrophoresis separates things ,ased on siCe and charge, therefore you can clearly separate .,A, .,4, and .,A( clearly on cellulose acetate ,:c they ha-e different $igrations. 9o, they fluoresce it, and .,A, .,4 and .,A( all settle down. )hen they stain the cellulose acetate to see how $uch is there. )hen, it produces density, and the density correlates with the concentration of each of the .,1s. .ow will they %now the percentN Gith a densito$eter it con-erts the density of the stain to the percentage. It turns out that .,A (( ( ! is the predo$inant ., in an adult (REDRE7!. .,A( is 1D(75 .,4 " 17. )hese are the nor$al, which are expressed as a percentage. (. Alpha thalasse$ias, auto rec, has a pro,le$ in $a%ing alpha glo,in chains. ?o .,A( and .,4 re#uire .,A to ,e $adeN Bes. )herefore, all will ,e e#ually decreased. )his will &') show up on an electrophoresis, ,:c all are e#ually decreased, therefore, it shows to ,e totally nor$al. )here are four genes that control alpha glo,in synthesis. ?eletion of one of these four will not cause ane$ia. ?eletion of ( genes " pro,le$ ,:c $ini$ally decreased, and therefore a $ild ane$ia. It is $icrocytic ,:c the glo,in part is decreased, $eaning you will get a $icrocytic ane$ia (decrease in ., conc1n, which will ,e the sti$ulus!. )his called alpha thalasse$ia $inor, seen in the far eastern pop1n and ,lac% pop1n. Gith a three gene deletion, that1s not good, and pt is really decreased (there is also a he$olytic co$ponent to it!. )he ,eta chains get irritated that there is no alpha chains around, so they fro$ their own ,eta glo,in chains. 9o, four ,eta chains get together and for$ .,.. If you do an electrophoresis, there will ,e a different result. .,. is a diff .,, and therefore will not $igrate to the sa$e place as other .,1s. 9o, you can dx this alpha thalasse$ia with ., electrophoresis (why its called .,. dC!. 4our gene deletions spontaneous a,ortions (usually, therefore not usually ,orn ali-e a%a hydrops fetalis!. La$$a chains for$ together (li%e the ,eta chains did earlier! and for$ a ., with > ga$$as, which is called ., 3arts. )his will show up on electrophoresis, ,ut won1t $atter ,:c ,a,y is dead already. Ghat is the spontaneous a,ortion rate in far eastN .igh ,:c this is where alpha thalasse$ia is $ost co$$only located. )herefore, if the incidence of spontaneous a,ortions is increased, what cancer ris% is increasedN Choriocarcino$a (increased hydatidifor$ $oles, which leads to choriocarcino$a!. 9o, there is a high incidence of choriocarcino$a in the far east ,:c of alpha thalasse$ia. 2x ?' &') gi-e 4e (will 4e o-erload the$!. 9o, just lea-e the$ alone. ((nd +CC jaundice " Lil,ert1s dC esp with lac% of food!. ". (e!a !)a%assemia ,lac%s, Lree%s, Italians. 3 (,y itself! " $a%ing nor$al ,eta chains5 3 (with a I/J! " $a%ing ,eta chains, ,ut not enough5 3 (with a I6J! " not $a%ing ,eta chains at all. 3eta thal is auto rec, and has to do with splicing defects, stop codons. )he $ost se-ere for$ is due to stop codon (therefore ter$inate synthesis of ,eta chains, and don1t e-en $a%e the$!. +i%* !)a%assemia: slightly decreased ,eta chains, pro, due to a splicing defect5 ,eta chains are slightly decreased, alpha chains are o%ay, delta chains are o%ay, ga$$a chains fine (confined to fetus!. 9o, .,A will decrease, and delta will get together (hence increase in .,A(! and ga$$a chains get together (hence increase in .,4!. )herefore, see a decrease in .,A and an increase in .,A( and .,45 this GI88 show up on electrophoresis. )his happened ,:c ,eta chain is decreased, and it showed a decreased .,A. It is just a $ild thalasse$ia and is -ery co$$on. 9o, only way to dx 3eta thal is with ., electrophoresis. Cannot do anything a,out it. .opefully it is not the se-ere type, where not $a%ing any ,eta chains a%a Cooley1s ane$ia and will not li-e past 06 y:o. Gill ha-e a constant transfusion re#uire$ent5 $any of these pts die fro$ 4e o-erload, or .ep C or $ultiple transfusions or .IK. +C in ,lac% pop1n ,etaDdelta thalasse$ia (decreased ,eta chains and decreased delta chains, so what1s left are alpha and ga$$a chains!. Ghat will the electrophoresis showN .,4. )his called hereditary persistence of .,4. &o ane$ia, just do$inant .,4. 4or thalasse$ias, %now they are genetic, what groups of people they are in, and that you ?'&1) do anything to the$, esp gi-ing 4e ,:c all their 4e studies are nor$al. H. Iron De'i ien y Anemia /IDA0: 1. Causes of 4e def ane$ia loo% at age ,rac%ets: a! *re$aturity e-eryday a ,a,y is not in utero, it is losing 4e (all their 4e stores are decreased, so ,a,y $ust ,e gi-en 4e supple$ents!. ,! &ew,orn chec% stool for their ,lood5 need to %now it1s not $o$1s ,lood, which can ,e swallowed. )his is done with the apt test. +ost of ,lood that co$es out of ,a,y1s $econiu$ is ,lood the ,a,y swallowed fro$ $o$, and it has .,A in it. .owe-er, if it was .,4 ,lood that ca$e out, the +CC is ,leeding $ec%el1s di-erticulu$. )herefore, ,leeding $ec%el1s di-erticulu$ " +CC 4e def in a new,orn and child. +ec%el1s di-erticulu$ is &') the cause of 4e def in an adult, ,:c $ost ha-e ,led ,y four years of age, and already would ha-e %nown pt has it.
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c! Go$an under E6 +CC 4e def " $enorrhagia, therefore need to get a good $enstrual hx5 due to ano-ulatory cycles (,etween (6D>6 y:o, due to o-ulatory cycles, inade#uate luteal phase, pregnancy related ,leeds, endo$etrial polyp that is ,leeding!. d! +en under E6 +CC 4e def " *<? (usually duodenal ulcer!. e! +en and wo$en o-er E6 +CC 4e def " Colon cancer (. 8a, )est seru$ 4e " low, )I3C " high, 7 sat1n (4e:)I3C! " low If you don1t ha-e 4e, sat1n is decreased ,:c no 4e to put on it. 9eru$ ferritin le-el " low I. ACD> related to infla$$ation. 4e is loc%ed in safety deposit ,ox, so you ha-e plenty, ,ut cannot get it out 9eru$ 4e"low5 )I3C"low (high 4e 9)'2;9 " decrease transferrin syn! 7 sat " low, seru$ ferritin " high )herefore, $ain test to distinguish AC?C fro$ 4e def " seru$ 4erritinM J. +i%* a%p)a an* -e!a !)a% &'2+A8 4e studies ,:c nothing to do with 4e, ,ut glo,in chains. 8. <i*ero-%as!i D ie s$ear without appropriate a$ount of ., in the cells, therefore, they are $ore than li%ely to ,e a $icrocytic ane$ia (4e def, AC?C, thalasse$ia, lead poisoning!. 9lide: ringed sidero,last (only seen in 3+, and is stained with *russian ,lue, which stains 4e ,:c $ito around the nucleus, all filled up with 4e called a ringed sidero,last this is pathogno$onic of a sidero,lastic ane$ia!. 9o if you thin% that 3A is causing the ane$ia, need to pro-e it. &eed to get 3+5 if you thin% alcohol is the cause, you ha-e to pro-e it. L. Lea* poisoning If you suspect lead poisoning5 just do a lead le-el (not a 3+ exa$!. cells with ,lue spots called ,asophilic stippling. ?o not need a special stain to see ,asophilic stippling (shows up on gie$sa stain!. 9ee ,lue dots lead denatures ri,onuclease, and the purpose of ri,onuclease is to ,rea% down ri,o1s5 if is denatured, and doesn1t ,rea%down, ri,oso$e persists. )herefore, they gi-e a great $ar%er in the peripheral ,lood ,asophilic stippling. If it1s an 2&A fila$ent, tal%ing a,out reticulocyte. If we were tal%ing a,out persistent ri,o " lead poisoning. 'n xDray epiphyses of finger of child5 only hea-y $etal that can deposit in the epiphysis of ,one is lead ($ercury cannot, arsenic cant, only lead can!. )herefore, can see deposits in epiphyses. )his is why they ha-e failure to grow. If you screw up the epiphyses of the %id, they will not ,e a,le to grow properly. Clinical scenario child eating paint:plaster leads to lead poisoning, ha-e se-ere a,do$inal colic, pro, with cere,ral ede$a, con-ulsions, se-ere $icrocytic ane$ia, see lead in intestines (flat plate!. Bou1ll see 4e in the intestines5 three things can cause this is 4e ta,lets ingested in a %id, lead, $ercury!. Also, there is a failure to thri-e. +echanis$ of cere,ral ede$aN 2elated to increased -essel per$ea,ility of ,rain and ,uildup of deltaDle$a-inylinic acid. If you ,loc% ferrochelatase, e-erything distal to the ,loc% will increase (protoporphyrin, deltale$a-inylinic acid! this is toxic to neurons, leading to cere,ral ede$a. ;xa$ple: guy at an auto$o,ile shop, co$plains of a,do$inal colic and diarrhea. )his is lead poisoning ,:c exposure to ,atteries. In plants, there is exposure to incineration of ,atteries, and pts are exposed to lead in auto factories ;xa$ple: $oonshine $a%e alcohol in old radiators, leads to lead poisoning ;xa$ple: pottery painter pottery is co$$only painted with lead ,ased paints. A lot ti$es they lic% the tip of the ,rush, and leads to lead poisoning. ;xa$ple: in certain country, they use leadD,ased pottery for dishes, which leads to lead poisoning. Adults will get the neuropathies slapping gait (perineal palsy!, wrist drop (radial palsy!, claw hand (ulnar palsy!, lead lines in teeth (usually get with colic and diarrhea! +. 9e7TI(C7Psa!7'erri!in: 4e def: l, h, l, l AC?C: l, l, l, h Alpha:,eta thal: n, h, h, h, do nothing a,out it 8ead poisoning (and sidero,lastic ane$ias 4e o-erload li%e he$ochro$atosis!: ., l, h, h ()I3C is low ,:c 4e stores are highM! in 4e o-erload e-erything is high, )I3C is 8'G Anemia Iron ?eficiency Ane$ia Ane$ia of Chronic ?isease Alpha and 3eta )halasse$ias 8ead o-erload w: he$ochro$atosis Iron 8'G 8'G &8 .IL. TI(C .IL. 8'G .IL. 8'G P sa!&ra!ion 8'G 8'G .IL. .IL. 9erri!in 8'G .IL. .IL. .IL.
Audio ?ay 0: .e$atology 4ile 0 .III. +a ro y!i anemias 31( and folate are in-ol-ed in ?&A synthesis, therefore, if you are 31( and:or folate def, you cannot $a%e ?&A, specifically ,:c you ha-e a pro, with $a%ing ?+* (deoxythy$idine $onophosphate!. )herefore, if you cannot $a%e that, you cannot $ature the nucleus (i$$ature nuclei do not ha-e a lot of ?&A in the$, ,ut as you $a%e $ore ?&A, the nuclei ,eco$e $ore $atured, and the nucleus ,eco$es s$aller and $ore condensed!. 3:c ?&A cannot ,e $ade, then you ha-e large nucleus, and all nucleated the cells in your ,ody are ,ig why they are called +E:A%o-%as!i anemias. A good pathologist can dx 31( and
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folate def in a cer-ical pap s$ear, when loo%ing at the s#ua$ous cells (cells loo% ,ig any cell with a nucleus has ?&A in it, so any cell with ?&A will ,e ,ig not just the he$atopoeitic cells that are huge, A88 nucleated cells in the ,ody are ,ig ie LI, s#ua$ous cells! 31( a%a co,ala$in5 31( has co,alt in it. Circulating for$ of folate is $ethyltetrahydrofolate (tetra " four!. *urpose of co,ala$in (31(! is to ta%e the $ethyl group off of $ethyltetrahydrofolate. )hen it1s called tetrahydrofolate. If you don1t get the $ethyl group off of folate, you will not $a%e ?&A. 9o, if you are 31( def, you can1t get the $ethyl group off and cannot $a%e ?&A. If you are def in folate, you can1t $a%e ?&A. Co,ala$in adds a $ethyl to group ho$ocysteine5 when you add a $ethyl group to ho$ocysteine, it ,eco$es $ethionine. +ethionine " aa for 1 car,on transfer rxns. (+ethyl " C.0!. If you are 31( or folate def, what are the seru$ ho$ocysteine le-elsN .igh. Gith a )ig) ser&m )omo ys!eine@ i! pro*& es !)rom-oses@ in %&*ing +I#sI i! *amages en*o!)e%ia% e%%s@ %ea*ing !o !)rom-oses@ an* pre*isposing !o +I. 9o, what is +CC of increased ho$ocysteineN It is &') ho$ocystinuria (rare auto rec dC!, ,ut 31( def or folate def, and folate is +C than 31(. )herefore, the +CC of increased ho$ocysteine is folate def, and ha-e an increased incidence of thro$,osis and +I. )his is why cardiologists order seru$ ho$ocysteine le-els. In folate def, no $ethyl group to add to ho$ocysteine (so ho$ocysteine increases!5 with 31( def, no $ethyl group to add to $ethionine to $a%e ho$ocysteine therefore $ethionine increases. )etrahydrofolate is the start of the cycle, and leads to production of thy$idilate synthase this is where ?&A is $ade. ?<+* is con-erted to ??), $a%ing ?&A. )herefore, this su,strate is necessary to $a%e ?&A. 9o, it is used in the $a%ing of ?&A ,y an enCy$e called dihydrofolate reductase which con-erts oxidiCed dihydrofolate to tetrahydrofolate. +any drugs ,loc% dihydrofolate reductase $ethotrexate, )+*D9+H. )he drugs ,loc% ?&A synthesis (ie decreasing ?&A synthesis! there,y leading to $acrocytic ane$ia. 9o, the functional 31( ta%es the $ethyl group fro$ tetrahydrofolate and gi-es it to ho$ocysteine to $a%e $ethionine. And tetrahydrofolate will start the cycle for $a%ing ?&A. A. (1" 1. 31( 2eactions: 31( is hu$iliated ,y ha-ing to transfer $ethyl groups. )his is an odd re#uest so whoe-er he as%ed said that they can ta%e care of e-en chained 4A1s, ,ut we ha-e a pro,le$ with '?? chained 4A1s ,:c we can only ,rea% down till proprionyl CoA, which leads to de$entia and proprioception loss. (1" )e%ps in o** )ain 9A me!a-o%ism . )herefore, it is in-ol-ed in proprionate $eta,olis$, which is $eta,olis$ of an odd chain 4A. *roprionate for$s $ethyl$alonyl CoA, where 31( co$es in and helps con-ert $ethyl$alonyl CoA to succinyl CoA, which can go into the )CA cycle. In 31( def, certain things will ,uild up, such as proprionate and $ethyl$alonyl CoA. +ethyl$alonyl CoA ,eco$es $ethyl$alonlylic acid, which is a sensiti-e and specific test for 31( def. 9o, with 31( def, get a $ethyl$alonlylic acid test (which will ,e increased!. 2eason for neurological pro,le$s is ,:c proprionate $eta,olis$5 without 31(, cannot con-ert odd chain 4A1s into succinyl CoA, and they ,uild up, and it screws up $yelin (cannot syn $yelin! and leads to de$yelination of posterior colu$ns, and of the lateral corticospinal tract, along with de$entia. 3:c it is a posterior colu$n dC, you will ha-e pro,s with proprioception, -i,ration5 ,:c you %noc% off the lateral cortical spinal tract, you will get <+& lesions (spasticity, ,a,ins%i!, and then de$entia. Gill always tell you that you can ha-e 31( def, and correct the ane$ia with high doses of folate, ,ut cannot correct the neurologic dC. )herefore, $ust $a%e the specific dx. 3:c if you thin% its folate def and gi-e folate, you will correct the he$atologic pro,le$, ,ut not the neurological pro,le$, therefore ha-e 31( def. 9o, in *i''eren!ia% o' *emen!ia, include 31( def (along with AlChei$er1s!. Bou don1t ha-e to ha-e ane$ia with 31(, ,ut can ha-e neurological pro,s. 9o, with de$entia, get a )9. le-el (to throw out hypothyroidis$!, and a 31( le-el to rule out 31( def ,:c these are 2;K;29I38; causes of de$entia. *ure -egan -s. o-oDlacto-egan: In o-oDlacto-egan ta%ing dairy products (which are ani$al products!, therefore, do not ha-e to ta%e 31( supple$ents. .owe-er, a pure -egan does ha-e to ta%e 31( supple$ents. (. &or$al se#uence of 31( a,sorption: .a-e to eat $eats or dairy products to get 31(. )he first thing 31( does is ,inds to 2 factor in sali-a. 2 factor protects 31( fro$ destruction ,y acid in the sto$ach. Intrinsic factor (I4! $ade ,y parietal cells in the ,ody fundus5 they also $a%e acid. I4 is not destroyed ,y acid, therefore does not need anything to protect it. 9o the 31(:2 factor co$plex goes into the duodenu$, where there is I4 waiting for it. 2 factor $ust ,e clea-ed off, which is done with enCy$es fro$ the functioning pancreas. )hen, I4 and 31( ,ind to e:o and ta%e a long trip. ?o not go to duodenu$ (4e country!, do not go to liga$entu$ of trietC in the jejunu$ (folate country!5 so they go all the way to the ter$inal ileu$, where there are receptors for I4, and it is rea,sor,ed. )his is the sa$e place ,ile salts are rea,sor,ed, and the sa$e place the Crohn1s dC hits. )herefore, it is fair to say that with Crohn1s dC, you also ha-e ,ile salt rea,sorption pro,le$s and 31( def. 0. Causes of 31( deficiency: a0 +CC (1" *e' , perni io&s anemia5 this is an autoi$$une dC with destruction of the parietal cells5 autoA,1s attac% the parietal cells and there are autoA,1s against I4 and destroys the parietal cells which are located in the ,ody and fundus. ;-erything gets destroyed leading to an atrophic gastritis of the ,ody and fundus. &o parietal cells " no acid " achyloridria, and no I4. Achyloridria is a $ajor predisposing factor for gastric adenocarcino$a. ,! Causes of 31( def: pure -egan5 chronic pancreatitis seen in alcoholics (this leads to 31( def ,:c can1t clea-e off the 2 factor!5 ?. latu$ (fish tapewor$ that eats 31( (rarest! fro$ fish in la%e trout in la%es of Chicago!5 ter$inal ileu$ dC (Crohn1s!. And ,acterial o-ergrowth due to peristalsis pro, and:or di-erticular pouches and:or stasis. Ghene-er there is stasis you1ll get ,acterial infection (also ,ladder infection!5 ,acteria lo-e 31( and ,ile salts with ,acterial o-ergrowth. All of these will lead to 31( deficiency.
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(. 9o%a!e 4olate is seen in ani$al and plant products, therefore not seen in -egans. 4olate has $any phar$ ties (ie dihydrofolate reductase!. Ghen you eat folate, it1s in a polygluta$ate for$, $eaning you cannot rea,sor, it in the jejunu$5 therefore it has to ,e con-erted to a $onogluta$ate for$. Intestinal conjugase (in the s$all intestine! is responsi,le for this. 5)a! *r&g -%o 6s in!es!ina% onQ&gaseE P)eny!oin. 9o, if they as% a,out pt on *henytoin, with $acrocytic ane$ia, hyperseg$ented neutrophils, neurological effects are &') present therefore folate def (,:c there are no neurological pro,le$s, this r:o ,1( def.! &ow you ha-e $onogluta$ate, which is a,sor,ed in the jejunu$. )here are ( things that inhi,it its a,sorption: (1! ,irth control and ((! alcohol /+CC 'o%a!e *e' , a% o)o%ism0. Gith 31(, ha-e ADR year supply in li-er, therefore its unco$$on to get. 4olate only has 0D> $onth supply so, e-en if you ha-e an excellent diet, you can ha-e folate def if you are ta%ing one of these two things. 9u$$ary: circulating for$ of folate is $ethyltetrahydrofolate, and 31( ta%es the folate off, and gi-es it to ho$ocysteine which ,eco$es $ethionine5 the $ethyltetrahydrofolate ,eco$es tetrahydrofolate, and with the help of dihydrofolate reductase, ?&A is $ade. ;xa$ple: pic with hyperseg$ented neutrophil (definition: E or $ore lo,esM!. .yperseg$ented neutrophil indicates 31( or folate def, e-en if you don1t ha-e ane$ia. It is the first thing that co$es up ,efore ane$ia. And if the neurological test is nor$al, it1s a folate def. )est for proprioception: 2ho$,erg test if you ha-e post colu$n dC, pro, with proprioception ,:c do not %now where your joints are5 does not show cere,ellar ataxia (will ha-e these with eyes opened A&? closed!. <se -i,rating tuning for% to see if pt has proprioception on the $alleous. .e$atopoetic cells are $ade outside the sinusoids in the 3+. It1s analogous to the cords of ,ilroth in the spleen (where there are fixed $acrophages and then, the 23C1s and G3C1s ha-e to get ,ac% into the sinusoids and circulate through holes. )hey get through, and are in sinusoids!. )he sa$e thing occurs in the 3+ they ha-e a place e#ui-alent to the cords of ,ilroth and that is where they are $ade. )o get into the circulations, they ha-e to fit through lil, narrow holes to get into the sinusoids in the 3+ and into the ,lood strea$. 9o$ething -ery ,ig will not ,e a,le to get through the lil holes and into the sinusoids. )herefore, $acrophages will want to feast on the $acrocytic cells (G3C1s, 23C1s, platelets! that cannot get into the sinusoids. 9o, the $acrophages %ill the$ all. 9o in the peripheral ,lood, will see &').I&L pancytopenia5 se-ere $acrocytic ane$ia, neutropenia, thro$,ocytopenia which is characteristic of 31( :folate def. (e-erything in the $arrow is too ,ig and cannot get out into the circulation!. < )i%%ing#s !es! good test for localiCing 31( def. Ge %now now that it1s a 31( deficiency, and we want to %now what caused it. 9teps for schilling test: Li-e radioacti-e 31( ,y $outh5 they then collect the (> hr urine to see if any co$es out in the urine and nothing co$es out, therefore pro-e that they ha-e a pro,le$ a,sor,ing 31(. 1st step: gi-e radioacti-e 31( and I4, collect urine for (> hrs, and piles in the urine " *ernicious ane$ia5 ,:c added what was $issing (I4!5 if it didn1t wor%, you can ;HC8<?; pernicious ane$ia. 9ay this didn1t wor%, then you: (nd step: gi-e 16 days worth of ,road spectru$ anti,iotic5 pt co$es ,ac% and again you gi-e the$ radioacti-e 31(5 see piles of radioacti-e 31( in the urine, what is dxN 3acterial o-ergrowth ,:c %noc%ed off the ,ugs eating 31( 9ay this didn1t wor%, then you: 0rd step: pancreatic extract, swallow pills, then gi-e radioacti-e 31(5 (> hrs later, see what happens5 if there is radioacti-ity in urine, pt has chronic pancreatitis. If that didn1t wor%, could ,e Crohn1s, wor$, etc. 9u$$ary: If 31( $ala,sorption was corrected ,y adding I4, pt has pernicious ane$ia If 31( corrected ,y adding an anti,iotic, pt has ,acterial o-ergrowth If 31( is corrected ,y adding pancreatic extract, pt has chronic pancreatitis. IG. Normo y!i anemias Ghen you do the corrections for the ane$ia and loo% for polychro$asia5 if correction is less than (7, it is a ,ad response (3+ not responding correctly!. 4irst two things you see: early I?A and AC?C re$e$,er that you ha-e to ha-e a nor$ocytic ane$ia first to ,eco$e $icrocytic. ?oesn1t occur o-ernight. )herefore, with a decreased ret ct (ie less than (7!, $ust include $icrocytic ane$ia1s in the differential, and you need to get a ferritin le-el. I?A goes through diff stages: first thing that happens decreased ferritin, then 4e decreases, )I3C increased, 7 sat decrease, and still won1t ha-e ane$ia. In other words, all 4e studies are A3&'2+A8 ,efore you ha-e ane$ia. )hen you get $ild nor$ocytic ane$ia, and e-entually $icrocytic ane$ia. A. Ca&ses: 1. 3lood loss less than a wee% " nor$ocytic ane$ia5 no increase in ret response ,:c nothing wrong with the 3+, and not enough ti$e (need ED@ days for 3+ to get re-1d up! so, after one wee%, would get an appropriate response. (. Aplastic ane$ia no $arrow5 if that is true, the peripheral ,lood will show pancytopenia (all he$atopoetic cells are destroyed in the $arrow!5 ha-e nor$ocytic ane$ia, thro$,ocytopenia, and neutropenia.
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0. +C %nown C " drugs: chlora$phenical used in roc%y $tn spotted fe-er, indo$ethacin, phenyl,utaCone, and thyroid related drugs >. (nd +CC " infections esp. .ep C (wipes out e-erything!5 aplasia of 23C " par-o-irus E. 2adiation and $alignancy A. ;arly I?A and AC?C (need to ha-e seru$ ferritin le-els! @. +echanis$ of nor$ocytic ane$ia with less then (7 ret ct renal failure, and decreased ;*' (can ,e gi-en exogenously! decreased in hep 3, C, and .IK. Athletes that =dope1 are gi-en ;*', to increase 23C1s to allow $ore ' ( deli-ery to ,ody (. +e )anisms o' )emo%ysis = " 3ays !o 6i%% an R(C: &or$ocytic ane$ias with correcti-e ret ct a,out 07: 1. ;xtra-ascularly (outside of the 3K!. )hey are %illed ,y $acrophages, usually in cords of ,ilroth in the spleen, so$eti$es in li-er sinusoids. ;-ery 23C $ust go to the cords of ,ilroth a few ti$es per day and get exa$ined ,y a $acrophage if the cell pic%ed up an IgL or C0,, it is $ar%ed for destruction -ia phagocytosis ,:c the $acrophage has receptors for IgL and C0,. If you don1t ha-e IgL or C0,, can still die ,:c the cell is in ,ad shape a,nor$al shape: ie sphere will not ,e a,le to fit through a ( $icron hole to get to the sinusoids it can1t therefore, spherocytes are re$o-ed extra-ascularly ,:c they cannot get out5 sic%le cells cannot get out either ,:c they ha-e a ,ad shape. Another reason for their destruction is ,:c they ha-e so$ething inside the$ that they shouldn1t a piece of nucleus5 what is this calledN .owell jolly ,ody5 $acrophage will get rid of it. )here are autoi$$une he$olytic ane$ias, and can ,e due to IgL or C0, on the surface of the 23C, or extra-ascular he$olytic ane$ias is where you ha-e a,nor$al shape (ie sphere, 9ic%le cell will not $a%e it out of the spleen ,:c re$o-ed ,y $acrophages!. ;nd product of phagocytosing an 23C: unconjugated ,iliru,in. Ghen the 23C is ,ro%en down, you ha-e he$oglo,in, and there is an enCy$e that splits he$e fro$ glo,in and the glo,in is ,ro%en into aa1s and therefore goes to the aa pool. )hen, ta%es the he$e, splits it open, and sa-es the 4e. &ow you ha-e protoporphyrin, and spit it out5 end result is unconjugated ,iliru,in in the $acrophage within the spleen. )hen, the $acrophage spits out the unconjugated ,iliru,in into ,lood strea$ (which is insolu,le ,:c it1s unconjugated!. )he unconjugated ,iliru,in then ,inds al,u$in and goes to the li-er and is conjugated. 9o, what clinical finding will you see in pts with extra-ascular he$olytic ane$iaN Faundice. ?oes that ,iliru,in get into the urineN &o. GhyN ( reasons: (1! 8ipid solu,le and ((! 3ound to al,u$in (al,u$in does not get into the urine! so you are jaundiced, ,ut doesn1t get into the urine (. Intra-ascular (within the 3K! Intra-ascular is less co$$on $eaning that you die within the 3K. .ow does that happenN Bou die within the -essel if you ,u$p into so$ething. ;xa$ple: congenital ,icuspid aortic -al-e with calciu$ there if you ,u$p into that, you would da$age yourself and die. ;xa$ple: if you ha-e Ig+ on the surface of the 23C (Ig+ is the $ost potent acti-ator of the co$ple$ent syste$!5 this will go fro$ 1DR, $eaning that it will sit on the 23C, acti-ate the co$ple$ent and dies intra-ascularly5 so, anything that is Ig+ $ediated " intra-ascular he$olysis. 9o, what will you release into the ,loodstrea$ if you are %illing the 23CN .,. ?on1t want to lose all of it and need to retreat it ,y getting ,ac% the aa1s and retrie-ing the 4e. 9pecific protein that is $ade in the li-er that is released when there is intra-ascular he$olysis )ap!og%o-in (a%a suicide protein ,:c for$s co$plex with ., and is phagocytosed ,y the $acrophage!, therefore gi-ing life to retrie-e the .,, therefore in pts with intra-ascular he$olysis, the haptoglo,in le-els decrease. Is it possi,le to get jaundiceN Bes, ,ut usually don1t ,:c $acrophage is phagocytosing. Intra-ascular he$olysis: he$oglo,inuria, and low haptoglo,in le-els 0. 9u$$ary: ;xtra-ascular " $acrophages re$o-e " unconj ,iliru,in is the end product " jaundice is the clinical $anifestation Intra-ascular " ., in urine, decreased haptoglo,in C. In!rinsi 1s. Ex!rinsi Hemo%y!i anemia: 1. Intrinsic so$ething wrong with 23C, causing it to he$olyCe: such as no spectrin, or not decay accelerating factor to neutraliCe co$ple$ent, no LA*? enCy$e in pentose phosphate shunt, or a,nor$al ., (ie .,9!. )herefore, so$ething wrong inside the ., $olecule, causing it to he$olyCe. (. ;xtrinsic nothing wrong with the 23C, just at the wrong place at the wrong ti$e5 ie it just happened to s$ash into the calcified -al-e (nothing was wrong with it, until it hit the -al-e!. )hen it will ,e dreading going to the cords of ,ilroth with destroy it ,:c it has ,een $ar%ed with IgL and C0, for phagocytosis. D. <ome!)ing in!rinsi a%%y 3rong 3i!) !)e R(C a&sing i! !o )emo%y>e ,ut there1s nothing wrong with the 3+ (,ut so$ething intrinsically wrong with the 23C!, and the correcti-e ret ct is greater than 07. +AD +C intrinsic pro,s +e$,rane defect (spherocytosis, paroxys$al nocturnal he$oglo,inuria!, A,nor$al ., (9C trait ?C!, Deficiency of enCy$e (LA*? def!. 1. +em-rane De'e !s: /a0 <p)ero y!osis: do no see a central area of pallor therefore $ust ,e a spherocyte and $ust ,e re$o-ed extra-ascularly. Clinically $anifest with jaundice fro$ unconjugated ,iliru,in. 9pectrin defect and A? dC5 spleno$egaly always seen o-er a period of ti$e. Lall,ladder (L3! dC is co$$on ,:c there is a lot $ore unconjugated ,iliru,in presented to the li-er and $ore conjugation is occurring and $ore ,iliru,in is in the ,ile than usual. 9o, whene-er you supersaturate anything that is a li#uid, you run the ris% of for$ing a stone5 if you supersaturate urine with Ca, you run the ris% of getting a Ca stone5 if you supersaturate ,ile with cholesterol, you will get a cholesterol
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stone5 if you supersaturate with ,iliru,in, you will get a CaD,iliru,inate stone. )herefore, pts ha-e L3 dC related to gallstone dC and then do a C3C with nor$ocytic ane$ia and a corrected ret ct that is ele-ated, and see ongeni!a% sp)ero y!osis. Ghat1s the diagnostic testN 's$otic fragility they put these 23C1s wall to wall in different tonicities of saline, and the 23C1s will pop (therefore ha-e an increased os$otic fragility!. 2x: splenecto$y (need to re$o-e organ that is re$o-ing the$ they will still ,e spherocytes and will not ,e a,le to for$ a ,iconca-e dis%!. /-0 Paroxysma% No !&rna% Hemog%o-in&ria " defect in decay accelerating factor. 9o when we sleep, we ha-e a $ild resp acidosis ,:c we ,reathe slowly (if you ha-e o,structi-e sleep apnea, the acidosis is worse!. Ghen you ha-e acidosis that predisposes the co$ple$ent that1s sitting on A88 cells circulating in peripheral ,lood. 23Cs, G3Cs, and platelets all ha-e co$ple$ent sitting on it. )here is no co$ple$ent destruction of these cells ,:c in our $e$,ranes we ha-e delay accelerating factor. )his factor causes increased degradation of the co$ple$ent so it doesn1t ha-e an opp to drill a hole in our $e$,rane, therefore we don1t wa%e up in the $orning with he$oglo,inuria, neutropenia and thro$,ocytopenia. 9o, if you are $issing decay accelerating factor, the co$ple$ent will ,e acti-ated and goes fro$ C1DR, leading to intra-ascular he$olysis. )hin% a,out the na$e (paroxys$al nocturnal he$oglo,inuria!: occurs at night, and when you wa%e up in the $orning, you pee out he$oglo,in. 9o, when you do a C3C, not only ha-e a se-ere ane$ia, ,ut also a neutropenia and a thro$,ocytopenia: pancytopenia!. ". A-norma% H-: <i 6%e Ce%% Trai!7D> Gith sic%le cell trait, there is &' ane$ia and &' sic%led cells in the peripheral ,lood. Bou can ha-e sic%led cells in a certain part of your ,ody in the renal $edulla within the peritu,ular capillaries (decreased '( tension!, ,ut not in the peripheral ,lood. )his is ,:c in 9C?C, the a$ount of sic%led ., in the 23C deter$ines whether it sic%les or not. +agi R , AFP5 if you ha-e A67 or $ore, .,9 can spontaneously sic%le. 'xygen tension in the ,lood also deter$ines whether a cell will sic%le or not. At lower '( tensions, cells are $ore li%ely to sic%le. )his is an auto rec dC, $eaning that ,oth parents $ust ha-e a,nor$al gene on their c1so$e (so its ( traits!5 therefore, (E7 co$plete nor$al, E67 heteroCygous asy$pto$atic carrier, (E7 co$plete dC (sa$e with cystic fi,rosis!. <C Trai! 1s. <CD>: (a! In si 6%e e%% !rai!, ,lac% indi-idual with nor$al *; and nor$al C3C, ,ut $icroscopic he$aturia, the first step is sic%le cell screen ,:c $icroscopic he$aturia is A8GAB9 a,nor$al and $ust ,e wor%ed up ,ut in ,lac%s " 1:T people ha-e the trait. 9o, 9C trait is what you are thin%ing of5 not renal stones, or IgA glo$erulonephritis, ,ut is 9C trait nor$ally. (,! <CD> ( things are happening: .e$olytic ane$ia (usually extra-ascular! can ,e -ery se-ere and co$$only re#uires a transfusion and 'cclusion of s$all 3K1s ,y the sic%led cells (,loc%age of circulation! lead to -asooclusi-e crisis, and this ische$ia leads to pain. )herefore, they are painful crisis (occur anywhere in the ,ody lungs, li-er, spleen, 3+, hands:feet (,actulitis!!. '-er ti$e, it leads to da$age of organs %idneys, spleen autoinfarcted (autosplenecto$y! in first 16 years of life, pt will ha-e spleno$egaly ,:c trapped 23C1s, and e-entually autosplenecto$y around age 1R (spleen will ,e the siCe of a thu$,!. After ( years, it is nonfunctional so e-en though you ha-e a ,ig:swollen spleen, it isn1t wor%ing. .ow will you %now what that has happenedN .owell Folly ,ody (23C with a piece of nucleus that should not ,e in the spleen if the spleen were wor%ing, a fixed $acrophage would ha-e ta%en care of it!. )his occurs at a,out ( yrs of age. )his is fortunate ,:c this is a,out the age where you can get pneu$o-ax. Gith a nonfunctional spleen what infection is guaranteedN 9trep pneu$oniae sepsis. +CC *ea!) in )i%* 3i!) <CD> , s!rep pne&moniae sepsis. )hey try to co-er with anti,iotics and pneu$o-ax pneu$o-ax can ,e gi-en at the age of ( and that1s a,out the ti$e when the spleen stops wor%ing (start to see .owell jolly ,odies!. 9lide with .owell jolly ,ody and slide with sic%led cells, then will as%, what1s wrong with the spleenN It1s dysfunctional5 .owell jolly would ha-e ,een re$o-ed if the spleen is functional. Ghen do they get their first sic%le cell crisisN Ghen little %ids gets painful hands, and are swollen up (called ,actulitis! does not occur at ,irth, ,:c .,4 inhi,its sic%ling and new,orns in new,orns, @6DT67 of their 23C1s are .,4. In 9C?C, A6D@67 23C1s ha-e .,4, while the rest are .,9M At this stage, there is enough .,4 to inhi,it the sic%ling5 howe-er, as the 23C1s are ,ro%en down and replaced, the .,4 decreases and .,9 increases, and ,y ADR $onths of age, there is a high enough concentration to induce sic%ling and their first -asooclusi-e crisis, producing ,actulitis. 9o, ,actulitis doesn1t co$e until ADR $onths ,:c .,4 inhi,its the sic%ling. 3one infarctions occur fro$ sic%ling the 3+. 'steo$yelitis these pts are suscepti,le to osteo$yelitis fro$ sal$onella due to a dysfunctional spleen. 9al$onella is destroyed ,y $acrophages. )he spleen nor$ally filters out sal$onella, ,ut is dysfunctional. +CC osteo$yelitis is staph, ,ut +CC in 9C?C pt " sal$onella. Ghat drug is used to decrease the incidence of -asooclusi-e crisesN .ydroxyurea. .ow does it wor%N It increases .,4 synthesis. $. De'i ien y o' en>yme: :APD *e'i ien y LA*? def is HDlin%ed recessi-e. +ost enCy$e def1s are auto recessi-e ie *K<, al,inis$, ho$ocystinuria!. Ghat are the two HDlin%ed recessi-e enCy$e def1sN LA*? def and 8eschD&yhan syndro$e (in-ol-es purine $eta,olis$ with $ental retardation, self $utilation, increased uric acid, def of .L*2)!.
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Llucose A phosphate has se-eral functions: (1! to $a%e glutathione, ((! to $a%e ri,ose E car,on sugars for $a%ing ?&A, and (0! to $a%e glycogen fro$ LA* (con-erted to L1*, <?*Dglucose and glycogen!. Key: with this enCy$e, we can $a%e &A?*., which is the $ain factor for $a%ing ana,olic types of ,ioche$ical rxn (ie steroid synthesis!. &A?*. will reduce oxidiCed glutathione to glutathione5 its jo, is to neutraliCe peroxide to water. Ghich -ita$in catalyCes this rxnN 2i,ofla-in. Ghich enCy$e helps glutathione neutraliCe peroxideN Llutathione peroxidase. Ghich trace $etal is in-ol-edN 9eleniu$. ;-ery li-ing cell $a%es peroxide as an end product, therefore e-ery cell $ust a way to handle it. Catalase present in all cells except 23C1s and it can neutraliCe peroxide. It is stored in peroxiso$es. 'ther way to neutraliCe peroxide is with glutathione (only thing a-aila,le to 23C1s ,:c they don1t ha-e catalase!. 9o, if you are deficient in this enCy$e, there is a pro,le$. 9o, peroxide increases to the point of he$olyCing 23C1s why would that occurN 3:c if you had an Infection, or if you too% an oxidiCing drug (ie sulfa drug, nitryl drug!, which will lead to a lot $ore peroxide lying around. *eroxide will not ,e a,le to ,e neutraliCed if you are deficient in catalase. 9o, what will happen is the peroxide will affect the .,. )he peroxide will cause the ., to clu$p and for$ .einC ,odies (., clu$ped up together!. Gill also affect the 23C $e$,rane ,:c it da$ages the $e$,rane so $uch that the pri$ary $echanis$ of destruction is intra-ascular. 8ittle ele$ent is extra-ascular, ,ut $ostly intra-ascular. It is precipitated ,y infections and:or drugs. " +C *r&gs: 10 prima;&ine $issionary got $alaria, recei-ed a drug, and (D0 days later the got he$oglo,inuria, chills, and a he$olytic ane$ia (this is pri$a#uine induced he$olysis!. "0 Dapsone is used in treating leprosy5 e-ery person with leprosy is gi-en a screen for LA*? def ,:c of the high incidence of producing he$olysis. 9ee this dC in the sa$e population as 3eta thal ,lac%s, Lree%s, Italians. 9lide: s$ear with acti-ely he$olyCing ,lood cells Hein> -o*ies when it goes into the cords of ,ilroth, the $acrophage will ta%e a ,ig ,ite out of it and so$eti$es, is a s$all ,ite out of the $e$,rane, and the cell goes to the peripheral circulation and is called a I-i!eD e%% (23C with little $e$,rane!. &eed to do special stains to I? .einC ,odies. In Lree%s or Italians with se-ere for$s of LA*? def, they can eat fa-a ,eans which can precipitate an episode (a%a fa-is$!. Dx when you ha-e an acute he$olytic episode, the last thing you want to get a diagnosis is to get an enCy$e assay. GhyN 3:c the only cells that are he$olyCed are the ones $issing the enCy$es. )he ones that ha-e the enCy$e are still gonna ,e there, so you ha-e a nor$al assay. 9o, &;K;2 use enCy$e assays for acti-e he$olysis. &eed to special stain to I? the .einC ,ody. Ghen the he$olytic episode is o-er that1s when the dx is confir$ed, this is done with a LA*? assay. 5i%% ge! a ;&es!ion on :APD *e'i ien y@ ei!)er *apsone re%a!e* or prima;&ine re%a!e*. G. A&!oimm&ne )emo%y!i anemias Gar$ reacting anti,odies are IgL and cold reacting is Ig+ +C autoi$$une he$olytic ane$ia " war$5 +CC of it " 8upus Ghen you ha-e autoi$$une dC in your fa$ily, you ha-e certain .8A types that predispose you to that autoi$$une dC. )herefore, you should not ,e surprised if you ha-e one autoi$$une dC you1re li%ely to ha-e another. 9o, pts with lupus co$$only also ha-e autoi$$une he$olytic ane$ia, autoi$$une thro$,ocytopenia, autoi$$une neutropenia, and autoi$$une ly$phopenia. 4or exa$ple: the +CC of hypothyroidis$ " hashi$oto1s thyroiditis5 these pts co$$only ha-e other autoi$$une dC1s ie pernicious ane$ia, -itiligo, autoi$$une destruction of $elanocytes!. 9o, if you ha-e one autoi$$une dC, you are li%ely to ha-e others (ie if you ha-e a he$olytic pro,, it is pro, autoi$$une related!. )his is ,:c of the .8A relationship. )herefore, if you ha-e a fa$ily that has an autoi$$une dC, what would ,e the single ,est screening test to useN .8A (ie if they ha-e the .8A type specific for lupus there are specific .8A1s for diff dC1s!. )herefore, .8A is the ,est way to see if pt is predisposed to so$ething. +CC a&!oimm&ne anemia , L&p&s5 it has IgL and C0, on the surface of the 23C, so it will ,e re$o-ed ,y the $acrophage. )his is an extra-ascular he$olytic ane$ia. .ow do we %now that there are IgL or C0, A,1s on the surfaceN Dire ! Coom-#s !es!: detect ?I2;C)8B the presence of IgL and:or C0, on the surface of 23C1s. Indirect coo$,s is what the wo$en get, when they are pregnant and they do an A, screen on you (loo%ing for any %ind of A,!5 so, when you loo% for A, in the seru$ (&') on 23C, on 9;2<+!, this is an indirect Coo$,s. )herefore, another na$e for the indirect Coo$,s " A, screen5 with direct coo$,s, we are detecting IgL and:or C0, on the 9<24AC; of 23C1s. you cannot do direct coo$,1s on platelets or neutrophils, ,ut only 23C1s. <o@ !)e !es! o' )oi e i' yo& s&spe ! an a&!oimm&ne )emo%y!i anemia is Coom-#s !es!. A. Dr&g in*& e* a&!oimm&ne )emo%y!i anemias: )here are 0 types of drug induced he$olytic ane$ia ((nd +CC autoi$$une he$olytic ane$ia " drug induced5 +CC " lupus! 1. PCN $echanis$: the ,po group of *C& attaches to 23C (lil piece of *C& is attached on 23C $e$,rane!. )his is ,ad if an IgL A, de-elops against it ,:c if it does, than the IgL attaches to the ,po group, goes to the spleen and is re$o-ed extra-ascularly5 this is an ie of type II .*B ;xa$ple: pt on *C& de-elops a rash what type of .*BN )ype I. ;xa$ple: *t on *C& de-elops a he$olytic ane$ia what type of .*BN Type II ". +e!)y%*opa a%a aldo$et. <se: antiD.)& for pregnant wo$an (other antiD.)& used in pregnancy " hydralaCine!. +ethyldopa and hydralaCine ha-e co$plications $ethyldopa can cause a he$olytic ane$ia5 hydralaCine can lead to drugDinduced lupus ((nd to procaina$ide for drug induced lupus!. +ethyldopa wor%s differently fro$ *C&: $ethyldopa $esses with 2h Ag on surface of 23C and alters the$. )hey are altered so $uch that IgL A,1s are $ade against the 2h Ag (our 'G& 2h Ag!. 9o, the drug is not sitting on the $e$,rane, it just causes for$ation of Ig: A,1s and they
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attach to 23C to ha-e $acrophage %ill it what type of .*B is thisN Type II. )herefore, $ethyldopa and *C& are type II for he$olytic ane$ia. $. S&ini*ine: this is the =innocent ,ystander1 ,:c i$$une co$plexes are for$ed. Puinidine acts as the hapten, and the Ig+ A, attaches5 so, the drug and Ig+ are attached together, circulating in the ,loodstrea$. )his is a different HPY = !ype III, and will die a different way, ,:c this is Ig+. Ghen Ig+ sees the i$$une co$plex, it will sit it, and acti-ate the classical pathway 1DR, leading to intra-ascular he$olysis, and haptoglo,in will ,e decreased, and in the urine, ., will ,e present. GI. +i roangiopa!)i )emo%y!i anemia 23C1s all frag$ented schistocytes (schisto $eans split!. +CC )roni in!ra1as &%ar )emo%ysis , aor!i s!enosis, in this dC, the cells hit so$ething5 therefore ha-e intra-ascular he$olysis, ., in the urine and haptoglo,in is down. )his is a chronic intra-ascular he$olysis, and you will ,e losing a lot of ., in the urine5 what does ., ha-e attached to itN 4e5 so what is another potential ane$ia you can get fro$ these ptsN 4e def ane$ia. ;xa$ple: will descri,e aortic stenosis (systolic ejection $ur$ur, (nd IC9, radiates to the carotids, 9>, increased on expiration, pro$inent *+I!, and they ha-e the following C3C findings: low +CK, and =frag$ented1 23C1s (schistocytes! this is a $icroangiopathic he$olytic ane$ia related to aortic stenosis. 'ther causes of schistocytes: ?IC (lil fi,rin strands split 23Cs right apart ,:c 23C is -ery fragile!5 thro$,otic thro$,ocytopenic purpura, .<9 see schistocytes. Ghen you ha-e platelet plugs e-erywhere in the ,ody, the 23Cs are ,anging into these things causing schistocytes and $icroangiopathic he$olytic ane$ia. ;xa$ple: runner1s ane$ia, esp. long distance you s$ash 23C1s as you hit the pa-e$ent5 -ery co$$only, you go pee and see ., in it5 to pre-ent, use ,athroo$ ,>. Another cause of he$olytic ane$ia: ma%aria = 'a% ipar&m ,:c you ha-e $ultiple ring for$s (ga$etocyte (co$$a shaped and ringed for$!. It produces a he$olytic ane$ia, which correlates with the fe-er. )he fe-er occurs when the cells rupture (the he$olytic ane$ia!. CHAPTER A. HE+ATOLO:Y: 5(C I. Non?neop%as!i Lymp)oi* Pro%i'era!ions: A. Ne&!rop)i%s when you ha-e acute infla$$ation " ie appendicitis, neutrophilic leu%ocytosis, left shift, toxic granulation, and leu%a$oid rxn. 8eu%a$oid rxn $eans that it loo%s li%e leu%e$ia ,ut it isn1t and it1s ,enign. <sually in-ol-es any of cell lines. Ghat causes leu%a$oid rxnsN )3 and sepsis. Bou see greater than 06DE6,666 cells in the ,lood. Kids get these a lot (ie otitis $edia!. Adult with otitis $ed " 1(,6665 %ids with 06,666 (exaggerated!. ;xa$ple: Per!&ss&s = 3)ooping o&g) = %ymp)o y!osis (A6,666! pediatricians are worried a,out A88 leu%e$ia, ,ut %id doesn1t ha-e ane$ia or thro$,ocytopenia5 %id co$es in pale, coughing. 8y$phocytes are $ature and are totally nor$al. 8y$phocytosis w: -iral infection or with pertussus. In a!ypi a% %ymp)o y!osis this is a ly$phocyte that is doing what it1s supposed to do when presented to and Ag. It1s responding to the Ag ,y di-iding and getting ,igger, so ,asically it1s an antigenic sti$ulated ly$phocyte. Ghen tal%ing a,out atypical ly$phocyte, the a,solute first thing that pops into the $ind is: monon& %eo%osis = E(.. 'ther dC that are seen with large, ,eautifully staining ,luish cells: C+K, toxoplas$osis, any cause of -iral hepatitis, phenytoin. ;3K is called the %issing dC ,:c the -irus holds up in the sali-ary glands. ;3K affects 3 cells and C? (1. +ono causes -ire$ia, generaliCed painful ly$phadenopathy, -ery co$$only get exudati-e tonsillitis, jaundice (hardly e-er seen!, increased transa$inases (off the chart!, and spleen enlarge$ent and can rupture. )herefore don1t play sports ,:c can ruptured spleen can occur, so a-oid contact sports usually for ADT wee%s. Also causes $acrocytic ane$ia -ia inhi,iting intestinal conjugase!. Audio ?ay 0: .e$atology 4ile E ;xa$ple: the ,oards will gi-e you a classic hx of $ono, and as% which tests you run, ,ut $onospot test is not on the choices ,:c that1s the trade na$e, so pic% heterophile anti,odies (hetero " diff, phile " lo-ing!. .eterophile A,1s are antiD horse 23C A,1s (or antiDsheep!5 they are different, hence IheteroJphile A,1s. 'nce you ha-e $ono, you always ha-e it and will ha-e 0D> recurrences o-er your lifeti$e ie reacti-ation consists of swollen glands, -ery tired, etc. ;3K li-es in 3 cells5 the atypical ly$phs in $ono are ) cells reacting against the infected 3 cells. (. +ono y!e " %ing of chronic infla$$ation, therefore expect $onocytosis in pts with chronic infections ie rheu$atoid arthritis, Crohn1s, ulcerati-e colitis, lupus, $alignancy
<i*e No!e: creatine gi-es energy ,:c it ,inds to phosphate, and that is the phosphate you get fro$ $a%ing A)* so what seru$ test is $ar%edly ele-ated in so$eone ta%ing creatine for their $usclesN CreatinineM 3:c the end product of creatine $eta,olis$ is Creatinine. )he 3<& is nor$al in this person. Gorthy ,oard #uestion. C. Eosinop)i%ia Bou would see eosinophilia in .ay fe-er, rash in pt with *C&, strongoloides *rotoCoa infections ?';9 &') produce eosinophilia, therefore it rules out a$a,iasis (pinwor$!, giardia, and $alaria. 'nly in-asi-e hel$inthes produces eosinophilia. Adult ascariasis does &') cause eosinophilia ,:c all they do is o,struct ,owels, it1s when the in-asi-e lar-ae for$ crosses into the lungs that causes eosinophilia. 9o anything that is )ype I .*B causes eosinophilia5 protoCoa do not cause eosinophilia5 ascariasis, and pinwor$s do &') cause eosinophilia (all others ie whipwor$s do ,:c they in-ade!. II. +ye%opro%i'era!i1e D>: Po%y y!)emia increased 23C ct, increased ., and .ct
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?ifference ,etween seru$ &a and total ,ody &aN yes. 9eru$ &a is $illie#ua-alents per liter of plas$a5 total ,ody &a is $illiliters per %g ,ody wt (the total a$ount you ha-e!. 9i$ilarly: R(C mass " total S of 23C1s in entire ,ody in $8:%g in ,ody wt R(C ! " S of 23C1s:$icroliter of ,lood , therefore its how $any you ha-e in a certain -olu$e of ,lood. Ghy is this a ,ig dealN ;xa$ple: went running and -ol depleted 23C ct would ,e he$oconcentrated, therefore would loo% li%e $ore 23C1s per $icroliter of ,lood (,:c you depleted the plas$a -olu$e!, ,ut what would the 23C $ass ,eN &or$al (not actually synthesiCing 23C1s!. 9o, there are ( types of 23C1s: relati-e and a,solute. Re%a!i1e " decrease in plas$a -ol causing an increase in 23C ct, ,ut the 23C $ass is nor$al. A-so%&!e increase is appropriate or inappropriateN Ghen would it ,e appropriateN 9yn of 23C1s tissue hypoxia, so, any source of tissue hypoxia would ,e an appropriate response. ;xa$ple: if you ha-e lung dC, hypoxe$ia, C'*?, high altitude these are ie1s of appropriate polycythe$ias. Ghat if we ha-e nor$al ,lood gases, ,ut didn1t ha-e tissue hypoxiaN )his would ,e an inappropriate polycythe$ia. 9o, there are two things to thin% a,out with in rease* R(C mass: po%y y!)emia r&-i1era, which is an ie of a ste$ cell proliferati-e dC of the 3+, $eaning that the ste$ cells are dictators, and nothing %eeps the$ in chec% a neoplastic dC5 they can ,eco$e leu%e$ias. 9o, it would ,e inappropriate to ha-e nor$al ,lood gases and no e-idence of tissue hypoxia and ha-e an increase in 23C $ass. (! T&mor or ys! 3i!) an ex ess pro*& !ion o' EPO : renal adenocarcino$a $a%ing ;*', causing an increase in 23C $ass this is inappropriate ,:c a tu$or is inappropriately $a%ing it. In su$$ary: polycythe$ia is relati-e or a,solute. 2elati-e $eans that you just lost plas$a -ol (ie fro$ running! with 23C ct increased, and $ass is nor$al. A,solute increase: is it appropriate or inappropriateN Appropriate anything that is a hypoxic sti$ulus for ;*' release. If there isn1t a hypoxic condition causing the ;*' production, then you are ectopically $a%ing ;*' fro$ a tu$or or cyst or you ha-e polycythe$ia ru,i-era (a $yeloproliferati-e dC!. III. +ye%opro%i'era!i1e *> neoplastic ste$ cell dC that has lost all regulation and nothing can inhi,it it any$ore. > dC1s that fit under this definition: 1. *olycythe$ia ru,i-era (. C+8 (only leu%e$ia in this category! 0. Agnogenic $yeloid $etaplasia 3+ is replaced ,y fi,rous tissue >. ;ssential thro$,ocythe$ia where a ste$ cell that $a%es platelets goes craCy and $a%e 1 $illion, A66 platelets for $icroliter, E. +yelodysplastic syndro$e A. Po%y y!)emia r&-i1era: > .1s: 1. Hyper1is osi!y (re$e$,er *ouseau1s law " )*2 " -iscosity:radius>!. Gith polycythe$ia, it will ha-e an increased resistance and )*2 will go up5 it will predispose to thro$,osis, which %ills you thro$,osis of anything ie dural sinuses5 +CC 3udd chiari " hepatic -ein thro$,osis5 coronary artery, 9+K, anything can ,e thro$,osed ,:c ,lood slugging around and this is why phle,oto$y is done. *hle,oto$y is perfor$ed to $a%e you 4e def they want to $a%e you 4e def whyN If you $a%e the$ 4e def, ,:c then it will ta%e longer to $a%e 23C1s, so you purposefully slow down the process. ". Hypo1o%emia only polycythe$ia that has an increase in plas$a -olu$e that $atches the increase in 23C $ass5 none of the other causes ha-e an increase in plas$a -ol (these are $easured with radioacti-e techni#ues!. 9o, it is -ery rare to see an increase in plas$a -ol with polycythe$ia, except for this case. GhyN +yeloproliferati-e dC1s ta%e years and years to de-elop therefore plas$a -ol is a,le to %eep up5 therefore ,oth increase together o-er ti$e. $. His!aminemia all cells are increased: 23C1s, G3C1s, platelets, including $ast cells and ,asophils. ;xa$ple: Classic hx: pt ta%es a shower and gets itchy all o-er ,ody this is a tip off for polycythe$ia ru,i-era whyN +ast cells and ,asophils are located in the s%in and te$perature changes can degranulate $ast cells, causing a release of hista$ine, leading to generaliCed itching (-ery few things cause generaliCed itching ,ile salt deposition in the s%in in pts with o,structi-e jaundice, and pts with $ast cell degranulation!, face is red loo%ing, too ,:c of hista$ine ,:c -asodilatation, leading to $igraineDli%e headaches. 2. Hyper&ri ema ,:c nucleated he$atopoetic cells are ele-ated, they then die, and the nuclei ha-e purines in the$. )he purines will go into purine $eta,olis$ and ,eco$e uric acid. ;xa$ple: pt on che$otherapy $ust also ,e put on allupurinol to pre-ent urate nephropathy and pre-ent renal failure fro$ uric acid. (allupurinol ,loc%s xanthane oxidase!. Ghen %illing cells you1re releasing $illions of purines when the nucleated cells are %illed and the tu,ules are filled with uric acid, leading to renal failure. +ust put the$ on allupurinol. )his called tu$or lysis syndro$e. )he sa$e thing occurs in polycythe$ia ru,i-era ,:c there is an increase in nu$,er of cells that e-entually die and you run the ris% of hyperurice$ia. (. R(C mass7p%asma 1o%7O" sa!7EPO *olycythe$ia ru,i-era h,h,& (inappropriate!, low (ha-e too $uch '( ,:c you ha-e piles of 23Cs and therefore suppress ;*' (it1s a hor$one!. )he hint was '( content"1.0> O ., O '( sat /p'( C'*?, tetralogy of fallot, high alt ., &, 8, . (appropriate polycythe$ia ,:c it1s responding to hypoxia! 2enal adenocarcino$a, hepatocellar carcino$a, any cyst (renal, esp. ie hydronephrosis, wil$1s tu$or! ., &, &, . (e-en with nor$al gas studies ,:c ectopically produced! 2elati-e *olycythe$ia &, 8, &, & I.. Le&6emias )hey are a $alignancy of the 3+ and $ets anywhere it wants.
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A. :enera% )ara !eris!i s o' Le&6emiaI !)ere'ore@ 3i%% a%3ays )a1e: 1. LeneraliCed ly$phadenopathy, hepatospleno$egaly, etc (. A,nor$al cells in the peripheral ,lood 38A9)9 ($yelo,lasts, ly$pho,lasts, $ono,lasts, $ega%aryo,lasts! so so$e a,nor$al ,lasts are in the peripheral ,lood 0. 3:c it is arising in the 3+, will always crowd out the nor$al he$atopoetic cells, and will A8GAB9 ha-e an ane$ia, usually nor$ocytic >. )hro$,ocytopenia ,:c crowding out the nor$al $ega%aryocytes fro$ $a%ing platelets E. <sually an increase in G3Cs ct with a,nor$al cells present A. Acute -s. chronic ?o a ,one $arrow test and loo% at ,lasts if ,lasts are Y067, this is chronic5 if the 7 ,lasts is U067, it is acute. )herefore the ,last ct tells if its acute -s chronic (. Age -ra 6e!s: 8no3 age -ra 6e!s 6D1> " A88 1ED0R " A+8 $yelo,last with Auer rods in peripheral ,lood >6DER A+8, C+8 (separate with 3+ A+8 with U067 and C+8 with Y067, R, ((, *hilly c1so$e! A6/ " C88 +C o-erall leu%e$ia regardless of age " C88 +CC generaliCed nontender ly$phadenopathy in pt A6/ " C885 not ,:c it1s a ly$pho$a, ,ut ,:c it $ets to ly$ph nodes!. C. Di''eren! Types o' Le&6emia: ;xa$ple: peripheral s$ear of >R y:o, 1E6,666 G3C ct, 17 $yelo,last in peripheral ,lood and 3+, generaliCed nontender ly$phadenopathy, hepatospleno$egaly, thro$,ocytopenia, and nor$al ane$ia dxN C+8 (loo% at age ,rac%et and 7 ,lasts!. )o pro-e, get R, (( study (a,l protooncogene with nonreactor tyrosine %inase acti-ity and goes fro$ R to (( and fuses with the cluster fusion gene!. 8A* leu%ocyte al%aline phosphatase stain can also ,e used. 8oo% at which neutrophils ta%e it up $ature neutrophils all ha-e 8A* in the$5 neoplastic neutrophils do not whyN 3:c they are neoplastic. 9o, if no stain, %now its neoplastic (nor$al cells ta%e up stain!. Called a 8A* score always low in C+8. 9o, the two tests: *hilly c1so$e and 8A* score, which is always low. ;xa$ple: tear drop cell ,:c there was a dictator in 3+, and cells ha-e to $o-e to the spleen, so there is a $igration of he$atopoetic cells fro$ the 3+ to the spleen. Ghen you ta%e up he$atopoesis anywhere other than the ,one $arrow, this is called extra$edullary he$atopoesis. 9o, the spleen in huge esp. in atherogenic $yeloid $etaplasia. 9o$e of the $ega%aryocytes go ,ac% to the $arrow to lay down collagen5 and $ega%aryocytes go ,ac%. 4i,rosis of the 3+ occurs (used to ,e called $yelofi,rosis $etaplasia!. 9o, not e-eryone left the 3+, and stay in the fi,rotic $arrow. 4or the$ to get to the spleen, they ha-e to wor% their way through strands of fi,rotic tissue, often ti$es da$aging their $e$,rane, leading to tear drop cells (so, it gets passed the =,ar,ed wire1 fi,rous tissue and getting into the sinusoids, they are tear drop cells in the peripheral ,lood!. 9o, pt with huge spleen, with tear drop cells a!)erogeni mye%oi* me!ap%asia. ;xa$ple: too $any platelets essen!ia% !)rom-o y!)emia ($a%es too $any platelets! ;xa$ple: > y:o pt that presents with sternal tenderness, fe-er, generaliCed nontender ly$phadenopathy, hepatospleno$egaly, nor$ocytic ane$ia, E6,666 G3C count $any of which had an a,nor$al appearance cells. Ghat is the dxN ALL /a &!e %ymp)o-%as!i %e&6emia. +C cancer in %ids5 the $ost co$$on type is: co$$on A88 Ag 3 cell leu%e$ia. C?16/5 calla/ Ag 3Dcell A88, associated with down1s syndro$e ;xa$ple: AE y:o, nor$al criteria, s$udge cells and nor$ocytic ane$ia. )hey also ha-e hypoga$$aglo,ine$ia ,:c they are neoplastic 3 cells and cannot change to plas$a cells to $a%e Igs. )herefore, +CC death in C88 " infection related to hypoga$$aglo,ine$ia. Ghat is the ?xN CLL ;xa$ple: A( y:o, nor$al criteria, special stain of )2A* (tartrate resistant acid phosphatase stain! )airy (%now the )2A* stain! e%% %e&6emia
;xa$ple: 0E y:o pt, with nor$al criteria, with E6,666 a,nor$al G3Cs and Auer rods (a,nor$al lysoso$es!, @67 ,last cells in the 3+. Ghat is the ?xN A+L. Know what Auer rods loo% li%e, %now the leu%e$ia that infiltrates gu$s (acute $onocytic ane$ia +E!, and acute progranulocytic ane$ia (+0! they always ha-e ?IC, has a translocation 1E,1@. 2x " retinoic acid (-it A causes ,lasts to $ature into ,R cells!. .. Lymp) no*es A. :enera% C)ara !eris!i s: 1. *ainful -s painless: ly$phadenopathy that is painful is not $alignant5 $ean that you ha-e infla$$ation causing it (does not always $ean infection! you are stretching the capsule, it1s an infla$$atory condition (lupus!, and that produces pain. Ghen you ha-e nonDtender, thin% $alignant, either (1! $ets or (! pri$ary ly$pho$a originating fro$ it. Always tell if painful:less. (. 8ocaliCed -s. generaliCed ly$phadenopathy: 8ocaliCed (ie exudati-e tonsillitis goes to local nodes5 ,reast cancer goes to local nodes. LeneraliCed (syste$ic dC ie .IK, ;3K, 8upus!. 0. ;xa$ples: (a! 3ruton1s aga$$aglo,ine$ia ger$inal follicle a,sent: 3Dcell (,! ?iLeorge syndro$e paratra,eculae $essed up: )Dcell country
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(c! .istiocytes (.an shculler Christian:letter$an sie-e dC! in-ol-es sinuses (d! 9CI? (adenine dea$inase def! 3 and ) cell deficiency, therefore no ger$inal follicle and no paratra,eculae ,ut will ha-e sinuses. (e! 2eacti-e ly$phadenopathy: +acrophage ta%es Ag, and presents to ger$inal follicles and they spit out a plas$a cell, $a%ing A,1s (. Non?Ho*g6in#s %ymp)oma 4ollicular ly$pho$a " +C &onD.odg%in1s 8y$pho$a: 3Dcell5 translocation 1>,1T5 and apoptosis gene %noc%ed off, so the cells are i$$ortal. 5)a! " !iss&es are resis!an! !o in1asion -y an er e%%sE Car!i%age an* e%as!i !iss&e ;xa$ple: (&r6i!!s5 caused ;3K5 )ranslocation T,1>, $yc oncogenes, starry s%y nor$al $acrophages loo%ing li%e s%y at night, S0 +CC cancer in %ids5 can cure5 +C ly$pho$a in %ids, usually in the a,do$en (ie payers patches, paraortic ly$ph nodes, also ,ut rarely in the jaw, or testes! ;xa$ple: pla#ue li%e lesions, no teeth, not a fungal infection actually the infla$$atory cells are really neoplastic5 so the helper ) cell in my osis '&ngoi*es is neoplastic, therefore it1s a ) cell $alignancy. In-ol-es the s%in and ly$ph nodes -s. <e>ary cell syndro$e which is seen in peripheral ,lood ($align helper ) cell that is in peripheral ,lood, in $ycosis fungoides! ;xa$ple: %id with ;+ of ecCe$atous rash all o-er generaliCed nontender hepatospleno$egaly, , ;+ of $ono$orphic cells which were C? 1/ cells histiocytosis H (%e!!erman sie1e *>! (,ir,ec% granules, loo% li%e tennis rac%et clostridiu$ tetani which has a spore also loo%s li%e a tennis rac%et! Audio day 0: .e$atology file A *ainful ly$phadenopathy " so$e type of infla$$atory condition, not $alignant *ainless ly$phadenopathy " $alignancy: +C $alignancy of ly$ph node " $etastasis +C pri$ary cancer of ly$ph node " non .odg%in1s ly$pho$a: follicular 3 cell ly$pho$a (translocation: 1>, 1T. )his %noc%s off apoptosis gene and the cell is i$$ortal!. C. Ho*g6in#s D> four different types. In .odg%in1s the cardinal signs are: fe-er, night sweats, and wt loss (usually )3 unless pro-en otherwise!. It is usually localiCed, nontender ly$phadenopathy. 'n $icro: the $alignant cell is 2eid 9tein,erg cells, 29 cells owl eyes D co$$on on ,oards (also giardia, C+K, ashoff nodule in rheu$atic fe-er!. 8ess S " ,etter prognosis5 $ore " worse )he $ost i$portant one is No*&%ar < %erosis: +C " nodular sclerosis, seen in wo$en5 it is nodular (hence the na$e!, and has lots of sclerosis (collagen deposition, so it1s hard and nonDpainful node!. Bou would see it in a wo$an with ly$ph node in-ol-e$ent in ( places: 1! anterior $ediastinu$ and (! so$ewhere a,o-e the diaphrag$D ie the cer-ical nodes, supercla-icular nodes, nec%. )his co$,ination of $ass in nec% and anterior $ediastinu$ " nodular sclerosis. Bou would see 29 cells on $icro. (. )er$s: poly and $onoclonal (this will help to understand the diff fro$ $ultiple $yelo$a and other things that increase ga$$a glo,ulin p!. 'n seru$ protein electrophoresis, al,u$in $igrates the farthest ,:c it has the $ost neg charge, whereas ga$$a glo,ulin just sits there. (a! *olyclonal: IpolyJ " $any, IclonalJ " plas$a cells, therefore you ha-e $any clones of plas$a cells ,:c the ga$$a glo,ulin region is where the ga$$a glo,ulins are. )hin% IgDaD$J to %now the order of $ost a,undant:greatest nu$,er of glo,ulin. )herefore, on electrophoresis, you see a little pea%, this is an increase in IgL ,:c it1s the $ost a,undant IgL this $a%es sense ,:c for chronic infla$$ation, the $ain Ig is IgL, and for acute infla$$ation the $ain Ig is Ig+. 9o, in chronic infla$$ation (ie Crohn1s, rheu$atoid arthritis, <C! there is an increase in IgL which will show a large diffuse ele-ation (a nice round $tn!. )his is called polyclonal ga$$opathy ,:c $any ,enign plas$a cells are $a%ing IgL. *olyclonal ga$$opathy always $eans ,enign and chronic infla$$ation. Gill not ha-e polyclonal ga$$opathy with acute infla$$ation (ie acute appendicitis!5 this not any rise in the ga$$a go,ulin region for acute infla$$ation the $ain Ig is Ig+ for acute. (,! +onoclonal " one clone of plas$a cells are $a%ing Ig1s5 other plas$a cells are not $a%ing Ig1s ,:c they are suppressed. 9o, when you see a $onoclonal pea%, this $eans it1s a $alignancy of plas$a cells. +eanwhile, all other plas$a cells are suppressed ,y i$$unologic $echanis$s. )he $alignant clone $a%es its own Ig5 $ost of the ti$e it is an IgL $alignancy. )hey are $a%ing $any light chains and get into the urine these are called 3ence Fones proteins. +onoclonal usually $eans $alignancy and always $eans $ultiple $yelo$a. (c! *ea%s (in order!: al,u$in, alpha 1, alpha (, ,eta, ga$$a ha-e a pt (E y:o, nonDs$o%er, had e$physe$a of the lower lungs, no alpha 1 pea% what is ?xN Alpha 1 antitrypsin def. .I. P%asma Ce%% Disor*ers: A. +&%!ip%e +ye%oma /++0
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++ is a -ery ,ad dC, incura,le, and unless you get 3+ transplant, you will die. It1s usually seen in people o-er E6, a little $ore co$$on in wo$en. )he $ost co$$on for$ is Ig %appa, which is a,undant. *las$a cells ha-e I8D1 (a%a osteoclast acti-ating factor!5 this is why you see lots of lytic lesions in the s%ull or ,ones. )he lytic regions are round, and nicely cut (in contrast to *aget1s dC, the lytic regions are fuCCy and not sharply cut!. Ghile in ++ lesions ha-e a fine, sharp (coo%ie cutter cut! ,order, ,:c I8D1 acti-ates osteoclasts, leading to the punched out lesions. ;xa$ple: if there was a lytic lesion in the ri,s and pt coughed, what would potentially happenN *athologic fractures and these are extre$ely co$$on. ;xa$ple: elderly wo$an coughs and de-elops se-ere pain you see lytic lesion of the ri,, so what does the pt ha-eN +ultiple $yelo$a Know what plas$a cell loo%s li%e has ,right ,lue cytoplas$ and nucleus is eccentrally located (around the nucleus are clear areas present!. 'n ;+, will see layer and layers of 2;2, ,:c they are constantly $a%ing protein (ri,o1s are where ri,oso$al 2&A sits on!. +ust %now what plas$a cell loo%s li%e on ;+ and gie$sa stain. 9u$$ary of $ultiple $yelo$a lytic lesions, 3ence Fones proteins, and seen in elderly pts. 1. Amy%oi*osis: is a clinical characteristic of ++ A$yloid on ;+ is a nonD,ranching, linear co$pound with a hole on the center of it. )hey always as% a #uestion on a$yloidosis ,:c it ends up in the differential dx for $ultiDsyste$ dC (syste$ic a$yloidosis!. A$yloid is a protein, ,ut what1s interesting is that $any other different proteins can ,e transfor$ed:con-erted into this uni#ue protein ie preD al,u$in, calcitonin (tu$or $ar%er for $edullary carcino$a of the thyroid!, light chains in ++, and triso$y (1. In )riso$y (1 (?own1s syndro$e!, the c1so$e (1 codes for ,eta a$yloid, and if you ha-e three of these, you will $a%e $ore ,eta a$yloid protein. And ,eta a$yloid protein is toxic to neurons5 so, if you ha-e triso$y (1 are $a%ing $ore ,eta a$yloid protein, then you will ,e losing $ore neurons ,:c you are losing $ore of this protein that is toxic to neurons. )his is why they always as% the #uestion a,out a pt dying at forty and on autopsy, you see atrophy of the ,rain and it re-eals senile pla#ues in frontal and te$poral lo,es, and will as% what pt had ?own1s syndro$e. All down1s pts will get AlChei$er1s. ?own1s pts die fro$ 1 of ( things: either fro$ (1! endocardial cushion defects which leads to heart defects and an A9? (in childhood! and a K9? or ((! AlChei$er1s dC (death ,:c chro$oso$e (1 is $a%ing too $uch ,eta a$yloid protein!. ;xa$ple: >6 y:o with AlChei$er1s dC has downs syndro$e. 3eta a$yloid is $ost i$portant protein. .II. Lysosoma% s!orage *>#s )wo different cells that they li%e to as% #uestions a,out. 1. Laucher dC: there is a $acrophage with a crin%led paper li%e appearance in the cytoplas$. )here are lysoso$es filled with glucocere,roside, therefore pt has Laucher dC. It1s an auto recessi-e dC with a $issing glucocere,roside. (. &ie$annD*ic% dC: ,u,,ly cytoplas$, se-ere $ental retardation, ,uildup of sphingo$yelin in the lysoso$es, therefore the pt has &ie$annD*ic% dC, $issing sphingo$yelinase. 0. *o$pe1s ?C: only glycogen storage dC that has lysoso$al storage " *o$pe1s5 only glycogen storage dC that is lysoso$al ,:c they are $issing an enCy$e to ,rea% glycogen down in the lysoso$es. .ow does pt dieN ?ie fro$ cardiac failure ,:c excess deposition of nor$al glycogen in the heart. 9u$$ary: ,u,,ly cytoplas$ " &ie$annD*ic% dC5 crin%led paper " guacher1s, ,oth are lysoso$al storage dC CHAPTER A: HE+ODYNA+IC DY<9UNCTION I. T)rom-ogenesis: T)e Coag&%a!ion <ys!em .e$ostasis: things in our ,ody that pre-ents clots fro$ de-eloping in 3K1s. If these clots were not pre-ented, the pt either has ?IC, thro$,otic thro$,ocytopenic purpura ())*!, or .<9, and all of the$ lead to death. 9o, why don1t we for$ clots in our s$all 3K1sN Zs$all ,lood -essels include arterioles, -enules, and capillaries, while s$all airways include ter$inal ,ronchioles, resp ,ronchioles, al-eolar duct, and al-eolus[. A. <o@ 3)y *on#! 3e 'orm %o!sE 3:c we ha-e coagulation factors such as: heparin, *LI(, *rotein C and 9, and tissue plas$inogen acti-ator. 9o all of these things are used to pre-ent little clots occurring in our s$all ,lood -essels. 1. .eparin (a LAL, a $ucopolysaccharide!. It is nor$ally found in the ,ody and helps pre-ent for$ation of clots. .ow does heparin wor%N It ;&.A&C;9 antithro$,in III. Antithro$,in III is $ade In the 8i-er (li%e all other proteins!. )herefore, heparin gets the credit for anticoagulating you, ,ut its antithro$,in III does all the wor%. Antithro$,in III neutraliCes $ost of the coagulation factors. 9o, we ha-e a little ,it of heparin in our s$all -essels, which pre-ents clotting fro$ occurring. (. *LI(, prostacyclin, $ade fro$ endothelial cells, a -asodilator. Ghen the -essel is -asodilated, and ,lood flows faster, it is $ore difficult for things to stic%5 therefore, it1s $ore difficult for a thro$,us to stic% ,:c it ,lows away so fast. )herefore, -asodilatation is antagonistic to for$ing thro$,i in anything ,:c e-erything is $o-ing too #uic%ly. *LI( also pre-ents platelet aggregation.
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0. *rotein C and 9 are Kit K dependent factors (as are factors (, @, R, 16!. 4unctions of protein C and 9: they I&AC)IKA); (ie neutraliCe or get rid of! two things factors E and T. )hey actually inhi,it factors E and T in our ,ody. )his is interesting ,:c antithro$,in III cannot inhi,it these. Antithro$,in III can only inhi,it serine proteases, and 4actor E and T are not serine proteases. >. tD*A (tissue plas$inogen acti-ator! this is what we use to dissol-e a clot in a pt with coronary thro$,osis it acti-ates plas$inogen, which produces plas$in. *las$in ,asically eats e-erything in site. (. De'i ien y in any o' !)e an!i oag&%an!s: 9o, if we are def in any of these things (heparin, *LI(, protein C and 9, and tD *A!, clots would for$. In other words pt will ,e thro$,ogenic. Ghy are pts on ,irth control thro$,ogenicN 3:c it increases the synthesis of E and T, increases syn of fi,rinogen, and inhi,its antithro$,in III. 9o, ,irth control pills are ,loc%ing heparin ,y inhi,iting A)III. )herefore, the estrogen of the pill is thro$,ogenic, there,y assisting in the for$ation of clots. ?eadly duo: wo$an on ,irth control and s$o%ing " ,ad5 s$o%ing is thro$,ogenic ,:c it da$ages endothelial cells (so ,oth are thro$,ogenic!. C. 9orma!ion o' a s!a-%e %o! 4or exa$ple: a pt is sha-ing and cut hi$self. .ow do we stop ,leeding when you cut a s$all 3K (not tal%ing a,out $uscular arteries need to plug that! we1re referring to an injury:cut:da$age of a s$all -essel (ie arteriole, -enule, capillary. Ghat will stop the ,leedingN )o deter$ine this we use ,leeding ti$e as ie: ,leeding ti$e is used to e-aluate platelet function. ;xa$ple: If pt has he$ophilia A and has no factor T, the pt will still ha-e a &'2+A8 ,leeding ti$e ,:c ,leeding ti$e has &').I&L to do with coagulation factors. 3leeding ti$e is purely a *8A);8;) thing. 1. .ow do they perfor$ the testN Cut the pt (inflict wound!, start stop watch, and da, wound e-ery thirty sec5 when the wound stops ,leeding, this is the pt1s ,leeding ti$e nor$ally it is @DR $ins. (. )he pathway of ,leeding ti$e: Ghen the -essel is cut, tissue thro$,oplastin is released (which acti-ates the extrinsic coagulation syste$, ,ut has nothing to do with ,leeding ti$e!. )he cut exposes collagen and of course .age$an factor (factor 1(! is acti-ated ,y the exposed collagen5 hence the intrinsic pathway is acti-ated, ,ut this has nothing to do with ,leeding ti$e, either. ;ndothelial cells and $ega%aryocytes $a%e an adhesion product (a type of glue! whose special purpose is to stic% to platelets -G4. -G4 is part of the factor T $olecule and is $ade in ( places $ega%aryocytes in the 3+ and endothelial cells. Ghat1s $ade fro$ $ega%aryocytesN *latelets5 which carry a little ,it of glue with the$ in their granules. Also, platelets are $ade in the endothelial cells. 9o, when you da$age the s$all 3K1s, -G4 is exposed and platelets ha-e receptors for -G4 which is ,asically an adhesion $olecule (just li%e neutrophils had receptors for the endothelial cell $ade ,y the endothelial cell!. If neutrophils cannot stic% to -enules, then they cannot get out to %ill ,ugs. 9a$e concept here platelets ha-e to stic% to ,efore they can do their thing so -G4 is the adhesion $olecule that allows the$ to do that. 9o, now the platelet stic%s called platelet adhesion. Ghen the platelet stic%s, it causes the platelet to release che$icals $ost i$p che$ical is A?* this is a potent aggregating agent, and causes platelets to stic% together. )hey start to help for$ a thro$,us to ,egin to stop the ,leeding. .owe-er this is not enough to co$plete the process. 9o, this is called the release rxn when the platelet stic%s, it causes the platelet to release che$icals, and the $ost i$p che$ical is A?*. Ghen platelets co$e ,y, they will stic% together (,:c of the A?*! and the ,leeding will go down. 3ut still not enough5 needs another che$ical. As soon as the platelet has the release rxn, it starts synthesiCing its own uni#ue su,stance )hro$,oxane A(5 platelets $a%e it ,:c they are the only cell in the ,ody that has thro$,oxane synthase. 9o, it can con-ert *gA( into )xA(, potent -asoconstrictor. )his is i$portant in stopping ,leeding, ,:c if you slow rate of ,lood flow, it will $a%e it easier for platelets to stic% together and the platelets won1t get washed away. As opposed to prostacyclin, which is a -asodilator the platelets cannot stic% ,:c the ,lood flow has increased. )xA ( is the -asoconstrictor in *rinC$etal1s angina. It1s also a ,ronchoconstrictor, so it has affects in asth$atics ,:c it helps 8) C>, ?>, and ;>. 9o, )xA( is a -asoconstrictor, a ,ronchoconstrictor, and a platelet aggregator. It puts the finishing touches on it and causes the platelets to really aggregate, and ,loc%s the injured -essels, and ,leeding ti$e has just ended. 0. Integration: *latelets do two things (1! release rxn, where che$ical were already $ade in it were released so, prefor$ed che$icals were released and ((! it $a%es its own che$ical called )xA (!. )his is analogous to +A9) C;889. 4or exa$ple: two Ig;1s ,ridged together, and pollen ,ridged the gap. )his caused the $ast cells to ha-e a release rxn (release of prefor$ed che$icals: hista$ine, serotonin, and eosinophil che$otactic factor!. )hese che$icals then started the infla$$atory rxn in a type I .*B rxn. )he $ast cell released arachidonic acid fro$ its $e$,rane and we ended up $a%ing *L1s and leu%otrienes. )hey were released 06 $inutes to an hour later and furthered:enhanced type I .*B (infla$$atory! rxns. 9o the $ast cell had a release rxn of prefor$ed ele$ents and it $ade its own *L1s:leu%otrienes. )hat is what platelets did: released its prefor$ed che$icals and $ade its own che$ical: )xA(. *lug is te$porary it is a ,unch of platelets stuc% together and held together ,y fi,rinogen, and is enough to pre-ent ,leeding (to stop ,leeding ti$e!, ,ut if you scratch or try to open the wound, it would start ,leeding again, so it1s not a sta,le plug. >. Conditions that arise with increased or decreased ,leeding ti$e: 8ets screw up ,leeding ti$e:
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(a! Ghat would ,e an o,-ious $ess up of ,leeding ti$eN )hro$,ocytopenia: decreased platelet count therefore if you ha-e less than R6,666 platelets, you will ha-e a prolonged ,leeding ti$e ,:c you will not ha-e enough to aggregate. Another dC that has a pro,le$ with adhesion $olecule defect is -G3 dC (+C genetic hereditary dC, A?! (,! +CC prolonged ,leeding ti$e " ta%ing aspirin5 $echanis$N Aspirin ,loc%s platelet C'H, not )xA( (,loc%ed ,y ?ipyrra$idal!. ;ndothelial cells ha-e C'H, too5 so why didn1t the endothelial cells inhi,it C'H fro$ $a%ing *LI(N )he platelet C'H -s the endothelial C'H reacts differently to aspirin. ?ifferent co$pounds act differently to nonDsteroidal. It1s a R:1 ratio (aspirin ,loc% platelet C'H $ore than endothelial C'H!5 cannot neutraliCe ,oth would ,e ,ad. 9o, aspirin is irre-ersi,le and other &9AI?s are re-ersi,le for >T hrs. 9o, if you too% an aspirin, it pre-ents platelets fro$ aggregating, and therefore they do not wor%, so if you cut yourself, the ,leeding ti$e will ,e increased. Aspirin inhi,its platelets fro$ aggregating5 no )xA(, so it won1t wor% and you will continue ,leeding. E. Continuation of Clotting: 2ecall that the release of tD*A which will acti-ate extrinsic syste$ and it also acti-ates the .age$an factor 1( ,:c of collagen ,eing exposed therefore the intrinsic syste$ is also acti-ated. ;nd product of coagulation is thro$,in, and thro$,in con-erts fi,rinogen into fi,rin. 9o, we ha-e pile of platelets stuc% together and they are ,ound with fi,rinogen. Ghat will happen right after the ,leeding ti$e endsN )he acti-ated thro$,in (produced ,y the extrinsic and intrinsic pathways! will con-ert the fi,rinogen (which is holding the platelets together loosely! into fi,rin, $a%ing a $ore sta,le platelet plug that you are not a,le to dislodge. 9o, who will re$o-e that platelet plug fro$ the -esselN *las$ininogen, and when it is acti-ated and plas$in are for$ed5 plas$in will drill a hole through it and recanaliCe, so the -essel is nor$al again. D. P%a!e%e! *e'i ien y 1s Coag&%a!ion *e'i ien y 9o, with ,leeding ti$e, the platelets (which are held together with fi,rinogen! for$ a te$porary he$ostatic plug. )his stops the ,leeding ti$e, ,ut it1s -ery unsta,le. Ghen the Coagulation syste$ $a%es thro$,in, it con-erts fi,rinogen into fi,rin, $a%ing a strong platelet plug. )his difference is -ery i$p ,:c it distinguishes a difference ,etween a platelet a,nor$ality -s coagulation factor deficiency 1. If you ha-e a platelet pro,le$, what will happen to ,leeding ti$eN *rolonged, ,:c if the pt cuts a -essel, what will happenN It will continue to ,leed (therefore a platelet pro,!. )herefore, in platelet a,nor$alities, you see ,leeding fro$ superficial scratches or cuts (pt continues to ,leed ,:c you can1t for$ a te$porary he$ostatic plug!. In addition, you $ess up the integrity of s$all -essels when platelets are $essed up, leading to petechia (he$orrhage only see in a platelet a,nor$ality pinpoint area of he$orrhage!, echy$oses (purpura!, epistaxis (nose ,leed, which is the +C $anifestations in platelet pro,le$!. &'&; of these $anifestations (petechia, echy$oses, epistaxis, and ,leeding fro$ superficial scratches! occurs in Coagulation factor deficiencyMMM (. Coagulation deficiency: ;xa$ple: pt w: he$ophilia A def in factor T5 what is ,leeding ti$eN &or$al. Ghat type of pro,le$s do these pts run intoN 8A); reD,leeding. ;xa$ple: appendecto$y e-erything went fine, pt wo%e up, starting $o-ing around and ,lood started co$ing out ($assi-e a$ounts of ,lood ca$e out of the wound and pt ,led to death!. 3:c the only thing that was holding the ,lood in was sutures and te$porary he$ostatic plugs. If you ha-e a Coagulation factor def, you cannot con-ert fi,rinogen into fi,rin, and the platelets will fall away, leading to late reD,leeding. *t is a,le to handle superficial scratches:cuts. .owe-er, will not hold -essel closed for too long ,:c late reD,leeding will ta%e place. 3est #uestion to as% to see if they ha-e a Coagulation def: ha-e you had a $olar tooth re$o-ed (ie a wisdo$ tooth!N 8et1s say she says yes5 )hen as%, did you ha-e any pro,le$s with ,leedingN &', (therefore pt does &') ha-e Coag factor def.!5 whyN ;xtraction of a wisdo$ tooth i$poses the greatest he$ostatic stress on the syste$ that e-er exists, its e-en worse after a thoraocto$y, and lots of surgical procedures. 9o if after extraction of a wisdo$ tooth no ,leeding occurred, then they ha-e nor$al Coag factors. ;xa$ple: If pt had a wisdo$ tooth extracted, and had he$ophilia A, pt had no pro,le$s with ,leeding5 howe-er, what is the '&8B thing holding the wound shutN 8il te$porary platelet plugs that are held together ,y fi,rinogen (not fi,rin!. ?entist tells you to wash $outh out (with salt or a little ,it of peroxide! when you get ho$e5 ,ad ,:c you will ,leed to death and suffocate on your own ,lood (all he$ostatic plugs are gone and pt ,leeds to death!. )his is 8A); re,leeding5 not fro$ superficial scratches. 'ther conditions of coagulation deficiency: +enorrhagia $ore of Coag def, than a platelet pro,le$, and the potential for .e$earthroses: where you ,leed into closed spaces. 9u$$ary: 9o, platelet pro,le$ (epistaxis, echy$oses, petechia, ,leeding fro$ superficial scratches! -s coagulation pro,le$ (late reD,leed, +enorrhagia, LI ,leeds, he$arthroses!. )his is all ,ased on %nowing what happens to s$all -essels. E. Tes!s 'or p%a!e%e! a-norma%i!ies 1. 4irst do platelet count: if you too% an aspirin you still ha-e a nor$al S of platelets, ,ut they don1t wor%. (. 9econdly do 3leeding ti$e assesses platelet function 0. )est for -G4N 2istocedin cofactor assay D if $issing -G4, ristocedin can1t cause platelets to clu$p ($ost sensiti-e test for dx1ing -G4 dC!. 9o, three tests that assess platelets: platelet count, ,leeding ti$e, ristocedin cofactor assay (for -G3 ?C! ;xa$ple: older $an with osteoarthritis prostate was resection and $assi-e ,leeds: if ha-e osteoarthritis, you ha-e pain, and if you ha-e pain, you will ,e on pain $edication, an &9AI?9, and will gi-e test results *):*)):platelet count all
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nor$al ,leeding ti$e is longer. 2x platelet pac% transfusion when you gi-e fro$ a donor, it GI88 wor% (donor1s platelets are nor$al!. 9o, if your ta%ing &9AI?s, platelets not wor%ing and if you ha-e a pro, during surgery, gi-e pt platelets fro$ donor. Audio day 0: he$atology file @ 9. Ex!rinsi 1s. In!rinsi sys!em: 1. 4actors in-ol-ed: ;xtrinsic " factor @ Intrinsic " factors 1(, 11, R, T 3oth share the sa$e final co$$on pathway factor 16. (Ghat is another syste$ that has a final co$$on pathwayN Co$ple$entwhether ,y the classical pathway, the alternate pathway, or ,y the +AC pathway, all includes C0! Ghat do we ha-e leftN 16, E, ( (*rothro$,in!, 1 (fi,rinogen! and then the clot. (. )ests in-ol-ed: a! *rothro$,in ti$e (*)!: ;-aluates the extrinsic syste$ all the way down to the for$ation of a clot so it only deals with @, 16, E, (, and 1. ;nd stage of the test is a clot in the test tu,e. I&2 " standardiCed way of doing it standardiCation techni#ue (sa$e e-erywhere in world!. ,! *artial thro$,oplastin ti$e (*))!: ;-aluates the intrinsic syste$ all the way down to a clot so it deals with 1(, 11, R, T, 16, E, (, and 1. ;xa$ple: *) is prolonged, ,ut *)) is nor$al, what is the factor defN @ 3:c the prothro$,in was prolonged5 this includes @, 16, E, (, or 1. And the *)) are nor$al, $eaning that 1(, 11, R, T, 16, E, (, 1 are all nor$al. 9o the only one responsi,le is @. ;xa$ple *)) is prolonged, ,ut *) is nor$al, what is the factor defN 4actor T (play odds!. GhyN If *)) is prolonged, it is 1(, 11, R, T, 16, E, (, and 1 that is the pro,le$. .owe-er the *) is nor$al, therefore @, 16, E, (, and 1 are nor$al. )herefore, its one the *)) factors (1(, 11, R, T!. Ge %now what he$ophilia A (next to -G3 ?C! is the +C factor def, therefore, if you play odds, it1s a factor T def. ;xa$ple: what did warfarin ,loc%N ;poxide reductase. 9o, that pre-ented the ga$$a car,oxylation of 4actors: (, @, R, and 16. 9o, what do you follow with warfarinN *). Ghat is the only factor you are not e-aluating to when you are doing a *) ti$e for a person on warfarinN 4actor R ,:c its part of the intrinsic syste$. Ghat is the *)) in a person on warfarinN *rolonged ,:c factors ( and 16 are -it K dependent factors in the final co$$on pathway. .owe-er, *) does a ,etter jo, in e-aluating warfarin ,:c 0 out of the > things that it1s in-ol-ed in are in the prothro$,in ti$e. 9o, ,oth *) and *)) are prolonged when you are on warfarin, ,ut *) is ,etter diagnostic tool. ;xa$ple: what do you follow heparin therapy withN *)) (e-aluates the intrinsic pathway!. 4actors that antithro$,in III %noc%s off: 1(, 11, @, 16, (, 1 are all neutraliCed ,y antithro$,in III. 9o, with pt on heparin, *)) is prolonged, what is the *)N *rolonged. It1s just that the *)) does a ,etter jo, at e-aluating heparin ($any factors antithro$,in III in-ol-ed with! 9o, 3'). *) and *)) are prolonged if on warfarin or heparin5 howe-er, it turns out that *)) is ,etter at e-aluating heparin and *) is ,etter for warfarin. II. 9i-rino%y!i sys!em: P%asmin *las$in lea-es cru$,s its ,rea%s down things (fi,rinogen, fi,rin, coagulation factors! thin% fi,rino8B)IC syste$. ,rea%s down a clot, there are $any pieces (ie fi,rin! left around, which are fi,rin degradation products. Ghen it
Ghat is the single ,est screening test for ?ICN D?*imers (,etter answer! or fi,rin split products. Ghat plas$in does is ,rea%s things apart, lea-ing cru$,s ,ehind and you ha-e degradation products. ? di$ers are the a,solute ,est test for ?IC (diD $eans (!. Ghen you for$ a fi,rin clot, factor 10 (fi,rin sta,iliCing factor! $a%es the clot stronger. .ow do you sta,iliCe strandsN 8in% the$ ,y putting connections ,etween the$ to $a%e the$ stronger (this is what factor 10 does!. 9o, how do you $a%e collagen strongerN 3y, lin%ing the$ to increase the tensile strength (factor 10 will put a cross,ridge in fi,rin!. Ghat ?Ddi$er is detecting are only those fi,rin factors that ha-e a lin% (ie when there are two of the$ held together, this what the test pic%s up!. Ghat does this a,solutely pro-eN )hat there is a fi,rin clot. ?o you see this in ?ICN Bes. ;xa$ple: Gould you see it if you ,ro%e apart a platelet thro$,us in a coronary arteryN (2e$e$,er a platelet thro$,us is a ,unch of platelets held together ,y fi,rin!. 9o, what would the ? di$er assay ,e if you ,ro%e apart that clotN Increased, you would see increased ? di$ers and would see the little fi,rin strands held together ,y cross lin%ing. )hey often do that to see if you ha-e recanaliCed or if you got rid of your thro$,us. ;xa$ple: it is often also seen with a pul$onary e$,olus, ,:c if you ha-e a pul$onary e$,olus, one test is a ? di$er ,:c you will for$ a clot that will acti-ate the fi,rinolytic syste$, and it will try to start ,rea%ing it down, and there will ,e a release of ? di$ers. 9ingle ,est test for ?IC. Lood test for pic%ing up pul$onary e$,olus, along with -entilation:perfusion scans. ;xcellent test to see if you ha-e reperfusion after gi-en tD*A ,:c it pro-es that if ? di$ers were present, a fi,rin clot $ust ,e present (fi,rin was there so it pro-es it!.
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A. <eni%e p&rp&ra: 9een on the ,ac% of hands of an old person they hit things and get senile purpura5 -essels get unsta,le as you get older and su,cutaneous tissue thins. Ghen you hit yourself, 3K1s rupture and you get echy$oses called senile purpura, an age dependent finding. 'nly present in places that nor$ally hit things, ,ac% of the hands and the shins. ;xa$ple: +o$ was put in old age ho$e and the children were gonna sue the old age ho$e for a,use. ?o the children ha-e a caseN &o, ,:c it has nothing to do with a,use and is an age dependent finding. ;xa$ple: now if they also saw echy$oses on ,uttoc%s and ,ac%, this is not a nor$al place to get trau$a related to just ,u$ping into things that would ,e a,use. 9enile purpura is the cause of echy$oses on the ,ac% of the elderly1s hand. ;-eryone will get this, e-eryone, no one is exe$pt. (. Os%er 5e-er Ren*& D> a6a )ere*i!ary !e%angie !asias: +any of these pts ha-e chronic 4e def ane$ia, related to persistent LI ,leeds. Bou can $a%e the dx with *; of the pt. )he pt will ha-e s$all red dots called telangiectasias and if you loo% on the lips and tongue you will see telangiectasias, and if you do endoscopy, you will see the little red dots throughout the LI tract. Ghat does this pt ha-eN 'sler Ge,er 2endu ?C a%a hereditary telangiectasias. It is the +C genetic -ascular dC. )herefore, you can see why you get chronic 4e def and ,leeds ,:c the telangiectasias will rupture. It is %ind of li%e the angiodysplasia of the s%in 9o, these are the two -essel dC1s: senile purpura and 'sler Ge,er 2endu dC, and also scur-y. I.. P%a!e%e! A-norma%i!ies 4indings of platelet pro,le$s: all ha-e a pro,le$ in $a%ing a he$ostatic plug, epistaxis (+C!, petechia, echy$oses, and ,leeding fro$ superficial scratches:cuts. ;xa$ple: 1( y:o %id, with <2I one wee% ago, presents with epistaxis. *erfor$ *;, and you see lesions that do &') ,lanch (need to %now the difference ,etween petechia and spider angio$as: petechias do not ,lanch ,:c ,leeding into the s%in5 spider angio$a GI88 ,lanch ,:c it1s an AK fistula!. *latelet count is (6,666. Ghat is your dxN Idiopathic thro$,ocytopenic purpura. +echanis$: IgL against the platelet. Ghat type of .*B is thisN )ype II. Gho is re$o-ing the plateletN +acrophages in the spleen (,:c IgL $ar%ed the platelet for destruction ,y the $acrophage!. )his is si$ilar to autoi$$une he$olytic ane$ia, ,ut this is autoi$$une ).2'+3'cytopenia. 2x if they are -ery sy$pto$atic, gi-e corticosteroids5 if not, lea-e alone and it will go away. ;xa$ple: wo$an with I/J spear$an A, test, epistaxis, petechia, generaliCed tender ly$phadenopathy, and spleno$egaly. *t has 8<*<9, autoi$$une thro$,ocytopenia, sa$e $echanis$: IgL autoDanti,odies against platelets, a type II .*B rxn, with $acrophage related re$o-al. A. TTP (thro$,otic thro$,ocytopenic purpura! and HU< (he$olytic ure$ic syndro$e! 3oth ha-e si$ilar pathophysiology. )hese are &') ?IC, therefore you are not consu$ing coagulation factors5 the *) and *)) are totally and une#ually nor$al. Ghat you see is a for$ation of a te$porary he$ostatic plug of s$all ,lood -essels (,leeding ti$e! and the coagulation syste$ con-erting fi,rinogen to fi,rin to for$ a strong platelet plug. 9o in ))* and .<9, so$ething in the plas$a da$ages s$all -essels throughout your ,ody, so that platelets stic% and platelets aggregate and e-entually for$ fir$ platelet plugs in all the -essels of the entire ,ody. Gould you consu$e all the platelets with all that stic%ing going onN Bes. Gill you ,leed ,:c of thatN Bes. Ghat will you see in your peripheral ,loodN 23C will ,e s$ashed, leading to schistocytes. )herefore you will ha-e a $icroangiopathic he$olytic ane$ia. *ts will ha-e thro$,ocytopenia, fe-er, renal failure (,:c glo$erular capillaries will ha-e these platelet plugs in the$!. A,solutely ha-e to ha-e schistocytes in the peripheral ,lood with he$olytic ane$ia to $a%e the dx. 1. ( causes of .<9: a! 61E@:.@ ;. coli (toxin producing ;. coli that can ,e present in undercoo%ed ,eef. )he toxin da$ages the -essel, leading to the dC, and this is called .<9. 'ne of the +C causes of acute renal failure in children " .<9. ,! 9higella toxin (-ery potent! that leads to shigellosis and then .<9. In ))*:.<9 will see low platelet count, prolonged ,leeding ti$e, and nor$al *):*)) ,:c you1re not consu$ing coagulation factors, ,ut only consu$ing platelets. .. Coag&%a!ion *e'i ien y In Coagulation deficiency, you different sign1s sy$pto$s, such as: delayed ,leeding ie go through operation with no pro,, then the pt starts $o-ing around that1s when it1s ,ad. Ghen pt has an operation and they start ,leeding out of the wound, the +CC is not a coagulation factor deficiency5 the +CC is due to suture slipped or a ,leed. Ghen you ha-e a coag deficiency, just ha-e to tie it off. ;xa$ple: $olar extraction with constant ooCing of ,lood ,:c nothing holding those s$all -essels together except a te$p he$ostatic plug need a tight fi,rin ,ond to plug it up. ;xa$ple: It is showing he$orrhage into the fascial co$part$ent of the thigh. In the %nee, there are repeated he$arthroses and the pt has he$ophilia A. Gill not see he$arthroses or ,leeding into spaces with platelet a,nor$alities, ,ut only coagulation factor deficiency. A. +&s! 6no3 !)e *i''eren e -e!3een )emop)i%ia A an* 15( D> (these are the %ey coagulation deficiencies!
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1. 15( D> $issing -G4, therefore there is a platelet adhesion defect, therefore, they ha-e all the signs and sy$pto$s of a *8A);8;) pro,le$. .owe-er, they also ha-e a factor T deficiency, ,ut it is -ery $ild and ne-er se-ere. 9o, they ha-e )G' a,nor$alities they ha-e a platelet defect A&? a coagulation factor defect. )his is why they can ha-e $enorrhagia and LI ,leedings (this the coagulation part of it!5 will also see history of epistaxis and they ,ruise easy. )here are 0 parts of the factor T $olecule: -G4, factor T coagulate (part of intrinsic syste$!, T Ag. )he T Ag has a carrier function: it carries around -G4 and factor T coagulant in the ,lood (so it1s a chauffeur! D so it functions as a carrier protein. All 0 of these can ,e $easured. ". Di''eren es in !3o *>#s: a! Lenetics: In pts with he$ophilia A it1s an H lin%ed recessi-e dC, therefore $ales get the dC. Ghereas -G?C is Autoso$al do$inant, and only one of the parents ha-e to ha-e the a,nor$ality and E67 of the %ids will ha-e the potential to get the dC. ,! &u$,er of deficient factors: .e$ophilia A only has one factor that is deficient: T anticoagulant5 they ha-e nor$al T Ag le-els and nor$al -G4 le-els. -G?C has A88 0 things decreased: T Ag, factor T anticoagulant ($ildly decreased!, and -G4. (. 5)a! *r&g an in rease !)e syn!)esis o' a%% !)ree o' !)ese 'a !or L mo%e &%esE )he drug co$es fro$ A?. and is called des$opressin (ddadp!. )his can increase the synthesis of all three factor T $olecules. It will help treat $ild he$ophilia A, and is the ?'C for -G?C. In wo$an, if they ha-e $enorrhagia and nor$al e-erything else, you ha-e -G?C. )hey put you on ,irth control and that too% the ,leeding away. In one of the cases, the ?r. ordered *), *)), and ,leeding ti$e tests. )he tests for *) and *)) were nor$al and the ,leed ti$e was nor$al. )he sensiti-ity for these tests is only E67, so do not depend on these. )he ristocedin cofactor assay is the test of choice for -G?C, and will ,e a,nor$al. ;strogen increases the synthesis of all factor T $olecules. 9o, ( things increase the synthesis of all the factor T $olecules: des$opressin and ,irth control pills (?'C for wo$en!. C. U<+LE <!ep ": AntiDphospholipids syndro$e (one of the causes of spontaneous a,ortion! includes: 8upus anticoagulant (not an anticoagulant, ,ut the opposite: thro$,ogenic! and antiDcardiolipin anti,odies. 3oth of these anti,odies cause -essel thro$,osis. 8upus anticoagulant is part of the syndro$e that produces -essel thro$,osis. Also seen in .IK pt. AntiDcardiolipin anti,odies ha-e a history of ha-ing a ,iological false / syphilis serology. 9o, here you are with K?28 and 2*2 ,eing positi-e. )o confir$, 4) A39 would ,e negati-e (test Ag is ,eef cardiolipin!. )herefore $a%es the K?28 and 2*2 false positi-e, ,:c the confir$atory test was negati-e. 9o why was the 2*2 positi-e in the first place, ,:c the test antigen is ,eef cardiolipin. )herefore syphilis anti,odies react to against that ,eef cardiolipin, and producing a positi-e reaction. 3ut so the antiDcardiolipin anti,odies. )herefore you get a ,iological false I/J with a syphilis serology. If you ha-e a wo$an with a ,iological false I/J syphilis serology, what is the -ery first test you should getN 9eru$ anti A&A anti,ody ,:c she can de-elop lupus. AntiDcardiolipin anti,odies are a -ery co$$on feature of 8<*<9. +atter of fact, a ,iological false I/J with a syphilis serology is a criteria for diagnosing 8upus. D. Dissemina!e* In!ra1as &%ar Coag&%a!ion /DIC0 ?isse$inated " all o-er the ,ody Intra-ascular " within the -essel Coagulation " clotting (for$ing clots throughout the ,ody! Ghat is consu$ed in a clotN 4i,rinogen, E, T, prothro$,in, platelets In clot tu,e for$ a clot on top is seru$ and the seru$ is $issing what is consu$e in a clot (fi,rinogen, E, T, prothro$,in, platelets!. )his is what you ha-e in ?IC consu$ing these coagulation factors, including platelets, in those clots throughout the ,ody5 therefore you ha-e ( dC1s at once. Bou ha-e (a! thro$,i in -essels, and at the sa$e ti$e you are (,! anticoagulated ,:c all you ha-e circulating around is seru$, you don1t ha-e plas$a ,:c you consu$ed the coagulation factorscalled a he$orrhagic thro$,osis syndro$e. )he syndro$e is -ery unusual and two things are happening at the sa$e ti$e. Ghat started all this offN )he intra-ascular coagulation is responsi,le for consu$ing all these things. 9o, what causes thisN +CC " 9eptic shoc% (+CC septic shoc% " ;. coli!, sna%e ,ite (not the neurotoxin types, ,ut the rattlesna%es!, and A2?9. Kery si$ple to recogniCe they ,leed fro$ e-ery orifice or scratch, and e-en if there is a puncture wound. Classic ?IC " ?x is easy, ,:c if you consu$ing all the Coagulation factors, *) and *)) prolonged and platelet count is decreased, d di$ers I/J. )he test for ?x is ?Ddi$er test. ;xa$ple: pt with a,ruptio placenta and had a$niotic fluid e$,olis$. A$niotic fluid gets into circulation of the $o$, which contains thro$,oplastin, so, death is fro$ ?IC, not fro$ the a$niotic e$,olis$. 3:c the thro$,oplastin within the a$niotic fluid precipitated ?IC. ;xa$ple: hereditary thro$,osis " young person w: ?K), not nor$al and fa$ily hx ;xa$ple: factor E leiden a,nor$al factor E that protein C and 9 cannot ,rea%down, therefore there is an increase in factor E, which predisposing to thro$,oses ;xa$ple: Antithro$,in III deficiency +CC wo$an ,irth control (therefore, the +CC is ac#uired can also ,e genetic ie pt with ?K), put on warfarin and heparin, and do a *)) is nor$al after heparin, so you gi-e $ore heparin, and the *)) is still
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nor$al. 9o, pt with ?K), gi-e heparin, *)) re$ains nor$al " A) III def. ,:c heparin wor%s on A) III. &or$ally, the heparin facilitates antithro$,in III there,y increasing the *)). In this case, no $atter how $uch heparin is injected, there is no change in *)), therefore there is no Antithro$,in III for the heparin to wor% on (this is how dx is usually $ade ,y $ista%e!. E. Coag&%a!ion *isor*ers s&mmary: *latelet ct:,leeding ti$e:*):*)) (,asic tests to e-aluate .e$ostasis! Aspirin: &, ., &, & Idiopathic thro$,ocytopenic purpura (+CC of thro$,ocytopenia in %ids!: 8, ., &, & ))*:.<9: 8, ., &, & .e$ophilia A: &, &, &, . -G?C: &, ., &, . (so, for la, tests, $ain diff fro$ he$e A is ,leeding ti$e! warf:hep: &, &, ., . (I&2 *) " warfarin, , *)) " hep! ?isease Aspirin I)* ))*:.<9 .e$ophilia A -G3 ?C Garfarin:.eparin ?IC .I. (%oo* :ro&ps A. Di''eren! -%oo* gro&ps an* 3)a! is '%oa!ing aro&n* in !)e ser&m: ' is $ost co$$on, A is (nd $ost co$$on, 3 is 0rd co$$on, and A3 is the rarest O: ha-e antiDA Ig+, antiD3 Ig+, antiDA3 IgL A: anti 3 Ig+ (: anti A Ig+ A(: nothing Ne3-orn: nothing, whyN )hey don1t ,egin synthesiCing Ig+ until after they are ,orn and only after (D0 $onths do they start synthesiCing IgL. E%*er%y: nothing ;xa$ple: an old person who is ,lood group A and ,y $ista%e recei-ed ,lood group 3, ,ut did not de-elop a he$olytic transfusion rxn whyN )heir le-els of A,1s are low when they get older that there wasn1t anything around to attac% those cells. (. Asso ia!e* Diseases: Ghich is associated with gastric cancerN A Ghich is associated with duodenal ulcerN ' <ni-ersal donorN ' (can gi-e their ,lood to anyone ,:c ha-e &' antiDA or antiD3 Ag!. Ghat is the only ,lood group ' can getN ' <ni-ersal recipientN A3 ,:c they ha-e no A,1s to attac% those cells C. O!)er An!igens: 1. 2h / antigen $eans that you are I/J for ? antigen (. ?uffy Ag is $issing in ,lac% pop1n5 therefore not as li%ely to get plas$odiu$ -i-ax ($alaria! ,:c the Ag the *. -i-ax needs to parasitiCe the 23C1s is the ?uffy ag and if you don1t ha-e the Ag the *. -i-ax can1t get it. (LA*? def, thalasse$ias, 9C?C pts protected fro$ falciparu$ they are protected ,:c they1re 23C1s ha-e a shorter lifespan so, the parasite cannot li-e out their cycle, and 23C1s a shorter lifespan! D. +aQor rossma! ): pt gonna get ,lood5 their seru$ is in a test tu,e, with the ,lood of the donor unit and they $ix the ( together so they $ix the pt1s seru$ with the donor1s 23C1s to see if they are co$pati,le5 loo%ing for anything in the pts seru$ that will attac% the antigens in the donor1s 23C1s. Another part of the wor%up for cross$atching is to do an anti,ody screen which is an indirect coo$,1s ,efore $ixing (re$e$,er that it detects the A&)I3'?B!. If this test is negati-e, the cross$atch is co$pati,le (so, there is no A, in the pts seru$ that will attac% the donor1s!. )his does not pre-ent a transfusion rxn, or that A,1s will de-elop later against the donor. Ghat is the chance that anyone has the sa$e Ag $a%eup as anotherN Qero. 9o, e-en if I get a ,lood group ' when I1$ group ', there is still an increase ris% of a, attac%. +oral of the storyN ?on1t transfuse unless it1s a,solutely necessary Audio ?ay 0: .e$atology T .II. <i*e No!es A. Puestions as%ed during the ,rea% a,out hypersensiti-ity: 8upus (not e-erything is type III! *ost strep (not e-erything is type III, either! can cause type II if its post strep. rheu$atic fe-er, howe-er, if it is post strep glo$erulonephritis, that is type III )hro$,ocytopenia and .e$olytic ane$ia " type II *C& rash " type I *latelet Count &8 8'G 8'G &8 &8 &8 8'G 3leeding )i$e .IL. .IL. .IL. &8 .IL. &8 .IL. *) &8 &8 &8 &8 &8 .IL. (G! .IL. *)) &8 &8 &8 .IL. .IL. .IL. (.! .IL.
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*C& he$olytic ane$ia " type II (IgL A,1s against the *C& group attached to the 23C $e$,rane! ;xa$ple: $ost co$$on A, in the <9A is AntiDC+K (e-eryone has ,een exposed!.
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Bou are safest fro$ getting .IK fro$ ,lood transfusion than fro$ all the other infections (1:A(E,666 per unit of ,lood chance of getting .IK therefore unco$$on get to get .IK fro$ ,lood!. )his is due to all the screening tests that they perfor$. )hey do the ;lisa test which loo%s for antiDgp1(6 A,1s (re$e$,er, it1s the gpD1(6 Ag that attaches to helper ) cell (C?>! $olecule!. 'n western ,lot, loo%ing for $ore (0 or >! A,1s, $a%ing it $ore specific, so if you get this I/J on 0 or $ore, you are a true positi-e. . Ghat is the +C infection trans$itted ,y ,lood transfusionN C+K, which is the +C o-erall infection. )hat is why this anti,ody is the $ost co$$on. Ghat is +CC post transfusion hepatitisN .ep C (1:0666! In new,orn, want to pre-ent graft -s. host dC and C+K ,:c no i$$une defenses, therefore, need to irradiate the ,lood. )he irradiation %ills off the ly$phocytes and since the C+K li-es in ly$phocytes, we %ill off the C+K -irus also. )his why we radiate ,lood ,efore gi-ing to new,orns. Accidental needle stic% fro$ a pt you %now nothing a,out what is the +C infection you can getN .ep 3. Accidental needle stic% fro$ .IK I/J pt5 what is the chance of getting .IK/N 1:066. Ghat do you do a,out itN Bou go on therapy as if you are .IK/. Lo on to triple therapy (( 2)I1s AQ) and a protease inhi,itor! for six $onths and get constant chec%s do *C2 test loo%ing for 2&A in the -irus ($ost sensiti-e!, do ;lisa test. In fact, the +C $echanis$ of a healthcare wor%er getting .IK " accidental needle stic% ?o not transfuse anything into a person unless they are sy$pto$atic in what they are deficient in. ;xa$ple: If you ha-e 16 gra$s of .,, and ha-e no sy$pto$s in the pt, do not transfuse. Bou should transfuse the pt if they ha-e C'*? and are starting to ha-e angina related to the 16 gra$s. ;xa$ple: E6,666 platelet ct no epistaxis " do not treat the$5 if they do ha-e epistaxis, treat the pt. ;-ery ,lood product is dangerous ,:c you can get infections fro$ it. (. 9res) 'ro>en p%asma should ne-er ,e used to expand a pts plas$a -olu$e to raise 3* use nor$al saline (it is too expensi-e and you run the ris% of trans$itting dC!. <se fresh froCen plas$a for $ultiple coagulation factor deficiencies ie would ,e legiti$ate to gi-e froCen plas$a to replace consu$ed factors, as in ?IC. ;xa$ple: pt with warfarin is o-er anticoagulation and ,leeding to death not to gi-e I+ -it K will ta%e to long to wor% (ta%es ADT hrs to wor%!, so the treat$ent of choice is fresh froCen plas$a to i$$ediately replace it. 9o, fresh froCen plas$a is li$ited to use of $ultiple factor deficiencies (ie cirrhosis of the li-er and you are ,leeding since $ost of the factors are $ade in the li-er, they are deficient in all proteins!. ?'C for heparin o-erdose is to gi-e prota$ine sulfate. C. 8no3 !)e *i'' !rans'&sion rxn#s 1. +C transfusion rxn " a%%ergi rxn (itching, hi-es, anaphylaxis! D this is an exa$ple of a type I .*B rxn ie ha-e unit of ,lood, and in their plas$a you are allergic to so$ething (ie *C&!5 2x " ,enadryl, antihista$ines (. (nd transfusion rxn " 'e-ri%e rxn5 it is due to .8A A,1s5 pt has .8A A,1s against leu%ocytes of donor Ag. 9o, when the unit of ,lood is transfused into $e, and there are so$e leu%ocytes with .8A A, on the$, $y A, will react against it, destroy the cell and release the pyogenes fro$ neutrophil, leading to fe-er. If I1-e ne-er ,een transfused, should I ha-e .8A A,1s against anythingN &oM Continuing #uestion: Gho is $ost at ris% for ha-ing a fe,rile rxn with transfusionN Go$an ,:c she is has ,een pregnant e-ery wo$an that has had a ,a,y has had a fetal $aternal ,leed, so so$e of the ,a,ies leu%ocytes got into the ,loodstrea$, and the wo$an de-eloped an anti .8A A, (the .8A1s are fro$ the hus,and, that ha-e ,een passed on to the wo$an!. 9o, the $ore pregnancies a wo$an has had, the $ore anti .8A A,1s she will de-elop ,:c of her pre-ious pregnancies. )his is also true for spontaneous a,ortions you can still get .8A A,1s. 9o, wo$en are $ore li%ely to ha-e transfusion induced fe,rile rxns ,:c they are $ore li%ely to ha-e antiD.8A A,1s (we should not ha-e hu$an ,eing1s .8A1s in our ,lood strea$ ,:c we ha-en1t ,een exposed to hu$an1s ,lood!. ;xa$ple: Gho has the greatest ris% in de-eloping fe,rile rxnN )he answer choices for this #uestion would ,e a new,orn, 1( y:o without transfusion, wo$an with one pregnancy, wo$an with spontaneous a,ortion, and $an. )he answer is wo$an with spontaneous a,ortion ,:c that is a pregnancy and there is a potential for .8A a,1s to lea% out of the fetus into the $other. 4e,rile rxn is a type II .*B rxn against the .8A A, (allergic rxn is type I! 0. Hemo%y!i !rans'&sion rxns are -ery rare. ;xa$ple: If you are ,lood group A, and gi-en group 3 ,y stupidity ,:c the pt has antiD3 Ig+ (re$e$,er that Ig+ is the $ost potent co$ple$ent acti-ator and that cell will not last only a,out 1 $sec! )his is ,:c the Ig+ will attac% it, C1DCR: +AC, anaphylatoxins are released, and shoc% will ensue -ery serious a%a clerical error!.
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;xa$ple: pt has A, against Ag on 23C1s in the unit you would thin% that this shouldn1t happen ,:c the cross$atch said it is co$pati,le5 and did an A, screen that was negati-e (Indirect Coo$,s!. .owe-er, so$e A,1s are not present, and you ha-e $e$ory 3 cells. 9uppose if I got ,lood transfusion 06 years ago, there are no A, titers now ,:c they would1-e gone away howe-er, there are $e$ory 3 cells5 these a,1s will ,e way ,elow the sensiti-ity of an A, screen, co$e out co$pati,le fro$ a cross$atch, and will ha-e neg indirect coo$,5 howe-er, after transfusion, $e$ory 3 cells would detect the foreign Ag. After the 3 cell detects the Ag, it will start di-iding in the ger$inal follicle and start di-iding and ,eco$e a plas$a cell, which would $a%e antiDcalla A,. )his can occur in a few hrs or $ay occur in a wee% depending on the A,. )hat1s the one they li%e on the ,oards *e%aye* )emo%y!i !rans'&sion rxn. ;xa$ple: wo$an postpartu$, difficult deli-ery (a,ruptio placenta! was transfused 0 units of ,lood. Ghen she left the hospital, she had an ., of ten. 'ne wee% later, she is jaundice and wee%, and has an unconjugated hyper,iliru,ine$ia and has an ., of T. Ghat is the dxN ., was less than what she left the hospital, and they will not $ention the coo$,s test! Ghat is $ost li%ely causeN .alothane (no ,:c that ta%es o-er a wee% to de-elop!, hepatitis (no, which ta%es ADT wee%s to de-elop!. Answer: delayed he$olytic transfusion rxn so, they $ight as% what test would you getN Indirect coo$,s test to pro-e it ,:c you will see the A, Coating the 23C. +oral of the storyN Trans'&se* 3i!) er!ain %e1e% o' H-@ 1 3ee6 %a!er )a1e Qa&n*i e an* %ess H- , *e%aye* )emo%y!i !rans'&sion rxn , !ype II HPY .III. A(O7R) in ompa!i-i%i!y A. A(O in ompa!i-i%i!y: If ,lood group ' wo$an ha-e a ,a,y, the $o$ will ha-e a pro,le$ with A3' inco$pati,ility ,:c $o$ already ha-e an A, that can cross the placenta (,lood group ' people ha-e anti A Ig+, anti 3 Ig+ and anti A3 IgL, nor$ally!. &or$ally, there is an anti A3 IgL A, which can cross the placenta, and attac% an A or 3 23C. 9o, there could ,e a pro,le$ in the -ery first pregnancy. ;xa$ple: $o$ is ,lood group ' negati-e and ,a,y is ,lood group A negati-e. Is there an inco$pati,ility of ,lood groupsN Bes. Is there an inco$pati,ility in 2h groupsN &o. Fust the ,lood groups, since the $o$ is ' while ,a,y is A. )he $o$ is ', she has anti A3 IgL, which will cross the placenta5 the A part of the A, will attach to the A part of the A cells of the ,a,y1s. )he ,a,y1s $acrophages of the spleen will destroy it, which is )ype II .*B, $ild ane$ia, and unconjugated ,iliru,in which is handled ,y the $o$1s li-er5 no %ernicterus, no pro,s with jaundice in the ,a,y ,:c in utero, the $o$1s li-er will ta%e care of it. Ghen the ,a,y is ,orn the ,a,y, it will ha-e a $ild ane$ia and jaundice. +CC jaundice in the first (> hrs for a new,orn " A3' inco$pati,ility (not physiologic jaundice of the new,orn that starts on day 0!. Ghy did the ,a,y de-elop jaundiceN 3:c the ,a,y1s li-er cannot conjugate ,iliru,in yet and $ust handle unconjugated ,iliru,in on its own now, so it ,uilds up. )his is an exchange transfusion rxn for A3' inco$pati,ility $ost of the ti$e is ,R, and put under <K 3 light. .ow does <K 3 light wor%N It con-erts the ,iliru,in in the s%in into diDpyrol, which is water solu,le and they pee it out (2x for jaundice in new,orn!. Ane$ia is $ild ,:c it is not a strong Ag and doesn1t holster a ,ris% he$olytic ane$ia. If you do a coo$,1s test, it will ,e positi-e ,:c IgL1s on the 23C1s. 9o always an ' $o$ with a ,lood group A or A3 ,a,y. )his can occur fro$ the first pregnancy (not li%e 2h sensitiCation where the first pregnancy is not a pro,le$!. In any pregnancy, if $o$ is ,lood group ', and she has a ,a,y with ,lood group A or 3, there will ,e a pro,le$ (,lood group ' " no pro,le$!. (. R) in ompa!i-i%i!y +o$ is 2h negati-e and ,a,y is 2h positi-e. ;xa$ple: $o$ is ' negati-e and ,a,y is ' positi-e (not A3' inco$pati,le, ,ut 2h inco$pati,le!. In the first pregnancy: deli-er ,a,y without going to a ?r, and there is a fetal $aternal ,leed, so$e of the ,a,ies ' positi-e A,1s got into $y ,loodstrea$, which is not good. 9o, $o$ will de-elop an anti 3 A, against it. 9o, $o$ is sensitiCed which $eans that there is an A, against that ? Ag and now $o$ is anti ?. 1 year later, $o$ is pregnant again, and still ' negati-e, and ha-e anti ? and the ,a,y again is ' positi-e. )his is a pro,le$ ,:c it is an IgL A,, which will cross the placenta, attach to the ,a,ies ? Ag positi-e cells (of all the Ags, the ? Ag hosts the worst he$olytic ane$ia!. 9o, the ,a,y will ,e se-erely ane$ic with 2h than will A3' inco$pati,ility. )he sa$e thing happens though ,a,y1s $acrophages phagocytose and $o$1s li-er will wor% harder. Ghen the ,a,y is ,orn, the ,iliru,in le-els are -ery high, a se-ere ane$ia occurs, and there is an excellent chance that an exchange transfusion will ,e necessary (RR7 chance!, so ta%e all the ,lood out (gets rid of all the ,iliru,in and sensitiCed 23C1s and transfuse ,:c ,a,y is ane$ic!. 9o, they will usually always ha-e a exchange transfusion. )herefore, for the first pregnancy, the ,a,y is not affected, and this is when the $other gets sensitiCed. pregnancies, the ,a,y will a lot worse. In future
.ow do we pre-entN +o$ will do an A, screen test and she is 2h negati-e. Around the (Tth wee%, gi-e her 2h Ig, which is prophylactic. )his is anti ?, which co$es fro$ wo$an5 it has ,een sensitiCed and heat treated and cannot cross the placenta. Ghy do they gi-e at (T wee%sN *t $ay get fetal $aternal ,leeds ,efore the pregnancy or a car accident or fall can cause ,a,ies ,lood to get into $o$1s circulation. 9o, $o$ has anti ? A,1s to sit on the ? positi-e cells and destroy the$, so $o$ won1t get sensitiCed. )hen, $o$ gi-es ,irth to ,a,y (lets say it is 2h pos!. ?o a *lyhowa,enti test and ta%es $o$1s ,lood to I? (if any ! fetal 23C1s in the circulation and count the$5 they can say how $uch is in there. ?epending on that, that will deter$ine how $any -iles of allergen Ig you gi-e the $o$ to protect her further (anti ? only last three $onths, and need to gi-e $ore at ,irth, especially if the ,a,y is 2h positi-e!. ;xa$ple: +o$: ' negati-e5 3a,y: A positi-e ( pro,le$s: A3' inco$pati,le and 2h inco$pati,le. 3ut, there is not going to ,e a pro, with sensitiCation. &o GhyN After deli-ery of ,a,y, so$e of the ,a,ies cells (which are A cells! get into the $o$1s ,lood (which $o$ has anti A Ig+! 5 those cells will ,e destroyed so fast, that in $ost cases the $o$ cannot generate A, against those cells ,:c they ha-e ,een destroyed. 9o, A3' inco$pati,ility protects against 2h sensitiCation. Bou still would gi-e 2h I$$unoglo,ulin. 9o if you are A3' and 2h inco$pati,le, 2h sensitiCation will ,e protected against.
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Kid with erythro,lastosis fetalis will ha-e 2h inco$pati,ility what do they die ofN .eart failure se-ere ane$ias will decrease -iscosity of ,lood, so they get a high output failure: 8.4, then 2.4, huge li-ers ,:c extra$edullary he$atopoesis ,:c they are so se-ere ane$ic. ;xa$ple: cross section of ,rainste$ fro$ %id what is the cause of color changeN Its yellowish due to %ernicterus pro, fro$ a ,a,y that had 2h inco$pati,ility. 2e$e$,er, it1s an unconjugated hyper,iliru,ine$ia ,:c it1s a he$olytic ane$ia and lipid solu,le5 li-er cannot syn it5 goes to ,rain and is -ery toxic leading to se-ere de,ilitating dC or death. Cardiology audiosD > hours total III. Rxn !o InQ&ry T)eory Cells in-ol-edD platelets, $onocytes, $acrophages, cytotoxic t cells with cyto%ines (neutrophils not in-ol-ed! Atherosclerosis in an aorta rxn to injury theory " injury to endothelial cells lining the elastic arteries and $uscular arteries what is injuring itN A$$onia in cig s$o%e, C' in cig s$o%e5 so, poisons da$age the endothelial cells5 8?8 da$ages it, and if its oxidiCed, it da$ages it worse5 -iral infections da$age it, too. C)%amy*ia pne&moniae /"n* +CC a!ypi a% pne&moniae0I p!s 3i!) +I = mos! )a* A-#s agains! C)%amy*ia pne&monia@ )omo ys!eine = a%% !)ese !)ings *amage en*o!)e%ia% e%%s Ghat happens when you da$age endothelial cellsN *latelets stic% to it and *?L4 is released into the artery and *?L4 causes s$ooth $uscle cells within the $edia to proliferate and they undergo hyperplasia and then, they che$otactically $igrate to the su,inti$al le-el. )hey ha-e all these s$ooth $uscle cells $igrating to the inti$a of the -essel. +onocytes ha-e access into the -essel ,:c it has ,een injured and $onocytes also ha-e L4s. As the 8?8 increases, the $acrophages phagocytose the$. +acrophages and s$ooth cells ha-e 8?8 w:in the$5 the 8?8 ,eco$es oxidiCed and a fatty strea% is produced. '-er ti$e, a fi,rofatty pla#ue de-elops, which is pathogno$onic of atherosclerosis. It can ,e co$plicated ,y dystrophic calcification, fissuring, thro$,osis and a co$plicated atherosclerosis. I.. Ar!eria% Disor*ers: A. A!)eros %erosis is a primary 'a !or 'or er!ain *>#s = CA?5 atherosclerotic stro%e relates to pla#ues5 a,do$inal aneurys$ due to wea%ening of the -essel5 nontrau$atic a$putation of lower extre$ity (peripheral -ascular dC!5 $esenteric angina, s$all ,owel infarction, reno-ascular atherosclerosis of the renal arteries. A!)eros %erosis on%y in1o%1es m&s &%ar ar!eries an* e%as!i ar!eries. Can s$all -essel, such as arterioles get hardenedN Bes. ;xa$ple: loo% at the spleen hyaline arteriolar sclerosis and hyperplastic arteriolar sclerosis (onion s%inning!. 1. Hya%ine ar!erios %erosis is a s$all -essel dC5 lu$en is narrow5 whene-er there is a lot of pin% staining stuff, this is hyaline. ;xa$ple: s$all -essel dC of dia,etes and .)& two $ajor dC1s that produces a s$all -essel dC with different $echanis$s: a. Dia-e!es: nonenCy$atic glycoslyCation a%a .,A1c5 glycoslyCation is glucose attaching to aa and protein. 4or .,A, its glucose attaching to aa and .,A, and the .,A is glycosylated. .,A1c le-els correlate with the ,lood glucose le-els of the last ADT wee%s, so this is the ,est way of loo%ing at long ter$ glucose le-els. All the da$age seen in dia,etes is due to glucose. 4or a dia,etic, you should ,e under A7, $eaning that you are in a nor$al glucose range. )here is nothing uni#ue a,out dia,etes except for a large glucose le-el, you %eep that nor$al, and it1s as if you don1t ha-e dia,etes. )he on%y !3o pa!)o%ogi pro esses are !)is: nonen>yma!i g%y osy%a!ion of s$all 3K1s including capillaries in the %idney, and osmo!i *amage. )hose tissues that contain aldose reductase lens, pericytes in the retina, schwann cells all ha-e aldose reductase and can con-ert glucose into sor,itol and sor,itol is os$otically acti-e suc%s water into it and those cells die, leading to cataracts, $icroaneurys$s in the eye ,:c the pericytes are destroyed and wea%ened and the retinal -essels get aneurys$s, and you get peripheral neuropathy ,:c schwann cells are destroyed. )hey all related to excess glucose. 9o, tight glucose control " nor$al life. Ghat does nonenCy$atic glycosylation to do the ,ase$ent $e$,rane of s$all -esselsN Its renders the$ per$ea,le to protein, so the protein in the plas$a lea%s through the 3+ and goes into the -essel wall, produces a hyaline change and narrows the lu$en. Ghat if there is nonenCy$atic glycosylation of the L3+N It will render it per$ea,le to protein called $icroal,u$inuria. )his is the first change to ,e seen in dia,etic nephropathy. 9o, what is the $echanis$N &onenCy$atic glycosylation. -. Hyper!ension ?oes not use nonenCy$atic glycosylation. It just uses ,ruit force and dri-es (,:c of increase in diastolic pressure! the proteins through the 3+ and produces the effect. Ghen we loo% at a %idney in .)&, it is shrun%en, has a co,,lestone appearance this is ,:c there is hyaline arteriolosclerosis of the arterioles in the cortex, ische$ia, and is wasting away with fi,rosis and atrophy of tissue. 8acunaer stro%es (tiny areas of infarction that occur in the internal capsule! are a hyaline arteriosclerosis pro,le$ related to .)&. ". Hyperp%as!i ar!erios %erosis 9een in $alignant .)&5 $ore co$$on in ,lac%s then whites, $ainly ,:c .)& is $ore co$$on in ,lac%s than whites. +ainly see this -essel dC in $alignant .)& (ie when pt has 3* of (>6:1A6!. (. Ane&rysm 1. De'ini!ion: area of outpouching of a -essel due to wea%ening of the -essel wall. Atherosclerosis can cause wea%ening of the a,do$inal aorta leading to an aneurys$.
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Ghat would ,e the analogous lesion in the lungs with wea%ening and outpouchingN 3ronchiectasis due to cystic fi,rosis with infection, destruction of elastic tissue leading to outpouching and dilatation of the ,ronchi. ;xa$ple: what is the LI aneurys$N ?i-erticular dC ha-e a wea%ening and outpouching of $ucosa and su,$ucosa ". La3 o' Lap%a e the wall stress increases as radius increases. In ter$s of this, once you start dilating it, it doesn1t stop ,:c as you dilate so$ething, you increase the wall stress and e-entually it ruptures. 9o, in other words, all aneurys$s will rupture it1s just a $atter of when. $. A-*omina% Aor!a Ane&rysm: Ghy is the a,do$inal aorta the +C area of aneurys$N 3:c there is no -asa -asoru$ or ,lood supply to the aorta ,elow the renal arteries. 9o, the only way a,d. aorta gets '( and nutrients is fro$ the ,lood that1s in the lu$en. 9o, part furthest fro$ it $gets screwed. )herefore, apart fro$ the part that is not getting $uch '( and nutrients, it will ,e $ore suscepti,le to injury, therefore atherosclerosis leads to wea%ening of the wall and aneurys$:injury occurs. a. +C co$plication a,do$inal aortic aneurys$ " rupture. )he !ria* o' s7s are: a sudden onset of se-ere left flan% pain ,:c the aorta is retroperitoneal organ and so it does not ,leed into the peritoneal ca-ity, ,ut into the peritoneal tissue. 9o, se1ere %e'! '%an6 pain@ HypoTN@ an* p&%sa!i%e mass on PE. )hese are three things that always occur when there is a ruptured aortic a,do$inal aneurys$. +C omp%i a!ion o' any ane&rysm , r&p!&re 2. Ane&rysm o' !)e ar ) o' !)e aor!a = +CC , !er!iary syp)i%is. *athology of syphilis is -asculitis of arterioles. Chancre, too. Its painless ,:c if you section it, you will see little arterioles surrounded ,y plas$a cells and the lu$en of the -essel is co$pletely shut, so it is ische$ic necrosis. In other words, it is ische$ia of the o-erlying tissue undergoing necrosis. 3:c ner-es are next to -essels, they are %noc%ed off, too, and it is painless. A%% o' syp)i%is is a 1as &%i!is. )hat is what the Treponema infects s$all -essels and arterioles. Ghat are they affecting in the arch of the aortaN )he -asa -asoru$5 the richest supply of -asa -asoru$ is in the arch, so its logical that the Treponema will pic% it leads to endarteritis o,literans (they are o,literating the lu$en!, ische$ia, wea%ening under systolic pressures, leads to depression in the arch of the aorta (loo%s li%e a catcher1s $itt!. Ghat will that do to the aortic -al-e ringN It will stretch it which $ur$ur will this lead toN Aortic regurg. +ur$urs can occur ,:c there is -al-ular da$age or ,:c the -al-ular ring is stretched. 9o, there can ,e stretching of the ring and nothing wrong with the -al-es, and ha-e a $ur$ur, or you can ha-e da$age to the -al-es and ha-e a $ur$ur. 9yphilis is an exa$ple of stretching of the aortic -al-e ring leading to a $ur$ur and aortic regurg. Aorta should ,e closing during diastole as you pu$p the ,lood out, and the 9K goes down, and ,:c the aortic cannot close properly, only so$e of the ,lood will drip ,ac% in. 9o you will ha-e $ore -olu$e of ,lood in the left -entricle in so$eone with aortic regurg. 4ran%Dstarling forces will ,e wor%ing. As you stretch cardiac $uscle, you increase the force of contraction. &or$ally, you ha-e a 1(6 $l1s of ,lood and get out T6, so the ;4 is T6:1(6 "AA7. 8ets say you ha-e (66 $ls of ,lood in the 8K ,:c ,lood is dripping ,ac% in, and fran%Dstarling force gets out 166 $ls of ,lood, which has an ;4 of E67. 9o this isn1t as efficient. )herefore, fran%Dstarling occurs in a pathologic condition. If you ha-e 166 $ls of ,lood co$ing out of your aorta, that1s not good ,:c their head is wo,,ling, and when they open their $outh you can see u-ula pulsating, can ta%e their nail and lift it up and see pulsations of the -essels under the nail, GaterDha$$er pulse, and when listening with the stethoscope of the fe$oral artery you can hear ?urasane1s sign. )his is all due to the increase in 9K co$ing out related to the fact that there is $ore ,lood in the 8K. syphilitic aneurys$s of the a,do$inal aorta is the classic exa$ple of this. Anato$y correlation: the 8eft 2ecurrent 8aryngeal &er-e wraps around the arch and therefore can get hoarseness. Again the +C co$plication is rupture. 4. Disse !ing aor!i ane&rysm: a. 8ey 'a !or !)a! a&ses a !ear in !)e aor!a is HTN ,:c it i$poses stress on the wall of the -essel. )here $ust ,e wea%ening the elastic artery and is caused ,y elastic tissue frag$entation. Cys!i me*ia% ne rosis: that1s where the LAL1s $ix together and there1s $ucinous $aterial w:in, and walls of aorta ru, upon itself, and when adding a little ,it of .)& leads to a tear. Ghere-er the area of wea%ness in the elastic artery is where the ,lood will dissect and tear ,lood can go to the pericardial sac, leading to cardiac ta$ponade. )his is called the proxi$al dissection (+C!. +ost of the tears up in the arch5 therefore you would thin% the pt $ay ha-e an a,sent pulse5 this is -ery co$$on in pts with tears that are proxi$al. Ghen it dissects, it closes lu$en to su,cla-ian artery and it usually dissects on the left and causes an a,sent pulse on left. -. C)es! pain in +I is diff than the chest pain in a dissecting aneurys$. +I has chest tightness radiating to left ar$ and jaw5 in aortic dissection, there is a tearing pain radiates to the ,ac%5 and is a retrosternal pain. *ulse on left is di$inished -s. the one on the right. 'n chest xDray, widening of the aortic %no,. Gith ,lood there, dia$eter of aorta will ,e enlarged, as seen on xDray, and this test is TE7 sensiti-e in detecting it, therefore it is the screening test of choice5 see widening of the proxima% aor!i 6no-. )o pro-e, do transesophageal ultrasound or angiography to confir$ dx. . +any *>#s an pre*ispose !o aor!i *isse !ions: (1! +ar'an syn*rome (eunochoid proportions ht of pel-ic ,ri$ to feet is greater than fro$ pel-ic ,ri$ to the head. Also, another definition is that ar$ span is greater than the height. A? inheritance, c1so$e 1E, defect in fi,rillin, which is a co$ponent in elastic tissue. ?ue to the defect in fi,rillin, the elastic tissue is wea% this is why they ha-e dislocated lenses and ha-e dissected aortic aneurys$s (+CC death in $arfans is +K*!. ((! E)%er Dan%os has a collagen defect, +CC of death (0! Pregnan! 3omen are suscepti,le to dissecting aortic aneurys$s ,:c in pregnancy they ha-e twice the a$ount of plas$a -ol -s. a nonDpregnant wo$an. )here is an increase of plas$a -ol ,y ( and 23C $ass ,y 1, so it1s a (:1 ratio of increasing plas$a -ol to 23C $ass5 which decreases the ., concentration. )hat1s why all pregnant wo$en ha-e decreased he$oglo,in5 usually around 11.E is their cutoff for ane$ia and the cutoff is 1(.E for nor$al wo$en. )his is ,:c of dilutional effect with excess in plas$a -ol. Apparently in so$e wo$en, the excess plas$a -olu$e for R $onths can cause wea%ening of the aorta and there,y causing an aneurys$.
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.. .eno&s Disor*ers:
62
A. <&perior 1ena a1a %&ng syn*rome in a s$o%er with pri$ary lung cancer, now co$plaining of headache and ,lurry -ision loo% at his retina and see retinal -ein engorge$ent, and congested dxN <&perior 1ena a1a %&ng syn*rome usually due to pri$ary lung cancer %noc%ing off the sup -ena ca-a, leading to ,ac%up of -enous ,lood into the jugular -enous syste$ and to the dural sinuses5 this is a -ery ,ad dC, and will lead to death. <sually treat with radiation to shrin% the tu$or to get nor$al ,lood flow. ?on1t confuse with Pan oas! T&mor associated with .orner1s syndro$e. 9o, 9KC syndro$e has nothing to do with .orner1s, as opposed to *ancoast. (. .ari ose .eins .I. T&mors o' (%oo* .esse%s: A. <!&rge 5e-er syn*rome Iwe, loo%s li%e a $ini $ap on their faceJ it1s a -ascular $alfor$ation in the face and notice it1s in the trige$inal ner-e distri,ution ($a%ing it easy to dC!. .owe-er, on the sa$e side of the ,rain there1s an AK $alfor$ation, predisposing to ,leeding. 9o, not only a -ascular $alfor$ation of the face, ,ut also an AK $alfor$ation in the sa$e side of the ,rain, which predisposes to ,leeding. Also, these pts are a little $entally retarded. (so$e pts show it on the entire side of the face! (. Os%er 5e-er Ren*& a6a Here*i!ary )emorr)agi !e%angie !asia s$all telangiectasia in LI. A? inheritance characteriCed ,y localiCed telangiectases of the s%in and $ucous $e$,ranes and ,y recurrent he$orrhage fro$ these lesions. C. <pi*er angioma7spi*er !e%angie !asia: If you press down on this, the little tentacles will go away (therefore it ,lanches! called spider angio$a. It is due to hyperestrinis$. )his is nor$al in pregnancy. If a $ale has spider angio$a, he has cirrhosis (+CC cirrhosis " alcohol!. Ghy would a $ale ha-e a spider angio$aN 3:c if you ha-e cirrhosis, you cannot $eta,oliCe estrogen so it ,uilds up, leading to gyneco$astia, war$ s%in, pal$er erythe$a, and spider angio$a related to hyperestrinis$. Another reason would ,e ,:c they cannot $eta,oliCe 1@ %etosteroids either, therefore they will ,e aro$atiCed those in the adipose tissue into estrogen. 9o, they are ( ways of getting hyperestrinis$ in cirrhosis. 9o, how is this different fro$ petechiaN It loo%s diff5 also, it will ,lanch when you press it in ,:c it1s an AK fistula in other words, the ,lood goes directly fro$ arteriole to a -enule and is ,ypassing the capillaries. D. Capi%%ary Hemangioma: pic of child with red lesion (not ,ilateral wide eye lesion so its not retino,lasto$a!5 what do you doN Lea1e i! a%one5 do not surgically re$o-e ,:c ,y T y:o, it will ,e gone so, lea-e capillary angio$as alone ,:c they will go away. E. (a i%%ary angioma!osis: Kaposi sarco$a is caused ,y the ..K T organis$. If there was a lesion seen only in AI?s pts that loo%s li%e Kaposi sarco$a, ,ut it1s not5 what is it due toN It1s due to ,acteria -a i%%ary angioma!osis *&e !o -ar!ene%%a )ensi%ai seen with sil-er stain. 2xN 9ulfa drug. )his organis$ also causes Cat 9cratch ?C. 9. Angiosar oma o' !)e %i1er co$$on causes IKA)J " Kinyl chloride (people who wor% with plastics and ru,,er!, Arsenic (part of pesticides, conta$inated water!, and )horotrast (a radioacti-e diagnostic agent thoriu$ dioxide!. .II. .as &%i!is <yn*romes A. Con ep! o' .as &%i!is: Kasculitis of s$all -essels (arterioles, -enules, capillaries!, $uscular arteries, and elastic arteries. All of these -asculitis present with different signs and sy$pto$s (ie li%e coagulation disorders -s. platelet disorders!. 1. <ma%% 1esse% 1as &%i!is RR7 of the ti$e it is due to a type III .*B, $eaning it is in-ol-es i$$une co$plex deposition, that will deposit in the s$all -essel, acti-ate co$ple$ent and attract neutrophils (CEa!, and will get fi,rinoid necrosis and da$age to the s$all -essel and PALPA(LE PURPURA5 (re$e$,er the old person with purpura on the ,ac% of the hand that was not palpa,le and was due to he$orrhage into the s%in, there was no infla$$atory pro,le$ it just ruptured into the s%in! ,ut if it was palpa,le, it would ,e considered a 9+A88 K;99;8 -asculitis not a platelet pro,le$. ;xa$ple: 8eu%ocytoclastic -asculitis (hypersensiti-ity -asculitis!5 nuclear dust " fi,rinoid necrosis and i$$une co$plex dC1s5 and .enochD9chonlein purpura. <o@ <+ALL .E<<EL 1as &%i!is , PALPA(LE p&rp&ra /a%3ays !o%* in !)e s!em o' !)e ;&es!ion0. ". +&s &%ar ar!ery 1as &%i!is *olyarteritis &odosa and Gegener granulo$atosis. )hese will get ).2'+3'9I9 of the -essel, not palpa,le purpura. Gill ha-e IN9ARCTION. ;xa$ple: Kawasa%i1s ?C in children Icri$sJ coronary artery -asculitis ,rash,infarction,$i, swelling get coronary artery -asculitis +CC +I in children " Kawasa%i1s dC ,:c part of the syndro$e, in addition to $ucocutaneous infla$$ation, des#ua$ation of s%in, and ly$phadenopathy, there is a coronary artery -asculitis thro$,osis occurs and little child will ha-e an infarction. <o@ in'ar !ion is 3)a! yo& see 3i!) a m&s &%ar ar!ery 1as &%i!is. ;xa$ples: *olyarteritis &odosa, Gegener granulo$atosis, Kawasa%i1s dC in %ids. $. E%as!i ar!ery 1as &%i!is Ghen you %noc% off an elastic artery, then you deal with arch -essels, and they will get pulseless dC")a%ayasu1s arteritis the -asculitis will ,loc% off the lu$en of one of the arch -essels, leading to <TRO8E< and can %noc% off the internal carotid. ;xa$ple: )a%ayasu1s young, far eastern lady with a,sent pulse. <o@ pa%pa-%e p&rp&ra , sma%% 1esse% 1as &%i!is In'ar !ion , m&s &%ar 1as &%i!is In1o%1es p&%se7s!ro6e , e%as!i ar!ery 1as &%i!is
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(. Tempora% Ar!eri!is unilateral headache, aches and pains all o-er ,ody, loss of -ision of sa$e side of headache, hurts when pt chews in te$poral area. )his is a granulo$atous (ha-e $ultinucleated giant cell! -asculitis of the te$poral artery, a type of giant cell arteritides. It can in-ol-e other portions of the artery including the ophthal$ic ,ranch and produce ,lindness. )hat1s why the sedi$entation rate is the '&8B screen discreet for te$poral arteritis. GhyN &ot that it is specific, ,ut ,:c this is an arteritis, (an infla$$ation! the sed rate should ,e ele-ated. If the sed rate is &') ele-ated, it could ,e a transient ische$ic attac%. )his is good screen ,:c it ta%es ti$e to ta%e a ,iopsy and loo% at it, and the pt could go ,lind. 9o, you $ust put the pt on corticosteroids i$$ediately (right there and then! just ,ased on hx alone. )he pt will ,e on corticosteroids for one year. It1s associated with poly$yalgia rheu$atica $uscle aches and pains. )hey want you to say it is poly$yositis, ,ut it isn1t. *oly$yalgia rheu$atica does not ha-e an ele-ation of seru$ CK, and ha-e aches and pains of $uscles and joints. In poly$yositis, it1s an infla$$ation of $uscle. C. (&erger *> /a6a !)rom-oangii!is o-%i!erans = smo6ers *> !5 Iew ,oogers and s$o%e $a%e $e so sic% $y fingers and toes curlJ $ales, young, digital -essel thro$,osis, leading to autoinfarction of their fingers, A&? toes. It1s an acute infla$$ation in-ol-ing s$all to $ediu$DsiCed arteries. Heno )?< )on%ein p&rp&ra: (,utt, joints, git, renal,s%in! (palpa,le purpura on ,utt, n legs, joint pro,s, and %idney pro,s! 1> y:o, <2I one wee% ago, presents with polyarthritis, joint pains, he$aturia, with 23C casts and palpa,le purpura of ,uttoc%s and lower extre$ity dxN .enochD9chonlein purpura " +C -asculitis in children i$$une co$plex (as is all s$all -essel -asculitis! anti IgA i$$une co$plex, and the 23C casts are due to glo$erulonephritis. ?o not confuse with IgA glo$erulonephritis 3erger1s dC E. 5egener gran&%oma!osis ?i' & )a* !o go %is!en !o 3agner in on er!@ yo& 3o&%* pre!en* & )a* !o &se !)e -a!)room or ge! pne&monia Cin'ar #n@ %&ng@ &r!@ rena% @ sa**%e nose @ an aT y %op)osamine rxD pt with saddle nose defor$ity (not congenital syphilis! also pro,s with sinus infections, <2I1s, lung pro,s with nodular $asses, and glo$erular dC dxN Gegener granulo$atosis (+CC of saddle nose defor$ity!. )his is a granulo$atous infla$$ation A&? -asculitis. )herefore, it in-ol-es the upper airways, lungs, and %idneys5 also, there is an A, that is highly specific for it ?ANCA /an!i?ne&!rop)i% y!op%asmi A-0. Rx ? Cy %op)osp)ami*e (which can lead to he$orrhagic cystitis and ,ladder cancer and how can you pre-ent the he$orrhagic cystitisN +esna!. 9. Po%yar!eri!is No*osa I panca, h,sag, %idney, heart pro,le$s, infarc1nJ $ale do$inant dC that in-ol-es $uscular arteries, therefore infarction is a part of it. .as p?ANCA A- an* a )ig) asso ia!ion 3i!) Hep ( s&r'a e Ag#emia. ;xa$ple: ha-e IK?A with chronic .ep 3 who has a nodular infla$ed $ass on the lower extre$ity and he$aturia (due to %idney infarct!5 what does the pt ha-eN *olyarteritis &odosa ,:c the pt has a chronic hep 3 infection therefore has hep 3 surface antigens. 9o, re$e$,er p?ANCA an* Hep ( s&r'a e Ag. :. (a !eria% in'e !ions: -essel in R+<9. )he ric%ettsial organis$s infect endothelial cells5 the spots are petechia5 unli%e other ric%ettsial dC1s with rash, this starts on the extre$ities and goes to the trun% (whereas others start on the trun% and to the extre$ities!. Also ha-e to re$e$,er the -ector: tic%. 'ther tic% ,orn dC1s: 8y$e dC (,orrelia ,urgdorferi ,. recurentis is relapsing fe-er, and has antigenic shifts5 it is a spirochete (8eptospira and syphilis are also spirochetes!. 9o, 0 spirochetes 8eptospira, )repone$a, 3orrelia (I38)J! 9. 9&ng&s that is wide angle, nonseptate , pt has ?KA, and cere,ral a,scesses related to fungus m& ormy osis (%now relationship of this fungus and ?KA!5 ?ia,etics co$$only ha-e $ucor in their frontal sinuses5 so when they go into %etoacidosis and start proliferating, they go through the cri,ifor$ plate into the frontal lo,es where they infarct it and infect it with the dC. .III. 9&n !iona% .as &%ar Disor*ers: Rayna&* D> )here are $any causes this5 so$e in-ol-e cold reacting A,1s and cold reacting glo,ulins. *eople who go outside in the cold weather will get 2aynaud1s and cyanosis in the nose and ears (that co$es and goes away!5 so, it is due to Ig+ cold agglutinin dC or cryoglo,ine$ia in old $an with .ep C. .owe-er, we ha-e other dC1s that are o%%agen 1as &%ar *> and first $anifestation is 2aynaud1s5 this in-ol-es a digital -asculitis and e-entually a fi,rosis progressi-e syste$ic sclerosis (a%a scleroder$a!, and its counterpart C2;9) syndro$e. Kasculitis of fingers and leads to fi,rosis will e-entually autoDa$putate finger (li%e 3erger1s!. CRE<T syn*rome Calcinosis (dystrophic calcification! and Centro$ere A, (specific for crest syndro$e!, 2aynaud1s, ;sophageal dys$otility, 9clerodactyly (finger that is -ery narrow!, )elangiectasia (-ery si$ilar to the pin point he$orrhages also seen in 'sler Ge,er 2endu!.OOOOOOOOOOO 'ther causes due to -asoconstriction co$$on in pts that ta%e drugs for $igraine drugs for $igraines cause -asoconstriction of -essels. 9o, 2aynaud1s can occur after ta%ing ;rgot deri-ati-es5 3uerger dC, too. T)ere'ore@ genera% a&ses o' Rayna&*#s: 1aso ons!ri !ion@ 1as &%i!is o' !)e *igi!s /ie CRE<T an* s %ero*erma0@ an* o%* rea !ing A-#s an* g%o-&%ins . IG. Hyper!ension /HTN0
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+CC death with .)& " +I ((nd " stro%e, 0rd " renal failure! ;ssential .)&" +C
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A. +&%!i'a !oria% In)eri!an e: Ghat racial group has highest incidence of .)&N 3lac%s. GhyN +ultifactorial inheritance (a%a polygenic inheritance5 other dC1s include: gout, CA?, )ype II dia,etes, affecti-e disorders, congenital pyloric stenosis, essential .)&!. )his $eans that you ha-e a tendency to 4'2 the dC, ,ut don1t necessarily get the dC. GhyN 3:c it1s +<8)IfactorialM ;xa$ple: I a$ ,lac%, what should I do to pre-ent fro$ getting itN I cannot get rid of genetics, and $y genetics are that I anno! ge! ri* o' sa%! in my &rine D retaining too $uch salt /3)i ) is !)e -asi me )anism o' essen!ia% HTN in -%a 6s an* e%*er%y !. 9o, cannot control genetics, ,ut I can control 0 things: (1! weight has a direct correlation with .)&5 ((! reduce salt inta%e5 and (0! exercise. ;xa$ple: fa$ily hx of gout, what can I do so I a-oid goutN A-oid red $eet, no alcohol (which will decrease purine $eta,olis$!. ;xa$ple: If you had a fa$ily hx of ?+ type II ,e s%inny (lean and $ean! as you lose adipose, upregulate insulin receptor synthesis and that alone could pre-ent you fro$ ha-ing the dC. (. +e )anism o' HTN ,:c you re!ain sa%! (it1s not the only $echanis$, ,ut the +C one!. Ghen you retain salt, what co$part$ent will the salt ,e retained inN ;C4 if that is true, what will ,e the plas$a -olu$e if you ha-e excess salt in your -ascular and interstitial co$part$entN Increased if your plas$a -ol is increased, your stro%e -olu$e will ,e increased which is your sys!o%i HTN /-7 in rease in PLA<+A 1o%0. Ghen you ha-e excess salt, salt wants to go into s$ooth $uscle cells (into peripheral resistance arterioles!. Ghen sodiu$ enters $uscle, it opens certain channels for Ca to go in5 Ca goes in and s$ooth $uscle will contract, so the peripheral resistance arterioles are -asoconstricting. )*2 " -iscosity:radius>5 we are decreasing radius, increasing resistance, and re!aining more -%oo* in !)e ar!erio%e sys!em /!)a! regis!ers as an in rease in *ias!o%i press&re0. )his is why the 2x of choice for essential .)& in ,lac%s and elderly " hydrochlorothiaCide ,:c you rid salt and water to decrease 3*5 howe-er, do not use if pt has hyperlipide$ia, so use AC; inhi,itors. Is this a high or low renin type of .)&N 8ow renin ,:c increased plas$a -olu$e " increased ,lood flow to the renal artery " decreased renin. 9o that1s the ,asic $echanis$ of .)&. C. Comp%i a!ions: .)& is a $ajor ris% factor for CA?, leading to +I /+CC *ea!)!. 9tro%e " S(. 3lood is located in glo,us pallidus and:or puta$en this is where al$ost all of the .)&1i-e ,leeds occur in the ,rain. )his is ,:c the lenticulostriate -essels (which are s$all -essels of the $iddle cere,ral artery! under increased pressure for$ aneurys$s called C)ar o! (o& )ar* ane&rysms, and they rupture. )his is not a good place to rupture. )herefore, this is not an infarct it is a he$ato$a it1s a ,lood clot right there. &eurosurgeons can suc% these out. )herefore the "n* +CC *ea!) is HTN#1e -%ee* . ;xa$ple: %idney that is too s$all with a pe,,ly surface due to hyaline arteriolosclerosis a s$all -essel dC is causing ische$ia of the %idney, atrophy of tu,ules, destruction of glo$eruli, shrin%age of %idney, and leads to %idney failure. )his is the $r* +CC *ea!) in HTN. +C o-erall a,nor$ality in .)& " 8K. ($ech: afterload pro, ,:c the heart has to contract against increased resistance and if it re$ains o-er a period of ti$e it will e-entually lead to heart failure. Audio Cardio-ascular ( CHAPTER H: CARDIO.A<CULAR THE HEART I. Hyper!rop)y o' !)e Hear!: Con en!ri /!)i 60 HPY#* )ear! 1s. Di%a!e* HPY )ear!: ( different etiologies, and they in-ol-e wor%. It re#uires a lot of wor% to contract and push ,lood thru a stenotic aortic -al-e, or increased )*2 fro$ .)&. )hese will cause an in rease* a'!er%oa* , on en!ri HPY. If you ha-e a -al-ular pro,le$, and ha-e excess -olu$e of ,lood in the -entricles increased preload " increased wor%. )herefore, the fran% starling goes into effect ,:c stretching and increasing preload in there, and you ha-e to wor% harder to increase the force of contraction this produces dilated .*B. )herefore, on en!ri HPY , a'!er%oa* pro-%emI *i%a!e* HPY , 1o%&me o1er%oa* , pre%oa* pro-%em /in rease* 1o%&me0 II. Hear! so&n*s = <1 )ear! so&n* " ,eginning of 9ystole " $itral and tricuspids close ($itral closes ,efore the tricuspid ,:c higher pressures! <" )ear! so&n* " ,eginning of ?iastole " pul$onic and aortic close (-ariation with respiration as diaphrag$ goes down they increase the intrathoracic pressure. 3lood is ,eing suc%ed into the right side of the heart, and the pul$onic -al-e will close later than the aortic -al-e. 9o, the second heart sound has a -ariation with inspiration the *( separates away fro$ A( ,:c $ore ,lood co$ing into the right heart, so the -al-e closes a little ,it later. <$ )ear! so&n* , nor$al under 0E y:o1s. After that, it is pathologic. 91 " ,eginning of systole and 9( " ,eginning of diastole5 o,-iously, 90 " early diastole. 90 is due to ,lood, in early diastole, going into a cha$,er that is -olu$e o-erloaded. 9o, ,lood fro$ the left atriu$ is going into o-erloaded cha$,er, causing tur,ulence, which is the 90 heart sound. 'nly hear <$ )ear! so&n* in 1o%&me o1er%oa*e* )am-er. It could ,e fro$ 8.4 (left -entricle o-erloaded! or 2.4 (right -ent o-erloaded!, so there are left sided 901s and right sided 901s it $eans -olu$e o-erload in the cha$,er. Analogy: ri-ers going into ocean leads to tur,ulence (ocean is the -entricle with a lot of fluid in it and the ri-er is the ,lood co$ing in during diastole5 the ri-er hits this large $ass of fluid in the -entricle, causing tur,ulence and an 90 heart sound!. <2 )ear! so&n* " late diastole this is when the atriu$ is contracting and you get the last ,it of ,lood out of the atriu$ into the -entricles, leading to 9> sound. 9>1s occur if there is a pro,le$ with co$pliance. Co$pliance is a filling ter$.
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9o, when tal%ing a,out co$pliance, referring it1s a,ility to fill the -entricle. )he left atriu$ is contracting, trying to get ,lood into a thic% -entricle5 the -entricle is nonco$pliant, and therefore resistance will occur. )his will create a -i,ration, leading to an 9> heart sound. An <2 )ear! so&n* is *&e !o a pro-%em 3i!) omp%ian e . )he left atriu$ is encountering a pro,le$ in putting ,lood in late diastole into the left -entricle and it doesn1t want to fill up any$ore. )his could ,e due to ( reasons: (1! ,:c it1s hypertrophied (it doesn1t want to fill any$orerestricting filling up! or ((! it1s already filled up and has to put $ore ,lood in an already o-erfilled cha$,er. <&mmary: <%i*es: Kol o-erloadedN &o 90. 9o can it ha-e an 9>N Bes. If you ha-e .)&, which type of heart will you ha-eN Concentric .*B. 9o, in .)&, which type of heart sound will you ha-eN 9>. Kol o-erloadedN Bes. 9o can it ha-e an 90N Bes5 can it also ha-e an 9>N Bes. Ghy can it also ha-e an 9>N 3:c it can1t fill up any$ore. Analogy: tur%ey dinner all filled up, ,ut always roo$ for desert lil -i,ration that occurs when it fills is an 9> heart sound. 9o you ha-e ,oth 90 and 9> heart sound " gallop rhyth$ (they ha-e 91, (, 0, and >!. .ow do you %now if its fro$ the left or rightN It is ,reathing. Ghen you ,reath in, you are suc%ing ,lood to the right side of the heart. A%% rig)! si*e* )ear! m&rm&rs an* a-norma% )ear! so&n*s /ie <$@ <20 in rease in in!ensi!y on inspira!ion this is $ore o,-ious ,:c there is $ore ,lood in there, and it e$phasiCes those a,nor$al sounds. *ro, get the$ on expira!ion 3i!) posi!i1e in!ra!)ora i press&res that are helping the left -entricle push ,lood out of the heart this is when a,nor$al heart sounds and a,nor$al $ur$urs will increase in intensity on expiration. 9o, all you ha-e to do is figure out that there is an 90 heart sound. OOOOO)hen, you ha-e to figure out which side it is co$ing fro$. 8ouder on expiration, therefore its fro$ the right side. ;xa$ple: essential .)& " left5 +itral regurg " right5 and +itral stenosis " $iddle. III. +&rm&rs <!enosis " pro, in opening, that is when the -al-e is opening, and that is when the $ur$ur occurs. Reg&rgi!a!ion " pro, in %osing the -al-e, that is when the -al-e is closing, and that is when the $ur$ur occurs. &eed to %now where -al-es are heard ,est right ( nd IC9 (aortic -al-e!, left (nd IC9 (pul$onic!, left parasternal ,order (tricuspid!, apex ($itral! this isn1t necessarily where the -al-e is, ,ut where the noise is heard the ,est. A. <!enosis: 1. <ys!o%i +&rm&rs: Gho is opening in sys!o%e , aor!i an* p&%moni 1a%1es " therefore, $ur$urs of aortic stenosis and pul$onic stenosis are occurring in systole. )his is when they are opening5 they ha-e to push the ,lood through a narrow stenotic -al-e. a. Aor!i <!enosis 8K contracts and it is encountering resistance D intensity of the $ur$ur goes up5 as it is pushing and pushing, it gets to a pea% and this is dia$ond shape configuration this is why it is called an eQe !ion m&rm&r. 9o, they often ha-e diagra$s of the configurations on these $ur$urs. Gith an ejection $ur$ur (aortic stenosis!, it will ha-e a crescendoDdecrescendo (hence, dia$ond shaped configuration!. 9o, with aortic stenosis, there is an ejection $ur$ur in systole, heard ,est at the right ( nd IC9, which radiates to the carotids, and the $ur$ur intensity increases on expiration, and will pro,a,ly hear an 9> -. P&%moni <!enosis heard ,est on left (nd IC9, ejection $ur$ur, and increases on expiration. ". Dias!o%i m&rm&rs: In diastole, $itral and tricuspid -al-es are opening. a. +i!ra% <!enosis (pro,le$ in opening the -al-e! who has the pro,le$N 8eft atriu$. .ere1s the pro,le$, the $itral -al-e doesn1t want to open ,ut it has to in order to get ,lood into the left -entricle. 9o, the left atriu$ will get strong ,:c it has an afterload to deal with it ,eco$es dilated and hypertrophied (the atriu$! which predisposes to atrial fi,, thro$,osis, and stasis of ,lood. 9o, the atriu$ is dreading diastole ,:c it has to get the ,uildup of ,lood into the left -entricle. Gith the ,uild up of pressure, the $itral -al-e IsnapsJ open, and that is the opening snap. All the ,lood that was ,uilt up in the atriu$ co$es gushing out into the -entricle, causing a $idDdiastolic ru$,le. 9o, you ha-e an opening snap 'o%%o3e* -y a r&m-%ing so&n* (due to excess ,lood gushing into 8K!. Gith $itral stenosis, there is a pro,le$ with opening the -al-e, and therefore you are under filling the left -entricle, and therefore will ,e no .*B ,:c you are under filling it. If you are ha-ing trou,le getting ,lood into it, you are not o-erwor%ing the -entricle5 the left atriu$ has to do $ost of the wor%. .eard ,est at the apex and will increase in intensity on expiration. /same on ep! 3i!) !ri &spi* s!enosis@ Q&s! a *i''eren! 1a%1e0. (. Reg&rgi!a!ion = pro,le$ in closing the -al-e. 1. <ys!o%i +&rm&rs: mi!ra% an* !ri &spi* are %osing in sys!o%e. a0 +i!ra% Reg&rg: If they are inco$petent and $itral -al-e cannot close properly. ;xa$ple: T6 $ls of ,lood " nor$al stro%e -olu$e5 lets say 06 $ls into the left atriu$ and only E6 $ls lea-es the aorta. 9o, an extra 06 $ls of ,lood in the left atriu$, plus trying to fill up and ha-e excess ,lood there way $ore ,lood ends up in the left -entricle and it ,eco$es 1o%&me o1er%oa*e*. 9o, how would the $ur$ur characteristics ,e if there is a pro,le$ in closing the -al-eN It will not ,e an ejection $ur$ur5 will just sound li%e IwhooooshJ all the way through, as ,lood all the way through systole is going through the inco$petent $itral -al-e, ,ac% into the left atriu$ therefore it is pansystolic or al$ost pansystolic so it1s a =straight line1 effect. 9o$eti$es, it will o,literate 91
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and 9(. <o@ is an api a% m&rm&r@ pansys!o%i @ <$ an* <2 /-7 in rease* in in!ensi!y on expira!ion. a pro-%em 3i!)
66
omp%ian e an* 1o%&me o1er%oa*@
-. Tri &spi* Reg&rg: it will ,e pansystolic, 90 and 9>, left parasternal ,order, and increases on intensity on inspiration!. ;xa$ple: IK?A with fe-er, pansystolic $ur$ur along parasternal ,order, 90 and 9> heart sound, accentuation of the nec% -eins, what is the $ost li%ely dxN Infecti-e endocarditis of tricuspid -al-e, which is the +C infection. 9o, it was extre$ely i$p to %now if the $ur$ur increased on inspiration (which is right sided!. If the #uestion said that the $ur$ur had increased on expiration, it would ,e Infecti-e endocarditis of the $itral -al-e (which is left sided!. ". Dias!o%i in!. +&rm&rs: 3an! !)e aor!i an* p&%moni 1a%1es !o %ose (what you just pu$ped out doesn1t want to co$e ,ac%
Aor!i Reg&rg (as seen in syphilis aneurys$ ,ut this is due to the stretching of the ring!. In systole the ,lood goes out and the -al-e should ,e closing properly , ,ut it doesn1t, so so$e ,lood will tric%le ,ac% in. ;xa$ple: T6 cc went out initially and 06 cc is dripped ,ac% in. As ,lood %eeps dripping ,ac% in, you will get a 1o%&me o1er%oa*e* cha$,er. ;-entually you will ha-e and ;?K of (66 $ls (instead of 1(6!. 9o, for aortic regurg, when you hear the $ur$urN After the ( nd heart sound ,:c it isn1t closing and ,lood is dripping ,ac% in that $a%es the sound of a high pitched ,lowing diastolic $ur$ur into the right second IC9, increases in intensity on expiration, 90 and 9> heart sounds, -ol o-erloaded, and ,ounding pulses. Ghat -al-e leaflet is dripping ,loodN Anterior leaflet of $itral -al-e. )his is one side of the outflow tract out of the aorta. Ghat $ur$ur does that createN A&s!in '%in! m&rm&r. If you ha-e aortic regurg with an Austin flint $ur$ur, you need to call the cardiac surgeon. &eed to replace the -al-e ,:c you are significantly dripping ,lood. )herefore, this $ur$ur is i$p ,:c when it is there, you ha-e to perfor$ surgery. I.. Hear! 9ai%&re: Le'! or Rig)! Hear! 9ai%&re 8eft .4 " lungs and *aroxys$al nocturnal dyspnea:pillow orthopnea 2ight " 8i-er A. Le'! )ear! 'ai%&re"forward failure, cant get ,lood out of the heart ,:c the 8K fails )herefore your left -entricle has to push against an afterload and fails5 or it has to deal with excess -olu$e and fails5 or you1-e had so $any infarcts that the left -entricle is no longer $uscle ,ut now fi,rous tissue and this reduces contractility and it fails. It1s a forward failure ,:c you are ha-ing pro,le$s getting ,lood outside of the heart. )his $eans that ;?K will increase ,:c you cannot get all the ,lood out ,:c you cannot push it out. )he pressure and -olu$e will go ,ac% in to the left atriu$, ,ac% into the pul$onary -essels, increase the hydrostatic pressure, and then pul$onary ede$a. Gith chronic left heart failure, this will lead to he$orrhage and al-eolar $acrophages will phagocytose 23C1s, leading to rusty colored sputu$. 'n cytology, you will see heart failure cells, which are al-eolar $acrophages that has phagocytosed 23C1s and is ,ro%en down to he$osiderin. P&%monary e*ema is a%3ays %e'! )ear! 'ai%&re. Le'! )ear! 'ai%&re is a *iagnosis o' symp!oms@ -7 !)e main symp!om in LH9 is *yspnea /<O(0@ )a1e !ro&-%e -rea!)ing -7 '%&i* in !)ere. (. Rig)! Hear! 9ai%&re: ?iagnosis of signs: 3ac%ward 4ailure5 cant get ,lood into the heart. 2.4 is a pro,le$ of the right heart getting ,lood through the pul$onary -essels to the left heart. 9o, if it fails, ,lood ,uilds up ,ehind it, and it is a ,ac%ward failure. 3:c if it cannot get ,lood through pul$onary -essels into the heart, ,lood will ,uild up ,ehind it, and hydrostatic pressures will ,uild in the -enous circuit. )his leads to nec% -ein distension5 also, will get hepato$egaly (which is painful!, and a nut$eg li-er ,:c of the increased pressures in the -ena ca-a are trans$itted to the hepatic -ein, which e$pties into it, then ,ac% into the li-er and the central -ein, then will get red dots all o-er li-er, which loo%s li%e a nut$eg. +CC onges!e* )epa!omega%y , RH9. Ghat caused the increased in hydrostatic pressure also going to produce pitting ede$a and possi,ly ascites therefore its $ore signs than it is sy$pto$s. 9o, ne 6 1ein *is!ension@ pi!!ing e*ema@ )epa!omega%y@ n&! meg %i1er@ as i!es. C. Examp%es o' LH9: Ghen you lie down to go to sleep, you can rea,sor, up to 1 liter of fluid ,:c it will go fro$ the interstiu$ to the -enous side ,:c there1s no effecti-e gra-ity. )herefore, there is extra ,lood going ,ac% to the right heart and into the left heart. .owe-er, what if you had left .4N )here will ,e excess ,lood co$ing ,ac% (that wasn1t there when you were standing up! and the left heart is ha-ing trou,le getting ,lood out, with e-en $ore ,lood co$ing ,ac% in. )hen the heart cannot handle it and goes ,ac% to the lungs, leading to dyspnea and continues for the next 06 $inutes this is paroxysma% no !&rna% *yspnea. ;-entually it settles down, you go ,ac% to sleep, wa%e up again, and it occurs again. *t realiCes that after you stand up, then it e-entually goes away therefore they put a pillow under the$ to decrease the dyspnea when they wa%e. )his is called pi%%o3 or!)opnea. If its one pillow orthopnea, its not that ,ad5 howe-er, if you ha-e to sit up, you ha-e serious left heart failure ,:c you are i$posing gra-ity. Fust ,y putting head on one pillow will decrease -enous return ,ac% to the heart. If you put ( pillows under, it will decrease the dyspnea e-en $ore ,:c of effecti-e gra-ity. 9o, pi%%o3 or!)opnea an* paroxysma% no !&rna% *yspnea are signs o' LE9T )ear! 'ai%&re. D. Trea!men!: If you ha-e heart failure (right or left!, what is the ,est nonphar$acologic treat$entN 2estrict water and salt. 5)a! !)e 6ing o' Rx o' H9E ACE in)i-i!or -7 i! *e reases a'!er%oa* AND pre%oa* a! !)e same !ime. ACE in)i-i!ors increase longe-ity ,y (1! decreased aldosterone, therefore decreased salt and water rea,sorption which decreases preload and ((! ,y ,loc%ing Angiotensin II, will lead to a decrease in -asoconstrictor effect on peripheral resistance arterioles, which will decrease afterload. *ts with spirono%a !one U ACE in)i-i!or did ,etter ,:c aldosterone will e-entually ,rea% through and ,eco$e ele-ated again, therefore AC; inhi,itor acting against aldosterone is not a per$anent suppression. 9o spironolactone which specifically ,loc%
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aldosterone, plus the AC; inhi,itor is an increase in prognosis. )herefore, now it1s nor$al to put the pt on spironolactone and AC; inhi,itor ,:c it will increase longe-ity. E. Hig) o&!p&! 'ai%&re 'ne cause is en*o!oxi s)o 6 peripheral resistance arterioles are dilated, therefore an increase in C0a, CEa, &', leading to increased -enous return to the heart and the heart e-entually gi-es up. )here are also $any other causes, and they relate to *ouseau1s law -iscosity:radius to the fourth power. 9o, if you -asodilate the peripheral resistance arterioles, and you decrease )*2, $ore ,lood returns to the right heart, the left heart has to deal with it, too, and pt runs the ris% of high output failure. 9o, one cause of the -asodilatation is sep!i s)o 6, while the other is !)iamine *e'i ien y. *ro,le$ in thia$ine def: A)* depletion : s$ooth $uscle cells and peripheral resistance arterioles need A)*, therefore they do not wor% as well, and there is -asodilatation of the peripheral arterioles, leading to high output failure. 9o, thia$ine def can produce high out put failure ,:c -asodilatation of those -essels. :ra1es#s *> hyperthyroidis$ thyroid hor$one increases the synthesis of ,eta receptors in the heart. Let an increase in force of contraction, and $ore ,lood. 9ystolic pressures are higher, and go into high output failure. A. 'is!&%as ie get sta,led in the leg5 and de-elop an AK $alfor$ation, where there is arteriole ,lood ,ypassing the $icrocirculation going directly to the -enous circulation and the ,lood co$es ,ac% faster to the heart than nor$al5 a ,ruit can ,e heard o-er the $ass and it will ,e pulsatile5 if you press the proxi$al portion of it, heart rate would slow (3renha$1s sign! these are all signs of AK fistula, leading to high output failure. <o@ $ examp%es o' )ig) o&!p&! 'ai%&re are en*o!oxi s)o 6@ gra1es@ an* A. 'is!&%as .. Congeni!a% )ear! *> A. 8no3 'e!a% ir &%a!ion (which -essels ha-e the least:$ost '(!5 re$e$,er that the ,a,y is &') exchanging ,lood with '( in the lungs. *ul$onary -essels in the fetus loo% li%e they ha-e pul$onary .)& they are so thic% that it is extre$ely hard to get ,lood through the pul$onary artery into the 8K ,:c -ery little ,lood can go there this is why ,a,y needs a patent ductus to get ,lood out. Ghere is '( co$ing fro$N Co$ing fro$ chorionic -illus dipping into la%e of ,lood, which deri-es fro$ $o$1s spiral arterioles. .a-e chorionic -illi dipping into ,lood and extracting '( fro$ it. ',-iously, this is not as good an ' ( source as the lungs5 therefore, you want a high affinity ., to ,e a,le to get what little '( is down in the area this is why ,a,ies ha-e .,4, ,:c of its high affinity to gra, '( fro$ the ,lood. 3ad news is that it gets the ' (, ,ut doesn1t want to gi-e it up (says $ine! it left shifts the cur-e. Ghat is co$pensatory responseN )his left shift causes tissue hypoxia, which will cause ;*' to ,e released and the %id will ha-e an 1T gra$ ., ,:c of this, all new,orns (in a sense! ha-e polycythe$ia. )his is the way around .,41s high affinity for ' ( $ore 23C1s $ade, $ore .,, and ,a,y gets $ore '(. Or*er o' O" passing: '( goes through syncytiotropho,last of chorionic -illus, into the cytotropho,last, then through the $yxo$atous stro$a of the chorionic -illus, then into the ,lood -essel. )he ,lood -essels of the chorionic -illis all coalesce to for$ the &m-i%i a% 1ein. )his has the )ig)es! O" on!en!. It goes to the li-er and it can go two ways: 1! into the hepatic sinusoids and recollects into the hepatic -ein and gets du$ped into the IKC5 and (! ductus -enosis and straight into the IKC. )hen it goes up the right side of the heart5 the fora$en o-ale is open in all fetuses (its not closed! so all this ,lood is co$ing up the IKC will it go straight across, through the fora$en o-ale and into the left atriu$, or will it go into the IKC into the right atriu$, down to through the tricuspid -al-e, and into the right -entricleN It will go through the fora$en o-ale. 9o, all this oxygenated ,lood will go directly fro$ the right atriu$ of the fora$en o-ale into the left atriu$, then the left -entricle and out the aorta. Ghat a,out 9KC ,lood -al-eN It is co$ing fro$ the superior part of the right atriu$ (its not gonna $a%e a left turn and go through the fora$en o-ale!. It will go straight down, through the tricuspid -al-e into the right -entricle. &ow, it will go out the pul$onary artery. )his is a *2'38;+ ,:c the pul$onary -essels are too thic% and it1s encountering this tre$endous a$ount of pressure. )o counter this pro,le$, %ept the patent ductus open (which is %ept open ,y the *L;(, a -asodilator, $ade ,y the placenta! so, there is a right to left shunt and ,lood can get out of the pul$onary artery and du$ped ,ac% into the aorta. )hen, when the ,a,y is ,orn and ta%es its first ,reath, the pul$onary -essels (that were all shut!, all open within a $illisecond, and ,lood is going through those pul$onary arteries and gas exchange is occurring through the lungs in literally seconds. Also, the patent ductus closes and for$s the liga$entu$ arteriosu$. )his is nor$al fetal circulation. Kessels with the least '( are the ( u$,ilical arteries, and the one with the $ost a$ount of '( is the u$,ilical -ein. (. <)&n!s: 8oo% at '( saturations (this is how they dx the$ they catheteriCe, $easure '( saturations in different cha$,ers, and %now which direction the shunts are going. &eed to get used to two ter$s step up and step down. If you ha-e a %e'! !o rig)! s)&n!, and ha-e oxygenated ,lood going into un'(1d ,lood, what is happening to '( saturation on the right sideN <!ep &p -7 mixing O"#* 3i!) &nO"#* -%oo*. If you ha-e a rig)! !o %e'! s)&n! with &nO"#* -%oo* going in!o !)e O"#* -%oo*N <!ep *o3n. )he '( saturation on the right side of the heart in ,lood returning fro$ the ,ody is @E7. )he '( saturation on the left side is RE7. C. .<D /+C0 Gho1s stronger D left or right -entricleN 8eft, therefore the direction of the shunt is left to right. 9o, oxygenated ,lood will ,e du$ped into the right -entricle, leading to step up. Also, it will pu$p it out of the pul$onary artery, leading to step up. 9o, you ha-e a step up of '( in right -ent and pul artery. Ghat if this is not correctedN Gith this $ech, you are -olu$e o-erloading the right side of the heart ,:c of all that ,lood co$ing o-er. )he outco$e of this will ,e p&%monary HTN (the pul$onary artery has to deal with $ore ,lood and $ust contract $ore leading to pul .)&! 'nce pul .)& occurs, right -entricle will ha-e a pro,le$ contracting
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and it will get hypertrophied. 9uddenly, you run the ris% of re-ersing a shunt ,:c then right -entricle could e-entually ,e stronger than the left. 9o, it will ,e a right to left shunt this is called Eisenmenger#s syn*rome. 9o, an uncorrected left to right shunt has the potential for producing ;isen$enger1s syndro$e. After re-ersal of the shunt occurs, pt will ha-e yanosis (a%a cyanosis tardi-e!. +ost K9?1s close spontaneously and so$e need to ,e patched. D. A<D &or$al for a fetus to ha-e a patent fora$en o-ale5 it is not nor$al once they are ,orn. Ghich direction will ,lood go through the fora$en o-aleN 8eft to right (,:c the left side is always stronger than the right!. )herefore, what will happen to the right atriu$N <!ep &p so it will go fro$ @E to T67. Ghat will happen to the right -entricle and pul$onary arteryN <!ep &p. 9o, 3)a! is !)e main *i'' in O" sa!&ra!ions in .<D 1s A<DE A<D is s!ep &p o' O" a%so in !)e rig)! a!ri&m. Are you -olu$e o-erloading the right heartN Bes. 9o do you run a ris6 'or Eisenmenger#sN Bes. Ghat else are at increased ris% forN *aradoxical e$,oliCation. Ghat if you weren1t luc%y enough to ha-e a ?K) in the leg, and it e$,oliCe up and the pressures of the right side of the heart are increasing, and you ha-e a patent fora$en o-ale will there ,e an e$,olus that can go fro$ the right atriu$ to the left atriu$ and will ha-e a -enous clot in arterial circulationN Bes this occurs in pts with A9?. +C !era!ogen !)a! )as A<D asso ia!e* 3i!) i!E 9e!a% a% o)o% syn*rome /174FFF0 E. PDA It1s nor$al in a fetus ,ut not when they are ,orn. Connection ,etween the aorta and pul$onary artery which is strongerN Aorta. 9o, oxygenated ,lood goes fro$ left and get du$ped in the pul$onary artery ,efore going into the lungs. 9o, what happens in the pul$onary arteryN 9tep up. 9o, now its T67 '( saturation !)e p&%monary ar!ery is !)e on%y !)ing !)a! )as a s!ep &p o' O". )hen will go under the lungs and the pul$onary -ein will ha-e the nor$al RE7 '( sat. 3:c there is an opening ,etween these, there is ,lood going ,ac% and forth during systole and diastole ma )inery m&rm&r where is it heard ,estN 3etween shoulder ,lades. Can you -ol. o-erload the right heartN Bes. *ul$onary .)&N Bes. &ow which way will the shunt goN Gill go the sa$e way when it was a fetus5 you will ha-e un'(1d ,lood du$ping into the aorta. Ghere does the ductus e$ptyN ?istal to the su,cla-ian artery so, the ,a,y will ha-e pin% on top and ,lue on ,otto$ ,:c du$ping un'(1d ,lood ,elow the su,cla-ian artery, therefore will ha-e *i''eren!ia% yanosis = pin6 on !op@ yano!i on -o!!om . Ghat is the teratogen assoc with *?AN Congenital 2u,ella. If you had a *?A, can you close it off without surgeryN Bes. .owN In*ome!)a in ? !)is is a po!en! N<AID@ 3)i ) 3o&%* in)i-i! P:E", and therefore would start constricting and close on its own. 9. Te!ra%ogy o' 9a%%o! +C cyanotic congenital dC: ItetraJ " four o-erriding aorta: its straddling the septu$5 pul$onic stenosis ,elow the -al-e, 2K., $e$,ranous septal defect (K9?!. Ghat deter$ines whether you get cyanosis or notN ?egree of pul$onic stenosis5 not all ,a,ies ha-e cyanosis and are acyanotic called a yano!i !e!ra%ogy5 why does this occurN 8ets say the degree of pul$onic stenosis is not that ,ad when the right -ent contracts, a lot of the ,lood goes up the pul$onary artery to get '(1d and less ,lood gets into the left -entricle, and therefore pro,a,ly will not ha-e cyanosis at ,irth. Ghat if it was a se-ere stenosis and when the right -ent contracts, -ery lil ,lood got up thereN +ost will ,e shunted right to left and there will ,e a step ?'G& in '( in the left -ent and ,a,y will ,e cyanotic. 9o, i! is !)e *egree o' p&%moni s!enosis !)a! *e!ermines 3)e!)er yo& )a1e yanosis or no!. Ghich of the groups of shunts is cardioDprotecti-e in a pt with tetralogy of fallotN *?A, A9? good lets say there is an A9?, therefore ,lood will go left to right ,:c we get '(1d ,lood e$ptying into the right atriu$. )his would cause a step up of ,lood into the right atriu$ (this is good!. .ow a,out a *?AN 8ets $a%e ,elie-e this occurs so, un'(1d ,lood pushed fro$ left fro$ the aorta down to the pul artery to get '(5 so$e of the un'(1d ,lood put ,ac% into the pul artery, where it gets '(1d and $ore gets out goo* !o )a1e PDA an* A<D /'oramen o' o1a%e0 3i!) !e!ra%ogy o' 'a%%o!. Rig)! !o %e'! %ea*s !o po%y y!)emia an* a rea% ris6 'or in'e !i1e en*o ar*i!is ,:c shunts going into left side, therefore can get -egetations going into the ,rain and other syste$ic organs. A%% ongeni!a% )ear! *e'e !s %ea* !o in'e !i1e en*o ar*i!is. :. Transposi!ion o' :rea! 1esse%s ;xa$ple: in Kartagener1s syndro$e with syndro$e with sinus in-ersus this not the case with transposition of great -essels ha-e a nor$al heart that is on the right side (e-erything isn1t re-ersed the way it is in sinus in-ersus!. Ghat1s transposedN &ot the right atriu$ it is still getting unoxygenated ,lood. Its not the left atriu$ it is still getting RE7 '( saturated ,lood fro$ the pul$onary -ein. T)e pro-%em is in !)e 1en!ri %es the right -entricle is ,eing e$ptied ,y the aorta5 and the left is ,eing e$ptied ,y the pul$onary artery. 9o, the thing that is transposed are the -entricles (the atria are fine!. )his is inco$pati,le with life unless you ha-e shunts: K9?, A9?, and *?A can wor%. .ow1s does this wor%N 9tart at the atrial side ha-e RE7 '( co$ing into left atriu$ and it is going fro$ the left to right5 there will ,e a step up of '( in the right atriu$ and therefore also a step up of '( in the right -entricle. 9o$e will go out the aorta and rest will go to the left -entricle. )his is good ,:c the left -entricle is ,eing e$ptied ,y the pul$onary artery, so the ,lood will ,e ta%en to the lungs to ,e oxygenated. 9o, these shunts are necessary. 'therwise, the right -ent ,eing e$ptied ,y the aorta would ,e all oxygenated ,lood and the left -entricle ,eing e$ptied with the pul$onary artery would not ,e o%ay. 9o, ,y ha-ing the shunts, can get around these defects. An A9? is necessary so you can get '(1d ,lood into the right atriu$, and fro$ the right atriu$ there will ,e a step up of '( in the right -entricle, which is ,eing e$ptied ,y the aorta5 o,-iously this ,lood isn1t RE7 saturated ($ay,e T67!, and this is why there is cyanosis in these patients. At least so$e ,lood can get out of the aorta and ha-e so$e '( to the pt and they can sur-i-e for a little while. 3:c of the right to left shunt, that ,lood is ,eing e$ptied ,y the pul$onary artery and that is going to the lungs and ,eing oxygenated. 9o, the shunts are necessary for life. 9o, with Kartagener1s, there is &') a co$plete transposition of -essels, ,ut a nor$al heart on the right side (called sinus in-ersus!. H. Coar !a!ion ha-e preductal and postductal *re " ,efore patent ductus5 post " after patent ductus (after the liga$entu$ arteriosu$! Pre*& !a% occur in )urner syndro$e and go straight into failure, therefore $ust ,e corrected i$$ediately. Pos!*& !a% are not present at ,irth and can occur at any ti$e during the pt1s adult life. I$portant to recogniCe ,:c they are a surgically correcta,le cause of .)&.
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9tenosis in aorta what is happening proxi$alN )here is trou,le getting ,lood through that, therefore there will ,e a $ur$ur heard ,est ,etween the shoulder ,lades a systolic $ur$ur. )here is a lot of pressure ,uilt up proxi$ally, so the prox aorta will ,e dilated and there will ,e a lot of pressure going into the -essels the su,cla-ian, internal carotids therefore the (P in !)e &pper ex!remi!ies 3i%% -e )ig)er !)an i! is in !)e %o3er ex!remi!ies. Also, with increased ,lood flow into the ,rain, at the junction where the co$$unicating ,ranches hit the $ain cere,ral ,ranches, we ha-e no internal elastic la$ina and no s$ooth $uscle there, therefore it is a wea% area (for A88 people!5 therefore, e1ery-o*y )as !)e po!en!ia% !o *e1e%op -erry ane&rysms. Ghat would exacer,ate, or $a%e the ,erry aneurys$ a realistic thingN HTN (any cause of .)& can cause ,erry aneurys$s ie A?*K?, essential .)&, the ,otto$ line is .)&, and ALL )yper!ensi1e p!s r&n !)e ris6 o' -erry ane&rysms we all ha-e the sa$e defect at the junction for$ any cause of .)& its not uni#ue to A?*K?, its in all cases of .)& other relations to .)& " su,arachnoid ,leeds, stretch:dilatation of aortic -al-e ring and therefore a $ur$ur of aortic regurg. All the pressure on the wall of the proxi$al aorta an a%so pre*ispose !o *isse !ing aor!i ane&rysm. Ghat is distal to thisN ?ecreased ,lood flow, %a&*i a!ion (angina of peripheral -essels so when they wal%, they will get calf pain, ,uttoc% pain, then they stop and it goes away, they wal% it hurts! this is all due to ische$ia, and the $uscle de-elop$ent to the lower extre$ities will not ,e too good, either. +uscle $ass will ,e decreased, 3* difference ,etween upper and lower extre$ities, and the ,lood flow to the renal arteries is decreased, leading to acti-ation of the 2AA will lead to .)&. 9o the HTN in p!s 3i!) Coar !a!ion is *&e !o a !i1a!ion o' RAA so it is a high renin .)&. 9o, if you can correct it the .)& will go away. Ghen there is a pro,le$ (ie a road,loc%!, we ha-e to go around it ie need collaterals. .owe-er, the aorta is not a good place to ha-e a road,loc% ,:c only ha-e two ways to get around the ,loc%: 1!(rarest! superficial epigastric artery, with the internal $a$$ary artery can get around this5 this is at the lateral ,order of hassel,ach (the superficial epigastric artery!. 9o, when you stic% your finger in the canal and ha-e an indirect inguinal hernia. 2ight through the $edial side will feel a pulsation (where the sup epigastric artery is!. (! intercostals on the undersurface of the ri,s and getting extra ,lood through the$ leading to no! )ing o' ri-s (-isualiCed on xDray!. .I. +aQor ris6 'a !ors 'or oronary ar!ery *>: Know the ris% factorsM Age is the $ost i$p ris% factor (cannot control! D>E for $ales5 EE for wo$en whyN .igher estrogen le-els, which affect .?8 le-els. 2is% factor for CA? is not 8?8, its .?8. .?8 -isits fatty strea%s, suc%s 8?8 out, ta%es it to the li-er to ,e $eta,oliCed. EE in wo$en ,:c that is the age of $enopause5 not ta%ing estrogens and that is the age when estrogens go down5 .?8 le-els go down and ris% goes up. 4a$ily history of pre$ature artery dC, cig s$o%ing, .*, .?8Y0E, dia,etes, 8?8 (cholesterol is not a ris% factor, 8?8 is! ,:c all therapeutic decisions are ,ased on 8?8 le-els, not cholesterol le-els. .?8 is a negati-e ris% factor: if your .?8 is greater than A6, you can su,tract one fro$ your $ajor ris% factor D ie ET y:o, ,ut .?8 is a,o-e A6, can su,tract the age ris% factor and will ha-e no ris% factors. .II. Is )emi Hear! Disease: 2 !ypes: Angina@ +yo ar*ia% In'ar !@ <&**en Car*ia Dea!) <yn*rome@ C)roni Is )emi Hear! Disease A. <&**en ar*ia *ea!) syn*rome " death within the last hr what will you see at autopsyN Gill &') see a coronary thro$,us, will see se-ere coronary artery atherosclerosis. 9o, usually these pts do not ha-e a thro$,us, ,ut do ha-e se-ere coronary artery dC, leading to ische$ia, *KC1s, -entricular fi,rillation (die of -entricular arrhyth$ia just li%e in +I!5 die so fast that there are no changes in the heart (ie pallor:Coagulation necrosis!5 see se-ere coronary artery dC and dx sudden cardiac death. Kery high ris% in s$o%ers. (. C)roni is )emia )ear! *> It1s a lot of our parents, uncles and aunts who ha-e coronary artery dC with little infarcts, or had a s$all heart attac%, ,asically tal%ing a,out su,endocardial infarctions. Ghat happens is that the $uscle gets replaced ,y fi,rous tissue and e-entually the poor 8K is all fi,rous tissue, with no $uscle therefore the ejection fraction is -ery low. Its 6.( instead of the nor$al 6.AA and they die fro$ heart failure. 4i,rous tissue does not ha-e contractility5 this dC is the ( nd +C indication for a heart transplant. C. Angina /+C !ype o' )ear! *>0 $ !ypes = exer!iona%@ prin>me!a%@ &ns!a-%e /res!ing0 angina 1. Exer!iona% chest pain on exertion, goes away within ED16 $inutes of resting5 9) depression on ;KL (1D( $$ depression! therefore a candidate for coronary angiogra$ to see what1s going on. (. Prin>me!a%#s seen in wo$en, occurs in $orning5 due to -asospas$ of the coronary arteries, &') atherosclerosis. In so$e people, )xA( is i$plicated for the -asospas$. <T *epression means s&-en*o ar*ia% is )emia. Coronary arteries penetrate the outside of the heart and go in, so the su,endocardial tissue get screwed ,:c its furtherest fro$ the ,lood supply. )herefore, with coronary artery atherosclerosis, and decreased ,lood flow, who gets screwedN 9u,endocardiu$ and it reacts to it with pain and 9) depression. Gith -asospas$ of coronary artery, get trans$ural ische$ia therefore there is ische$ia throughout the entire thic%ness of the $uscle this produces 9) ele-ation. 9o, *rinC$etal1s angina has 9) ele-ation ,:c trans$ural ische$ia. 0. Uns!a-%e a%a preDinfarction angina get angina on resting. Classic hx: initially had sta,le angina, now pt just get it when they are sitting. )his $eans that they will need angioplasty and put into the hospital. ?o not put on tread$ill, they will die. Ghat -eins do they useN 9aphenous -ein o-er 16 years will ,eco$e arterialiCed (it will loo% exactly li%e an artery!. If you ta%e a -ein, and put arterial pressures into it, it will change its histology and loo% exactly li%e an artery. )hey ha-e a high tendency for fi,rosing off after 16 years ,:c they are -eins. Internal $a$$ary is an artery, therefore won1t ha-e the sa$e pro,le$ ,:c it is used to those pressures. )hey will re$ain patent, ,ut cannot do four -essel ,ypass with one internal $a$$ary artery. 9o, they use the saphenous -ein, which has the tendency to undergo fi,rosis o-er ti$e ,:c they are arterialiCed under pressure. )hey can also use the internal $a$$ary. D. A &!e +I )hro$,us co$posed of group of platelet cells ,ound together with fi,rin. )*A doesn1t ha-e a pro,le$ with this ,:c it just ,rea%s the fi,rin ,onds to destroy the clot. It has a $uch ,igger pro,le$ with the ,rea%down of a -enous clot ,:c those ha-e $ore fi,rin. )he thro$,oses:clots in the heart do not ha-e that $uch fi,rin. Another factor to deal with is reperfusion injury '(1d ,lood goes into
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injured tissue, superoxide free radicals for$, Ca for$, and a few of the injured $yocardial cells will die. 'nce those die, it will still i$pro-e longe-ity. 1. Comp%i a!ions o' +I: a0 LAD oronary ar!ery is +C -essel thro$,osed, and supplies entire anterior part of your heart and the anterior (:01s of the inter-entricular septu$. 9o, there will ,e paleness, with the ant (:01s %noc%ed off. Ghere are $ost of the conduction ,undlesN Anterior (:01s. 9o, if you ha-e co$plete heart ,loc% that re#uires ectopic pace$a%er, what is the $ost li%ely -essel thro$,osedN 8A?. Ghen you ha-e 8A? occlusion, you ha-e %assi a% signs = pain ra*ia!ing !)e Qa3@ pain *o3n !)e %e'! arm@ s&-s!erna% )es! pain. -0 RCA " (nd +C thro$,osed artery which supplies the entire posterior part of the heart and the posterior 1:0 of the -entricular septu$ and the entire right -entricle. 9o, it supplies the post heart, post 1:0 of the septu$ and the entire right -entricle. )he $itral -al-e has two -al-es with papillary $uscles postero$edial papillary $uscle and postero$edio papillary $uscle. 9o, what supplies the posteriorN 2CA. Also ha-e the 9A node and AK node. )he 9A node has an e#ual distri,ution ,etween left and right. .owe-er, the A. no*e )as a B4P s&pp%y 'rom !)e -ran )es o' !)e RCA this ,rings up interesting co$plications. ;xa$ple: pt with $itral regurg $ur$ur, which is related to postero$edial papillary $uscle dysfunction, or $ay ,rea% what is the pro,le$N )hro$,osis of the 2CA ,:c the 2CA supplies that papillary $uscle. 9o, $itral regurg $ur$ur that occurs during +I would ,e due to 2CA. I' yo& 6no 6 o'' !)e A. no*e@ !)is is sin&s -ra*y ar*ia@ an* a!ypi a% )es! pain . )he 2CA is dangerous ,:c so$eti$es pt will get epigas!ri pain, which is an atypical pain. )his si$ulates L;2?5 ie pt sent ho$e with pepto ,is$ol, and ends up dying at ho$e (,:c of $issed dx!. )hey should ha-e ,een sent to hospital. )herefore, elderly pt with epigas!ri pain o&%* -e :ERD or oronary ar!ery !)rom-osis o' !)e RCA. ". :ross7mi ros opi 'ea!&res &eed to %now when the heart is softest and has a chance for rupturing this is ,etween 0D@ days. Ghen do you see gross $anifestation of ,eing a pale infarctN (> hrs ,egin seeing paleness. Coagulation necrosis in >DA hrs. ;xa$ple: 8A? thro$,osis ,:c see pale anterior (:0 of heart. 2upture pericardiu$ filled with ,lood (he$opericardiu$! $ost are interior, and therefore is fro$ the 8A? thro$,osis how does this $anifest itselfN ?ay 0 or day > co$plain of chest pain, ha-e $uffled heart sounds, nec% -ein distension, and %now they ha-e ruptured. ;xa$ple: rupture of post $edial papillary $uscle and it was infracted, therefore the 2CA is the cause of the rupture so, what would the $ur$ur ,eN +itral regurg 'n day 0 pt goes into heart failure, ha-e a pansystolic $ur$ur, increases on expiration, and 90 and 9> heart sound. It wasn1t there a day ,efore $eaning the posterior $edial papillary $uscle was dysfunctional ,:c it was infracted or it ruptured. 9o, it1s so$ething that wasn1t there ,efore and suddenly arise ,etween days 0D @. Gill go into heart failure ,:c $assi-e -olu$e o-erload and go right ,ac% to the lungs. ;xa$ple: rupture of ant wall ;xa$ple: rupture of papillary $uscle, and the postero$edial one is +C ;xa$ple: Coag necrosis ;xa$ple: inter-entricular septu$ ruptures, therefore a left to right shunt and a step up. +ost inter-entricular ruptures are 8A? thro$,oses. ;xa$ple: m&ra% !)rom-&s ($ural " wall! in this case, $ural is a thro$,us, on the wall. )hey are al$ost always 8A? thro$,i ,:c need a place to stic%. Gith anterior +I, always gi-e aspirin and put pt on warfarin:heparin why do they do thatN )o pre-ent $ural thro$,us fro$ for$ing. 9o, when you ha-e an anterior pro,, they will anticoagulate you. +&ra% !)rom-i are mixe* %o!s they are not a pure -enous li%e clot or a platelet li%e clot, they are $ixed. .ere1s how it wor%s: you ha-e a trans$ural infarction and therefore injury to endothelial cells of the heart, therefore platelets will stic% so platelets are the first things that stic% and then ,:c the $uscle is not contracting that well (,:c infracted $uscle does not contract!, there is stasis, and so on top of the platelets is a -enous li%e clot, which Coagulation factor E,T, and 23C1s, so its $ixed (platelets with fi,rin and -enous clot fro$ stasis!. Gith aspirin, you not only pre-enting a coronary thro$,us with decreasing platelet aggregation, ,ut also pre-enting a $ural thro$,us fro$ initially for$ing ,:c it inhi,its the platelets fro$ aggregating. Also, -y p&!!ing on 3ar'arin an* )eparin, you pre-ent the other part of the clot fro$ for$ing. ?on1t want these ,:c it can e$,oliCe and therefore are -ery dangerous. $. 9i-rino&s peri ar*i!is can occur ( ti$es in a person with +I: 1! 1st wee% get a friction ru,, chest pain (relie-ed when leaning forward and worse when leaning ,ac% D a 0 co$ponent friction ru,!. )hat1s due to trans$ural infarction and increased -essel per$ea,ility. And (! hx of trans$ural infarct, co$es in A wee%s later with fe-er, $uscle aches and pains, and a 0 co$ponent friction ru, in the chest " Dress%ers#s syn*rome @ 3)i ) is an a&!oimm&ne peri ar*i!is. Ghen had infarct, da$age of the pericardial surface led to autoA,1s against pericardial tissue. )his too% A wee%s to ,uild up, and they start attac%ing the pericardiu$ leading to syste$ic sy$pto$s related to i$$unologic rxn " ?resslers1s. )herefore, " !ypes are 1s! 3ee6@ no! a&!oimm&ne@ an* A 3ee6s@ a&!oimm&ne. 3asically treat with &9AI?9. 2. La!er omp%i a!ions = 1en!ri &%ar ane&rysm ;xa$ple: pt 0 wee%s out of +I chest ,ulges what under thereN +assi-e pectoralis $ajor ie sys!o%i -&%ge o' peri ar*i&m is 1en!ri &%ar ane&rysm. 3lood is collecting in the aneurys$ and $a%ing the chest ,ulge out. )his is a late $anifestation %now it1s a -ent aneurys$5 the +C co$plication is &') rupture, this aneurys$ is lined ,y scar tissue and therefore will not rupture . +CC *ea!) in a 1en! ane&rysm , )ear! 'ai%&re. +ost of heart has scar tissue, which leads to decreased ejection fraction, therefore, *ie o' HEART 9AILURE no! r&p!&re. ;xa$ple:Acute +I wasn1t it is 'i-ro&s !iss&e@ 3)i ) is 3)i!er an* more pa! )y. 4i,rous tissue (scar! can ,e anywhere fro$ 0 wee%s to 16 years
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+ust loo% at ;4 (ejection fraction! ,efore lea-ing hospital5 if you don1t ha-e a good ;4, pro,a,ly will die. If you ha-e a low ;4, you had a ,ig infarct, with a lot of $uscle that was destroyed. )herefore, ;4 is the ,iggest prognostic factor. If its close to 6.AA, that1s good. 3ut if your 6.>, ie its -ery ,ad. 4. Ho3 *o 3e *x +IE C8?+( is *x o' )oi e &ot an ;KL ,:c it has only an T67 sensiti-ity showing a new # wa-e, 9) ele-ation. )hey ha-e great specificity: )roponin I5 CKD+3 is an isoenCy$e of creatinine %inase ha-e CKD++, +3, and 33. C8 = +( is pri$arily in cardiac $uscle. )herefore, when you infarct the $uscle, you will see a pri$ary increase in cardiac $uscle, and when the $uscle is infracted, will see an increase in that enCy$e. 9tarts to go up at A hrs. *ea%s in (> hrs, and gone in 0 days ,:c if CK +3 is present after 0 days defines 2;infarction. 9o, the reappearance of CKD+3 " 2;infarction. Troponin I ele-ates a few hrs earlier than CK +3 its goes up at a,out > hrs, and pea%s in a,out (> hrs, too. It lasts @ days, which is good. .owe-er, cannot dx reinfarction. 9o, after day 0 )roponin will still ,e there and therefore, you cannot dx reinfarction. CKD+3 replaces 8?. isoenCy$es. LDH isoen>yme: &or$ally, 8?.( is higher than 8?.1. .owe-er, LDH1 is in ar*ia m&s %e. 9o, when you ha-e an infarct, you release 8?.1, and 1 ,eco$es higher than ( which is called the flip. Ghen you infarct through the $uscle, 1 will ,e higher than (, and that is the flip. )his occurs in a,out 1T hours and pea%s in a,out 0 days and last for a wee%. +ost of the ti$e, we use 8?. enCy$es if the pt ca$e in (D0 days after sy$pto$s and CKD+3 will ha-e ,een gone ,y then. )hen, loo% at 8?. isoenCy$es, and recogniCe that there is a flip and realiCe that there was an +I few days ago. )his will ,e replaced ,y )roponin 1 ,:c its ele-ated during this ti$e period. .III. .a%1&%ar Hear! Disease A. +i!ra% .a%1e Pro%apse +C $itral -al-e lesion $ore co$$on in wo$en5 too $uch -al-e and loo%s li%e a parachute (air goes under a parachute and fills it up sa$e with ,lood! ,lood will prolapse into left atriu$, and when it stops, it causes a clic%. *rolapse $eans that so$ething is co$ing out ie rectal prolapse. 9o, with $itral -al-e prolapse, it is extending into the left atriu$. Ghen it stops, and cannot go in any$ore, it stops and causes a clic%, and it followed ,y a short $itral regurg $ur$ur. 9o, it goes Iclic% $ur$ur, clic% $ur$urJ (not Isnap $ur$urJ opening snaps occur in $itral and tricuspid stenosis!. Ghat is the pathologyN +yxo$atous degeneration. Ghat LAL $a%es up the -al-eN ?er$atan sulfate, therefore its an excess of der$atan sulfate in the $itral -al-e, and it ,eco$es redundant (too $uch of it!, ,lood goes under it and causes a clic% and $ur$ur. Is it closer to 91 or 9(N It deals with preload. If we increased -ol of ,lood in the left -entricle, then the clic% and $ur$ur will co$e closer to 9( ,:c it ta%es longer for all the e-ents to get ,lood out. If we decrease the a$ount of ,lood co$ing into the left -entricle (decrease preload!, the clic% and $ur$ur co$e closer to 91. 9o, when standing and ha-e +K*, what is preload -s. lying downN It is less. 8ess preload " less ,lood in the -entricle " clic% and $ur$ur closer to 91. &ow, let1s say pt lies down clic% and $ur$ur closer to 9( ,:c increasing preload. )hey will as%: what will happen to clic% and $ur$ur with anxietyN Ghat will happen to heart rate with anxietyN Increase. )herefore, will ha-e less ti$e to fill -entricles, therefore will co$e closer to 91. Pueston on exa$inations I A$erican tourist ca$e ,ac% with diarrhea (. Aor!i <!enosis +C -al-ular cause of syncope with exercise +CC angina with exercise. +CC $icroangiopathic he$olytic ane$ia answer is giardisisJ
)his will an ejection $ur$ur, right (nd IC9, radiation into the nec%, systolic, increases in intensity on expiration. Intensity of $ur$ur with different positions: what will increase the intensity of the $ur$ur (what will $a%e it worse and therefore louder!N Increasing preload in the -entricle. Gith decreased ,lood in the -entricle, it will decrease the intensity of the ejection $ur$ur ,:c it has to go out the stenotic -al-e. If you are putting $ore ,lood into the 8K and need to get it out, it will increase the intensity D this is i$p ,:c it differentiates it fro$ hypertrophic cardio$yopathy. Ghy do they get angina with exerciseN *ulse is di$inished and therefore the stro%e -olu$e will decrease. 9o, when do the coronary arteries fill upN ?iastole. Gith less ,lood there (,:c couldn1t get it out and had to get it through the -al-e!, there is thic%ened $uscle and less ,lood going to the heart, leading to angina. 9o, this is the +C -al-ular lesion leading to angina. Also, with syncope with exercise, ,:c you ha-e decreased cardiac output, you will faint. C. +i!ra% s!enosis 9lide: )hro$,i, left atriu$ is dilated5 m&rm&r in *ias!o%e (stenosis pro, in opening and this -al-e opens in diastole, leading to snap and ru$,le!, heard at apex and increases in intensity on expiration. +CC mi!ra% s!enosis = r)e&ma!i 'e1er /a &!e0. 2heu$atic fe-er D-egetations5 due to group A ,eta he$olytic streptococcal infection. <sually occurs as postDpharyngitis. As opposed to post streptococcal glo$erulonephritis, this can ,e pharyngitis or a s%in infection. +ost of ti$e rheu$atic fe-er is fro$ a pre-ious tonsillitis. Ghen you culture ,lood in pts with rheu$atic fe-er, it will ,e negati-e. Gill not ,e a,le to grow the organis$s ,:c its not an infecti-e endocarditis. It is an i$$unologic $echanis$. 5i!) s!rep@ + pro!ein is !)e pa!)ogeni 'a !or 'or gro&p A s!rep . Certain strains ha-e Ag1s si$ilar to the heart and joints. 9o, when we $a%e A,1s against the group A strep, we are also $a%ing Ag1s against the heart (our own tissue! therefore we attac% our own heart, joints, ,asal ganglia and elsewhere. )his is called mimi ry ,:c we are de-eloping A,1s against our own tissue, ,:c there are si$ilar Ag1s in the + protein of the ,acteria, so i!s is a%% imm&no%ogi M +C -al-e in-ol-ed is the $itral -al-e. )he -egetations are sterile and line along the closure of the -al-e. )he -egetations usually do not e$,oliCe. 8no3 Jones ri!eria 'or *x o' a &!e r)e&ma!i 'e1er ie young person, few wee%s ago had an exudati-e tonsillitis, now presents with joint pain and swelling and
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dyspnea, rales in the lung, pansystolic $ur$ur, apex, and increases in intensity on expiration, 90 and 9> heart sound due to acute rheu$atic fe-er. ?x is rheu$atic fe-er. +C symp!om is po%yar!)ri!is. )hey li%e this #uestion ,:c in children, there is a li$ited *7* 'or po%yar!)ri!is = i! in %&*es Q&1eni%e r)e&ma!i ar!)ri!is@ Heno ) < )on%ein p&rp&ra@ r&-e%%a@ a &!e r)e&ma!i 'e1er. Ho3e1er@ none o' !)ese )a1e symp!oms o' )ear! 'ai%&re an* mi!ra% ins&''i ien y ex ep! 'or a &!e r)e&ma!i 'e1er. 9o, if they as% you the +C -al-ular lesion in acute rheu$atic fe-er, it is &') $itral stenosis. It ta%es 16 years to ha-e a stenotic -al-e ($itral stenosis!. 9o, the $ur$ur that you hear is $itral 2;L<2L, ,:c all parts of the heart are infla$ed, leading to friction ru,, $yocarditis (infla$ed $yocardiu$!, and endocarditis (these are the -al-es with the -egetations!. 9o, will get $itral regurg $ur$ur with acute rheu$atic fe-er. 'ther features of Fones criteria: joints, cardiac a,nor$alities, erythe$a $arginatu$ (s%in Cit!, su,cutaneous nodules (li%e rheu$atic nodules on the extensor surfaces they are exactly the sa$e!. 2h nodules and nodules associated with acute rheu$atic fe-er are exactly the sa$e. )hey are ,oth i$$unologic dC1s. 8ate $anifestation of Fones1 criteria is a,nor$al $o-e$ents called 9yndha$1s chorea. ;xa$ple: pt with acute rheu$atic fe-er (grade 0, pansystolic, apex, rales, 90 and 9>, nodules, erythe$a $arginatu$! D A wee%s later ha-e 9yndha$1s chorea. A<O !i!er is imp@ !oo = -7 i!#s a gro&p A s!rep in'e !ion an* i!s e%e1a!e*. Aschoff nodules reacti-e histiocytes in the $yocardiu$5 only find with ,x on death. 9u$$ary: i$$unologic dC, will not culture out group A strep in the ,lood, Fones criteria (polyarthritis, +C carditis, su,cutaneous nodules, erythe$a $arginatu$, 9yndha$1s chorea. Ie $itral stenosis, loo%ing fro$ left atriu$, down to the -entricle loo%s li%e a fish$outh (fish$outh appearance!. ;xa$ple: what is the $ost posteriorly located cha$,er of you heartN 8eft atriu$. 9een ,est on transesophageal ultrasound. 3:c it is posteriorly located, and enlarged when dilated, it can press on the esophagus, leading to dsyphagia with solids (not li#uids!. Also, it can stretch the left recurrent laryngeal ner-e and cause hoarseness. )his is called Orner#s syn*rome. ;xa$ple: if they ha-e an irregular irregular pulse, what does that $eanN A!ria% 'i-ri%%a!ion. ?oes it surprise you that they get thro$,us in the left atriu$N &o. 3:c there is a lot of stasis ,:c ,lood is ha-ing trou,le getting through, leading to stasis and thro$,oses. 9o, ha-e to anticoagulate the pts, which is a ,ad co$,o. Atrial fi, / thro$,us " ,ad co$,o. Ghen you picture A fi,, its li%e a -i,rator and lil chips can co$e off and e$,oliCe this is -ery co$$on in patients with +I)2A8 9);&'9I9. +.P -al-e is ,eing prolapsed into atriu$, ,:c it is so redundant, and, chordae tendinae will rupture, leading to acute $itral insufficiency. )his is not co$$on in +K* $ost of the ti$e it is asy$pto$atic. +C sy$pto$atic thing " palpitations. " gene!i *>#s 3i!) +.P asso : +ar'an#s an* E)%er Dan%os syn*rome. +arfan pt and pt died suddenly, whyN &') dissecting aortic aneurys$ (do not die i$$ediately with dissections get pain, radiation and cardiac ta$ponade! answer is +K* and conduction defects. 9o, p! 3i!) mar'an an* *ies s&**en%y@ !)is is *&e !o +.P an* on*& !ion *e'e !s /no! *isse !ing aor!i ane&rysm0. Tri &spi* reg&rg %now a,out IK?A with infecti-e endocarditis. Car inoi* syn*rome in order to ha-e carcinoid syndro$e, $ust ha-e $etassis to li-er of carcinoid tu$or. 9erotonin and the tu$or nodules gets into hepatic -ein tri,utaries and gets into the -enous ,lood and ,athes the right side of the heart, and serotonin produces a fi,rous tissue response of the -al-es. 9o, will get tricuspid insuff and pul$onic stenosis. )hese are the ( -al-ular lesions assoc with carcinoid syndro$e. ()I*9! IG. In'e !i1e en*o ar*i!is +itral -al-e with -egetations and rupture chordae tendinae5 -egetations are ,ig and ,ul%y and destroying the -al-e (hence, infecti-e!. Ghat is +CCE <!rep 1iri*iansI "n* +CC , <!ap) Ghile ,rushing teeth, ha-e a transient strep -iridians infection. If you ha-e an underlying cardiac dC, then you run the ris% of de-eloping a ,acterial endocarditis ,:c just ,rushing your teeth can cause it to get into the ,loodstrea$5 with da$aged -al-es, it can seed into it and produce -egetations. 9taph aureus can affect a &'2+A8 -al-e '2 a da$aged -al-e. +C -al-e in-ol-ed in infecti-e endocarditis " $itral -al-e5 (nd +C -al-e " aortic -al-e If you are an IK?A (who inject into -eins!, +C -al-e in-ol-ed " )ricuspid -al-e, (nd +C is aortic Tri &spi* in1o%1e* " +ur$ur of tricuspid regurg, pansystolic, increased on inspiration Aor!i 1a%1e in1o%1e*: aortic regurg, high pitched diastolic after 9( 9taph is S1 (+CC! for IK?A If you ha-e o%on an er7&% era!i1e o%i!is (any type of ulceration of the colonic $ucosa!, there is a uni#ue type of infecti-e endocarditis this is s!rep -o1is " gro&p D s!rep = ommon%y in1o%1e* 3i!) *>#s !)a! pro*& e &% era!ion o' !)e o%oni m& osa = ie UC or o%on an er. His!ory o' o%on an er an* )a1e in'e !i1e en*o = organism is s!rep -o1is /no! s!ap)0. Aortic -al-e close relationship of $e$,ranous portion of the septu$ with the aortic -al-e. 9o, why did pt get -egetations of the aortic -al-eN 3:c they got K9? that was not pic%ed up. If you ha-e congenital heart dC, you ha-e an increased ris% for infecti-e endocarditis. K9? that so$eone did not pic% up caused aortic -al-e to get infecti-e and cause aortic regurg. )herefore, on the test, will ,e $itral -al-e infecti-e endo, or aortic infecti-e endo with a K9?. 9plinter he$orrhages5 *ainful " osler1s nodes5 painless " janeway lesion5 in eye 2oth spot (red with white center just li%e Kopli% spots in $easles, which are red with a white center!. )his is why it is called the Kopli% spot of the eye. Ghat do they all ha-e in co$$on (aside fro$ the fact that they are seen in infecti-e endocarditis!N 9plinter he$orrhages, 'sler1s nodes, janeway lesions, 2oth spots, and glo$erulonephritisN A%% are !ype III HPY. All these lesions are i$$une co$plex -asculitis. Kegetations all o-er surface of the -al-e and pt has a I/J seru$ A&A dxN Li-man sa s en*o ar*i!is = p! )as L&p&s (8i,$an sacs is not the +C lesion of the heart with 8upus pericarditis is!5 8i,$an sacs is the (nd +CC, which is fi,rinoid necrosis li%e rheu$atic fe-er. +arantic -egetations in $ucous secreting colon cancer " *araneoplastic syndro$e (it is $arantic endocarditis in a pt with colon cancer!. Acute rheu$atic fe-er loo%s li%e it. G. +yo ar*i!is 1s. Peri ar*i!is
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'n the test, if you ha-e an infection #uestion, it is Coxsa 6ie 1ir&s. +CC of $yocarditis and pericarditis5 +CC -iral $eningitis " Coxsac%ie -irus. Cause of hand, foot and $outh dCN Coxsac%ie -irus .erpangina is due to Coxsac%ie1s -irus. ;xa$ple: *t with heart failure did an endo$yocardial ,x and it had ly$phocytic infiltrate in there, and it was due to Coxsac%ie1s $yocarditis. )o dx, need to do a ,x of su,endocardial tissue, and will see ly$phocytic infiltrate (as expected with A&B -irus!. )herefore, ie, pt in heart failure, ,x of $yocardiu$ has ly$phocytes " Coxsac%ie1s -irus $yocarditis Chest xDray see water ,ottle config this pt as $uffled heart sounds (cannot hear anything!, when the pt ,reaths in, nec% -eins distend (shouldn1t happen ,:c when you ,reath in and increase neg intrathoracic pressure, the nec% -eins should collapse on inspiration!, radial pulse is decreased on inspiration, when you ta%e 3* there is a drop of 16$$.g during inspiration. ?xN Peri ar*ia% e''&sion Ghat the na$e of the triadN 3ec%1s triad. Ghat is the na$e of the signN 8&ssma&%#s sign. Ghat is the drop of 16 $$ ., on inspirationN P&%s&s para*ox&s. .ow does all this occurN 3:c there is an effusion of the pericardial sac, $eaning that that heart cannot fill up (,:c there is fluid around it! leading to $uffled heart sounds. 9o, when you ,reath in and ,lood is supposed to get into the right side of your heart, it cannot expand. 9o, the nec% -eins distend instead of collapse, which is called Kuss$aul1s sign. Ghat e-er happens to right side of the heart affects the left side of the heart ,:c the left side recei-e ,lood fro$ the right side. 9o, there is no ,lood going into the right heart, and therefore, no ,lood is going out of the left heart, either. 9o, on inspiration, ,lood cannot get out of left side (,:c ,lood is not co$ing out of the right heart!, leading to a drop in pulse )en e p&%s&s para*ox&s. Always see these things together: nec% -ein distension, drop in pulse $agnitude, and drop in 3*, Kuss$aul1s sign, pulsus paradoxus " peri ar*ia% e''&sion. .owe-er, this is not what they will as% you they will as% what is 'irs! s!ep in managemen!E E )o ar*iogram shows that they ha-e fluid (pro-es it ,:c need to call surgeon to do pericardiocentesis!. Ghat is i! +C *&e !oE Peri ar*i!is. 5)a! is !)e +CC peri ar*i!isE Coxsa 6ie. Ghat if wo$an has this and a I/J seru$ A&AN 8upus. Any young wo$an that has an unexplained pericardial or pleural effusion is lupus until pro-en otherwise. GhyN 9erositis " infla$e serosal $e$,ranes its gonna lea% fluid, leading to effusions. And is a feature of 8upus. E. Cons!ri !i1e peri ar*i!is In third world countries, )3 is +C. In <9A, due to pre-ious cardiac surgery ,:c ha-e to go through pericardiu$. 9lide of a heart and thic%ened pericardiu$, no fluid, so when you ,reathe in ,lood goes to right heart, fills up and hits wall called peri ar*ia% 6no 6 therefore !o *i''eren!ia!e peri ar*ia% e''&sion 'rom ons!ri !i1e peri ar*i!is@ )a1e m&''%e* )ear! so&n*s in e''&sion 3i!) no 6no 6 in peri ar*ia% e''&sion@ an* in )a1e some 'i%%ing &p 3i!) a peri ar*ia% 6no 6 in ons!ri !i1e peri ar*i!is. Ghite stuff in pericardiu$ is dystrophic calcification, and can see it on xDray. *t goes to 2ussia and gets diarrhea " giardiasis! GI. Car*iomyopa!)ies 8arge left -entricle and right -entricle A. Conges!i1e ar*iomyopa!)y /a6a *i%a!e* ar*iomyopa!)y0 ;xa$ple: wo$an A wee%s postpartu$, and do a chest xDray and she has a generaliCed cardio$egaly heart is huge, has effusions at ,oth lung ,ases dxN Congesti-e cardio$yopathy5 this is a dC of the cardiac $uscle and has $any causes. *t has ,oth left and right heart failure. Causes: A wee%s postpartu$ (don1t %now why!, Coxsac%ie1s $yocarditis, alcohol, drugs5 +CC transplants is due to congesti-e cardio$yopathy. Cardiotoxic drugs daunoru,icin, tricyclics " drug induced cardio$yopathies " congesti-e cardio$yopathy. Alcoholic with ,ig heart due to thia$ine def " congesti-e cardio$yopathy. (. Hyper!rop)i ar*iomyopa!)y +CC sudden death in a young athlete " )yper!rop)i ar*iomyopa!)y. )hic%ness of septu$ -ery thic% with an asy$$etric .*B5 whyN 3:c the inter-entricular septu$ is thic%er. 3lood flow of left -ent goes through narrow opening (ant leaflet of $itral -al-e so, if you ha-e aortic regurg, ,lood will hit anterior leaflet of $itral -al-e and produce Austin flint $ur$ur!. Ghy is this a narrow openingN 3:c it is too thic%. If we too% a laser to ,urn it off, could open it up5 so, where is the o,struction in hypertrophic cardio$yopathyN Its not at the le-el of the aortic -al-e, ,ut ,elow it. Ghy does it o,structN Kenturi pheno$enon things go through a narrow opening #uic%ly and there is a negati-e pressure ,ehind it. Ghen ,lood, under increased force of contraction is forced through, the negati-e pressure ,ehind it suc%s the anterior leaflet ,ehind the septu$ and stops the ,lood, leading to o,struction of ,lood flow. Ghat can we do to $a%e this ,etter (what can we do to reduce the intensity of the $ur$ur and ha-e the pt ha-e ,etter C'!N *ut $ore ,lood into the -entricle increase preload and decrease o,struction ,:c it would pull it away ,:c there is $ore ,lood in it. All these things that increase preload will $a%e the intensity of the $ur$ur less and i$pro-e the pt. 9o, if you are standing up, will that i$pro-e the dCN &o, ,:c would decrease preload, leading to a harsh systolic $ur$ur. .owe-er, if lying down, there is increased -enous return to the right heart, and increased ,lood in the -ent, this would decrease intensity of $ur$ur. ?igitalis would ,e contraindicated ,:c it would increase force of contraction, $a%e it go faster and $a%e it o,struct #uic%er. A ,eta ,loc%er would ,e good5 Ca channel ,loc%er would also ,e good ,:c it would decrease force of contraction, slow the heart rate, and increase preload. )his is +CC sudden death in a young athlete. If you too% a section of the septu$, its not a nor$al septu$ its disorganiCed, and the conduction ,undles are $essed up, leading to conduction defects D with conduction defects, run the ris% of K. tach and death at any ti$e. )his a,nor$al conduction syste$ and asy$$etric septu$ is responsi,le. Ie 1A y:o ,,all player that died suddenly what do you see at autopsyN .ypertrophic cardio$yopathy. +echN A,nor$al conduction C. En*o ar*ia% 9i-roe%as!osis (ie of restricted cardio$yopathy! If it is restricti-e, so$ething is pre-enting the -entricle fro$ filling up. )his is the +C dC causing restricti-e cardio$yopathy in children, and is called endocardial 4i,roelastosis. )his dC is the +C reason why a child needs a heart transplant. If the child does not get a transplant, they will die. 'ther causes of restricti-e cardio$yopathy *o$pe1s, 4e o-erload, a$yloid. D. Car*ia myxoma
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TE7 in the left atriu$, 1E7 in right 3R, $o-a,le can $o-e o-er and ,loc% orifice of $itral -al-e, leading to syncope. )hey can e$,oliCe (they are -ery soft and ha-e ,its and pieces inside the$!. .a-e a lot of jun% inside the$, which lea%s out. It can lead to fe-er, and other signs and sy$pto$s. 9yncope cannot figure it out5 then get a transesophageal ultrasound and see it. 9o, this is the +C primary -B !&mor o' !)e )ear! in a*&%!s. )hey *es ri-e !&mor in )ear! o' 6i* this is r)a-*omyoma (,R tu$or of cardiac $uscle! they are assoc with auto do$. dC, which oneN T&-ero&s s %erosis. 9o, if they tal% a,out a tu$or in the heart of a C.I8?, do not pic $yxo$a (seen in adults!5 it1s a rha,do$yo$a and is $ore li%ely in a child with tu,erous sclerosis. CHAPTER L: RE<PIRATORY I. A?a gra*ien! = 6no3 )o3 !o a% &%a!e: Al-eolar '( and arterial p'( are ne-er the sa$e. )he difference ,etween the two is called al-eolar arterial gradient. 2easons for it: (1! Kentilation and perfusion are not e-enly $atched in the lungs. Ghen standing up the -entilation is ,etter than perfusion in the apex, whereas perfusion is ,etter than -entilation at lower lo,es. )his explains why al$ost all pul$onary infarctions are in the lower lo,es perfusion is greater there. Also, this explains why reacti-ation )3 is in the apex )3 is a strict aero,e and needs as $ore '(, and there is $ore -entilation in the upper lo,es (higher '( content!. &or$ally, al-eolar '( is 166 and the arterial p'( is RE. 9o, nor$ally, the gradient is E $$.g. As you get older, the gradient expands, ,ut not that $uch. +ost people use their upper li$it of nor$al in other words, ha-e a -ery -ery high specificity of 06 $$.g. If you ha-e an A?a gra*ien! o' $F mmHg or )ig)er !)ere is a pro-%em . It is -ery high specificity (a%a **K truly ha-e so$ething wrong!. )he concept is easy you would expect the gradient ,twn the al-eolar '( and the arterial '( to ,e greater if you ha-e primary %&ng *>. Ghat will do thisN Kentilation defects (produces hypoxe$ia, and therefore prolongs the gradient dropping the *'( and su,tracting, and therefore a greater difference ,twn the two!, perfusion defect (ie pul e$,olus!, and diffusion defect. 3ut the depression of the $edullary resp center ,y ,ar,iturates does not cause a difference in ADa gradient. 9o, pro%onge* A?a gra*ien! !e%%s yo& !)e )ypoxemia is *&e !o a pro-%em in !)e %&ngs /1en! per'&sion7*i''&sion *e'e !0. A norma% A?a gra*ien! !e%%s yo& !)a! some!)ing o&!si*e !)e %&ngs !)a! is a&sing )ypoxemia /resp a i*osis = in resp a i*osis@ PO" 3i%% go *o3n0. Causes of resp acidosis: pul$onary pro,s (C'*?!, depression of resp center (o,struct upper airway fro$ epiglottitis, larygiotracheo,ronchitis, cafX coronary (paralyCed $uscles of resp!, Luillain 3arre syndro$e, a$yotrophic lateral sclerosis, and paralysis of diaphrag$. )hese all produce resp acidosis and hypoxe$ia, ,ut the ADa gradient will ,e &'2+A8!. 9o, prolonged ADa gradient, so$ething is wrong with the lungs. If ADa gradient is nor$al, there is so$ething '<)9I?; of the lungs that is causing a resp pro,le$. 4ew things $ust always ,e calculated: anion gap (with electrolytes! and ADa gradient for ,lood gases all you need to do is calc al-eolar '(. Ge can a% &%a!e !)e A?a gra*ien! " 6.(1 x @10 " 1E6 (6.(1 is the at$ospheric '(5 and @A6 $inus the water -apor"@10!. 9o, 14F min&s !)e pCO" (gi-en in the ,lood gas! *i1i*e* -y F.L (resp #uotient!. 9o, nor$al pC'( " >6, and >6:.T"E6 and 1E6DE6 " 1665 so, now that I ha-e calc the al-eolar '(, just su,tract the $easured arterial p'( and you ha-e the ADa gradient. )his is -ery si$ple and gi-es a lot of info when wor%ing up hypoxe$ia. II. Upper Respira!ory Disease: A. Nasa% Po%yps: 0 diff types of nasal polyps +C is an allergic polyp. &e-er thin% of a polyp in the nose of %id that is allergic as an allergic polyp. Allergic polyps de-elop in adults after a long ter$ allergies such as allergic rhinitis ;xa$ple: E y:o child with nasal polyp and resp defects, what is the first step in $anage$entN 9weat test ,:c if you ha-e a polyp in the nose of the %id, you ha-e cystic fi,rosis5 it1s not an allergic polyp. (. Tria* As!)ma ta%e an aspirin or &9AI?, ha-e nasal polyps and of course ha-e asth$a. )hey don1t tell you the pt too% aspirin and that the pt has a polyp. )he aspirin or &9AI? is the answer ,ut this is how they will as% the #uestion: 0E y:o wo$an with chronic headaches or fi,ro$yalgia. *t has so$e type of chronic pain syndro$e and will not tell you that the pt is on $edication, and she de-elops occasional ,outs of asth$a what is the $ech of the pt1s asth$aN 3:c she is ta%ing an &9AI?. Ghat they won1t tell you that she has a polyp and that she is on an &9AI?5 howe-er, if a pt is in pain or has chronic pain, it is safe to assu$e the pt is on pain $edication (ie an &9AI?, +otrin or aspirin!. +ech of asth$a fro$ pain $edication: what do aspirin:&9AI?s ,loc%N C'H, therefore arachidonic acid cannot for$s *Ls ,ut the 8ipoxygenase pathway is left open. 9o$e people are -ery sensiti-e to this and 8) C>, ?>, and ;> are for$ed, which are potent ,ronchoconstrictors, leading to asth$a. It is &') a type I .*B rxn. It is a che$ical $ediated non type I .*B rxn. <o@ )roni pain an %ea* !o as!)ma -7 o' aspirin sensi!i1i!y. Another assu$ption you ha-e to $a%e: any well ,uilt $ale on ana,olic steroids (ie foot,all player, wrestler! with intraperitoneal he$orrhage produce ,enign li-er cell adeno$as which ha-e the tendency of rupturing. C. Laryngea% ar inoma /a s;&amo&s e%% ar inoma0 Concept of synergis$: +CC " 9$o%ing5 (nd +CC " alcohol Alcohol and s$o%ing ha-e a 9B&;2LI9)IC effect which leads to laryngeal carcino$a. ;xa$ple: lesion in this slide is a laryngeal speci$en which of the following ha-e the greatest ris% factorN Answer a% o)o% AND smo6ing (this is true for any s#ua$ous cancer fro$ the esophagus to the $outh to the larynx!. 9$o%ing " +CC cancer in $outh, upper esophagus and larynx. Alcohol can do the sa$e thing, so if you are s$o%er and alcohol consu$er, you can dou,le your ris%. +C sy$pto$ assoc " hoarseness of the throat.
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;xa$ple: epiglottis5 what can infect itN .. influenCa what is the sy$pto$N Inspiratory strider. ;xa$ple: 0 $onth old child died with inspiratory strider dxN Croup parainfluenCa5 this is a )2AC.;A8 infla$$ation. Ghereas epiglottitis is elsewhere. 3oth produce upper airway o,struction. III. Respira!ory Dis!ress <yn*romes: A. Hya%ine mem-rane *> /Neona!a% Resp *is!ress syn*rome0 If so$ething has a lot of pin% in it, what is itN .yaline Key to understanding this dC is $assi-e atelectasis 1. 5)a! is a!e%e !asisE Collapse of airways. Ghy did these airway collapseN &o surfactant (a%a lecithin:phosphotidyl choline:phosphotidyl glycerol they are all surfactant!. 9o, deficient of surfactant causes atelectasis ,:c: Co%%apsing press&re in !)e air3ays , s&r'a e !ension7ra*i&s o' air3ay. 9o, on expiration, nor$ally the airway will ,e s$aller ,:c there is a pos intrathoracic pressure. If you decrease the radius, you will increase the collapsing pressure in the airways. )herefore, on expiration (in all of us!, we ha-e to decrease surface tension (which is what surfactant does! ,y doing this, it %eeps the airways open on expiration, pre-enting atelectasis. ". T)ree a&ses o' RD<:
a.
*re$aturity: surfactant ,egins syn early, ,ut it pea%s at 0(D0E wee%, so if you are ,orn pre$aturely, you will not ha-e enough surfactant, and ,a,y will de-elop increased ris% of de-eloping 2?9. 9o$eti$es $other has no choice and $ust deli-er ,a,y, or else it will die, and there is so$ething you can do to the $o$ so the ,a,y has $ore surfactant: gi-e $other glucocorticoids ,:c they sti$ulate surfactant synthesis. ;xa$ple: what can you do to increase surfactant (,ut glucocorticoids wasn1t one of the answer choices! thyroxine (thyroid hor$one! (as does prolactin!5 does that $ean you gi-e thyroxine ,> deli-ering the ,a,yN &o, will gi-e $o$ and ,a,y hyperthyroidis$. ?ia,etes: gestational dia,etes " wo$an who wasn1t pregnant, ,eco$es pregnant, and then o,tains glucose intolerance after deli-ery so if a dia,etic gets pregnant, this is not called gestational dia,etes, ,ut a dia,etic that got pregnant. Its i$p that a wo$an in pregnancy has good glucose control ,:c if she is hyperglyce$ic, ,a,y will ,e, too. 3:c ,a,y is hyperglyce$ic, it will sti$ulate insulin synthesis, and insulin has a negati-e effect on surfactant syn and will decrease its synthesis. C section ,:c the ,a,y is not deli-ered -aginally, there is no stress. 3:c the ,a,y has not ,een stressed, the AC). and cortisol are not released, and surfactant is not $ade. Ghereas a child that is deli-ered -aginally has a lot of stress and therefore a lot of AC). and cortisol is ,eing released, which sti$ulates surfactant release. 9o, C section predisposes to 2?9.
b.
,.
9o, these are the three $ain causes (pre$aturity, dia,etes, and C section!. $. Comp%i a!ions an* asso ia!e* on*i!ions: a. ;xa$ple: why are the ,a,ies of poor glyce$ic control ,ig ($acroso$ial!N )he ,a,y1s insulin is increased to %eep the glucose down. Insulin will increase storage of triglyceride in adipose (it increases fat storage!. Ghere is $ost of the adipose locatedN Centrally. 9o, one of the reasons why they ha-e $acroso$ia is ,:c insulin sti$ulates synthesis of )L and deposition of fat. Also, insulin increases upta%e of aa1s in $uscle (li%e growth hor$one!. 9o, it will increase $uscle $ass. 9o, !)e reason 'or ma rosomia is in rease* a*ipose an* m&s %e mass@ -o!) *&e !o ins&%in. )his also explains why they get hypoglyce$ia when they are ,orn. )he $other1s hyperglyce$ia is co$ing into the ,a,y, causing the ,a,y to release insulin5 the $o$ent insulin is $ade and the cord is cut, and no $ore increase in glucose, glucose goes down, and leads to hypoglyce$ia. ,. 9uperoxide free radical da$age seen in retinopathy of pre$aturity and ,lindness and ,ronchopul$onary dysplasia. c. Ghy do ,a,ies with 2?9 co$$only ha-e *?AN 3:c they ha-e hypoxe$ia. Ghen a nor$al ,a,y ta%es a ,reath, it starts the process of functional closure of the ductus. .owe-er, with hypoxe$ia after they are ,orn, it re$ains open, and they ha-e a $achinery $ur$ur. d. .yaline $e$,ranes are due to degeneration of type II pneu$ocytes and lea%age of fi,rinogen, and it congeals to for$ the $e$,rane. 9o, they will gi-e a classic history for 2?9, and then will as% for the pathogenesis of hypoxe$ia in the ,a,y. )his is a $assi-e -entilation defect ,:c e-erything is collapsing. )his is a 9.<&) pro,le$, which leads to a $assi-e interpul$onary shunt. 2x"*;;* therapy positi-e end exp pressure ,:c these airways are collapsed and you need to get '( into the$ and surfactant. 9o, gi-e '( and at the end of expiration, pu$p in pressure, which %eeps airways open on expiration, so you can %eep '( in the$. ;xa$ple: pic with type II pneu$ocyte (with la$ellar ,odies loo% li%e onion, and hyperplastic arteriolosclerosis ,:c they are concentrically shaped!. )hese la$ellar ,odies contain surfactant. )his would I? it as a type II pneu$ocyte. )hey co$$only gi-e ;+s of the lung with an al-eolar $acrophage. +acrophage has =jun%1 in the cytoplas$. )he type II pneu$ocyte is the repair cell of the lung and synthesiCes surfactant. (. A*&%! Respira!ory Dis!ress <yn*rome /ARD<0
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In ter$s of A2?9, essentially it is the sa$e as 2?9 in pathophys, ,ut is &;<)2'*.I8 related injury. In 2?9 you1re not $a%ing surfactant ,:c you are too pre$ature or ha-e too $uch insulin and just ha-e collapsed al-eoli. 3<) in A2?9 its ,:c you ha-e too $uch infla$$ation5 there is no infla$$ation in 2?9. +CC ARD< , sep!i s)o 6 /+CC sep!i s)o 6 , E o%i 'rom sepsis 'rom an in*3e%%ing a!)e!erI +CC DIC , sep!i s)o 60. ;xa$ple: In the IC< if a pt co$e in with dyspnea and its within (> hrs of ha-ing septic shoc%, pt has A2?9. If pt is in septic shoc% and within >T hrs of ad$ission and is ,leeding fro$ e-ery orifice, he has ?IC. <o@ 'irs! *ay , sep!i s)o 6@ se on* *ay , ARD<@ !)ir* *ay , DIC. Pa!)ogenesis: &eutrophils get into the lung in septic shoc% and start destroying all the cells of the lung (type I and II pneu$ocytes!. 9o surfactant production decreases and result is $assi-e atelectasis (collapse!. .owe-er, this is neutrophil related (the neutrophils are destroying the type II pneu$ocyte. )he reason why they get hyaline $e$,ranes in the A2?9 is ,:c the neutrophils ha-e to get in the lungs ,y going through the pul$onary capillaries, so they put holes in the$ as they get out of the ,loodstrea$ and into the lungs (this is why it is called lea%y capillary syndro$e!. All the protein and fi,rinogen get in and produce hyaline $e$,ranes. )herefore, you can actually see hyaline $e$,ranes in A2?9. 9o, there is $assi-e collapse and the pathophys is intrapul$onary shunting. )his is the sa$e in 2?9, ,ut A2?9 is neutrophil related, which is a ,ad prognosis. I.. Pne&mo!)orax 9pontaneous pneu$othorax and tension pneu$othorax A. <pon!aneo&s pne&mo!)orax +CC spon!aneo&s , r&p!&re* s&-p%e&ra% -%e- ha-e pleura and right underneath is a ,le, (air poc%et!. )he ,le, (air poc%et! ruptures causing a hole in the pleura, so that part of the lung collapses. 3:c what1s %eeping it expanded is neg intrathoracic pressure, which %eeps the lungs expanded. 9o, if you put a hole in the pleura, then the at$ospheric pressure is not negati-e, ,ut is the sa$e as the air you are ,reathing. 9o, there is nothing to hold it open and therefore it collapses. Ghen parts of the lung collapse, there are things that will ta%e up the slac%. 'ne of those is the diaphrag$. If you collapse part of the lung, the diaphrag$ will go up on that side to ta%e up the open space on that has ,een left. &ot only that, if there is a collapse on one side, the trachea will go to the side that there is space. 9o, will ha-e !ra )ea% *e1ia!ion !o !)e si*e o' !)e o%%apse@ an* !)e *iap)ragm is &p@ %ea*ing !o spon!aneo&s pne&mo!)orax . <sually seen in tall $ale they ha-e ,le,s that rupture and lead to spontaneous pneu$othorax. Can also get in scu,a di-ers ,:c they co$e up too #uic%ly, which leads to rupture of the ,le,s. (. Tension pne&mo!)orax ?iff fro$ spontaneous pneu$othorax. +C due to %nife injuries into the lung. )here1s tear of pleura (flap!, sp when you ,reathe in the flap goes up and on expiration it closes. 9o, the air stays in the pleural ca-ity. 9o, e-ery ti$e you ,reathe, the flap goes up, air stays in, and on expiration it closes. 9o, for e-ery ,reath you ta%e, it %eeps increasing and the pressure in the lung. )he lung hasn1t collapsed yet. T)e in rease in press&re s!ar!s p&s)ing !)e %&ng an* !)e me*ias!in&m !o !)e opposi!e si*e. Ghen it pushes it, it co$presses the lung and it leads to co$pression atelectasis (it is not deflated ,:c of a hole there isn1t a hole it1s a tear that when the air went in it went up and it shut on expiration, and that pos pleural pressure is pushing e-erything o-er to the opposite side!. )his co$pression will push on the 9KC, right -ent, and left atriu$ on the opposite side. )his will co$pro$ise ,lood return and ,reathing, leading to a $edical e$ergency. 9o, it1s li%e filling tire up with air, ,ut cannot get out. Air is filling pleural ca-ity and cannot get out. It %eeps ,uilding up and starts pushing e-erything to the opp side. Gith a pos intrathoracic pressure, the diaphrag$ will go down (goes up in spontaneous pneu$othorax!. .. P&%monary In'e !ion A. Pne&monia 1. " 6in*s = Typi a% an* A!ypi a% Typi a% wa%e feeling nor$al, then suddenly de-elop a fe-er, producti-e cough A!ypi a% slow, insidious onset (feel ,ad o-er few days! ". Comm&ni!y 1s. Noso omia% /)ospi!a% a ;&ire*0 If you get pneu$onia in the omm&ni!y and it1s typical, it is 9trep pneu$oniae. If you get pneu$onia in the co$$unity and it is atypical, it1s $ycoplas$a pneu$oniae. 'rganis$s in the hospital (noso omia%! " ; coli, *seudo$onas, 9taph aureus (will not get strep pneu$oniae in the hospital!. $. Pro*& !i1e o&g) in Typi a% pne&monia Reason 'or pro*& !i1e o&g) in !ypi a% pne&monia: )a1e ex&*a!e /p&s0 an* signs o' onso%i*a!ion in !)e %&ng 9lide: yellow areas with $icroa,cesses which are consolidation in the lung. Ie lo,ar pneu$onia " see consolidation in lung, within al-eoli, causing consolidation. )herefore, with typical, see consolidation and pus in the lung. *hysical dx1tic tools of lung consolidation: decreased percussion, increased )K4 (when the person tal%s, feel -i,rations in chest if ha-e consolidation in ie the upper left lo,e, will ha-e increased )K4 ,:c it is a consolidation, co$pared to the other side so, in rease* T.9 in*i a!es onso%i*a!ion!, ha-ing an I; to AJ (egophony! sign (pt says ; and you hear A!, whispered pectorilo#uy (pt whispers I1, (, 0J and I will hear it -ery loud with the stethoscope!. )herefore, *e rease* per &ssion@ in rease* T.9@ egop)ony@ an* pe !ori%o;&y , onso%i*a!ion.
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Ghat if there is a pleural effusion o-erlying the lungN 'nly thing you would ha-e is decreased percussion (this separates pleural effusion fro$ pneu$onia!. 2. A!ypi a% pne&monias T)ey *o no! )a1e a )ig) !emp an* *o no! )a1e pro*& !i1e o&g) -7 !)ey are in!ers!i!ia% pne&monias. )hey ha-e infla$$ation of the interstitiu$ there is no exudate in the al-eoli which is why you are not coughing up a lot, and therefore do not ha-e signs of consolidation. 9o, will not ha-e increase )K4, I; to AJ, with an atypical. Atypical pneu$onia has an insidious onset, relati-ely nonproducti-e cough, no signs of consolidation. +CC !ypi a% pne&monia , s!rep pne&moniae /6no3 !)e pi 0 = gram CUD *ip%o o , PCN : &s /a6a *ip%o o &s0 = Rx
+CC a!ypi a% pne&monia , my op%asma pne&moniaeI "n* +CC , C)%amy*ia pne&moniaeI which are all interstitial pneu$onias. 3ronchopneu$onia: +C due to strep pneu$onia, and co$$unity ac#uired. consolidation on chest xDray strep. *neu$onia. a0 .ira% pne&monias 10 R)ino1ir&s " +CC co$$on cold5 they are acid la,ile $eaning that it won1t lead to gastroenteritis in the sto$ach ,:c is destroyed ,y the acid in the sto$ach. &e-er will ha-e a -accine ,:c 166 serotype. "0 R<. +CC ,ronchiolitis whene-er you infla$e s$all airways, its leads to wheeCing. )his is a sma%% air3ay *> an* -ron )io%i!is is +C *&e !o R<. an* pne&monia. 9o, pne&monia an* -ron )io%i!is is +C *&e !o R<. in )i%*ren. $0 In'%&en>a drift and shift ha-e he$agglutinins, which help attach the -irus to the $ucosa. .a-e neura$inidase ,ore a hole through the $ucosa. An!igeni *ri'! , minor )ange7m&!#n in either he$agglutinins or neura$inidase5 do not need a new -accine5 an!igeni s)i'!, maQor )ange7m&!#n in either he$agglutinins or neura$inidase need a -accine. T)e 1a ine is agains! A Ag. -0 (a !eria% pne&monias 10 C)%amy*ia psi!!a osis fro$ ,irds (ie parrots, tur%eys!. "0 C)%amy*ia !ra )oma!is a little %id was ,orn and a wee% later he was wheeCing (,ig ti$e!, pneu$onia, increased A* dia$eter, ty$panic percussion sounds, no fe-er, eyes are crusty (,oth sides!, weird cough s!a a!o o&g) /s)or! o&g)s0. He go! i! 'rom )is mom#s in'e !e* er1ix. /+CC onQ&n !i1i!is in " n* 3ee6 , C)%amy*ia !ra )oma!is0. /+C o1era%% o' onQ&n !i1i!is is in'%amma!ion o' ery!)romy in *rops0. 0 Hospi!a%?a ;&ire* gram?nega!i1e pne&monias 10 Pse&*omonas water lo-ing ,acteria, therefore see in pt in IC< when on a 2;9*I2A)'2. pt water unit with green producti-e cough with. "0 8%e-sie%%a fa$ous in the alcoholic5 howe-er, alcoholic can also get strep pneu$onia. 9o, how will you %now strep -s. Kle,siellaN Alcoholic with high spi%ing fe-ers, producti-e cough of +<C'I? appearing sputu$ the capsule of Kle,siella is -ery thic%. 8i-es in the upper lo,es and can ca-itate, therefore can confuse with )3. $0 Legione%%a atypical cough, nonproducti-e cough, -ery sic% can %ill you, fro$ water coolers (water lo-ing ,acteria!, seen in $ists in groceries or at restaurants. ;xa$ple: classic atypical pneu$onia, then pt had hyponatre$ia this is 8egionella. 8egionella just doesn1t affect the lungs, also affects the other organs such as li-er dC, in!ers!ia% nep)ri!is and %noc%s off the juxtaglo$erlur cells, and %ills the renin le-els, low aldosterone and therefore lose salt in the urine, %ea*s !o )ypona!remia (low renin le-els with low aldosterone!. 2x " erythro$ycin (. 9&nga% In'e !ions T)e !3o sys!emi '&ng&s are Can*i*a an* His!o 1. Can*i*a seen in indwelling catheters (usually those in the su,cla-ian!. And get Candida sepsis ". His!op%asmosis " +i*3es! ('hio:)ennessee -alley! carried ,y dung of starlings and ,ats often seen in ca-e explorers, or spelun%ers. )hey de-elop nonDproducti-e cough. .isto is the only syste$ic fungus that has yeasts phagocytosed ,y al-eolar $acrophages. $. Cryp!o o &s " Pigeons loo%s li%e $ic%ey $ouse yeast for$s are narrow ,ased ,uds. ;xa$ple: &B exec with pigeons roosting in air conditioner and de-eloped non producti-e cough. ;xa$ple: painter de-eloped resp infection wor%ed on 3roo%lyn ,ridge with pigeons, how do you treatN Amp)o!eri in (. 2. (%as!omy osis " 9; <9A " s%in and lung infections5 ,road ,ased ,ud 8o,ar pneu$onia. 9lide: lo,ar
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4. Co i*ioi*omy osis: 9G <9A (new +exico, AriCona, southern Cal. " coccidio$ycose has spherule endospores (%now the pic!. ;xa$ple: in 8A earth#ua%e, a S of people had nonproducti-e coughthe arthrospore (the infectious for$! is in dust. Gith the earth#ua%e, dust co$es up, ,reathe it in. ;xa$ple: $an that is an Indian artifact explorer in the sonaran desert, which is in AriCona, and is a CAK; explorer that de-eloped nonproducti-e cough this is COCCIO+YCO<I< (not .isto ,:c not the +idwest!. A. Aspergi%%&s 0 different $anifestations:dC1s: 1! lo-es to inha,it a,andoned )3 fungus ca-ities '&ng&s -a%% (aspergillo$a, a -ery co$$on cause of $assi-e he$optysis!. ;xa$ple: left upper lo,e ca-itary lesion and asp lo-e to li-e in there " fungus ,all (! -essel in-ader5 therefore will in-ade the -essels in lung, leading to !)rom-osis an* in'ar !ion 0! allergies the $old, leading to extrinsic as!)ma and type I .*B 9o, three $anifestations: fungus ,all, in-asi-e -ascular dC producing he$orrhagic infarctions of the lung, and asth$a. ;xa$ple: pic of corona co$ponent of Aspergillus (loo%s li%e a crown! septate is -ery characteristic ($ucor$ycosis is nonseptate and has wide angles, while Aspergillus has narrow angles in its ,udding and corona1s!. H. PCP /Pne&mo ys!i!is arinii pne&monia 4ungus (used to ,e a protoCoa! ,:c $ore things in the cell wall that loo% li%e a fungus. It1s associated with .IK, +C AI?s defining lesion (as soon as the helper ) cell ct is (66, it usually shows up!. <sed to ,e +CC death in AI?s pt, ,ut now has gone down, ,:c as soon as your C?> ct is (66, dr. will put pt on prophylactic therapy with )+*D9+H. Ghen ta%ing T+P?<+G an* pro!e !ing agains! PCP@ would other organis$ is the pt protected fro$N Toxop%asmosis. (so, you get ( for 1!. +CC space occupying lesion within the ,rain in a pt with AI?s" )oxoplas$osis <een 3i!) si%1er s!ain: cysts of *C* can ,e seen loo% li%e ping pong ,alls, seen in al-eoli, leading to al-eolar infiltrate, leading to dyspnea, tachypnea, foa$y ,u,,ly infiltrate, on chest xDray, loo%s all white out ,:c of the in-ol-e$ent of the lung howe-er, not only seen in lungs, can ,e seen in any part of the ,ody also seen in ly$ph nodes of .IK I/J. 'ther organis$s that are only seen with sil-er stain: ,artenella henselae (,acillary angio$atosis!, 8egionella (not -isualiCed with gra$ stain, therefore use ,utulyNNN sil-er stain! L. T( 'rganis$ in upper lo,e of lungs (play odds! )3 see ca-itary lesion, which is reacti-ation )3 (not pri$ary!. *ri$ary )3 is the lower part of the upper lo,e or the upper part of the lower lo,e and close to the pleura (%ind of in the $iddle of the lo,e!. *ri$ary )3 has a Lhon focus and a Lhon co$plex. +ost people reco-er5 when pt is i$$unoco$pro$ised, it leads to reacti-ation and goes into the apex and produces a ca-itary lesion. T)ere is no :)on 'o &s or omp%ex in rea !i1a!ion T(@ on%y primary T(. O!)er !)ings !)a! a1i!a!e in &pper %o-es: Ghich syste$ic fungus is the I)3J of the lungsN .istoplas$osis Ghich cancer can ca-itate in the lungN 9#ua$ous Cell carcino$a of the lung Ghich ,acteria (that has a ,ig $ucous wall around it! can also produce ca-itations in the upper lo,eN Kle,siella pneu$oniae. Ghat is acid fast stain stainingN +ycolic acids. 9o, just ,:c so$ething is ca-itating the upper lo,e, it is not necessarily )3. C. 9oreign (o*ies If you are s!an*ing or si!!ing &p, foreign ,odies will go to pos!ero-asa% segmen! o' !)e rig)! %o3er %o-e. )his is the $ost posterior seg$ent of the right lower lo,e. If you are lying down (+C way to aspirate things!, foreign ,ody will go to superior seg$ent of the right lower lo,e. If you are lying on the right side, can go to ( places 1! $iddle lo,e (! posterior seg$ent of right upper lo,e (this is the '&8B one that is in the upper lo,e. If you are lying down on your left, and aspirate, it will go to the lingula. 9u$$ary: <i!!ing7s!an*ing , pos!ero-asa% segmen! o' rig)! %o3er %o-e (a 6: s&perior segmen! o' rig)! %o3er %o-e Rig)!: mi**%e or s&p segmen! o' rig)! %o3er %o-e Le'!: %ing&%a D. A-s ess +CC a-s ess , aspira!ion o' orop)aryngea% ma!eria% 9een co$$only in street people that do not ha-e good dentition, $ay ,e drun% and fall and oropharyngeal $aterial will ,e aspirated. Aspirate consists of aero,es and anaero,es, leading to putrid:stanch s$ell. )he aspirate is a $ixture of all these organis$s: +ixed aero,es and anaero,es, fuso,acteriu$, ,acteroides. Can get a,secces in the lung fro$ pneu$onia: staph aureus, Kle,siella (howe-er, +CC is aspiration!, see fluid ca-ities in lung on xDray. .I. P&%monary .as &%ar Disease: A. P&%monary Em-o%&s
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( types of e$,oli tiny ones that produce wedge shaped he$orrhagic e$,oli or can chip off large ones. Ghere do $ost *ul e$,oli e$,oliCe fro$N +C 9I); for thro$,osis is the deep -eins of the lower leg. )his is &') the $ost co$$on site for e$,oliCation5 it is the fe$oral -ein (this is the +C site for e$,oliCation!. +a%es sense ,:c -enous clots propagate toward the heart (deep -eins to the fe$oral -ein, and the fe$oral -ein is a larger -essel, therefore it is $ore li%ely to chip off!. 9o, the fe$oral -ein is the +C site for e$,oliCation to the lung. )he deep -eins are the +C site where deep -enous thro$,osis ,egins. (when it get to the fe$oral -ein, it is dangerous for e$,oliCation!. 9o, s$all ones produces he$orrhagic infarct that is only if you ha-e an underlying lung dC. If I ha-e a s$all e$,olus, pro, won1t infarct ,:c don1t ha-e a,nor$al lungs. .owe-er, if you ha-e preexisting lung dC you will infarct. TE7 of the ti$e e$,olus will not produce infarct. .owe-er, in the 1E7, $ost of the pts with infarcts ha-e preexisting lung dC (ie they are s$o%ers!. )he other type of e$,olus is a saddle e$,olus (it is huge! and ,loc%s off the orifices of the pul$onary -essels and pul$onary arteries. If you %noc% off at least 0 out of the E orifices, you are dead in a $illisecond, so there is no infarction ,:c you don1t ha-e ti$e to infarct. It produces acute right heart strain and i$$ediate death. < reening !es! o' )oi e: .en!i%a!ion per'&sion s an = 3i%% )a1e 1en!i%a!ion@ no per'&sionI on'irma!ory !es! is p&%monary angiogram. .II. Res!ri !i1e P&%monary Disease Res!ri !i1e so$ething is restricting it fro$ filling. ;xa$ple: restricted filling of the heart " restricti-e cardio$yopathy. 'r restriction in filling up of the lungs with air. .a-e ( ter$s: omp%ian e /'i%%ing !erm@ inspira!ion !erm0 an* e%as!i i!y /re oi%@ expira!ion !erm0I 4or restricti-e lung dC, picture a hot ru,,er ,ottle for restricti-e lung dC. )he hot ru,,er ,ottle is difficult to =,low up1, therefore omp%ian e is *e rease* and it is hard to fill the lung up with air. 9o, what1s pre-enting it fro$ ,lowing upN 4i,rosis (interstial fi,rosis, +C1ly!. If you get the hot water ru,,er ,ottle filled with air and let the air out, what happens to the elasticityN Increases. 9o, co$pliance is decreased and cannot fill it up, ,ut once you do fill the lung up, it co$es out #uic%ly ( e%as!i i!y in reases!. ;xa$ple: pt with sarcoid diff to fill lungs, ,ut get it out fast (due to fi,rosis!. 9o, all )8C, 2K, )K (all lung capacities ha-e all e#ually decreased!. 4;K1:4KC on spiro$eter ta%e a deep ,reath (ie pt with sarcoid! 4;K1 (a$ount you get out in one sec nor$ally it is > liters! is decreased, 4KC (total that got out after deep inspiration! is decreased (,:c increased elasticity! this is the sa$e as 4;K1, so the ratio is often 1. &or$ally, the 4KC is E liters, and the 4;K1 is nor$ally > liters so, the nor$al 4;K1:4KC ratio is >:E "T67. 3:c the elasticity is increased, the 4KC is the sa$e as 4;K1, and therefore the ra!io is in rease* to 1 instead of 6.T. Examp%es o' res!ri !i1e %&ng *>#s: 1. Pne&mo oniosis air,orne:dust,orne dC1s fa$ous in ,ig cities (8A, &B!. Cole wor%er pneu$oconiosis esp. in west Kirginia:*enn, ha-e an anthrocotic pig$ent that causes a fi,rous rxn in the lung, leading to restricti-e lung dC. .a-e an increased incidence of )3, ,ut not cancer. ". <i%i osis 9and,lasters get graffiti off things, or wor% in foundries and deal with roc%s (ie #uartC!, and ,rea% the$ down, and ,reathe in dust, leading to silicoses!. .a-e nodules in the lung that are hard has roc% (literally! ,:c there is #uartC in the$ and it loo%s li%e $etastatic dC in the lung (silica dioxide which is sand in the lung! again, increased of )3, not cancer. If pt happens to ha-e rheu$atoid arthritis, and also has one of these pneu$oconiosis (ie Cole wor%ers!, ha-e a potential for a syndro$e, which is called caplan syndro$e. Cap%an syn*rome consists of rheu$atoid nodules in the lung (sa$e as extensor surfaces in the ar$!. 2heu$atoid arthritis co$$only in-ol-es the lung with fi,rosis. And rheu$atoid nodules can for$ in the lung. T)e om-o o' r)e&ma!oi* ar!)ri!is /r)e&ma!oi* no*&%es0 in !)e %&ng@ p%&s pne&mo oniosis /si%i osis7as-es!osis7Co%e 3or6ers0 , ap%an syn*rome. $. As-es!os as,estos fi,ers loo% li%e du$,,ells (therefore eC to recogniCe!. )hese are called ferruginous ,odies. As,estos fi,ers coated with iron, therefore can call the$ either as,estos ,odies or ferruginous ,odies. +C pul$onary lesion assoc with as,estos is not cancer it is a fi,rous pla#ue with a pleura, which is ,R (not a precursor for $esothelio$a!. +C an er asso 3i!) as-es!os , primary %&ng an er@ " n* +CC , meso!)e%ioma@ 3)i ) is a ma%ignan y o' !)e serosa% %ining o' !)e %&ngs. If you are a s$o%er and ha-e as,estos exposure, you ha-e an increased chance of getting pri$ary lung cancer. )his is a good exa$ple of synergis$ (other causes of lung cancer (9CC! include s$o%ing, alcohol!. As,estos / s$o%er " will get cancer. )here is no increased incidence of $esothelio$a with s$o%ing (not synergistic!. ;xa$ple: 2oofer for (E years, nons$o%er (do tell you, ,ut you had to %now that (E years ago, all the roofing $aterial had as,estos in it5 in other parts of &B, $any ,uildings were torn down, and there was as,estos in the roofing of those ,uildings, which was inhaled ,y $any people, and 16D06 years later they de-eloped pri$ary lung cancer or another co$plication of as,estosis!. Ghat would he $ost li%ely getN *ri$ary lung cancer (pri$ary pleural pla#ue was not there!. If he was a s$o%erN *ri$ary lung cancer. +esothelio$a ta%es (ED06 years to de-elop. 8ung cancers ta%e a,out 16 years to de-elop. 8ung cancers are $ore co$$on, and you die earlier. Ghat is the $ain cause of as,estos exposureN 2oofers or people wor%ing in a na-al shipyard (,:c all the pipes in the ship are insulated with as,estos!, also in ,ra%e lining of cars and headgear.
2. <ar oi*osis ,"n* +CC res!ri !i1e %&ng *>. ;xa$ple: classic xDray ly$ph nodes (hilar ly$ph nodes are ,ig!, haCiness seen, too, which is interstial fi,rosis. <ar oi* is a gran&%oma!o&s *> that has &' relationship to infection ( a&se , &n6no3n!. Ca&ses a non asea!ing gran&%oma (not caseating ,:c no relationship to )3 and syste$ic fungal infections!. )he lungs are A8GAB9 in-ol-ed (lungs are the pri$ary target organ!, and $ore co$$on in ,lac%s. ;xa$ple: ,lac% person, 0E y:o, with dyspnea, see hilar nodes on xDray, u-iitis (,lurry -ision this is infla$$ation of the u-eal tract this dC always affects so$ething in the face, and the face the (nd +C site a lesion will occur with this dC, can also in-ol-e sali-ary glands or lacri$al glands so$ething in the head:nec%:face area (,ehind the lungs!. )his dC is a dx of exclusion, therefore $ust rule out
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anything that causes granulo$a ()3, .isto!, along with the correct physical presentation " 9arcoidosis. Rx , s!eroi*s. AC; enCy$es are -ery high in these pts ,:c granulo$as in %idney5 )yper a% emia $acrophages (epitheloid cells! $a%e 1DalphaDhydroxylase. If they are $a%ing 1DalphaDhydroxylase, what is the $ech of hypercalce$iaN .yper-ita$inosis ?. you are second hydroxylation $ore -it ? and therefore ha-e excess -it ?, and -it ? pro$otes rea,sorption of calciu$ and phosphorus, leading to hypercalce$ia. T)is is !)e +C nonin'e !io&s a&se o' gran&%oma!o&s )epa!i!is /T( is !)e +CC o' in'e !io&s )epa!i!is@ "n* +C , pne&mo oniosis0. 4. Hypersensi!i1i!y pne&moni!is /'armer#s %&ng@ si%o'i%%ers *>@ -ysinosis! )hese are restricti-e lung dC1s. ?on1t confuse far$er1s lung and silofillers dC they are 3'). seen in far$ers. 9o, re$e$,er one, the other is the otherM <i%o'i%%ers *> = put things in silos, which is a closed space, and fer$entation of gas occurs, the gas is nitrogen dioxide ;xa$ple: far$er went into a roo$ in his ,arn and suddenly de-eloped wheeCing and dyspnea, whyN 3:c he too% in nitrogen dioxide, which is a fer$enting pro,le$. (silo can explode ,:c gas fro$ fer$entation!. 9armer#s %&ng = !)ermop)i%i a !inomy es /a mo%*0. ;xa$ple: on tractor, dust ,eing ,lown up in the air and ther$ophilic actino$yces (which is a $old! is inhaled5 leading to hypersensiti-ity and .*B pneu$onitis and they end up with a restricti-e lung dC. (ysinosis wor%er in textile industry, and they get dyspnea. )hese are the .*B and restricti-e lung dC1s. :oo*pas!&re syn*rome 3egins in the lungs with a restricti-e lung dC (with coughing up ,lood he$optysis!, and ends up -ery shortly with renal dC (therefore, it starts in the lung and ends in the %idneys!. )his is a restricti-e lung dC. .III. O-s!r& !i1e %&ng D> A. Dea%s 3i!) omp%ian e7e%as!i i!y on ep! In o-s!r& !i1e %&ng *>@ no pro- ge!!ing air in@ -&! )a1e a pro-%em in ge!!ing !)e air o&!. Ghy don1t you ha-e a pro,le$ getting it inN 3:c the elastic tissue support is destroyed, so it is -ery eC to fill up the lungs. .owe-er, ,:c the elastic tissue support is destroyed, it is -ery difficult hard to get it out ,:c it collapses on expiration, so you can get air in, ,ut cannot get air out. In a pt with o,structi-e air dC, they ,reathe in with no pro,le$, ,ut ha-e trou,le getting it out. 9o, so$ething is left o-er in the lung cannot get all the air out, therefore the residual -olu$e is increased (whene-er so$ething is left o-er, it is called the =residual1!. 9o, if you cannot get air out, then the residual -olu$e increases, which $eans that the )8C will increase, which $eans that the diaphrag$ will go down ,:c as the lungs are o-er inflated, and the A* dia$eter will go out. 9o, with o,structi-e lung dC, you ha-e increased A* dia$eter and diaphrag$s go down (depressed!. )here is only a certain a$ount of expansion your chest can go. ;-entually, the chest starts to co$press other -olu$es (as you trap air and residual -olu$es go up!. 9o, tidal -olu$e starts decreasing, -ital capacity goes down ,:c the residual -ol is increasing and you are co$pressing other -olu$es. <o@ TLC an* R. in reases@ e1ery!)ing e%se *e reases. 'n spiro$eter, 4;K1 is -ery low (usually 1 nor$ally it is >!. In other words, you ha-e a ,etter 4;K1 with restricti-e lung dC ,:c you can get air in. )he 4KC (total a$t they can get out! is 0 liters (-s. E liters!. 5)en yo& *o a ra!io o' 9E.179.C@ !)e ra!io )as *e rease*@ )en e *is!ing&is)ing res!ri !i1e 'rom o-s!r& !i1e *>#s. C%assi COPD x?ray: hard to see the heart, with depressed diaphrag$s (at le-el of u$,ilicus!, increased A* dia$eter dxN Classic o,structi-e dC xDray pro, getting air out, therefore the diaphrag$ is down and A* dia$eter is increased. ;xa$ple: 0 $onth old can ha-e this sa$e finding due to 29K ;xa$ple: &ew,orn with Chla$ydia tracho$atis pneu$onia ,:c he is trapping air. (. T)ere are 2 !ype o' o-s!r& !i1e %&ng *>#s: )roni associated with s$o%ing are ,ronchitis and e$physe$a. -ron )i!is@ -ron )ie !asis@ emp)ysema@ as!)ma . )he ones
1. C)roni (ron )i!is P&re%y a %ini a% *x , P! )as pro*& !i1e o&g) 'or $ mon!)s o&! o' !)e year 'or " onse &!i1e years. Ghere is the dCN )er$inal ,ronchioles (you ha-e $ain ste$ ,ronchus, seg$ental ,ronchi, ter$inal ,ronchioles, resp ,ronchioles, al-eolar ducts, al-eoli!. As soon as you hit the ter$inal ,ronchioles, these are s$all airway5 it is all tur,ulent air up to ter$inal ,ronchioles. After that, it is parallel ,ranching of the airways. )he tur,ulent air hits the ter$inal ,ronchioles and then hits a $assi-e cross sectional airway where you can go diff path1s ,:c parallel ,ranching of the s$all airways. 9o, the airflow changes fro$ tur,ulent to la$inar airflow. 3y the ti$e you hit the resp unit, it is not $o-ing the air. +os! sma%% air3ay *>#s are in'%amma!ion o' !)e !ermina% -ron )io%es@ %ea*s !o 3)ee>e. )er$inal ,ronchioles are the site of chronic ,ronchitis. )his is the sa$e area as asth$a and ,ronchiolitis. +ore prox to the ter$inal ,ronchioles, in ,ronchitis, you will get a $ucus gland hyperplasia, and a lot of crap is co$ing up (that1s the producti-e part!. )he actual area of o,struction is the ter$inal ,ronchiole. .a-e go,let cell $etaplasia and $ucous plugs. )hin% a,out ha-ing one ter$inal ,ronchiole and one $ucous plug this is affecting a $ajor cross sectional area of lung ,:c all the parallel ,ranches that deri-e fro$ here will not ha-e C'( in the$, and they are trying to get air past the $ucous plug, ,ut cannot. 9o, !)ere is a HU:E 1en!?per'&sion misma! ). )his is why they are a%%e* -%&e -oa!ers = !)ey are yano!i . )hey ha-e $ucous plugs in the ter$inal ,ronchioles and cannot rid C'(. ". Emp)ysema &ot in the ter$inal ,ronchioles. It is in the resp unit ( resp &ni! is 3)ere gas ex )ange o &rs cannot exchange gas in the ter$inal ,ronchioles a%a nonresp ,ronchiole!5 it is the pri$ary place for expiratory wheeCe and s$all airway dC, howe-er. :as ex )ange o &rs in !)e resp -ron )io%e@ resp a%1eo%ar *& ! an* a%1eo%i. 'nly need to
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%now " emp)ysemas: en!ro%o-&%ar an* pana inar. ;$physe$a affects gas exchange and where it affects the airway is $ore distal, co$pared to chronic ,ronchitis (proxi$al!. 9o, when you ha-e e$physe$a with all the infla$$ation associated with it, not only destroy the resp unit, ,ut also the -asculature associated with it. )herefore, !)ere is an e1en %oss o' 1en!i%a!ion an* per'&sion. <o@ 3i%% NOT )a1e re!en!ion o' CO" in !)ese p!s. Ghen you ha-e a pro,le$ with a $ucous plug in the ter$inal ,ronchiole, which is way $ore prox and a great cross sectional area of the lung is affected, there is gonna ,e a pro,le$ there5 howe-er when you are out this far (in e$physe$a! and also destroying the -essels, you 3i%% no! )a1e an in rease in CO". )his is why they are called pin6 p&''ers, and this is why $any of the$ ha-e resp al%alosis. a0 Cen!ro%o-&%ar = mos! asso ia!e* 3i!) smo6ing an* in1o%1e* 3i!) !)e &pper %o-es. 9o, it is an upper lo,e e$physe$a, and the pri$ary portion of the resp unit that is destroyed is the resp ,ronchiole (this is the -ery first thing that s$o%e hits!. &eutrophils will da$age it ,:c all people that s$o%e ha-e $ore neutrophils in their lungs, and s$o%e is che$otactic for neutrophils. A88 s$o%ers ha-e increased neutrophils in their lungs. Ghat does alphaD1 antitrypsin doN It1s an antielastase (its only purpose is to destroy elastases produced ,y neutrophils that is its function. If you are a s$o%er, that is denatured. 9o, you also ha-e an ac#uired alphaD1 antitrypsin def!. ?on1t ha-e ade#uate alphaD1 antitrypsin, and ha-e too $any neutrophils in the lungs. )his is a terri,le co$,o. )his why neutrophils ha-e no pro,le$ in destroying the elastic tissue support of the respiratory ,ronchioles. 9o, you ,reath air in, which is no pro,le$5 ,ut you try to get it out, and there is no elastic tissue support and leads to lung expansion this is why ,le,s are found there are ,ig cystic spaces in the lung it has trapped air in there ,:c there is no elastic tissue, so when it tries to get ,y, it just expands. )his is en!ro%o-&%ar emp)ysema o' !)e UPPER %o-es. -0 Pana inar Emp)ysema (re$e$,er =pan1 $eans e-erything ie in pancytopenia, A88 the cells decreased!. 9o, panacinar $eans that the ;&)I2; resp unit is decreased ,:c it is associated with NO a%p)a 1 an!i!rypsin. )his is a genetic dC auto rec = !)e LI.ER *oes no! ma6e i!. 9o, at a young age, you de-elop destruction of entire resp unit of the 8'G;2 lo,es, so !)is is a LO5ER %o-e emp)ysema. 9o, you can see that the resp ,ronchioles are %noc%ed out, the al-eolar ducts are %noc%ed out, al-eoli %noc%ed out. 9o, you ,reathe in, and this entire resp unit catches it this is in the lower lo,es. 9$o%ers, which ha-e an ac#uired alphaD1 antitrypsin def, can get an ele$ent of panacinar e$physe$a in the lower lo,es, too. 9o, s$o%ers can get ( e$physe$a1s: centrolo,ular e$physe$a in the upper lo,es (which %noc%s off the resp ,ronchiole! and in the lower lo,es, get a panacinar type of pattern. )herefore, can get upper A&? lower lo,e e$physe$a, and ( diff types of e$physe$a. $. (ron )ie !asis .a-e ,ronchiectasis see ,ronchi going out to the pleura (a,nor$al!. Ghen you see ,ronchi going out further than the hilu$, this is ,ronchiectasis. +e ): in'e !ion@ *es!r& !ion o' !)e e%as!i !iss&e s&ppor!@ *i%a!a!ion o' !)e air3ays . 9eg$ental ,ronchi5 fill with pus. ;xa$ple: pt has a producti-e cough of IcupfulsJ (not just a ta,lespoon! of pus, ,:c they are trapped. a! Causes: 1! +CC ,ronchiectasis in <9A " ys!i 'i-rosis. If parent with child has cystic fi,rosis, will see huge pus co$ing out of ,ronchi, a couple ti$es per day. (! +CC ,ronchiectasis in 0rd world countries " T(. 0! 8ar!agener#s syn*rome (a%a i$$otile cilia syndro$e!. R/( configuration arrange$ent with cilia and $icrotu,ules. )he pro,le$ with i$$otile cilia syndro$e is an a,sent dynein ar$. )he R $icrotu,ules on the outside ha-e ar$s that %eep the$ together these dynein ar$s are $issing. 9o, when these ar$s are $issing, the cilia cannot $o-e. 9o, the places with cilia not $o-ing are affected: these places are sinuses (why sin&si!is is a pro,le$!, -ron )ie !asis (,:c there is cilia psuedostratified colu$nar epitheliu$ is affected!, $ales and fe$ales are in'er!i%e (,:c the tail on the sper$ cannot $o-e the tail is a $odified cilia they head is $o-ing, ,ut the tail is wea%. Go$en are infertile5 too, ,:c the fallopian tu,e needs cilia to carry the egg down. Organs are %o a!e* on !)e opposi!e si*e /*ex!ro ar*ia@ 3i!)OUT !ransposi!ion o' grea! 1esse%s0. 2. As!)ma Can ,e extrinsic (type 1 .*B! and intrinsic: In-ol-es che$icals people in the wor%place can get triad asth$a, which in-ol-es people ta%ing &9AI?s +any people, ie athletes will get exertional asth$a and wheeCe cro$olyn &a is the ?'C for these patients. Cold te$ps can cause asth$a. )ype I .*B has nothing to do with these causes of asth$a. )he wheeCing is due to infla$$ation of the ter$inal ,ronchioles it is not due to s$o%ing, ,ut ,:c factors li%e 8) C>, ?>, ;>, *L1s causing infla$$ation and narrowing of the airways. IG. L&ng Can er A. Perip)era%%y %o a!e* 1s. en!ra%%y %o a!e* 1. Cen!ra%%y %o a!e* /mains!em -ron )&s0: .a-e the highest association with s$o%ing. Include s#ua$ous cell carcino$a and s$all cell carcino$a. )hese are generally centrally located, hence $ainste$ ,ronchus types of locations. 9#ua$ous cell are $ore co$$on than s$all cell carcino$as. ". Perip)era%%y %o a!e*: A*eno ar inomas (the $ore co$$on pri$ary lung cancer, $ore co$$on than s#ua$ous! are $ore peripheral than central. 9hifted to the periphery ,:c of the filters of the cigarettes. )he filters pre-ented the large carcinogens fro$
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passing in, ,ut the s$all carcinogens still passed through, and they are not trapped in the $ain ste$, ,ut trapped in the periphery. )here are at least 0 or > types of adenocarcino$a. 'ne o,-iously does ha-e a s$o%ing relationship, while the others do not. )he ones that do not ha-e a s$o%ing relationship include ,ronchiolar al-eolar carcino$a, and large cell adenocarcino$a of the lung (scar cancers!. (. Cy!o%ogy: %now what s#ua$ous cancer loo%s li%e with a pap s$ear. A lot of people thin% that the *apanicolaou stain is only done for cer-ical carcino$a. )his is not the case. T)is is a 'amo&s s!ain (pap s$ear! &se* 'or a%% y!o%ogi a% spe imens on 'or a%% organs. T)e s!ain s!ain#s 6era!in -rig)! re*. 9lide: (pic! pt that is a s$o%er with a centrally located $ass. 9howing sputu$ sa$ple with a *apanicolaou (pap s$ear! stain has red %eratin, which is s#ua$ous cell carcino$a. If this were a cer-ical pap s$ear fro$ a wo$an that is >6 years of age, this is s#ua$ous cell carcino$a. )he %eratin is staining ,right redM (,right red cytoplas$ " %eratin " s#ua$ous cell carcino$a!. *apanicolaou stains %eratin ,right red. ;xa$ple: s$all cells that loo% li%e ly$phocytes this is sma%% e%% ar inoma. )his is $ore difficult to dx, ,:c so$eti$es diff to tell the difference fro$ ly$phocytes. 9lide shows $alignant cells. 9$all cell carcino$a is the $ost $alignant cancer of the lung. 2xN 2adiation and che$o (not surgery!. T)ese are a&p&! !&mors 3i!) ne&rose re!ory gran&%es an* <?1FF Ag posi!i1e. )hey can $a%e A?. and AC).. A slightly less $alignant tu$or with auput origin is the -ron )io ar inoi*. It is a low grade $alignancy of the sa$e types of cells that produce s$all cell carcino$a. 9o, they can in-ade, $et, and produce carcinoid syndro$e if they $a%e increased a$ount of serotonin. )hey don1t ha-e to $ets to produce carcinoid syndro$e it just goes straight into the ,loodstrea$. It is -ery unco$$on. C. Can er: +C cancer of lung " $ets ie see $any $etastatic nodules all o-er lung5 if you play odds, what is the pri$ary cancerN ,reast (which the +C $et to the lung, or in other words, it is the +C cancer of the lung!. <&mmary o' %&ng an er in !)e %&ng: +C an er , me!s +C primary an er , primary a*eno ar inoma o' !)e %&ng@ 'o%%o3e* -y s;&amo&s an* sma%% e%% ar inoma. 5ors! an er /3ors! prognosis0: sma%% e%% ar inoma. Horner#s syn*rome pancoast tu$or:superior sulcus tu$or tu$ors that are in the upper lo,e posteriorly (in post $ediastinu$!5 $ost of the ti$e is caused ,y s#ua$ous carcino$a in that area. Ghat1s happening hereN )u$or is locally in-ading into the local part of the lower trun% of the ,rachial plexus, so can get lower trun% ,rachial plexus li%e findings, and can also affect the superior cer-ical ganglion. )his is in the posterior $ediastinu$, therefore will end up with .orner1s syndro$e5 as a result, will end up 6no 6ing O99 sympa!)e!i a !i1i!y p!osis (lid is lower!, an)y*ro&s (lac% of sweating!, miosis (in sy$pathetic, which is fight or flight, nor$ally ha-e $ydriasis, which dilates the pupil with fight or flight, want as $uch light as possi,le, therefore dilating pupil, ,ut this is cut off, leading to $iosis!. ?o not confuse with 9KC syndro$e5 this is just ,loc%ing off 9KC. +yasthenia has to do with thy$o$a, which is located in the anterior $ediastinu$. ;xudate -s. transudate (Y 0 gra$s, without $any cells in it! +CC pleural effusion due to transudate " .4 ;xudate " protein U 0 gra$s, and has cells in it (ie pneu$onia1s, pul$onary infarction! CHAPTER B: :I I. Diseases o' !)e +o&!) A. Herpes simp%exI .erpes la,ialisD(fe-er ,listers and cold sores!5 pri$ary herpes is a syste$ic infection. .a-e fe-er, -ire$ia, generaliCed ly$phadenopathy, and goes away5 it stays in the sensory ganglia (dor$ant in the sensory ganglia! e-ery now and then it can co$e out with stress, $enses, whate-er, and will for$ -esicles. 2ecurrent herpes is no longer syste$ic there is no $ore fe-er, and no $ore ly$phadenopathy. 'ther -irus that re$ain latent herpes Coster re$ains latent in the sensory ganglia5 can in-ol-e the s%in, lips, der$ato$es. 9o, primary )erpes is sys!emi @ re &rren! )erpes is no!. /No 'e1er , no %ymp)a*enopa!)y!.If we enroot and stain, will see inclusion in herpes it is a $ultinucleated cell with internuclear inclusions. 3iopsy of a $ultinucleated cell fro$ a pt with .IK, with $ultiple internuclear inclusions herpes esophagitis. (. Hairy Le&6op%a6ia )his is not an AI?s defining lesion, ,ut I9 a preAI?s type of infection as is thrush, shingles. 8ocated on the lateral ,oarder of the tongue. .as nothing to do with dysplasia (leu%opla%ia!. It is a result of an in'e !ion 'rom E(.. 9o, do not get the idea that it is a preneoplastic lesion. 9tart seeing this ,efore the helper ) cell count get to (66. 2x D Acyclo-ir C. T)r&s) /ora% an*i*iasis0 In an adult, therefore can assu$e that it is in an i$$unoco$pro$ised patient, where there is a defect in cellular i$$unity. In %ids (new,orns!, they can get it fro$ the $o$ on the way out. .owe-er, it is not a sign of i$$unoco$pro$ise. 9o, adult " IC1d
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D. Ex&*a!i1e !onsi%%i!is $FP )an e !)a! i! is gro&p A -e!a )emo%y!i s!rep . HFP )an e !)a! i! is a 1ir&sI a*eno1ir&s@ E(.. 9o, when you see exudati-e tonsillitis, cannot assu$e it is ,acteria and i$$ediately gi-e *C&. .ow do you pro-e it is group A strepN 8atex agglutination test. 9o, $ost pus tonsils are not ,acteria. ;xa$ple: It is group A strep, and 0 wee%s later, has ,ilateral rales, pansystolic $ur$ur apex radiating into the axilla, polyarthritis dxN 2heu$atic fe-er. Ghen you do a ,lood culture what would you findN &othing it1s not an infecti-e endocarditis. E. Le&6op%a6ia Ghite lesion, pla#ue li%e, try to scrap off, ,ut won1t co$e off " clinical dx of leu%opla%ia what is the first step in $anage$entN 3x )rue in the -ul-a:penis area white or reddishDwhite pla#ue li%e lesion that does not scrape off first step in $anage$entN 3x. GhyN 2ule out dysplasia and:or in-asi-e cancer. 9. Can er o' !)e mo&!) +CC s#ua$ous dysplasia and cancer " s$o%ing (nd +CC " alcohol If you do ,oth, you increase the ris% of ,oth. In-asi-e s#ua$ous cancer " color change Lo3er %ip an erE <;&amo&s e%% ar inoma Upper %ipE (asa% e%% ar inoma Keracious carcino$a fro$ chewing to,acco (s#ua$ous carcino$a!5 also has a .*K -irus associated with it. :. .yperpig$entation dxN A**ison#s Addison1s: diffuse pig$entation, low cortisol le-els, increased AC). (AC). has $elanocytes sti$ulating properties!5 -ery first place you see hyperpig$entation is in the 3uccal $ucosa. H. Pe&!>?Jeg)ers 3lotchy (not diffuse! areas of hyperpig$entation. Po%yps in sma%% in!es!ine. )his is one of the exceptions to rule for polyps in the s$all intestine. +ost polyps in the LI located in the sig$oid colon5 howe-er, polyps of *eutC Feghers are located in the s$all intestine, and they are ha$arto$as, therefore they are not neoplastic, and their a,ility to change to cancer is Q;2'. II. Diseases o' !)e <a%i1ary :%an*s P%eomorp)i a*enoma a6a +&mps 7 mixe* !&mor ( &') a terato$a, ,ut a $ixed tu$or it has two diff types of tissues, sa$e cell layer!. It is the +C sali-ary gland tu$or o-erall, and is in the +C location the parotid. +&mps para$xyo-irus, increase in a$ylase5 is the incidence of orchitis highN &o5 does it cause infertilityN &o, whyN 3:c its unilateral if it were ,ilateral then it would a $uch greater chance. <sually in older teenage $ales or $ale adults is where orchitis will occur. Can also occur in fe$ales D oophoeritis +C unilateral, therefore infertility is rare. III. Diseases o' !)e esop)ag&s A. Dysp)agia an* o*ynop)gia , *i''i &%!y s3a%%o3ing +ost of the ti$e, there will ,e EDA clues per #uestion. A pt has pro,le$ swallowing foods, is it solids or li#uidsN If the pt can ta%e down li#uids and not solids (*i''i &%!y in s3a%%o3ing so%i*s!, it is *&e !o o-s!r& !ion can ,e due to esophageal we, in *lu$$er Kinson syndro$e, I?A with glossitis and cheilosis and an esophageal we,, esophageal cancer If pt )as pro-%em s3a%%o3ing so%i*s AND %i;&i*s@ i! is a peris!a%sis pro-%em@ which is -ery ,ad. If it1s the upper 1:0 of the esophagus (which is all striated $uscle!, it is due to $yasthenia gra-is (,:c it affects striated $uscle!. If it1s the $iddle 1:0 (co$,o of s$ooth and striated $uscle!. And if it1s the lower 1:0 (s$ooth $uscle! it1s due to 9cleroder$a (a%a progressi-e syste$ic sclerosis and C2;9) syndro$e! and achalasia. 9o, they will tell you i$$ediately if they can swallow li#uids and:or solids, or neither (which is a peristalsis pro,le$!. .ow can you distinguish *99:C2;9) fro$ achalasiaN In achalasia, they -o$it up the food they ate when they go to ,ed at night5 or they will tell you pt has 2aynaud1s, indicating that it is C2;9). O*ynop)gia , PAIN9UL s3a%%o3ing5 always a,nor$al In .IK pt " Candida esophagitis is it AI?s definingN Bes. +C fungal infection in .IK " Candida Ghen it gets into the esophagus, it is AI?s defining Ghen it is a thrush, it is *2; AI?9 lesion (not aids defining! He%p'&% )in!s 3i!) o!)er *iseases: Pa%pa-%e p&rp&ra , imm&ne HPY !ype III , Heno ) < )on%ein /+C0 Epis!axis , p%a!e%e! pro-%em /*on#! !)in6 )emop)i%ia0V!)ey gi1e %&esJ Pansys!o%i m&rm&r in reases on inspira!ion , !ri &spi* reg&rg Pansys!o%i m&rm&r in reases on expira!ion , mi!ra% reg&rg
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(. Tra )eoesop)agea% 'is!&%a 3lindly ending esophagus (prox esophagus ends ,lindly! distal esophagus arri-es fro$ the trachea. Ghat does the $o$ ha-eN *olyhydra$nios a$niotic fluid is ,a,y urine, so ha-e to recycle it, or $o$ will ha-e ,ig ,elly. 9o, the ,a,y swallows it and it is rea,sor,ed in the s$all intestine. 9o, if you ha-e o,struction in the esophagus, or proxi$al portions of the duodenu$, $o$ will ha-e polyhydra$nios. 9o, there are ( answers: 1! )racheoesophageal fistula (! duodenal atresia in ?own1s syndro$e these ( are associated with polyhydra$nios. )hey ,loc% the a,ility to rea,sor, a$niotic fluid, leading to polyhydra$nios. Also, when these %ids eat, food gets caught and %ids cough and sputter ,:c the distal esophagus arises fro$ the trachea and leads to distension of the sto$ach. )his is -ery characteristic. C. Wen6er#s *i1er!i &%&m Area of wea%ness cricopharyngeous $uscle. It has a lil slit in ,etween the fi,ers of it. &ot the whole area is cut (which would ,e a true di-erticulu$ this is a false di-erticulu$!. It goes out and gets a pouch. )he pouch collects food and leads to halitosis. )hey ha-e a tendency of regurgitating undigested food out of the nose. D. A )a%asia Peris!a%sis pro- = pro- 3i!) re%axa!ion o' !)e LE<, therefore it is in spas$ all the ti$e. GhyN If you ,x that area, this $eans that the ganglion cells are $issing. Ghat dC does this re$ind you ofN Hirs )spr&ng *>. Ghat is in those ganglion cellsN Kasointestinal peptide (KI*!. Ghat is its functionN )o relax the 8;9. 9o, when you destroy those ganglionic cells, not only do you destroy the $o-e$ent of the lower esophagus, ,ut you also reduce KI* le-els. 9o, you ha-e constant constriction of the 8;9, leading to ,ird ,ea%. *rox portion is dilated. E. Parasi!es ?C of 9outh A$erica where the leish$ania for$s in-ades the ganglion cells of the 8;9 and the rectu$ produce ac#uired achalasia and .irschsprung dC " C)aga#s *>, -ector " redu-id ,ug (a%a %issing ,ug!5 swelling of the eye signN 2o$ana1s. Ghat does it do in the heartN Causes $yocarditis and chronic heart failure congesti-e cardio$yopathy. )his is one of the $ore co$$on causes of heart dC in 9outh A$erica. 9. (arre!! esop)ag&s <lcerated $ucosa in the distal esophagus. 3x: see glandular $etaplasia5 therefore see go,let cells and $ucous cell (which shouldn1t ,e there!. )hey are there ,:c the esophagus cannot protect itself fro$ esophageal injury. )herefore, run the ris% of adenocarcino$a of the distal esophagus. ;xa$ple: If the lesion in esophagus, dsyphagia of solids, ,ut not li#uids, lesion in noted in distal esophagus do &') pic% s#ua$ous cell carcino$a this is in the +I? esophagus. If it is distal, it is adenocarcino$a, and the precursor lesion is 3arrett1s esophagus. :. Esop)agea% 1ari es ?ilated su,$ucosal esophageal -eins " therefore pt has cirrhosis, who was an alcoholic. *t also has portal .)& the left gastric -ein is in-ol-ed (one of the ,ranches off the portal -ein is left gastric -ein!. )he left gastric -ein drains the distal esophagus and proxi$al sto$ach. Ghat drains into the left gastric -einN ACygous -ein. Ghere does the left gastric -ein drain intoN *ortal -ein. .owe-er, ,:c of cirrhosis, portal -ein cannot e$pty ,lood sufficiently into it, the hydrostatic pressure increases5 you re-erse ,lood flow into the left gastric -ein, splenic -ein, and other -eins, and end up producing -arices that rupture. Hema!emisis " -o$iting ,lood Hemop!ysis " coughing up ,lood Hema!o )e>ia " ,lood pouring out of anus (actual dripping of ,lood not coating of stool with ,lood, that is seen in anus!. +CC " di-erticulosis5 not di-erticlulitis ,:c the -essel is next to the di-erticular sac, so if it were =Dtitis1, it would ,e scarred off. Gith Dosis, it is intact, and just ha-e to erode it, leading to A $8 ,leed. H. +a%%ory 5eiss <yn*rome )ear at esophagoDgastric junction. ;xa$ple: let1s say its young wo$an (play odds! what does she ha-eN 3uli$ia. Classic ;xa$ple: alcoholic with retching (trying to -o$it, ,ut nothing is co$ing out causes tre$endous pressures, leading to tear (he$ate$isis! or puncture (3orha-e1s D this is when the air gets into the pleural ca-ity, and leads to .a$an1s crunch of the anterior $ediastinu$!. 9o, seen with ,uli$ia and leads to 3orha-e1s (-s. an alcoholic!. I. Esop)agea% an er 9#ua$ous cancer (not distal, ,ut $id!5 +CC1s " s$o%ing and alcohol ((nd +CC! ?ysphagia seen in this pt D initially, pt cannot swallow solids, ,ut can ta%e down li#uids. ;xa$ple: E6 y:o, $ale, alcoholic, wt loss, pro, swallowing foods, not li#uids dxN ;sophageal cancer s#ua$ous cell carcino$a of the $idDesophagus (play odds!. ;xa$ple: pic of trachea and see cartilage rings, and elastic artery (esophageal in $iddle! this is esophageal cancer. I.. Diseases o' !)e <!oma ) A. Congeni!a% Py%ori <!enosis ;xa$ple: $ale, 0 wee%s old and started 1omi!ing non -i%e s!aine* '%&i* a! $ 36s5 palpated the a,do$en and felt a %not in 2<P and see hyperperistalsis. )his is &'& ,ile stain fluid at 0 wee%s. Congenital *yloric 9tenosis 5)a! i' i! is *&o*ena% a!resia in a *o3n#s 6i*E )hat would ,e a! -ir!) 1omi!ing of ,ile stained fluid. And dou,le ,u,,le sign atresia (lac% of de-elop$ent of the lu$en! is distal to where the ,ile duct co$es in, so ,ile can still enter the proxi$al portion of the duodenu$ this is why it is ,ile staining ,:c there is no $o-e$ent, there will ,e air trapped in
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there, and air is trapped in the sto$ach, therefore there is air in the sto$ach and prox duodenu$ a dou,le ,u,,le sign. Also, $o$ will ha-e polyhydra$nios. 9o, do not confuse congenital pyloric stenosis (which has no relationship to down1s! with duodenal atresia. It does ha-e $ultifactorial inheritance5 therefore it can ,e increased in future children. Can see pyloric stenosis, as it has thic%ened. )o 2x, split the $uscle (called pyloroplasty!. (. N<AID &% ers &on steroidal will ,loc% *L;(, which is responsi,le for the $ucous ,arrier of the sto$ach, and -asodilatation of the -essels, $ucous secretion, and secretion of ,icar, into the $ucous ,arrier. 9o, when you ta%e &9AI?9 for a period of ti$e, the whole thing is destroyed. 8eads to $ultiple ulcers and significant ,lood loss o-er ti$e. )hey are punched out. C. H. py%ori <i%1er s!ain /as is PCP@ Legione%%a@ -ar!ene%%a )ensi%ai0. Co$$a shaped organis$s (li%e ca$pylo,acter!, ,ut found out that they ha-e different cell walls and etc. &asty ,ug ,:c it $a%e lots of cyto%ines and urease which con-erts urea to a$$onia, and is one of the reasons why they can ,urrow through the $ucous layer a$$onia is -ery toxic this is the test we use when we ta%e ,x of gastric $ucosa, we do a urease test on it and if its positi-e, %now . pylori is in it. Can also use serological tests A,1s against it. It1s only good for the first ti$e. GhyN 3:c the A,1s do not go away and, therefore cannot dx reacti-ation or recurrent. After that it is useless ,:c won1t tell anything ,:c will always ,e positi-e ,:c A,1s stic% around. Ghere does perni io&s anemia )i!E (o*y an* '&n*&s. )hat is where the parietal cells ha-e autoA,1s destroying the$, and I4 leading to atrophic gastritis. )his is &') where . pylori exerts its affect. H py%ori a''e !s !)e py%or&s an* an!r&m. It destroys the $ucosa, leading to atrophic gastritis of the pylorus and antru$. )his is where cancers are. +ost cancers are along the %esser &r1a!&re o' !)e py%or&s an* an!r&m (exact sa$e place where gastric ulcers are!. )he . pylori li-e in a $ucous ,arrier and therefore is protected. +CC s!oma ) an er , H py%ori. . pylori can also cause $alignant ly$pho$as of the sto$ach (low grade!. Ghy don1t we e-er ,x a duodenal ulcerN 3:c they are ne-er $alignant. 3ut gastric ulcers ha-e a chance of ,eco$ing $alignant therefore need to ,iopsy gastric and not duodenal ulcers. 'nly reason they ,x a gastric ulcer is ,:c they are trying to rule out whether it is cancer ($alignant! or not they %now it1s an ulcer and it has a 07 of ,enign $alignant. &e-er ha-e to ,x a duodenal ulcer, so just lea-e alone. H py%ori is more ommon%y asso 3i!) *&o*ena% PUD !)an gas!ri . Ghy do you get $elana with upper LI ,leedsN <pper LI " anything that is a ,leed fro$ the liga$entu$ of trietC where the duodenu$ hits the jejunu$ and up. Ghy is it ,lac%N Acid acts on ., and con-erts it to he$atin. .e$atin is ,lac% pig$ent, leading to $elana. )his is i$p to %now, ,:c if you ha-e ,lac% tarry stools, and its RE7 chance that is an upper LI ,leed, and if you play odds, it is pro, a duodena ulcer (-s. a gastric ulcer!. 9o, ., is con-erted ,y acid to he$atin, which is a ,lac% pig$ent. Ko$iting of coffee ground $aterial " ,lood clots acted upon ,y acid and changes to he$atin. ;xa$ple: *t, an executi-e under great stress, and sudden onset of se-ere epigastric pain that radiates into the left shoulder. 4irst step in wor% upN 4lat plate of the a,do$en5 see air under diaphrag$. 'ddsN ?uodenal ulcer. Ghy did he ha-e shoulder painN Air got out, settled under the diaphrag$, irritated ner-e S> (phrenic!, and got referred pain to the der$ato$e (which is the sa$e der$ato$es! D. R)ini!is P%as!i a: A*eno ar inoma o' !)e s!oma ) Gith signet ring cells. ;xa$ple: E( y:o fe$ale with weight loss and epigastric distress. 9he had an upper gastrointestinal series, noted that sto$ach did not $o-e (no peristalsis!, and then she died. ?xN 2hinitis plastica cells that are in-ading the wall of the entire sto$ach, called signe! ring e%%s (which are stained with $ucocarnine cells, are pin% signet cells are li%e a dia$ond ring, and the dia$ond has ,een pushed to the periphery!. )he $ucous is inside, $a%ing the cell loo% e$pty, and pushing the nucleus to the side (just li%e fatty change of the li-er!. .owe-er, these are $alignant neoplastic glandular cells, and are characteristic of rhinitis plastica type of gastric adenocarcino$a. +isconception: 8r&6en-erg !&mor is not a tu$or that is seeding out to the o-ary. )his tu$or is due to he$atogenous spread to the o-ary. )here is no such thing as a signet ring carcino$a of the o-ary (there is no pri$ary cancer of the o-ary that loo%s li%e this!. T)e signe! ring e%%s ame 'rom s!oma ) an er !)a! )as me!as!asi>e !o o1aries , 8r&6en-erg !&mor. +ost are ulcerati-e tu$ors in the lesser cur-ature of the pylorus and antru$. 8eather ,ottle sto$ach -ery hard due to all of the cancer cells and the fi,rous response to it. Lastric cancer is declining in <95 other countries it is a pri$ary cancer D Fapan, ,:c s$o%ed products. 'ther ethnic cancers: nasopharyngeal carcino$a " china5 sto$ach cancer and .)8K 1 " Fapan5 3ur%itts ly$pho$a " Africa. If there was a nontender $ass in left supracla-icular area and pt with epigastric distress one wee% ago dxN +etastatic gastric adenocarcino$a. Cer-ical cancer can also $etastasiCe here. 8eft supracla-icular node drains a,do$inal organs5 therefore pancreatic cancers ,ut $ostly the sto$ach cancers $etastasiCe there. )he right supracla-icular node $ets are fro$ lung cancer.
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.. +a%a-sorp!ion +eans ,ad a,sorption of e-erything: fats, car,s, and proteins. steatorrhea " screening test for $ala,sorption.
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?iagnosis point of -iew we loo% for increased fat in the stool "
A. 9a! Diges!ion: 1! &eed lipases to ,rea% down fat into ( $onoglycerides and 4A1s, so you need a functioning pancreas. (! &eed -illi of the s$all intestine ,:c if we didn1t, the s$all intestine would ha-e to ,e a $ile long. Killi increase the o-erall a,sorpti-e surface without increasing the length. 9o, if you don1t ha-e the$, you decrease the a,sorpti-e surface, and will lose the $onoglycerides and 4A1s. )herefore, you need a functioning 9I with -illi. 0! &eed ,ile salts to e$ulsify the fat and ,rea% it down to $icelles (tiny particles that are 1 $icron in dia$eter! and chy$lo$icrons. ;$ulsifying agents are $any ti$es in dishwashers ,:c need to get fat off plates. 4at will co$e to the surface and ,rea% up into $icelles, which are easier to a,sor,. 9o, need functioning pancreas, ,ile salts, s$all intestine that has -illi in order to rea,sor, fat. (i%e sa%!s are $ade in the li-er fro$ cholesterol. Cholesterol cannot ,e degraded5 it either solu,iliCed in ,ile (therefore run the ris% of cholesterol stones! or is con-erted to ,ile acids. Cannot ,rea% down cholesterol. \ 3ile salt deficiency is seen in: a! li-er dC5 ,! anything that o,structs ,ile flow will produce ,ile salt def5 c! ,acterial o-ergrowth can eat and ,rea%down ,ile5 d! ter$inal ileal dC, ex. Crohn1s dC cannot recycle5 and e! Cholestyra$ine: resins used for treat$ent of hyperlipide$ia, can produce ,ile salt def. )his is the +'A of resins, ,y ,inding and then excreting the$, ,:c if you are not recycling the$, you will $a%e $ore. Ghat1s happening in the li-erN <pregulation of 8?8 receptors synthesis, ,:c need to $a%e $ore ,ile salts, therefore need to suc% $ore out of the ,lood and will $a%e $ore 8?8 receptors. )hese drugs will e-entually ta%e $ore cholesterol out of the ,lood and lower it, so you can $a%e $ore ,ile salts. It also ta%es drugs with it, so it1s not good for people ta%ing $eds, ,:c you will lose these $eds in the stool, along with ,ile salts. ?C1s: screening test is loo%ing for fat in stool (steatorrhea! let1s say it is positi-e. 9o, we ha-e to figure which if the 0 areas is the cause of the $ala,sorption pancreatic def, ,ile salt def, or so$ething wrong with the s$all ,owel (+C!. (. Ce%ia D> /spr&e0 *ic of s$all ,owel lesion and a s%in Cit that has an association with it. )his is celiac dC (autoi$$une dC!, and the s%in Cit is *erma!i!is )erpe!i'ormis. Ce%ia *> is an a&!oimm&ne *> agains! g%&!en 3)ea!@ esp. g%ia*in . It is -ery co$$on and is the +CC of $ala,sorption in this country. 9o, when you eat wheat products, the gluten is rea,sor,ed into the -illi and there are A,1s against gliadin, and leads to destruction of the -illi (just li%e A,1s against parietal cells or intrinsic factors, which destroy e-erything around it!. 9o, the A,1s attac% gluten that has just ,een rea,sor,ed ,y the food, which will cause destruction of the -illus. And there are no -illi here it is flat5 ,lunting of -illus so you are not a,le to rea,sor, fat, proteins, or car,s. )here is no -illus surface. )he glands underneath are fine, howe-er. )he -illi are a,sent. )here is a 1FFP )an e o' *erma!i!is )erpe!i'ormis asso ia!ion 3i!) &n*er%ying e%ia *>. Derma!i!is )erpe!i'ormis is an a&!oimm&ne *>@ an* i! is a 1esi &%ar %esion o' !)e s6in loo%s li%e herpes of the s%in. )hey will show pic of a der$atitis herpetifor$is, and will as% what the cause of diarrhea isN A,1s against gluten (gliadin!. C. 5)ipp%e#s *> An infection of the s$all infection due to an organis$ that you cannot gra$ stain. ). whippelii only seen with ;+5 cannot ,e cultured. 9ee flat ,lunted -illi and foa$y $acrophages (loo% li%e &ie$ann pic ,u,,ly $acrophages5 can also ,e fro$ an .IK I/J ,:c it loo%s li%e Ghipple1s, ,ut isn1t!. )he $acrophages ha-e distincti-e *A9Dpositi-e stains. HI. posi!i1e p! and acid fast stain pt with helper ) cell count of 166. .a-e an acid fast stain with the foa$y $acrophages *&e !o +AI (this is $ore co$$on that )3!, and an a&se 5)ipp%e %i6e *> 3i!) ma%a-sorp!ion. Ghipple1s, ,eing an infection, has syste$ic signs and sy$pto$s: fe-er, ly$phadenopathy, polyarthritis, generaliCed pain. It1s an infection therefore can ,e treated with anti,iotics. 9o, there are " *>#s !)a! a&se ma%a-sorp!ion: e%ia *> an* 5)ipp%e#s *> . 'ther dC1s are dC1s of the pancreas )roni pan rea!i!is /+C in a% o)o%i s ( reasons for $ala,sorption in alcoholics a lipase def related to chronic pancreatitis, or ,ile salt def due to cirrhosis, or ,oth in an alcoholic!. D. Diarr)ea 3est way to classify is to su,di-ide into 0 types: 1. In-asi-e: ,acteria in-ades (. 9ecretory: the ,acteria produces toxins and that will sti$ulate cA+* (or other $echanis$s! causing the s$all ,owel to secrete s$all a$ounts of I9')'&IC fluid, which is &aCl. 0. 's$otic: lactase deficiency. Also produced ,y laxati-es, and other in,orn errors of $eta,olis$. 9ecretory and os$otic diarrheas are high -olu$e diarrheas and you go fre#uently, whereas in-asi-e diarrhea is a s$all -olu$e diarrhea. 3est:cheapest test to get in a pt with diarrhea " fecal s$ear for leu%ocytes. If there are &') any neutrophil don1t worry ,ecause not in-asi-e. If there are infla$$atory cells then you $ust do fecal s$ear test for ca$pylo,acter or shigella.
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a! 's$otic diarrhea (fits in with os$otic water $o-e$ent! is when there is so$e os$otically acti-e su,stance in the ,owel lu$en that is suc%ing water out of the ,owel, causing a high -olu$e, hypotonic loss of fluid. ;xa$ple: lactase def. " ,rush ,order or disaccharidase deficiency, a ,rush ,order enCy$e. In a classic case ,ut they will not tell you it1s a lactase def, instead will tell you it1s a disaccharidase def or e-en a ,rush ,order enCy$e def. 9o if you1re lactase def, it $eans that any dairy products which contains lactose (which ,rea%s down into glucose and galactose! can1t ,e indigested. 9o it will go to the colon, and act as desserts to the anaero,ic ,acteria which will eat the lactose and produces hydrogen gas, and other gases, and acids, and get acidic stools. )he hydrogen gases causes the ,loating, distention, and incredi,le explosi-e diarrhea. ,! 9ecretory diarrhea: two things to %now, Ki,rio cholerae and ;);C (tra-eler1s diarrhea!. )hese are not in-asi-e diarrhea, therefore when you do a ,owel ,iopsy there will not ,e one iota of infla$$ation, it1s perfectly nor$al. It1s purely a toxin that acti-ates a pu$p either cA+* (Ki,rio! or so$e other pu$p: guanylate cyclase (;. coli!. )reat$ent: when you gi-e fluid replace$ent to patients with -. cholerae, you need to gi-e glucose along with the fluids. )his is ,:c you need glucose to coDtransport &a that was in the fluids. 9ide note: &eed to %now the other ;. coli related toxins: ;.;C: '1E@:.@5 ;I;K5 and ;agg;C. c! In-asi-e diarrhea: the +C in <9 is caused ,y ca$pylo,acter jejuni, and shigella is a close second. Classic case: a person with low -ine(N! diarrhea, with so$e ,lood in it, and on gra$ stain there were co$$a shaped or 9Dshaped organis$s that1s ca$pylo,acter jejuni. 3oth of these organis$s can produce pseudo$e$,ranes. )herefore all pseudo$e$,ranes does not necessarily $ean you will see C. difficile. d! *arasites that causes diarrhea: :iar*ia: owl eyes that $o-e. )his is the +CC of diarrhea due to a parasite in the <9. )reat$ent: $etronidaCole. Cryp!ospori*i&m par1i: +CC of AI?9 diarrhea is a partially acidDfast organis$. It stic%s to the wall of the colon. Classic case: there is a pt that has AI?9 and has diarrhea, and when they stain it, there are oocysts that are partially acidDfast. It will %ill if you are i$$unoco$pro$ised. )he treat$ent is al$ost worthless. It co$es at the end when the helper )Dcells are near E6 or @E, and that1s when all the organis$s that will %ill you: +AI, cryptosporidiu$, toxoplas$osis, and C+K all co$es in at the end. *. carinii co$es in around (66 helper )Dcells. C%os!ri*i&m *i''i i%e: )his is an autopsy pic of an older wo$an who was in the hospital with pneu$onia, and she de-eloped diarrhea. Ghat was found on autopsyN Gell, it is safe to say that if she had pneu$onia, then she was ta%ing anti,iotics. 9o this is pse&*omem-rano&s o%i!is@ a&se* -y %os!ri*i&m *i''i i%e. )his occurs when ta%ing anti,iotics that wipe off the good organis$s, lea-ing ,ehind c. difficile. ;-ery,ody has c. difficile in their stools, ,ut ;. coli, entero,acter fragilis are %eeping it in chec%. 3ut when ta%ing anti,iotics such as a$picillin (+C!, clindo$ycin ((nd +C! for a period of ti$e, you %noc% off the good guys, gi-ing c. difficile a chance to proliferate and $a%e toxins that da$age the superficial layers of the colon. )he ,acteria doesn1t in-ade, it1s the toxins that do. )his is analogous to c. diphtheria, which also has a toxin that da$ages and produces pseudo$e$,ranes ,ut the organis$ does not in-ade. )he ri,osylation thing, and the ;longation factor ( (;4D( allows for protein elongation! are $essed up, therefore cannot elongate proteins. )he first step in $anage$ent is to do a toxin assay of stools, not gra$ stain ,:c there are lots of gra$ stain organis$s in the stools, not ,lood culture ,:c it1s not in the ,lood. T)e s reening !es! o' )oi e is !oxin assay o' s!oo%J )he treat$ent is to gi-e $etronidaCole, used to gi-e -anco$ycin ,:c c. difficile ,eca$e resistant to it. +etronidaCole itself can produce pseudo$e$,ranous colitis ,ut you ta%e that chance. .I. Diseases o' !)e <ma%% In!es!ine A. <ma%% -o3e% o-s!r& !ion: 9ee classic step ladder appearance of airDfluid le-els: air, fluid, air, fluid (step ladder appearance!. Ghen you ha-e a hollow -iscous that peristalsis, you get a certain characteristically pain, called COLIC pain. It isn1t li%e a cra$py pain with no painfree inter-als5 colic%y pain is when you ha-e pain, a painfree inter-al, pain, and then a painfree inter-al. )he inter-als are not consistent, so$eti$es you ha-e a 1E $in painfree inter-al, and other ti$es if $ay ,e longer or shorter. )his is colic%y pain5 it $eans )')A8 s$all ,owel o,struction. 3y the way, the ,ile duct does not ha-e peristalsis, therefore you do not get colic%y pain, and instead you get cra$py pain. Bou ha-e to ha-e peristalsis to get colic%y pain, it has to $o-e. And what1s it doing is trying to $o-e against that o,struction and that1s causing the pain. 3:c you cannot perstalse you get stagnation of the food proxi$al to where-er the o,struction is, and get airDfluid le-els. ?istal to the area of o,struction there is no air. In o,struction, there are two things that can happen: ons!ipa!ion or o-s!ipa!ion. Constipation is where you ha-e a pro,le$ with stooling, which does not necessarily $ean o,struction. ',stipation $eans that not only do you ha-e constipation you also ha-e a pro,le$ passing gas, that $eans you ha-e co$plete o,struction. 9o you ha-e to as% the pt whether they ha-e passed any stools or gas. +CC o' o-s!r& !ion: a*)esions 'rom pre1io&s s&rgeries. 9lide: those are water$elon pits, with a narrow lu$en. 3ut if the case read that this pt did not ha-e per-ious surgeries and had colic%y pain, this is due to the ,owel ,eing trapped in the in*ire ! ing&ina% )ernia. ;xa$ple: there was a weight lifter who de-eloped colic%y pain in the 28P area, had no pre-ious surgery, the $ost li%ely cause is indirect inguinal hernia. Geight lifters often ti$es create indirect inguinal hernias. <i*e no!e: there was a pic of Do3n#s syn*rome %id. )riso$y (1 (a,nor$al nu$,er of chro$oso$es! is due to nondisjunction (une#ual separation during the first stage of $eiosis I! ,ut not all down1s ha-e triso$y (1. 3ut if the %id had nor$al >A chro$oso$es, this is due to Ro-er!sonian !rans%o a!ion. In this case, they would ha-e >A chro$oso$es ,ut on one of those chro$oso$es (1, will ,e another chro$oso$e attached to it. )hey will ha-e three functional chro$oso$e (1. )he two LI diseases that are +C1ly seen in ?own1s are *&o*ena% a!resia (dou,le ,u,,le sign! and Hirs )spr&ng *>.
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(. Hirs )spr&ng *>: the ner-es are there ,ut the ganglionic cells are $issing. 9o, what happens if it1s $issing in the rectu$, the stools cannot get ,y, e-en when there is an opening, ,:c there is no peristalsis. 9o the stools just stay there. 9o, the dilation of the proxi$al colon has ganglionic cells, and there peristalsis occurring and you can1t get the stools thru the rectal area. 9o this $eans that the rectal a$pulla has no stools in it. ;xa$ple: if you ha-e a child that didn1t pass the $econiu$ in (> hours and a rectal exa$ was perfor$ed. If there was NO s!oo%s !)a! ame o&! on exam i! means Hirs )spr&ng *>. If on exa$, there was stools on the finger, it $eans tight sphincter. T)is is a *> o' !)e o%on. C. In!&ss&s ep!ion: $ost occur in children, and it1s when the ter$inal ileu$ intussuscepts goes into the cecu$. )here will ,e colic%y pain ,:c you are o,structing, and not only that, you are co$pro$ising ,lood flow, so you get the ,leeding. )hey will say: a ( y:o %id, with colic%y pain and ,loody stools. )hey $ight way there is an o,long $ass in the 2<P. In so$e %ids, it spontaneously co$es out, ,ut if not, then the radiologists will do ,ariu$ ene$a, and put a little pressure there, and he re-erts it. 9o you get co$plete ,owel o,struction and infarctions. D. .o%1&%&s: )wisting of the colon around the $esentery ,:c there1s too $uch of it causing co$plete o,struction and infractions due to co$pro$ising ,lood flow.
E. :a%%s!one i%e&s usually seen in older people, $ore wo$en, and ha-e signs of colic%y pain, and o,struction. )he gall,ladder stone falls thru the fistula and settles into the ileocecal -al-e and causes o,struction. 9ee a flat plane of the a,do$en that produced air in the ,iliary tree. 3oo$, there1s your ?x. )here is a fistula that is co$$unicating the gall,ladder with the s$all ,owel therefore air can get in the s$all ,owel and the ,iliary tree. Air in !)e -i%iary !ree 3i!) o%i 6y pain is ga%%s!one i%e&s. D> o' ga%%-%a**er. 9. +e oni&m I%e&s , ys!i 'i-rosis .II: Diseases o' !)e Co%on A. .as &%ar *iseases o' !)e o%on: 1. Is )emi (o3e% D>: )he s$all ,owel $ore co$$only infracts than the large ,owel, ,:c it has only one ,lood supply. )he entire s$all ,owel, the ascending colon, and the trans-erse colon are all supplied ,y the 9+A (superior $esenteric artery!. 9o, what is the $ain diff in a s$all ,owel infarct -s. an ische$ic ulcer causing ,loody diarrhea in the splenic flexureN )he difference in *resentation. )hey ,oth can ha-e ,loody diarrhea. .owe-er, the sma%% -o3e% in'ar !ion will ?I44<9; a,do$inal pain (all o-er not one specific area!. In is )emi o%i!is, it will point to specific area on right side of a,do$en. )his differentiates ,twn a s$all ,owel infarct fro$ a s$all infarct in the colon (can pinpoint area!. ". Angio*ysp%asia (nd +CC Hema!o )e>ia, with di-erticulosis ,eing S1. It1s in the cecu$ ,:c law of 8aplace (wall stress and radius!. )he dia$eter of the cecu$ is ,igger than any other part of the colon. 3:c the dia$eter is greater, the wall stress is greater. )herefore, putting stress on the -essels in the wall of the cecu$, it actually pulls the$ apart and produces telangiectasias. As a result, it predisposes to angiodysplasia ,:c increased wall stress. If one of the$ ruptures to the surface, you can end up with significant ,leed. A -ery co$$on cause of .e$atocheCia in older people. 9o, if di-erticulosis is ruled out, angiodysplasia is pro,a,ly it. (. +e 6e%#s Di1er!i &%&m7 <ma%% In!es!ine D>: 1. R&%e o' "#s: (7 of pop1n5 ( inches fro$ ter$inal ileu$5 ( ft fro$ the iliocecal -al-e5 ( c$ in length5 ( y:o or younger5 and (7 of carcinoid tu$ors occur in +.?. +C co$plication " ,leeding. 3:c it is a di-erticulu$, it can ,e infla$ed, and leads to di-erticulitis. ;xa$ple: )ema!emisis@ pain in RLS area@ me%ana dxN +ec%el1s (in-ol-ed $elana A&? he$ate$isis definitely not <C or Crohn1s!. ;xa$ple: new,orn with a sinus and u$,ilicus was draining poop dxN *ersistent -itelline duct (sa$e as $ec%el1s so$eti$es it is open all the way through, therefore there is a co$$unication ,etween the s$all ,owel and u$,ilicus, so feces co$ing out of u$,ilicus, which is persistence of the -itelline duct. If you ha-e urine co$ing out of the -itelline duct, this is persistence of the uracus. 9o, 'e es,1i!e%%ine *& !@ &rine , &ra &s. C. <igmoi* Co%on +C location for cancer in the entire LI tract " sig$oid colon +C location for polyps in the entire LI tract " sig$oid colon +C location for di-erticula in the entire LI tract " sig$oid colon )he area of wea%ness is where the ,lood -essels penetrate the -al-e. )he $ucosa and su,$ucosa will herniate right next to the -essel. )his is -ery ,ad =next door neigh,orJ. Ghen feces are stuc% (fecalith!, can erode that -essel, and can see why *i1er!i &%osis is !)e +CC o' Hema!o )e>ia = massi1e %o3er :I -%ee* . )hese extend outside of the lu$en, which is di-erticulosis. If you see polyps in the lu$en, do not confuse with polyposis po%yps go INTO !)e %&men, not out. D. Di1er!i &%osis +C omp%i a!ion , *i1er!i &%i!is5 has +A&B co$plications.
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Di1er!i &%i!is " 8eft side appendicitis (appendicitis dx: 28P pain, +c3urney1s pt, re,ound tenderness, fe-er, and neutrophilic leu%ocytosis! this is the sa$e presentation in di-erticulitis!, ,ut di-erticulitis occurs in the 88P area, in an elderly person. +CC 'is!&%as omm&ni a!ions in !)e :I , *i1er!i &%osis. Gith a fistula, there is co$$unication ,etween ( hollow organs. )he +C 'is!&%as are o%o1esi %e 'is!&%a#s, which is a fistula ,etween the colon and the ,ladder, leading to ne&ma!&ria = air in !)e &rine. +CC o' o%o1esi %e 'is!&%a is *i1er!i &%ar *> . )hey can rupture, and the rupture can cause peritonitis. .III. In'%amma!ory (o3e% D>: Cro)n#s an* UC Crohn1s in-ol-ed the ter$inal ileu$ T67 of the ti$e. 9o$eti$es it just in-ol-es the ter$inal ileu$, so$eti$es it in-ol-es the ter$inal ileu$ A&? the colon, and so$eti$es it just in-ol-es the colon. Crohn1s li%es the A&<9, <C li%es the 2;C)<+ (they ha-e a preference for which part of the lower part they li%e!. Crohn1s li%es to produce fistulas and fissures of the anus5 <C li%es the rectu$, producing ,loody diarrhea. Crohn1s ju$ps around, trans$ural, noncaseating granulo$as. <C doesn1t ju$p5 it stays in continuity, and in-ol-es the $ucosa:su,$ucosa. Dx o' Cro)n#s is simp%e = ie i%eo e a% 1a%1e@ as en*ing o%on@ !ermina% i%e&m = !)ere is a !ransm&ra% in'%amma!ion 3i!) a 1ery narro3 %&men = !)ere'ore !)e presen!a!ion 3i%% -e o%i 6y@ RLS pain@ 3i!) *iarr)ea in yo&ng person. No!)ing ex ep! Cro)n#s pro*& es o%i 6y pain in !)e RLS in a yo&ng personJ If is a 0rd world county, what is itN )3 ($. ,o-is!. In this country, if we get intestinal )3 fro$ swallowing it and it will ,e + .),. In third world countries, it produces presentation sa$e as Crohn1s5 this occurs ,:c they do not ha-e pasteuriCation5 +. ,o-is is the +CC5 this is where payer1s patches are. <!ring sign on ,ariu$ study, loo%s li%e a string see that it is trans$ural and that it is seg$ental. )he proxi$al -al-e is dilated ha-e to push stool through that ,ut you can1t. 9ee co,,lestones and ulceration in Crohn1s dC. 8inear ulcers are apthus ulcers. Non asea!ing gran&%oma is )ara !eris!i o' UC. UC a%3ays -egins in !)e re !&m, can stay there, or can $o-e up in continuity and in-ol-ed the whole colon, ,ut it ne-er in-ol-es the ter$inal ileu$. It is in-ol-es the whole colon, it is called pancolitis, and this has the highest incidence of cancer. 9o, the $ore in-ol-e$ent and greater duration " greater chance of cancer related to <C. *seudopolyps see ulcerated $ucosa and su,$ucosa. *seudopolyps are residual polyps that are infla$ed, it is infla$ed ,loody $ucosa. ;-erything is ulcerated off, and you see the su,$ucosa of the colon. <C has the highest incidence with cancer, .8A 3(@ an%lyosis spondylitis, and is the +CC of sclerosing pericholangitis (sclerosis:fi,rosis around co$$on ,ile duct, producing o,structi-e jaundice and high incidence of cholangiocarcino$a!. Know the diff in <C -s. Crohn1s. IG. T&mors o' !)e Co%on Po%yps +C po%yp in en!ire :I , )yperp%as!i sig$oid colon. po%yp it is a little nu,,in a%a he$arto$as (therefore not neoplastic!, usually in
T&-&%ar a*enoma: loo%s li%e a straw,erry on stic%, therefore has a stal% with straw,erry, which is the precursor lesion for colon cancer. J&1eni%e Po%yp: 9lide: co$ing out of child1s ,utt %id with polyp in rectu$5 a%% Q&1eni%e po%yps %o a!e* in !)e re !&m an* are )amar!omas /no pre an ero&s0. 8ets say it is an adult and the polyp is stic%ing out (a reddish $ass! dxN In!erna% )emorr)oi*s. R&%e: in!erna% )emorr)oi*s -%ee*@ ex!erna% )emorr)oi*s !)rom-ose. )herefore, when you ha-e ,lood coating the stool, it is internal he$orrhoid. Internal he$orrhoids are &') painful, ,ut they do prolapse. Adult with so$ething reddish stic%ing out of their ,utt " prolapsed internal he$orrhoid. In!erna% )emorr)oi*s -%ee* an* pain%ess@ 3)i%e ex!erna% !)rom-ose an* are pain'&%. <essi%e Po%yp /1i%%o&s a*enoma0 loo%s li%e the -illous surface of the s$all intestine (hence na$e -illous adeno$a!5 these are lil fingerDli%e excrenses of the s$all intestine, hence the na$e -illous adeno$a. T)ese )a1e !)e grea!es! ma%ignan! po!en!ia%@ an* are &s&a%%y in !)e re !a% sigmoi*. 3:c they are -illous:finger li%e they ha-e a lot of $ucous coating the stool5 $ucous secreting -illous. )hey ha-e a E67 chance of ,eco$ing $alignant. 9o, tu,ular adeno$as are precursors for cancer (siCe deter$ines $alignant potential if they are a,o-e ( sono$eters, they are -ery dangerous! and -illous adeno$as lead to cancer, too. 9ami%ia% po%yposis need to ha-e o-er 166 polyps to ha-e fa$ilial polyposis. )his dC is autoso$al do$inant, uses A*C suppressor gene, ras, and pE05 A*C is the $ajor one. Gill always get cancer in the$, usually ,etween 0ED>6. )herefore, will need to prophylactically re$o-e the ,owel. )he autoso$al do$inant dC is fa$ous for late $anifestations, penetrance, and -aria,le expressi-ity (as are all other A? dC1s!. )his $eans that they will not ,e ,orn with polyps at ,irth (they start de-eloping ,twn the ages of 16D(65 in A?*K?, they do not ha-e cysts are ,irth, they start de-eloping ,twn 16D(65 in .untington1s chorea, do not ha-e chorea at ,irth, ,ut around 0ED>6 years, and they ha-e late $anifestations. A''e !e* o%on )as po%yps an* -rain !&mors , T&r o! syn*rome (li%e tur,an! therefore, you ha-e a polyposis syndro$e with ,rain tu$or5 this dC is auto rec (not do$inant!. :ar*ner#s syn*rome: .a-e $ultiple polyps in there, plus ,R salt tissue tu$ors: des$oids and osteo$as in the jaw. G. Car inoi* T&mors Along with auput tu$ors. All carcinoid tu$ors are $alignant, ,ut ha-e low grade potential. A lot of it depends on their siCe and if they are going to $ets. ?epends on their siCe in sono$eters if they are greater than ( sono$eters they ha-e the a,ility to $ets. +C %o a!ion 'or ar inoi* !&mor , !ip o' !)e appen*ix ha-e a ,right yellow color, ,ut they are NE.ER !)e a&se o' ar inoi* syn*rome whyN 3:c the tip of the appendix will ne-er ,e greater than ( sono$eters. 9o, where is the +C %o a!ion o' ar inoi* !&mor !)a! CAN -e asso ia!e* 3i!) ar inoi* syn*romeE Termina% I%e&m = !)ey are a%3ays grea!er !)an " sonome!ers. Ghat do all carcinoid tu$ors $a%eN <ero!onin. 3:c the appendix and ter$inal ileu$ are drained ,y the portal -ein, the serotonin $ade goes to the portal -ein, goes to the hepatocyte, is $eta,oliCed into E
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hydroxyactoactitic (N! acid and is pee1d out5 therefore it is not in the ,loodstrea$. )herefore, there are no signs of flushing and diarrhea ,:c there is no contact with the syste$ic circulations. .owe-er, if you $ets to the li-er, then those $etastatic nodules that are $a%ing serotonin can du$p so$e of it into the hepatic -ein tri,utaries. )his does ha-e access to the syste$ic circulation ,:c goes to IKC to 2ight side heart, and this is why you get right sided lesions I TIP<D , !ri &spi* ins&'' an* p&%moni s!enosis. <ero!onin is a -asodilator in so$e cases, ,ut a -asoconstrictor in other cases. .owe-er, in ter$s of serotonin syndro$e, it1s a -asodilator !)a! a&ses '%&s)ing /3)i ) is !)e +C symp!om o' ar inoi*0@ 'o%%o3e* -y *iarr)ea /"n* +C0. If it has access to syste$ic circulation, it has high le-els of E hydroxyacetoacitic (N! acid, which is the screening test of choice ,:c it is the $eta,olite of serotonin. 9o, -7 ma6ing an* LO<IN: a %o! o' sero!onin@ 3)a! aa an -e *e'i ien!E Tryp!op)an is *e'@ !)ere'ore !)e 1i!amin Nia in is *e'@ !)ere'ore an )a1e pe%%agra. Yo& &sing &p a%% !)e Tryp!op)an an* ma6ing sero!onin ins!ea* o' nia in. GI. Co%on an er &eurosecretory granules on ;+ colon cancer5 %e'! si*e o-s!r& !s@ rig)! si*e -%ee*s. )his is easy to understand ,:c the left colon has a s$aller dia$eter than the right. 9o, when the cancer de-elops in !)e %e'! o%on and wants to for$ a polyp, it goes around ann&%ar /nap6in ring0, and produces constriction. 'pen ,owel in left colon, see one edge of the cancer on each side of the ,owel and ,owel is constricted ha-e signs of o,struction (left side o,structs, right side ,leeds!. In the rig)! o%on, ,:c of there is a ,igger dia$eter5 it has a ,igger chance of going out and for$ing a polyp. )herefore, it is sitting in the stool, leading to a ,leed (therefore left side o,structs, right side ,leeds!. 9o, which is side is $ore li%ely to ha-e 4e defN 2ight sided lesion. Ghich is $ore li%ely to ha-e alteration in ,owel ha,its (constipation:diarrhea!N 8eft sided. T&mor mar6er 'or o%on an er , CEA / ar inoem-ryoni Ag !. &ot used to dx colon cancer, ,ut used to follow it for 2;'CC<22;&C;. +CC relates to diet (lac% of fi,er in stool therefore, $ore fi,er you ha-e, the less chance of colon cancer ,:c you are getting rid of lipocolic acid!. Age is also a ris% factor (pts o-er E6!5 s$o%ing is a ris% factor that is assoc with colon cancer. *olyposis coli syndro$es also ha-e an association (fa$ilial polyposis, Lardner1s syndro$e, turcot1s syndro$e! &') *eutC Feghers, hyperplastic polyps, or ju-enile polyps!. GII. Diseases o' !)e Appen*ix: Appen*i i!is Co-ered with pus5 +CC appendicitis in adults " fecalith " i$pacted stool. 9o when you i$pact stool it presses on the sides of the appendix, and leads to ische$ia, then get a ,rea%down of the $ucosa, ;. coli gets in there and acute appendicitis occurs. T)is is !)e <A+E me ) 'or *i1er!i &%i!is (the di-erticular sacs also get fecaliths in the$ and the sa$e exact thing happens the pathogenesis of acute di-erticulitis and acute appendicitis is exactly the sa$e!. 9o, fecalith, ische$ia along the wall, infla$$ation, ; coli. Another analogy: acute cholecystitis except it is not a fecalith, ,ut is a stone in the cystic duct pushes on the side, leads to ische$ia, acute cholecystitis, ; coli. 9o, there is a concept there 3e )a1e a &!e )o%e ys!i!is@ *i1er!i &%i!is@ an* appen*i i!is a%% re%a!e* !o some!)ing o-s!r& !ing !)e %&men@ a&sing m& osa% *amage@ an* E o%i in'%amma!ion . In acute cholecystitis it1s a stone, while acute appendicitis and di-erticulitis is due to a fecalith. Ghat the +CC o' appen*i i!is in )i%*renE +eas%es an*7or a*eno1ir&s in'e !ion. )hen, acute appendicitis occurs ,:c there is ly$phoid tissue in the appendix. Gith $easles or adeno-irus infection, get )yperp%asia o' %ymp)oi* !iss&e in !)e appen*ix@ an* an o-s!r& ! !)e %&men an* se! &p in'%amma!ion 'or m& osa% inQ&ry an* %ea*s !o a &!e appen*i i!is. 9o@ in )i%*ren@ i! &s&a%%y 'o%%o3s a 1ira% in'e !ion. As opposed to adults, where it is due to fecalith. CHAPTER 1F. LI.ER I. (i%ir&-in me!a-o%ism: +ost of the ,iliru,in in our ,lood is unconjugated and deri-ed fro$ the 23C1s when they are old, phagocytosed and destroyed. <nconj ,iliru,in is the end product, goes to the ,loodstrea$ and ,inds with al,u$in, goes to the li-er and is ta%en up. +ajority of ,iliru,in is fro$ ,rea%down of 23C1s (RR7!, which is all unconj. &one of this is in the urine ,:c it is lipid solu,le. 9o, it gets ta%en up ,y the li-er and is conjugated. Any ti$e the cytochro$e p>E6 conjugates ,iliru,in, or $eta,oliCes any drug, it renders it water solu,le. 9o, we ha-e a lipid solu,le unconjugated ,iliru,in is con-erted to conjugated ,iliru,in (direct ,iliru,in!, which is water solu,le. 'ne of the purposes of the li-er is to render lipid solu,le drugs water solu,le, so you can pee the$ out. 9o, we conjugate it and ha-e water solu,le ,iliru,in. 'nce ,iliru,in is ta%en up ,y the li-er, it is ne-er close to a -essel. 9o, there is no way it can get into a -ascular channel (once it is ta%en up ,y the li-er!. 9o, if direct conjugated ,iliru,in is in our urine, this is ,:c so$ething happened (either in the li-er or ,ile duct! to ha-e caused it to get there ,:c it shouldn1t ha-e access to our ,lood strea$. 9o, it is ta%en up in the li-er, conjugated, and pu$ped into the ,ile ductules5 which go into the triad, goes up the co$$on ,ile duct, so$e is stored in the L3 and goes into the s$all intestine through the co$$on ,ile duct. )herefore, ,ile contains conjugated ,iliru,in. Its also contains ,ile salts, cholesterol and estrogen, ,ut has conjugated ,iliru,in that we will get rid of. 9o, this conjugated ,iliru,in ta%es a long trip down to the colon and the ,acterial ha-e ,een waiting for the conjugated ,iliru,in and will ,rea% it down ,ac% into unconjugated ,iliru,in. )hen, it continues to ,rea% it down. )he ,acteria ,rea%s it down to sterco,ilinogen (what it used to ,e called!. 9terco,ilinogen oxidiCes to sterco,ilin produces the color of stool. )his ter$ is no longer used. &ow, it is called uro,ilinogen (which $a%es the color of the pig$ent!. It is easier to understand the concept. 9o, !)e &n onQ&ga!e* -i%inogen is -ro6en *o3n !o &ro-i%inogen . All porphyrins are colorless when they are in an =Dogen1 co$pound5 howe-er, when you oxidiCe the$, they ha-e color. 9o, &ro-i%inogen@ 3)en i! -e omes oxi*i>e* in !)e s!oo%
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-e omes &ro-i%in@ 3)i ) is !)e o%or o' s!oo%. A s$all portion of uro,ilinogen is rea,sor,ed out of the colon. +ost of it goes ,ac% to the li-er. A little of it goes to the %idney and ends up in the urine, where it get oxidiCed into uro,ilin. )his is the cause of the color of urine. 9o @ !)e same pigmen! !)a! o%ors s!oo% is responsi-%e 'or o%oring &rine . Ge were taught that sterco,ilinogen is in the stool and uro,ilinogen is in the urine5 howe-er, sterco " uro, so the sa$e co$pound is responsi,le for color change in feces and urine. )hey are not diff pig$ents, they are the sa$e. 9o, if you ha-e o,structed ,ile flow (in the li-er or C3?!, what should the color of the stool ,eN 8ight colored ,:c the uro,ilinogen would not ha-e access to the stool to color it. Also, would not ha-e uro,ilinogen in the urine. )his leads to jaundice. II. Ja&n*i e )o calculate jaundice, they ta%e the total ,iliru,in and find out the percentage of ,iliru,in that is conjugated (direct ,iliru,in!. ;xa$ple: total is 16, conj " E, therefore conj ,iliru,in " E67. 9o, they su,di-ide jaundice into 0 types conjugated ,iliru,in less than (67 (therefore $ost of it is unconjugated!, ,twn (6DE67 (therefore so$e is conj and unconj!, and greater than E67 ($ost of it is conjugated ,iliru,in!. Its also $eans that you ha-e o,struction. If it is &n*er "FP, this primary &n onQ&ga!e* )yper-i%ir&-inemia. 9o what can increase unconj ,iliru,inN Hemo%y!i anemias@ sp)ero y!osis@ <CD>@ A(O )emo%y!i *> o' !)e ne3-orn@ R) )emo%y!i *> o' !)e ne3-orn@ p)ysio%ogi Qa&n*i e o' !)e ne3-orn (,:c they cannot conjugate it!. 9o, there is increased unconjugated ,iliru,in ,:c ,rea%ing down $ore 23C1s, ha-e pro,le$s with conjugating enCy$es either too i$$ature or they are $issing enCy$es (Craig%er NaQQar syn*rome!. 9o, we are either $a%ing too $uch ,:c we are ,rea%ing down too $any 23C1s or we ha-e a pro,le$ with conjugating enCy$es which is little ,a,ies with physiologic jaundice dC of the new,orn, or rare dC1s where we are deficient in the enCy$e (Craigler &ajjar!. )he dC1s -!3n "F? 4FP are hepatitis. Hepa!i!is " infla$$ation of the li-er (not just so$e of it, all of it!. 9o, ,:c it1s a sic% li-er, it doesn1t want to ta%e up the unconjugated ,iliru,in. <nconj li-er ,uilds up ,ehind the li-er. Infla$$ation in the li-er will $ay,e destroy the architecture in the li-er and ,rea% open ,ile ducts that ha-e conj ,iliru,in in the$. &ow, ,:c you ha-e disrupted the architecture, there is a possi,ility of water solu,le ,iliru,in to get into the ,lood strea$ (,:c there is necrosis of li-er cells and ,ile ducts so you will get conjugated ,iliru,in in there, too! D leading to (6DE67. )his in %&*es a%% !)e )epa!i!is /in %&*ing a% o)o%i !. If it is grea!er !)an 4FP, this is a &' 32AI&;2 it is clearly an o-s!r& !ion o' -i%e. Ge ha-e intrahepatic o,struction (in!ra)epa!i )o%es!asis!, $eaning that you are ,loc%ing ,ile flow in the li-er (triad is ,loc%ed!. Also ha-e ex!ra)epa!i )o%es!asis (outside of the li-er!. )here is only one thing outside the li-er that can lead to this C(D / ommon -i%e *& !0. )herefore, so$ething is o,structing that a stone in the co$$on ,ile duct that ca$e fro$ the L3 (play odds!. Can also ha-e carcino$a of the head of the pancreas ,:c ducts go through the head of the pancreas. As a result, you ha-e co$plete ,ile duct o,struction. 9o, there is intrahepatic cholestasis and extrahepatic cholestasis. 9o, what will happen is li%e water ,ehind a da$. If you ,loc% ,ile flow, it will ,ac% up where does it ,ac% upN 3ac%s up to where it was $ade (the li-er cells re$e$,er this is an excess of conjugated, direct ,iliru,in!. In the li-er cells, it ,u,,les outside, and has access to the sinusoids and now is in the ,lood strea$. 9o, the predo$inant factor in the ,lood strea$ is CONJU:ATED -i%ir&-in, which is water solu,le. 9o, will )a1e 1ery *ar6 ye%%o3 &rine an* !)e s!oo% 3i%% -e LI:HT o%ore*. )his co$,o )ig) onQ -i%ir&-in@ -i%ir&-in in !)e &rine (.A9 to ,e conjugated ,:c it1s in the urine and therefore water solu,le!, an* %ig)! o%ore* s!oo%s , O(<TRUCTION (nothing else can do this, and it is either intrahepatic or extrahepatic!. A. Congeni!a% Un onQ&ga!e* )yper-i%ir&-inemias 1. :i%-er!#s syn*rome 9een if you fast for o-er (> hrs and get jaundice, A?, ,R (therefore do not need a ,x!. +e ): pro- in !a6ing &p -i%ir&-in an* pro- in onQ&ga!ing -i%ir&-in, therefore it is pre*ominan!%y an &n onQ&ga!e* )yper-i%ir&-inemia. 9o, if you want to see if pt has it, do (> hr fasting test. 9o, get ,aseline ,iliru,in when they are not jaundiced and don1t eat for (> hrs and co$e ,ac%. Ghen they co$e ,ac% they are jaundiced. 8et1s say the ,aseline is 1, and you dou,le the ,aseline after (> hrs, pt has Lil,ert1s syndro$e. ;x. pt co$es ,ac% after fasting test and is (.E. "n* +CC Qa&n*i e , :i%-er!s syn*rome /+C , )ep A0. ;x. resident that gets jaundice, ,ut didn1t ha-e needle stic% " he has Lil,ert1s dC ,:c was fasting (enCy$e le-els are nor$al, high unconj ,iliru,in le-els!. 2xN &othing ". Craig%er NaQQar (. Congeni!a% ConQ&ga!e* )yper-i%ir&-inemias D&-in Jo)nsonI Ro!or syn*romes: Lenetic dC1s in-ol-ing pro, getting rid of C'&F ,iliru,in in the ,ile ducts. 9o, this is pre*ominan!%y a onQ )yper-i%ir&-inemia. In ?u,lin Fohnson, ha-e a ,lac% colored pig$ent that ,uilds in the li-er and get ,lac% li-er. III. Li1er 9&n !ion Tes! /L9Ts0 Ghat are !ransaminases used forN )hey are in*i es o' %i1er e%% ne rosis (hepatitis!. A9) (9L')! and A8) (9L*)!5 ALT is $ore specific ,:c it is only found in the li-er5 A<T is in $uscle, 23C1s and li-er. )herefore, if you ha-e a 1ira% )epa!i!is, with $assi-e li-er cell necrosis, which would ,e the predo$inant transa$inases ele-atedN ALT. ;x: (E66 A8) and ((66 A9). 9o A8) will ,e the $ain li-er cell enCy$e e%e1a!e* in *i''&se %i1er e%% ne rosis.
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In a% o)o%i )epa!i!is, this is not what happens. )here is a reason: A<T is present in the $ito of hepatocytes. A8) is not it1s in the cytosol. Alcohol is a $ito poison (re$e$,er that it uncouples!. A9) is predo$inantly in $ito, and when pt has alcoholic hep, A<T is )ig)er !)an ALT (forget the (:1 relationship!. )herefore, if you see A9) higher than A8), this is due to alcoholic li-er dC. Could ,e fatty change, alcoholic cirrhosis, and alcoholic hepatitis. If it1s KI2A8 hepatitis, A8) is ,igger than A9). 9o, what are the enCy$es of '39)2<C)I'& (o-s!r& !ion o' -i%e *& !s!N A%6a%ine p)osp)a!ase an* :amma g%&!amy% !rans'erase. )ransa$inases will also ,e up, ,ut not to the sa$e degree. La$$a gluta$yl transferase is located in the 9;2. Ghen the 9;2 is re-1d up, it undergoes hyperplasia (ie due to drugs: alcohol, ,ar,s, rifa$pin, and phenytoin!5 you not only increase the $eta,olis$ of the drug, ,ut also increase the synthesis of ga$$a gluta$yl transferase. 9o, what would the classic thing you would see in any a% o)o%i %i1er *>E A<TMALT@ a%ong 3i!) INCREA<ED gamma g%&!amy% !rans'erase . )here is a pro,le$: al% phos is in other things other than the li-er in ,one (osteoplastic acti-ity!, placenta. 9o, how will you %now where the al% phos co$es fro$ (ie if it1s fro$ ,ile duct o,struction -s. other things!N 8oo% at gamma g%&!amy% !rans'erase -7 i!s spe i'i 'or !)e %i1er (so, if al% phos up, loo% at ga$$a gluta$yl transferaseM!. I' !)e gamma g%&!amy% !rans'erase I< e%e1a!e* a%ong 3i!) a%6 p)os@ !)is is (ILE DUCT O(<TRUCTION. A%-&min pro!ime , mar6er o' se1eri!y o' %i1er *amage. It is $ade in the li-er, therefore if you ha-e se-ere li-er dC (ie cirrhosis!, it will ,e decreased. ;-en ,etter than that is prothro$,in ti$e ,:c coagulation factors are $ade there ($ost are $ade there -G4 is not, howe-er!. 9o, if you ha-e li-er da$age, the production of coagulation factors will ,e decreased, and *) will ,e prolonged (increased!. 9o, a%-&min %e1e%s an* PT are !)e " -es! !es!s 'or %i1er se1eri!y /PT is a %i!!%e -e!!er !)an a%-&min!. )here is only one autoA, that is i$portant: an!i =mi!o A-s in primary -i%iary irr)osis. T&mor mar6ers: a%p)a 'e!o pro!ein is a mar6er 'or )epa!o e%%&%ar ar inoma. Can also use a%p)a?1 an!i!rypsin ,:c it is $ade in the li-er (it is in rease* in hepatocellular carcino$a!. If you ha-e fractionation of ,iliru,in (less than (67, (6DE67, and E6/ 7!, can start d:d5 then gi-e transa$inase le-els see how it correlates with li-er dC: transa$inases correlate with -iral hep and conj ,iliru,in of (6DE6, or o,structi-e li-er dC (al% phos, ga$$a glut! and conj ,iliru,in o-er E67. I.. .ira% Hepa!i!is A. +C on )epa!i!is: +C hep " A (followed ,y 3, C, ?, ; in that order! A and ; " fecal oral5 all the others are trans$itted parentally .ep A " &o chronic carrier state .ep ; " produces a chronic carrier state only if you are pregnant, leading to chronic li-er dC .ep ? " 2e#uires .ep 3 to infection .ep A " ?aycare centers (therefore should get -accine to pre-ent5 out,rea%s can occur in daycare centers! .ep A " Fail .ep 3 " IK?A .ep C " *ost transfusion .epatitis .ep 3 " +C infection ,y accidental needle stic% (. <ero%ogy: HA.: anti A Ig+" ha-e hep A5 anti A IgL " had it and won1t get it again HC.: anti C IgL A,1s are &') protecti-e and $ean that you ha-e the dC5 there are no %nown protecti-e A,1s HD.: (sa$e as .CK! anti ? IgL " ha-e the dC, and no %nown A,1s will help cure5 if you are antiD? IgL positi-e it $eans you ha-e the acti-e dC now 9o, only protecti-e A,1s are .AK, .3K (surface A,!, and .;K. Hep ( /H(.0 9irs! mar6er !)a! omes &p is s&r'a e Ag /H(sAg0. It co$es up a,out 1 $onth after you ha-e the infection. Bou don1t %now you ha-e it and are asy$pto$atic. )he enCy$e studies are nor$al. )he next thing that co$es up is the ,ad guys: E Ag /H(eAg0 an* H(. DNA, -7 !)ese are on%y ones !)a! are in'e !i1e. )hen the first A, co$es up a lil after the ?&A and ; Ag, which is ore A- Ig+ /An!i?H( 0 (this is expected ,:c the first A, against acute infla$$ation is Ig+!. )he $ajority of people with .ep 3 reco-er (a,out R67!5 those with .IK/ ne-er reco-er and will ha-e chronic cases ,:c they ha-e no i$$une response to %noc% it off. If you do reco-er the 'irs! !)ings !o go a3ay are E Ag /H(eAg0 an* H(. DNA. )he %as! o' !)e Ag#s !)a! goes a3ay is s&r'a e Ag /H(sAg0. 9o, surface Ag is the first to co$e and the last to lea-e (li%e a Ihouse within a houseJ loo% at the chart and will see that 9 Ag is the ,ig house and ; Ag and .3K ?&A are the lil houses under ,ig house!. In other words, it is I+*'99I38; to ,e ; Ag positi-e and 9 Ag negati-e (E Ag an* DNA ome &p a'!er < Ag an* %ea1e -e'ore!. <&r'a e A- doesn1t co$e up until a,out 1 $onth after < Ag is gone, so there is this gap, which is a = 3in*o3# with nothing ele-ated (only has one A, there5 9 Ag, ; Ag, .3K ?&A are all gone, and 9 A, not there yet!. 9o, how do you %now the pt .A? .ep 3N Core Ig+ doesn1t lea-e it stays there and ,eco$es IgL o-er ti$e. 9o, the $ar%er for that 3in*o3 perio* when all the ,ad guys are gone and surface A, hasn1t arri-ed yet, is ore A- Ig+ (which tells you that you .A? .ep 3 and are in the process of reco-ery!. )here is no way you are infected during this period whyN 3:c ; Ag and .3K ?&A are not there. )herefore, you are not infecti-e it just $eans that you .A? .ep 3 and are in the process of reco-ering. YOU ARE NOT IN9ECTI.E this is ,etween the Eth and Ath $onth.
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9o, if you had .ep 3, there should ,e ( A,1s that you ha-e: ore A- Ig: an* s&r'a e A- Ig:.
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If you ha-e ,een 1a ina!e*, cannot ha-e anything ,:c you had yeast $a%e surface Ag, which is what the -accine consists of. )he only ,ad A, you can get fro$ injecting surface Ag is A,1s against it. 9o, only A, you will ha-e if you were -accinated is <&r'a e A-. &') core A, IgL ,:c were not injected with that. Core A, is not a protecti-e A,. C. C)roni )epa!i!is is a definition: IHo3 %ong )a1e yo& )a* s&r'a e AgED I' i!#s more !)an A mon!)s , you ha-e chronic .ep 3. 9o, are you infecti-e or notN are you an infecti-e carrier or healthy carrierN Bou auto$atically %now if you are an in'e !i1e )roni arrier i' yo& )a1e H(. DNA. )his $eans that you are a patient with chronic .ep 3 that is infecti-e. 9o, you1re a wal%ing haCard, and your inti$ate contacts need to ,e i$$uniCed ,:c the dC can ,e trans$itted sexually to those people, or ,y IK (IK?A1s!. I' yo& are nega!i1e 'or E Ag an* H(. DNA -&! are s&r'a e Ag posi!i1e@ !)en i! ma6es yo& a C)ea%!)yD arrier (this does not $ean you are healthy you are still a chronic carrier of .ep 3!. If you are a healthy carrier, howe-er, the chances of reco-ery are excellent ,:c in a,out one year, 9 Ag will disappear and 9 A, will co$e up. Gill also ha-e core A, IgL at this ti$e this $eans that you ha-e a good chance of total reco-ery. Also ha-e a goo* )an e o' re o1ery 3i!) E Ag -7 p! is a an*i*a!e 'or A%p)a I9N !)erapy /DOC0. Ne1er gi1e or!i os!eroi*s !o any )roni 1ira% in'e !ions. D. Re1ie3: Ghat we expect in acute hepatitis 3 (what would the $ar%ers ,e!N 9 Ag, ; Ag, .3K ?&A, and core Ig+ Ghat if the pt is in the window periodN Core Ig+ Ghat if had .ep 3, ,ut ha-e reco-ered fro$ itN Core A, IgL and surface A, IgL Ghat if pt was -accinated (what is the '&8B thing you should ha-e!N 9urface A, IgL Ghat if you ha-e at the end of A $onths 9 Ag, core Ig+, with e-erything else negN .ealthy carrier Ghat if you ha-e after A $onths surface Ag, ; Ag, .3K ?&A and core A, Ig+N Infecti-e carrier. .. In'%amma!ory Li1er Disor*ers A. Ame-iasis: En!amoe-a )is!o%y!i a = 'rganis$ is resistant to acid swallow it and will not die in presence of acid. It exDcysts in the cecu$, within an al%aline en-iron$ent. .as a che$ical that can drill a hole through the $ucosa, leading to flas% shaped ulcers, and leads to -%oo*y *iarr)ea. <nfortunately, ,:c the cecu$ is drained ,y the portal -ein, and is for$ing an ulcer, there is a chance that it can drill and hole, get into the portal -ein tri,utary and get to the right lo,e of the li-er, where it will produce an a,scess. It will start dissol-ing the li-er hence ter$ ancho-y paste a,scess ,:c it loo%s li%e ancho-y paste (a ,rownish li#uid!. If it wants to, it can drill a hole through the right diaphrag$, go to the lungs, and produce an effusion, and go anywhere it wants in the syste$ic circulation ,rain. 2x $etronidaCole. Trop)o>oi!es (slide! with red particles in the$, which are 23C1s. )he only protoCoa that can phagocytose is En!amoe-a )is!o%y!i a /no o!)er amoe-a an p)ago y!ose R(C#s! this is a -ery characteristic finding. +etronidaCole is used in the treat$ent of giardiasis, ;nta$oe,a histolytica, -aginosis, c diff, and trichinosis. (. Hy*a!i* *> 1. ?efiniti-e -s. inter$ediate host De'ini!i1e )os! " sexually acti-e wor$s that ha-e the a,ility to $ate and lay eggs. In!erme*ia!e )os! " only ha-e the lar-al for$5 do not ha-e sexually acti-e adults. )hese are the stages: Adult, egg, lar-a. Adult lays eggs, and the eggs de-elop into lar-a. If you ha-e the lar-a for$ in you, it will stay there ,:c that it1s the end stage for$. If you ha-e the egg for$, it will de-elop into a lar-a, ,ut the lar-a can1t go anywhere else. If you ha-e the adult for$ in you, it will gi-e an egg, which changes to lar-a. 8ar-a for$ cannot go anywhere it is the end stage for$. <)eep )er*er#s *> /gono o &s 1ermi &%aris or &ni%i &%aris /E00 )he sheep dog eats so$e sheep $eat (there are lar-al for$s in the sheep5 therefore, the sheep is the inter$ediate host!. ?og eats sheep, and has lar-a in the dog. )he lar-a for$ de-elops into an adult within the dog, and the dog ,eco$es the definiti-e host. )he dog has sexually acti-e wor$s inside it and the wor$s lay eggs within the dog. ?og is petted, gets eggs on their hand and into pts food, which is eaten. 9o, now, the pt has the egg, which de-elops in the lar-a (cannot go any farther ,:c lar-al for$ is end stage!, and the pt (hu$an! ,eco$es the inter$ediate host. 9o, the sheep is an inter$ediate host, the dog is the definiti-e host and the sheep herder is an inter$ediate host. ?o not want to rupture these cysts, ,:c if the fluid gets into the a,do$inal ca-ity, leads to anaphylactic shoc%. C. T. so%i&m /pig !ape3orm0 Bou go to a ,ar,ecue and eat undercoo%ed por% (lar-a in the pig $eat, which is eaten!. )he lar-a de-elop into the adult for$ within the pt (so, there is a sexually acti-e wor$ inside!. 9o, pt ,eco$es definiti-e host, while the pig was the inter$ediate host. &ow you ha-e a fa$ily $e$,er that is a definiti-e host (has sexually acti-e wor$s inside the$! lets say this fa$ily $e$,er is $a%ing salad that night, and didn1t wash their hands, so so$e of the eggs got into the salad. )he pt eats the salad with the eggs in it. Ghat is the egg going to for$ inside $eN 8ar-a. Ghat is this called cystocerci. ?o they for$ adultsN &o, stops there. )herefore, pt has cystocercosis. Ghat are the %ar1ae going !o *oE T)ey %i6e !)e eye an* !)e -rain /3)ere !)ey 'orm a ys! in !)e -rain@ a% i'y an* %ea* !o sei>&re a !i1i!y 'or !)e res! o' !)e p!#s %i'e0. 9o, in this dC, the pt can ha-e two for$s of it. If pt ate the infected pig, they can ,e the definiti-e host. If you get the egg in your $outh, you ,eco$e an inter$ediate host, and the egg can ,eco$e lar-a, which will go on to cystocercosis. 9o the lar-ae for$ is the dangerous for$ in ). soliu$. (+C 9:; of cataracts " glucocorticoids!
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+CC " 2.4 )hro$,us in portal -ein will &') lead to nut$eg li-er ,ecause portal -ein is ,efore e$ptying into the li-er. Gould you ha-e ascitesN Bes. *ortal .)&N Bes. KaricesN Bes. 3ut is li-er ,ig and congestedN &o. )hro$,us in hepatic -ein: is called 3udd Chiari syndro$e (+CC polycythe$ia 2u,i-era, (nd +CC " ,irth control pills!. Gould you ha-e a nut$eg li-erN Bes hepatic -ein e$pties the li-er. Bou get a huge li-er, and is a surgical e$ergency and die 1667 of the ti$e if you don1t ha-e surgery. 9o, these are pre:post hepatic thro$,oses /Pre)epa!i , por!a% 1ein@ pos!)epa!i , )epa!i 1ein0. .II. A% o)o%i %i1er *> +C mani'es!a!ion is 'a!!y )ange /s!ea!osis0. 3:c alcohol $eta,olis$, ha-e &A?.1s, acetate, and acetyl CoA. &A?.1s $ess with pyru-ate and con-ert it into lactate leading to fasting hypoglyce$ia, and $eta,olic acidosis. Acetyl CoA can $a%e 4A1s and glycerol 0 phosphate and )L and fatty change, or can ,e con-erted into %etone ,odies, which causes an increased anion gap: $eta,olic acidosis. 4atty change is re-ersi,le if the alcoholic stops drin%ing. A% o)o%i )epa!i!is is -ery ,ad5 can ha-e hepatic encephalopathy, ascites, etc. Alcoholic hep is diff fro$ fatty change ,:c there is fe-er, neutrophilic leu%ocytosis, -ery high A9)UA8), and ga$$a gluta$yl transferase is up. Bou1re ,ig ti$e sic% and if you do not stop drin%ing you will die. It is -ery serious syste$ic dC. If pt hospitaliCed for alcoholic hep, is released and ta%es alcohol, they will die. 9ee +a%%ory -o*ies (u,i#uinated %eratin $icrofila$ents!. )oxic co$pound that causes cirrhosis is acetaldehyde ,ound to a protein, not acetaldehyde ,y itself. Ito cell nor$ally is the cell that stores Kit A. In an alcoholic the acetaldehyde protein co$plex sti$ulates the Ito cell to $a%e fi,rous tissue and collagen. )he Ito cell, which is responsi,le for storing -it A, is now putting down collagen tissue and is responsi,le for causing fi,rosis. 4i,rous tissue is a ,ig part of alcoholic tissue dC. .III. C)o%es!asis C)o%es!asis " o,struction to ,ile flow, due to a stone in the C3?. ;x: ha-e a cholesterol stone with a deep green colored li-er. 3ile is ,loc%ed, which has conj ,iliru,in in it and is ,ac%ed up into the li-er. )he conj ,iliru,in will e-entually reflux into the sinusoids, and leads to ,iliru,in in the urine and light color stools, with &' uro,ilinogen in the urine. )he yellow urine is due to water solu,le conj ,iliru,in in the urine. Ghat enCy$es are ele-atedN Al% phos and ga$$a gluta$yl transferase. Ghat is the $ech for getting rid of cholesterolN 3ile. 9o, you reflux cholesterol, ,iliru,in and ,ile salts (they are all recycled!. Gould it surprise you that they ha-e hypercholesterole$ia, tooN &o ,:c it is recycled. )he ,ile salts deposit in the s%in, leading to itching. " o!)er a&ses o' )o%es!asis: 3ile duct radical, surrounded ,y fi,rous tissue, ,loody diarrhea with 88P cra$py pain, jaundice what is the I3?CN UC Co$$on ,ile duct surrounded ,y fi,rous tissue dxN Primary s %erosing )o%angi!is. +CC pri$ary sclerosing cholangitis " UC Ghat cancer can de-elop ,:c it in-ol-es the ,ile ductN C)o%angio ar inoma (+CC in this country, in 0rd world countries, it is due to Clonorchis sinensis Chinese li-er flu%e!. IG. Primary (i%iary irr)osis E6 y:o wo$an with generaliCed itching, find enlarged li-er on *;, nor$al ,iliru,in (no jaundice!, al% phos and ga$$a gluta$yl transferase are huge (o,structi-e type of enCy$es!, transa$inases are ele-ated dxN *ri$ary ,iliary cirrhosis, which is an a&!oimm&ne *> !)a! %ea*s !o gran&%oma!o&s *es!r& !ion o' !)e -i%e *& !s in !)e por!a% !ria* why doesn1t she ha-e jaundiceN 8et1s say you ha-e 1 $illion triads, ha-e the dC and %noc% off (E6,666 of the$. 9till ha-e @E7 that can handle the ,iliru,in load. 0 years later, only ha-e E67 (E66,666 destroyed!. 9till no jaundice, e-entually, $ore %noc%ed off and get jaundice way down the line. 9o, the reason why pt won1t get jaundice is ,:c pt has a reser-e that can handle the ,iliru,in. )herefore, there is no reason to ha-e jaundice early and it co$es late. Ghat is the A, to order in this ptN An!i?mi!o )on*ria% an!i-o*ies (anti$icroso$al " hashi$oto1s!. G. Dr&g e''e !s 3irth control ('C*! and ana,olic steroid ha-e the sa$e effect on the li-er. T)e OCP an* ana-o%i s!eroi*s -o!) pro*& e in!ra)epa!i )o%es!asis. ;x. wt lifter (assu$e he1on steroids! de-elops jaundice, and -iral serology is negati-e, high al% phos and ga$$a gluta$yl " due to steroids (not hepatitis!. 'ne of the +CC1s jaundice in pregnancy is ,R intrahepatic cholestasis. )his is ,:c of the estrogen during pregnancy, which produces intrahepatic cholestasis. 2xN ?eli-er ,a,y (goes away after deli-ering ,a,y!. 8ets say wo$an ta%es 'C* and gets jaundice5 when she ,eco$e pregnant, she will de-elop jaundice, too ,:c of the estrogen effect. 9o, intrahepatic cholestasis is a nor$al co$plication of 'C*1s and ana,olic steroids. (o!) o' !)ese *r&gs a%so pre*ispose !o a -B %i1er !&mor@ a%%e* %i1er e%% a*enoma a6a )epa!i a*enoma. It has a nasty ha,it i! %i6es !o r&p!&re@ %ea*ing !o in!raperi!onea% )emorr)age /3)i ) an 6i%% yo&0. ;xa$ple: wt lifter (assu$e he1s on ana,olic steroids! who is lifting and suddenly ,eco$es hypotensi-e and collapses. 4ind a,nor$al li-er:ca-ity what is $ost li%ely causeN 2uptured li-er cell adeno$a ,:c pt is on ana,olic steroids. <o@ OCP#s an* ana-o%i s!eroi*s )a1e " simi%ar e''e !s: -o!) an pro*& e -B in!ra)epa!i )o%es!asis /3)i ) goes a3ay i' yo& s!op !)e *r&g0 an* %i1er e%% a*enoma 3)i ) is s&s ep!i-%e !o r&p!&re. 4or wo$en, if they are on ,irth control, then get off it to get pregnant let1s say they ha-e a li-er cell adeno$a they did not %now a,out (that de-eloped with 'C* use!, then get pregnant, then get an intraperitoneal he$orrhage, and then what is d:dN 2uptured ectopic pregnancy or rupture intraperitoneal he$orrhage. 9tep (: pregnant wo$en ha-e the tendency to ha-e splenic artery aneurys$ " rupture. GI. Hemo )roma!osis
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;xa$ple: )yperpigmen!e* p! = a*&%! !)a! is *i''&se%y )yperpigmen!e* an* )as *ia-e!es /!ype I *ia-e!i 0 , -ron>e *ia-e!es , )emo )roma!osis , 9e o1er%oa*@ a&!o re @ rea-sor- !oo m& ) 9e. .e$osiderosis is ac#uired iron o-erload ,y ,eing an alcoholic. Iron supple$ents are contraindicated in the elderly ,:c it will create he$osiderosis and ha-e iron o-erload. 3ac% to he$ochro$atosis: it1s an autoso$al recessi-e dC and what happens is that instead of rea,sor,ing 16D1E7 of iron fro$ foods, you are a,sor,ing 1667 of iron. )arget organ is the li-er. Ghene-er 4e is a,sor,ed into cells, it produces hydroxyl free radicals. 9o, the 4e doesn1t da$age anything, it1s the free radicals (the hydroxyl free radicals 4enton rxn!. If you are da$aging li-er cells, will lead to fi,rosis and cirrhosis. T)ey ALL )a1e irr)osis in 9e o1er%oa*, ei!)er -y )emosi*erosis or )emo )roma!osis. In cirrhosis, you see li-er with ,rownish pig$ent, *russian ,lue stain (to see 4e!, and a K;2B .IL. incidence of hepatocellular carcino$a. Can also go elsewherepancreastherefore can ha-e ;H'crine and ;&?'crine dysfunction, leading to $ala,sorption. ?estruction of islet cells leads to -ery ,rittle type I dia,etes. Also deposits in s%in and lead to hyperpig$entation (,ronCe loo%!. )his is a co$,o of 4e depositing there and ,y sti$ulating $elanocytes, therefore there is 4e pig$entation and $elanin. Can go into joints and lead to polyarthritis, can go to pituitary, leading to hypopituitaris$, can go to heart and produce restricti-e cardio$yopathy. .ow you do s reen 'or iron o1er%oa*E <er&m 'erri!in. <er&m 9e , )ig). Ex ess 9e s!ores@ !)ere'ore *e rease* syn o' !rans'errin. T)e TI(C is *e rease*. P sa! is in rease*@ ser&m 'erri!in is in rease*. RxE P)%e-o!omy. ?o not use chelation therapy. )hey purposely $a%e you 4e def. )his dC is the next to the $ost co$$on autoso$al rec dC. Hemosi*erosis , ACSUIRED 9e o1er%oa* = 'rom a% o)o%. GII. 5i%son#s *> 8ayser 9%eis )er ring ,rown ring around cornea. Ghat is degeneration calledN Hepa!o%en!i &%ar *egenera!ion. P! 3i!) a-norma% mo1emen! / )orea0 *isor*er@ *emen!ia@ an* irr)osis. A&!o re essi1e. De'e ! in ri**ing C& in -i%eI so@ !)e C& -&i%*s &p an* a &m&%a!es in !)e %i1er. Kery toxic. 9o, o-er a period of $onths to years, you go fro$ chronic acti-e hepatitis to cirrhosis. Ghen you get a total Cu le-el, what does it includeN 4ree Cu and ,inding protein for Cu. T)e -in*ing pro!ein is a%%e* er&%op%asmin. 9o, so$e Cu is attached to ceruloplas$in. 9o, the total Cu $easured includes ,ound and free. RE7 of a nor$al total Cu le-el is related to Cu attached to ceruloplas$in. 9o, $ost of the total Cu le-el is ,ound to ceruloplas$in, not the Cu that is free. <o@ B4P in a norma% person !)e !o!a% opper is C& !)a! is -o&n* an* ina !i1e !o er&%op%asmin. 9o, is ceruloplas$in a proteinN Bes. 9o, with cirrhosis, are you synthesiCing ceruloplas$inN &o. )herefore, there is a decrease of ,inding protein for Cu. 9o, 'ree & in rease*. <o@ !)e !o!a% C& %e1e% is *e rease* /-7 %ess er&%op%asmin0@ -&! !)e 'ree C& is in rease* /more &n-o&n*0. 2xN *C&a$ine (Cu ,inder!. 8enticular nucleus $essed up (caudate nucleus in .?! GIII. Cirr)osis &e-er focal, always diffuse. )he ,u$ps all o-er it are called regenerati-e nodules. Know that li-er tissue is sta,le, therefore it1s usually in the Lo phase, and so$ething has to sti$ulate it to go into the cell cycle to di-ide. )he li-er has an a$aCing regenerati-e capacity. 2egeneration of li-er cells are hepatocytes with no triad, no central -ein, and no sinusoids. J&s! 3a%% !o 3a%% )epa!o y!es 3)i ) are 3or!)%ess. 3u$ps are regenerati-e nodules, no triad5 there are just wall to wall hepatocytes surrounded ,y fi,rous tissue. 9tarts off as $icronodular (less then 0 $$! and ends up $acronodular (o-er 0 $$!. 9o, ha-e li-er, ,ut cells not wor%ing. .ow is a portal -ein gonna ,e a,le to e$pty into the li-er when there are no sinusoid:triadsN It1s a pro,le$ portal .)&. Comp%i a!ions: *itting ede$a, ascites, esophageal -arices, and $eta,olic pro,s ( anno! me!a-o%i>e es!rogen, leads to gyneco$astia!. Cannot loo% at gyneco$astia, ha-e to feel it. <i*e e''e !s o' pro-%ems o' es!rogen me!a-o%ism: 9ide note: )here are 0 ti$es in a lifeti$e where $ales can de-elop gyneco$astia. 1. &ew,orns $ales ha-e ,oo,s ,:c estrogen fro$ $o$5 new,orn girls with periods ,:c estrogen fro$, then drop off, leads to ,leeding. (. +ales also get ,oo,s in teens (pu,erty!. 0. +ales also get ,oo,s when they turn old ,:c testosterone goes down and estrogen goes down, leading to gyneco$astia so, get ,oo,s (gyneco$astia! three ti$es throughout life, and this is nor$al. ;xa$ple: 10 y:o unilateral su,al-eolar $ass, what is $anage$entN 8ea-e it alone. Lyneco$astia is not always ,ilateral, it is usually unilateral. Go$en ha-e diff siCe ,reasts ,:c each ,reast has different suscepti,ility to estrogen, progesterone, and prolactin. +en do not ha-e ,reast tissue, therefore $ore li%ely that one will enlarge, the other will not. *al$er erythe$a (related to estrogen!, spider angio$a, -it def1s, dupatron1s contracture in pal$ (fi,ro$atosis increased fi,rous tissue around the tendon sheaths, causing fingers to coil in, co$$only assoc with alcoholics! these are all estrogen a,nor$alities. Co$plication of Ascites adult with ascites spontaneous peritonitis due to ; coli. Child with nephrotic syndro$e and get ascites and spontaneous peritonitis, what is the organis$N 9trep pneu$oniae. 9o, adults with ascites and spontaneous peritonitis " ; coli, while %id with ascites and spontaneous peritonitis " 9trep pneu$oniae. GI.. Hepa!o e%%&%ar ar inoma &odularity5 Cancer in hep -ein tri,utary (ie!. )his cancer al$ost always de-elops in the ,ac%ground of cirrhosis. It is -ery rare for hepatocellular carcino$a to de-elop without cirrhosis present. 9ince alcohol is the +CC1s cirrhosis, is it also the +CC of cancerN &'. +CC#s )epa!o e%%&%ar ar inoma , pigmen! irr)osis: )emo )roma!osisI )epa!i!is ( an* C. )his cancer can produce ectopic hor$ones ;*' (leads to (ndary polycythe$ia!, insulin li%e L4 (leads to hypoglyce$ia!. )u$or $ar%er: alpha feto protein. ;xa$ple: pt with underlying cirrhosis, and is sta,le. 3ut suddenly the pt ,egins to lose wt and ascites is getting worse. ?o a peritoneal tap and it is he$orrhagic (do not assu$e it is trau$atic fro$ the needle, unless they say it!. If there is ,lood in the acidic fluid it is pathologic ,leeding. 9o, !)is )x /3! %oss@ -eginning !o *e!eriora!e s&**en%y@ -%oo* in a i*i '%&i*0. 8no3 i! is )epa!o e%%&%ar ar inoma@ -&! 3i%% as6 = 3)a! !es! *o yo& *oE A%p)a 'e!o pro!ein. +any tu$ors in li-er " $ets, pro, fro$ lung5 lets say it1s a nons$o%er, what is the pri$ary cancerN Colon cancer, ,:c he is a nons$o%er, therefore it won1t ,e fro$ a pri$ary lung cancer, so the ( nd +CC is colon cancer and it doesn1t ha-e a high association with s$o%ing.
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2e$e$,er the (nd $ost co$$on cause: exa$ple of a s$all ,owel o,struction, the +CC is adhesion fro$ pre-ious surgery, ,ut if the pt did not ha-e any surgeries then it1s due to indirect inguinal hernia. :ALL(LADDER DW I. As6 a-o&! pa!)ogenesis o' s!one = !oo m& ) )o%es!ero% in -i%e or !oo %i!!%e -i%e sa%!s. Bou will ha-e a supersaturated stone with cholesterol will get )o%es!ero% s!one /+C s!one0. 'r, too little ,ile salts, ,oth lead to stones. Anything that causes ,ile salt def (cirrhosis, o,struction, Cholestyra$ine, Crohn1s dC! can lead to gallstones ,:c too lil ,ile salts. II. Pigmen! s!ones Bellow stones (%now they are not cholesterol stones! (E y:o fe$ale, 2<P cra$py pain, fe-er, point tenderness, neutrophilic leu%ocytosis, stones re-ealed on ultrasound. C3C showed a $ild nor$ocytic ane$ia and a corrected reticulocyte ct of T7. 9pleno$egaly on *; and fa$ily hx of splenecto$y. DxE Congeni!a% sp)ero y!osis5 ,:c she has ,een he$olyCing 23C1s all her life, she puts a lot of ,iliru,in into conj ,iliru,in and therefore has supersaturated ,ile with ,iliru,in, and for$s Ca -i%ir&-ina!e s!ones !)a! are Qe! -%a 6. 9een with ultrasound. Ghat is the s reening !es! o' )oi e for stonesN <ltrasound. 9creening test of choice for anything in the pancreas " C) reason why is ,:c ,owel o-erlies pancreas and $esses up ultrasound, therefore not as sensiti-e. Always put C) for pancreas5 L3 " ultrasound (can tell dia$eter of C3? to tell if there is a stone in it!. PANCREA< I. Cys!i 9i-rosis Cystic fi,rosis growth alteration ,:c $ucous in ducts of the pancreas. 9ee a!rop)y ,:c ,loc% lu$en of exocrine ducts, and pressure goes ,ac% to the glands and that pressure atrophies the glands, %ea*ing !o ma%a-sorp!ion. Can cystic fi,rosis also lead to dia,etesN Bes ,:c e-entually fi,rose off the islet cells, leading to !ype I *ia-e!es, too. +o%e &%ar -io: c1so$e @ with 0 nucleotide deletion, and those 0 nucleotides codes for phenylalanine. 9o, you are *e' o' p)eny%a%anine in !)e ys!i 'i-rosis !ransmem-rane reg&%a!or pro!ein /C9TR0. 9o, all its $issing is phenylalanine. +ost things, after they are $ade in the ri,oso$e in the 2;2, ha-e posttranslational $odifications in the Lolgi apparatus, which is where the real defect is. T)e rea% pro-%em is 3)en i! ge!s !o !)e :o%gi appara!&s = i!#s s&ppose* !o -e mo*i'ie* an* se re!e* !o !)e e%% s&r'a e. I! en*s &p -eing *egra*e* in !)e e%%@ an* yo& en* &p )a1ing !)e C9TR. 9o, the pro, is in the Lolgi apparatus it screws it up, and ne-er $a%es it to the surface, therefore has no function. 9o, what does it doN In !)e s3ea! g%an*s@ norma%%y@ i! 3o&%* rea-sor- Na an* C% o&! o' !)e s3ea! g%an*. (7 !)ey are *e' in !)is@ !)ey are %osing sa%!@ 3)i ) is !)e -asis o' !)e s3ea! !es!. 0 y:o %id, failure to thri-e, chronic diarrhea, resp infection, $o$ states that the ,a,y taste1s salty when she %isses the ,a,y. )his is the gi-e away for C4, ,:c they lose considera,le salt and ,eco$e salt depleted when they are o-erheated. Ghy are all the secretions so thic% in the lungs, pancreas, and ,ile ductsN C4)2 regulator what does it doN In %&ngs, need to ha-e salt and secretions in the lu$ens of the resp tract to %eep it -iscous (to %eep it nice and loose!5 if you are $issing C4)2, &a is rea,sor,ed '<) of the secretions in the airway (therefore a lil dehydrated!. And, chloride cannot ,e pu$ped into the lu$en of the airway so you are ta%ing away the ( i$p ingredients with this pu$p: ta%ing &a out and not putting Cl in. )herefore these secretions are thic% li%e concrete. )he sa$e is true for secretions in the pancreas (&a pu$ped out and Cl not put in!. +CC *ea!) , pse&*omonas aer&ginosa. 9er!i%i!y: what is chance of $ale with cystic fi,rosis ha-ing childrenN 6DE7 ($ost are infertile!5 for fe$ales, they can get pregnant, ,ut only ha-e 067 chance of getting pregnant. )he pro,le$ is that the cer-ical $ucous is as thic% as concrete and therefore the sper$ cannot penetrate, and that is one of the reasons why they are infertile II. A &!e pan rea!i!is +C due to alcohol5 (nd +CC " stone caught in accessory ducts of the pancreas. Epigas!ri pain 3i!) ra*ia!ion in!o !)e -a 6 (,:c it1s a retroperitoneal organ!. A$ylase is ele-ated. Characteristic pain:
.a-e an hx of acute pancreatitis5 after 16 days, ha-e a $ass in the a,do$en and they as% what do you doN C) what is itN Pan rea!i pse&*o ys! D a lot of fluid accu$ulates around an infla$ed pancreas and for$s a false capsule and has a potential to rupture (not good to ha-e a$ylase in peritoneal ca-ity!. 2<P with dystrophic calcification (dots on xDray!5 what do you thin% it isN Pan rea!i!is. Is it acute or chronicN C)roni ,:c there are so $any. Is this pt li%ely to ,e an alcoholicN Bes. Ghat else would you expect ie which of the following you expectN 9teatorrhea (one of the causes of $ala,sorption need enCy$es!, or $ay say you ha-e ,ile salt def (no, ,:c pancreas has nothing to do with ,ile salts!, he$orrhagic diathesis (yes, Kit K def related to $ala,sorption!, etc Car inoma o' !)e )ea* o' !)e pan reas = +CC , smo6er@ "n* +CC , )roni pan rea!i!is@ pain%ess Qa&n*i e /main%y onQ&ga!e* -i%ir&-in0@ %ig)! o%ore* s!oo%s@ pa%pa-%e :( /Co&r1oisier#s sign0. C sign per$anently indenting the duodenu$, do ,ariu$ study, also a sign of pancreatic cancer. A &!e pan rea!i!is 3i!) in'%amma!ion. Ghat will that do to peristalsis of that duodenu$ next to itN .ow does the ,owel react to the presence of infla$$ation next to itN I! s!ops peris!a%sing (not through the entire ,owel, just there!. If this is true, there would just ,e air in the area it doesn1t peristalses what is this calledN <en!ine% sign (sentinel is so$eone that is supposed to %eep watch! %eep watch of whatN Infla$$ation (so, !)e sen!ine% sign 6eeps 3a! ) o' in'%amma!ion !5 the
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classic area is the pancreas. )his is a%%e* %o a%i>e* i%e&s /i%e&s@ -y *e'ini!ion is %a 6 o' peris!a%sis0. 5)ene1er !)e -o3e% %a 6s peris!a%sis@ 3i%% see air a &m&%a!e an* 3i%% ge! *is!ension. Ghat if you ha-e a seg$ent of ,owel that is distended in the 28PN .as to ,e infla$$ation, the cecu$ is in the 28P and appendix could ,e the reason. 9o, appendicitis producing sentinel1s sign. CHAPTER 11: 8IDNEY I. Cas! $old of whate-er is going on in the nephron:tu,ule. It is a protein that is congealing around whate-er is present in the tu,ule at that ti$e5 there is a $old $ade, and is passed into the urine and we can see it under the $icroscope. T)is is imp -7 no3 3e *o no! )a1e !o *o a rena% -x o' !)e rena% !&-&%es -7 !)e as! 3i%% !e%% yo& 3)a! is going on. ;xa$ple: if you ha-e glo$erulonephritis (infla$$ation of the glo$erulus!, you ha-e da$aged the capillaries and get he$aturia, so the 23C1s are in the nephron and trapped in the cast, and will ha-e an 23C cast that tells you there is a glo$erulonephritis occurring. ;xa$ple: Gith renal tu,ule necrosis, the tu,ules are sloughing off with coagulation necrosis. )his will for$ a cast and is called renal tu,ular cast, and will tell you there is renal tu,ular necrosis. ;xa$ple: $an:wo$an with acute pyelonephritis with neutrophils in-ading the interstitiu$ and the tu,ules, there are cast of neutrophils (G3C casts!, telling $e there is infection of the %idney. ;xa$ple: spilling lipid in urine in nephrotic syndro$e and for$ cast of fat and a fatty cast that you can see and polariCe in the urine. II. Urina%ysis T)e 'irs! !)ing !)a! *isappears in rena% 'ai%&re is !)e a-i%i!y o' !)e 6i*ney !o on en!ra!e &rine . )his occurs ,efore Cr:3<& thin% a,out increasing, or e-en ha-ing renal tu,ular casts. ;xa$ple: ta%ing urine in the $orning and doing the specific gra-ity of the urine and seeing what it is. 3:c, spe i'i gra1i!y an !e%% yo& i' i! is on en!ra!e* or *i%&!e &rine. If the specific gra-ity is greater than 1.6(0, this $eans that the pt is concentrating urine and that the %idneys are A39'8<);8B &'2+A8 (this is a C.;A* test!. ;xa$ple: let1s say I did a specific gra-ity of urine o-ernight and it is 1.616 this is -ery hypotonic urine, and it $eans that the pt could not concentrate, and that the pt is in renal failure. (3<&:Cr will not help deter$ine this!. )he urine that should ,e concentrated is fro$ a pt that is sleeping o-ernight. Hya%ine as! = as! o' a pro!einI mos!%y -B7)arm%ess (all other casts ha-e pathological significance!. III. Crys!a%s: Uri a i* rys!a% loo%s li%e a star5 p. of the urine has to ,e acidic to for$ a uric acid crystal. *t with gout want to stop crystals fro$ for$ing, and you %now they for$ in low p., what do you want to do with the urineN Al%aliniCe it. .ow can you do thatN Car,onic Anhidrase inhi,itor (acetaCola$ide!. 3y ,loc%ing ,icar,onate recla$ation will al%aliniCe the urine, and pre-ent stones fro$ for$ing. 9o, si$ple $anipulation of the p. can pre-ent urate nephropathy. Ca% i&m Oxa%a!e rys!a% loo% li%e the ,ac% of an en-elope5 why is this i$p to %nowN ;xa$ple: street person co$es in, stupurous, has increased anion gap $eta,olic acidosis. ?o a urinalysis, and see ,unch of calciu$ oxalate stones what did he drin%N ;thylene glycol. Ghat is the +C s!one 3e passE Ca oxa%a!e. 9o if you ha-e a Ca 'xalate stone, you will ha-e crystals associated with it. Horse 6i*ney joined at their lower poles. Gill as% what is restricting the $o-e$ent of the %idneyN I+A it traps the %idney. I.. Cys!i *> o' !)e 6i*ney A. In'an!i%e po%y ys!i 6i*ney *>, which is auto recessi-e5 therefore it is present at ,irth. ?o you thin% this ,a,y is urinatingN &o, therefore has oligohydra$nios (decreased a$niotic fluid!. 9o, ,a,y is in an a$niotic sac, with hardly any a$niotic fluid around it, and therefore ha-e $alfor$ation due to pressure. 8oo% at the nose and ears5 this is a%%e* Po!!ers 'a e@ 3)i ) is a sign o' o%igo)y*ramnios in po%y ys!i 6i*ney *>: '%a!!ene* nose@ %o3?se! ears@ an* re esse* )in0. )his child wasn1t a,le to ,reath, and when it tried to ,reath, it couldn1t5 the lungs are hypoplastic they ne-er fully de-eloped ,:c the %id couldn1t fill the$ up. )hese cysts are also seen in the pancreas, the li-er and just inco$pati,le with life. (. A*&%! po%y ys!i 6i*ney *isease: AP8D> 9o$e autoso$al do$inant dC show *enetrance ha-e the a,nor$ality when they loo% for it on the gene, ,ut do not express it. (so you ha-e the genetic a,nor$ality, ,ut ha-e ne-er expressed it in your life!. )hat1s the good news the ,ad news is that you can trans$it it to your child, therefore it is difficult to recogniCe on the pedigree. ;xa$ple of penetrance: fa$ilial polyposis " 1667 penetrance if you ha-e the gene, you ha-e the dC. ;xa$ple of inco$plete penetrance: $arfan a,nor$ality on c1so$e 1E, nor$al parents, they do not express the gene, ,ut passed on to child (this is inco$plete penetrance!. A*K?C is another exa$ple of inco$plete penetrance. 9o, A*K?C is an autoso$al do$inant dC that is not present at ,irth ,:c A? dC ha-e *e%aye* mani'es!a!ions. 9ee cysts ,y 16D1( years of age, always get HTN 3)i ) 3i%% !)en pre*isposes " !ypes o' -%ee*s: (1! C)ar o!?(o& )ar* ane&rysms (a ,lood clot! and ((! see ,lood all o-er the ,rain, due to su,arachnoid he$orrhage, therefore the ,lood is due to r&p!&re -erry ane&rysm. <&-ara )noi* )emorr)age " Iworst headache of $y lifeJ, ,lood in su,arachnoid space. +.P /mi!ra% 1a%1e pro%apse0: ;xa$ple: hx of .)&, a,nor$ality of ultrasound in the renal pel-is, and had clic% $ur$ur (therefore +K*! dxN A*K?C. )here is a high assoc of +K* with this. Di1er!i &%osis also has a high incidence. ;xa$ple: pt with .)&, a,nor$ality on ultrasound in renal area, lost A66 $ls of ,lood all of a sudden, leading to he$atocheCia (+CC he$atocheCia " di-erticulosis!.
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.. :%omer&%ar s!&'' A. Nomen %a!&re o' !)e 8i*ney *>: C?i!isD , !ype III HPY = !)ere'ore i!#s an imm&no%ogi *> /g%omer&%onep)ri!is0 ;xa$ple: 8ipoid nephrosis does that ha-e type IIIN &o ;xa$ple: 4ocal seg$ental glo$erular sclerosisN &o ;xa$ple: ?ia,etic glo$erulosclerosisN &o. ;xa$ple: IgA glo$erulonephritis, diffuse $e$,ranous glo$erulonephritisN Bes
98
Ghen we say =diffuse1, this $eans that ;K;2B glo$erulus has so$ething wrong with it on renal ,x. Ghat is =focal1N not all glo$eruli in-ol-ed. Ghat if dC is focal and dC in the glo$erulus is focalN .a-e a pro,le$ this is called 4ocal 9eg$ental Llo$erulus Ghat does proliferati-e $eanN .a-e lots of the$. 9o, you ha-e $any nuclei. If all the glo$eruli ha-e a lot of nuclei, this is diffuse proliferati-e glo$erulonephritis If you just see thic% $e$,ranes, its $e$,ranous glo$erulonephritis If you see ,oth increased cell and thic%ened $e$,raneN +e$,ranoproliferati-e glo$erulonephritis (. Ana!omy7s )ema!i )he order is: ,lood, endothelial cells of the capillaries, underneath there is a 3+, and then the -isceral epithelial cells (loo%s li%e feet " podocytes5 which ha-e spaces in ,etween the$ called slit pores! that line the ,ow$an1s capsule. Gho ma6es7syn!)esi>es !)e :(+E .is era% epi!)e%ia% e%%s /po*o y!es0. Ghat %eeps Al,u$in out of the urine nor$allyN 9trong negati-e charge of the 3+. Gho is responsi,le for strong IDIof the 3+N A :A: a%%e* )eparan s&%'a!e@ 3)i ) )as a s!rong neg )arge. If we i$$unologically da$age the -isceral epithelial cell, what do we auto$atically also da$ageN )he 3+, which $eans you1re gonna spill a lot of protein in the urine, which $eans you potentially can ha-e nephrotic syndro$e if you spill U0.E gra$s in (> hrs!. C. Tes! on Rena% (x <!ains routine . ] ; he$otoxylin stains, sil-er stains. Imm&no'%&ores en! stain pattern can ,e linear or granular (a%a lu$py ,u$py!, which are the only ( patterns. )hese patterns are i$$une co$plexes or patterns:A,1s that they are detecting. )a%e ,x, and ha-e A,1s with a fluorescent tag on the$. Ie want to see IgA in the glo$erulus and ha-e anti IgA A,1s with a fluorescent tag if there are any, it will attach to it and $a%e a fluorescent tag. )here are also tags for IgL, C0, fi,rinogen so can get an idea of what1s in the glo$erulus and an idea of what pattern it is in (ie linear -s. lu$py ,u$py granular pattern!. It doesn1t tell us where these things are, it just tells us that they are there. Ghat tells us where i$$une deposits and i$$une co$plexes are located are E+. 9o, we do stains, fluorescence, and ;+. .ow can we tell that the podocytes are fusedN Can only tell ,y ;+ ,:c its so s$all. .I. Di''eren e -e!3een A- re ogni!ion 1s. imm&ne omp%exes ?etect with A, which ha-e ( Ag recognition sites on the A,. :oo*pas!&re syn*rome is an Ig: an!i (+ A-#s. 9o, they get in the ,lood they get into the glo$erular capillary and are directed against the 3+. Ghere-er there was a spot on the 3+ you will see an IgL A,. )here wouldn1t ,e one spot on the 3+ without IgL. 9o, what if we do a fluorescent tag for IgL o-erlying the glo$erulus what would you seeN Gould see outlines of all the 3+1s of the entire glo$erulus. It is linear. +CC %inear pa!!ern on imm&n&'%&ores en e , :oo*pas!&res. Imm&ne omp%exes Ag with A, attached and is circulating in the ,loodstrea$, hence Ag?A- omp%ex ie %&p&s , imm&ne omp%ex *>: Ag , DNA@ A- , an!i?DNA they attach to e:o and float around and deposit in certain places5 in this case it will deposit in the glo$erular capillary5 !ype III HPY /-7 imm&ne omp%ex0. 3:c they are i$$une co$plexes, they are larger than indi-idual A,1s ,:c they are Ag and A, attached together therefore they are ,igger, ha-e diff solu,ilities, ha-e diff charges they won1t fit nice and neat in the glo$erulus. 9o, depending on the siCe and charge will depend on where they locate the$sel-es. Ie if too ,ig, will locate under the endothelial nucleus. 9o, this would ,e called a su,endothelial $e$,rane they are so ,ig that they fit under a podocyte (they cannot get through the 3+!. 8upus is li%e this, too they cannot get passed the 3+ and hangout under the endothelial cells. Pos! s!rep :+ = -a !eria% Ag 3i!) A- agains! /imm&ne omp%ex0@ 3)i ) is 1ery sma%%@ an* 1ery so%&-%e. T)ey an go a%% !)e 3ay pas! !)e (+ an* *eposi! &n*er !)e epi!)e%ia% si*e = !)is is a s&-epi!)e%ia% *eposi!. 9o, how do you find out where the deposits areN Cannot see with i$$unufluorescence, ,ut will ,e a,le to see with ;+ ,:c they are electron dense ($eaning that they increase the density where-er they are!. 9o, i$$une co$plexes ha-e diff solu,ilities, diff charges, and rando$ly go underneath the endotheliu$, under the su,epithelial surface5 they will not ha-e a nice s$ooth linear pattern li%e anti ,ase$ent $e$,rane A,1s. ;xa$ple: *> !)a! isn#! %inear /so i!s no! :oo*pas!&res0 = i! o&%* -e any imm&ne omp%ex *> = %&p&s@ pos! s!rep@ IgA g%omer&%onep)ri!is. Can get a hint of what the dC is, depending on what is in there ie what is the on%y g%omer&%ar nep)ri!is !)a! yo& an on%y *x 3i!) imm&n&'%&ores en eE IgA g%omer&%onep)ri!is. 3:c if you are gonna call it glo$erular nephritis, this $eans that there is no IgL in there, ,ut IgA. 9o, the only way to accurately dx IgA glo$erulonephritis is to pro-e that it is IgA and nothing else. :ran&%ar7%&mpy -&mpy pa!!ern = 3)en yo& see !)is@ 3)a! *oes i! meanE Imm&no omp%ex !ype III *>I remem-er an!i (+#s an* an!i (+ A-#s agains! !)e (+ is no! a !ype III@ -&! a !ype II. 5)ereas@ imm&ne omp%exes are !ype III.
.II. Nep)ri!i 1s. Nep)ro!i :%omer&%onep)ri!is T)ere are " !ypes o' g%omer&%onep)ri!is: nep)ri!i nephritic and ,eco$e nephrotic!
or nep)ro!i
(cannot ,e ,oth at sa$e ti$e5 howe-er, it can start out
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A. Nep)ri!i <yn*rome: Has &ni;&e as! that is red, and loo%s li%e ,iconca-e dis% R(C as!s (uni#ue to nephritic dC1s!5 ,:c you ha-e infla$$ation you will spill protein, ,ut not greater than 0.E gra$s in a (> hr period (,:c if it did, it would ,e nephrotic! so it is $ild to $oderate proteinuria. Bou are spilling protein, ,ut not to the sa$e le-el as nephrotic, therefore 3i%% no! ha-e pitting ede$a, ascites, etc If are infla$ing the glo$erulus, will you ha-e oliguriaN Bes all the glo$erular capillaries ha-e swollen up, L42 would decrease, and this would lead to oliguria. Are you decreasing the a,sorption or not filtering &aN yes. 9o does the &a ,uild upN Bes therefore run the ris% of .)&. <o@ %assi a%%y 3)a! yo& see in nep)ri!i *>#s is )ema!&ria@ R(C#s as!s@ o%ig&ria@ HTN@ an* mi%*7mo*era!e pro!ein&ria /!)is is !)e *e'ini!ion0 (. Nep)ro!i <yn*rome: .as a different cast ('a!!y pi!!ing e*ema. as!!, )a1e grea!er !)an $.4 grams o' pro!ein in a "2 )r &rine samp%e. 5i%% a%so )a1e
9o, if you started out nephritic (23C casts, $ild:$oderate proteinuria! and all of a sudden you start seeing pitting ede$a, start seeing o-er 0.E gra$s of protein in the urine o-er (> hrs, and fatty casts then nephritic has ,eco$e nephrotic. .III. Nep)ri!i <yn*romes A. Pro%i'era!i1e :%omer&%onep)ri!is All the glo$eruli are diffuse, too $any nuclei (. Pos! s!rep :N ;xa$ple: scarlet fe-er ( wee%s ago, presents with he$aturia, 23C casts, $ild to $oderate proteinuria, .*, perior,ital puffiness. ;+: lu$en of capillary, ,u$p on lu$en is endothelial cell, underneath is 3+ (grayish!, and epithelial cells under. .as ,oulders that are denser than the nor$al glo$erular 3+ these are i$$une co$plexes. In this case, it the ,acteria is the AgDA, i$$une co$plexes. Ghich side are they closer toN Closer to epithelial side, therefore they are su,epithelial deposits hence post strep L+&. C. L&p&s :N ;xa$ple: 0E y:o fe$ale with I/J seru$ A&A with a ri$ pattern ($eaning you ha-e anti ?&A A,1s present!. L&p&s a%mos! a%3ays in1o%1es !)e 6i*ney. )here are A types, and the impor!an! one !o 6no3 is !ype I., which is a *i''&se pro%i'era!i1e g%omer&%onep)ri!is@ which is the +C o-erall one seen in 8upus. .as $any nuclei, therefore proliferati-e5 has wire loops. (orient to ;+! deposits in 3+ are anti ?&A deposits. Gould you agree that they are in the endothelial cellN Bes. 9o what is this locationN 9u,endothelial deposits. *odocytes with slit pores in ,twn are not fused ,:c if they were, it would ,e nephrotic syndro$e. Also see lu$en, endothelial cells and deposits. I$$une co$plexes are so ,ig they can1t get through the 3+. D. Cres en!i :N Llo$erulus surrounded ,y proliferating cells that are parietal cells ,:c not in the glo$erulus, and has crescent shape, hence the na$e crescentic glo$erular nephritis. )his is the 5OR<T g%omer&%ar nep)ri!is !o )a1e -7 in $ mon!)sI p!s 3i%% go in!o a &!e rena% 'ai%&re an* *ie &n%ess p! is on *ia%ysis. +any dC1s ha-e a crescentic glo$erulonephritis, ,ut the only one I need to %now is :oo*pas!&resI !)is is a NEPHRITIC *>I !)is *> )as res en!i g%omer&%onep)ri!is on -x /!)ere'ore a (AD *x0. IG. Nep)ro!i <yn*romes: *t with casts (fatty casts!, polariCed speci$en with $altese cross this is cholesterol in the urine. Ghen cholesterol is polariCed, it loo%s li%e a $altese cross. T)ese 'a!!y as!s are pa!)onognomi 'or nep)ro!i syn*rome. Lreater than 0. E gra$s protein for (> hrs, fatty casts in the urine, ascites, pitting ede$a, ris% of spontaneous peritonitis if you are a child. 'rganis$N 9trep pneu$onia in %ids, ; coli in adults. A. Lipoi* nep)rosis a6a +inima% C)ange D>: ;xa$ple: ;+ of T y:o ,oy that had an <2I one wee% ago, and now is all swollen, has pitting ede$a throughout ,ody (anasarca! and ascites, nor$oDtensi-e, no .)&5 saw nothing on renal ,x5 ,ut then did a ;+ see 23C in glo$erular capillary lu$en. 9o, see endothelial cells, see 3+ (without electron dense deposits!, podocytes (fused! '&sion o' po*o y!es is AL5AY< seen in any a&se o' nep)ro!i syn*rome. +altese crosses in urine. ?xN Lipoi* nep)rosis. All pt with nephrotic syndro$e ha-e hypercholestere$ia. 9ince they ha-e glo$erular dC and so$e of the cholesterol can get into the urine, so$e can for$ casts in the urine. A%a $ini$al change dC. Ghy is this happeningN .as lost neg charge in L3+, therefore al,u$in can get through. )hese pts ha-e a select proteinuria the only protein in these pt1s urine is al,u$in, and it is greater than 0.E gra$s per (> hrs. 2x corticosteroids (usually goes away in 1 year ne-er to co$e ,ac% again!. )he +CC nep)ro!i syn*rome in 6i*s. (. 9o a% <egmen!a% :%omer&%os %erosis
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;xa$ple: p! !)a! is HI. CUD@ pitting ede$a therefore loo% at urine and note that is greater than 0.E gra$s o-er (> hrs. .as fatty casts in urine and has .)&. ?o ,x, and already %now what you are gonna see ,:c it the +CC nep)ro!i syn*rome in AIDs p!. 'n ,x, so$e of the glo$eruli are a,nor$al and others are nor$al, ,ut only a part of the glo$erulus is $essed up. )herefore, it is focal seg$ental. 3:c the renal ,x with ;+ and i$$unofluorence did &') show deposits, therefore it1s glo$erulosclerosis. 9o, this is called focal seg$ental glo$erulosclerosis. )his is !)e +C %esion in AIDs p!s an* I.DA#s. &ext to rapidly progressi-e crecentric glo$erulonephritis, this is the next worse glo$erular dC. C. Di''&se mem-rano&s g%omer&%onep)ri!is ;xa$ple: adult with pitting ede$a, o-er 0.E gra$ per (> yrs, fatty casts. ?o a ,x and see not $any =dots1 therefore not a proliferati-e dC. .owe-er the 3+ is thic%er. ?xN Di''&se mem-rano&s g%omer&%onep)ri!is , +CC nep)ro!i syn*rome in a*&%!s. )his is su,epithelial deposit. Epimem-rano&s spi6es = spi6e %i6e %esion on !)e o&!si*e o' :(+ seen 3i!) si%1er s!ain " diffuse $e$,ranous glo$erulonephritis (only one that loo%s li%e that!. +any things can cause this (drugs, cancer, nothing, infections!5 so$e the drugs include &9AI?s, .ep 3, captopril (%ing of treat$ent of dia,etic nephropathy and heart failure!, $alaria, syphilis, colon cancer (i$$une co$plex is antiDC;A A,1s!. ;-entually leads to renal failure and can die unless you get a renal transplant D. Type I an* II +em-ranopro%i'era!i1e :%omer&%onep)ri!is /en*s in C?i!isD !)ere'ore i! is !ype III HPY = imm&ne omp%exJ0 1. )ype I has a relationship with .ep C how do you re$e$,erN +e$,ranous " .ep 3 (also re$e$,er the -asculitis *olyarteritis &odosa!, +e$,ranoproliferati-e " .ep C (also re$e$,er cryoglo,ine$ia!. 9o, !ype I is a s&-en*o!)e%ia% *eposi! !)a! pro*& es nep)ro!i syn*rome. (. )ype II is less co$$on, and has an Auto A, against C0, called C0 nephritic factor. It causes C0 con-ertase to ,eco$e o-eracti-e and is constantly ,rea%ing co$ple$ent down. 9o, the lowest co$ple$ent le-els you will see is in type II glo$erular nephritis this is called dense deposit dC ,:c the entire 3+ an i$$une co$plex. !ram !ra 6s $esangial cell (structural co$ponent of the glo$erular capillary! the $esangial cell is extending itself ,etween the 3+ and the endothelial cell, $a%ing it loo% li%e a tra$ trac%5 so, it1s a $esangial process ,twn the 3+ and endothelial cell tra$ trac% +e$,ranoproliferati-e dC E. Dia-e!i :%omer&%os %erosis Classic sign: ,ig round ,alls on . and ; stain. Ghen there is excess red in the cell, thin% )ya%ine ar!erio%os %erosis5 this is a s$all -essel dC of dia,etes and .)&. )he -ery first -essel that is hyaliniCed is the efferent arteriole. 8et1s say it is hyaliniCed. 9o, ,:c the lu$en is narrow in the efferent arteriole, the L42 will increase. 9o, what is the Cr clearanceN Increased. 9o, in early dia,etic nephropathy, there is an in rease* :9R an* Cr %earan e. GhyN 3:c the efferent arteriole is hyaliniCed and o,structed. Is this ,adN Bes as a result the glo$erulus will ta%e a pounding for the next ten years leading injury called hyperfiltration da$age. Ghat is the process where glucose attaches to an aa in a protein!N &onenCy$atic glycosylation. 8ets say this is also going on ,:c the pt is not watching hi$self too well, therefore 3e are nonen>yma!i a%%y g%y osy%a!ing !)e :(+. Ghat would happen when you glycosylate a 3+ what is it per$ea,le toN *rotein. 9o, ha-e all this pressure on the glo$erular capillary ,:c the efferent arteriole and also nonenCy$atically glycosylating the L3+, so its per$ea,le to protein. 9o, tons of protein going into the urine. Ghen you initially start seeing it, is called mi roa%-&min&ria. Gill the standard dipstic% for protein detect thatN &o. )here are special dipstic%s that are a-aila,le to detect this called $icroal,u$inuria dipstic%s. 9o, what does it $ean when your dia,etic pt has a I/J dipstic% for $icroal,u$inuriaN Ha1e !o gi1e p! ACE in)i-i!or ,:c you want to stop progression of this. .ow will it wor%N Afferent arteriole is controlled ,y *L;(5 the efferent arteriole is controlled ,y A) II (which constricts it!. 9o, when you gi-e an AC; inhi,itor, what happens to A) II le-elN It decreases. 9o, ,:c A) II decreased, you ta%e off the -asoconstricti-e ele$ent it has on it. ;-en though it was hyaliniCed, it will open then lu$en, ta%ing pressure off the glo$erulus, and decrease the filtration rate. 9o, the constant pounding on the glo$erulus is ta%en away. &eed to get glycosylated ., (.,A1c! under A7, ,ut the AC; inhi,itor cant do it all, so $ust ha-e perfect glyce$ic control, otherwise will go into chronic renal dC. If they can do this, the AC; in)i-i!or 3i%% pre1en! !)e *>. T)e ACE in)i-i!or a%so )e%ps HTN . *in% stuff is type IK collagen in the $esangiu$. It ,uilds up, eC to see ,ig circle (,ig ,alls:golf ,alls:Christ$as ,alls! a%a Ki$$elstielDGilson nodules this is nodular glo$erular sclerosis. 9. Amy%oi* 8i%e to deposit in the %idneys. Its a special protein. <!ain 3i!) Congo re*@ an* a'!er yo& po%ari>e i!@ i! )as a /granny smi!)0 app%e green -ire'ringen e. 8ight green is what the a$yloid is supposed to loo% li%e when you polariCe it with a Congo 2ed stain. A$yloid and dia,etic glo$erular sclerosis are nephrotic syndro$es. :. <&mmary nep)ro!i : 8ipoid sclerosis " +CC nephrotic in %ids 4ocal seg$ental glo$erulosclerosis " IK?A1s, AI?s ?iffuse +e$,ranous glo$erulonephritis " +C in adults )ype I and II +e$,ranoproliferati-e glo$erulonephritis " type I with hep C relationship, type II with autoA, against C0 (lowest co$ple$ent le-els seen! ?ia,etic nephropathy A$yloid
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G. Com-o o' Nep)ri!i an* Nep)ro!i <yn*rome A. IgA :%omer&%onep)ri!is /-&rger#s *>0
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IgA glo$erulonephritis is a KA2IA&) of .enoch 9chonlein purpura ,:c it is an i$$une co$plex dC, anti IgA A,s (so is .enoch 9chonlein palpa,le purpura in ,uttoc%s of legs, polyarthritis, LI ,leed, he$aturia (23C casts!! 'n i$$unofluorence, e-erything shows up in the $esangiu$. ;xa$ple: in 6i*s, presents with episodes of gross he$aturia, goes away, co$es ,ac% a few years later5 in a*&%!s, presents with episodic ,out of $icroscopic he$aturia. 9o, ha-e a lil he$aturia, goes away, and co$es again. 8il proteinuria, no .)&. Ghen it starts getting worse (16 years later!, that1s when it will ,e ,ad (so its not ,R!. I! is !)e +C o' a%% g%omer&%onep)ri!is an* is !ype III HPY. GI. (UN7Cr = Prerena% A>o!emia Can separate prerenal aCote$ia -s. renal failure (UN " ,lood urea nitrogen and Cr " end product of creatine $eta,olis$. <rea can ,e filtered and rea,sor,ed in the prox tu,ule (so its not a perfect clearance su,stance!5 Cr is only filtered in the %idney and is rea,sor,ed or secreted. (lnulin clearance is ,etter!. I' yo& !a6e !)e norma% (UN %e1e% /1F0@ an* norma% Cr %e1e% /1mg7*L0@ 3i%% )a1e !)e norma% ra!io o' 1F:1. Ghen you ha-e prerena% a>o!emia, there is an increase in 3<& (this is what aCote$ia $eans!. *re " ,efore, therefore there is so$ething wrong =,efore1 the %idney in other words, there is nothing wrong with the %idney, ,ut the C' is decreased (fro$ any cause D ie C.4, +I, hypo-ole$ia, cardio$yopathy, etc!. Any!)ing !)a! *e reases CO 3i%% %ea* !o prerena% a>o!emia -7 !)e :9R 3i%% *e rease. If you ha-e less renal ,lood flow, you will filter less and the L42 will decrease. 9o, when it decreases, it gi-es the prox tu,ule $ore ti$e to rea,sor, little ,it $ore urea than nor$al. 9o, there is increase prox tu,ule rea,sorption of urea. Ghat a,out CrN Ge %now that it is not rea,sor,ed, ,ut you do ha-e to get rid of it through the %idneys. 9o, e-en though it is not rea,sor,ed, the L42 is decreased, there is a ,ac% up of Cr and will not ,e a,le to clear it as fast. )herefore, there will ,e an increase in seru$ Cr. )here is little $ore of an increase is urea ,:c it is ,eing rea,sor,ed than with Cr. 9o, there is a disproportionate increase of 3<&:Cr. All you ha-e to re$e$,er is 1E:1. 9o, grea!er !)an a 14:1 (UN7Cr , prerena% a>o!emia. ;xa$ple: the pt has C.4, 3<& is T6 and Cr is (. 9o, ,oth are ele-ated, ,ut the 3<&:Cr ratio is >6:1, indicating that it is prerenal aCote$ia, and the pt does &') ha-e A)&. 8ets say pt truly has rena% 'ai%&re o%ig&ria@ rena% !&-&%ar as!s@ a &!e rena% 'ai%&re. )his 3i%% a''e ! !)e (UN7Cr ESUALLY ,:c so$ething is wrong with the %idney, therefore the sa$e effect on the 3<& is the sa$e on Cr. 4or ,oth, urea has to ,e filtered out of the %idney and it has failed ,oth increased proportionate to each other ,:c ,oth ha-e the sa$e pro,le$ and %idney is screwed up5 cannot get rid of urea, can1t get rid of creatinine, so they increase in proportion to each other ,:c the urea is not ,eing rea,sor,ed any$ore ,:c the %idney is in shoc%. ;xa$ple: 3<& " T6, Cr " T, therefore the 3<&:Cr ratio is 16:1, and pt is in renal failure. 9o, e-en though the 16:1 is $aintained, still ha-e renal failure ,:c it has increased so $uch. I' !)e ra!io is 14:1@ i! is prerena% a>o!emiaI i' i! is in rease* an* s!i%% 1F:1@ i!s rena% 'ai%&re. GII. A &!e Rena% 9ai%&re A. A &!e T&-&%ar Ne rosis: +CC , Is )emi A &!e T&-&%ar Ne rosis this is what you worry a,out the $ost when the CO *e reases@ p! *e1e%ops o%ig&ria. Ghen a pt1s C' decreases, and ha-e prerenal aCote$ia, you ha-e a decrease in L42, which is another cause of the oliguria. 9o, decrease in C' and oliguria is K;2B 3A?, and start to see 3<&:Cr go up need to %now if its prerenal aCote$ia, or renal aCote$ia to distinguish, get a 3<&:Cr. It its 1E:1, its still prerenal. 3ut it can progress to renal failure ische$ic acute tu,ular necrosis. +CC is )emi a &!e !&-&%ar ne rosis , no! !rea!ing prerena% a>o!emia. <o@ is )emi ATN is !)e 3ors! !)e ge! an* !)e (UN7Cr ra!io 3i%% -e norma%@ -&! in rease* in 1a%&es /ie LF7L0 Coag&%a!ion ne rosis: 9loughs off, ,loc%s lu$en and contri,utes to oliguria, and see casts in the urine. )he casts are renal tu,ule casts. 9o, om-o o' rena% !&-&%ar as!s@ o%ig&ria@ (UN7Cr o' 1F:1 , ATN. Ghy does this ha-e such a ,ad prognosisN Ghen pt has ische$ic necrosis, not only are you %illing the tu,ular cells, ,ut the 3+ also gets da$aged, so the structural integrity of the tu,ule is ,eing ta%en away, which is not good. Ghen you ha-e li-er da$age, and da$age li-er cells, and the cells regenerate, the cells are not regenerating sinusoids and triads, ,ut only the$sel-es. If the 3+ isn1t there, and the patient has reco-ered fro$ A)& or is in the process of doing that, can you regenerate a tu,ular cell without a 3+N &o. 9o, the $ore necrosis, the $ore 3+ are destroyed, the worse the prognosis ,:c cannot regenerate and cannot get ,ac% nor$al function. )his is why it is such a ,ad dC. T)ere are " par!s o' !)e nep)ron !)a! are mos! s&s ep!i-%e !o is )emia = 3)a! are !)eyE <!raig)! por!ion o' !)e prox !&-&%e an* !)i 6 as en*ing %im- o' !)e me*&%%ary segmen! /3)ere !)e Na787" C% o?!ranspor! p&mp is0. )hese two parts undergo coagulation necrosis and sloughing off. 9o, will see these fall off in the proxi$al tu,ule and also in the thic% ascending li$, of the $edullary seg$ent. (. Nep)ro!oxi ATN: Lenta$ycin, AL1s. If they are nephrotoxic, what is the first thing they will filtered fro$ the glo$erulusN *roxi$al tu,ule. 9o, nep)ro!oxi !&-&%ar ne rosis re%a!e* !o *r&gs in1o%1es !)e proxima% !&-&%e . And, the 3+ re$ains intact5
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therefore the prognosis of nephrotoxicity is way ,etter for ( reasons: only affecting the proxi$al tu,ules and not affecting the 3+. )he +CC nep)ro!oxi i!y , A:#s /"n* +CC , in!ra1eno&s pye%ograms0. Ghat is L42 in T6 y:oN It is decreased the Cr is > $ls:$in5 which is nor$al in older people. Cr clearance decreases along with L42 as they get older5 so, if you are gi-ing a drug without nephrotoxicity the sa$e dose as a young person, you will ,e %illing the older person. )his is o,-iously occurring ,:c AL1s are the +CC A)& and doctors are not decreasing the dose of the drug to decrease nephrotoxicity. GI.. T&-&%ar an* In!ers!i!ia% Disor*ers o' !)e 8i*ney A. A &!e Pye%onep)ri!is: .ow do you separate it fro$ a lower <)IN Kery easily. *yelonephritis is seen $ore in wo$en ,:c of their short urethra. A &!e pye%onep)ri!is is a sys!emi in'e !ion an* is an in'e !ion o' !)e 6i*ney proper. .ow does it get into the %idneyN At the ureto-esicular junc, the $uscle s#ueeCes so there is no reflux of urine fro$ the ,ladder into the ureter. )his is true in nor$al people. .owe-er, not all people ha-e a nor$al -esicoureteral junction. 9o, what happens in a pt with a ,ladder infection and the junction is inco$petent, it leads to 1esi o&re!a% re'%&x, and the infected urine refluxes up into ureters, and leads to ascending infection that goes all the way up to the %idneys. 9o, they will as% you, C3)a! is !)e me ) o' ALL UTI#sED /&re!)ri!is@ ys!i!is@ pe%1i!is@ or pye%onep)ri!is0 = *&e !o as en*ing in'e !ion 'rom !)e -eginning o' !)e &re!)ra. ;-ery wo$an (has nothing to do with cleanliness! has the sa$e ; coli serotype in her stool at the introutus of the urethra and her -agina. 9o, with trau$a or certain serotypes of ; coli, it can ascend up the urethra into the ,ladder. If the pt has an inco$petent ureto-esicular junc, up the ureters into the %idneys. 9o, all <)I1s are ascending fro$ the ,eginning of the urethra on up. Gith a &!e )o%e ys!i!is@ )a1e pain'&% &rina!ion /*ys&ria0@ in rease* 're;&en y@ s&prap&-i pain@ NO 'e1er@ no '%an6 pain@ NO 5(C as!s /3i!) ne&!rop)i%s in !)em0 = 3)yE (7 !)e 5(C as!s *e1e%op in !)e rena% !&-&%esI !)ey *o no! *e1e%op in !)e &re!er or !)e -%a**erI !)ey *e1e%op in !)e 6i*ney in !)e !&-&%e. <o@ 'e1er@ '%an6 pain@ an* 5(C as!s , ACUTE PYELONEPHRITI<. 9o, its an as en*ing in'e !ion *&e !o in ompe!en! 1esi o&re!a% Q&n . )his usually shows up in new,orn girls (and will ,e a pro, for rest of li-es!. ;xa$ple: %idney with white spots " a,scesses seen in pyelonephritis. If you ha-e constant acute attac%s of pyelonephritis, can ,eco$e chronic. )herefore ha-e increased ris% of .)& and renal failure. (. C)roni Pye%onep)ri!is ;xa$ple: scarred %idney (on cortex!, ,lunting of the calyces (occurs under the scar!, seen on intra-enous pyelogra$s dxN C.2'&IC pyelonephritis. 9o, -%&n!ing o' !)e a%y es , CHRONIC pye%onep)ri!is. C. A &!e Dr&g?in*& e* in!ers!i!ia% nep)ri!is Can *r&gs produce a nephritis in-ol-ing the interstitiu$ and tu,ulesN Bes can ,e acute and chronic and eC to diagnose. GhyN 3:c will ha-e fe-er, and de-elop a rash. 9e1er U Ras) (o,-iously due to drug, ,:c started after ta%ing the drug!, o%ig&ria, eosinop)i%i&ria (eosinop)i%s in !)e &rine = pa!)ognomoni !. )his is called a &!e *r&g in*& e* in!ers!i!ia% nep)ri!is. )his is $ore and $ore co$$on, and is a -ery co$$on cause of chronic renal failure. 9o, put pt on drug, get fe-er, rash, oliguria " discard:stop drug (ne-er gi-e again! this is a co$,o of type I and IK .*B. Ana%gesi nep)ropa!)y ;xa$ple: discoloration in renal $edulla, pale infarct, renal papilla sloughed off ringed signed5 and on pyelogra$s there will ,e nothing there just an e$pty space. ?xN Ana%gesi nep)ropa!)y. )his 'rom om-o o' a e!aminop)en an* aspirin o1er a %ong perio* o' !ime. A e!aminop)en is producing free radicals. 3:c of the poor circulation in the $edulla, there is free radical da$age on the tu,ular cells of the $edulla. Aspirin will ,loc% *L;( (a -asodilator!, therefore angiotensin II (a -asoconstrictor! is in charge of the renal ,lood flow. Kasoconstrictor of the efferent arteriole. )he peritu,ular capillaries arise fro$ the efferent arteriole. 9o, with -asoconstriction of the efferent arteriole, pt is affecting peritu,ular capillaries going around collecting tu,ules and renal $edulla. 9o, is that producing ische$iaN Bes. 9o, pt )as 'ree ra*i a% *amage an* is )emia %ea*ing !o ana%gesi nep)ropa!)y . )his is why the renal papilla necroses, sloughs off, and leads to rena% papi%%ary ne rosis. 9o, aspirin an* a e!aminop)en !oxi i!y. Dia-e!i nep)ropa!)y /-7 a&ses is )emia0@ a &!e pye%onep)ri!is /-7 a-s ess 'orma!ion0@ <CD> an* !rai!@ an a%% %ea* !o ana%gesi nep)ropa!)y. G.. C)roni rena% 9ai%&re De'ini!ion: P! )as (UN7Cr ra!io 1F:1 'or more !)an $ mon!)s. If ,oth %idneys failed: will not ,e a,le to excrete the things we nor$ally get rid of (so those !)ings 3i%% -&i%* &p ie salt!5 ;*' production will decrease, leading to normo y!i anemia 3i!) a orre !e* re!i &%o y!e ! o' %ess !)an "P. Gill not ,e a,le to get rid of organic acids, leading to me!a-o%i a i*osis, increased anion gap. Gith $eta,olic acidosis, ,ones try to ,uffer all the acid. 3:c the ,ones are ,uffering the extra . ion, ,one dC can de-elop, leading to os!eoporosis. )he prox tu,ules are $essed up in the renal tu,ules, and 1Dalpha hydroxylase will decrease (this responsi,le is hydroxylating Kit ?!5 so, with renal failure will also ha-e )ypo1i!aminosis D (-it ? def!. )his $eans that there will ,e )ypo a% emia and )ypop)osp)a!emia, leading to os!eoma%a ia. 9o, there are two ,one dC1s osteoporosis (,:c ,uffering and wearing away ,one $atrix! and osteo$alacia5 also, *). is reacting to chronic hypocalce$ia and leads to se on*ary )yperpara!)yroi*ism (also affects the ,one!. )he ,un:Cr ratio is T6:T. 9o, if you %now nor$al renal func you %now what happens.
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G.I. O!)er Pro-%ems re%a!e* !o 6i*neys:
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;xa$ple: pt has essential .)& o-er 16 yrs, and pt is not co$pliant with $edication %idney with co,,lestone appearance " nep)ros %erosis. <nderlying dC causing it: hyaline arteriolosclerosis ,:c there is decreased ,lood flow, tu,ular atrophy, glo$eruli are fi,rosing off, renal function is going down, and leads to renal failure. ;xa$ple: lets say the pt wa%es up with a ,ig headache and ,lurry -ision. *t is getting diCCy, goes to dr, and pressure is (>6:1>6, in the retina, dude has papilloede$a with fla$e he$orrhages and hard and soft exudates, grade > hypertensi-e retinopathy, 3<&:Cr are T6:T *xE +a%ignan! HTN (a%a flea ,itten %idney petechia -isi,le on surface of %idney see -essel changes ie hyperplastic arteriolosclerosis, and the 3K1s are rupturing, leading to petechial lesions on the cortex called flea ,itten %idney!. )his is all you ha-e to %now. )hey can also as% Rx: I. ni!ropr&ssi*e !o ge! !)e (P *o3n. 9o, they ha-e C&9 ede$a with papilloede$a, and if the 3* isn1t lowered, they are gonna die. ;xa$ple: %idney with a,nor$al areas that are pale and depressed so, if you ta%e a section through one of these, and you see an irregular irregular pulse, will see pale infarction with coagulation necrosis ,:c what you are loo%ing at are in'ar !s. Irregular irregular pulse is fro$ atrial fi,, and atrial fi, is $ost dangerous for em-o%i>a!ion. 9o, these infarcts are fro$ m&%!ip%e em-o%i, leading to $ultiple pale infarcts of the %idney. )his is &') pyelonephritis ,:c has $icroa,cesses ;xa$ple: atrophy due to dilatation of the renal pel-is, leading to )y*ronep)rosis. 9o, if you ha-e hydronephrosis and increased pressure pressing on the cortex and $edulla, what happens to thatN :e! is )emia an* a!rop)y = 3)i ) is a%%e* ompression a!rop)y. )his is -ery si$ilar to cystic fi,rosis ducts filled with $ucous the pressure is i$pacted ,ac% to the glands, and they undergo co$pression atrophy. Cortex and $edulla are -ery thin, along with -ery dilated renal pel-ices. +CC , s!one ;xa$ple: s!ag)orn a% &%&s = &rine pH is a%6a%ine an* sme%%s %i6e ammoniaI !)ere'ore@ !)ere m&s! -e a &rease pro*& er@ an* !)is is Pro!e&s. (7 i! is a &rease pro*& er@ they ,rea% urea down to a$$onia, and get an al%aline p.. )his is why a s!ag)orn a% &%&s is +g ammoni&m p)osp)a!e, and only de-elops in infections in pts that ha-e urease producers. ; coli are not urease producer and proteus species are and they predispose to these stones. ?o not pass these stones (too ,ig!, therefore need to extract these (surgery!. 9o, &rease pro*& er@ a%6a%ine pH@ ammonia sme%% !o !)e &rine. G.II. T&mors o' !)e 6i*ney If you see a $ass in a %idney, and its an adult, it is a rena% a*eno ar inoma. If it1s a %id, it1s a Gil$1s tu$or. 9o, if you see a $ass in the %idney, its pro, not $ets (,:c not $any things go there!, its not ,R, pic% cancer. <o@ a*&%! , rena% a*eno ar inoma@ 6i* , 5i%ms !&morI !)ey *eri1e* 'rom !)e proxima% !&-&%e an* !)e +CC , smo6ingI !)ey ma6e %o! o' e !opi )ormones: EPO@ para!)yroi* )ormone /%ea*s !o )yper a% emia0@ in1a*e !)e rena% 1ein. Ce%%s are %ear@ '&%% o' g%y ogen. ;xa$ple: flan% $ass in child, .)& " Gil$s tu$or5 .)& occurs ,:c it1s $a%ing renin5 usually unilateral. .istology: cancer where pt is duplicating e$,ryogenesis of a %idney e-erything is pri$iti-e. Can see rha,do$y,lasts5 li%es to $ets to lung If AD@ 'rom #some 11@ an* )a1e " %assi 'in*ings: aniri*ia /a-sen! iris0@ an* )emi)yper!rop)y o' an ex!remi!y /one ex!remi!y is -igger !)an ano!)er0 = !)is is a sign !)a! !)e 3i%ms !&mor )as a gene!i -asis. *apillary lesion in the ,ladder " transitional cell carcino$a ()CC! Ghat is the +CC transitional cell carcino$a of the ,ladderN 9$o%ing ?ye use to loo%N Aniline dye5 what is che$otherapy agent used to 2x Gegener1sN Cyclophospha$ide. co$plications of Cyclophospha$ideN .e$orrhagic cystitis and transitional cell carcino$a. .ow do you pre-ent thisN +esna. G.III. Urinary Tra ! In'e !ion +C urine a,nor$ality seen in the la, ;xa$ple: arrow pointing to neutrophils in urine5 23C1s in it, too, ,acteria ; coli (play odds!. 9o, see ne&!rop)i%s@ R(C#s an* -a !eria. T)e *ips!i 6 3i%% pi 6 &p a%% !)ree o' !)ese !)ings. CUD *ips!i 6 'or -%oo* *&e !o R(Cs. .e$aturia is -ery fre#uent and so$eti$es a lot of ,lood co$es out ()emorr)agi ys!i!is! and $ost of the ti$e its E o%i, ,ut so$eti$es it can ,e fro$ adeno-irus. Also, the *ips!i 6 )as %e&6o y!e es!erase and it1s $easuring the enCy$e in the leu%ocyte. +ost urinary pathogens are nitrate reducers, $eaning that they con-ert nitrate to nitrite. 'n a *ips!i 6@ !)ey )a1e a se !ion 'or ni!ri!es. 3:c ; coli is a nitrate reducer, there should ,e nitrites in the urine, which are dipstic% I/J for that. 9o, you ha-e a pt, wo$an or $an, who has dysuria, increased fre#uency, suprapu,ic pain and ha-e a urine sedi$ent of neutrophils, 23C1s, ,acteria or dipstic% findings of he$aturia, leu%ocyte esterase pos, nitrate I/J , UTI
Ghat are the
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Is i! %o3er or &pperE I' !)e p! )as 'e1er@ '%an6 pain@ 5(C %o3er.
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as!s i!s &pper@ i' none o' !)ese !)ings are presen!@ i!s
;xa$ple: pt with dysuria, increased fre#uency, neutrophils in the urine, few 23C1s, no ,acteria, I/J leu%ocyte esterase, urine culture is neg, and sexually acti-e person, dxN C)%amy*ia = norma% &rine &%!&res *o no! pi 6 &p C)%amy*ia !ra )oma!is. I! is !)e +C <TD. In $en, called nonspecific urethritis, in wo$an its called acute urethral syndro$e. Ge also use the ter$ called sterile pyuria. Ge don1t ha-e ,acteria present, ,ut do ha-e neutrophil present. 'n routine stool culture, its neg. 9o, one a&se o' s!eri%e py&ria is C)%amy*ia in'e !ion an* !)e o!)er one is T(. +C organ !)a! mi%i!ary T( goes !o , 6i*ney@ !)ere'ore 3i%% )a1e T( in !)e &rine@ an* i! 3i%% -e s!eri%e -7 &%!&res *o no! pi 6 &p. <o@ remem-er C)%amy*ia an* T( as a&ses o' s!eri%e py&ria. Day 2 Las! par! Penis ;$,ryo: what is the e$,ryology of )ypospa*iasN 'pening on the undersurface (you pee and it goes on your shoes! failure of closure of urethral fold Epispa*iasN 'pening on upper surface (pee and goes in face!5 defect in genital tu,ercle Peyronie#s *>: li%e ?upuytren1s contracture Priapism per$anent erection, seen co$$only in 9C?C ,c of the 23C1s and sic%le cells trapped in the -ascular channels. +C an er o' !)e penis " s;&amo&s ,c lac% of circu$cision. It is $ore co$$only seen in an uncircu$scri,ed pt they usually do not clean (poor hygiene! predisposes the smegma is ar inogeni . Tes!i %e Cryptorchid testis testicle doesn1t want to co$e down. )here are two phases in the decent of a testicle: transa,do$inal $igration down to inguinal canal. +I4 is responsi,le for this. )he second part of the trip is androgen dependent. )his includes testosterone and dihydrotestosterone. 9o, the first phase is fro$ +I4 and the second phase is androgen dependent. &eed testicle down ,y two years of age ,c if not, has a ris% of se$ino$as. 9till at ris% if you get it down. 8ets say you went in, and it loo% atrophic and other testicle loo%s nor$al, ha-e to ta%e nor$al one out, too ,c it is also at ris%. 9o, $ust ha-e testes exa$ines to $a%e sure you don1t ha-e a se$ino$a. Ana%ogy: in turners, they are infertile and ha-e $enopause ,efore $enarche, ,c ,y two years of ages, they ha-e no follicles in their o-aries, and this is called a strea% gonad. )his is an o-ary without any follicles. )his is analagous to cryptorchid testes: just li%e the cryptorchid testes predisposes to se$ino$as (which is a ger$ cell tu$or!, so does the strea% gonad predispose to a ger$ cell tu$or howe-er, do not call the$ se$ino$as in wo$en, ,ut *ysgerminomas. 9o, in pts dx1d with )urner1s syndro$e, they surgically re$o-e ,oth o-aries ,c of the great ris%. )hey don1t %eep the$ in there ,c lead to cancer. Or )i!is $u$ps Epi*i*ymi!is less than 0E " & gonorrhea:chla$ydia, greater than 0E " pseudo$onas .ari o e%e on left side ,c sper$atic -ein connected to left renal -ein, wheras the sper$atic -ein on the right is connected to the IKC5 ,c of this, the pressures increase, and a -aricocele on the left, leads to increased heat and is one of the $ost co$$on causes of infertility ie what would happen if you ,loc%ed the left renal -einN Gould de-elop a -aricocele. 9o, if you ,loc% the left renal -ein, you will increase the pressure in the sper$atic -ein and will lead to a -aricocele. Torsion sper$atic cord twisting5 when there is a torsion of the sper$atic cord, it shortens it. )his $eans that the testicle will go up into the inguinal canal. )his is painful. Bou will lose your cre$asteric reflex (in nor$al $ale, if you scatch the scrotu$, it will contract, which is lost in torsion of the testicle!. Hy*ro e%e persistence of tunica -aginalis5 when you ha-e ,ig scrotu$, you don1t %now whether its ,ig ,c there is fluid in it, or its ,ig ,c there is a testicle in it. 9o, what do you doN )ransillu$inate. If it transillu$inates, it is hydrocele. If it doesn1t its cancer. d:d for painless enlarge$ent of testicle : cancer, cancer, cancerMM (why they don1t e-en do ,x, just re$o-e! <eminoma +C (,est prognosis!5 huge cells with ly$phocyctic infiltrate. )hey are the counterpart of a wo$an1s dysger$ino$a. )hese will $elt with radiation, )a1e %i!!%e -e!a ) :5 $et to paraortic ly$ph nodes whyN 3c they ca$e fro$ the a,do$en, and that1s where they will go. +C !es!i &%ar !&mor in )i%*E Yo%6 sa !&mor5 tu$or $ar%erN Alpha feto protein 5)a! is 3ors! !es!i &%ar an erE )orio ar inoma = not the sa$e prognosis of a gestationally deri-ed choriocarcin$a in a wo$an you1re dead ;xa$ple:: (E yo $ale with unilateral gyneco$astia and dyspnea. Chest xray re-eals $ultiple nodular $asses in the lung. 9o, gyneco$astia and $ets dC, D what is the pri$ary cancerN testicle choriocarcino$a. 9ource of gyneco$astia: (HC: is %i6e LH@ an* !)ere'ore i! s!im&%a!es proges!erone in !)e ma%e@ 3)i ) in reases *& ! gro3!) an* -reas! !iss&e an* %ea*s !o gyne omas!ia Audio file ST 2enal ( &rine
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;xa$ple:: sa$e scenario, ,ut older $an will lead to $alignant ly$pho$a 9o, older pts get $alignant ly$pho$a (not as pri$ary dC, ,ut fro$ $ets!5 the testes $ets a lot , esp in leu%e$ia and ly$pho$as <&mmary: Gorst " choriocacino$a +C " 9e$ino$a +C in %ids " yol% sac tu$or +C in old " $ets $alignant ly$pho$a Pros!a!e .yperplasia occurs in the periurethral portion of the prostate gland. )his is why you get dri,,ling and urinary retention as the $ost co$$on sy$pto$. *rostate cancer is in the periphery of the prostate gland within the periphery of your finger. 9o, when you press on it, you feel hardness. ;xa$ple @E yo $an with urinary retention and ,ladder is up the u$,ilicus and has dri,,ling what is the $ost li%ely causeN &') prostate cancer whyN 3c for prostate cancer to do that, it has to in-ade all the way through the prostate gland to the urethra:,ladder nec%. )his is prostate .B*;2*8A9IA ,c it is already around the urethra, and this is the +CC, not cancer. Ghat $ale hor$one is totally responsi,le for prostateN ?ihydrotestosterone in e$,ryogenesis, this hor$one fuses the la,ia to for$ a scotru$, extends the clitoris to for$ a penis and $a%es a prostate gland. 9o, prostate .*B and cancer are &') testosterone dep cancers, ,ut dihydrotesterone dep cancers. If you use a E alpha reductase inhi,itor, that will increase testosterone. )his drug will decrease ?I.B?2');9)'9);2'&; +C cancer in $en " prostate cancer *roduces osteo,lastic $ets. Day 4 Audio file S1 Lyn1 Hirs&!ism an* .iri%i>a!ion .irsutis$ " increased hair in nor$al hair ,earing areas KiriliCation " hirstuis$, plus $ale secondary sexual characteristics (Cits, acne, deeper -oice!, clitoro$egaly (pathogno$onic! )estosterone is predo$inantly synthesiCed in the o-ary. +ost testosterone in a wo$an is fro$ the o-ary. ?.;A sulfate is RE7 fro$ adrenals, and is an androgen. )herefore, if a pt has hirstuis$, ha-e to get two tests get a testosterone le-el ha-e to fractionate it ,c so$eti$es the total can ,e nor$al, ,ut the free test can ,e increased, and you get a ?.;A sulfate test. 9o, if testeterone is predo$inantly ele-ated, it is co$ing fro$ the o-ary and if ?.;A is ele-ated, it is co$ing fro$ the adrenals. If it is adrenal orgin, it consists of hydroxylase def (adrogenital syndro$e!, Cushings, etc.. .irstuis$ fro$ the o-aries is a co$$on pheno$enon. 9o, when you are e-aluating hirsutis$, loo% at ?.;A le-els (adrenal origin! and testosterone le-els(o-arian origin!. 'ne of the co$$on causes of o-arian origin are polycystic o-arian syndro$e. Po%y ys!i o1arian syn*rome +CC )irs!&ism , po%y ys!i o1arian syn*rome /or i*iopa!)i 0 (Also due to stro$al hyperplasia stro$a of the o-ary can $a%e testosterone, or tu$ors others o-ary! )his dC is a hypothala$icDpit a,nor$ality where 49. is suppressed and 8. is increased. If you %now what 8. does, it $a%es the pathophys easy. In a wo$an, 8. is responsi,le for synthesis of theca interna (which is around the de-eloping follicle!. ?uring the proliferati-e phase of the cycle, what is predo$inantly ,eing synthesiCed is the 1@ %eto steroids ?.;A and androstenedione. )he androstenedione is con-erted ,y oxydoreductase into testosterone. )hen, the test goes across the $e$,rane of the de-eloping follicle into the granulosa cells, where there is aro$atase. 49. is put in there. )hen, the aro$atase in the granulosa cell con-erts test into estrodiol and this is where the wo$an gets her estradiol (fro$ the aro$atiCation process!. 8. is responsi,le for synthesis of 1@ %eto steroids and testosterone in the o-aries. )his is why we will see hirstuis$ in a wo$an with polycystic o-arian syndro$e (,c increase of 1@ %etosteroids, ?.;A, androstendione, and testosterone!. ',esity is a co$$on correlation with this dC. )his $a%es sense ,c excess adipose " $ore aro$atase, so the sex hor$ones test and androstenedione can ,e con-erted to estrogens in these pts. Androstenedione is aro$atiCed into estrone (a wea% estrogen!. )estosterone is aro$atiCed into estradiol, which is a strong estrogen. 9o, we ha-e a paradox ha-e a wo$an with signs of excess androgens (hirsutis$, acne not signs of -iruliCation!. At the sa$e ti$e, these are ,eing con-erted to estrogens so will ha-e endo$etrial hyperplasia and therefore ha-e a ris% of endo$etrial caricino$a. 9o, there is a co$,o of increased androgens and increased estrogens. It is the increased estrogens that causes suppression of 49. -ia negati-e feed,ac%, while there is a *'9I)IK; feed,ac% on 8.. 9o, ,c increased estrogens, pt is constantly suppressing 49. and constantly increasing 8., so the cycle repeats itself. 9o, you can ,rea% the cycle with an 'C* ,c the progestin in it will ,loc% 8.. 9o, why do they ha-e cystsN 4unctions of 49. is to prepare the follicle. Also, they increase the aro$atase acti-ity. If the 49. is constantly suppressed, the follicle degenerates and lea-es ,ehind a cystic spaces where the follicle used to ,e. 9o, pt has *'8Bcytic o-arian syndro$e related to chronic 49. suppression. Can feel these ,y pel-ic exa$ and seen with ultrasound.
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+ens!r&a% *ys'&n !ion
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Dysmenorr)ea " painful $enses (pri$ary and secondary +CC pri$ary is too $uch *L4 a *L that increases contraction of the uterine $usculature. )he +C secondary cause is endo$etriosis!. )here are also pro,le$s with dysfunctional uterine ,leeding this is &') a ,leeding a,nor$ality related to a ,leeding:organic cause. 9o, in other words, it is not ,leeding fro$ an endo$etrial polyp, its not ,leeding fro$ a cancer5 this type of ,leeding is a hor$one i$,alance that causes a,nor$ality in ,leeding. +CC a,nor$al ,leeding in young lady fro$ $enarche to (6 yrs of age " ano-ulatory ,leeding. 9o, if a young lady is ,leeding, that is the usual cause. Ghat is occurringN )here is a persistent estrogen sti$ulation that is occurring on the $ucosa, and not enough progesterone sti$ulation. 9o, they de-elop a lil hyperplasia, there is a ,uild up of $ucosa as the $onth progresses, and then e-entually the stro$a sloughs off and leads to significant ,leeding. 9o, its $ainly an estrogen pri$ed uterus, without the effect of progesterone and they do not o-ulate related to this. )his is the +CC. Amenorr)oea *ri$ary a$enorrhea and secondary a$enorrhea Ghen you thin% a$enorrhea, it can ,e a pro, with the hypothala$us:pituitary. In other words, is the hypothala$us putting out Ln2. or notN Is the pit putting out 49.:8. or notN 9o, is it a hypothala$icDpit a,nor$alityN Is it an o-arian pro,N +ay,e the o-ary is not $a%ing enough estrogen. Is its an end organ pro,N )his is anato$ically related $ay,e she doesn1t ha-e a -agina D Ro6i!ans6y?8&s!er?Ha&ser syn*rome, or $ay,e she has an i$perforate hy$en she1s ,een ha-ing periods all along, and has ,lood ,uilt up ,ehind it, or cer-ical stenosis (?;9 exposure! these are all anato$ical reasons for the a$enorrhea. As)erman#s syn*rome secondary a$enorrhea, wo$an has repeated dilatation and curotoshes(N!, where the stratu$ ,asalis is scraped away5 ha-e to lea-e so$ething ,ehind fro$ which you can proliferate endo$etrial $ucosa if you scrape all the way down the the $uscle, will not ,e a,le to $enstruate again, and will scar e-erything off, leading to an infertile wo$an. 9o, a$enorrhea is pri$ary or secondary : hypothala$icDpit pro,le$, o-arian pro,, or end organ pro,. 49. and 8. le-els help in distinguishing those 0. If pt has hypothala$icDpit pro,, what would 49. and 8. ,eN 8ow. If had a pri$ary o-arian pro,le$, what would they ,eN .igh. If you ha-e an end organ defect, what would 49. and 8. le-els ,eN &or$al. Ghat is the first step in the wor%up of any case of a$enorrheaN *regnancy test. T&rner#s syn*rome: *ri$ary cause of a$enorrhea, we,,ed nec%, fe$ales +ajority are H', therefore do not ha-e a ,arr ,ody. ?efects in ly$phatics. Can $a%e dx at ,irth -ia *; see swelling of hand and feet (ly$phede$a! " turners Ge,,ed nec% is due to ly$phatic a,nor$alities get cystic hygro$as, which are dilated ly$phatics in the nec% area and fill with ly$phatic fluid and stretch the s%in ,c they stretch the s%in, loo%s li%e we,,ing. .a-e preductal coarctations. ?o not ha-e +2. so$e cases are $osaics H'HH and there is a re$ote possi,ility that they $ay ,e fertile. )here are also H'HB1s that are $osaic1s. ha-e $enopause ,> $enarche. All of there follicles are gone ,y the age of (, and this is the strea% o-aries (gonad!. )herefore, they are suscepti,le to dysger$ino$as (se$ino$as are in $ales are analogous!. U!erine Disor*ers A*enomyosis glands and stro$a within the $yo$etriu$ -ery co$$on cause of dys$enorrheal, dyspyrunia, $enorragiah, hysterecto$y5 does &') predispose to cancer. En*ome!riosis functioning glands and stro$a outside the uterus ($yo$etriu$ is I&9I?;!5 +C location " o-ary, causes ,leeding in the o-ary see chocolate cyst (endo$etro$a1s D not cancer, just endo$etriosis of the o-ary!, tu,e, in pouch of ?ouglas ;xa$ple: good #uestion to as% if pt has endo$etriosis: I?oes it hurt when you defecate N Bes. .ow a,out when your period goes awayNJ &o, it goes away this is endo$etriosis ,c there is ,leeding in the rectal pouch of the pouch of ?ouglas (there is endo$etreosis there!. )he rectu$ is filled with stools, and streches the pouch of ?ouglas, leading to pain. 9o, pain on defecation during the period leads to endo$etriosis. En*ome!ria% Hyperp%asia 4ro$ unopposed estrogen. Always dangerous to ha-e unopposed estrogen, $eaning no progesterone effect, ,c then pt runs ris% for endo$etrial cancer. +CC endo$etrial cancer " endo$etrial .*B due to unopposed estrogen *ouch of ?ouglas can collect seeding fro$ o-arian cancer, pus fro$ *I?, unclotted ,lood fro$ ruptured ectopic pregnancy (low part of a wo$an1s pel-is includes: -agina, cer-ical os, uterus, ,ladder! En*ome!ria% an er: ;arly -s late $enarche early is worse ,c longer ti$e for estrogen to circulate ;arly -s 8ate $enopause late is worse ,c $ore estrogen exposure ',ese -s not o,ese o,ese ,c the estrogen factor in adipose ($ore aro$atase!, therefore, o,ese wo$an are $ore suscepti,le to cancers related to estrogen D ,reast cancer, endo$etrial cancer, o-arian cancer
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)ype II dia,etics are at increased ris% ,c T67 of type II pts are o,ese (so, the o,esity is the cause of increased ris% of endo$etrial cancer!. Can er an* age -ra 6e!s >E " cer-ical EE " endo$etrial AE " o-arian EE yo, post$enopausal is when you usually see endo$etrial carcino$a. Any wo$an that has ,een in $enopause for o-er 1 yr, and then has re,leeding has endo$etrial cancer until pro-en otherwise. 1st step in $anage$entN ;ndo$etrial 3x Leiomyoma +C ,R tu$or in a wo$an 8eio$yosarco$a $itosis pro,5 +C sarco$a of the uterus5 ,ig ,ul%y tu$ors (as are all sarco$as!5 leio$yo$a is &') a precursor for leio$yosarco$a. ;xa$ple: young wo$an sudden onset of se-ere lower a,do$inal pain m&s! *o a pregnan y /%oo6 a! -e!a =HC: %e1e%0 !es! !o r&%e o&! e !opi pregnan y. O1arian masses
9urface deri-ed deri-ed fro$ the surface of the o-ary Ler$ cell types D dysger$ino$as ($en ha-e these, too! 9ex chord stro$al tu$ors $a%e estrogens (ie granulosa cell tu$ors D therefore can ha-e hyperestrinis$ which leads to ,leeding and endo carcino$as!, so$e $a%e androgens (sertoli leydig cell tu$ors of the o-ary assoc with -iruliCation and hirstuis$!. ($ales just ha-e ger$ cell tu$ors! 9o%%i &%ar ys! +CC o' o1arian mass in a yo&ng 3oman , 'o%%i &%ar ys! 4ollicle that ruptured, not neoplastic, accu$ulates fluid and leads to peritonitis. It is ,ad if its on the right side ,c it can ,e either ruptured follicular cyst, appedicitus, ectopic pregnancy (ruptured!, *I?5 loo% at with ultrasound <nder 0E yo, $ost o-arian $asses are ,R '-er 0E yo, $ost o-arian $asses ha-e a greater potential of ,eing $alignant. <&r'a e* *eri1e* (o-erall +C! +C surfaced deri-ed " serous cystadeno$a (3R!5 serous cystadenocarcino$a ($alignant! (these are the +C o-erall ,R and $alignant o-arian tu$ors! )hese are also the +C that are ,ilateral, and the cystadenocarcino$a has pso$$o$a ,odies (,luish colored due to apoptosis, destruction of the tu$or cell and replace$ent with dystrophic calcification!. Also seen in papillary carcino$a of the thyroid and in $eningio$a1s ;xa$ple:: AE yo, ,ilateral o-arian enlarge$ent (re$e$ they tend to arise at this age! Any wo$an that is o-er EE and has palpa,le o-aries is cancer until pro-en otherwise ,c a post$enopausal wo$an should ,e ha-e o-aries that are atrophying. ;xa$ple:: A( yo wo$an with o-arian $ass on the right already %now its ,ad ,c shouldn1t ha-e a palpa,le o-ary. Cys!i !era!oma )ooth, se,aceous glands, cartilage, s%in, thyroid,, +C o-erall ger$ cell tu$or, usually 3R If it is $a%ing thyroid, it is called stru$a o-ary <ex )or* s!roma% !&mors +C " fi,ro$as (3R! +eigs syndro$e: o-arian fi,ro$a, ascites, and right side pleural effusion goes away when you ta%e the o-ary out. Lranulosa cell tu$or of o-ary: low grade $alignant tu$or5 what does the granulosa cell nor$ally doN It aro$atiCes androgens and estrogens, so a granulosa cell tu$or is $ore than li%ely an estrogen producing tu$or. 9ignet ring cells is this a pri$ary cancer, or $ets fro$ another siteN 9ite is fro$ sto$ach called a %ru%en,urg tu$or5 !)ere is NO primary o1arian an er !)a! )as signe! ring e%%s. :es!a!iona% Disor*ers P%a en!a Chorionic -illus outside layer " syncytiotropho,last, clear cells under the outside layer " cytotropho,last5 which is $a%ing hor$onesN 9yncytiotropho,last. Ghat hor$ones is it $a%ingN 3DhcL and .u$an *lacental 8actogen (.*8! growth hor$one of pregnancy. stro$a. Kessels coalesce into u$,ilical -ein, which has the highest o( content. Neop%asms o' )orioni 1i%%&s: .as $yxo$atous
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Hy*a!i*i'orm mo%e can ,e co$plete (>A, HH, ,oth H c1so$es co$e fro$ father called androgenesis! or partial (triploid, AR c1so$es, can ha-e a fetus present! )he co$plete $oles ha-e a greater propensity to $o-ing on to choriocarcino$a. Ca&ses o' )orio ar inoma: 1E7 of choriocaricno$as are fro$ preexisting hyadifor$ $ole (E7 fro$ spontaneous a,ortion (E7 fro$ nor$al pregnancy .yatidifor$ $oles are ,R tu$ors of the chorionic -illus5 choriocarcino$as are a $alignancy of the tropho,lastic tissue (do not see chorionic -illi!. 8o-es to go to the lungs and responds well to che$otherapy (can e-en go away in the presence of $ets! (reas! *icture a sche$atic with nipple, lactiferous duct, $ajor ducts, ter$inal lo,ules (where $il% is $ade!, and the stro$a &ipple " *agets dC of the ,reast 8actiferous duct " Intraductal papillo$a (+CC of ,loody nipple discharge of wo$an under E6! ,R papillary tu$or, if you press on it, ,lood will co$e out of the areola +ajor ducts " where $ost of the cancers arise fro$ in-asi-e ductal cancers, $edullary carcino$as, $ucinous carcino$as )er$inal lo,ules (where $il% is $ade! +C tu$or " lo,ular carnico$a, is fa$ous ,e 3I8A);2A8 (so, lo,ular tu$ors are to the ,reast as serous tu$ors are to the o-ary in ter$s of their ,ilatterallity!5 mammograp)y *oesn#! pi &p %o-&%ar an ers. +CC o' mass in -reas! o' 3oman &n*er 4F , 'i-ro ys!i )ange
+CC o' mass in -reas! o' 3oman o1er 4F , an er: infiltrating ductal carcino$a (not intraductal this $eans that we are not pic%ing up the cancer early enough ,y $a$$ography and pic%ing up in the intraductal phase, and our techni#ues are insensiti-e so we are $issing the ductal stage and we are pic%ing up the cancer when it has in-aded to pic% up early, need to get at E$$ or less!. 9o, if they are intraductal, has a good prognosis ;xa$ple: 0E yo wo$an with $o-a,le $ass in ,reast that gets ,igger as the cycle progresses " fi,roadeno$a )hese are the $ost co$$ons in ter$s of age and location 9lide: 'i-ro ys!i )ange cysts, lu$py ,u$py in ,reast, $ore painful as the cycle progresses ,c they are hor$one sensiti-e ;xa$ple:: ductal hyperplasia cannot see5 precursor lesion for cancer that are estrogen sensiti-e epithelial cells in the ducts (just li%e the endo$etrial glands are estrogen sensiti-e, the glands lining the ducts are estrogen sensiti-e!. < %erosing a*enosis in ter$inal lo,ules, ,R part of fi,rocystic change (see cysts! 9i-roa*enoma +C !&mor !)a! mo1es aro&n* in !)e -reas! in a 3oman &n*er $4 , 'i-roa*enoma is the neoplastic co$ponents the glands or the stro$aN It1s the stro$a as it grows, it co$presses the ductste$s, so they ha-e slit li%e spaces5 -ery co$$on. ;-en if you %now it1s a fi,roadeno$a, still get a ,x (reas! Can er 9lide: .ow do you %now its ,reast cancerN nipple is hard as a roc% when ,reast cancers in-ade the stro$a, they elicit a fi,ro,lastic and elastics tissue response, $a%ing it hard this is good ,c it $a%es it palpa,le. T)is is 3)y a 3oman o1er 4F@ !)a! )as a pain%ess pa%pa-%e mass@ i!s an er. I' i!s pain'&% an* &n*er 4F@ i!s rare%y an er /'a! ne rosis@ 'i-ro ys!i )ange0. 9o, the $agic word is painless.
'uter #uadrants of the ,reast are the +C sites ,c this is where $ost of the ,reast tissue is. )herefore, this would ,e the +C site for ,reast cancer. )he (nd +C site is around the areola. 9lide: nipple ,eing suc%ed in, whitish $ass, stellate (classic for in-asi-e cancer!5 on $a$$ography, see density with spicules co$ing out and has calcified. )his is highly predicti-e for cancer. Ghat is the first step in $anage$ent of a palpa,le $assN 4&A ,c can $a%e a dx and tell if its solid or cystic (this is also the first step in $anage$ent of cold nodule in thyroid, not ultrasound!. 9lide: intraductal cancer netli%e arrange$ent, called co$edocarcino$a, jun% that co$es out (li%e caseous necrosis!5 has er,D( oncogene (aggressi-e cancers!. 9lide: in-asi-e cancer, see tu$or cells in-ading stro$a5 see Indian filing sign of in-asi-e lo,ular cancer5 seen $ore often in infiltrating ductal carcino$a 9lide: ecCe$atous dC around the nipple " pagets dC of the ,reast rash around nipple cancer of the duct that has spread to the s%in 9lide: infla$$atory carcino$a worst, red, di$pled s%in ,c the ly$phatics are plugged with cancer underneath and the ly$phatic fluid lea%ed out, ,ut the liga$ents are still attached, ,ut increasing the fluid in the interstiu$, and as it expands out, it di$ples p1doeu orange so, infla$$atory carcino$a loo%s li%e that ,c its ly$phatic filled with tu$or, and is the worst of the worst.
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9lide: lo,ular carcino$a +C cancer of the ter$inal cancer (at the end of the ducts!5 it is fa$ous for ,ilaterality
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9lide: ly$phede$a is a wo$an that is postradical $asectecto$y5 when you are doing a $odified radical $astecto$y, what are you re$o-ingN )he entire ,reast including a nipple, lea-ing ,ehind pec $ajor, axillary resection, and ta%ing pec $inor. +C co$plication " winged scapula (,c cut the long thoracic ner-e! T)e %&mpe !omy re$o-es the underlying tu$or with a good ,order of nor$al tissue around it, ta%e a few nodes fro$ the axilla (,c ha-e to use for staging ,c they go to lower axillary first!, and then you do radiation of the ,reast (good for ,reast conser-ation sa$e prognosis as $astecto$y! ;xa$ple:: ;2AD*2A " estrogen receptor:progesterone receptor assay what does it $eanN 2elationship ,etwn estrogen and its receptor synthesis. 9o, if you are in a reproducti-e period of your life when estrogen is a,undant, the receptors will ,e downregulated. )his is why in wo$en that are young, in the reproducti-e period of their life, ha-e ,reast cancer and are ;2*2A negati-e ,c this is what we would expect ,c estrogen would down regulate receptor synthesis. Ghereas, if you are post$enopausal, it leads to up regulation of the receptors and those wo$en are ;2*2A positi-e. 3ut what does this $eanN It $eans that the tu$or is responding to estrogen and need to ta%e away that estrogen affect ,c it is feeding the tu$or. .ow can you ta%e it awayN )a$oxifen this is wea% estrogen, so it hoo%s into the receptor of ,reast tu$ors, so if there is any left ,ehind, nor$al estrogen in a wo$an can1t get into it and won1t ,e a,le to feed the tu$or. 9o, it1s a ,loc%er of the receptor. Co$plicationsN +enopausal type sy$pto$s5 also, it is an estrogen so you ha-e the ris% of endo$etrial cancer. A ,enefit in the post$enopausal state with an ;2A *2A pos wo$an is that it does pre-ent osteoporosis. 9o, cannot gi-e estrogen to a wo$an that is ;2A *2A pos, ,ut is a candidate for ta$ox and will prolong recurrence. Audio file ?ayE S( Lyn( (3ut it is ;ndocrine! C) "": En*o rine Disor*ers Primary 1s <e on*ary 1s Ter!iary .ashi$otos " destruction of the thyroid gland " *2I+A2B hypothyroidis$ (the gland screws up the hor$one! .ypopituitaris$ and hypothyroidis$ " 9;C'&?A2B hypothyroidis$ (no )9. to sti$ulate! .ypothala$ic ?C " 9arcoidosis destroying )2.: );2)IA2B (no )2.! ;xa$ple: adeno$a on parathyroid producing *). leading to hypercalce$ia " pri$ary hyperparathyroidis$ ;xa$ple: ha-e hypocalce$ia:-it ? def, and as%ed the parathyroid to undergo hyperplasia, that is called 9;C'&?A2B hyperparathyroidis$ ;xa$ple: what if after a long ti$e *). %eeps ,eing $ade " tertiary hyperparathryroidis$ (rare! O1era !i1i!y 1s &n*era !i1i!y o' g%an*s <!im&%a!ion !es!: if pt has underacti-e gland, would use sti$ulation test to see if the gland is wor%ing. <&pression !es!: if pt has o-eracti-e gland, would use suppression test to see if gland will stop wor%ing. +ost of the ti$e, things that cause o-eracti-ity, we CA&&') suppress the$. )here are ( exceptions where we suppress the$, and they deal with o-eracti-ity in the pituitary gland 1!pro%a !inoma can ,e suppressed ,c it can pre-ent the tu$or fro$ $a%ing prolactin5 ,ro$ocriptine suppresses it (dopa$ine analog nor$ally, wo$en do not ha-e galactorrhea ,c they are releasing dopa$ine, which is inhi,iting prolactin (therefore dopa$ine is an inhi,itory su,stance ,ro$ocriptine is also used for treating par%inson1s ,c ,ro$ocriptine is a dopa$ine analog (which is what is $issing in par%insons dC! (! Pi!&i!ary C&s)ings: ,R tu$or in the pitiuitary that is $a%ing AC). you CA& suppress it with a high dose of dexa$ethasone. )hese are the only two exceptions for a tu$or $a%ing too $uch stuff. ()here is no way to suppress a parathyroid adeno$a $a%ing *)., or an adrenal ade$ona $a%ing cortisol, or a an adrenal tu$or fro$ synthesiCing aldosterone these are A<)'&'+'<9! ;xa$ple: pt with hypocortisolis$ lets do an AC). sti$ulation test will hang up an IK drip and put in so$e AC).5 collecting urine for 1@ hydroxycorticoids ($eta,olic end product of cortisol! and nothing happens so what is the hypocortisol due toN Addison dC gland was destroyed therefore, e-en if you %eep sti$ulating it, you will not ,e $a%ing cortisol. ;xa$ple: 8et1s say after a few days you see in an increase in 1@ hydroxycorticoids, then what is the cause of hypocortisolis$N .ypopituitaris$ in other words, it1s atrophic ,c its not ,eing sti$ulated ,y AC)., ,ut when you ga-e it AC). o-er a period of ti$e, it was a,le to regain its function. 9o, with that single test, you are a,le to find cause of hypocortisalis$. Can also loo% at hor$onal le-els ie Addison1s causing hypocortisalis$, what would AC). ,eN .igh5 if you ha-e hypopituitaris$ causing hypocortisalis$, what would AC). ,eN 8ow
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Hypopi!&i!arism
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+CC in a*&%!s , non'&n !ioning pi!&i!ary a*enoma (within sella turcica in the sphenoid ,one, hence surgery is transphenoidal surgery, where the expanded sella turcica is!. *it Adeno$a usually nonfunctioning and destroys the nor$al pituitary o-er ti$e as it grows, leading to hypopituitaris$. <)ee)ans /pos!par!&m ne rosis0 ;xa$ple:: ha-e a pregnant wo$an, has a,ruptio placenta and goes in to hypo-ole$ic shoc%, ,ut get out5 doing fine and ,reast feading ,a,y at ho$e, ,ut suddently stops ,reast $il% production dxN *ostpartu$ necrosis therefore she has infarcted her pituitary (coagulation necrosis!, and this is residual pitiuatary /T)is is no! %i;&e'a !i1e ne rosis - !)e pi!&i!ary is no! par! o' !)e -rain0. +ech is ische$ia and coagulation necrosis. *regnant wo$an ha-e a pituitary gland two ti$es the nor$al siCe. *rolactin is ,eing synthesiCed ,ut a pregnant wo$an does not ha-e galatorrhea ,c the estrogen and progesterone inhi,it release. 9o, the $o$ent you gi-e ,irth, the inhi,itory effect is released and start ha-ing galactorrhea. )his is the (nd +CC hypopit in adult. +C in 6i*s , raniop)arnygioma 2ath%e1s pouch origin this is part of the e$,ryological de-elop$ent of the pituitary gland pieces of it re$ain and can ,eco$e neoplastically transfor$ed into a craniopharygio$a. Its not a $alignant tu$or, ,ut a ,R tu$or in a ,ad place. It is +C supraDsellar (a,o-e the sella! and it goes down and destroys the pituitary, ,ut li%es to go forward and ,u$ps into optic chias$, leading to -i!empora% )emianopsia, leading to -isual field defect. ;xa$ple:: child with headaches and -isual field defect do a sche$atic of it and will as% what the cause is craniopharyngio$a tu$or of rath%e1s pouch origin. :ro3!) Hormone Ghen you ha-e a tu$or that is expanding in the sella turcica, different releasing factors (hor$ones! decrease in a certain succession. )he first thing that is destroyed is gonadotropin. 9o, in a wo$an, what would happenN 9he would ha-e a$enorrhea (secondary a$enorrhea!. Ghat if I were a $an (what is the analogous condition!N I$potence5 i$potence is to a $ale as a$enorrhea is to a fe$ale. I$potence " failure to sustain an erection during atte$pted intercourse. )he next thing that goes is growth hor$one (which has ( functions: 1! in reases aa &p!a6e and (! in1o%1e* in g%& oneogenesis (hor$one that produces ,one and tissue growth is insulin li%e growth factorD1, which is present in the li-er a%a so$ato$edins5 so, L. release will sti$ulate the li-er to release IL4D1 to cause growth of ,ones linearly and soft tissue!5 an adult with the loss of growth hor$one will not get s$aller, ,ut will ha-e the effects of lac% of growth hor$one: will start to lose $uscle $ass and will ha-e fasting hypoglyce$ia ,c L. is nor$ally gluconeogenic. 9o, its not there and not contri,uting is func to glucogngeogenesis, leading to hypoglyce$ia. Ghat would you see in a childN *ituitary ?warfis$. Gould see )ypop%asia (inco$plete de-elop$ent of so$ething!. 9o, pit dwarfisi$ is an inco$pletely de-eloped child, ,ut e-erything loo%s nor$al. Ghat is the ,est sti$ulation test to see if you are L. or IL4D1 defecientN 9leep. Bou grow when you sleep exactly at E a$ (that1s when L. co$es out!. 9o, the ,est test is sleeping, then chec%ing ,lood at E a$ (if it isn1t your def!.Ghy is histidine and arginine deficientN )hey are essential to nor$al growth of a child ,c they sti$ulate growth hor$one. )hese are ,asic aa1s. )his is why wt lifters ,uy arg:his supple$ents. 9o, ,est test is sleep, followed ,y $easuring arg and his le-els. )he third hor$one to go is )9., which leads to hypothyroidis$ (therefore low )9. and low )> cold intolerance, ,rittle hair, fatigue, delayed reflexes!. )he next thing that goes is AC). , leading to hypocortisalis$. Gill ,e fatigue will a low cortisol le-el. Gill also lead to hypoglyce$ia ,c cortisol is gluconeogenic. )hat last thing to lose is prolactin. Dia-e!es Insipi*&s Central (lac%ing A?.! -s &ephrogenic (%idney doesn1t respond to A?.! Central: one of the co$$on causes is car accident, leading to head trau$a. )he head is shifted and stal% is se-ered. 'ne of the first things that goes is A?. ,c it is $ade in the supraopitic para-entricular nucleus of the hypothala$us. In the sa$e ner-e it is $ade in, it goes down the stal% and is stored in the *'9);2I'2 pituitary. 9o, if you se-er that stal%, you se-er the connection and leads to A?. def. Also def in all the releasing factors that are $ade in the hypothala$us that sti$ulate the pituitary, leading to hypopituitaris$ (e-entually ,ut initially will ha-e s:s of ?I " polyurea and thrist!. &ephrogenic: ha-e A?., ,ut doesn1t wor% on the collecting tu,ule to $a%e it per$ea,le to free water. 'ther polyurea1s (?+ $ech " os$otic diuresis, polydipisia $ech " drin% too $uch water (psychological pro,le$!, hypercalce$ia leads to polyurea!. Constantly diluting, ,ut will ne-er ,e a,le to concentrate urine5 9IA?. is the exact opposite, where A?. is always there, and will constantly concentrating, and will not ,e a,le to dilute. In ?I, constantly diluting urine, losing free water, and will ne-er ,e a,le to concentrate the urine. 9o, you are losing all the water, and seru$ &a will go up, correlating with an increased plas$a os$olality (,c $ost of plas$a os$olality is &a!. To !es!: res!ri ! 3a!er in a nor$al person, if you restrict water, the plas$a os$olality will go up to (R( (the upper li$it of nor$al for the os$olality!, @E6 urine os$olality D what does that $eanN *t is concentrating the urine. 9o, if you are depri-ing a nor$al pt of water, it should concentrate the urine5 water is ,eing retained get into the ;C4 to get the seru$ &a into nor$al range. ;xa$ple: pt restricted water and ha-e a 01R and 01( plas$a os$olality (which is ele-ated!. 9o, they ha-e hypernatre$ia. If you loo% at urine os$olality, it is 116 and RT. 9o you %now that ha-e ?I. 9o, how do you distinguish central fro$ nephrogenicN Li-e the$ A?. (a%a -asopressin!. 9o, you gi-e it to the$ and see what happens to urine os$olality. I' i! in reases grea!er !)a! 4FP 'rom !)e -ase%ine: !)en i!#s en!ra%. I! i!s %ess !)an 4FP i!#s nep)rogeni . 9o, ga-e A?. to first guy and it urine os$olality change to EE6, indicating that he has central ?I. 4or the second pt, A?. was gi-en, ,ut only a lil increase in urine os$alality, indicated nephrogenic ?I.
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A romega%y
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Ghat is cheapest way for screening for acro$egalyN As% for an old pic of the pt 16 years ago. Ligantis$ in %id ,c epiphyses ha-en1t fused, therefore an excess in L. and IL4D1 lead to an increase in linear growth. 3ad dC ,c can die fro$ cardio$yopathy. 9o, they ha-e excess L. and excess IL4D1. 9o, what if you1re an adult with acro$egalyN Gill not get taller ,c the epiphyses ha-e fused, ,ut ,ones will grow wider. 'ne of the ,ones in the head that does that is the frontal ,ones, so they stic% out. 9o, get a gorilla li%e increase in the frontal lo,e (,c it increases siCe of the sinuses!, so the hat siCe will increase. Bour hands get ,igger, feet get ,igger, and e-ery organ in the ,ody gets ,igger. Also, you produce a cardio$yopathy, which leads to death. :a%a !orr)ea7Pro%a !inoma +en do not get galactorrhea ,c we don1t ha-e enough ter$inal lo,ules to $a%e the $il%. 9o, if a $ale has a prolactino$a, do not expect hi$ to ha-e galactorrhea. )his has $any causes. Ghen wo$an co$es in with it, $a%e sure you as% what drug they are on D ,c there are $any drugs that can sti$ulate prolactin synthesis. ;xa$ple:: 'C*1s, hydralaCine, Ca channel ,loc%ers, psychotropic drugs. *ri$ary hypothyroidis$ can also ,e a cause, therefore get a )9. le-el. GhyN 3c if you ha-e hashi$oto1s, not only is )9. increased, ,ut you also ha-e increased )2.. )2. is used as a sti$ulation test for prolactin. 9o, you $ust rule out hypothyroidis$ in a wo$an with galactorrhea (so in this case, there is nothing wrong with the pituitary, ,ut the thyroid, leading to galactorrhea!. <o@ m&s! r7o )ypo!)yroi*ism. If all this is ruled out and pt has high prolactin le-el, dx is prolactino$a (any ti$e there is a prolactin le-el o-er (66 it is always a prolactino$a!. Ghen pts ha-e prolactino$a, why do they de-elop a$enorrheaN 3c prolactin has a negati-e feed,ac% on Ln2.. 9o, this is a cheap ,irth control pill for the first three $onths after pregnancy ,c $o$ is ,reast feeding, and the high prolactin le-els are feeding ,ac% on the pituitary on Ln2.. T)yroi* )hyroid studies do &') ha-e to %now resin )0 upta%e and )> indexes5 0 things need to %now: )>, )9., I 101 upta%e If )9. is nor$al, the thyroid is nor$al. If )9. is decreased, pt has hyperthyroidis$ or hypopituitaris$. If )9. is increased, ha-e high pri$ary hypothyroidis$. )hyroid ,inding glo,ulin is the ,inding protein for thyroid hor$one Ghat is the ,inding protein for^ cortisolN )ranscortin5 calciu$N Al,u$in5 4eN )ransferrin5 CuN Ceruloplas$in5 what 7 of ,inding sites occupiedN 067!. 0 of R ,inding sites on )3L are occupied ,y thyroid hor$one. 4ree )> le-el. Ghen we $easure total )> le-el, there is free )> and ,ound )>. )he free )> is the part that is $eta,olically acti-e and is con-erted to )0. )his part is doing all the wor% (that part that is ,ound is not!. Ghat happens if you are on an 'C* with an increase of estrogenN )3L and transcortin increase. 9o, increased syn )3L, and is i$$ediately 1:0 occupied (R sites on )3L, and 1:0 occupied ,y )>, so that is 0 )>1s!. 3c e-erything is in e#uili,riu$, the thyroid senses that it lost 0 )>1s and replaces the$ i$$ediatetly. 9o, has the 42;; )> alteredN &o. 9o what is the )9.N &or$al. Ghat is the )>N Increased (,ut the free hor$one le-el and )9. not altered!. 9o, an increase )> with a nor$al )9. $eans the pt is on estrogens. )his is true for any wo$an on estrogen or any pregnant wo$en. 9o, the total )> is ele-ated ,c increased )3L (not ,e increased free hor$one le-el! and it auto$atically has 0 sites occupied ,y )>!. 9a$e is true for cortisol if pt is pregnant or on 'C*, cortisol is ele-ated ,ut do not ha-e signs of cushings. GhyN 3c transcortin is increased ,c estrogen increasing the synthesis of it, so there is $ore cortisol ,ound to it, ,ut the free cortisol le-els are still nor$al. ;xa$ple:: if foot,all player:wt lifter, assu$e pt is on ana,olics. )hey wor% the opposite. Ana,olics ,rea% down proteins that you nor$ally would use for other things to ,uild up and put the$ into $uscle. )he proteins it li%es to go after is ,inding proteins. 9o, when they are on ana,olics, thyroid ,inding glo,ulin is decreased ,c the aa1s that you would ha-e used to $a%e the ,inding protein are instead utiliCed to $a%e $uscles stronger. 9o, they won1t wor% if you are not wor%ing aa supple$ents. ;xa$ple: pt on ana,olics, so less )3L ,eing synthesiCe ,c proteins ,eing used elsewhere ($uscles!. )he sa$e nu$,er of site are occupied, ,ut $issing )3L. 9o, free )> is the sa$e, ,ut $issing )3L. 9o, if a person has a low )> with a )9., they are on ana,olic steroids. If a wo$an has a high )> and a nor$al )9., what is she onN ;strogen. If a person has high )> and low )9., what do they ha-eN .yperthyroidis$. If pt has low )> and increased )9., what do they ha-eN Primary )ypo!)yroi*ism. ?o not need resin )0 upta%e to $a%e these dx1s. I 1$1 &p!a6e is a radioacti-e test (re$e$,er that thyroid hor$one is tyrosine with iodine on it!. (Ghat are other things in-ol-ed with tyrosineN +elanin, tyrosine tyrosinase, dopa$ine goes into the golgi apparatus and ,eco$es $elanin, phenylalanine, dopa$ine, dopa, &;, epi (catechola$ines!, if you put iodides on tyrosine you ha-e thyroid hor$one!. 9o, with hyperthyroidis$ (ie gra-es!, thyroid gland will ,e $a%ing $ore thyroid hor$one. Gould we need $ore iodide to do thisN Bes. 9o, if you ga-e a pt radioacti-e iodide, will there ,e increased upta%e of radioacti-e iodide in that o-eracti-e glandN Bes. 9o, will ha-e increased I101 upta%e. Ghat if I were ta%ing excess thyroid hor$one to lose weight what would that do to $y )9. le-elN 9uppress it. 9o, when that pt is ta%ing too $uch hor$one, the gland has atrophied. 9o, if you ha-e a radioacti-e I 101, would there ,e an increased
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upta%eN &o ,c is has atrophied. 9o, radioacti-e I 101 is the $ain way to distinguish whether a person has true e-idence of hyperthyroidis$ (L8A&? is $a%ing too $uch thyroid hor$one! -s so$eone that is surreptitiously:purposely:un%nowingly ta%ing too $uch thyroid hor$one and producing hyperthyroidis$. I 101 is the ,est test to distinguish these two types of hyperthyroidis$. 9o, if its increased, pt has gra-es (gland is using it!5 if its decreased, pt is ta%ing thyroid hor$one. ;xa$ple:: pt fro$ wt loss clinic they are ta%ing thyroid hor$one, so they will lose wt at the expense of hyperthyroidis$ 9lide: $idline cyst dxN T)yrog%ossa% ys!. 2e$e$,er that the thyroid gland was originally at the ,ase of the tongue and $igrates down the $idline to the current location. 9lide: cyst in anolateral portion of nec% dxN 3ranchiocleft cyst (%now all ,ranchiocleft deri-ati-es esp the one in the head area!. T)yroi*i!is (infla$$ation of the thyroid! )he only i$p one is hashi$oto1s :ra1e#s D> exophal$os Uni;&e !o :ra1e#s D> excess LAL1s deposited in or,ital fat, and pushing the eye out (pathono$ognic for gra-es!5 apathetic gra-es '8? people with gra-es dC ha-e heart pro, with atrial fi,. )hey get heart $anifestations. 9o, any pt with atrial fi,, $ust get a )9. le-el to rule out gra-es. s7s )yper!)yroi*ism: heat intoleranc, sinus tachy, atrial fi,, ,ris% reflexes, diarrhea, systolic .)&, hypercalce$ia, increased ,one turno-er (all sy$pto$s are adrenergic they are all catechola$ine things whyN )> increases the synthesis of ,eta receptors (catechola$ines are cousins of )hyroid hor$one and they wor% together. All the sy$pto$s are adrenergic. Ghat is the I&I)IA8 2x of gra-esN 3eta ,loc%ers (,loc%ing adrenergic response, then gi-e *)< to stop the gland fro$ $a%ing it can stop all the sy$pto$s with ,eta ,loc%er except one sweating! so, thyroid studies on gra-es pt: )> is high, )9. is low, I 101 is .IL. Audio 4ile ?ayE S0 ;ndoc In )yper!)yroi*ism@ want to always loo% at the face and will see perior,ital puffiness, which is seen a lot ,c of LAL1s (also in -ocal cords, leading to hoarseness, ti,ial area leading to nonpitting ede$a! +i!ra% .a%1e Pro%apse also has an increase in LALs ,c der$atan sulfate is responsi,le for causing excess and redudency of the -al-e!. Also seen in .ashi$otos. Lra-es is due to IgL A, against )9. receptor, causing it to synthesiCe too $uch. Ghat type of .*B rxn is thisN )ype II (A, against the receptor!5 +L is also type II .*B (ha-e A, against receptor which is destroying the receptor!. In hashi$oto1s thyroiditis, they also ha-e an IgL against the receptor, except instead of acti-ating the gland, it inhi,its it. 9o, in .ashi$oto1s and Lra-es, these are ,oth autoi$$une dC1s ,ut at opposite ends of the spectru$. 'ne as sti$ulatory IgL while the other has an inhi,i,itory one. 9o, an o-erlying sy$pto$ that they ,oth ha-e is preti,ial $yxede$a and LAL deposition. Ghere do you see a decrease in LAL1s (ie $eta,olis$ of LAL1s!N 8ysoso$al storage dCs .urlers, .unters need lysoso$al enCy$es for ,rea%ing down der$atan sulfate, etc s7s )ypo!)yroi*ism = wea%ness (+C! ,c all pts with hypothyroidis$ ha-e proxi$al $uscle $yopathy, so they cannot get up out of chairs , seru$ CK1s are ele-ated. Also ha-e ,rittle hair, course s%in, slow $entation, perior,ital puffiness, delayed reflex, diastolic .)& 9lide: ,x of thyroid gland in .ashi$otos1s no follicle, ,ut do see ger$inal follicle ,c there is autoi$$une destruction of the gland. )here are cytotoxic ) cells that destroying it, and are synthesiCing A,1s (IgL A,s, hence you see the ger$inal follicles!, and therefore loo%s li%e a ly$ph node!. Gill see a low )>, high )9., low I 101 (not necessary to do this test!. ;xa$ple: pt on estrogen what will happen to )>N Increase )9.N &or$al (no need for I 101 this is ,ad ,c ,a,ies thyroid would ta%e it up and its thyroid would ta%e it up and leads to cretinis$! thyroid hor$one is responsi,le for ,rain growth in the first year, so it i$p to do thyroid hor$one screens to a-oid cretinis$ (will ,e se-erly +2 ,c ,rain depends on thyroid hor$one for de-elop$ent!. ;xa$ple: Lra-e1s dC )> high, )9., low, I 101 high ;xa$ple: pt on ana,olic steroids )> low, )9. nor$al ;xa$ple: .ashi$otos )> low, )9. high, I 101 low ;xa$ple: factitious (ta%ing too $uch thyroid hor$one and ha-e hyperthyroidis$! )> high, )9. low, I 101 low ($ain factor that distinguishes fro$ gra-es! :oi!er Anyti$e thyroid is ,ig. 8ots cysts. +CC goi!er , Io*ine *e' +ost often due to low iodide le-els, so they ha-e hypothyroidis$ or ,orderline hypothyroidis$, so the glands are getting re-1d up, )> goes up and )9. goes down (so )9. will ,e sti$ulating it, then not, then it is, etc..!.
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2x of choice thyroxine 9o$eti$es ha-e a nodule nodules that de-elop in the thyroid gland get he$orrhaged. )here is sudden increase in he$orrhage due to cyst. ?x with 4&A. )hen, gi-e thyroid hor$one and $any ti$es these things will get s$aller. In this country, we iodiniCe salt, so don1t see $uch. .owe-er, so$e places people ha-e iodine poor diets ie Lreat 8a%es in Chicago area, 3ritain5 when they get gra-es dC, due to increase in )0 ,c they are iodide def and do not ha-e enough iodine. Co%* no*&%e 1s Ho! No*&%e +eans if nodule is ta%ing up I 101 or not. If it does not, there is an area of lucency, and therefore cold. If it is hot, there will ,e a ,lac% dot. GhyN 3c if the nodule is autono$ously $a%ing thyroid hor$one, what is the )9.N ?ecreased. If the )9. is decreased, would that suppress the nor$al portion of the thyroidN Bes, so it undergo atrophy and not ta%e it up, leading to ,lac% dot (wouldn1t see anything else!. Ghat is chance that a cold nodule is $alignant in a wo$anN 1ED(67. +ost cold nodules in an older wo$an are ,enign. +ost are cysts. A s$all 7 is follicular adeno$a. Any cold nodule in a +A& is cancer until pro-en otherwise. Any cold nodule in a child is cancer until pro-en otherwise. Any *;29'& that has ,een exposed to radiation and has a cold nodule has CA&C;2 (papillary carcino$a of the thyroid radiation exposure in head:nec% area!. Can ers o' !)e !)yroi* &eed to ,x (cannot tell if $alignant just ,y loo%ing at it! this is true for follicular adeno$a, so$ething ,R, $ultinodular goiter. ?one with 4&A.
1. 2. 3.
Papi%%ary an er would show up with a cold nodule, and has Psammoma -o*ies. *apillary carcino$as $ets to cer-ical ly$ph nodes next to the$. )hey co$$only do this, and ha-e a good prognosis. )his is the only assoc with radiation. Annie orphan nuclei. 9o%%i &%ar an er (nd +C type, in-ades -essels. ?o not go to ly$ph nodes. 9pread he$atogenously, therefore often go to lungs and ,one. +e*&%%ary ar inoma so$e cases are sporadic and other cases ha-e A? relationship5 assoc with +;& syndro$es ($ultiple endocrine neoplasia I, IIa, II,! *in% stain stain with congo red and see polariCed apple green ,irefringence " a$yloid A (which ca$e fro$ calcitonin!5 what is the tu$or $ar%erN Calcitonin (which is the screening test of choice!
;xa$ple: where would the cancer ,e located in the ,ody where the tu$or $ar%er is con-erted into a$yloidN +e*&%%ary ar inoma o' !)e !)yroi* +EN I pit tu$or, parathyroid adeno$a, pancreatic tu$or (usually Qolinger ;llison, leading to peptic ulcer!. +EN IIa $edullary carcino$a, pituitary , pheochro$ocyto$a +EN II- $edullary carcino$a, pheochro$ocyto$a, $ucosal neuro$a .ow do you screenN 2et protooncogene (uni#ue to coding for receptors in this syndro$e!. Prognosis /-es! !o 3ors!0: Papi%%aryM9o%%i &%arM+e*&%%ary PARATHYROID :LAND *t can ha-e tetany with a nor$al total Ca. Ca is ,ound and free it1s the free Ca that is $eta,olically acti-e (which is true for A&B hor$one the part that is ,ound is totally $eta,olically inacti-e!. 9o, who does Ca interact withN *). 9o, if Ca is low, the *). is high, and if Ca is high, *). is low. 2oughly 1:0 of the ,inding sites in al,u$in are occupied ,y Ca. 9o, in other words, roughly >67 of the total Ca is ,ound to al,u$in. >@7 is ioniCed Ca floating around and the rest is phosphate and sulfates. )he ioniCed Ca is the $eta,ollicaly acti-e for$. +CC o-erall of hypocalce$ia " hypoal,u$ine$ia. .a-e low al,u$in le-el, therefore decreased le-el, and less of al,u$in ,inds Ca. 9o, ,efore you loo% at *). le-els, loo% at al,u$in le-els if that is low, this is the cause of hypocalce$ia. )his is not affecting the free hor$one le-el, just that al,u$in is decreased. )his the sa$e as )3L ,eing decreased, leading to decreased )>. A%6a%osis /resp or me!a-o%i 0: ha-e decreased . ions, and p. is increased. Ghat are the acidic aa1sN Lluta$ate, Aspartate. Ghy are they acidicN .a-e C''. groups (as opposed to ,asic aa1s , which ha-e $ore ,asic &. groups!. )he reason why al,u$in is such a great ,inder of Ca is ,c it has the $ost negati-e charges in the ,ody, ,c it has the $ost acidic aa1s in it. 9o, if you ha-e an al%alotic state the C''. groups ,eco$e C'' IDI groups. 3c if you ha-e less . ions, its C''JDI. 9o, al,u$in has +'2; of a negati-e charge in an al%alotic state, which $eans it can ,ind $ore Ca. 9o, where does it get it fro$N IoniCed free Ca (so a ,unch of ioniCed free Ca ,inds to the the al,u$in!. .owe-er, we ha-e &') altered the total, just too% it. It doesn1t affect the total, ,ut it ?';9 decrease the ioniCed Ca le-el, leading to );)A&B. 9o, total is the sa$e, ,ut the ioniCed le-el has decreased. Ghat is the $ech of tetanyN .a-e threshold for the A* ,efore the ner-e is sti$ulated. )hen you ha-e a resting $e$,rane potential. 9o, a decreased ioniCed Ca le-el will lower the threshold for acti-ating the ner-e and $uscle. If its DA6 for nor$al threshold. *t is partially depolariCed, therefore doesn1t ta%e a lot to acti-ate the $uscle or the ner-e (which is the $ech of tetany! so you are lowering the threshold. In hypercalce$ia, the opposite occurs and you are increasing the threshold, so it ta%es $ore ioniCed Ca to acti-ate the ner-e. *). on y axis and Ca in x axis ht of s#uare " *). and width " Ca Lo3 ser&m Ca@ %o3 PTH , primary )ypopara!)yroi*ism +CC , pre1io&s !)yroi* s&rgery ;xa$ple: pt goes in to re$o-e thyroid cancer (these days they autotranplant it to the ar$!
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;xa$ple: new,orn with cyanosis, irrita,le and xray of chest shows not anterior$ediastinu$ shadow dxN ?iLeorge hypoparathyroidis$ and no thy$us ;xa$ple: %o3 Ca@ )ig) PTH , se on*ary )ypopara!)yro*ism so whate-er is causing the hypocalce$ia is causing a co$pensatory increase in *). (called secondary hypoparathyrodis$ the +CC of this is renal failure ,c these pts ha-e hypo-ita$inosis ?, which decreases Ca and increases *).!. 9o, any decrease in Ca with cause a co$pensatory increase in *).. ;xa$ple: )ig) Ca@ )ig) PTH , primary )yperpara!)yroi*ism " gland is not o,eying negati-e feed,ac%. )his is +CC hypercalce$ia is a co$$unity5 If pt is in a hospital, +CC hypercalce$ia " $ets to ,one ($alignancy induced!. +ost hypercalce$ia pts are as$pto$atic5 if they A2; sy$pto$atic, they ha-e stones (Ca stones, which is the +C sy$pto$atic presentation for hypercalce$ia!. 8a,s: increased Ca, increased *)., low phosphate (nor$ally *). increases Ca rea,sorption and decreased phophorus rea,sorption!. Al$ost always o-er E6 yo ;xa$ple: )ig) Ca@ %o3 PTH , a%% o!)er a&ses ex ep! primary )yperpara!)yroi*ism. +C due to $alignancy. Can *). li%e peptide cause hyperCaN Bes (so if you $easure *). it will ,e nor$al!. 9#ua$ous cell of the lung, renal adenocacino$a, or $ets to ,one (,rea%ing ,one down!, sarcoidsis (leading to hypercalce$ia!, $ultiple $yelo$a (leading to hypercalce$ia! all will ha-e 8'G *).. 9o, what is the eC1est way to deter$ine hyperCa in a ptN *). le-el (if its high, its pri$ary hyperparathyroidis$5 if its low, its all the causes ie $alignancy!. ADRENAL :LAND C&s)ing <yn*rome *<2*8; striae, o,esity, thin extre$ities +CC " pt on long ter$ steroid therapy (ie pts with renal transplants, pt on i$$unosuppressant, 8upus! If this is excluded, need to thin% of 0 sources: pituitary Cushings, adrenal Cushings, ectopic Cushings. Ghich of the three will ha-e the highest AC). le-elsN ;ctopic (s$all cell carcino$a!. Ghich would ha-e the lowest AC). le-elsN Adrenal. GhyN 3c its $a%ing cortisol, which would suppress the AC).. *it Cushings is usually a ,R tu$or $a%ing AC).. )here are ( good screening tests for Cushings (when you ha-e excluded the fact that they are not on steroids!. )he screening tests are: (> hr urine test for free cortisol. )his is loo%ing for cortisol in the urine, not attached to any protein (so it1s free!. It $ust $ean that you ha-e a lot of excess of it to ha-e that $uch of it in your urine. )his is the 3;9) screening test for Cushings. )his test distinguishes Cushing1s syndro$e fro$ Cushingoid o,esity. ;xa$ple: see o,ese pt with Cushing1s sy$pto$s and you thin% they ha-e Cushings5 howe-er, get a (> hr urine cortisol test and it1s nor$al. If it1s increased, they truly ha-e Cushings in other words, they ha-e RR7 sens and specificity. )hey will as% a,out *exme!) s&ppression !es! (low -s high dose!. Ghat is dexa$ethasoneN It1s a cortisol analog. If you gi-e dexa$ethasone to a nor$al person, it will suppress AC).. If you suppress AC)., the cortisol le-els with ,e low, indicating the cortisol le-els are suppressi,le. 9o, what happens when you gi-e a 8'G dose of dexa$ethasone in a pt with Cushings will you suppress their cortisolN &o. 9o, you see a lac% of suppression. )herefore pt has cushing1s. .owe-er the 8'G dose just tells you pt has Cushings, not what %ind they ha-e, so it just a screening test (if you did a (> hr cortisol urine le-el, it would ,e positi-e!. 2e$e$,er that there are two endocrine dC1s that you CA& suppress *I)<I)A2B Cushings and prolactino$a. 9o, if you gi-e high dose of dexa$ethasone, you are a,le to suppress the AC). release ,y the pituitary and cortisol goes down. It will not ,e suppressed in adrenal and ectopic Cushings (s$all cell!. Z2ead last sentence if you get a long #uestion[ ;xa$ple: for one of these, they will descri,e Cushings, and as% a,out dex$eth suppression first thing to do is loo% at high dose suppression if its suppressed, its auto$atically pituitary cushings (not a hard #uestionM! 9o, why do the pts loo% li%e thisN *t has hypercortisolis$, which is gluconeogenic. 9o, need su,strates for gluconeogenesis $ain su,strate is aa fro$ $uscles. Ghere are the $uscles locatedN Ar$s and legs so pt will get a ,rea% down of $uscle in the extre$ities, which is why they ha-e thin ar$s and thin legs. )hen will get alanine transa$inated and get pyru-ate. 9o, will always ha-e thin ar$s and extre$ities. 3c it is gluconeogenic, what will the glucose ,eN .igh. Ghat does that do to insulin releaseN Increases it. Ghat does insulin do to fatN Increases fat storage. Ghat part of the ,ody ha-e the $ost adiposeN 4ace and trun%. 9o, you are getting an increase in deposition of )L in the face and trun% and ,ac%. 9o, the thin extre$ities is due to ,rea%ing down $uscle for aa1s in gluconeogenesis. )he $oon facies, ,uffalo hu$p and truncal o,esity is due to increase in insulin and fat deposition. )he stretch $ar%s are due to o,esity, and they are purple ,c cortisol decreases collagen synthesis. Gill get structurally wea%er collagen. Its li%e purpura within the stretch $ar% (li%e senile purpura!. 3rea% down the -essels ,c increase in cortisol. ;xa$ple: Tro&ssea&#s sign sign of tetany5 this pt has .)&, hypernatre$ia, hypo%ale$ia, and $eta,olic al%alosis dxN *ri$ary aldosteronis$. (ha-e tetany ,c al%alosis neg charges on al,u$in are increased, and ioninCed Ca le-el decreases!. A%a Conn1s syndro$e A*rena% +e*&%%a !&mors +C in a*&%!s , p)eo )romo y!oma /,R, .)&! (so, adult, .)&, tu$or in adrenal $edulla " pheo!5 ha-e unsta,le .)& anxiety, sweat a lot5 get a (> hr urine test for K+A and $etenephrine (these are $eta,olic endproducts of &; an ;pi (so, anxious, sweating, .)&!. Are there assoc with pheochro$ocyto$aN Bes +;& IIa and +;& II,, neurofi,ro$atosis (ie pt with neurofi,ro$atosis with .)& what test you getN K+A and $etanephrine (> hr urine, ,c high assoc with pheo!. +C in %ids " neuro,lasto$a (+A8IL&A&)!
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3oth of these are fro$ renal $edulla, ,oth are neural crest origin, ,oth produce .)&. *heo " adults 5 neuro D %ids
115
5a!er)o&se 9ri*eri )sen <yn*rome &. $enigitidis ;xa$ple:: 1( yo, gra$ IDI diploccocus, high fe-er, nuchal rigidity, spinal tap found neutrophils and gra$ IDI, %id then =crashed1 started to get petechial lesions all o-er the ,ody, hypo-ole$ic shoc%, died, on autopsy ,oth adrenal glands are he$orrhaged ?xN Gaterhouse 4reidric%son +CC meningi!is 'rom 1 mon!) !o 1L yrs o' age , N meningi!i*is. It is the '&8B $eningitis with petechial lesions (and they always $ention this!. 9o, if they gi-e $eningitis and petechia, %now is & $eningitis. If they are hypo-ole$ic, they he$orrhaged their adrenals and went into hyp-ole$ic shoc%, also, they ha-e no cortisol or $ineralocorticoids. Ca&se o' )ypo or!iso%ism !)a! is )roni , A**ison#s *> +CC Addisons " autoi$$une destruction of the gland (used to ,e )3 due to autoi$$une destruction!. )he entire adrenal cortex is destroyed, therefore the $ineralocorticoids and glucocorticoids are low. 9o, there is low cortisol with .IL. AC).. Ghat does that do to $elanocytesN Increases the$, leading to hypig$entation in the $outh and elsewhere. )here is &' aldosterone. )here are ( pu$ps (&a:K pu$p and proton:K pu$p!. Are you gonna lose &aN Bes which will lead to hyponatre$ia and .B*;2%ale$ia (pea%ed ) wa-es!. Gill you ,e a,le to get rid of the protons in the urineN &o therefore will ha-e $eta,olic acidosis. 9o, you ha-e hyponatre$ia, hyper%ale$ia, $eta,olic acidosis, hyperpig$entation. ;xa$ple: a$,iguous genetalia what is first step in $anage$entN C1so$e analysis ha-e to find out what the genetic sex is. It1s HH. 9o, pt has a$,iguous genetalia, fe$ale, phenotypically cannot tell, so i!#s 'ema%e pse&*o)ermap)ro!i*e = (play odds! adrenogenital syndro$e due to "1 )y*roxy%ase *e'. 1@ hydroxylase is responsi,le for 1@ %etosteriods (include ?.;A, androstenedione, and are wea% androgens!. Androstenedione can ,e con-erted into testosterone and testosterone into dihydrotestosterone. 1@ hydroxycorticoids are 11 deoxycortisol and cortisol <o@ i' yo& )a1e an in rease in 1H )y*roxy or!i oi*s@ !)is is an in rease in 11 *eoxy or!iso% an* or!iso% I' yo& )a1e an in rease in 1H 6e!os!eroi*s@ /1H@ 8<0 i!#s an in rease in DHEA an* an*ros!ene*ione. 5)en yo& )a1e an en>yme *e'@ !)ings prox !o !)e -%o 6 in rease an* !)ings *is!a% !o !)e -%o 6 *e rease 5i!) "1 )y*roxy%ase *e'@ decrease $ineralcorticoids and glucocortiocoids and increase androgens, lead to a$,iguous genetalia (excess androgens!, lose salt, high AC)., therefore hyperpig$ented 5i!) 11 )y*roxy%ase *e' decreased cortisol, decreased aldost, ,ut increased 11 deoxycorticosterone (wea% $ineralcoricoid!, increased 1@ hydroxy1s and 1@ %etos lil girl will ha-e a$,iguous genitalia, lil ,oy will ha-e precocious pu,erty (excess androgens!, .)& 1H )y*roxy%ase *e' no androgens, increased in $ineralocorticoids (.)&!, so if it1s a lil ,oy he won1t ha-e test and will loo% li%e a fe$ale ,c no de-elop$ent (no external genitalia ,c no 1@ %eto1s, test, or dihydrotest!. In a lil girl she will ,e underde-oped. Is%e! e%% !&mors 'nly ( to %now: Insulino$as and Q; syndro$e Q;: $a%ing too $uch gastrin, leads to peptic ulcers Insulino$a: is pt injecting or do they really ha-e insulino$aN Ghen you ,rea% proinsulin down into insulin, you release C peptide, so for e-ery insulin $olecule that is released, there is C peptide that is released with it. 9o, if you inject hu$an insulin into yourself, and produce a low glucose le-el and C peptide will ,e 9<**2;99;?. If you ha-e a islet cell tu$or, glucose will ,e low, insulin will ,e high and C peptide will ,e I&C2;A9;?. ;xa$ple: pts that ha-e access to insulin get this (?rs, nurses, phar$acists! Audio file ?ayE S> +usculos%eletal Dia-e!es +e%%i!&s Type 1 A,solute insulin deficiency Anti,odies against islet cells ?KA .8A relationship Insulin used (always! Type " 4a$ily history of dia,etes ',esity A$yloid in islet cells .yperos$olar nonD%etotic co$a Insulin used when e-entually pt get resistant to 94< *A).'L;&;9I9: ( $echanis$s:
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1! Osmo!i Damage )issue has to ha-e aldose reductase: only ( ha-e the$: i! 8ens, glucose sor,itol, os$otic reacti-e, a,sor,s water into the lens 2etinal -essels in lens get wea%, then destroyed due to $icroa,sesses and can rupture and lead to ,lindness. ii! 9cwann Cells: +CC cause of peripheral neuropathy is ?ia,etes: +;C.: os$otic da$age (! Non?en>yma!i :%y osy%a!ion 2enders the 3+ per$ea,le to proteins: .yaline arteriolosclorosis, dia,etic nephrophathy .,A1c: long ter$ control of ?+. 9lide: 2etina in a dia,eticD$icroaneurys$s (red dots! 9lide: 2etina in a dia,eticDneo-asculariCation ;xa$ple: E6 yr old, ,lurry -ision5 gets a prescription fro$ a opto$etrist, new glasses, one $onth later, ,lurry -ision again. Lets new prescr, one $th later, ,lurry -ision again. ?x: ?ia,etes. Llucose is ,eing con-erted to sor,itolDwater is going in and changing the refracti-e index. Classic #uestion. .AK; to get a 4A9)I&L 38''? L8<C'9;. 8a,: 4asting glucose U1(A $g:dl on two separate occasions. ;xa$ple: 3eh 9c lin%: )he 439 le-el has ,een decreased fro$ 1>6 $g:dl to 1(A $g:dl. Is this increasing the specificity or the sensiti-ity of the testN A: .IL. 9ensiti-ity. 3y ,ringing it lower ie closer to the nor$al range, you are going to ,e a,le to pic% up $ore people with dia,etes. Ghen it was 1>6, it was high sp: to eli$inate false positi-es. 9o it was une#ui-ocally a dia,etic if it was U 1>6. Llucose tolerance test, don1t worry a,out it. :es!a!iona% Dia-e!es ?ef: Go$an who did not ha-e dia,etes, ,ut after ,eco$ing pregnant de-elops dia,etes. 2is% factors for ,a,y: 2?9, pre$ature deli-ery Go$en with L?, are at a higher ris% for de-eloping dia,etes later on. A$yloid in 3eta islets: )ype ( Anti,odies against islets5 infla$$ation: )ype1 (Coxac%ie -irus i$plicated! .8A correlation: HLA DR$ an* DR2,Type 1I propensity for de-eloping )ype 1, if certain en-iron$ental factor co$es in such as infection: Coxsac%ie, $u$ps, ;3K .8A3(@: An%ylosing 9pondylitis ;n- factors: Chla$ydeal Infection <lcerati-e Colitis, 9higellosis *soriasis +&s &%os6e%e!a% <ys!em &eed to identify crystals in syno-ial fluid :o&! Pse&*ogo&! 2ho$,oid crystals in syno-ial fluid""pseudogout 3ut *seudogout could also ha-e needleDshaped crystals (li%e those of $onoDsodiu$ urate in Lout! which $a%es ?? difficult. 9o you use a special filter to $a%e the whole slide red and then the crystals are $ade to loo% yellow or ,lue. Ghen the color of the crystals is yellow when the plane of filter is parallel to the analyCer" Nega!i1e%y -ire'ringen! ,:OUT
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;ast west direction: color is ,lue and parallel to analyCer"Posi!i1e%y -ire'ringen! , P<EUDO:OUT (calciu$ pyrophosphate! Ar!)ri!is Os!eoar!)ri!is *rogressi-e wearing down of articular cartilage 9o$eti$es leads to reaction to injury: 9*<2 for$ation^at the $argin of the joint" .e,erden1s node: osteophyte in the joint &ote the enlarge$ent of the ?I* (.e,erden_s nodes! and *I* joints (3ouchard_s nodes!, enlarge$ents represent osteophytes. R)e&ma!oi* Ar!)ri!is
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Infla$$atory joint dC5 enlarged +C* joints 2h factor sets up the infla$$ation: Ig+ A, against IgL. IgL is in syno-ial fluid. Ig+DIgL for$ co$plexes, acti-ate the co$ple$ent syste$, da$age the joint, syno-ial fluid gets infla$ed, starts growing and growing, starts growing o-er the articular cartilage" *A&&<95 hyperplastic syno-ial fluid. (different fro$ )ophus! Foints can get fixed, and an%ylosed and cannot $o-e. ?on1t get fixing of the joint in 'A. If rheu$atoids don1t %eep $o-ing their joints, and if it is not controlled using antiDinfla$$atory drugs then e-entually they cannot $o-e it at all. 9lide: 2heu$atoid nodules. Can ,e seen in 2heu$atic fe-er as well. ;xa$ple: older pt ha-ing trou,le eating and swallowing crac%ers, feels li%e there is sand in $y eye all the ti$e. 'n exa$ination: eyes and $outh are dry. ?xN <Qogran#s <yn*rome. *t with 2A and autoDi$$une destruction of lacri$al glands, sali-ary glands. Keratoconjuncti-itis sicca 2heu$atoid nodules in lung / pneu$oconiosis""Caplan 9yndro$e )reat$ent of 2A" +ethotrexate ;xa$ple: *t with 2A, de-elops a $acrocytic ane$ia with hyperseg$ented neutrophils, neuro exa$ is nor$al, interstitial fi,rosis in lung. Ghat is the drugN +ethotrexate :o&! , po*agra 3ig toe, usually first one to ,e in-ol-ed5 usually at night. +onosodiu$ urate crystals are precipitated and ta%en up ,y the neutrophils that phagocytose it and release che$icals^infla$$atory reaction. ?on1t define Lout ,ased on <ric acid le-el. ;le-ated uric acid does not necessarily lead to gout. A,out (E7 of people $ight ha-e ele-ated uric acid. ?x: .A9 to ,e ,y presence of uric acid crystals in the joint. )reat$ent: Indo$ethacin to control infla$$ation. Cause: o-er production (2x"allopurinol: ,loc%s Hanthine oxidase! or under excretion of uric acid (UR67 of cases! 2x"uricosuric drugs li%e pro,enecid and 9ulfinpyraCone C)roni :o&! , !op)&s: deposition of $onosodiu$ urate in soft tissue^$alleolus Kery disa,ling as it erodes the joint. 2x" allopurinol 9lide: )ophus that was polariCed showing +9< crystals 9lide: HDray of digit showing erosion ,y tophus :ene!i s o' :o&!: +ultifactorial inheritance AK'I? red $eats (full of purines! AK'I? Alcohol. +echanis$: +eta,olic acidosis: uric acid has to co$pete with other acids for excretion in proxi$al tu,ule. Alcohol increases all the lactic acid, and ,eta hydroxyl ,utyric acids. 9o all these acids co$pete and win against uric acid, and get excreted. <ric acid %eeps waiting and waiting5 and ,uilds up and causes gout.
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An6y%osing spon*y%i!is /A<0 .8A3(@ association
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9lide: &ote anterior flexion which often results in restricti-e lung disease. .unched o-er, restricts $o-e$ent of chest ca-ity, ,lood gas a,nor$alities, (6 yr old, $orning when he wo%e up, sudden pain in sacroDlu$,ar region. Infla$$atory reaction seen on HDray, as the day progresses pain decreases. ;-entually, the infla$$ation spreads to the -erte,ral colu$n, and it fuses""J3a$,oo spineJ Also de-elop: <-eitis, Aortitis, iridocyclitis, ,lurry -ision, e-entually go ,lind. ;xa$ple: Lenetic dC where degenerati-e arthritis in -ert col, on autopsy, ,lac% cartilage5 urine on exposure to air turns ,lac%. A%6op!on&ria Aut rec, ho$ogentisic acid oxidase enCy$e def 9lide: (6 yr old, dysuria, increased fre#, urinalysis" leucocyte esterase positi-e, sterile pyuriaDDsexually acti-e, had nonDspecific urethritis, conjuncti-itis, was treated. It was Chla$ydia tracho$atis conjuncti-itis, ,ut one wee% later, got sterile conjuncti-itis and tendonitis in Achilles tendon. 9o patient with nonDinfectious conjuncti-itis, pre-iously had Chla$ydia tracho$atis infection and then de-eloped conjuncti-itis and arthritis (.8A 3(@ positi-e!: Rei!erXs syn*rome Ano!)er En1 !rigger in HLA("H posi!i1e p!: <lcerati-e Colitis <ep!i ar!)ri!is *&e !o *issemina!e* gono o emia
&ote the hot %nee and the pustule on the wrist, on aspirating: gra$ negati-e diplococcic 9)?" 9exually )rans$itted ?isease 9"9yno-itis"joints )" )enosyno-itis" joints in hands and feet ?" ?er$atitis"pustules +CC of septic arthritis in <9" Lonorrhoea 4or it to ,eco$e disse$inated, need to ,e deficient in the final pathway of Co$ple$ent syste$: C4?CB (so$e say CADCR! 9lide: &ote the Ixodes tic% (-ector of 3orrelia ,urgdorferi and 3a,esia $icroti!, note the erythe$atous rash in the ,otto$ screen D the tic% ,ite is in the center of the rash and the rash extends out in concentric circles fro$ that point, the rash is called ery!)ema )roni &m migrans (pe,,le thrown in water! *athogno$onic of LymeXs *isease ;arly for$ 2x: tetracycline C)roni Lyme#s Disease: Apart fro$ disa,ling joint disease: $yocarditis plus ,ilateral 3ell1s palsy: C& KII in-ol-ed / pt will ha-e 3a,esiosis Idiopathic: is usually <nilateral 3ell1s *alsy" .erpes 9i$plex A,o-e *t de-elops .e$olytic ane$ia, what did he see in his peripheral ,lood s$earN 3a,esia $icroti (ring for$ si$ilar to *las$odiu$ falciparu$! Remem-er: !)e Ixo*es !i 6 )as !)e reser1oir 'or (orre%ia -&rg*or'eri /3)i!e !ai%e* *eer !)a! )as (a-esia mi ro!i0 AND (a-esia mi ro!i intraDerythrocytic parasite 2x: Ceftriaxone (one Disor*ers Os!eogenesis imper'e !a 9lide: Kid with an eye,all, ,lue sclera: A? disorder with defect in synthesis of type I collagen, note the ,lue scleraD loss of collagen in sclera allows ,luish color of choroidal -essels to shine through: Os!eogenesis imper'e !a (&') foreign ,odyM! I,rittle ,one diseaseJ cant ,rea% ,one down Puestion: what1s the defectN ?efecti-e synthesis of type 1 collagen Puestion: what1s the $echanis$ of de-elop$ent of ,lue scleraN Collagen in sclera, type 1 is defecti-e, so it is so thin, so you can see the underlying choroidal -eins that gi-es the ,lue color. Os!eope!rosis , Cmar-%e -one *iseaseD
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?efect in too $uch ,one: defect in osteoclasts
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Os!eoporosis 9lide: ?ecreased width of inter -erte,ral cartilage. &ote the collapse of the -erte,ra due to loss of ,one $ass: patients lose $ore ,one than is replaced 9lide: ?owager1s .u$p +ech: *ost$enopausal osteoporosis is due to the loss of the inhi,itory effect of estrogen on the release of interleu%in 1 fro$ osteo,lasts5 not enough estrogen to stop the acti-ity of Interleu%inD1 (osteoclast acti-ating factor! fro$ ,rea%ing your ,one down. 'steoporosis: '-erall reduction in ,one $ass. 3oth $ineral A&? organic co$ponent. G.'8; $ass of ,one is reduced. 'steo$alacia: ?ecreased $ineraliCation of ,one: organic part of ,one is nor$al. Cartilage is o%, osteoid is o%5 its not getting $ineraliCed ?x of osteoporosis: ?ual ,ea$ A,sorptio$etry: density of the ,one in whole ,ody is $easured. &on in-asi-e, -ery easy. +C 'ra !&re: ompression 'ra !&re: lose stature, "n* +C 'ra !&re: Colle1s fracture of distal radius. Puestion: Is swi$$ing a good exercise for pre-enting osteoporosis: &'. 3ecause no stress on ,ones. It is great exercise for aero,ics. 3ut it does not pre-ent osteoporosis. Gal%ing is good. Geight ,earing is e-en ,etter than wal%ingM Gal% with ?u$,ellsM Let aero,ics and inc in ,one $assM .AK; to stress ,one to ,uild it up. ;xa$ple: In space, lac% of gra-ity and astronauts are gi-en ,isphosphonates, Kit ? and calciu$ to get ,one density ,ac%: ,ecause serious pro, of osteoporosis in space. )ip: reproducti-e wo$en need to: 1! ;xercise (! 1E66 $g of Ca e-eryday 0! >66DT66 units of Kit ? >! Kit pill that contains Iron (one T&mors Exos!osis /os!eo )on*roma0 &ote the cartilaginous cap on the surface of the ,one. )his causes a protu,erance of the ,one. )his is the $ost co$$on ,enign ,one tu$or. C)on*rosar oma o' !)e )ip +C ma%ignan! one Os!eogeni sar oma 9lide: &ote $etaphyseal origin of the cancer and extension into the $uscle, note the splinter of periosteu$ that is ele-ated which would correspond to Cod$an_s triangle 9lide: HDray of proxi$al hu$erus showing the `sun,urst` appearance of osteogenic sarco$a that is extending into the $uscle, osteogenic i$plies that the cancer is $a%ing ,one Adolescent, sun ,urst app, cod$ans triangle, %nee area""'steogenic 9arco$e <&ppressor :ene re%a!ions)ip: 2, suppressor Chro$oso$e 10 +&s &%ar Disor*ers D& )enne#s +&s &%ar Dys!rop)y Lower1s $aneu-er ;le-ated 9eru$ CK, A,sence of dystrophin protein 9ex lin%ed recessi-e, $issing ?ystrophin gene Kariant: 3ec%er1s dystrophy: $a%e dystrophin ,ut it is defecti-e Analogy: alfa 1 antitrypsin def: +CC of .CC in children Adults get panacinar e$physe$a: $any diff su, types of alfa 1 antiDtrypsin: 1! A,sent alfa 1 antiDtrypsin: get pan acinar e$physe$a. (! Alfa 1 antiDtrypsin is present ,ut it cannot get '<) of the hepatocytes: so get .CC
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Audio file ?ay E SE 9%in
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+yo!oni *ys!rop)y ? +C a*&%! *ys!rop)y@ AD )riplet repeat dC repetition of triDnt1s (there are > dC1s with this a,nor$ality .?, 4ragile H ha-e $acrorchidis$ (,ig testes in adolescents!, 4riedrich1s ataxia, +yotonic dystrophy!. In future generations, dC gets worse anticipation. )herefore, can anticipate that in future dC1s it will get worse. generation, there are $ore triplet repeats added on, leading to a $ore defecti-e protein and the dC gets worse and worse. 4or each
;xa$ple: genetic counselor telling couple that they ha-e a dC, where if are to ha-e children, the dC will ,e fatal in their children. )he couple didn1t listen to their counseler, had a child and the child died only after 1 $onth. Ghat was it and what is this: an ie triplet repeat disorder (anticipation! +uscle wea%ness in face (so $outh is drooped open!. ;xa$ple: pt with failure to release grip on golf stic% (or when sha%ing hand! they cannot relax their $uscle grip, dia,etes, cardiac a,nor$ality +yas!)enia :ra1is AutoA, against Ach receptor it1s an IgL A,, therefore is an ;xa$ple: of type II .*B, li%e Lra-e1s, which is an IgL A, against the receptor (,y definition, this $a%es it type II!. Ghether you destroy the receptor or just ,loc% it is irrele-ant. Ach cannot hoo% into it and therefore there is $uscle wee%ness. )he first $uscles are the lids, which leads to lid lag. )hey also get dou,le -ision ,c $uscles of the eye are $essed up, leading to diplopia. ;-entually, they get dysphagia for solids and li#uids (gets stuc% in upper esophagus, ,c this is where there is 9)2IA);? $uscle!. ;-entually $uscle dC pre-ails throughout. 4eel energiCed in the $orning and feel tired at night. )ensilon test positi-e. Can die. 2x is acetylcholinestrase inhi,itors. 3y gi-ing an inhi,itor, ,loc% the ,rea%down of Ach and ,uild up Ach. Gith few receptors you ha-e in there, there is a larger chance of hoo%ing up to the receptors and pt does well. .owe-er, e-entually, no receptors there and it doesn1t $atter how $uch Ach is there, so pt is screwed. )hen, her only option is a thy$ecto$y. )he thy$us is in the anterior $ediasti$un. )ric% #uestion: they can as%, what is the pathologyN )hey can descri,e +L and as%, what do you expect to see in the $ediastinu$N ?o &') put thy$o$a. )his is a $alignancy of the thy$us and does occur in 1ED (67 of cases, ,ut isn1t the +C pathology seen in the thy$us in a pt with +L. 9ee ger$inal follicles in the thy$us (re$e$,er, this ) cell country, not 3 cell country, so its a,nor$al to ha-e ger$inal follicles here! they are the ones $a%ing the A, causing the +L. 9o, ,y doing a thy$ecto$y for 2x, you are re$o-ing the A, producing tissue. 1:0 pts get a co$plete cure. 1:0 get a partial cure, and 1:0 die ,c they waited too long for thy$ecto$y and 2x and didn1t ha-e receptors, anyway. 9o, 3 cell hyperplasia is the +C thing you see, not thy$o$a. )his where the A, is ,eing $ade. L&p&s 3utterfly distri,ution on the face ($alar rash! 'f all the autoi$$une dC1s this one is the $ost li%ely one to ha-e a I/J A&A (RR7 sensiti-ity!. )he A,1s you want to order to pro-e that its lupus are antiD9$ith A, (which has a 1667 spec, therefore no false pos therefore 1667 **K! for lupus, $eaning that if you test I/J for this A,, you ha-e 8upus. )he other A, is anti ds?&A this not only indicates that you ha-e lupus, ,ut also that you ha-e KI?&;B dC. )hat has a RT7 spec, too. 9o, these are two good A,1s to confir$ lupus. +orning stiffness is present in lupus (si$ulates 2h arthritis:photopho,ia!, rash, pericarditis5 8; cell prep Anti ?&A A,1s are phagocytosed ,y neutrophils, and they ha-e altered ?&A. &ot specific for lupus (waste of ti$e!. Progressi1e <ys!emi < %erosis7CRE<T )ight face, telangiectasia, 2aynauds, dysphagia (solids and li#uids!, dystrophic calcification, sclerodactly5 if %idneys in-ol-ed, it is progressi-e syste$ic sclerosis, &') C2;9) (doesn1t in-ol-ed %idneys!. Derma!omyosi!is 2acoon eyes, ele-ated seru$ CK, rash o-er the *I* (goutren1 patches!, highest assoc with underlying cancer. <Qogrens syn*rome Assoc with rh arthritis, autoi$$une A,1s destroy sali-ary glands leading to dry $outh, lacri$al glands leading to dry eyes. ;xa$ple: ,x of lower lip which is a confir$atory test its loo%ing to see if there is destruction of the $inor sali-ary glands see ly$phocytes (which is confir$atory dx!. A,1s are antiD99a (a%a antiD2o! and antiD99, (a%a antiD8a! (99 " 9jogren1s syndro$e!. AntiDro can also ,e in lupus pts, and can cross the placenta and disrupts the ,a,y1s conduction syste$ (leads to co$plete heart ,loc%!. <6in (asa% e%% ar inoma (upper lip! <;&amo&s e%% ar inoma (lower lip! Psoriasis sil-ery lesion that is red and raised. Can in-ol-e the hands, scalp pts thin% they ha-e dandruff (a%a se,orreic der$atitis fro$ $alaseCia furfura!, ,ut they really ha-e psoriasis. 'n ,lac% person won1t see red lesion, will see sil-er one. 2ash at pressure points esp the el,ow. A!opi *erma!i!is child with allergic diathesis starts dC5 ha-e ecCe$a (a%a atopic der$atitis!5 type I .*B.
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Con!a ! *erma!i!is ie to $etal (nic%el!5 type IK .*B ;xa$ple: pathophys is e#ualant to whatN I/J **?, ,c ,oth are type IK .*B <e-orr)ei Derma!i!is ?ue to Malassezia furfur (a fungus! IC pt (ie AI?s! )his is a preAI?s lesion Tinea api!is ;xa$ple: pt with ,ald spot on head, fluouresces and seen with ,lac% light ,lac%light (<KDA light! Can cause )inea capitis /no3 Tri )op)y!on !ons&rans is +CC0 3c the fungus in-ol-es the inner portion of the shaft, there are no fluorescent $eta,olites, and is 5oo* %ig)! nega!i1e
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All the other superficial der$atophyte infections including Tinea orporis (ring wor$! ;xa$ple: red outer edge and clear center, what is first step in wor%upN 9crape outside and do K'. prep, and see hyphae and yeast for$s. A%% o!)er s&per'i ia% *erma!op)y!e in'e !ions /ex ep! Tinea api!is0 are *&e !o !ry )op)y!on r&-ra. Ghat is the color around )inea capitisN 2ed (" ru,ra! (how to re$e$,er it!. +o%%&s &m on!agios&m 9andy li%e $aterial in crater, children, self inoculate *ox-irus $a%es these (?&A -irus! Kolcano crater loo%, with sandy stuff in it Pi!yriasis Rosea ;xa$ple: rash on ,utt non pruritic rash, &'& I&4;C)I'<95 o,long loo%ing with red on outside and pale in $iddle. Bou thin% this is ) corporis, ,ut its o,long (and not circular!. ?o a K'. prep, find nothing5 then put topical steroids and doesn1t go away5 0 days later co$es ,ac% with rash in the line of langer in Christ$as tree li%e distri,ution5 not an infectious dC, %i6e a )era%* ras)I no! a '&ng&s Dysp%as!i Ne1&s syn*rome ;xa$ple: precursor lesion for $alignant $elano$a5 if you ha-e o-er 166 ne-i all o-er ,ody, you ha-e dysplastic ne-us syndro$e Kery co$$on +ust go to der$atologist once a year ,c need to loo% at dysplastic ne-i. Could ,e a precursor lesion for $alignant $elano$a. 2 *i'' !ypes o' ma%ignan! me%anoma Ghat is first step in $anage$entN ;xcision ;xa$ple: superficial spreading $alignant $elano$a (+C! ;xa$ple: on face of older pt 8entigo $aligna $elano$a5 irregular ,order, corn colored, 8;A9) li%ely to $et of all $alignant $elano$as. ;xa$ple: ,lac% pop1n do not get $alignant $elano$as ,c the ,lac% pig$ent in the s%in pre-ents <K light da$age and propensity for cancer. howe-er, there is one type of cancer they $alignant $elano$a they CA& get: ,lac% pt with dyspnea, on xray find $ultiple $ets all o-er ,ody. 3x is done and pt has $alignant $elano$a, which part of the ,ody would you exa$ine to find the pri$ary dCN <nder the nails, pal$s or sole of the feet this is Acrolentiginous $alignant $elano$a (=acro1 $eans edge of:tip of! this is the +'9) ALL2;99IK; of all the $elano$as. )his has nothing to do with radiation. *agets dC loo%s si$ilar ;xa$ple: &odular $alignant $elano$a also -ery aggressi-e. T)e mos! impor!an! !)ing a''e !ing prognosis is *ep!) o' in1asion (%ey to prognosis $agic S is .@A $$!. If its less than .@A, its not gonna $et. Toxins ( poisonous spiders (%a 6 3i*o3 .as a neurotoxin causes spas$ of the $uscles in the upper thighs and a,do$en so strong its al$ost li%e tetanus5 pain $uscle contractions, esp in the a,do$en. )here is an anti-eno$, painful ,ite ;xa$ple: person went down into their cellar, lifted ,oxes, felt sharp pric% on finger, and de-eloped contractures o-er a period of hrs due to ,lac% widow ,ite. (ro3n re %&se spi*er (a%a -iolin spider! *ainless ,ite, has a necrotoxin, leading to ulcer 9o, neurotoxin for ,lac% widow, necrotoxin for ,rown reclous 5)ere is re ep!ors !o an*rogensE <e-a eo&s g%an*s (this is why $en get $ore Cits than wo$an testosterone will release lipid rich $aterial which gets into the hair follicle. )hen, if you ha-e proprionu$ acnei (anaero,e! it has lipases that ,rea%down fat fro$ the se,aceous gland and produces 4A1s that irritate the follicle and end up with acne. 9o, $en $ore li%ely to get it ,c they ha-e acne It all occurs in the erector pili $uscle of the s%in. 9o, there are androgen receptors se,aceous glands and erector pili $uscle.
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Dr&g &se* !o pre1en! )irs&!ismE <pirono%a !one (sa$e drug used to ,loc% aldosterone!5 this drug is good ,c it ,loc%s androgen receptors and therefore pre-ents hirsutis$. Can also lead to gyneco$astia. CN< 9pinal fluid deri-es fro$ choroid plexus in the -entricles. In the lateral, 0rd and >th -entricles. Its an ultrafiltrate of plas$a. Ghat is the difference in seru$ and spinal fluidN Gay $ore protein in spinal fluid ,c it1s an ultrafiltrate. CellN .ardly any cells in spinal fluid (none!. LlucoseN 8ower in spinal fluid a,out A67 of what it is in seru$ (if the spinal fluid glucose le-el were low, then so$ething is in there utiliCing it for energy such as ,acteria or fungus or cancer cells!. Is there anything +'2; in spinal fluid than seru$N Chloride (way higher in spinal fluid than seru$! D around 1(6. )hese are i$p ,c there are injuries to the head. ;xa$ple: ,ase,all that hits the eye in an or,ital ,lowout fracture can potentially ,rea% cri,rifor$ plate, leading to dripping fluid out, which could ,e snot, seru$, or spinal fluid. 9o, its i$p to %now diff1s ,twn the two. ;xa$ple: wac%ed in the head fluid out of ear (otorrhea!, he$orrhage leads to ,attle sign. )his is a fracture of the ,asilar plate and there is spinal fluid there. +ost of the fluid co$es out the a#ueduct of syl-ius which is the +CC of hydrocephalus in children ,c it gets ,loc%ed off until you get a ,uild up of spinal fluid in the 0rd -ent and lateral -ent, which is a narrow area and leads to hydrocephalus. )hen, it co$es to the fourth -ent and needs to get out ,c it needs to get into the su,arachnoid space. 9o, it goes through the fora$en of 8usch%a and +agendie, so fluid goes out. ?ura $eans strong it1s tightly adherent to the periosteu$. 9o, when pt has epidural he$ato$a (,lood clot ,etwn ,one and dura!. )he only pressure that can split the periosteu$ away fro$ dura is arterial pressure. 9o, !)is is !)e one 3)en !)e mi**%e mengia% ar!ery r&p!&res, and can ,e done with arterial pressure (not -enous!. It gets into the su,arachnoid space (to protect us a cushion against da$age!. Let rid of spinal fliud in arachonoid granulation. ZA tu$or can arise fro$ the arachnoid granulations $eningio$a.[ It goes through the arachnoid granulations, (there are &' 8B+*.A)IC9 I& 32AI&! and the dural sinuses and conglo$erate into the jugular -ein, which is e$ptied into the right side of the heart. 9o, when you do a -alsal-a and the nec% -eins distend, that pressure trans$its all the way ,ac% to the dural sinuses, to the arachnoid granulations through the spinal fluid , and right down the the needle in the su,arachnoid space at 8> and the pressure goes up. )his is called #ua%ens step $aneu-er. It is a great test for when you are doing a spinal tap to see if the entire su,arachnoid space is patent. If you don1t see that $ano$eter go up, there is so$ething ,loc%ing the spinal fluid $ore proxi$ally. ;xa$ple: when you wt lift, you shouldn1t hold your ,reath ,c the pressure are huge and and lead to a herniated dis%. Ten!ori&m Cere-e%%i @67 of ,rain tu$ors in adults are supratentorial (in-ol-e cere,ral cortex! @67 of ,rain tu$ors in %ids are infratentorial (cere,ellar, cystic astrocyto$a, $edullo,lasto$a! Hy*ro ep)a%&s Co$$unicating -s &onco$$unicating Co$$unication of spinal fluid in -entricles with su,archnoid space. Non omm&ni a!ing +C 9o$ething is pre-enting spinal fluid in the -entricles fro$ getting into the su,arachnoid space +CC , s!enose* A;&e*& ! o' <y%1i&s 'r so$ething going in the >th -ent, ependy$o$a in %ids will ,loc% it off, or $eningitis in ,ase of ,rain ()3!, leads to scar tissue ,c ,loc%s fora$en of $agendie and lusch%a. Comm&ni a!ing 9till co$$unicating, ,ut still a ,uild up of pressure. 'ne cause could ,e tu$or of choroid plexus (papillary loo%ing!. 9o, if you ha-e a tu$or there, you ha-e a greater ultrafiltrate of plas$a and would ,e $a%ing $ore plas$a. Also, would ,e $a%ing $ore spinal fluid. )here would still ,e a co$$unication with here, ,ut the pressure would ,uild up ,c $a%ing $ore than you co$$only do. +ore co$$only, what if you ha-e a su,arachnoid ,leed or $eningitisN )hen pt has scarred off arachnoid granulations and ha-e no way of draining it out. 9o, still ha-e a co$$unication, ,ut cannot get rid of it (+C!. Arno%* C)iari +a%'orma!ion ;xa$ple: pull down spinal cord. )his would ,ring the $edulla into the cer-ical region and $ay,e a lil part of the cere,ellu$. 8eads to hydrocephalus and platy,asia (flattening of the ,ase of the s%ull! Dan*y 3a%6er syn*rome Cere,ellar -er$is is not de-eloped Hernia!ion Ghy would we herniate in the ,rainN 3c there is cere,ral ede$a and no other place to go. )he fa$ous ones are tonsillar herniation through the fora$en $agnu$. (fro$ the cere,ellu$! cere,ellar herniation has ,een s#ueeCed into the fora$en $agnu$, and has constriction. Can cause i$$ediate death.
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<ncal herniation $edial portion of the te$poral lo,e herniates through the tentoriu$ cere,elli and pressing against $id,rain, leads to he$orrhage (duret1s he$orrhage!. Also an oculo$otor ner-e that is gonna ,e co$pressed. 9o, this will lead to opthalo$oplegia (82A9'>, 0!, so e-erything inner-ated ,y C& III is paralyCed. Gith oculo$otor ner-e palsy, it is down and out. (down and in is C& > palsy if C& A is paralyCed, will loo% cross eyed!. 8oo% at pupil. ;xa$ple: +2I of ori,it, na$e $uscles *arasy$pathetic constrict the pupil (nor$ally! , sy$pathetics dilate (nor$ally! 9o, if you $ess up the parasy$pathetics, which nor$ally constrict, it will lead to $ydriasis. )he first sign of uncal herniation is $ydriasis of pupil on side of herniation (so it dilates on that side!. Also, posterior cere,ral artery can get ,loc%ed with uncal herniation, leading to post lo,e infarction. 8no3 -rains!em an* CN#s an* )o3 i! re%a!e* !o )ernia!ion Papi%%e*ema Any cause of increased incranial pressure Kit A tox 8ead poisoning deltaDa$inole-ulinic acid leads to increased per$ea,ility Audio file ?ayE SA C&9 Hy*ro ep)a%&s +CC " stenosis of the a#ueduct of syl-ius &onco$$unicating. Let hydrocephalus ,c the sutures ha-e not fused if you $iss hydrocephalus in adult and sutures ha-e fused, will lead to dilatation of the -entricles and e-entually o-er years, the pressure will turn ,ac% to nor$al ,c the increased pressures %eep the choroid plexus fro$ $a%ing so $uch ?e$entia, ataxia, urinary incontinence. A%a nor$al pressure hydrocephalus (,c pressures nor$aliCe! T&-ero&s < %erosis AD .a$arto$as (noneoplastic proliferation of things! Kentricles ha-e ,u$ps called tu,ercles which are ha$arto$as which ha-e proliferation of astrocytes. )hey produce ha$arto$as that ,ulge into the -entricle, called candle stic% dripping. .e$arto$as of the %idney called angio$yolipo$as, +2, cardiac tu$ors (rha,do$yo$as!, shagreen patches, areas of hypopig$entation, woods light shine out Anen ep)a%y Gorst of neural tu,e defects A,sent ,rain .er!e-ra% ar ) *e'e !s <pina -i'i*a o &%!a tufts of hair co$e out, -ert arches do not touch, no $eninges co$e +eningo eo%e $eninges co$e out +eningomy%o e%e ,oth $eninges and spinal cord co$e out .igh alpha feto protein le-els in ,lood of $other5 decreased in downs syndro$e .a-e to ,e on folate to pre-ent neural tu,e defects (neural tu,e finished for$ing ,y 06 days, so $a%e sure she is on folate if she is trying to get pregnant!. Ne&ro'i-roma!osis Al,right syndro$e (precocious pu,erty, cafX au lait, ,one Cits! 9turge we,er CafX au lait (coffee colored non raised lesions! spot, plexifor$ neurofi,ro$as, hyperpig$entation in the axilla (axillary frec%ling!, neurofi,ro$as A? , therefore late $anifestations (esp for neurofi,ro$atosis!, penetrance, -aria,le expressi-ity (you are expressing the dC, ,ut diff le-els of how se-ere the dC is! ;xa$ple: pt with HTN and pic, what test would you getN 2elationship of neurofi,ro$a with pheochro$ocyto$a, therefore get a (> hr urine for K+A and $etanephrine. A o&s!i s )3annoma ;xa$ple: pt with sensorinerual hearining loss ,R tu$or of 9chwann cells around C& T +eningiomas 'ptic ner-e glio$as <yringomye%ia ;xa$ple: pt that wor%s in factory and one of wor%ers says you are ,urning your hand and pt didn1t notice this, on exa$ loss of $usculature (loss of 8+&! in intrinsic $uscles of the hand, loss of pain and te$p in cape li%e distri,ution across ,ac%. Can1t feel pain (not A89 in A89, first place of de-elop$ent of loss of $uscles is here, so don1t confuse5 ,ut A89 is <+& and 8+& loss, *<2; +')'2 , so if pt has pain, ie, this is sensory and not A89! 3ig cystic ca-ity %noc%ing off spinothala$ic %noc%ing off pain and te$p. can %noc% off the corticospinal tract and anterior horn cells, so it will ,e a C'+3' of sensory A&? $otor loss for syringio$yelia. In'e !ions
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+eningi!is 1s en ep)a%i!is +eningitis infla$$ation of $eninges and nuchal rigidity5 if you $o-e your head or extend your %nee, you will stretch the $eniges, leading to pain (stretching infla$ed $eninges!. ;ncephalitis sleeping sic%ness they are always sleeping and drowsy5 they ha-e $ental status a,nor$alities (not nuchal rigidity! *us at the ,ase of the ,rain can possi,ly ,loc% lush%a and $ajendie, leading to o,structi-e hydrocephaly and nonco$$unicating Ghen you 2x $eningitis, use steroids and A,s. whyN 9teroids pre-ent scar tissue for$ation and co$plications that arise with it (ie hydrocephalus!. )his is standard )3 $eningitis 2x ()3 in ,rain causes -asculitis and scarring! ?eafness is a co$plication of $eningitis. Ra-ies ;xa$ple:: $eningitis, cere,ral a,cess, 2a,ies (+CC in 9tates " s%un%s, dogs in 0rd world! &egri ,odies (per%inje cell inclusion! C+. *eri-entricular calicifications ;xa$ple: section of %id (,rain! D see white stuff going around -entricles +C congental infection " C+K Ghat ,ody fluid is ,est to culture fro$N <rine +eningi!is Ghat is +C $eningitis:sepis in first $onth of lifeN Lroup 3 strep strep agalactae ,c $any wo$en ha-e this organis$ in their -agina, so they are carriers. *re$ature ruptured $e$,ranes lets the organis$ get up, get an chorioa$nionitis and into the ,loodstrea$. (nd +CC is ; coli 0rd +CC is listeria $onocytogenes (gra$ / rod with tu$,ling $otility as does )richo$onas -aginalis! Ghat food should pregnant wo$en a-oidN 9oft cheeses (ie feta cheese, ,ut listeria is present!. +C in 1 $onth 1T yo " & $eningitides (not . influenCa ,c -accination! +C in 1T/ " 9trep pn ;xa$ple: E( yo $an, nuchal rigidity, tap shows increased protein, increased neutrophils and decreased glucose dxN 9trep pn. what is the gra$ stainN Lra$ / diploccus Cryp!o o &s India in% see narrow ,ased ,ud for Cryptococcus Gho do you thin% this is inN IC1d pts Ghat is +C i$$unodef in <9AN AI?s +CC $eningitis in AI?s ptsN Cryptococcus +& ormy osis In frontal lo,e, therefore fro$ a dia,etic in %etoacidosis ;xa$ple: special stain on AI?s pt with C? > ct of E6, C) showed space occupying lesion ?xN Toxop%asmosis ;xa$ple: pig herder, and long ti$e pro,le$ with focal epileptic seiCures (dilating therapy! $ultiple calcified and cystic lesions in ,rain dxN Cys!i er osis ;xa$ple: Faco, CruetCfeltds fro$ prions ($ad cow! who is $ost li%ely to getN &europathologists, neurosurgeons, ,eef, lettuce fro$ AriCona (cow $anure on it! Tra&ma!i %esions Epi*&ra% )ema!oma (a,o-e dura! hit in head $iddle $eningeal ha-e to fracture ,one (under arterial pressures, can separate dura fro$ periosteu$!. Ghen you get E6 $ls of ,lood, you get uncal herniation and die. Ie get hi$, say they are o%, A hrs later epidural he$ato$a and death <&-*&ra% )ema!oma rupture of ,ridging -eins ,etwn dura and arachonoid $e$,rane. If you ha-e cere,ral atrophy, then the space ,wtn the dura and arachnoid $e$,ranes is ,igger. 3ridging -eins dangling, ,rea% and get a he$ato$a. 4luctuating le-els of consciousness. 8eft untreated lead to de$entia. ?o C) to r:o epi and su,dural he$ato$a (also for stro%es if its a he$orrhagic stro%e! <!ro6es 9lide: 3rain: one side is ,igger. Atherosclerotic stro%e5 pale infarct of ,rain. At ,ifurcation, there is an atherosclerotic pla#ue and thro$,us. &o ,lood flow to ,rain and it infracted, starts ,rea%ing down, no reperfusion, so it re$ains a pale infarct. If the thro$,us did ,rea% apart, and reperfusse the ,rain, the ,lood in the goes into the area of infarction and is called a he$orrhagic infarct. .owe-er, this usually doesn1t occur and pale infarcts $ore co$$on. If no ,lood, and there is infarction, pt is a candidate for heparin therapy. '-er ti$e, if pt sur-i-es, ends up with cystic space where there was infarction and this is called li#uefacti-e necrosisDDpale infarct, li#uefacti-e necrosis.
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9lide: he$orrhagic infarct ,lood is to edge of ,rain this is an e$,olic infarct, usually fro$ left side of the heart. )he -essel it always goes to is $iddle cere,ral artery. It gets into the Circle of Gillis and into the $iddle cere,ral. If you e$,oliCe down, will go into the superior $esenteric )he reason it is he$orrhagic is ,c pt will get ,rea%down of fi,rinolytic syste$ of the e$,olus and leads to reperfusion. Instead of ,eing a pale infarct, it1s a he$orrhagic infarct. 9o, ,oth a atherosclerotic stro%e and he$orrhagic stro%e are ,oth infarcts one is pale and the other is he$orrhagic. 9lide: HTN, pressures cause lenticulostriate -essels to co$e up and supply this area of the ,rain. ?eri-e fro$ the $iddle cere,ral aneurys$s, called Charcot 3ouchard aneurys$ and it ruptures, leading to giant he$ato$a and ,lood clot. .orri,le prognosis. 9o, e$,olic stro%e goes to surface of the ,rain and if it1s in the ,asal ganglia, i!#s a%3ays an in!ra e-ra% -%ee* 'rom HTN. ;xa$ple: s&-ara )noi* )emorr)age $ostly due to rupture congenital ,erry aneurys$. +C at the junction ant co$$ ,ranch of ant cere,ral artery 8ess co$$on cause of 9A.: A. ma%'orma!ion 9turge Ge,er on sa$e side as s%in lesion of the face, there is an AK $alfor$ation La &nar in'ar !s s$all areas on the ,rain5 unusual ,c they hit areas of the ,rain. ?epending on where in the internal capsule, can ha-e a pure $otor stro%e or pure sensory. +C due to .)& +&%!ip%e < %erosis /+<0 +C *emye%ina!ing D> /a&!oimm&ne0 = +< <%i*e:de$ylinated: white $atter has $yelin it, grey doesn1t. If you are destroying white $atter, then you1ll see grey underneath. P%a;&es o' +<. ( ways to de$ylinate 1! %noc% off cell that $a%es $yelin in the ,rain (oligodendrocytes in ,rain, schwann cell in *&9! -iruses do this su,acute sclerosis, progressi-e $ultifocal leu%oencephalopathy, .*K they affect the oligodendrocyte5 (! can also ha-e A,1s against $yelin and not the oligodendrocyte, which is +9 paresthesias &ystag$us, ataxia, optic neuritis with ,lurry -ision (+CC o' Op!i Ne&ri!is, +< ,c de$ylination of optic ner-e! In!ern& %ear op!)a%map%egia (de$ylination of +84! D pathogno$onic <pina% !ap 3i%% s)o3 in rease* pro!ein@ norma% g%& ose@ in rease %ymp)s Hy*ro ep)a%&s Ex .a &o 9e-ere atrophy of ,rain and -entricles loo% ,igger than they should ,e ?e$entia A%>)eimer#s D> Classic lesion: senile pla#ue, neurit1s, a$yloid (3etaMM! so ,eta a$yloid is toxic and the $ore you ha-e the $ore toxic pathogno$onic of alChei$ers, on c1so$e (1, therefore seen in down1s, neurofi, tangles (in any de$entia and .?! AlC pro,s in higer le-els de$entia 'nly way to dx is autopsy (confir$ation! see senile pla#ues Par6inson#s D> 2esting tre$or
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