GOLJAN High Yield - Systemic Pathology Notes

PATHOLOGY NOTES DR. GOLJAN SYSTEMIC PATH— EEE Note: This material is copyrighted. All rights reserved, GOLJAN HIGH YIELD NOTES FOR USMLE STEP 1° Note: This material is copyrighted. All rights reserved. No part of this publication may be reproduced in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher (Edward F. Goljan, M.D.) Abbreviations commonly used: AD = autosomal dominant, AR = autosomal recessive, COD = cause of death, Dx ~ diagnosis, MC = most common, MCC = most common cause, PaO; oxygen in arterial blood, PB = peripheral blood, Rx = treatment, Sa0. blood, SXR = sex-linked recessive artial pressure of ‘oxygen saturation of arterial Systemic Pathology RBC disorders ‘© Peripheral blood pictures on USMLE: 1. hypersegmented neutrophit- folste/B,, deficiency 2. microcytic hypochromic cells A. RBCs that have increased pallor can be assumed to be microeytic B, iron deficiency C. anemia of chronic disease (ACD) D. thalassemia E. _ sideroblastic anemia sickle eells~ sickle cell anemia not trait have sickle cells in the peripheral blood 4. target cells A. bullseye B. alcoholic liver disease CC. hemoglobinopathy spherocytes- A. _no-central area of pallor B. ~ congenital spherocytosis C. ABO hemolytic disease of newborn 6. tear drop- A. myelofibrosis B. thalassemias 7. Howell Jolly bod; pleen surgically removed or dysfunctional spleen as in HbSS disease, 8. _platelet— small, red, anucleate cell 9. lymphoeyte- black dot with a thin rim of eytoplasm 10, Auer rod~myeloblast with immature nucleus and splinter-like structures in the eytoplasm 11. atypical lymphocyte— ‘A. big cell with abundant sky blue cytoplasm B, _ infectious mono/CMV /toxoplasmosis/viral hepatitis/phenytoin 12. eosinophil ‘A. large red granules that do not cover the nucleus: same color as RBCs B. type hypersensitivity C. invasive helminthic infectionsNote: This materi is copyrighted. All rights reserved. 13. basophil- A. _ large purple granules that do cover the nucleus: granules darker than RBCs B. _ myeloproliferative diseases 14. rouleau~ RBCs with stack of coins effect: increased ‘sedimentation rate 15, _schistocytes— A. fragmented RBCs seen in microangiopathic hemolytic anemias B. thrombotic thrombocytopenic purpura C. hemolytic uremic syndrome D. DIC 16. reticulocyte A. special supravital stain: thin filaments represent RNA B. increased in: (1) hemolytic anemias 2) 5-7 days after blood loss, 3) after Rx of iron deficiency (4) Byy/folate deficiency 17, Heinz bodies— A. special stain: large blue inclusions with involvement of the RBC membrane B, G6PD deficiency 18. coarse basophilic stippling~ A. routine stain: persistent B. Pb poisoning ‘Bone marrow pictures on USMLE* megaloblastic marrow— A. all the cells appear big due to large, immature nuclei: e.g., giant band neutrophils B. _ B,2/folate deficiency 2. mayslofibrosis=marrow is composed of fibrous tissue: large cells represent megakaryocytes 3. aplastic:anemia~ empty marrow with predominantly fat, and islands of lymphocytes 4. multiplemyeloma— plasmablasts with bright blue cytoplasm, eccentric ‘huclei, perinuclear halo 5. ringed sideroblast— A. Prussian blue stain for iron: ring of blue around the nucleus of a normoblast B. _ indicate a defect in heme synthesis: sideroblastic anemias due to alcohol, pyridoxine, Pb poisoning, Exythropoiesis: 1. definition- ‘A. production of RBCs in the bone marrow B. dependent on erythropoietin (EPO) synthesized in the kidneys 2. stimuli for EPO- A. low PaO: hypoxemia B. anemia <7 gm/dL C. left shifted oxygen dissociation curve (ODC) 3. peripheral blood (PB) reticulocytes— A. manifestation of EPO stimulated marrow B. reticulocytes require 24 hours to become mature RBCs C. reticulocytes have RNA filaments: identified with supravital stainsNote: This material is copyrighted, All rights reserved. D. E. H. reticulocyte count is the most cost effective method of determinin marrow is responding appropriately to anemia: ca reticulocyte count is normally reported as a perc reticulocyte count is f following formula (1) corrected reticulocyte coun represents the normal Het @) example: patient's Het = 15% _Reticulocyte count = 9% Corrected count = 3% (15/45 x 9% = 396 corrected count >3% is considered a good response to anemia, (1) _ blood loss >7 days (takes 2) hemolytic anemias () Rx of iron deficiency with iron (4) Rx of Biz deficiency with Biz (5) Rx of folate deficiency with folate corrected reticulocyte count <2% is considered a poor response (somethi ‘wrong in the bone marrow): (1) iron deficieney @)__ anemia of chronic disease (ACD) @) _Biyfolate deficien (4) aplastic anemia (5) _ blood loss <1 week ed effective erythropoiesis \ge: normal 0.3—1.5% ‘st corrected for the degree of anemia (if present) with the patient Het / 4 ) x reticulocyte count, w arrow ~5~7 days to respond) Signs and symptoms of anemias: Byj/folate deficiency glossitis By: deficiency— posterior column/lateral corticospinal tract signs exercise intolerance dyspnea high output failure— deer ke ased viscosity of blood lowers total peripheral resistance lonychia (spoon nails)-iron deficiencyAouayoyp 2 (uouo> sow) Soustoryap aseuatiospsyap aeydsoi POM |< S80] poojg » 6joway onypedorTuvoso4yy 2 ep uour Sieg ue on¢jowioy SUMWUIOIMY » (sep 15>) 580} pooig P239P Dee supp (GVW) 9999p Day o1suLNUy t + secre ter PISO Toe STOTT PHT THRESH MOS IST PITTI) nail Shem, demyrody toms % & (U0 001-08 AW) semawy apssomsoy St dure) ofpay passa) aye byrne Aouatoxjap (usuryaqoa) tg « enuassejeyy « jony Jo BIWaUy « Aouatayjap 08> ADW) srywauy 2 (ADIN) auunjo4 seynasndio3 weayy Jo seq 94) uo eyuoNy Jo uoNEDYSsE1>, 2) Sip aay _ ,Note: This material is copyrighted. All rights reserved, Microeytic anemias: see Tables/schematies Iron studies: 300, 400 Iron 300 200 100 A B c D serum iron A. bar A represents the normal B. area in black is iron bound to transferrin: arrow with solid line C. height ofthe bar isthe transferrin level: arrow with interrupted line D. iron concentration is determined by stripping it off of the transferrin molecules with acid: iron in bar A= 100 TIBC is measured by adding iron to the patient specimen in order to fill up all available binding sites on transferrin A. iron bound to all the transferrin sites is then measured: TIBC in bar A = 300 B. there is an inverse relationship of transferrin with ferritin store inthe bone marrow (1) decreased ferritinstores, increases liver synthesis of transferrin; increases TIBC (2) _ increased ferritin stores, decreases liver synthesis of transferrin: decreases TIBC % saturation is a caleulation: % saturation of iron = iron/TIBC x 100 = 100/300 x 100 = 33% , serum ferritin— st sine best icon stuly x A. ferritin (storage form of iron) is found in all tissues (particularly in hepatocytes) and in macrophages (largest amount) in the spleen/bone marrow: there is a very small amount of circulating ferritin that closely correlates with the amount of storage iron that is available for Hb synthesis B. _ ferritin is low in iron deficiency, high in ACD, and high in iron overload disease iron deficiency bar B A. serum iron low: ~20 B, TBC high: ~500 (iron stores are decreased) C. % saturation low: 4% anemia of chronic disease bar C A. serum iron low: ~20 B, _TIBC low: ~200 (iron stores are increased in ACD) C. % saturation low: 20% D. serum ferritin is highaeewngs WIV y | omay > sseanuss WIV Vt ~ omy | cao Gc) aq (ec 2) °V aH (dt v aH Moroway 4 ouopy + SuEYD UEqOAE A4Q yy 1080)49 ysejqours0y, ukydsodojoag + Sujuosiod poo7 wos * | aseyepoypouay + omy ©P VO.) yo Kharsong (eyspuoyronia) foqory B}ApUoY, Pefop av 1o2fap Souayofep wosy + ewosoqry SISONVUAS wrEGD UIGOID, bafep vruassopyy sussquiow jsejqous0N (pesna.) upsaaysueay, vase aos wou. sssyomea >)Microcytic Anemins ‘Anes Pathogenesis Treatment [Laboratory Tests] Iron deficiency | + | Hb synthe- ferrous sulf- | Serum iron— J | ats eins sit! gheconate | thrombocyt- | synthesis « stools turn osis in chronic cases + microcytic and normocytic cells reason for T RDW * Decrease in nal: milk baby + Child bleeding Mecke!"s + Pregnancy- * net loss of 500 mg are not taken, * + Female S0 yrs~ GI bleed: R/O colon cancer succession— * no anemi stores —> fe TIBC, 1 % saturation, in: normocytic—> mic rocytic black ‘Anemia of «Tb synthe sis of tranferr- int binding e ry: TBC inflammation— micro- ‘© Hbis rarely <9 gavdL. * Rx underlying disease Serum iron— + TBC Serum ferritin« J lib synthesis— AR diseases {That can-Americans tear drop * B-thal- * African-Ameri- cel can, target cells «Terms severity B-globin chains have not been synthesized yet ated f° inor (B/B")~ mild protective effect ag malari ajor (Cooley's anemia, B°/B* )— hemo- © Hereditary persistence of HbF- + variant of f-thal noted in African-Americans, + absent f and 8 chain and y chains unite to form HbF, which © o-thal~ * Asians, * Affi- ib Bart's disease: Hb Bart’s t, + B-hal min- or: T in HbAy and HbFpasinbas sisejqozapt “Buys —mo.awen 20g © 1 -OMLL + | -woxy unaag « eyuoue 24) Jo snes oq) wo spuadog « eyuae oy) Jo. asnua ayy uo spusdag « SauuaIpURS LL 3 PIZBOET ep (a) uRopHca © Suoq wy 588/q0 “sopis pada» sequaue ansejqouapis uuAydiodoyoud aMkoosyphta 204) = dd soskydido uy -sodop -skva-x auog, 7 DML | -twoay wnaag « {dda Oma + ‘uiospuss Ayia qd -20g « 4 ‘antau jeipes coup ws14m + -Auyedoanou yesoy) Saiper qq ourgsuoow sorted | suo Azonod » ‘Auoro9y soneg seat pasvq-ad plo Bunva‘This material is copyrighted. All rights reserved. iron overload diseases bar D A. examples (1) sideroblastic anemias: Pb poisoning @) hemochromatosis @) hemosiderosis B, serum iron high: ~200 €. IBC low: ~200 (iron stores are high): note how the serum iron and TIBC are the D. — % saturation high: 100% serum ferritin is high USMLE scenarios: 1. PICA*for elay and ice~ iron deficiency 2. year old with 94% HbR- A. hereditary persistence of Hab F (variant of P-thalassemia) B. absent B and & chain synthesis with 9 concomitant increase in Hgb F (c and 7 chain synthesis) HbA and HbA: are absent high HDF prevents clinical symptoms of thalassemia uniform distribution of HbF in all RBCs compatible with life Differential features of the mierocytic anemias: bolded areas represent key differential points Fedeficieney ACD — a,fi-Thal minor Sideroblastic (Pb poison) Mcyv Low Low Low Low Serum iron Low Low Normal High TIBC High Low Normal Low % Saturation Low Low Normal High Serum ferritin Low High Normal High RDW High Normal Normal Normal RBC count Low Low High Low RBCFEP High High Normal High (Pb poison) Hbelectro. Normal Normal e-thal: normal Normal B-thal: THb A> and F Marrow iron Absent High Normal High Miscellaneous Ferritin best Hb electro. Coarse basophilic gold standard stippling ringed sideroblasts FEP = free erythrocyte protoporphyrin, MCV = mean corpuscular volume, TIBC = total iron binding, capacity, RDW = red blood cell distribution width Macrocytic anemias: see Nutrition notes, see Tables and schematic ‘© Sites for reabsorption or iron, folate, B, 1. duodenum iron A. Billroth II (distal stomach to jejunum, duodenum blind loop) associated deficiency B. malabsorption syndromes decrease iron reabsorption: e.g, celine disease jejunum- folate A. malabsorption syndromes decrease reabsorptioncot N‘-Methyl-F (tin folate and By, deficiency) Homocysteine Methyl-Cbl_ FH, (replenished bs Dihydrofolate reductase (inhibited by methotrexate, aaa aa yovesih Rescue Dihydrofolate (oxidized = Sy “Ly Lal be Lee Citvovorum factor replenishes 8 et om (leukoversin tesa “16 iz, Ff 7 ty lo Font oia, &, p —wame) pant Asa 4 “nemaig Vitamin By in propionate metabolism By Propionyl CoA. —P>Methylmalonyl CoA ——P Succinyl CoALaboratory Tests ented neutrophils~>5 nuc- ical disease akan monoglutamate; #birth control pills, # alcohol malignancy: eg. leukemia ‘© Serum folate { supply of folate += Serum homocysteine—* 1, «also tin Bu; deficiency, * vessel damage and thrombosis * Urine FIGIU (forminoglutamic acid)~ T Serum LDH 1 destruction of RBCs[iia deficiency | « Defect in ‘As above for DNA synthesis + Proprionate suceinyl CoA (TCA cycle) hody/fundus: #0 tor, #no acid # Pure vegan diet-B, al disease * site of in complex reab- disease ‘hronic pane! cleave off R factor from R factor- Bys complex, ¢ R factor from saliva protects Br. from acid destruc tion « Bacterial overgrowth— * diver- salar disease, * 1 peristalsis fro jomic neuropathy, * replace- ‘ment of muscle with collagen: progressive systemic sclerosis = PA patient= * sell waxy complexion, + elde women of Scandinavian origin # Glossitis— + smooth, sore + atrophy of papilla ne disease PA MCC Bidet ‘« Atrophie gastrit ‘and fundus * ant cell/F antibodies destroy predisposes to cancer * Malabsorption— loss of + Neurologi sensation and prop- disease, + UMN signs: corticospinal tract disease, dementia # Serum homocyste ine-? + Urine methytmato- nie acid most ser tests = Sehilling test + correction of B,amalab-Note: This material is copyrighted, All rights reserved. B. birth control pills and aleohol decreases monoglutamate reabsorption By, terminal ileum A. Crohn's disease/resection of terminal ileum decreases reabsorption B. also decrease in bile salt reabsorption—> malabsorption Vitamin By: (cobalamin) and folate: 1. sources of Br~ meat/dairy products B. not present in vegetables/fruits sources of folate— A. beer: cannot become folate deficient by drinking too much beer B. _fruits/vegetables C. grains functions of both folate and B,,~ DNA synthesis functions of By; onl ‘A. propionate metabolism: propionyCoA—+ methylmalonyl-CoA + By.» succinyl-CoA B. succinyl CoA used in: (1) TCA cycle as a substrate for gluconeogenesis 2) heme synthesis function of folate only— 1-carbon transfers to other intermediates for the synthe A. amino acids B. purines C. pyrimidines Br metabolism— Bj) requires intrinsic factor (IF) for reabsorption in the terminal ileum: IF is synthesized in parietal cells located in the body/fundus Br. is initially bound to R factor in saliva: R factor prevents gastric acid destruction of By pancreatic enzymes cleave off R factor: this allows By. to bind to IF Biy-IF complex is reabsorbed in the terminal i Biz is bound to transcobalamin in the plasma: delivered to metabolically active cells or stored in the liver (6-9 y supply) folate metabolism— A. folate is in a polyglutamate form in vegetables/grains-—> (1) converted into monoglutamates in GI by intestinal conjugase: enzyme is inhibited by phenytoin-> (2) monoglutamate is reabsorbed in jejunum: reabsorption blocked by alcohol and birth contro! pills > @) folate circulates in blood as methyltetrahydrofolate B. _ 3-4 mths supply of folate in liver: dietary deficiency common in aleoholies B,,/folate in DNA synthesis (see schematic)— A. By removes methyl group from methyitetrahydrofolate (1) methyl transferred to homocysteine: homocysteine converted into methionine 2) methyltetrahydrofolate becomes tetrahydrofolate (THF) (3) THF converted into N*'". methylene tetrahydrofolate—> (4) N*".methylene THF + thymidylate synthetase + deoxyuridine monophosphate — dihydrofolate (DHF) (S) DHF (oxidized form of THF) + deoxythymidine monophosphate (used for DNA. synthesis)—>Note: This material is copyrighted. All rights reserved. (6), DHT is converted by dihydrofolate reductase back into THF (reduced form) 9. causes of By; deficieney— A. pernicious anemia (PA): (McC @) autoimmune destruction of parietal cells (3) autoantibodies against IF and parietal cells (4) loss of IF leads to Biz deficiency (8) _achlorhydria: increases serum gastrin levels (6) chronic atrophic gastritis, of body/fundus: predisposition to gastric adenocarcinoma B. pure vegan diet C. chronic pancreatitis: cannot cleave off R factor . D. fish tapeworm E. bacterial overgrowth in small bowel: (1) bacteria destroy Bi2-IF complex 2) also destroy bile salts leading to malabsorption of fats F, _{erminal ileal disease normal site for B;,IF reabsorption: e.., Crohn's disease 10. causes of folate deficiency A. alcoholism: @) MCC of folate deficiency (2) not deficient in folate in a beer drinking alcoholic oor diet: elderly pregnaney/lactation: uses up folate disseminated cancer: uses up folate phenytoin: blocks intestinal conjugase birth control pills/aleohol: block uptake of monoglutamates in jejunum inhibition of dihydrofolate reductase: (methotrexate (2) trimethoprim 11. S/S of B,;/folate deficieney— A. macrocytic anemia: delayed nuclear maturation of hematopoietic cells B. glossitis C. diarrhea: (1) malabsorption 2) _ affects duplication of stem cells in the intestine 12. S/S unique to Br: deficiency A. subacute combined degeneration B. posterior column demyelination (1) _ lack proprioception @) lack vibratory sensation (3) positive Romberg's test C. lateral corticospinal tract demyelination (1) _ positive Babinski 2) upper motor neuron disease @) spasticity D. dementia 13. S/S unique to PA~ A. achlorhydria B. chronic atrophic gastritis body/fundus OmronNote: This material is copyrighted. All rights reserved. C. gastric adenocarcinoma autoantibodies correction of Shilling’s test with addition of IF lab findings in By/folate deficiency- A. large nucleated cells with immature nuclear features: cells are called megaloblastic B. pancytopenia: megaloblastic cells in the bone marrow are destroyed by macrophages before they enter the sinusoids C. _hyperseamented neutrophils: (1) >5 nuclear lobes @) excellent marker for B,y/folate deficiency D. increased plasma homocysteine levels: no methyl group to transfer to homocysteine to produce methionine if either B,, ot folate deficient lab findings unique to folate deficiency- ‘A. increased formiminoglutamic acid (FIGIu): usually metabolized by THF B. decreased serum folate C. decreased RBC folate: best test for folate deficiency lab findings unique to By: deficieney— A. decreased serum By, B. increased urine methylmalonic acid: build-up methylmalonyl-CoA proximal to the block C inste2524 Propionates (odd chained faty acids) cause demyelination and CNS findings non-radioactive Biz is first given to bind to all available transcobalamin in the peripheral blood (1) prevents any reabsorbed radioactive B,; from binding to transcobalamin (2) _ forces it to be excreted in the urine, radioactive By, given by mouth followed by 24-h urine for % radioactive Bis reabsorbed: no radioactive By: in 24-h urine confirms By: deficiency, + iftcorrected with addition of IF to oral radioactive Bx: patient has pernicious anemia D. _ ifcorrected after antibiotic therapy: patient has bacterial overgrowth E. _ifcorrected with addition of pancreatic extract followed by intake oral radioactive By patient has chronic pancreatitis Rx of folate deficieney— folate in pharmacologic doses can correct Bis deficiency but not the neurologic abnormalities Rx of Bi deficiency IM By:Note: This material is copyrighted. All rights reserved. Differential comparison of pernicious anemia (PA), other causes of By: deficiency and folate deficiency: Pernicious anemia | Other By, | Folate deficiency deficiencies | MCV Increased Tnereased Tnereased Pancytopenia Present Present Present Hypersegmented neutrophils | Present Present Present Megaloblastie bone marrow | Present Present Present Autoantibodies against IF and | Present ‘Absent ‘Absent parietal cells ‘Chronic atrophic gastri Present ‘Absent Absent (body and fundus) ‘Achlorhydria Present Absent [Absent Serum gastrin levels Tncreased Normal Normal Risk of stomach Increased None None adenocarcinoma Plasma homocys Tnereased Increased Tnereased Urine methylmalonic acid Increased Increased Normal Urine forminoglutamic acid | Normal ‘Normal Increased (FIGLu) Neurological disease Present Present None Schilling's test Corrected by add- | Not corrected | Not used ing intrinsic factor | by adding intrinsic factor Normocytic anemias: see Tables 2" USMIRIS8&hatios: 1, jamemia:since birth, splenomegaly= probable congenital spherocytosis: do splenectomy GOPD deficiency ‘cause of Paeumococeus infection in HBSS= autosplenectomy or functional asplenia (Howell Jolly body’ indicates absent or dysfunctional spleen ‘primaquine~ often precipitates hemolysis in G6PD deficiency Patient with hemolytic anemia post dapsone (sulfur drug, used in leprosy) and:aspirin— 6. peripheral smear with sickle cells in patient With osteomyelitis: Salmonetia species 1. extravascular y chart of mechanisms of hemoly is in the hemolytic anemias: ‘A. macrophage removal and destruction of RBCs: (1) abnormally shaped RBCs (e.g, spherocytes, sickle cells) (2) IgG and or C3 coating RBCs (e.g., autoimmune hemolytic anemia) B. increase in unconjugated bilirubin 2. intravaseular— A. intravascular destruction of RBCs B. RBCs damaged by (Q) calcified aortic valve in aortic stenosis (MCC) @) fibrin clots in DIC (3) _ platelet thrombi in thrombotic thrombocytopenic purpura and hemolytic uremic syndromeeuadoyfourd ~9a9 « «+ ‘uynqoya aso oydngynue + ‘exoowsynue + RTM» uoreqwe|d -sueay sous ‘2409 J0pisu0 pro sak Qg> + ‘jwour onde « vyuodonnou pi par -erposse wonsayut —A9AaT & viuod -orfooquionp -Suypaarg © wUIOUIKi» “189 WDIS Dey sede » —wrHaUy © wopeprY © AOH/EINVN “wonaayuy « auoz \qLduoud + ‘Joowayduresoyy9 ‘osm UMOWKY OWN + ~SBNIG © qurayna] arnoe 403 ys | souszu0q awospuds s,tuosue -addns —-aswastp 1129 wars « oyu -adoydoued © ymoue auseidy /p0o}q 404 sun Jo yonsdip « ‘seen’ joors Bs9pl0 + —fe101198) « sys9) quy ayppads oN « smoyduuds uuorsnysues, Dee Perea ‘Suypaayq yeusoqu ywe9 | Jus quem pareioosse ou sosnyoeay pei0uray Aq pamoi}o} sommyoe Siajad —saampovag © uuaajds pasmdna —s59 -us9pua} LI >] 49M © cod yyfiudn 0} auydns woy Fuysou ways J asjnd -oue o1J08 paunidny » ‘eunest :omn -idiu 2yu9jds + -smoaueyaosiyl © spue papts-Yya} < 4901109 popIs-iydise ‘plo sieak os<@ uy oyOP DE si9A0oun 9UITes, TeUOH %6'0 Jo worsryu + ‘woop Qery S10 noun pur 1si1p ss0] poor ayuoayojanay ‘59, KOWIOGET aD upwaTL, ‘equa Yq > Wad SHASO|NISH paTBITOD HH! IN ais SASOMIONip rood WORRA paunaa0 sey a UOUL U 49]]14 OURO pu 499 ‘asme ato wey | -Uwo SIV puodes —492UE UO}O & ‘a1ow 0} anp aq eu pur bey10}28 14490491 Aoueut poroadsns st s1se)sey xq Mouse au0, DAT POE, asvasip yous 214049 Jo OOW-smputjom soy2quiat « aswastp reuaet | up -ayodoayp Aa ©FINA 29) 1891 Koyo uy uo9 (895 s,mne4) 989) mnsas paypOy & Bynayn9q aynay « swHospucs 4e11}3-ppng, -2]0098 fjyeuL0U AVd «sou ~eaquiowt jj99 sisk SROqMORA USA sqEdSy u “1ouiay Sey uaroyap wo. jo 8 Ieuam;30u 7 4a}ea wwBNg | onewordurss » uyed jourwopqy « Temskxozeg | ALY f+ '2u0 quo Say p + -tusyaads sauyooea UH pue xeaow entuaue 21 Kjowsy sunuiwoyne “Aoug anr@ ysnu ~asop pue siso | sojped jennueo + "poo jeso OY + —ehuoue ap sjouy my] -kooHeyd ofvyd | ou SOM asuap eu 96590 Fe 5184) sovfoosands jo sommes paxnbay «| -oiovu sejnosen —soyfoo1oydg ~0Uay utBoq sorfoo104ds xo] -enxo—vjusaue | sysop iA SH AjOWII uasow ETSickle call Howell bodies— sign of ‘© Target cells © Trait has a normal smear Pathogenesis/epidemiology: | Clini ‘+ Hemolytic anemia— * Two main problems-* chronic hemolytic anemia, * vaso extravascular macrophage ive disease~ + sickled ct nonsickled cells stick to endothelium # Vasoaceh 2 organ damage, * hands and feet (dact nfant, # bone infarcts with pai ch syndrome: # fever, ¢ lung i RBC precursors filling the cords, * anemis = Com; new, re ; affinity prevents deoxygenation « Splenie sequestration erisis- + splenomegaly from sickle cell tions— * aseptic necrosis femoral head: ¢| triggered by a parvovirus infection, * is: #no RBCs produced, #no marrow eytosis: RBCS are produce 1g spleen by 2-3 yrs t decade before spleenve — mam — GePD ‘* Hemolytic © SXR disease w Avoidance [+ Active hemolysis-* | deficiency anemia mac- | © weak variant occurs in body preparation is « Protection against faleip- arom malaria the enzyme while RBC membrane, ‘omy is of no | RBCs have the enzyme + lack of GOPD: i benefit «# Asymptomatic (non- reduction i hemolytic) state an enzyme assay is used portion of the membrane hemolytic episodes- * lag phase of 2-3 d, + antibiotics: sulfa ‘» Fava beans— precipitate hemolysis in Mediterranean variant zal resent with o Black, Buck, rita pnt ies arith depsrng poe Omd parent 75 Emaar ae As ya nipenen of Dai i towel by deme 2? mp > Una ten lien} fusr dg fs ax ly dy an srsyant asterssroyda5ai aeydo-soew ssy90)9 89 “su yueysys0a uy uyngors “hAL® Snip og oda pag Sy CFI yee ona “aaa | E79 | AT 27M swuade 0 ot WT ee es viv so BUNTY bony ergs” bee edlyyyen'e a seg oe —e ~Kyouray jo ad $ W2]¢ ssIssyour a4 sejnoseanst » VHIV Jo ad uuem ¢ ‘SE uyywoo £9 20,/pue sad4y uurem pu pjoo oq ~Aypedo -uapeqdurdy pazyjesauas © suoysayur «9 (TBD) PID # + squi005 yoaarpA » | * 7 acs-siar Dee a AynssuasiodAy, SOY Jo 998-J3ns Uo £3 1 suon ues “quia 540 yexowss aed rou 01 2p -oue an djoursy ‘sunuinyosny{q pasorkaoend soxojduioo QH-uigorondey « “> + -uygordordey wnaas © oye ‘Soseuruesuen payenoja.¢ “pquroue andjoursy ¢ :eiscun -oid ¢ -amoupucs ¢VTaI ssouuns aoue; -duoj uy eywous s,r94un; ‘auoapucs 2yuaan ay Ajour9y vandand -sdoyds0quioayy poquiosys, ola -omyp snoquuosyp snjd vojaeyde -Aysopun ayy yyss sane, DOWN —#1s0uD}s OPO ~sayhoopsiyps «‘Note: This material is copyrighted. All rights reserved. c. haptoglobin svels decreased: haptoglobin binds to free Hb in plasma and is removed D. hemoglobinuria: often leads to iron deficiency E.__hemosiderinuria (Anemia Type of hemolysis | Congenital spherocytosis Extravascular { Congenital elliptocytosis Extravascular _| [Sickle cell anemia/variants Extravascular (major), intravascular (minor) Glucose 6-phosphate dehydrogenase Intravascular (major) extravascular (minor) | deficiency _| Autoimmune hemolytic anemia (warm IgG] Exravascular |Ltype) Autoimmune hemolytic anemia (cold IgM | Intravascular type) “Mieroangiopathic anemia ~[Tintravascular a Questions used during the board review: ‘WA 19-year-old Aftican American woman presents with fatigue and exercise intolerance. She has a bistory of menorrhagia. A CBC reveals a mild microcytic anemia, a low normal WBC eount tet Haber Pyatelet count. A corsected reticulocyte count is <2%, ‘Which of the following vets of laboratory data best represents the hematologic findings in this patient? jerum Iron | TIBC | % Saturation | RBC Count _| Ferritin | A. [normal ‘normal_| normal high normal | B. How low low high ¢. Dow high Tow low D. [high low high ‘high | E. [normal [normal | normal [ normal} C A= thalassemia, B= ACD, D= iron overload, E eo Which of the following charactetizes pernicious anemia rather than Bis def causes? A. Increased plasma homocysteine levels B. Increased urine methylmalonic acid C. Decreased vibratory sensation D. Hypersegmented neutrophils E. _ High serum gastrin levels F (other differences include achlorhydria, autoantibodies against intrinsic factor and parietal cells, correction of Schilling’s test with intrinsic factor) iency from other Which of the following would you expect in this patient if a blood sample w insertion of an IV line with 0.9% normal saline? SELECT 3 A. Normal hemoglobin and hematocrit B. Normal effective arterial blood volume C. Increased central venous hydrostatic pressure D. Decreased mixed venous oxygen content E, _ Decreased pulmonary capillary wedge pressureNote: This material is copyrighted. All rights reserved. "A.A year old African American child with sickle cell anemia presents with a high fever and nuchal rigidity. Seleral icterus and hepatosplenomegaly are present. A CBC rev, hormocytic anemia and @ WBC count of 21,000 cells/L. with left shit spinal tap reveals turbidity, increased protein, CSP and a blood culture to reveal. A. gram positive diplococei B. gram negative diplococei C. gram positive cocci D. gram positive rods E, _ gram negative coceobacilli A (Streptococcus pneumoniae) reals a moderately severe A urinalysis is normal, A and neutrophils, You would expect a gram stain of WBC disorders: see Tables ‘S Test for infectious mononucleosis: heterop hile antibody, which detect RBCs antibodies against horse ‘ Classification of polycythemia: = Subtype of Polycyth- | Causes/Diseussion emia | Absolute polyeythemiar | Chronic obstructive pulmonary disease: 1LMCC in this category low | Appropriate: stimulus of | PaO, tissue hypoxia High altitude residents Lpereentage of oxygen is 21% but the atmospheric pressure is decreased— low PaO; Cyanotic congenital heart disease: Light to left shunt~ low PaO, Hypoventilation syndromes (sleep apnen, Piekwickian syndrome; respiratory acidosis low PaO; {aft shifted oxygen dissociation curve: decreased release of aaygen to issue” A. CO poisoning: (1) low SaOs, (2) normal PaO, B.| tnethemoglobinemia: (1) low SaO;, 2) normal PaO;, C. increased Hb F Absolute polycythemia: | Polyeythemia rubra vera: normal PaOySaO, and low enti oietin Inappropriate~ no Renal disorders: L.increased erythropoietin— A. normal PaO,/Sa0. hypoxic stimulus normal PaOy/Sa0,, (1) renal adenocarcinoma/Wilm’s tumor, (2) cysts Endocrine disorders: Cushing’s syndrome- cortisol and 17-ketosterov | stimulate erythropoi Miscellaneous: Luterine leiom: cerebellar hemangioblastoma— incidence of renal adenocarcinom: erythropoietin production Relative polyeythemia: | Smoker's polycythemia: unexplained effec oF earbow monoxide in| | dus to decreased plasma | smoke increases RBC mass nicotine decences plasma volume by | volume, normalRBC | vasoconstriction mass iyomas— compression of urelers, 2. Part of von Hippel disease: increased | a, Schepatocellular carcinoma ectopic Stress polycythemia (Gaisbock’s syndrome): individuals under constant L stress— typically males with hypertension and obesity [ Volume depletion: volume contraction hemoconcentrates RBCsBenign Quanti Leukocyte Disord Characteristics ‘Clinieal Findiogs | Laboratory Findings fons—* MCC, + e.g., acute append- | « Variable * CBC with a 100 WBC differential count * Bone marrow exam= usually not necessary stress * Blood cultures i ‘+ Mycloproliferative disease + polycythemia suspected ‘ubra vera, * chronic myelogenous leukemia ‘* Metabolic disease—* urcmia, + ketoacidosis Hematologic disease— acute hemolytic in body cavities nfection is + Drugs that decrease adhes synthesis— * torticosteroids, epinephrine + Endocrine— + pheochromocytoma, + Cush- ing’s syndrome molecule * Miscellaneous~ + smoking, + tumor necrosis Leukemoid reac- + Exaggerated | « Infections + TB, + whooping ‘+ Frequently conf | * Leukocyte alkaline phosph- tion benign leukocyte | infectious lymphocytosis, + perforated acute | used with leukemia | atace (LAP) score— + LAP is + 30,000 to >50,000 | response to infec- Present in specific granules: leukocytes/uL, tion common in tion may —_| children and volve- + neutro- | malignancy: espe- © No blasts presentwon yews pasvasou snsioa yOajoP uonempeut snsiaa equoue onsejde no a[fu :urexo MoauEM 9UOg © aao¢ x sadsapy ~BastA ppipung -¥3ung © SaeSHOMY-UESTAY UF up ounou « ‘sjsdas aanyeBau wre uy suyxoiopus { -stsaypuds ajna9jout wo1soqpY | © yayue proveunays + oud -onjnau ounuumoyne :owospucs 6 A> + “1S rojuadonnou auntmumoyne + —wononaysog | « yeday ADH/INVN + ‘etuadosynau :proydds « ~$980; peurshxosed ¢ “Ao -qoud uononnsap + ‘uoyonpoad + ~S1apa0syp 21dojovewoHt © uopoapord f° ‘anos THs? 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Seus yun ‘ons) ayy Jo suoryeut spou any aes —1\, spou sany 04 -O1N -ddsuesy mosaeur ou0% ‘uyed 2409 + i pwaraans ysogt auyqeserg snyd eo sista pun parsed + ody « —urexa Mouse ato | ‘ruadoyfooquiosy 599 Ajuowwos siseiq + —S3u1puy DEAL © Byuaue spsomoN 6 | aifu jo savak 09-S1 woomoq eyuI2 4H] DW ya9 ways jeuo]3 © Yel DIMoOKE wou ano LWW 4s 's,oupausing iq) Brurayjnayo -yyhaa omnoe -9141 vou aynae ~SW 0z-S1 -ofadui 21n98 -FL 8401-5 son Koojnu -eifoad one —9 %0p-0F uoneuMeW WY -7W f-¢ “IW parenusrayy1p snousojasur seywyn3y -ydurgjuou ayn9yNote: This material is copyrighted, All rights reserved, © Differential diagnosis of the polycythemia disorders: bolded areas represent good differential points _ Condition RBC mass Plasma Sa0; Erythropoietin volume PRV Tnoreased Increased | Normal | Decreased ‘Copp Increased ‘Normal | Deereased_| Increased Cyanotic CAD [increased Normal Decreased | Increased Renal adenocarcinoma | Increased Normal Normal | Tnereased Volume depletion Normal [ Deereased__| Normal | Normal PRV = polycythemia rubra vera, COPD = chronic obstructive lung disease, CHD = cyanotic congenital heart disease ‘How to recognize leukemia and leukemia types: 1, acute vs chronic > A. bone marrow exam revealing >30% blast cells is acute leukemia. €-— B. _ blast count not high in chronic 2. usual profile A. anemia: usually normoeytic B. thrombocytopenia: CML only leukemia that may have thrombocytosis C. high WBC count with blast cells: may be a normal count, but blast cells will be present ‘generalized lymphadenopathy hepatosplenomegaly F. bone pain G. fever use age brackets to pick out most likely choice A. 60CLL (1) also MCC of generalized lymphadenopathy in the elderly @) also MC overall leukemia & Summary of laboratory tests iu hematology: Laboratory Test Comments ‘Osmotic fragility Increased in congenital spherocyiosis, Decreased tn conditions | vith target cell (excess RBC membrane) Sugar water test/Ham/s test | Sugar water test is the screen and Ham's text the conlinalon Text for paroxysmal noctumal emoglobinuria~ absent decay L accelerating factor, Hemoglobin electrophoresis Gold standard test for identifying an Inorease tn nommal Hib (om Hb A; and F in B-thalassemia) or an increase in an abnormal Hb (e.g. Hb SS, Hb SC). Enzyme assays Confirmatory test in glucose G-phosphate dehydrogenase deficiency in quiescent stage and pyruvate kinase deficiency Serum iron Decreased in iron deficiency and anemia of chronic inflammation | (ACD). Increased in sideroblastic anemias (e.2, lead poisoning) and iron overload conditions (e.g., hemosiderosis, hemochromatosis)Note: This material is copyrighted. All rights reserved. Total iron binding capacity «TIBC) Percent saturation of transferrin [Serum ferritin [Tron stain Free RBC protoporphyrin | tevels (FEP) [Serum Bis [Serum folate/RBC folate [Urine forminoglutamic acid [rine methyimatonic acid Serum homocysteine Serum lactate dehydrogenase (LE) Unconjugated bilirubin (Serum haptoglobin Urine hemosiderin | Sickle cell sereen [Donath-Landsteiner antibody Direct/Indirect Coombs test | Reticulocyte count Heinz body preparation "| Correlates with transferrin levels. Increased in iron deficiency Decreased in ACD and iron overload disease Decreased in iron deficiency and ACD. Increased in iron overload states. Decrease in iron deficieney. Increased in ACD and iron overload diseases. - Prussian blue stain. Absent iron in iron deficiency. Increased iron in ACD, sideroblastic anemia (identifies the ringed sideroblast) and iron overload states. Increased in iron deficiency, ACD, and lead poisoning. Decreased in pyridoxine (B6) deficiency - Decreased in Biz deficiency and increased in polycythemia rubra vera and chronic myelogenous leukemia Decreased in folate deficienc; Increased in folate deficiency. Increased in By deficiency Increased in By, and folate deficiency (MCC). Increased in any condition with RBC hemolysis (eg intravascularfextravascular hemolytic anemia, ineffective erythropoiesis in B,y/folate deficiency) or with massive breakdown of cells (e.g. leukemia). Increased in extravascular hemolytic anemias (eg, congenital spherocytosis, autoimmune hemolytic anemia), Decreased in intravascular hemolysis and severe extravascular hemolysis (Fb leaks out of phagocytosed RBCS), Increased in chronic intravascular hemolysis (eg, microan pathic hemolytic anemia, paroxysmal nocturnal hemoglobinuria), Solubility test and metabisulfite test. Positive in Hb AS, Hb SS, Hb SC, Hb Sithalassemia _ Bithermal antibody. Positive in paroxysmal cold hemoglobinuria Detect IgG, IgM or C3 on the surface of RBCs (direct Coombs) or detect IgG or IgM antibodies in serum (e.g., anti-D; indirect Coombs), Gold standard test for autoimmune hemolytic anemias. Positive in ABO and Rh hemolytic disease of the newbom, Supravital stain to identify RNA filaments in young RBCs. Gold standard test to evaluate effective erythropoiesis. Increased > 3% in hemolytic anemias, treatment phase of iron deficiency, Byp/folate deficiency and in blood loss >7 days old. Increased in disorders that metastasize to the marrow (e.g., breast metastasis to bone) or in primary diseases of the marrow that push reticulocytes out (€.g,, acute/chronic leukemia). Decreased <2% in most of the microcytic anemias (exceptions: lead poisoning, severe « and B- thalassemia), Bi, and folate deficiency, aplastic anemia, anemia of renal disease, blood loss < 5~7 days. Supravital stain to identify denatured Hb in RBCs secondary to peroxide deficiency damage in glucose 6-phosphate dehydrogenaseNote: This material is copyrighted. All rights reserved. Total iron binding capacity Correlates with transferrin levels. Increased in iron deficiency «TIBC) Decreased in ACD and iron overload disease Percent saturation of Decreased in iron deficiency and ACD. Increased in iron overload transferrin states. [Serum ferritin [Tron stain [Free RBC protoporphyrin levels (FEP) [Serum By Serum folaidRBC folate [Urine forminoghutamie acid [rine methyimatonic acid Serum homocysteine Serum lactate dehydrogenase (LE) Unconjugated bilirubin ‘Serum haptoglobin Urine hemosiderin | Sickle cell sereen |Donath-Landsteiner antibody Direct/Indirect Coombs test Reticuloeyte count Heinz body preparation Decrease in iron deficieney. Increased in ACD and iron overload diseases. - Prussian blue stain. Absent iron in iron deficiency. Increased iron in ACD, sideroblastic anemia (identifies the ringed sideroblast) and iron overload states. Increased in iron deficiency, ACD, and lead poisoning. Decreased in pyridoxine (B6) deficiency - Decreased in Biz deficiency and increased in polycythemia rubra vera and chronic myelogenous leukemia Decreased in folate deficiency. Increased in folate deficiency. Increased in By deficiency Increased in By, and folate deficiency (MCC). Increased in any condition with RBC hemolysis (eg intravascular/extravascular hemolytic anemia, ineffective erythropoiesis in B,y/folate deficiency) or with massive breakdown of cells (e.g. leukemia). Increased in extravascular hemolytic anemias (eg, congenital spherocytosis, autoimmune hemolytic anemia), Decreased in intravascular hemolysis and severe extravascular hemolysis (Fb leaks out of phagocytosed RBCs), Increased in chronic intravascular hemolysis (eg, microan pathic hemolytic anemia, paroxysmal nocturnal hemoglobinuria), Solubility test and metabisulfite test. Positive in Hb AS, Hb SS, Hb SC, Hb Sthalassemia _ Bithermal antibody. Positive in paroxysmal cold hemoglobinuria Detect IgG, IgM or C3 on the surface of RBCs (direct Coombs) or detect IgG or IgM antibodies in serum (e.g., anti-D; indirect Coombs), Gold standard test for autoimmune hemolytic anemias. Positive in ABO and Rh hemolytic disease of the newbom, Supravital stain to identify RNA filaments in young RBCs. Gold standard test to evaluate effective erythropoiesis. Increased > 3% in hemolytic anemias, treatment phase of iron deficiency, Biy/folate deficiency and in blood loss >7 days old. Increased in disorders that metastasize to the marrow (e,g., breast metastasis to bone) ot in primary diseases of the marrow that push reticulocytes out (€.g,, acute/chronic leukemia). Decreased <2% in most of the microcytic anemias (exceptions: lead poisoning, severe & and B- thalassemia), Bi, and folate deficiency, aplastic anemia, anemia of renal disease, blood loss < $~7 days. Supravital stain to identify denatured Hb in RBCs secondary to peroxide damage in glucose 6-phosphate dehydrogenase deficiencyNote: This material is copyrighted. All rights reserved. | Leukocyte alkaline phospha- Stain of neutrophils and seore based on the intensity of the sta | tase (LAP) score Marker of mature neutrophils. Increased in benign neutrophil disorders but decreased in chronic myelogenous leukemia, Immunophenotyping of Gold standard test to subelassify the type of eell involved in acue] lymphocytes lymphoblastic leukemia, ‘Tartrate resistant acid ‘ey stain for identifying neoplastic B cells in hairy cell leukemia; | phosphatase (TRAP) stain Philadelphia chromosome 12:22) located on “chromosome 22 in chronie myelogenous [ leukernia, | Heterophile antibody test Test to identify the unique heterophile antibody Tm Tnleaiow | mononucleosis. Heterophile antibodies in mono are against horse | RBCS (most sensitive antigen, used in slide test, sheep RECs, and povine RBCs. IM antibodies do not react against guinea pig kidney (GPK), Blood mixed with GPK does not elump, but when hone RBCS added it does clump. Ani viral capsid antigen-IgM and IgG, ani early angen aa] Epstein-Barr nuclear antigen in the evaluation of heterophle —_Lantibody negative infetious mononucleosis. | ‘7A febrile 23 year old college coed presents with fatigue and difficulty with swallowing. Physical €xam reveals exudative tonsilltis, palatal petechia, cervical lymphadenopathy, and tender hhepatosplenomegaly. A CBC reveals a mild mierocytis snemin ymphocytie leukocytosis with 20% of the lymphocytes exhibiting atypical features, an expect this patient to have, z A. alow TIBC B. anormal serum ferritin C. an elevated total bilirubin . D. E. heterophile antibodies normal serum AST arid ALT titers A 65-year-old man with an elevated RBC count has a history of gout, frequent headaches, and Trias ptt bathing. He presents with a sudden onset of abdominal pain and bloody diarrhea, Wish ofthe following sets of laboratory data best represent this patient. hematologic disease? RBC Mass [Plasma Volume _ | S02 Erythropoietin A. [Iinereased [Normal Decreased [Increased B. [Increased | Normal Normal [Increased CC. Tincreased — [increased Normal [Low D._ [Normal | Decreased Normal | Normal S202 = oxygen saturation CA = COPD, cyanotie CHD, B= ectopic EPO production, D = relative polyeythemia (volume depleted)Note: This material is copyrighted. All rights reserved. Lymph nodes/Plasma cells/Histiocytes/Spleen ‘= Reactive lymphadenopathy 1. clinieal— A. painful lymph node B. localized in localized disease: e.g., tonsillitis, C. generalized in systemic disease: 2. lymph node relationships— A. germinal follicle contains B cells: absent in Bruton's agammaglobulinemia: also no plasma cells B. _parafollicular area contains T cells: absent in DiGeorge syndrome C. sinus contains histocytes (1) increased histiocytes in histiocytosis X (2) _ sinus histiocytosis in nodes draining cancer @) histiocytes are CD, positive HIV, infectious mono = Malignan 1. clinical A.2€ painless, hard lymph nodes B. localized in localized disease: e.g., axillary nodes in breast cancer C. generalized in: Q) leukemia @) non-Hodgkin's lymphoma ® Follicular B cell lymphoma: 1, MC malignant lymphoma in adults 2. example of translocation of t14;18 leading to inactivation of apoptosis gene: see Neoplasia notes Burkitt's lymphoma: 1. MC lymphoma in children 2. located in abdominal cavity— A. paraortic lymph nodes B. terminal ileum C. “starry sky" appearance under low power 3. high grade B cell malignaney A. EBV relationship B, 8:14 translocation of c-mye oncogene ‘F Mycosis fungoides: 1. CD, Thelper cell malignancy 2. skin invasion produces nodular lesions and Pautrier's microabscesses (malignant ‘T cells) 3. systemic disease 4. called Sezary syndrome when PAS posit Histiocytosis X: 1. mainly childhood disease histiocytes are CD, positive _ 2. types A fe T cells are present in blood (1) benign histiocytes @)__ lytic lesions in bone with pathologic fractures 15Note: This material is copyrighted. All rights reserved. « @ 8 a gynptns ” B. Hand-Schuller-Christian disease 2) malignant @ G (2) triad of exophthalmos, diabetes insipidus, lytic lesions in the skull CC. Leterer.Siwe disease (2) malignant: infants and young children (2) diffuse eczematous rash (@)_ organ involvement (4) _ lytic lesions in bones 3. USMEE/seenario— two year old with eezematous rash and organomegaly and biopsy of skin revealed CD, positive cells ‘@ Hodgkin's disease (HD) 1. clinical ‘A. RScell is the neoplastic cell: see question #1 p. 186 of Review book for picture (1) canbe aB or Tcell (2) _ must be present to Dx Hodekin's B, nodular sclerosing MC type C___ fever, night sweats, weightloss often confused with TB D. _ prognosis corresponds with number of RS cells and type of Hodgkin's E. death by second malignancies due to alkylating agents: e.g., non-Hodgkin's lymphoma 2. summary of the subtypes of Hodgkin's Disease (HD): note how the types move from those withthe Teast number to the greatest number of RS cells, from best prognosis to poorest Hodgkin's disease | Comments _ « = = = « = = « = a prognosis, and from a young age to an older age subtype | Lymphocyte 3% HID. Male dominant. Asymptomatic young male with isolated node or node predominant ‘group (cervical or supraclavicular). Hard to identify RS cells. Usually stage I. Best survival (90% 5 year survival). Increased incidence of second malignancy (NHL) due to alkylating agents used in Rx of HD. i Nodular sclerosing | 60% HD. Female predominant. Stage IA MC presentation’fanterior mediastinal | nodes _and_cervical/supraciavicufar). RS variants are called lacunar cells. Collagen separates nodular areas. ~70% 5 year survival. Mixed cellularity | 30% HD. Male dominant. Middle age. RS cells easy to find. ~ survival. Lymphocyte 5% HD. Men >40-50 years old. Most aggressive HD. ~20% 5 year survival. depleted HD = Hodgkin's disease, RS = Reed Stemberg cell & X-ray with multiple lytic lesions in the hip in a patient with anemia and hypercalcemia: 1. multiple myeloma— see table for description of all monoclonal gammopathies ies (includes amyloidosis)- 2. _ summary of monoclonal gammopathis (Disorder ‘Comments: ] Monoclonal gammopathy | ~60% of all eases of MG (MGUS is MCC of monoclonal spike). | of undetermined Most are an IgG M-spike. Majority pursue a stable course, Some significance (MGUS) __ | develop multiple myeloma or related disorder. | Multiple myeloma (MM) | ~20% of all cases of MG. MC primary malignancy of bone, More ‘common in African-Americans than whites (2:1). Rare under 40 years old. Increased tisk with radiation exposure. M-spike in 80-90% and urine BJ protein (light chains) in 60-80%, M-spike usually 16Note: This material is copyrighted. All rights reserved. bone pain, pathologic fr thrombocytopenia Infection MC COD. macroglobulinemia secreting excessive IgM. ‘Yet types) and urine, Sheets of malignant plasma cells >10% of cells in marrow. Increase B-, microglobulin portends a poor survival (correlates with degree « plasma cell proliferation). Suspect MM in any middle aged to elderly patient with unexplained anemia, bi recurrent infection, unexplained hypercalcemia, without hypertension. Skeletal svstem: | je lesions (“punched out”), | Hematologic system: anemia, rouleaux, increased sedimentation rate, Urinary system: nephrocalcinosis (from hypercalcemia) MCC acute renal failure, Light chains are toxic to tubules and produce a giant cell reaction, Prone to primary amyloidosis involving kidne; Endocrine system: hypercalcemia due to local release of os activating factor by plasma cells Waldenstrom’s Clinical: monoclonal proliferation of Iymphoplasmacytoid cells Clinical: hyperviscosity syndrome (85-95%), hepatosplenomegal, lymphadenopathy, anemia. BJ protein in ~80%, Heavy chain diseases (a, | M protein part of heavy chain devoid of light chains located in serum Amyloidosis ‘Amyloid resulting Derived from di MM), serum associated like nin, and kidneys. 21. Amyloid toxi >40, involved, (calcitonin derived amyloid) uv a fibrillary protein that deposits into interstitial tissue organ dysfunction. Properties of amyloid: twisted B- pleated sheet (B-fibrilloses). Cong red positive and demonstrates apple green bi Granny-Smith apple) under polarized light. Electron microscopy linear, non-branching fiber with hollow cores. ferent proteins: light chains (association with invloid (SAA, an acute phase reactant in inflammation), prealbumin, 8 amyloid proteins, and peptide hormones fringence (like a Two main types of amyloidosis: pri derived) and secondary (reactive) rheumatoid arthritis, TB, leprosy ‘Common sites of involvement: heart, spleen, tongue, adrenals, liver imary_amyloidosis (light chain (SAA. derived, , renal adenocarcinoma), Cardiovascular system: restrictive cardiomyopathy in the elderly due to prealbumi Gastrointestinal system: macroglossia, malabsorption, hepatomeg with increased alkaline phosphatase Musculoskeletal system: carpal tunnel syndrome common, Renal system: renal failure is MC COD (ney CNS: Alzheimer’s disease (f-amyloid protei derived amyloid rrotic syndrome) coded by chromosome to neurons, MC COD in Down’s syndrome patients Diagnosis: Bx of rectal mucosa, gingiva, omental fat pad, or the organ Other types of amyloidosis: medullary carNote: ‘This material is copyrighted. All rights reserved. ® Summary chart of important disorders of the spleen: Disorder yystemic infections! inflammation Comments Infectious mononucleosis: splenomegaly invariably present. Ruptures with trauma (contact sports) more than spontaneous. Kala azar: massive splenomegaly in visceral leishmaniasis. Leishmania in macrophages. Malaria: MCC of splenomegaly in third world countries. Autoimmune disease: splenomegaly common in SLE and rheumatoid arthritis. SLE has hyperplastic arteriolosclerosis (onion skinning of the penicillary arteriole) Neoplastic disorders “Hypersplenism Sickle cell disease Portal hypertension (PH) Splenic infarction Congenital asplenia ‘Splenectomy Myeloproliferative disease: splenomegaly invariably present (massive In agnogenic myeloid metaplasia). Extramedullary hematopoiesis common (tilineage hematopoiesis in sinusoids) Leukemia: splenomegaly invariably present often massive (chronic Iymphoeytic leukemia). Red and white pulp involved in most cases. Red pulp only in hairy cell leukemia. Malignant lymphoma: NHL and HD commonly produce splenomegaly. Metastatic malignant lymphomas are MC splenic malignancy Hypersplenism is an exaggeration of normal splenic function. RBCs, WBCs and platelets, either singly or in combination are sequestered and destroyed. Portal hypertension in cirrhosis is MCC. Feltv's syndrome is the combination of rheumatoid arthritis, splenomegaly, and autoimmune | neutropenia. Sickle cell disease Begins with splenomegaly owing to entrapment of RBCs In the cords and sinuses. Spleen non-functional at early age (~2 years old) Markedly reduced in size (infarction) in late adolescence (called autosplenectomy), PH most commonly secondary to cirrhosis. Increased portal vein pressure produces congestive splenomegaly. Hypersplenism common. Most are pale infarets secondary to emboli originating in the left side of the heart (c.g., thrombus, vegetations). Commonly produce left upper quadrant pain and friction rubs (fibrinous exudate on capsular surface) Congenital asplenia associated in >80% of cases with malformations in the heart. Splenectomy (or functional asplenia [sickle cell disease]) predisposes to infections (septicemia, peritonitis). Streprococcus pneumoniae followed by Hemophilus influenzae are MC infections. Hematologic abnormalities with splenectomy: presence of nucleated RBCs, Howell Joily bodies (nuclear remnants in the cytoplasm), increased reticulocytes (RBC membrane is not removed by macrophages), target cells (excess membrane cannot be removed), Heinz bodies (denatured Hb), and an increase in platelets (thrombocytosis)Note: This material is copyrighted, All rights reserved. ty Coagulation: see schematic © Factors preventing small vessel clotting: 1, heparin— enhances antithrombin III (ATID), which neutralizes most serine protease coagulation factors: XIl, XI, IX, X, prothrombin (Il), thrombin 2 PG A. synthesized by endothelial cells B. vasodilator C. inhibits platelet aggregation tek 3. protein Cand S— ( V/stama) K-cepardortt) ‘A. inactivate factors V and VIII B. enhance fibrinolysis 4, tissue plasminogen activator A. release of plasmin B, destroys coagulation factors and clots © Pactors acting as procoagulants (form clots) in small vessel injury: 1. thromboxane A:- A. synthesized by platelets B. _vasoconstrictor/bronchoconstrictor C. enhances platelet aggregation D. _ cyclooxygenase blocked by aspirin and NSAIDs 2. von Willebrand factor— A. VIlLvWF B. synthesized by endothelial cells and megakaryocytes: platelets carry some VI-vWF C. platelet adhesion factor: platelets have receptors for VINL:vWF 3. extrinsic and intrinsic coagulation system o i Normal events small vessel injury: sequence of events 1. vessel injury > 2. activation of factor VII in the extrinsic coagulation system by tissue thromboplastin and activation of factor XII in the intrinsic system by exposed collagen (VII can directly activate 1X in the intrinsic system)—> 3. platelets stick to VII-vWF adhesion) > 4. stimulus for platelet release of ADP from dense bodies causing platelet aggregation and synthesis of TXA; —> 8. temporary platelet plug with fibrinogen draped over it (fibrinogen receptors on platelets) stops bleeding (end of the bleeding time)» 6. thrombin generated by coagulation pathway stimulation converts fibrinogen into fibrin and forms a stable platelet plug ~> plasmin destroys the plug and reestablishes blood flow . 1 Bleeding ine BD: Durst est Hoe. Conlon factor de ts 1. detects platelet abnor 2. causes of a prolonged BT- \ A. thrombocytopenia no VIILvWF for platelet adhesion patient on aspirin: MCC, due to no TXA» for aggregation renal failure in damaged endothelial cells via their receptors (platelet rod carl igusNote: This material is copyrighted. All rights reserved. (1) qualitative platelet disorder due inhibition of platelet phospholipid (2) reversed with DDAVP (desmopressin acetate) (3) _ reversed with birth control pills * Ristocetin cofactor assay: 1. best test for VI-vWF fan“ 2. normal platelets clump when ristocetin is added to a test tube 3. platelets without VIT-vWF or the receptor for VIII:vWF- Bernard-Soulier disease (thrombocytopenia and giant platelets) do not clump Summary of platelet tests: 1. platelet count: normal number does not always mean they are functional~ e.g., patient on aspirin 2. bleeding time~ tests platelet function 3. __ristocetin cofactor assay- detects VIII:vWF or its receptor on platelets = Prothrombin time (PT): 1, deteets extrinsic coagulation system factors down to formation of a clot~ VII (extrinsic system) -» X > VI (prothrombin) — I (fibrinogen) —> clot 2. international normalized ratio ‘A. for patients on warfarin B. standardizes the test throughout the world so all test results are the same regardless of the reagent used 3. PT is best test for liver synthetic function Extrinsic system Vu © Partial thromboplastin time (PTT): see above schematic 1. deteets intrinsic coagulation system factors (XIL, XI, IX, VIL) down to formation of a elot— XII > XI-+ IX > VIII + X ~ V + II (prothrombin) -> I (fibrinogen) + clot 2. used to follow heparin therapy and factor deficiencies Fibrinolytic system tests: 1. fibrin (ogen) split products- X, Y, D, E fragments after plasmin breakdown of fibrinog or a fibrin elot 2._, D-dimers- a measures cross-linked fibrin monomers in a fibrin clot B, cross-links indicate factor XIII activity in forming a stable clot & USMLE picture of an elderly patients hands with st finding and not a sign of patient abuse le: purpura:? normal age-dependentNote: This material is copyrighted, All rights reserved. Signs and symptoms of vessel instal epistaxis nosebleeds (MC symptom) bleeding from superficial scratches~ no temporary platelet plug easy bruising petechia and ecchymoses— A. these donot blanch since they represent bleeding into subcuta B. capillary hemangiomas and spider angiomas blanch with pressure mucosal bleeding % USMLE scenatio: 1, URFima child followed by epistaxis and petechia 2. idiopathic thrombocytopenic purpura~ A. MCC of thrombocytopenia in children lity and platelet problems B. IgG antibody against platelets: type II hypersensitivity C. no splenomegaly D. megakaryocytes are present in marrow E, responds well to corticosteroids 7 Autoimmune thrombocytopenia in adults 1, most commonly associated with SLE- A. IgG antibody against the platelet: type II hypersensitivity B, splenomegaly usually present unlike ITP in children Rx (1) corticosteroids» @) _splenectomy—> @) alkylating agents (4) IV y-globulin if bleeding cannot be controlled: blocks Fe receptors for IgG on macrophages 2, other eauses of autoimmune thrombocytopenia. A. drugs: (Q) quinidine (type I hypersensitivity) (2) heparin (antibody against heparin attached to platelet membrane) B. viruses: HIV (MC hematologic abnormality) r ‘Thrombotic thrombocytopenic purpura: 1. small vessel damage (unknown plasma factor) with consumption of platelets ible causes of endothelial cell damage: infectious diseases diseases: progressive systemic sclerosis, hypertension drugs- e.g., mithramycin, birth control pills anti-phospholipid antibodies preeclampsia B. platelet thrombi: (1) not DIC, since coagulation factors are not consumed @) only platelets are consumed @) abnormal VIIL:vWF in endothelial cells may contribute to platelet aggregation . vasoconstriction (1) endothelin (vasoconstrictor) release in damaged endothelial cells @) decrease in nitric oxide and PGI2— normally, they are vasodilatorsNote: This material i copyrighted, All rights reserved. microangiopathic hemolytic anemia— A. RBCS hit platelet plugs—> B. _ schistocytes: must be present to secure the Dx fever CNS problems renal failure Rx with plasmapheresis hemolytic uremic syndrome in children similar except kidney is worst hit while in TTP the brain is worst hit 0157:H7 serotype of E. coli: 1. 2 3. hemolytic uremic syndrome— A. renal failure B, anemia with schistocytes C. thrombocytopenia, D. _ CNS findings: less common than TTP organism proliferates in undercooked beef or produce contaminated with F. coli~ e.g, unpasteurized apple cider Shigella toxin can also produce HUS ‘Thrombocytosis: causes— 1 Bs 3. 4 5. chronic iron defieiency: common mmaney: common splenectomy infections myeloproliferative diseases: e.g., polycythemia vera Signs and symptoms of coagulation disorders: 1. tate rebleeding— ‘A. temporary platelet plug is only mechanical block of small vessels B. bleeding after wisdom tooth removal or from the incision site in any type of surgery bleeding into joints (hemarthroses) and closed spaces only severe types like hemophilia A and B with very low factor levels, : 3. mucous membrane bleeding- Gl and GU bleeds Hemophilia A: 1. SXR 2 lab ‘A. prolonged PTT B. normal PT C. low VII:C D. normal VItl:antigen and VIL: vWF 3. clinical- see previous discussion 4 Re ‘Classical VWD: A. recombinant factor VIII for severe cases B. _DDAVP (vasopressin) for mild cases: increases synthesis of all factor VIII moleculesNote: This material is copyrighted, All rights reserved. C. prolonged PTT D. low VII:C E. low Vill: antigen F, _ low ristocetin cofactor assay: decreased VIl:vWF 3. MC genetic coagulopathy 4. elinical~ A. menorrhagia B. mucous membrane bleeding 5. Re A. DDAVP (desmopressin) B. birth control pills in women with menorrhagia: estr molecules eryoprecipitate: (1) blood product containing VILL, fibrinogen, XIII @) rarely used fen increases synthesis of all VIII vagulant (cireulating anticoagulant, inhibitor) and prolonged PTT: lab findings 1. normal PT prolonged PIT after mixing 0.5 ec of normal plasma with 0.5 ce of patient plasma, the PTT is repeated and is still prolonged: antibodies inhibit VIlL:coagulant in the normal plasma as well 4. _atrue factor Vill:coagulant deficiency: correction of the PTT after adding normal plasma Antiphospholipid syndrome: 1. definition antibodies directed against phospholipids bound to plasma proteins 2. types of antibodies A. lupus anticoagulant: (1) misnomer: actually causes clotting 2) usually produces a prolonged PTT @) PTT not corrected with addition of normal plasma @)__ PTT corrected by adding phospholipid B. _anticardiolipin antibody: (1) cause of a biologic false positive syphilis serology @) seen in SLE, HIV, other disorders (3) causes thrombosis, 3. clinical syndromes— A. repeated abortions: placental bed clots B. strokes ©. thromboembolism D. hepatic vein thrombosis Vitamin K deficiency 1. causes bleeding A. vitamin K y-carbexylates I, VIL, IX, B. _ y-carboxylation allows calcium to bind to these factors in a clot C. absence of y-carboxylation leaves vitamin K dependent factors non- is anticoagulated 2. causes of K deficiency ‘A. newboms lack bacterial colonization for vitamin K synthesis X, protein C at nctional: patientNote: This material is copyrighted. All rights reserved. (Q) require IM injection of vitamin K at birth: no vitamin K in breast @) vitamin K levels normally decrease between days @) danger of intracerebral hemorhage if newborn is not protected: called hemorthagie disease of the newborn malabsorption antibiotic Rx sterilizes bowel: MCC in a hospitalized patient ‘warfarin blocks epoxide reductase (normally keeps vitamin K in functional K1 state) (1) vitamin K non-functional @) _ratpoison contains warfarin 3. alcoholic with cirrhosis ‘A. could be problem with liver synthesis of vitamin K: prolonged PT not corrected with IM vitamin K B. could be problem with malabsorption of vitamin K from bile salt deficiency or chronic pancreatitis: prolonged PT corrected with IM vitamin K S _USMLE question of child taking rat poison: 1. contains warfarin— will cause bleeding 2, Rx with IM vitamin K if not medically si medically significant bleed pos ificant bleeding use fresh frozen plasma if a * Vitamin abnormalities associated with prolonged PT: 1. vitamin K deficiency 2. vitamin E toxicity: ‘A. inhibits synthesis of vitamin K dependent factors B. synergistic with warfarin a Patient on warfarin: 1. mechanism— A. blocks vitamin Ks ability to y-carboxylate factors Il, VII, IX, X, protein C and $ B. _ blocks epoxide reductase: normally keeps vitamin K in its active KI state 2. prolonged PT and PTT- PT is better test for following patients than PTT 3. bleeding MC complication~ _ A. if overanticoagulated and seriously bleeding give fresh frozen plasma B. IM vitamin K, if bleeding not serious Ss 4. previously y-carboxylated vitamin K dependent factors must disappear before patient is fully anticoagulated (USMLE)~ A. reason why heparin is given along with warfarin B. Viland protein C have the shortest half-life (6 hours) . C. prothrombin has the longest half-life of ~4 d 2 5. hemorrhagic skin necrosis: ‘A. usually a patient who is a heterozygote with protein C deficiency and 50% factor level B. when put on warfarin, patient will have 0% protein C levels in 6 hours due to short half-life of protein C: causes thrombosis of vessels in the skin before the patient is fully anticoagulated Patient on heparin: 1. prolonged PT and PTT- PTT is the better test to follow patients 2. overanticoagulated- give protamine sulfate 3. heparin is MC drug associated with thrombocytopenia in the hospital 4. prevents venous clot formation A. does not dissolve the clotNote: This material is copyrighted. All rights reserved. pic B. canbe used in pregnancy C. complications: (1) bleeding @) thrombocytopenia (3) osteoporosis pathogenesis— A. intravascular consumption of clotting factors B. _ consumption of fibrinogen, V, VIN, prothrombin, platelets clinical~ diffuse oozing of blood from all breaks in the skin plus mucous membranes A. endotoxic shock: MC B. infections: meningacoccemia C. rattlesnake envenomation D. amniotic fluid embolism ‘A. prolonged PT and PTT B. low fibrinogen CC. _ imoreased split products and D-dimer: best tests for DIC (USMEE) D. thrombocytopenia E, _ schistocytes: RBCs hit fibrin clots A. Rx underlying disease causing DIC B. _use blood components to keep the patient alive: basically adding more fuel to the fire C. heparin; blocks. thrombin, hence preventing clots. and consumption of coag factors (bw (652) Hereditary thrombosis syndromes: clinical- A. venous thrombosis and pulmonary emboli at early age B. clots in unusual placesve.g., dural sinuses A. factor V Leiden (1) MC hereditary thrombosis syndrome 2) _ protein C and $ cannot degrade factor V B. _ATIII deficiency (1) ne prolongation of PTT after starting heparin 2) give massive doses of heparin and the PTT will eventually prolong, (3) send home on warfarin (4) birth control pills is MC acquired cause protein C and S deficiency (2) cannot inactivate V and VIIL (2) start with heparin and very low doses of warfarin so that hemorrhagic skin necrosis does not occurNote: This material is copyrighted. All rights reserved = _ Fxamples of hemostasis abnormalities: j Bleeding time | Platelet count) PT PIT Interpretation | ira [Prolonged ‘Normal Normal ‘Normal, Agpirinor NSAIDs __| bb Prolonged ‘Normal Normal” [Prolonged | von Willebrand's e. ‘Normal ‘Normal Normal [Prolonged | Hemophilia A | a Prolonged Low Normal [Normal [1TP, TTP, HUS e ‘Normal ‘Normal [Prolonged [Prolonged | Warfarin or heparin _| [(ab) | Prolonged Low Prolonged | Prolonged | DIC (ae) [Normal [Normal Normal, ‘Normal, Blood loss. | ‘Questions used during the board review: Which of the following is more often associated with mild hemophilia A than classical von Willebrand's disease? ‘Normal PT. Prolonged PTT Low VIILAg levels ‘Normal bleeding time Treatment with desmopressin acetate moop> |A febrile 65-year-old man with urinary retention secondary {0 prostale hyperplasia develops ‘RDS complicated by endotoxie shock. Within 24 hours he has oozing of blood from all puncture ree cateraive ecchymoses, and mucosal bleeding, Which of the following tests MOST USEFUL as an initial sereening test? A. Dedimer assay B. Prothrombin time C. Bone marrow aspirate D. Partial thrombopfastin time E. _ Examination of the peripheral blood A (DIC) © Vitamin K deficiency is MOST LIKELY present in a patient. vith liver discase who is being treated with a broad spectrum antibiotic With traveler's diarrhea who is being treated with ciprofloxacin ‘bn heparin therapy for prevention of @ pulmonary embolus with lactase deficiency who currently has watery stools who has taken warfarin 3 hours ago qe PoOORP ee eee 26Note: ‘his material is copyrighted, All rights reserved. Immunohematology * Glycoproteins: 1. sto which are attached short, branch-ebained oligosaccharides 2 ns include: cell surface antigenicity: e.g., blood group antigens on RBCs components of mucin: ¢,g,, mucous layer covering the stomach mucosa tumor markers: e.g., prostate specific antigen * ABO blood groups: 1. H gene- codes for a transfira that attaches fucose to a glycolipid to form H ant 2. A gene~ transferase product attaches N-acetylgalactosamine to H antigen to produce A 3 transferase product attaches galactose to H antigen to form B antigen 4. Ogene~ A. inactive B. _ORBCs are only surfaced by H antigen 5. AB RBCs~ have H antigen with A or B sugar moieties 6. blood group O- universal donor: refers to transfusion of packed RBCs not whole blood no antigens on surface and cannot be destroyed must receive O blood increased incidence of duodenal ulcers, have 3 antibodies: (anti-A [gM Q) anti-B IgM @) _anti-a,B IgG (can eross the placenta) 7. blood group AB- A. universal recipient B. no antibodies to destroy transfused RBCs 8. blood group A- A. has anti-B IgM B. increased incidence of gastrie cancer 9. blood group B- has anti-A IgM 10. ABO typing of mother and father to see if the child is the A. AB parents cannot have an O child B. —O parents cannot have an AB, A, or B child spopPNote: This material is copyrighted. All rights reserved. e ce ® ABO blood group summary _ oe Type | Antibodies | Whites | Blacks | Asians | Native | Comments Americans | 0 ‘anti-A TeM 3% [40% | 79% Universal donor (no anti-B IgM, antigens on the surface) anti-A,B IgG Anti-A,B IgG is respon- (can cross. the | sible for ABO incompa- placenta) tibility. Can only receive © blood (antibodies | would destroy A, B, or AB blood). Predisposi- tion for duodenal ulcer disease, a antikBlgM [40% [27% [28% | 16% Predisposition for gastric | careinom: = B aniAGM (1% [20% [27% [4% [AB none present [4% |4% [5% | <1% Universal recipient (no - | antibodies). Rh positive 1. means the patient has D antigen other Rh antigens C, c, E, e, d (does not exist) Lewis antibodies: 1, naturally occurring IgM antibodies 2. no clinical significance 3. no risk of hemolytic disease of newborn (HDN) Dufly antigens 1. uncommon in African-Americans 2. surface receptor for P. vivax- African-Americans lacking the antigen have protection against malaria antigens: 1. anti is a cold agglutinin (IgM) A.-M. pneumoniae infections B. possible cold type of autoimmune hemolytic anemia 2. anti-i (IgM) A. infectious mononucleosis B. possible cold type of autoimmune hemolytic anemia Patient who is going to receive a packed RBC transfusion: 1, must perform an antibody sereen on patient serum: 2. major crossmateh— ‘A. purpose is to see if the patient has antibodies that will destroy donor RBCs B. patient serum against donor RBCs indirect Coombs test C. good quality control on whether patient had any antibodies reacting against donor RBC antigens : D. type I hypersensitivity reaction E. does not prevent patient from (Q) developing antibodies against donor RBC antigensNote: This mater r is copyrighted. All rights reserved. (2) _ patient from getting infection: CMV MC, HCV, HIV, HBV ‘MC antibodyin U.S:(USMEE): anti CMV antibody ‘Most common infection transmitted by blood transfusion: CMV, not HCV, which is the MCC of posttransfusion hepatitis, MCC of post-transfusion hepatitis: HCV ‘MC infection transmitted by accidental needle stick: HBV, which has @ high viral burden in bloo HIV risk post-transfusion: 1:676,000 risk per unit HBV risk post-transfusion: 1:200,000 risk per unit HCV risk post-transfusion: 1:3300 risk per unit Risk of HIV posi ivity post-accidental needle stick: 1 1:30 2. MC way of becoming HIV positive in medical personnel 3. Rx with triple therapy for 6 months + repeat HIV serology on a regular basis Fresh frozen plasma: 1. contains all coagulation factors 2. clinical uses multiple factor deficiencies: A. DIC B. _ liver disease C. vitamin K deficiency 3. hepatitis risk Packed RBCs: 1, high hematocrit~ contains some plasma 2. transfuse only if patient is symptomatic and does not respond to medical therapy 3. hepatitis risk Platelet transfusion: 1, raises platelet count 5000-10,000 cells/uL per unit 2. _ transfuse platelets only if the patient is symptomatic 3. hepatitis risk Cryoprecipitate: 1. blood produce containing- ‘A. all factor VIII molecules B. fibrinogen C. factor XMM, fibronectin 2. hepatitis risk Febrile transfusion reaction: 1. patient has anti-HLA antibodies against HLA antigens on donor leukocytes causes the release of pyrogens from destroyed donor leukocytes type Il hypersensitivity patients must have previous exposure to foreign HLA leukocyte antigens in order to devel antibodies A. common in pregnancy- fetal maternal bleeds B. spontaneous abortions C. previous transfusionNote: o rv ‘This material is copyrighted. All rights reserved. Allergic transfusion reaction: 1. MC type of reaction 2. patient develops hives against proteins in donor unit 3. type I hypersensitivity Hemolytic transfusion reaction: 1. units are ABO incompatible— ‘A. patient receives wrong blood type (1) eg, patient A (has anti-B IgM) and donor blood is B-> @) e4g,, anti-B IgM attaches to B positive donor cells (3) _ activates complement system—> (4) _ intravascular hemolysis B. type Il hypersensitivity reaction 2. patient has undetected antibodies that react against donor RBC antigens— A. extravascular hemolysis B. jaundice, drop in Hb, positive direct Coombs: reaction may be delayed in some cases C. type IT hypersensitivity Hemolytic disease of the newborn (HDN) due to ABO incompatibility’ 1, O mother with A or B baby- A. O people normally have anti AB IgG, which crosses the placenta: (1) antibody attaches to baby RBC antigens and splenic macrophages destroy RBCs (2) mother’s liver handles unconjugated bilirubin released by fetal macrophages (3) baby develops a mild anemia: weak antibody compared to anti-D antibodies may occur in first pregnancy no increase in severity with future pregnancies spherocytes in cord blood: not present in Rh HDN positive direct Coombs on cord blood RBCs mild hemolytic anemia: rarely requires an exchange transfusion 3. clinical: A. MCC of jaundice in first 24 hs: babies liver cannot handle excess UCB load B. protects against Rh sensitization: (1) _O patients have anti-A [gM, anti-B IgM, and anti-AB-Ig @2) anti A or B IgM antibodies immediately destroy fetal RBCs in matemal circulation Rh immune globulin: 1, anti-D from pooled human donors ‘A. passive immunization B. does not cross the placenta C. _ givento pregnant women who do not have ant D. no hepatitis risk at 28th week 2. baby is Rh positive and mother does not have anti-D- A. amount of Rh immune globulin to give is based on Kleihauer-Betke tes: (1) _ testis performed on maternal blood @) detects amount of fetal-maternal bleed (fetal RBCs resistant to alkali and acid) B, _ give Rh immune globulin within 3 days C. immune globulin destroys fetal RBCs in maternal circulationNote: This material is copyrighted. All rights reserved. = Rh EDN 1. mother Rh negative and baby Rh positive 2. first pregnancy with Rh+ baby has no effect on baby 3 mother could be exposed to fetal RBCs with D antigen during delivery and develop antibodies purpose of Rh immune globulin is to prevent this from oceurr’ 4. if'subsequent pregnancies have Rh babies A, — matemal anti-D InG antibodies cross placemta-» B. attach to fetal RBCs-> C. RBCs extravascularly removed by fetal macrophages in the spleen» D. unconjugated bilirubin (UCB) is end-product of hemolysis (mother’s liver handles UCB)-> F> _ fetus develops anemia (severe anemia, chance of heart failure and hydrops fetalis)-» F. bilirubin pigment can be detected in amniotic fluid (optical wavelength of 450) and ‘mapped on a Liley graph to determine severity of hemolysis > G — atdelivery, baby cannot handle UCB load and i often exchange transfused to prevent kernicterus 5. exchange transfusion A. removes UCB B. removes antibodies C. corrects anemia Cross-section of by Rh hemolytic disease of the newborn nstem with yellowish discoloration in a child: probably kernicterus from Wb of unconjeseted by liek Question used during the board review: o th A B. < D, E. A blood group O, Rh-negative woman is pregnant with her fist child. She has a negative Screen and no previous administration of Rh immune globulin, She delivers Positive baby. The baby develops unconjugated hyperbilirubinemia 8 hours after birth, Which «i antibody blood group A, Rh- ie following statements correctly describes this case? She is Rh compatible with hér baby She is ABO compatible with her baby She is a candidate for Rh immune globulin Negative direct Coombs’ of baby’s cord blood Jaundice is secondary to Rh incompatibility with destruction of fetal cellsTrapiedeh) : Cathecton ob deepleeg ppessane in He sa Thich jv ar Cuse 4 Liing the R ven tiiols o Note: This material is copyrighted. All rights reserved. Cardiovascular system * Summary of physical diagnostic signs in cardiovascular disease: Abbreviations used~ first heart sound, S;: second heart sound, S,: third heart sound, S,: fourth heart sound, MV: mitral valve, TV: tricuspid valve, AV: aortic valve, PV: pulmonic valve, TPR: total peripheral resistance 1, valve locations for auscult A. mitral valve (MV) at cardiac apex B. tricuspid valve (TV) along left sternal border C. pulmonic valve (PV) in the left 2nd and 3rd intercostal space (ICS) D. aortic valve (AV)- in the left sternal border or right 2nd ICS. 2. cardiac cycle relationships- P wave: atrial depolarization PR interval: atrioventricular conduction time QRS: ventricular depolarization Sc: comes just before the QRS Si: comes at the same time as the QRS T wave: ventricular repolarization, or recovery Sx: comes just after the T wave Si heart sound— closure of the MV and TV during systole MY closes before TV normally not split corresponds with carotid pulse accentuated in early mitral stenosis when valve is still pliable heart sound— closure of the AV and PV in diastole zortic component (A2) precedes the pulmonic component (P:) Sy splits on inspiration owing to blood entering right heart: (1) negative intrathoracic pressure from diaphragm moving down Q) delayed closure of PV @) becomes a single sound on expiration D. A; accentuated in essential hypertension E. _Pyaccentuated in pulmonary hypertension Inspiration A <> P, (separates) Expiration A;P2 (single sound) paradoxical split of S:~ ‘A. P3comes before A2 and split occurs on expiration rather than inspiration B. due either to delay in AV closure or early closure of PV: e.g, left bundle branch block Which delays AV closure) 6. fixed splitting of S; A. Sz is split during inspiration (normal) and expiration (abnormal) B. due to delayed PV closure AV closure AV C. eg, atrial septal defect where blood is always moving from the right atrium and PV closes even later than it normally does 7. physiologic Ss— ‘A. normal in children and young adults B. occurs in early diastole QmmoopE oppyrsoee atrium into theNote: This material is copyrighted. All rights reserved. C- due to rapid ventricular filling with vibration of valve cusps and ventricular wall or impact of ventricle against chest wall or sudden limitation of longitudinal expansion of Lv pathologie 8, A. abnormal afier 40 y old B. due to blood entering a volume overloaded left or right ventricle (1) eg. volume overloaded left or right ventricle in left heart failurevright heart failure _- @) _eg., AV/MV regurgitation or PV/TV regurgitation first cardiae sign of congestive heart failure: increased ventricular volume sreshes the MY or TV ring-» volume overload from mitraVtricuspid regurgitation D. _leftsided S; increases in intensity on expiration F ecitt-sded S; increases on inspiration (more blood in right heart on inspiration) Sy heart sound~ ‘A. coincides with atrial contraction in late diastolic filling and the wave in the jugular venous pulse Be due to increased resistance to ventricular filling (decreased compliance) followin vigorous atrial contraction C. decreased compliance may be due to: (1) ventricular hypertrophy (efUright) or (2) _ already volume overloaded ventricle (leftvright) D. Sy is absent in atrial fibrillation E, _ left-sided S, increases in intensity on expiration F. afitht-sided S. inereases on inspiration (more blood in tight heart on inspiration) 1mid-systolic ejection clicks in MV/TV prolapse— F_SIGK is due to ballooning of excess valve tissue into the atrium during systole B. click is usually followed by a regurgitation murmur C+ maneuvers that cause click/murmur to come closer to $ are those that decrease volume in the lefUright ventricle so systole oceurs faster: (1) standing up (decreased venous return to the heart) (2) Valsalva maneuver G) anxiety (increased heart rate decreases filling of ventricle in diastole) D. maneuvers that cause clickimurmur to come closer to S; are those thse increase the volume of blood in the ventricles so systole takes longer to occur: (1) lying down (increased venous return to heart) (2) "sustained clenching of fist (increases afterload the ventricles heve to contract against) ‘opening snap in MV/TV stenosis— A. occurs MV/TV (less common) stenosis Be due to nonpliable valve which has difficulty in opening in diastole until atrial contraction forces it open opening snap earty in diastole indicates severe disease: correlates with intense atrial contraction pening snap that occurs later in diastole indicates less severe stenosis: correlates with Jess intense atrial contraction to open the valve heart murmur characteristics. A. occur in systole and/or diastole B. mechanisms (1) structural valvular diseaseNote: This 14, 16, 17. aterial is copyrighted. All rights reserved. @) anemia @) _ innocent (unrelated to structural or physiologic alteratio C. murmurs radiate (1) AV stenosis radiates into the neck @) MV regurgitation radiates into axilla D. graded 1 to 6: (1) grade 3 easy to hear @) _ grade 4 t0 6 often accompanied by palpable precordial thrill ) grade 6 audible without stethoscope E. — murmur/heart sound intensity with respirations (1D) right-sided murmurs and abnormal heart sounds increase on inspiration @) _ left-sided heart murmurs/abnormal heart sounds increase on expiration continuous murmurs— A. occur through systole and diastole B. cervical venous hum in children is MCC C. patent ductus arteriosus (PDA): called a machinery mu innocent murmur~ A. occur in ~$0% of normal children e.g.,normal child) B. due to turbulent pulmonary artery blood flow in systole C._ lowgrade (1 or 2) D. best heard with patient in supine position FE. — decreases with sitting/standing stenosis murmurs— ‘A. problems with opening valves B. _ valves opening in systole: AV/PV C. valves opening in diastole: MV/TV D. AVIPY stenosis (ejection type @) crescendo! decrescendo due to blood forcibly moving through constricted opening (3) _ produce concentric hypertrophy of lefUright ventricle, respectively E, _MV/TV stenosis mid-diastolic murmur occurs after opening snap regurgitation (insufficiency) murmurs problem with closing valves: incompetent valves closing in systole: MV/TV valves closing in diastole: AV/PV MV/TV regurgitation: (1) _ even intensity pansystolic (holosystolic) murmur due to blood refluxing into atria throughout systole 2) _ volume overload of atria and ventricles (nypertrophy/dilatation) E. _AV/PV regurgitation () high pitched blowing murmur directly after S: 2) volume overload of ventricles (hypertrophy/dilatation) Valsalva maneuver A. holding breath against a closed glottis: creates positive intrathor B. physiologic effects: (1) decreases venous return of blood to right heart 2) decreases cardiac output PORP ic pressuresNote: This material is copyrighted, AM rights reserved. (3) _ increases heart rate as compensation for drop in cardiac output effect on murmurs (1) increases intensity of systolic murmur in’ idiopathic hypertrophic. subaortic stenosis (hypertrophic cardiomyopathy): decreases left ventricle volume which accentuates the degree of obstruction to blood flow into the aorta @)__ moves systolic click/murmur closer to §; in mitral valve prolapse (3) decreases intensity of ejection murmur of aortic stenosis: less blood ejected through the stenotic valve left parasternal heave A. sign of right ventricular hypertrophy B, right ventricle is located under the sternum C. hypertrophy due to (1) pulmonary hypertension (called cor pulmonale) Q) PV stenosis 3) TV regurgitation pericardial knock~ A. sign of constrictive pericarditis B. cardiac chambers hit thickened (often calcified) pericardium when filling in diastole C. causes: (@) TB worldwide @) cardiac surgery in this country pericardial friction rub— A. sign of pericarditis B. scratchy 3 component sound heard on auscultation over the precordium: C. due to separation of fibrinous exudate on visceral/parietal pericardial surface during the cardiac cycle D. causes (1) coxsackievirus infection (MCC) @) transmural acute myocardial infarction 3) Dressler’s autoimmune pericarditis post infarction (4) _ systemic lupus erythematosus (MC manifestation of SLE) () acute cheumatic fever pulse pressure A. difference between systolic and diastolic pressure (normally 30 to 40 mm Hg) B. causes of a narrow pulse pressure— (1) decreased stroke volume: a aortic stenosis b. idiopathic hypertrophic subaortic stenosis € shock (cardiogenic, hypovolemic) (2) increased total peripheral resistance (TPR) due to arteriolar vasoconstriction: hypertension causes of a widened pulse pressure: (2) increased stroke volume: a. AV/MV regurgitation b. hyperthyroidism 2) decreased TPR due to arteriolar vasodilatation: a. endotoxemia b. thiamine deficiency . warm shock in metabolic acidosisis material is copyrighted, All rights reserved, (3) increased venous return to the right heart from arteriovenous fistulas (arterial venous communications that bypass the microcirculation) a. traumatic (MCC) b. mosaic bone in Paget's disease (4) decreased TPR due to decreased viscosity of blood: severe anemia 22. arterial pulses~ ‘A. normal arterial pulse (1) normal upstroke is due to a. interaction between the driving force of left ventricular contraction and b. compliance (elasticity) of the vessel (2) initial, rapidly ejected stroke volume is called anacrotie limb (3) _ pulse amplitude of upstroke modified by: a. clasticity of arterial wall b. amount of stroke volume © total peripheral arteriolar resistance (TPR) 4. blood pressure (4) down stroke is modified by a. vessel compliance (elasticity) b. TPR () closure of aortic valve causes a momentary reversal in blood flow: produces a dicrotic noteh in the down stroke (smaller, secondary positive wave in the down stroke is due to: elastic recoi the aorta and aortic valve elderly patients: (1) aorta loses elastic a. rigid b. less complianv/less distensibility (2) _ same stroke volume is distributed in an aorta with a smaller radius leading to an increased systolic pressure: possibility of systolic hypertension bounding pulses (Corrigan pulse, water hammer pulse) (1) _ increased stroke volume: a. AV/MY regurgitation b. hyperthyroidism ¢. high output cardiac failure (2) decreased TPR: arteriolar vasodilatation (sce above) 3) _ arteriovenous fistulas: see above pulsus paradoxus: (1) diminution in amplitude of pulse/blood pressure with inspiration: a. drop in blood pressure drop >10.mm Hg during inspiration b. normally drops a little on inspiration as blood filling the RV pushes on the interventricular septum and decreases the LV volume (2) _ pathophysiology of pulsus paradoxus: a. due to impedance of inflow of blood into the right heart during inspiration—> automatically reduces the cardiac output and drops the blood pressure—> neck veins distend on inspiration (called Kussmaul's sign, neck veins should collapse on inspiration as blood is sucked into the right heart by the negative intrathoracic pressure created by the diaphragms moving down)Note: TThis material is copyrighted. All rights reserved. 3) causes: a. pericardial effusion (MCC) b. decreased lung compliance: « interstitial edema in severe asthma severe pulmonary edema * interstitial fibrosis Beck's triad signs of pericardial effusion A. neck vein distention on inspiration: B. hypotension: decreased cardiac ou C. muffled heart sounds: fluid in the 24. jugular venous pulses (JVPs)— x Si normal JVPs (1) 3 positive waves: a, ¢, and v (2) 2negative waves: x and y B. awave: (1) _ positive wave due to atrial contraction in late diastole (2) occurs after the P wave in an ECG (3) disappears in atrial fibrillation (4) giant a wave: a. due to restricted filling of right heart b, eg, TV stenosis, pulmonary hypertension Cc. ewave (1) positive wave due'to right ventricular contraction in systole causing bulging of the tricuspid valve into the right atrium (2) correlates with S; and upstroke of carotid pulse D. xwave (1) __ large negative wave occupying most of systole (2) due to downward displacement of TV valve when blood is ejected out of the right ventricle into the pulmonary artery E. vwave: (1) positive wave due to right atrial filling in systole when the TV is closed @)_wiant c-v wave: due to TV regurgitation as blood refluxes up into the right atrium during systole (1) _ negative wave occupying most of diastole 2) due to opening of TV with rapid flow of blood into the right ventricle in diastoleChyhomicrens Note: This material i copyrighted, Allright reserved. ‘© _ Lipoprotein fractions in blood: Lipoprotein. | Protein [TG | CH Comments fraction Chylomicrons | 2 8 [3 Learries diet-derived TG- A. saturated fats surfaced by apolipoprotein Bus, C. falsely elevates tot TG level if not fasting, D. small amount of CH in chylomicrons does not alter serum CH levels: no need to fast 2phystology- assembled in the small intestine and delivered to the peripheral circulation via the lymphatics VLDL Learries liver-derived TG- A. also carries liver derived CH, B. surfaced by apolipoprotein B 2.LDL is derived from VLDL in the peripheral blood capillary lipoprotein lipase removes TG from VLDL and leaves CH behind in the LDL fraction 1“bad cholesterol”- A. derives from VLDL, B. surfaced by apolipoprotein B100 2. LDL attaches to LDL receptors on cells (USMLE)- A. inhibits HMG CoA reductase: prevents further synthesis of CH, B. decreases LDL receptor synthesis, C. increases esterification by acyl-CoA acyltransferase 3nfunctions of CH(USMLE)~ A. steroid synthesis, B. vitamin D synthesis, C. bile salt synthesis, D. cell membrane synthesis 1."good cholesterol”— apolipoprotein A accompanies HDL and parallels HDL concentration —Pactwwtes GCAT 2, funetions~ A. reservoir for apolipoproteins C and E that are subsequently attached © to circulating chylomicrons and VLDL, B. HDL removi atherosclerotic plaques (reverse CH tra delivers CH to the liver for disposal 3. synthesis increased A. estrogen, B. exercise, C. r wine i igh density lipoproteins, HMG CoA = 3-hydroxy-3-methylglutaryl coenzyme , LDL = low density lipoproteins, PH = phospholipid, TG = triglyceride, VLDL = very low density lipoproteins ‘ Fredrickson's phenotypie/genotypic classification: 1. type I- deficiency of APO Cll or capillary lipoprotein lipase 2. type II- ._polygenic hypercholesterolemia: 85% (MC type) familial hypercholesterolemia pathogenesis (1) absent or defective LDL receptors or (2) defective internalization of LDL complex + tat CoP clinical findings in familial hypercholesterolemia: A B. familial combined hypercholesterolemia C D, ~ (1) premature coronary artery disease (CAD) and myocardial infarcts ol ese Reductese (2) Achilles tendon xanthomas are pathognomonic (75%) Abie . ~> xanthalismas: ake 4159 5¢ 38Note: This material is copyrighted, All rights reserved. F, laboratory findings (@ LDL>190 mg/dL @) CH>260 mg/dl @) normal TG or increased TG (type IIb if increased) 3. type INI milial dysbetalipoproteinemia: "remnant disease B. pathogenesis: (1) absent or defective apo E @) chylomicron and intermediate density lipoprotein (IDL) remnants are not cleared laboratory (1) CHand 7G equally elevated (2) identify APO E isoforms 4. type IV- A. familial hypertriglyceridemia: MC type B. _ pathogenesis: decreased catabolism of VLDL C. clinical: (1) increased incidence of atherosclerosis involving coronary arteries and peripheral vessels 2) eruptive xanthomas (papules with TG) | D. laboratory (0) hypertriglyceridemia turbid infranate> @) slightly increased CH type V- A. familial hypertriglyceridemia with exacerbating factors like diabetic ketoacidosis or alcoholism B. pathogenesis: combination of type I and type IV (1 + IV combine to equal a type V phenotype . clinical (1) common in alcoholics and diabetic ketoa (2) hyperchylomicronemia syndrome: a. abdominal pain b. pancreatitis €. eruptive xanthomas D. laboratory: supranate—> (1) markedly increased TG with normal LDL infranate—> 2) supranate and infranate present: see Lab Medicine notes V) mechanisms, which idosis * Lipid deposits: 1. Achilles tendon xanthoma— familial hypercholesterolemia 2. 4 xanthelasma— ‘A. yellow plaque on eyelid B. consider type Il hyperlipidemia 3. arcus ser ‘A. rim of white around the outer part of the comes B. consider increased LDL if a young patient or normal age-related change if older patient 4. eruptive xanthomas~ A. yellow papular lesions over the body B. due to increased triglyceride: type TV or type V 39is material is copyrighted. AM rights reserved. PS Most common vessels involved in atherosclerosis in descending order: abdominal aorta~ no vasa vasorum below orifices of renal arteries coronary artery popliteal artery descending thoracic aorta internal carotid Atherosclerosis: 1. reaction to injury theory- factors damaging endothelial cells ‘A. chemicals in cigarette smoke (e.g., carbon monoxide) B. LDLioxidized LDL C. previous Chlamydia pneumoniae infection D. increased serum homocysteine: folate deficiency MCC 2. fibrous plaque A. pathognomonic lesion of atherosclerosis B. smooth muscle cells with CH deposits beneath intima C. macrophages with CH deposits General complications of atherosclerosis 1. aneurysm formation A. weakening of vessel wall with outpouching due to arterial pressure (1) _ Law of Laplace states that wall stress increases with increased radius _—\ Q)-’-all aneurysms must enlarge as wall stress increases Veoq Vaseeum”B, Yiabdominal aortic aneurysms is the MC type (picture on USMLE) Iafow Rens! A*feeiS C, abdominal aorta is the MC site for atherosclerosis she voxel Canrbe dew ) mote Cesily b/c 4 4 doesnt bo Dwar bed su 2. coronary artery disease— ischemic heart disease A. angina: MC manifestation B. acute myocardial infarction C. sudden cardiac death: (Q) death within 1 hour (2) severe coronary artery atherosclerosis (3) usually no'thrombosis present D. chronic ischemic heart disease peripheral vascular disease— A. predominantly lower extremity B, clinical (pain Q) _pulselessness (3) _paresthesias (4) pallor (©) paralysis (©) gangrene: common in diabetics (7) intermittent claudication: pain on walking which is relieved by resting (8) _Leriche syndrome: a, aortoiliac disease in male with impotence (hypogastric arteries involved) b. claudication ©. atrophy of calf muscles d. —diminished/absent femoral pulses ase: may hear a bruit over involved vessel 40Note: This material is copyrighted, All rights reserved 4. circle of Wills disease A. cerebral infarction (@) usually pale infarct @) MC type of stroke B. cerebral atrophy (1) due to laminar necrosis of neurons in layers 3, $ and 6 of the cerebral cortex @) apoptosis of neurons "red" neurons on H and E stains C. atherosclerotic aneurysms: e.g, basilar artery 3. vertebrobasilar artery disease~ A. transient ischemic attacks: (1) dizziness @) vertigo B. brain stem infarction “ 6. internal carotid artery disease- A. transient ischemicatiacks: due to embolization of plaque material with neurologic deficits lasting <24 hours B. atherosclerotic stroke: (1) usually occur at bifurcation of the internal carotid artery (2) due to platelet thrombus overlying atherosclerotic plaque @) _ prevented by aspirin (4) ticlopidine used in aspirin allergy: problem with neutropenia () control of high blood pressure is the single most important factor that prevents strokes C. embolic stroke (1) _ embolism of atheromatous plaque material, or @) emboli from left heart 7. renal artery disease— A. renovascular hypertension MCC of secondary hypertension B. elderly men with severe atherosclerosis and uncontrollable hypertens C. high renin hypertension D. epigastric bruit 8. celiac, superior and inferior mesenteric artery disease A. small bowel infarction: (1) usually thrombosis/embolism involving superior mesenteric artery Q) bowel distention/pain (3) bloody diarrhea B, large bowel: (1) symptoms occur in splenic flexure area: overlap area of blood supply involving superior mesenteric/inferior mesenteric artery 2) mesenteric angina: abdominal pain in splenic flexure area 30 minutes after eating @) _ ischemic colitis: splenic flexure pain + bloody diarrhea (4) ischemic strictures: healing of infarction by fibrosis leads to large bowel obstruction from stricture formation Aneurysms of the vascular system SK UltRe Saund is He gold stndued for despesing 1 abdominal aortic aneurysm an aneudysm A. MC type of aneurysm: pietureomUSMLE B. MC in men over the age of 55 €. pathogenesis 4Note: This material is copyrighted. All rights reserved. (2) weakening of the wall by atherosclerosis owing to no vasa vasorum below the renal artery orifices @) Law of Laplace states that as the diameter increases the wall stress progressively inereases: further enlargement and rupture is inevitable ()_ often accompanied by a popliteal artery aneurysm: danger of thrombosis requiring leg amputation D. clinical (1) majority are asymptomatic @) symptomatic: a. pulsatile mass with mid-abdominal to lower back pain b. abdominal bruit (50%) © rupture MC complication (3) rupture triad: 4, abrupt onset of severe, back pain (most rupture into the left retroperitoneum) —> Jeff flank pain b/e acee is Reltpeeipavea! Ais b. hypotension pulsatile mass E, diagnosis: (2) abdominal ultrasound is gold standard test @) size and risk for rupture color the Rx berry aneurysm- A. young or middle aged adults B. most commonly located at bifurcations of cerebral vessels: e.g., anterior communicating artery with anterior cerebral artery C. pathogenesis: (1) most are congenital: not usually atherosclerotic in orig 2) vessels tack an internal elastic membrane and muscle wall at bifurcations of cerebral vessels D. associations: any cause of hypertension predisposes to berry aneurysms: (Q) essential hypertension @) adult polycystic disease (10-15%) 3) _ coarctation of the aorta (increased pressure in cerebral vessels) clinical: () headache @) subarachnoid hemorrhage: a. severe, occipital hetdache b. “worst headache I ever had" followed by a loss of consciousness F. diagnosis (@) CT scan/MRI as a sereen @) angiography confirms myeotic aneurysms~ A. weakening of the vessel wall secondary to an infectious processes: (Deg, septic embolis @) infective endocarditis (3) fungal vasculitis B. clinical (1) thrombosis @) rupture (Aspergillus, Mucor, Candida are vessel invaders)Note: This material is copyrighted. Al rights reserved 4 4a al ye av! a syphilitic aneurysm— A. males 40-55 ys of age B. cardiovascular manifestation of tertiary syphilis C. pathogenesis (DT. paitidum produces endarteritis obliterans ic infiltrate) of vasa vasorum of ascendin itis with plasma and transverse portions of arch of anris GR leads ischemia of outer adventitialimedial tence L sph Weakening of aorta» oe Scar with retraction ofthe underlying endothelial tissue Producing "tree barking” De of the endothelial surface—+ aneurysmal dilatation of aorta» dilatation of aortic valve rings aortic regurgitation-> death from heart failure or rupture D. clinical {3} _ Sati Fegurgitation wth dilatation hypertrophy of leh ventricle (2) respiratory difficulties from airway encroashnery @) brassy cough fiom left recurrent laryngeal nent invitation: stretched by dilated aorta {2 _amains: due coronary arteriaostia narrowing by fibrosis () "bounding pulses (water hammer pulse) E. diagnosis (1) aortography a atsification inthe arch of aorta highly predictive ofa syphilitic aneurysm dissecting aortic aneurysm— A. mean age of 60-65 B. men > women C. MC eatastrophie disorder of aorta D. MC aneurysm of ascending aorta E. pathogenesis: ) pathology: a. elastic tissue fragmentation (95%) b. mucoid degeneration: cystic medial necrosis © nents in the midate and outer part of the media 2) associations fb: Marfan’s syndrome (defect in fibilin) be* Bhlers-Danlos syndrome (defect in collagen) © -> pregnancy (increased plasma volume) 2+ copper deficieney cofactor in iysyl oxidase) © coarctation of aorta (wall stress) £ trauma cause of dissection (D°Shypertension applies a shearing force tothe intimal surface» intimal tear usually within 10 cm of the aortic valve 6 Column of blood dissects under arterial pressure through the areas of weakness and progresses proximally and/or distally @) eventual sites of rupture: 4. pericardial sac (MC COD)Niteopeussile =» used +, t bye Note: This material is copyrighted. All rights reserved. . WW Ay ssech toed, Ht VY disseching Heh C ane + il mel venrt-hyaaeteng r b. mediastinum peritoneum 4d. reentry throug types of dissections (type A aneurysm: a. MC and worst type b. _ involves ascending aorta 2) _ type B aneurysm: begin below the subclavian artery and extend distally H. clinical: (1) acute onset severe retrosternal chest pain with radiation into the back (2) AV regurgitation: due to dilatation of aortie valve ring (3) _ signs of cardiac tamponade (4) loss of upper extremity pulse (5) stroke 1. diagnosis: (1) _ increased aortic diameter on chest x-ray (80%) (2) retrograde arteriography is gold standard test (3)__ overall long-term survival 60% J. (patientprofilevon"USMEE- anterior chest pain, widening of the aortic root on echocardiogram, death in 3 days by tamponade nother tear to create a double barreled aorta Overview of venous system. 1, superficial veins (e.g., superficial saphenous veins) drain into the deep vei communicating (penetrating) branches. 2. valves prevent blood flow from the deep into the superficial venous system- exception is around the ankles, blood flow is from the deep venous system to the superficial system Phlebothrombosis and thrombophlebitis: 1, phlebothrombosis— thrombosis of a vein without inflammation. 2. _yenous elots in descending order of frequency A. deep vein in the calf B. femoral vein C. popliteal vein D. iliac vein predisposing factors for phlebothrombosis ‘A. damage to the vessel endothelium (e.g, B. stasis of blood flow (e.g., bedrest) C. _hypercoagulability (e.g, oral contraceptives) 4. clotting process~ A. begins in stasis areas such as the venous sinuses of the calf muscles and in the valve cusps B. platelets form the initial clot in the valve cusps €. developing clot extends beyond the next branching point at which juncture the clot becomes a venous clot (red thrombus) consisting of a mixture of RBCS and fibrin D. venous clot propagates towards the heart in the direction of blood flow: danger of embolization 5. clinical ‘A. swelling, pain, edema distal to the thrombosis B. development of varicosities and ulceration. flammation, varicose veins)Note: This material is copyrighted. All rights reserved. deep venous thrombosis (DVT) in the lower extremity— Produces deep venous insufficiency: post-phlebitic syndrome deep saphenous vein thrombosis leads to an increased venous pressure and increased blood flow to veins around the ankles which communicate with the superficial system veins in the ankles rupture resulting, a swelling, hemorrhage, ulcers) Q) _ seei varicosities in the superficial saphenous system complications of venous thrombosis include A. thromboembolism: @) potential for a pulmonary embolism with infarction (2) femoral vein MC site for embolization B. thrombophlebitis C. varicose veins Doppler (duplex) ultrasonography- A. best screening test for detection of deep venous thrombosis B. X-ray venography is gold standard test thrombophlebitis~ A. pain and tenderness along the course of a superficial (not deep) vein B. causes: (1) MCC is superficial varicose veins Q) _ phlebothrombosis @) intravenous catheters (4) _ intravenous drug abuse clinical: (1) palpable cord (2) pain, induration, heat, erythema migratory thrombophlebitis subtype of thrombophlebitis A. venous thrombi disappear at one site and reappear at another may be a paraneoplastic sign of underlying pancreatic cancer (Trousseau's sign) = Varicose vein 1. definition 4. abnormally distended, lengthened and tortuous veins associated with (1) superficial saphenous veins: MC site 2) distal esophagus in portal hypertension @) anorectal region (e.g., hemorrhoids) (4) left testicle (varicocele) superficial saphenous vein varicosities MC in women (1) primary varicose veins are due to a, valvular incompetence (sentinel valve) b. weakened vessel walls © positive family history 4. occupation of the individual: standing secondary varicose veins: a. damage of the valves from previous thrombophlebitis or b. deep vein thrombosis.Note: This material is copyrighted. All rights reserved. ‘Thoracic outlet syndrome: 1. definition abnormal compression of the neurovascular compartment in the neck 2. causes: AL cervical rib B. _ spastic scalenus anticus muscle C. positional changes in the neck/arms Subclavian steal syndrome: 1. definition— due to proximal obstruction of the first portion of the subclavian artery 2. causes reversal of blood flow in the vertebral artery (produces cerebral ischemi supply blood to the arm ‘Superior vena caval (SVC) syndrome: 1. secondary to extrinsic compression of the SVC from a primary lung cancer (90%) 2. puffiness and blue to purple discoloration of the face, arms and shoulders 3. CNS findings of dizziness, convulsions, and visual disturbances (con; veins). 4. distended jugular veins ) to ested retinal e Lymphatic disorders: 1. lymphatic vessels have an incomplete basement membrane- predisp. ‘tumor invasion 2. acute lymphangitis A. inflammation of lymphatics (“red streak") B. Streptococcus pyogenes MCC: e.g., cellulitis 3. lymphedema interstitial collection of iymphatie fluid due to: A. congenital disease: (2) Milroy’s disease 2) Tumer’s syndrome B. _ blockage of the lymphatics: (1) radiation post-mastectomy @) peau dorange of breast in inflammatory carcinoma @) filariasis 4. chylous effusions. A. collection of lymphatic fluid in a body cavity B. contains chylomicrons with TG plus mature lymphocytes C. causes of chylous effusions in pleural cavity (1) MCC is malignant iymphoma @) trauma to thoracie duct ses to infection and Benign/malignant vascular tumors and tumor-like conditions: 1, Sturge-Weber syndrome (SWS) syndrome— ‘A. port wine stain in the distribution of the ophthalmic branch of the trigeminal nerve B, _ CNS vascular abnormalities often located in the leptomeninges on the ipsilateral side: (1) caleify (look like railroad tracks) Q) bleed @) focus for seizure activity €. mental retardation 2. hereditary hemorrhagic telangiectasin (Osler Weber Rendu disease) A. AD disease: MC genetic vascular disorder B. small aneurysmal telangiectasias on the skin/mucous membranes 46Note: This material is copyrighted. All rights reserved, C. epistaxis D. Gi bleeds: iron deficieney spider telangicctasias— ‘A. small arteriovenous communications B. associated with hyperestrinism: (1) pregnancy Q) cirrhosis compression of the “body” of the spider causes the blood flow to the “legs” to disappear: petechia do not blanch (USMILE), angiomyolipoma~ A. hamartoma composed of blood vessels, muscle and mature adipose tissue B. MC inkidneys C. association with tuberous sclerosis bacillary angiomatosis— A. infectious disease caused by Bartonella henselae and Bartonella quintana B. associated with AIDS: simulates Kaposi's sarcoma €. benign capillary proliferation on the skin and/or visceral organs D. silver stains identify them in tissue E. _ organism also causes eat scratch disease capillary hemangioma~ A. benign tumor’? hamartoma of mature capillary channels B. “strawberry type” commonly seen on the face in newborns: (1) slightly raised, bright red, lobulated vascular tumors 2) 80% totally gone by 8 years (3) no treatment necessary (USMILEY cavernous hemangioma- A. MC benign tumor of the liver/spleen, and placenta (called cholangioma) B. may rupture in liver/spleen C. association with von Hippel-Lindau disease: (AD disease @) cavernous hemarigiomas of the cerebellum (cerebellar hemangioblastoma), brain stem, eyes () increased incidence of renal adenocarcinoma and pheochromocytoma ‘A. sarcoma derived from vessel endothelium B. _ liver angiosarcomas: associated with exposure to: (1) vinyl chloride (MC) Q) arsenic @) _ thorotrast C. electron microscopy reveals Weibel-Palade bodies: (1) _ structural hallmark of endothelial cells @) contain von Willebrand's factor D. histochemical stains positive for factor VIIL Kaposi's sareoma— A. malignant tumor arising from endothelial cells (some debate on this origin) B, immunodeficiency variant develops in patient's taking immunosuppressive drugs (¢ renal transplant patient) C. AIDS variant: (2) MC cancer in AIDSNote: This material is copyrighted. All rights reserved. = (2) AIDS-defining lesion s (3) due to Herpesvirus 8 (4) _ solitary to multiple red-purple lesions that prog a plaque to a nodule that uleerates (8) _ microscopic: a. spindle cells (neoplastic element) with increased mitotic activity b. _ hemosiderin deposition (6) locations: a. skin (MC location, picture on USMIB) b. mucocutaneous surfaces (oropharynx MC location) €. visceral locations (lung, GI tract, Iymph nodes) 8 from a flat lesion (macule) to OM Re A. chemotherapy B. _intralesional c-interferon (USMIE) 10, lymphangiosarcoma- complicates chronic lymphedema due to modified radical mastectomy © Large vessel vasculitis: 1. definition: aorta to large/medium sized muscular arteries giant cell (temporal) arteritis- A. >50 years of age B. women more often involved than men (2:1) C. multifocal granulomatous vasculitis with multinucleated giant cells D. _ primarily involves the temporal artery and extracranial branches of the carotid art E. clinical: q (Q) fever 2) unilateral headache along course of temporal artery: MC symptom (3) jaw claudication (4) temporary/permanent blindness on ipsilateral side (5) _polymyalgia rheumatica: a. above signs and symptoms plus pain and morning stiffness (>30 minutes) in neck, shoulders, and hip b. no elevation of serum CK, unlike polymyositis FR. lab; (1) _ elevated erythrocyte sedimentation rate (ESR): best screening test @) definitive diagnosis: temporal artery biopsy . Rx steroids 3. Takayasu arteritis (pulseless A. Asian women <50 years old B. granulomatous vasculitis involving aortic arch vessels C. clinical (1) absent upper extremity pulse 2) blood pressure discrepancy between extremities: low in upper and higher in lower extremities (3) _ Raynaud's phenomenon visual disturbances stroke D. diagnosis: angiography -ase)— 48Note: This material is copyrighted. All rights reserved. ‘Medium to small muscular artery vascul 1, polyarteritis nodosa (PAN). A. B. Hedloss MC in middle aged men necrotizing immune vasculitis of small to medium sized arteries (1) immunocomplex vasculitis: a. type ll hypersensitivity b. _immunocomplexes may involve HBsAg (2) activation of neutrophils/monocytes by anti-neutrophil cytoplasmic antibodies: P-ANCA type (3) _ release of enzymes by neutrophils contributes to inflammation pathology (1) _ lesions are in different stages of development: acute or healing st (2) _ focal vessel involvement leading to aneurysm (3) _neutrophilic/eosinophilic infiltrate clinical associations: _HBY antigenemia: 30-40% 2) “hypersensitivity to drugs: e.g, intravenous amphetamines target organs (order of decreasing frequency) (1) kidneys: a, vasculitis/glomerulonephritis b. infarction 2) | coronary arteries: aneurysms (3) | liver: calcification of cystic duct artery (4) | Giract: bowel infarction (5) |-skin: painful nodules representing vasculitis in subcutaneous fat (6) “tung: not commonly involved in classic PAN clinical () fever (2) _ pain in areas of involvement (3) _ multisystem disease with infarction Jab: (1) _ peripheral neutrophilic leukoeytosis/eosinophilia @) anemia @) positive HBsAg (4) anti-neutrophil cytoplasmic antibodies with perinuclear staining: p-ANCA (5) hematuria with RBC casts: glomerulonephritis H. diagnosis: (1) arteriography and/or biopsy of palpable nodulations in the skin or organ involved @) _ renal failure MC COD 2. Kawasaki Disease— A. afflicts children <5 years old B. _ peak incidence in spring €. probable immune mechanisms involved D. transmural inflammation of vessels with neutrophils and mild fibrinoid necrosis: (2) leads to aneurysms/thrombosis (2) coronary artery vasculitis clinical: (1) MCC ofan acute myocardial infarction in children 49Note: This material is copyrighted. All rights reserved. (2) erythematous rash of trunk and extremities with desquamation at finger tips ) mucosal inflammation: cracked lips, oral erythema (4) erythema, induration, swelling of hands and feet () localized lymphadenopathy F. lab: (1) _ neutrophilic leukocytosis @) _ thrombocytosis: characteristic finding @) high ESR (4) abnormal ECG if myocarditis present G. diagnosis: echocardiogram sereen for coronary aneurysm H.R (J) _ intravenous gamma globulin Q) _ steroids contraindicated: increase risk for coronary aneurysms 3, thromboangiitis obliterans (Buerger’s disease)- Gaoye's 4sAese ‘A. young to middle aged cigarette smoking males B. _ unknown product in tobacco smoke: toxins produce direct damage to endothelium C. inflammatory vasculitis: (1) involves the whole neurovascular compartment of medium sized and small arteries in the extremities 2) thrombus in vessels contains focal neutrophilic microabscesses: vessels eventually fibrose D. clinical: (1) claudication in the feet or hands @) Raynaud's phenomenon ) distal gangrene of the digits often requiring amputation (common USMLE picture) E. diagnosis: biopsy F. Rx: early stages of vasculitis frequently cease on discontinuation of smoki ‘Small vessel vaseulitis 1. definiti ‘A. involves arterioles, capillaries and venules B. small vessel vasculitis (hypersensitivity vasculitides); (1) leukocytoclastic venulitis: vasculitis usually involves post-capillary venules @2) inflammation is at the same stage in all vessels (unlike PAN): a. neutrophilic infiltrate b, nuclear debris ¢. _fibrinoid necrosis (3) _ majority are type ITT immunocomplex diseases (4) all present with "palpable purpura”: purpura due to platelet abnormalities or rnon-immunologic weakness of small vessels is not palpable 2. Henoch-Schdnlein purpura (HSP)- A. MC vasculitis in children B. immune vasculitis mostly occurring in children following an upper respiratory infection (1) IgA-C3 immunocomplexes deposited in vessel walls @) IgA nephropathy (Berger's disease) may be part of the syndrome complex C. clinic (1) _ palpable purpura commonly limited to the lower extremities/buttocks ston — Fae Conphe df 0Note: This material is copyrighted, All rights reserved. 2) polyarthritis 3) abdominal pain: sometimes with melena (4) renal disease: hematuria due to focal proliferative glomerul D. lab: (2) neutrophilic leukocytosis @) normal platelet count @) increased IgA. E. Rx: steroids 3. autoimmune disease and vasculitis A. immunocomplex vasculitis B. types of autoimmune disease Q) SLE 2) rheumatoid arthritis (3) _ progressive systemic sclerosis, C. target organs: (skin @) kidneys @) bra 4. serum sickness. A. prototype of systemic immunocomplex disease B, soluble immunocomplexes due to antigen excess C. particularly common in the Rx of rattlesnake envenomations with horse-based antitoxins: antibodies are synthesized against foreign antigens followed by the formation of immunocomplexes with further exposure to antitoxin D. clinical ()) fever @) urticaria @) generalized lymphadenopathy (4) arthritis (S) _glomerulonephritis E. serum sickness-like prédrome in HBV and HCV ‘F Miscellaneous vasculitides: 1. Wegener’s Granulomatosis (WG)— A. childhood to middle age: mean age of 40 B. necrotizing granulomatous inflammation: (1) upper/lower respiratory tract @) necrotizing granulomatous vasculitis in kidneys 3) _anticneutrophil cytoplasmic antibodies (c-ANCA type): activate neutrophils monocytes with subsequent vessel/tissue damage clinical, (1) sinusitis (2) saddle nose deformity a, nasal cartilage destroyed treat Wu] Cytlo phoophem b. absent nasal hairs G) upper airway collapse ¥ (4) lung disease: &. recurrent pneumonia b. large angiocentrie densities on x-ray SINote: This material is copyrighted. All rights reserved. 4 (8) necrotizing glomerulonephritis: renal failure labs (1) neutrophilic/eosinophilic leukocytosis @)_anticneutrophil cytoplasmic antibodies with diffuse cytoplasmic pattem (c- ANCA): specific for Wegener's and marker of disease activity E, diagnosis: biopsy FRx (1) cyclophosphamide: danger of he carcinoma (2) steroids @) high mortality if left untreated lymphomatoid granulomatosis— A. similar to Wegener's granulomatosis B. differences from WG: (1) absence of upper respiratory involvement (2) progresses to a malignant lymphoma in 50% of cases Raynaud’s phenomenon~ A. arterial insufficieney of the digital v (1) primary disease (rare) (2) most often secondary to other diseases B. _ pathogenesis: () association with collagen vascular disease: a SLE b. progressive systemic sclerosis (first sign): starts as vasculitis of ve and ends with fibrosis ©. CREST syndrome: + calcinosis of finger tips/eentromere antibody * Raynaud's phenomenon © esophageal motility problems © sclerodactyly (teeter Araee © telangiectasia 2) association with cold reacting (IgM) antibodies/globulins: a. eryoglobulinemia: usually elderly patient with rheumatoid arthritis or patient with HCV b. cold agautinin diseases @) other associations: a. thromboangiitis obliterans b. Takayasu's arteritis © ergot poisoning (vasoconstriction) 4. thoracic outlet syndrome m (1) cold temperatures and stress are stimuli that may trigger the color changes of the fingers—> white blue— red @) ears and nose cyanotic (3) _ often relieved by warmth infections vasculitis— A. fungal vasculitis: vessel invading fungi (Candida stitis and ional cellNote: This material is copyrighted. All rights reserved, Q) Aspergillus B) Mucor species B. Rocky Mountain spotted fever (1) rickettsial disease caused by Rickettsia rickettsiae (2) transmitted by the hard tick Dermacentor andersa @) _ organisms invade vessel endothelium of arterioles/venules (4 inflammation and rupture of weakened vessel-> classic petechial lesions b on the soles and palms of hand» spread to. trunk (centripetal spread (8) classic triad: — 4 b. fever ©. _ history of tick bite disseminated meningococcemia (Neisseria meningitidis) (small) vessel. vascul hemorrhage: 2) _ sepsis precipitates DIC ) Waterhouse Friderichsen's syndrome: acute adrenal insufficiency due to hemorrhage D. disseminated gonococcemia (Neisseria gonorrhoeae) (1) small vessel vasculitis located on the hands, wrist, and feet 2) septic arthritis: usually knee @) _C5-C9 deficiencies E. viral vasculitis: (2) hepatitis B and C: immunocomplex Q) rubella F. infective endocarditis: immunocomplex vasculitis: (1) Roth's spots in retina @) _Janeway’s lesions on hands (painless) (3) Osler's nodes on hands (painful) (4) glomerulonephritis USMLE scenarios on vascular disease: 1+ most appropriate Rx for an elderly woman with a headache localized to the side of her ‘head accompanied by diffuse muscle aches andl pains, and an elevated ESR A. temporal arteritis with polymyalgia B. _ Rx with corticosteroids 2. weight lifter with weakness inthe hand, numbness/aid absent pulse A. thoracic outlet syndrome B. scalenus anticus muscle spasm or cervical rib compresses the subclavian artery and brachial plexus picture of hemangioma on fuse ofa child leave it alone caleification of digital vessels diabetes mellitus MCC of am arteriovenous fistula- trauma A. usually a knife injury B. may cause high output cardiac failure steeds om peprrhrey 4 's associated with capillary thrombosis and petechial ‘F Classification of hypertension: 1. essential hypertension 95% 2, secondary hypertension— A. renal disease:Note: This material is copyrighted. All rights reserved. G. H, (1) renovascular disease: MCC secondary hypertension a, elderly male with atherosclerosis, b. middle aged female with fibromuscular hyperplasia (2) renal parenchymal disease adrenal disease: (1) Cushing's syndrome @) pheochromocytoma (3) Conn's (primary aldosteronism) parathyroid disease: primary hyperparathyroidism thyroid disease: (1) _ severe hypothyroidism: diastolic hypertension 2) Grave's disease: systolic hypertension vascular disease: coarctation of the aorta CNS disease: (1) increased intracranial pressure @) poliomyelitis gynecologic disease: toxemia of pregnancy: pregnancy induced hypertension drugs: (1) oral contraceptives (MCC in women in reproductive age): estrogen increases liver synthesis of angiotensinogen 2) alcohol (3) cocaine ‘Essential hypertension: 1, systolic blood pressure correlates with stroke volume 2. diastolic blood pressure correlates with state of contraction of total peripheral tance (TPR) arterioles. diastolic blood pressure is the amount of blood in the arteries while the heart is filling up in diastole amount of blood in arteries is related to the arterioles, which control the TPR abbreviated Poiseuille's equation states that total peripheral resistance (TPR) = viscosity of blood/(radius of the arterio (1) vasodilatation of arterioles has greatest effect on lowering TPR (2) vasodilation of arterioles decreases TPR and decreases the diastolic blood pressure (3) vasoconstriction of arterioles increases TPR and increases diastolic blood pressure 3. MC type of hypertension A. B. high incidence in African-Americans pathogenesis in most cases: (1) retention of sodium raises the plasma volume leading to an increase in stroke volume (increased systolic pressure) @) sodium in smooth muscle cells of peripheral resistance vessels (arterioles) opens up calcium channels leading to vasoconstriction and an inerease in diastolic pressure 3) _African-Americans have low renin hypertension: due to an increase in plasina volume pathology associated with hypertension: (1) concentric left ventricular hypertrophyNote: This material is copyrighted. All rights reserved. MC complication b. potential for left heart failure 2) acute myocardial infarction: MC COD (3) hyaline arteriolosclerosi a. insudation of protein into walls of arterioles by increased luminal pressure narrow vessel lumen b. produces small vessel ischemia (4) nephrosclerosis in the kidneys: shrunken kidneys of hypertension b. cortical atrophy due to hyaline arteriolosclerosis eventual proteinuria and chronic renal failure (5) intracranial bleeds in the putamen area: due to ruptured Charcot-Bouchard aneurysms of lenticulostriate vessels © lacunar infarets: a. due to hyaline arteriolosclerosis b. pure motor or sensory strokes mntuated As 4. clinieal~aci @ Renovascular hypertension: 1, MC secondary eause of hypertension— ‘A. pathogenesis (1) _ atherosclerosis of renal artery orifice in male @) fibromuscular hyperplasia of renal artery in a woman: a. _ hyperplasia of smooth muscle in arteries narrow lumen b. "beaded" appearance of arteries noted with arteriogram clinical: (2) severe hypertension (2) epigastric bruit C. laboratory (1) high renin hypertension @) involved kidney has increased renal vein plasma renin activity @) _ uninvolved kidney has suppressed renal vein plasma renin activity (4) captopril markedly increases baseline plasma renin activity a. used as a screening test along with a renal scan b, renal scan shows decreased uptake of affected kidney, decreased size of affected kidney, decreased excretion in affected kidney Plasma renin activity (PRA) in different conditions: 1. sodium depletion ‘A. increased PRA B. volume depletion stimulates renin release upright posture~ ‘A. increased PRA B. decreases venous return to heart» decreases cardiac output—> stimulation of renin release C. recumbent posture does the opposite: increases venous return» incteases cardiac output-> decreases renin release catecholamines- A. _ increased PRA B. directly stimulate renin releaseNote: This material is copyrighted. All rights reserved. C. _ Beblockers do the opposite captopril (ACE inhibitor)~ A. increased PRA B. excellent screen for renovascular hypertension: (1) see exaggerated levels post-stimulation of negative feedback on renin 2) potential for renal failure if bilateral renal artery stenosis is present (USMLE), a. angiotensin II is primary modulator of intrarenal blood flow: in both kidneys b. ACE inhibitor reduces AT I levels and causes renal failure wing to block of angiotensin Il and loss Lasix A. increased PRA B. stimulation of RAA system from volume depletion 6. aldosterone blocker (spironolactone)~ A. increased PRA B. volume depletion from sodium loss C. Loss of negative feedback of aldosterone on renin renovascular hypertension— increased PRA malignant hypertension increased PRA 9. young hypertensives- A. increased PRA B. sympathetic nervous 10. African-American hyperten A. decreased PRA B. _ increased blood volume from sodium retention C. reason why diuretics are first choice in Rix 11. sodium overload/primary aldosteronism. A. decreased PRA B. increased blood volume from sodium retention 12. elderly hypertensives A. decreased PRA B. volume overload suppresses renin Concentric hypertrophy of left ventricle: due to increased afterload~ 1, essential hypertension MCC 2. aortic stenosis Hypertrophy and dilatation of left ventricle: due to volume overload of the vent 1, aortic or mitral valve regurgitation 2. left to right shunts with increased return to left heart 3. aortic valve ring dilatation A. dissection B. aonttis 4. mitral valve ring dilatation~ left heart failure = Left heart failure (LHF): 1. mechanisms of heart failure- A. diminished ventricular contraction: (1) ischemia MCC @) replacement by fibrous tissueNote: This material is copyrighted. All rights reserved. 3) myocarditis B. non-compliant (restricted filling) () amyloidosis @) iron overload @) glycogen in Pompe's disease C. increased workload: Q) increased afterload @) _ increased preload (volume overloaded) D. blood builds up behind the failed left heart increase in left ventricular volume/pressure—> increase in left atrial pressure—> increase in pulmonary venous pressure—> hydrostatic pressure overrides pulmonary capillary oncotie pressiire-» pulmonary ‘edema clinical findings A. symptoms outnumber signs B. decreased cardiac output: forward failure C. dyspnea: stimulation of J receptors in pulmonary interstitium D. pulmonary edema: due to increased pulmonary venous hydrostatic pressure E. left ventricular dilatation Q) volume overload 2) _Frank-Starling mechanisms at work lefi-sided S; heart sound: volume overloaded left ventricle lefi-sided S, heart sound: decreased compliance mitral regurgitation: (1) stretching of mitral valve ring @)__Pansystolic murmur at apex with radiation into axilla (increases with expiration) 1. paroxysmal nocturaal dyspnea andior pillow orthopnea at night: (1) "increased venous return at night due to lack of gravity effect when Iy cannot be handled by the let heart-> blood backs up into the lungs @) standing up or placing pillows under the head decreases venous return to the heart J. cough: (1) sputum rusty colored from alveolar macrophages phagocytosing RBCs @) “heart failure” cells 3. systolic dysfunction type of LHF— A. due to decreased contractility 1) ejection fraction (EF) <0.40 @) EF =stroke volume/left ventricular end-diastolic volume @) normal EF = 80/120 = 0.66 B. causes: ischemic injury MCC CG Rx (1) _ use of inotropic agents (e.g, digitalis) @) decrease afterload with vasodilators (e.g. A 4. diastolic dysfunction type of LHF~ A. due to decreased compliance of left ventricle: (1) places increased load on the left atrium @) pulmonary edema common Bom down inhibitors)‘Note: This material is copyrighted, All rights reserved. ® Right heart failure (RHE) L @) EF>04 B. causes: (1) left ventricular hypertrophy @) restrictive cardiomyopathy (3) _ hypertrophic cardiomyopathy C.__ Rx: increase preload by slowing heart rate (e USMLE scenarios A. chest x-ray appearance in heart failure: (1) prominent congestion of blood in the upper lobes 2) _perihilar congestion: “‘bat-wing configuration @) Kerley lines: represent fluid in the interlobular septa (4) _ patchy interstitial and alveolar infiltrates () pleural effusion B. microscopic appearance of lung in heart failure: (1) pulmonary edema: transudate @) alveolar macrophages with hemosiderin ("heart failure" cells) . calcium channel blockers, B-blockers) mechanisms A. LHF is MCC B, right ventricular infarction blood builds up behind the failed right heart increase in right ventricular volume/pressure—> increase in right atrial pressure—> increase in jugular venous pressure—> hydrostatic pressure overrides pulmonary capillary oncotic pressure—> dependent pitting edema + ascites clinical findings— A. signs outnumber symptoms B, decreased cardiac output: backward failure C. volume overload of right ventricle D sided Ss heart sound: volume overload sided S, heart sound: decreased compliance uspid regurgitation: (2) stretching of tricuspid valve @) _ pansystolic murmur at left parasternal border (increases with inspiration) congestive hepatomegaly: (nutmeg liver @) increased LDH isoenzyme 3) _ increased serum transaminases H. increased hydrostatic pressure in venous system: (1) ascites @) dependent pitting edema (3) jugular neck vein distention F to left heart failure (LHF)— A B. c D. E, Fr decrease preload and afterload ACE inhibitor decreases preload (blocks aldosterone) and afterload (blocks angiotensin TI): spironolactone added owing to eventual increase in aldosterone C. diuretics decrease preload 58Note: This material is copyrighted. All rights reserved. D. restrict salt and water (decreases preload) High output failure 1. mechanisms— A. increase stroke volume: (1) hyperthyroidism @) increase blood volume decrease blood viscosity: severe aniemia vasodilate peripheral resistance arterioles (decrease total peripheral resistance) (1) increases venous return tothe heart 2) causes of vasodilatation 4. thiamine deficiency b. endotoxie shock in early phases © metabolic acidosis D. arteriovenous fistula: (1) direct communication of arterial with venous system bypasses the microcirculation @)__ increases venous return to the heart @) causes of AV fistulas oF a, surgically produced in radial artery for renal dialysis b. trauma: © knife wound usual cause * pressing afferent vessel causes slowing of heart rate (Bran: sign) © hear bruit over the soft tissue mass ¢. Paget's disease of bone: arteriovenous fistulas develop in soft bone 2, USMLE correlation of high output failure with Poiseuille’s equation A. abbreviated equation: total peripheral resistance (TPR) = viscosity of blood/(radius of the arteriole)" B. vasodilatation has greatest effect on lowering TPR: see above causes C. decreasing viscosity, decreases TPR: see anemia * USMEE question of fetal circulation (know this very well):/ 1, USMILE question on what is lower in umbilical artery blood of a normal fetus versus ‘maternal arterial blood answer is POs is lower in A. chorionic villus in the placenta isthe primary site of Ox/CO; exchange for the fetus B. normal values in pregnancy, 2) normal hematocrit (Het) is ~359% @) 0; saturation (Sa0,) @) arterial PO, is ~105 mm Hg C. fetal Hb has a high affinity for O»: ideal for gas exchange in chorionic villi of the placenta D. fetal laboratory parameters: (1) Het of ~35%: a. higher than mothers b. high Het also increases viscosity @) increased percentage of HUF (70% at birth) (3) _left-shifted ODC from HBF umbilical vein has an SaQ ~80% and PO; 30-35 mm Hg: (1) thas the highest amount of oxygen in the fetal circulation 39‘his material is copyrighted. All rights reserved. (2) _itcarries oxygenated blood from the chorionic villus to the fetal liver (3) ~30% of the umbilical vein blood (SaO; of ~80%) mixes with hepatic blood (S20, of 26%), which contains portal vein blood nusoid a. Sa0; after mixing of umbilical vein blood with sinusoidal blood is ~67% b. sinusoids are drained by the hepatic vein, which empties into the inferior vena cava (IVC) (4) remaining umbilical vein blood enters ductus venosus: drains directly into the we ©) IVC S20; before entering the fetal right atrium is ~679%: most IVC-derived biood is directly shunted through a patent foramen ovale into the left atriun (Sa0, ~60%) (©) _ most SVC-derived blood enters right ventrcte: 8, fetal pulmonary arteries are hypertrophied from chronic vasoconstriction secondary to a low fetal PO, b, most blood entering the pulmonary arteries is shunted into the patent ductus arteriosis and from there into the descending aorta (right 10 left shunt; placenta-derived prostaglandin (PGE) keeps patent ductus open ©. descending aorta SaO; is ~58% and the PO; is 20-23 mm Hg (7) blood in the aorta flows towards the placenta via two umbilical arteries, which have a a, lower PO (20-23 mm Hg) than matemal arterial blood (PO; ~105 mm Hg) b. higher O, affinity than matemal arterial blood, owing to the presence of more HUF in the fetal RBCs, which lef-shifts the ODC greater O; capacity than maternal arterial blood (HF has a higher affinity for Os than adult HbA) ‘Congenital heart disease (CHD) and what oxygen saturations would be in each type: see schematics of all the CHDs step up of oxygen is compatible with a left to right shunt~ oxygenated blood (a0; 95%) from the left heart enters unoxygenated blood (SaO; 75%) with a step up of O» to ~80% in the right heart step down of oxygen is compatible with a right to left shunt unoxygenated blood (Sa0; 75%) from the right heart enters oxygenated blood (SiO: 95%) with a step down of O; to ~80% in the left heart snmenger's syndrome- excess blood in the right heart from a left to right shunt causes volume overload, which produces: (1) pulmonary hypertension @) right ventricular hypertrophy B. reversal of shunt occurs when right ventricular hypertrophy overrides left ventricle pressures: patient develops cyanosis (called cyanosis tardive) ventricular septal defect (VSD) A. MC congenital heart disease: (1) _ usually spontaneously corrects itself (2) defect in the membranous septum (3) associated with ori du chat (partial deletion of chromosome 5) and trisomy 18 initially a left to right shunt through a defect in the membranous septum: (1) step up of O; to 80% in the right ventricle and pulmonary artery 60PSG Wie A \ a x Bs Sa Lvs siltation © [eet | (maamcr) (Samm) = Samra en ts than ght] | umur” || eyenoss + Lesbetaviananey]| eon tort with PH J, 7 WA Trconsoax) hypararcon 5 auton ue pal St Tax * Blood pressure] phe < asaly BS (creme A. WH } Ee, —— eL ~ re Pi ncichigje Pesca ~ | roguton arey J senseus Pon aaenltal beartdiseae. (A) epresents a ventricular septal defect, (B an atl septal detect. © a Ir aera ai a tl Satcation of the dora, tetralogy of Fallot and ) iarapostion oie gene ease Ti ak vennaca ele dlect, A, sore valve: DA, ductus areconus NC. inferior wins ate Ee ea oa eelsco [fomoenNote: This terial is copyrighted. AM rights reserved, 2) volume overload of right heart may lead to Eisenmenger's synd atrial septal defect (ASD) A. B. c D. MC adult CHD association with fetal alcohol syndrome initially a left to right shunt through a patent foramen ovale (A) _ step up of O; to ~80% in the right atrium, right ventricle, and pulmonary artery @) volume overload of right heart may lead to Eisenmenger’s syndrome fixed splitting of S: patent ductus arteriosus (PDA)- A B. association with congenital rubella initially a left to right shunt from the aorta to the pulmonary art arteriosus: (Q) step up of O; to ~80% in the pulmonary a (2) left atrium has 95% Sa0, ) volume overload of right heart may lead to Eisenmenger's syndrome: a. pulmonary artery empties unoxygenated blood into the aorta (step down in through the ductus Sa02) unoxygenated blood enters aorta distal to the subclavian artery . patient is pink in the upper extremities and cyanotic in the lower extremities 4. called differential cyanosis tetralogy of Fallot A, B. MC cyanotic congenital heart disease tetralogy includes: (1) overriding aorta: least common anomaly @) sp @) _inftavalvular pulmonic stenosis (4) right ventricular hypertrophy eyanosis depends on the degree of pulmonary valve stenosis: | (1) cyanotic at birth if the stenosis is not significant, since most of the uunoxygenated blood enters the pulmonary artery for oxygenation in the lungs @) cyanosis is present at birth if the stenosis is significant, since the majority of blood is shunted from right ventricle into the left ventricle and out the aorta presence of an ASD and PDA are cardioprotective (USMLE): (J) left to right shunt of ASD adds oxygenated blood into RA and steps up right- sided Sa0y @) left to right shunt of PDA takes unoxygenated blood in the aorta and dumps the blood into the pulmonary artery for oxygenation in the lungs ‘complete transposition of the great vessels— A. association with matemal diabetes usually @ PDA, ASD, and VSD are present pathophysiology: (1) venous blood normally empties into the right atrium via the vena cava (S10; 75%) (2) oxygenated blood (S20, 95%) normally enters the left atria via the pulmonary (3) _ the aorta is transposed and empties the right ventricle (4) _ the pulmonary artery is transposed and empties the left ventricle (8) _ oxygen saturations are as follows: 6Note: This material is copyrighted. All rights reserved. step up of SaO; to ~80% in right atrium as oxygenated blood from the left atrium empties into the right atrium through the ASD right ventricle with SaO; ~80 is emptied by the aorta (patient has cyanosis) some right ventricle blood is shunted right to left through a VSD into the left ventricle (step down of SaOs to 80%) left ventricle is emptied by the pulmonary artery for oxygenation in the lu only vessel with Sa0> of 95% is the pulmonary vein only chamber with S20; of 95% is left atrium ® Postductal coaretation: 1. constriction of aorta is distal to the ligamentum arteriosum 2. clinical ‘A. proximal to the aortic constriction: (1) _ systolic murmur between the shoulder blades (2) increased blood pressure/musculature in upper extremities (3) dilatation of proximal aorta (subject to a dissection) (@) dilatation of aortic valve ring with aortic regurgitation (8) _ increased incidence of congenital bicuspid aortic valve (©) increased intracranial blood flow: circle of Willis vessels prone to bery aneurysm formation and rupture distal to the aortic constriction: (1) decreased blood pressure/musculature of lower extremity 2) _ leg claudication from ischemia (3) decreased renal blood flow leads to diastolic hypertension: renin/angiotensin/aldosterone system collateral circulation: (1) intercostal arteries (rib notching) (2) superficial epigastric artery anastomoses with intemal mammary artery D. Turner's syndrome: preductal coarctation that is symptomatic at birth ‘USMLE scenarios on CHD~ 1. im» Kartagener's: syndrome-(situs inversus, immotile cilia syndrome), theresis:n0 ‘transposition: the heart is totally normal but is located on the right side 2. chamber with the highest PO; in'a PDA= left atrium or left ventricle or aorta 3. pulmonary artery SaO; in aPDA~ step up of S20, to ~80% Major coronary artery risk factors (National Cholesterol Education Panel 1993): 1. age is the most important overall risk factor~ A. male 245 y old B, _ woman 255 y old history of premature coronary artery disease (CAD) or stroke current cigarette smoking, enhances atherosclerosis~ chemicals in smoke damage endothelial cells hypertension with blood pressure >140/90 mm Hg~ CAD is MC COD in hypertension HDL <35 mg/dL A. enhances atherosclerosis B. _ HDLis the major risk factor for women in their reproductive years C. LDL is the major risk factor for males regardless of ageNote: This material is copyrighted. All rights reserved. 6. diabetes mellitus- ‘A. enhances atherosclerosis B. CAD is MC COD in diabetes LDL >160 mg/dL— ‘A. enhances atherosclerosis B. oxidized LDL poses an even greater risk for CAD than native LDL C. vitamin E neutralizes oxidized LDL 8. HDL 260 mg/dL A. negative risk factor for CAD B. subtract I risk factor from the above major risk factors Factors responsible for myocardial O; demand: 1, heart rate (HR)- A. a3 HR increases, contractility increases: (1) more action potential per unit time @) more O; consumption B. reducing HR, reduces O consumption C. _HIR>180 bpm decreases the length of diastole, which decreases filling of the coronary arteries and left ventricle ular wall pressure A. an increase in wall pressure increases O: consumption B, wall pressure increases when: (1) ventricles are hypertrophied or (@) when the radius of the ventricle is decreased owing to noncompliant muscle (most often the result of ischemia) Factors responsible for myocardial O; supply 1. coronary artery blood flow- A. most important factor B. coronary arteries fill in diastole C. clinical correlations: (1) decreased cardiac output in aortic stenosis causes less filling of coronary arteries and the potential for angina @) _aorttis in syphilitic aneurysm leads to narrowing of coronary ostia and angina (3) _ increasing heart rate decreases time for filling of coronary arteries (4) subendocardium gets the least amount of oxygen from the coronary arteries 2. left anterior descending (LAD) coronary artery- A. supplies entire anterior portion of left ventricle: (1) danger of rupture in a transmural myocardial infarction @)__ prone to mural thrombosis in anterior myocardial infarctions B. supplies anterior 2/3rds of interventricular septum: (1) danger of permanent bundle branch blocks in anterior myocardial infarctions @) permanent pacemaker is often required 3. right coronary artery (RCA)- A. supplies the entire posterior and inferior part of the left ventricle: responsible for epigastric pain in a myocardial infarction B. supplies the entire right ventricle: right ventricular infarction C. supplies posteromedial papillary muscle: danger of papillary muscle rupture and mitral regurgitation in myocardial infarctions D. supplies most of the blood to the arterioventricular node: danger of sinus bradycardia——————— * Note: This material is copyrighted. All rights reserved. & USMLE picture of coronary vessel: description— 1. atherosclerosis: slit like spaces 2. dystrophic caleification: biue bloiches 3. fibrofatty plaque: directly beneath endothelium “4. -platelet thrombus: red mass blocking the lumen Types of ischemic heart disease: angina pectoris~ MC type ‘acute myocardial infaretion~ MC COD in the United States, 3. sudden cardiac death ! 4 chronic ischemic heart disease © Angina pectoris variants: 1. exertional (classical) angina— A. MC variant B. severe fixed coronary artery atherosclerosis C. sudden onset of exercise-induced substernal chest pain lasting 1~15 min: relieved by resting and/or nitroglycerin D. Dx (1) exercise ECG (stress test) reveals ST depression: indicates subendocardial ischemia @) confirmed with arteriography: intracoronary artery ultrasound recently used 2. Printzmetal’s angina~ ‘A, secondary to coronary artery vasospasm: ? vasoconstrictive effects of thromboxane A2 released from small platelet thrombi overlying non-occlusive atherosclerotic plaques B, chest pain at rest c. Dx (1) stress ECG reveals ST elevation @) represents transmural ischemia 3. unstable (crescendo) angina~ A. severe, fixed, multivessel atherosclerotic disease B. eccentric stenosis of vessels with disrupted plaques with thrombosis present (1) nonocelusive thrombus @) _ release vasoconstrictive compounds like TXA2 C. frequent bouts of chest pain at rest D. Dx (1) stress ECG is unsafe @) ~20% progress to an acute myocardial infarction in 3 m 4. surgical procedures for Rx of coronary artery disease— A. percutaneous transluminal coronary angioplasty (PTCA)~ MC procedure B. coronary artery by-pass graft (CABG) Cause of thrombosis after angioplasty: localized dissection - ‘Vessels used in the CABG procedure: 1. internal mammary artery- A. _ best graft pateney B. 90% patency rate after 10 years saphenous veins ‘A. 40-50% patency rate after 10 years B. “arterialization” of the vessels, fibrosis, and occlusion 64Note: This material is copyrighted. All rights reserved. udden cardiae death: death within 1h severe atherosclerotic CAD die of ventricular arrhythmia association with smoking and non-Q wave infarctions si 1 3. 9.usually no occlusive vessel thrombus 4 5. Chronic ischemic heart disease: repeated infarcts with replacement of cardiac tissue by fibrous tissue leading to systolic dysfunction Gross (G) and Microscopic (M) changes in an acute myocardial infarction (AMD) 6. 0-4 is~ no G/M change 4-12 hs A. no Gchange B. _ Mshows coagulation necrosis after 6 hs 12-24 is A. Gshows early pallor B. _Mshows more advanced coagulation necrosis 134 A. G- definite pallor B. __M~neutrophilic infiltrate + advanced coagulation necrosis 3 74 A. period of maximal softness B. time for ruptures C. macrophages move in to remove dead tissue 7-10 a- A. Gis the same as 3-7 d B. —M shows collagen deposition AMI complications: 4. 5. arrhythmias— A. MC complication B. ventricular arrhythmias c. Mccop . heart failure— usually in first 24 h rupture- A. MC on the 3rd to 7th day B, usually anterior wall rupture with tamponade: thrombosis of the left anterior descending (LAD) coronary C. _ posteromedial papillary muscle rupture: (Q) right coronary artery (RCA) thrombosis @) acute onset of mitral regurgitation and heart failure D. ventricular septum rupture (LAD thrombosis @)_leftto right shunt mural thrombus~ danger of embolization periearditis— A. first week in transmural infarction: (1) friction rub @) fibrinous pericarditisNote: This material is copyrighted. All rights reserved B. __Dressler’s syndrome: (1) autoimmune pericarditis 6-8 wks later (2) _ systemic signs/symptoms: fever, joint pains, friction rub 6. ventricular aneurysm- A. late complication B. precordial bulge during systole C. heart failure is MC COD rognosis~ depends on ejection fraction USMLE ppictiiré of healed myocardial infaretion: blotchy fibrosis unlike sheets of pale staining tissue as in a pale infarction Lab abnormalities in an acute myocardial infaretion: 1. increase in CK-MB- A. begins in 4-8 hs B. CK-MB peaks in 24 hs C. disappears in 1.53 d D. reappearance of CK-MB >3 dis a reinfarction 2. imerease in troponin-1 A. begins in 2-6 hs B. peaks in 15-24hs €. gone in7d D. will likely replace LDH isoenzymes E. _ cannot identify reinfarction 3. LDH ya flip~ i A. begins to appear in 10 hs: (1) LDH; is normally > LDH (2) LDH; has highest concentration in cardiac muscle (3) AMI causes greater release of LDH, than LDH; leading to an LDH, flip B. peaks in2-3d gone in 7d D. — mainly used to identify AMI after 3 d 4, imerease in AST- A. begins 6-12 hs B. peaks 1-2d C. gone in 5-94 a Sequence of microscopic findings and their correlation with changes on ECG in an acute myocardial infarction: 1, peaked T waves~ correlates with area of ischemia in the myocardial tissue at the periphery of the infarct 2. ST segment elevation A. correlates with injured myocardial tissue around area of necrosis B. many of these cells die during reperfusion: (1) superoxide free radicals @)__ called reperfusion injury 3. symmetric T wave inversion correlates with area of ischemia 4. Qwave-area of necrosis 66his material is copyrighted. All rights reserved. F Rheumatic fever: 1. pathogenesis A. cross-reactivity (mimicry) of antigens in M proteins of group A streptococcus are similar to those to the patients heart and other tissues B, blood cultures are negative: itis an immunologic reaction and not a septicemia C. group A streptococeal infection usually begins a pharyngitis 2. __Aschoff body is the pathognomonic lesion of rheumatic fever~ area of fibrinoid necrosis and reactive hisioeytesin myocardial tissue 3. Jone’s eriteria for ac A. polyarthritis— (1) MC initial presentation @) no permanent joint damage (3) differential diagnosis: a. juvenile rheumatoid arthritis b. Henoch-Schoniein purpura B. carditis (1) pericarditis 2) myocarditis: MC COD in acute RF G) endocarditis 4, mitral valve vegetations: develop along the ine of closure ofthe valve b. mitral regurgitation (not stenosis) denham's chorea GY late manifestation (2) self limited D. subcutaneous nodules (1) fibrinoid necrosis in nodules (2) occur on extensor surfaces (3) _ histologically the same as in sheumatoid arthritis B. erythema margin (1) circular ring of eryshema around normal skin @2) vegetations on margin of the valve» erythema marginatum F. minor criteria (1) clinical findings a. arthralgias b. fever (2) lab: elevated ESR or C-reactive protein (3) ECG: prolonged PR interval (first degree block) supporting evidence of antecedent streptococcal infections (1) positive throat culture for group A streptococcus (2) positive latex agglutination test (3) elevated or rising anti-streptolysin © (ASO) titer F Mitral stenosis: 1, MCC is chronic rheumatic heart disease 2. pathophysiology— ‘A. volume overload in the left atrium and lungs B, decreased cardiac output 3. physical Dx A. accentuated S, due to closure of a non-pliable valve or1B 5 Puimonary hypertension eH ‘att atnal pero + eta AG CApioesen Aauring systole Pansystole murmur fegurgtation alg present ] Stonate tv opening) + Opening saap *Diastote rumble / > =a (Se) rh xy ry ~~ Concent Wa =] sve fom. | | citar Crease oven) { av comport ‘High-peoned dastl Pulse pressure ‘wing murmur + Anginalsyncope wth Sa FIGURE 10-3, Schematics of acquired valvular diseases of the heart, (A) represents mitral stenosis, B) mitral veguration, () aortic stenosis, and (D)aorte regurgitauon. (See Figure LOZ lor ist of abbreviations)Note: This material is copyrighted. All rights reserved B, opening snap (OS) occurs when the non-pliable valve gives way under increased left atrial pressure C. OS followed by a mid-diastolic rumbling murmur heard best at apex with the patient in the lateral decubitus position: increases with expiration D. accentuated P; indicates pulmonary hypertension (PH) from chronic pulmonary venous congestion E. right ventricular hypertrophy secondary to PH 4. clinical A. dyspnea and hemoptysis secondary to pulmonary congestion B. atrial fibrillation secondary to left atrial dilatation/hypertrophy (1) danger of systemic embolization C. dysphagia for solids: (1) due to left atrial enlargement @) left atrium is the most posteriorly located chamber and compresses the esophagus: requires transesophageal ultrasound to evahuate its size D. _hoarseness from irritation of the recurrent laryngeal nerve (Ortners syndrome) = Mitral valve prolapse (MVP) 1, MC valvular disease in the young population 2. pathogen A B. c D. valve leaflets (anterior and/or posterior (MC) undergo myxomatous degeneration (USMLE): (2) _ increased glycosaminoglycans (dermatan sulfate) (2) causes redundant (voluminous) valve leaflets )_ tricuspid valve involved in 20-30% leaflets prolapse into the left atrium during systole like a parachute AD inheritance pattern in some cases association with Marfan's/Ehlers Danlos syndromes 3. s lonmty erimppiriti BNote: This material is copyrighted. All rights reserved. 5. Rx- pericardiocentesis 4 Constrictive pericarditis: 1. causes A. TB MCC worldwide B. previous heart surge 2. pathophysiology~ A. heart cannot completely fill B. pericardial knock when ventricles hit thickened pericardium ‘© ECG questions on USMLE: short QT interval hypercalcemia prolonged QT interval~ hypocalcemia Unwave- hypokalemia peaked T wave hyperkalemia ‘SPdepression— subendocardial ischemia ‘STielevation— transmural ischemia/infarction prolonged PR interval— ‘AW first degree heart block B. common finding in patients on digitalis 8. atrial fibrillation 9. ventricular premature beats/tachyeardia 10, guterior myocardial infaretion= new Q waves in anterior leads I through TV Li. inferior wall acute tiyoeardial infaretion— new Q waves in Il, II, and aVE 12, Wolff-Parkinson-White- } A. short PR interval with a normal P wave B, delta wave on upstroke of R wave C. aberrant bundle by-passes AV node is MCC in United States | Questions used during the board review: ‘A 72-year-old man presents with a sudden onset of left flank pain. In the emergency room, the patient is hypotensive, A’pulsatile mass is palpated in the abdomen. Which of the following is | MOST responsible for the pathogenesis of this patient's condition? A. Atherosclerosis l B.A defect in fibrillin } C. Adefect in collagen D. _Long-standing hypertension E. Immune destruction of elastic tissue A (ruptured abdominal aortic aneurysm) A 42 year old man with a history of cardiac death in his family presents with a sudden onset of severe, retrosternal chest pain with radiation of the pain into his back. His left pulse is absent. A high pitched diastolic blowing murmur that increases with expiration is heard immediately after SocThere is widening of the aortic knob on a chest x-ray. The mechanism for this patient's condition is MOST CLOSELY related to. atherosclerosis a defect in fibrillin a defect in collagen an infectious process fan acute myocardial infarction Ds moam>Note: This material is copyrighted. All rights reserved B (dissecting aortic aneurysm) © A 26-year-old woman presents with a history of chest Palpitations particularly when anxious Fhysial exam reveals a mid-systolic ejection click followed oy murmur, The click and murmur mane, {reser to Si when the patient is standing and closer ic Sz when the lying down, The JSchanism for this patient's valvular disorder is MOST CLOSEL ¥ related to, A. adefect in fibrillin B. an infectious process C. immunologic damage D. _ myxomatous degeneration E, _adefect in collagen synthesis D (mitral valve prolapse) © Ar {2stolic ejection murmur that decreases in intensity when the Patient is lying down and increases in wale iY when standing up. An echocardiogram reveals abnornal movement of the anterior mitral Falve leaflet against an asymmetrically thickened interventricular septum. The patient MOST A. mitral valve prolapse B. _ hypertrophic cardiomyopathy C. acongenital bicuspid aortic valve cardiac myxoma of the left atrium E> infective endocarditis involving the mitral valve B (hypertrophic cardiomyopathy) ‘A 65-year-old man on the Sth day of hospitalization for an acute anterior myocardial infarction has LIKELY hag, Pest Paia aed an increase in both CK-MB and topone ra Patient MOST LIKELY has, A. papillary muscle dysfunction a right Ventricular infarct C. ventricular aneurysm D. amyocardial rupture E. reinfarction z ‘7 Which ofthe following is present in BOTH let and right hear failure? A. Ssheart sound B. Pillow orthopnea €. Pulmonary edema D. Neck vein distention E. Dependent pitting edema A (hoiceB in LHF, choice C in LHF, choice D in RHF, choice E in RHF) 75 "™ avert)Note: This material is copyrighted, All rights reserved. ‘You would expect a patient with an atrial septal defect to have which of the following oxygen saturation (SaO;) findings obtained by cardiac catheterization? | Normal | Patient | Patient | Patient | Patient | Patient | Sa0;% | A B E [Righatriam [75 75 20 [80 Right ventriele_| 75. 80 80 80. Pulmonary | 75 80 80 =] artery [Pulmonary vein | 95 3 95 5 Left ventricle | 95 95 95 80 Aorta 9 ~ 95 a [80 SaO; = oxygen saturation B (A= VSD, B= ASD, C= PDA, D = Tetralogy, E = transposition) ‘® A.30 year old man with a viral myocarditis who develops hypotension, neck vein distention a drop in blood pressure on inspiration, and muffled heart sounds most likely has A. _ hypertrophic cardiomyopathy B. constrictive pericarditis . _hypovolemie shock D. pericardial effusion E, a dissecting aortic aneurysm D (Beck's triad of pericardial effusion) lems 9-11 Aortic stenosis Aortic regurgitation Mitral stenosis Mitral regurgitation ‘Tricuspid regurgitation moop> ‘FA 70 year old man with diminished pulses and a history of angina and syncope with exercise has an ejection type murmur radiating into the carctid arteries A ‘* A.58 year old man with left heart failure has an $3 and $4 heart sound and @ Pansystolic murmur located at the apex that increases with expiration D A 29 year old intravenous drug abuser has fever, a giant c-v wave, and a pansystolic murmur along the left sternal border that increases with inspiration F ‘Which of the following types of hepatitis is associated with @ vasculitis characterized by p-ANCA, antibodies? A. Hepatitis A B. Hepatitis B C. Hepatitis C D. Hepatitis D E. Hepatitis E B (polyarteritis nodosa) 16Note: This material is copyrighted. All rights reserved. A 7 year old boy presents with a low-grade fever, arthralgias colicky abdominal pain, and a papihle urparie rash limited tothe lower extremities. Laboratory suds reves! a aucec porn a uinalysis with red blood cell (RBC) casts, hematuria, and mild proteinuria we Ai a gormal Hb, Het and platelet count. Which ofthe fllowing isthe most kel A. Idiopathic thrombocytopenia purpura (ITP) B. Systemic lupus erythematosus (SLE) C. _ Poststreptococcal glomerulonephritis D. Rocky Mountain spotted fever Henoch-Schonlein vasa: Note: This material is copyrighted. All rights reserved. Respiratory system: a Arterial blood gas (ABG) interpretatio 1, review Fluids and Hemodynamics and Acid-Base 2. respiratory acidosis: A. B. € pH<7.35 PCO; > 45 compensation is metabolic alkalosis (1) HCO, <30 mEq/L is acute respiratory acidosis (2) HCO; >30 mEq/L is chronic respiratory acidosis 3. respiratory alkalosis: A B, c 4, metabolic acidos A. B. c pH>7.43 PCO; <33 metabolic acidosis is compensation: (1) HCO; 218 mEq/L is acute respiratory alkalosis @) HCO; <12 mEq/L is chronic respiratory alkalosis pH<7.35 HCO; <2 respiratory alkalosis is compensation: PCO; decreased 5. metabolic alkalosis: A B. c pH>7.45 HCO; >28 respiratory acidosis is compensation: PCO; increased 6. mixed disorders: A. B. 1G = pulmonar if the pH is normal (7.35~7.45), it must be a mixed disorder since there is no full compensation if pH is very low, it must be 2 acidoses: e.g., cardiorespiratory arrest with respiratory acidosis + metabolic acidosis if pH is very high, it must by 2 alkaloses: e.g., respiratory alkalosis and metabolic alkalosis) example: salicylate intoxication MC mixed ABG asked on USMLE: 1) normal pH @) PCO; <2 a. respiratory alkalosis b. salicylates overstimulate the CNS respiratory center @) HCO; <2 a, metabolic acidosis b. salicylate is an acid and salicylates damage mitochondria leading to tissue hypoxia and lactic acidosis, y function tests in restrictive and obstructive lung disease: see schematic 1. _restrietive lung disease— A. problem in getting air into the lungs: decreased compliance B. elasticity is increased: once air is in the lungs, it comes out rapidly on expiration C. all volumes and capacities are equally decreased D. forced expiratory volume in I second (FEV ue) is decreased:FIGURE 11-1. Schematic of the normal lung volumes and ¢a- pacities and the forced expiratory volume 1 second (FEV,..) and forced vital capacity (FVO) in a normal person (A), a person with restrictive ung disease (B), and a person with obstructive lung disease (C). FRC (functional residual capacity) represents the volume of gas that remains in the lung at rest at the end of a Aormal respiration and is the most reproducible part of a pulmonary function test, since it does not require patient effort. Person A (normal individual) has an FEVijn of 4 L and an FVC of 5 L, with FEVi/FVC ratio = 0.80. Person B with restrictive lung disease has a “miniaturiéed” curve of person A. Note that the FEVige and FVC are the same (3 L) owing to the increase in elasticity in the lungs, hence FEVie/FVC ratio = 1.0, Person C with the obstructive pattern is having difficulty in expelling air from the lungs owing to decreased lung elasticity. FEViee = 1 L, FVC = 3L, and FEVise/FVC ratio = 0.33. Both people B and C have reduced values for FEVie. and FVC when compared with the normal person; however, person B with restrictive lung dis ease has values between those of the normal individual and person C with obstruction. Person B has decreased compliance in the lungs, hence less air enters the lungs, but owing to the increased elasticity, the air that is in the lungs is expelled fast Person C has increased compliance (air easily enters the lungs); however, reduced elasticity causes the lungs to trap air on expiration, hence FEVise and FVC are much lower than in person B a the FEViw/FVC ratio is reduced. TLC, total lung capacity; TV, tidal volume: VC, vital capacityNote: This material is copyrighted, All rights reserved. (1) FEVigc is how much air a person can expel from the lungs in 1 second after a maximal inspiration Q) normal FEV. is 4 liters @)__ usually <3 liters in restrictive disease E, forced vital capacity (FVC) is decreased: (1) FVC is how much air the patient can expel fi inspiration @) normal is 5 titers @)_ often the same value as FEV F, _tntio of FEViug/FVC is increased () normal is 4/5 = 0.80 @) in restrictive disease, itis usually increased (3/3 = 100%) m the lungs after a maximal due to increased elasticity of the lungs 2. obstructive lung disease A. problem with getting air out of the lungs rather than into the lungs: (1) compliance increased Q) elasticity decreased B. residual volume is increased, since all the air cannot get out ofthe lungs: (1) this automatically increases the total lung capacity @) other volumes and capacities are decreased forced expiratory volume in 1 second (FEV yu) is decreased (1) normal FEVige is 4 liters 2) _ usually <2 liters in obstructive disease D. forced vital capacity (FVC) is decreased (A) normal is $ liters @) usually <2 liters, due to decreased elasticity ofthe lungs ratio of FEV icd/FVC is decreased: Q) normal is 4/5 = 0.80 2) _ in obstructive disease, it is usually decreased (1/3 = 0.33) Pacing Summary of pulmonary function tests in obstructive and restrictive lung dis - [Parameter Obstructive Restrictive 7] Total lung capacity (TLC) | Increased Decreased Residual volume (RV) Increased Decreased 1 (Tidal volume (TV) Decreased Decreased Vital capacity (VC) Decreased Decreased FEV se Decreased Decreased FVC Decreased Decreased | FEV aJ/FVC Decreased Normal to increased Decreased Decreased = forced expiratory volume 1 second, FVC = forced vital capa ‘0 = diffusion capacity with carbon monoxide ity, DL ‘Causes of an increased alveolar-arterial gradient (A-a gradient): 1. Ava~ difference between the alveolar PAO; and arterial PaO; inthe lungs 2. causes of increased gradient ‘A. ventilation without perfusion () eg, atelectasis @) produces intrapulmonary shunting 3) _ giving 100% O; does not increase the PaO,Note: This material is copyrighted, All rights reserved. B. _ perfusion without ventilation: (2) eg, pulmonary embolus @) increased dead space @) giving 100% O; does increase PO: since normally ventilated lung can make up the difference C. diffusion abnormalities: ¢.g., interstitial fibrosis, right to left shunts in the heart: €.g., cyanotic congenital heart disease 3. formula used to calculate A-a gradient A. PAO: =% oxygen (713)- PaCOy/ 0.8 B. using normal values~ PAO; = 0.21 (713) - 40/0.8 = 100 mm Hg 4. causes of hypoxemia with a normal A-a gradient. ‘A. depression of the respiratory center in the medulla (1) eg, barbiturates Q) CNS injury B. _ obstruction of upper airway: () ©g, café coronary 2) epigiotttis (3) croup C. chest bellows dysfunction: e.g., paralyzed diaphragm ‘© Nasal polyps: 1. allergic A. MC type B. occurs in adults 2. aspirin-related: A. called triad asthma: (1) take aspirin 2) develop asthma 3) nasal polyps B. usually occurs in patients with chronic pain syndromes CC. non-immune mechanism: (1) aspirin blocks cyclooxygenase and leaves the lipoxygenase pathway open 2) LTC-, D., E, are increased, which cause bronchoconstriction 3. cystic fibrosis~ any child with nasal polyps and a history of repeated respiratory infections and diarrhea should have a sweat test Laryngeal carcinoma: 1. causes~ A. smoking: MCC B. alcohol C. asbestos 2. site ‘A. supraglottic area is MC location B. squamous cell carcinoma clinical— A. — hoarseness 80r Note: This material is copyrighted. All rights reserved, F Atelectasis; 1. MCC of fever 24 hs after surgery 2. pathophysiology A. collapse of alveoli due to mucus blocking terminal bronchioles B. _ distal resorption of air through the pores of Kohin clinical- signs of consolidation: on A. increased tactile fremitus /(ibeafiow of che B. decreased percussion CC. _ clevated diaphragm (diaphragm moves up when alveoli collapse) D. chest lag on inspiration when takin) 7 Surfactant: 1. drugs that increase surfactant synthesis— A. glucocorticoids~ women who must deliver prematurely are given glucocorticoids to increase surfactant synthesis in the baby B. thyroxine correlation— A. Laplace's law states that collapsing pressure of alveoli P = 2 T (surface tension}/r (radius of alveoli) B. surfactant decreases surface tension and keeps the alveoli open on expiration C. surfactant (1) lecithin (phosphatidylcholine) @) synthesized by type II pneumocytes (3) _ stored in lamellar bodies Respiratory distress syndrome: 1. pathogenesi: A. decreased surfactant in fetus due to: (1) _ baby is premature @) poor glycemic control in mother with di a. hyperglycemia in mother—> b. hyperglycemia in fetus increase in fetal release of insulin—> , insulin inhibits surfactant synthesis) sarean section no stress on baby—> no increase in cortisol widespread atelectasis—> massive intrapulmonary shunting—> hyaline membranes composed of protein from vessel leakage (diffusion defect) clinical A. respiratory difficulty shorily after birth B. cyanosis complications A. superoxide free radical damage: (1) retrolental fibroplasia @) bronchopulmonary dysplasia necrotizing enterocolitisNote: This material is copyrighted. All rights reserved. C. intraventricular hemorrhage D. patent ductus arteriosis with machinery murmur: due to persistent hypoxemia 5. Rxof RDS- ‘A. positive end-expiratory pressure (PEEP) keeps airways fiom collapsing on expiration B. delivery of surfactant via PEEP therapy C. oxygen * Adult respiratory distress syndrome (ARDS): 1. causes A. endotoxie shock MCC B. gastric aspiration ©. trauma D. pneumonia in E. smoke inhalation baer fetat > Bary tollaye 2. pathophysiology- wv eeefi 0 / A. non-cardiogenic pulmonary edema B. _neutrophil-related injury with destruction of type Il pneumocytes (loss of surfactant) and damage to pulmonary capillaries ("leaky capillary syndrome C.massive intrapulmonary shunting from loss of surfactant is the most important abnormality D. _ hyaline membranes from protein leaking from capillaries 3. separate from cardiogenic pulmonary edema by pulmonary capillary wedge pressure (measure of left ventricular end-diastolic pressure)— A. low in PCWP in ARDS B, increased PCWP in cardiogenic shock 4. high mortalicy = Spontaneous pneumothorax: 1. causes A. idiopathic: qa) McC @) tall, thin males @) rupture of subpleural bullae in apex of lung B. _ iatrogenic: eg., needle puncture of lung after performing a C.-Marfans syndrome pathogenesis~ portion of the lung collapses: pleural cavity pressure is the same as the atmospheric pressure 3. clinical A. sudden onset of pleuritic type of chest pain B. _ tympanitic percussion note C. absent breath sounds D. diaphragm elevated E, _ trachea deviates to the side of the collapse 4. (USMILE:scenario= sudden onset of pleuritic chest pain in a scuba diver with collapsed lung, elevation of the diaphragm, and shift of trachea to the side of the collapse: spontaneous pneumothorax ‘Tension pneumothorax: 1. cause~ A. penetrating trauma tot belavian vein stick lungs‘This material is copyrighted, All rights reserved. 3. Typical vs atypical pneumonia typi A ‘tension pneumatoe: (1) occur in patients with S. aureus pneumonia (c.g., cystic fibrosis) (2) _intrapleural blebs occur that may rupture pathophysiology— A. B. c D, E. tear in the pleura allows air into the pleural cavity but prevents its exit increased intrapleural pressure shifts the mediastinal structures to the opposite side: compromises blood flow into the heart and out of the heart diaphragm is depressed on the affected side breath sounds absent on affected side tympanitic percussion note Rx- insert needle into the pleural cavity to relieve pressure B. c D. ical sudden onset of symptoms high fever productive cough: usually positive gram stain for bacteria signs of consolidation on physical exam and x-ray Streptococcus pneumoniae MCC chest x-ray is first step in management insidious onset low grade fever non to mildly productive cough no signs of consolidation (interstitial pneumonia) Mycoplasma pneumoniae MCC followed by Chlamyelia pneumoniae (TWAR agent) Community-acquired vs nosocomial pneumonia community acquired~ MC due to Streptococcus pneumoniae nosocomial— 1 2. A B. develops while in the hospital organisms in deScending order: () E.coli @) P. aeruginosa (MC if a respirator is involved) QB) S aureus Differential for rusty colored sputum: 1 2 3. 4. Streptococcus pneumoniae pneumonia chronic congestive heart failure heart failure cells mitral stenosis Goodpasture’s syndrome ‘= Summary tables of infectious disease Microbial pathogen Epidemiology Clinical Rhinovirus MCC (25-30%) of common cold, Main | Increased mucus secretions, sneezing reservoir are school children. Direct hand to | and coughing. URI MC infection in hand transfer of infected materiab/respiratory | clinical prac droplet infection. ~100. serotypes (vaccine unlikely).Note: This material is copyrighted, All rights reserved. Respiratory syneytial ‘virus (RSV) MCC _ of interstitial pneumonia (20%) and bronchiolitis with wheezing (50%) in infants, Late fall/winter. Hand to hand transfer of infected material/respiratory droplet infection, Dx with direct immunofluorescent techniques or ELISA test nasopharyngeal swabs. Rx: ribavirin for very severe infections Tnfluenzaniras Significant cause of mortality especially among those over 55 years of age who have | underlying renal, cardiac or lung problems, Type A virus produces pandemics and epidemics (most severe form). Type B produces epidemics. Type C is involved in sporadic cases. Hemagglutinins bind the virus to cell receptors in the nasal passages. Neuraminidase dissolves mucus and facilitates the release of viral particles from | the infected cell. Local epidemics result from minor changes in the antigenicity of the organisms, called antigenic drifts (point mutations). Pandemies are due to antigenic shifts, which involve mutations in hemagglutinin (need new vaccine). Mild cold to bronchitis to severe pneumonias (with exudate). Preum- onia often has a superimposed bacterial pneumonia (Staphylococcus aureus). Vaccine is effective in preventing flu in 70 to 90% of healthy young people. In older people, it is only 50% effective in preventing flu but 85% effective in preventing death. Reve syndrome may occur in children. Rx: amantadine (inhibits viral uncoating or transcription of viral RNA) Rubeola (regular measles) Chlamydia Symptoms of rubeola begin to appear alter the 7-14 d incubation period is finished Omithosis, or psittacosis, is a zoonosis (@ Fever, cough, conjunctivitis, and (excessive nasal mucu production) initially occur. Koplik spots in the mouth precede the onset of the maculopapular rash. Pneum- onia is the MC COD. Warthin Finkeldy multinucleated giant cells, Primarily results in interstitial psittaci disease contracted from animals). Inhalation | pneumonitis. Rx: erythromycin. of C. psittaci from psittacine birds (parrots, parakeets, pigeons, and turkeys) Chlamydia Droplet infection without an __avian | Rx: tetracycline. pneumoniae | intermediate. 5% of community acquired TWAR) atypical pneumonias. Seroepidemiologic L relationship with coronary artery disease. Chlamydia [Newborn pneumonia. ~10 to 20% of | Presents with staccato cough, con- trachoma newborns that pass through an infected birth | junctivitis, tachypnea, bilateral inspir canal develop pneumonia atory crackles, scattered expiratory wheezes, and hyperinflation (trp ai), febrile. Eosinophilia, Rx: eryhro- mycin Coxiella burnetit fever) @ Only rickettsia transmitted without a vector, Inhalation. Contracted by dairy farmers, veterinarians associated with the birthing process of infected sheep, cattle and goats and handling of milk in these animals, USMLE: person shoveling sheep dung. Sudden onset of high fever, headache, chest pain, myalgias. Interstitial pneumonia. Other problems: granulomatous hepatitis (50%), infective endocarditis. Rx: doxycyclineNote: This material is copyrighted, All rights reserved. Mycoplasma | MCC of primary atypical _pneumonia. | pnewnoniae | 15-20% of pneumonias in adolescents. 50% of pneumonias in military recruits. Incubation period 1-2 wks Nonproductive cough. Upper respira: tory tract symptoms (pharyngitis, earache) precede pneumonic manifestations. Interstitial pneumonia. Low grade fever. Complications: bullous myringitis (hemorthagic vesicles on the membranes), erythema multifo ike lesions), and Stevens Johnson syndrome (involves skin and mucus membranes in a disseminated manner), cold autoimmune hemolytic anemia due to anti I. Lab: increased cold agglutinin titers. Rx: erythromycin or tetracycline. Microbial (Gram Stain ‘Comments Pathogen _| Streptococcus | Gram*lancetshaped [MCC of community acquired typical pneumonia mewmoniae _| diplococcus | (bronchopneumonia or lobar pneumonia), Rx: erythromycin Staphylococeus | Gram * coccus Pneumonia commonly follows influenza infections (MC aureus bacterial pathogen). Major pathogen in cystic fibrosis. Common cause of nosocomial pneumonia, Hemorshagic pulmonary edema, abscess formation, and tension Peumatocysts (intrapleural blebs), which may rupture and produce pneumothorax. Yellow colored sputum, ‘Hemophilus | Gram rod ‘Common cause of pneumonia in eystic fibrosis and COPD. influenzae Rx: TMP/SMX. Acute epiglottis in children. Dec incidence due to immunization, Cause of inspiratory stridor ‘Thumbprint sign on lateral x-ray of neck, Rx: cefuroxime Pseudomonas | Gram -thin rod Water loving bacteria transmitted by respirators. Common aeruginosa cause of nosocomial pneumonia and MCC of pneumonia in gystic fibrosis. MC_pneumonia_in_ICU (due to | respirators), Blood vessel invader (hemorrhagic infarctions) Green colored sputum (pyocyanin). Rx: antipseudomonal B- lactamase susceptible penicillins (e.g., mezlocilln) Klebsiella Gram-fatrod with | Pneumonia commonly associated with aleoholies and MC pneumoniae | capsule pneumonia in nursing homes. Blood-tinged, mucoid sputum. Tends to involve the upper lobes and cavitates like reactivation TB, Lobar consolidation and abscess formation are common. Rx: third generation cephalosporin Nocardia Strict aerobe. Gram + | Granulomatous —microabscesses inthe lungs in asteroides filamentous bacteria. | immunocompromised patients. Rx: TMP/SMX Partially acid fast | Actinomyces | Anaerobe. Gram + | Draining sinuses in the jaw, chest cavity, and abdomen Israeli filamentous bacteria, | Sulfur granules contain bacteria, Rx: ampicillin or penicillin Legionella Gram - rod (need IF | Water loving bacteria (water coolers), Pneumonia with dry | mewmophita | sain or Dieter silver | cough, malaise, Mucke symptoms bloety meme oe | stain | striking fever. Other findings: arthralgias, renal, a nd CNS |Note: This material is copyrighted. All rights reserved, [— | Njcobacterium Strict aerobe. Acid- findings. Macrophage rather than a neutrophil response in | tissue. Can produce hyponatremia secondary to hypo: reninemic hypoaldosteronism from in ephritis. Rx erythromycin or tetracycline + rifampin Droplet infection. Primary TB: upper part lower lobe, lower tuberculosis | fast Part of upper lobe. Ghon complex. Usually resolves Reactivation TB: upper lobe, cavitary lesion. Kidney MC extrapulmonary site. _| Candida Not dimorphic. Bud: [Vessel invasion produces hemorthagie Inarsisy Rx albicans ding yeasts and pseudo- | amphotericin B or fluconazole hypha. Lung disease contracted from infect ions of indwelling catheters, | Cocetdioides immitis Dimorphis, Spherules with endospores in tis sues, Inhaling arthro- spores while living or passing through the Southwest or San Joa- 4quin valley in Califor- nia ("valley fever") _quakes (USMLE) Flu-like symptoms and erythema nodosum (painful nodules on lower Jegs). Pneumonia may be localized (egg. shell cavity in lower lobes), “coin lesions”, miliary spread in the lungs and/or throughout the body. African-Americans, Mexicans, and Filipinos have severe infections. Lab culture, ‘direct visualization of the spherules with endospores, skin test (useful), and serologic tests (useful) Rx: fluconazole Cryptococcus neoformans Histoplasma capsulatum jot dimorphic, Bud- ding yeast with narrow based buds. Found in pigeon excreta (around buildings, outside of: fice windows, under bridges). MC fungal opportunistic infection Dimorphic. MC systemic fungal infection. MC in Midwest, Inhal- ation of spores. Assoc- jation with bats, birds (Starlings), cave exp- lorers (spelunkers), abandoned warchous- es. Yeast rophages, Primary lung disease (40%). Produces a granulomatous reaction, if immunity is intact but no inflammatory reaction if immunocompromised. Lab: culture, direct visualization of the organisms and by serologic tests. Rx: amphotericin B or fluconazole Simulates TB lung disease. Dormant phase like TB (ean | reactivate). Produces coin lesions, consolidation, miliary spread, cavitation. Old infection’ sites characteristically contain caleified granulomas. MCC of sclerosing mediastinitis (fibrous tissue in mediastinum with encroachment on all mediastinal structures). Lab: culture, direct visualization in tissue (organisms in macrophages) skin tests (useful), and serologic tests (useful). Rx itraconazole (moderate disease), amphotericin B (severe disease)Note: This material is copyrighted. All rights reserved. Blastomyces | Dimorphie, Yeasts dermatitidis (Gkin has a verrucoid appearance resembling hhave broad based buds. | squamous carcinoma) and/or lung. Male dominance. Lab: Primarily along the | culture, direct visualization of the yeast forms in tissue. Rx: Southeast coast and | itraconazole into Midwest. Along inland waterways with beaver dams. Inhalat- Aspergillus | Not dimorphic. Fruiting | Aspergilloma refers to @ fungus ball (visible on wray) oF fumigatus body and narrow-angl: | matted hyphae and fruiting bodies that develops in a ed, ing septate | preexisting cavity in the lung (e.g., old TB site), Cause of hyphae. massive hemoptysis. Allergic bronchopulmonary disease involves both type I and type Ill hypersensitivity reactions. IgE levels increased. Vessel_ invader with hemorrhagic infarctions and a necrotizing bronchopneumonia. Common sinus infection in AIDS. Lab: culture, direct visualization. Rx: amphotericin B or itraconazole Absidia, Not dimorphic, Wide: [Clinical settings: diabetes, immunosuppressed patients Mucor, | angled hyphae without | Vessel invader and produces hemorrhagic infarcts in the Rhizopus septa lung, Invades the frontal lobes in diabetic ketoacidosis, Lab: culture, direct visualization. Rx: amphotericin B Preumocyatly | Reslassfied as fmgus. | Opportunistic infection. MC initial AIDS-defining Infeaon, carinii | Cysts attach to type | Lungs are dry and consolidated. Patients present with low. | pneumocytes. Poorly | grade fever, dyspnea and tachypnea. Bronchoalveolar | visualized with gram | lavage and lung Bx identify organisins. Chest x-ray: diffuse stains but stain well | alveolar and interstitial infiltrates. Rx: TMP/SMX. Given with silver and Giemsa | prophylactically when CD, counts <200 cells/uL. stains. Foamy alveolar infiltrate. Occurs when CD, T helper count <200 cellu Parasites with ‘Ascaris, Strongyloides, hookworm, larval phase in lungs ‘© USMLE scenarios with respiratory disease: L problems in cystic fibrosis patients associated with P. aeruginosa~ A. pneumonia B. bronchiectasis CC. sepsis D. _ tension pneumothorax from ruptured pneumatocysts MCC of pneumonia in eystie fibrosis P. aeruginosa cave explorer im Arizona with respiratory infection~ coccidioidomycosis (not histoplasmosis, too dry a climate and mainly in Ohio and Midwest) bridge painter in New York City with respiratory infection— ‘A. most likely histoplasmosis (starling dung) or eryptococcus (pigeons) B. may ask what to Rx the patient with: amphotericin respiratory problem associated with exposure to pigeons dung on window sill or under abridge cryptococcus 87Note: This material is copyrighted. All rights reserved. diseases where Streptococcus pneumoniae is MCC A. community acquired pneumonia meningitis in adults >18 otitis media spontaneous peritonitis in children with ascites sepsis in children with HbSS disease F. simu diseases where Pseudomonas aeruginosa is MCC~ ICU pneumonia (respirators) COD in bum patients COD in cystic fibrosis cellulitis/osteomyelitis in puncture wounds of foot in patient's with rubber footwear malignant external otitis in diabetes ecthyma gangrenosum hot tube folliculitis diseases where Hemophilus influenizae'is MEC- acute epiglotttis (decreased due to Hib immunization) MG/AIDS-defining tnfection~ Pneumocystis carinii pneumonia elderly man, who lives at home with his wife, develops pneumonia~ Sirepiococcus pneumonia chest x-ray-with right middle lobe pneumonia (obscures right margin of the heart) ‘A. probably related to obstruction by a bronchogenic earcinoma B. could also be aspiration with the patient lying down on the right side afebrile infant with staceato cough, signs of hyperaeration, conjunctivitis~ Chiamy ‘trachomatis pneumonia Lung abscesses: 2 A. aspiration of oropharyngeal material is MCC: mixed aerobe/anaerobe infection B. lobar pneumonia C. hematogenous spread air/fluid level on x-ray Lung locations with aspiration: standing/sitting— posterobasal segment right lower lobe lying down on back- superior segment right lower lobe (MC site for abscess) lying on right side- A. right middle lobe B. posterior segment of right upper lobe lying on left side lingula Pulmonary embolus: 1. source- femoral vein pathophysiology— A. perfusion defect: increases dead space B. _ majority of peripheral emboli do not infarct the lungs C. produce mild hypoxemia clinical setting A. postpartum B. post-operativeNote: This material is copyrighted. All rights reserved. r e sudden onset of dyspnea and tachypnea: MC symptom and sign, respectively fever pleuritic chest pain perfusion scan first step in work-up respiratory alkalosis mild hypoxemia increased A-a gradient pulmonary angiogram gold standard for Dx, SUSMLLE scenario gross photo ofa large saddle embolus in a patient on prolonged bed rest usually die of acute right heart strain Pulmonary hypertension: 1. causes A G. D. chronic hypoxemia: (2) hypoxemia vasoconstricts pulmonary vessels and vasodilates peripheral vessels Q) high altitude residents (3) chronic lung disease loss of pulmonary vasculature: ¢ q@ corp (2) restrictive lung diseases left to right shunts with eventual volume overload of right heart mitral stenosis with backup of blood into pulmonary veins pathology As B. c lini A B. c D. atherosclerosis of pulmonary arteries smooth muscle hypertrophy of pulmonary vessels angiomatoid lesions sal accentuated P2 cor pulmonale: Q) pulmonary hypertension (PH) leads to right ventricular hypertrophy @) definition applies to primary PH of pulmonary artery or PH due to lung disease ©) _ does not apply to PH and RVH of cardiac origin of primary origin a eg,, mitral stenosis b. left to right shunts primary PH occurs mainly in young women: progressive dyspnea, chest pain, syncopal episodes pruning of pulmonary arteries noted on x- Immotile cilia syndrome (Kartagener's syndrom: 1, absent dynein arm in cilia clinical~ A situs inversus’ (1) vessels and chamber in the heart are still normal (USMILE) 2) nota complete transposition infertility in males/females bronchiectasis sinus infectionsr Note: This material is copyrighted, All rights reserved. Restrictive lung di 6 es: decreased compliance and increased elasticity due to intersti fibrosis A. pneumoconioses MCC: dust borne diseases B. sarcoidosis C. hypersensitivity lung diseases D. drugs: see Environmental pathology notes coal worker's pneumoconio: A. exposure to coal dust B. "black lung" disease C. increased incidence of TB but not cancer D. Caplan syndrome: rheumatoid nodules in lung + coal worker's pneumoconiosis silicosis- A. exposure to silica dust. sandblaster B, nodular, fibrotic masses in the lungs: filled with silica erystals C. increased risk for TB but not cancer D. association with Caplan's syndrome asbestosis A. exposure to asbestos: (1) pipecfitterin shipyard @) roofer for over 20 ys no risk for TB smoker + asbestos exposure predisposes to primary lung cancer > mesothelioma non-smoker + asbestos exposure predisposes to primary lung cancer > mesothelioma asbestos body (feruginous body) looks like a dumbbell (ibe hypersensitivity pneumonitis- farmer’s lung: (1) _ inhalation of thermophilic actinomycetes 2) _ see Immunopathdlogy notes B. silo fille’ inhalation of nitrogen dioxide fumes C._ byssinosis: (1) "Monday morning bues" (2) patient works ina textile f Hamman Rich lung A. honeycomb hung B, end-stage of alveoltis syndromes: interstitial pneumonitis syndromes~ e.g, usual interstitial pneumonitis sarcoidosis A. granulomatous disease of unknown etiology primarily targets the ungs: noncaseating granulomas in hilar nodes and parenchyma uveitis with blury vision salivary gland enlargement x cx}; 4404S ) MCC of non-infectioW’grat 5 hepatitis F. nodules in skin cont Gab (1) increase in angiotensin converting enzyme @) anergy to common antigens @) low CD, T helper cell counts~ used up in producing granulomas -overed by iron) tory and has contact with cotton, linen, hempNote: ‘This material is copyrighted. All rights reserved. @ hypercalcemia Obstructive lung disease: 1. type: A. chronic bronchitis: (MC type @) _ clinical Dx~ productive cough >3 mths for 2 consecutive yrs B. emphysema . bronchial asthma D. _ bronchiectasis 2.__summary chart comparing chronic bronchitis with emphysema—__ [Parameter Emphysema Chronic Bronchitis | Onset of dyspnea Sputum production Appearance | Progressive, constant, severe [ Seant “Pink puffer” (not cyanotic), thin, weight loss Intermittent and often exacerbates with in Increased and purulent “Blue bloater” (cyanotic respiratory acidosis), obese due to [AP diameter Increased (hyperinflation) Less hyperinflation than emphysema Breath sounds Diminished owing to hyperinflation Wheezes and sibilant rhonchi PaO: PaCO; Mild hypoxemia at rest. iormal to low (respi alkalosis, reason for “pink puffer”) Moderate to severe hypoxemia Tnereased owing to respiratory | acidosis trap CO; behind terminal bronchioles filled with mucous Total lung capacity Markedly increased ‘Normal to slightly increased Residual volume Markedly increased Mildly increased Cor pulmonale Infrequent until late in the disease ‘Commonly present Ventilation’ perf Matched losses of ventilation (respiratory unit) and perfusion (loss of capillary bed) 3. types of emphysema Major mismatch owing to primary involvement of the terminal bronc! ‘ole (proximal to the respiratory uni hence more units are aff A. emphysema involves portions ofthe respiratory unit a) @ 8) respiratory bronchiole) alveolar duct Cs alveoli B. & centrilobular emphysema: a @ @) primary type in smokers destruction of elastic tissue support in the respiratory bronchiole upper lobe involved C. panacinar emphysema: i a a @) i-1 antitrypsin (AAT) deficiency a. primary AR disease b, acquired in smokers: chemicals in smoke inactivate AAT involves the er alveoli) lower lobe disease respiratory unit (respiratory bronchiole, alveolar duct, and identify x-ray of a patient with emphysema look for increased AP diameter and depressed di 1Note: This material is copyrighted, All rights reserved. 4. bronchieetasis— A. cystic fibrosis is the MCC in the United States: TB is the MCC in third world countries pathogenesis: (1) obstruction and infé 2) dilated bronchi extend to the Jung periphery C. clinical: cough up cupfuls of foul smelling sputum 5. bronchial asthma— A. MC chronie respiratory disease in children B. episodic, hyperreactive, reversible, small airway disease that primarily targets the terminal bronchioles C. causes: (1) exposure to allergens a. MCC b. IgE-mediated type I hypersensitivity (2) non-immunologic a, aspirin/NSAID sensitivity b. cold temperature ce exercise d. environmental pollutants e smoke D. clinical (1) episodic wheezing @) nocturnal cough @) _ increased AP diameter due to air trapping ) lab findings: (nll) Catena y) (1) _respiratory’alkalosis~ may progress into respiratory acidosis if bronchospasm is not relieved @) hypoxemia Weer Autre Aerielae @) decreased FEVise, values ft MS alt (4) eosinophilia ad thimalie arlene (5) postive kin tex forall 0 Aeypiralor. deidlosis +» 5 Fp (1) albuterol medinaler for mild disease Tithe. iamediddly 2) corticosteroid mediholer for moderate to severe disease, fo Ruleady Sipe © Lung cancer: . J nee 1. causes— sere) Pbtneacaley x A. see neoplasia ioteeveg B. decreasing incidence in men/increasing incidence in women €. 2nd MC cancer in men and women D. MCC of death due to cancer in men and women 2. MC primary cancers in descending order— A. adenocarcinoma B, squamous carcinoma: ectopically secrete PTH-like peptide (hypercalcemia) C. small cell carcinoma: ectopically secrete ACTH (ectopic Cushings) and ADH (SiADH) MC cancers of lung- metastasis: A. breast MCC B, renal adenocarcinoma‘his material is copyrighted. All rights reserved. ©. choriocarcinoma D. colorectal cancers lung sites ‘A. centrally located: (1) squamous cell Q) small cell B. _ peripherally located: adenocarcinon smoking relationships A. squamous and small cell cancers: strongest relationship B. adenocarcinoma: @) MC primary lung cancer in smokers and non-smokers @) _ bronchioloalveolar carcinoma has no smoking relationship eal cough MC symptom ‘weight loss hemoptysis: sometimes massive Pancoast tumor (superior sulcus tumor): (1) squamous cancer at lung apex involving brachial plexus and superior cervical ganglion (Horner's syndrome) @) Homer's syndrome includes ipsilateral lid lag, miosis, anhydrosis superior vena caval syndrome F. clubbing sites for metastasis outside hilar lymph nodes A. adrenals MCC site B. iver ©. brain ¥ D. _ bone: lytic metastases ~ Mrdeiasis ~ sheeting prognosis A. best for squamous B. worst for small cell: usually non-operable bronchial carcinoid— A. low grade malignant APUD tumor B. clinical (hemoptysis @) local metastasis @) carcinoid syndrome without need to metastasize "USMLE question about s roofer for 25 years and a smoker for 10 years: 1, greatest risk is for primary lung cancer Primary lung cancer is more common than a mesothelioma, whether a smoker or not mesothelioma— A. no smoking relationship B. asbestos relationship in most cases C. highly malignant tumor originating from the pleura D. takes 20-30 yrs to develop ‘Crunching sound is noted in the neck and anterior chest in a patient involved in a head-on {collision (USMLE): ruptured esophagus (Boethaave's syndrome)— 1, Hamman’s sign in the chest due to subeutaneous emphysema from air dissecting into the tissueNote: This material is copyrighted. All rights reserved. other scenarios could be an alcoholic who is retching or a bulimic who is vomiting * Solitary coin lesions: 1. causes— A. MCC is granulomatous disease: e.g., TB, histoplasmosis B. most are benign in patients < C. most are malignant in patients >50 years old D, _ calcifications and lack of growth are benign features 2. bronchial hamartoma— A. solitary coin lesion B. localized overgrowth of cartilage: not a neoplasm C._ “popeom type” of configuration on x-ray Mediastinum: 1, anterior mediastinum MC involved with disease A. thymoma MC tumor followed by nodular sclerosing Hodgkin's disease B. neuroblastoma in children, ganglioneuroma in adults are MC overall mediastinal tumors: located in posterior mediastinum 2. thymus and myasthenia gravis~ ‘A. thymic hyperplasia is MC finding in thymus: germinal follicles composed of B cells that synthesize antibodies against acetylcholine receptors B. thymoma is less common finding: pure RBC aplasia sometimes noted with thymomas thymectomy is sometimes used in Rx of myasthenia gravis 3. middle mediastinum pericardial cyst MC disorder & Pleural 1. lab findings that distinguish a transudate from exudate in pleural fluid— A. PF protein/serum protein ratio >0.5 is exudate B. PF LDH/serum LDH 046 is exudate C. PF LDH two-thirds the upper limit of normal of the serum LDH is exudate 2. PF exudates A. pneumonia MCC B. pulmonary infarction: hemorrhagic exudate C. cancer: hemorrhagic exudate PF transudates— congestive heart failure MCC PF findings in TB- exudate with a lymphocyte dominant cell count 5. PF with amylase- A. acute pancreatitis: left-sided pleural effusion B. _Boerhaave’s syndrome Questions used during the board review: ‘In which of the following clinical scenarios involving patients with lung disease would you expect pulmonary function studies to exhibit decreased compliance, increased elasticity, and an increased FEV ag/FVC ratio? A. 6 year old child with recurrent respiratory infections and steatorthea B. 28 year old non-smoking male with bilateral lower lobe emphysema C. $6 year old smoker with productive cough, dyspnea, and cyanosis D. 10 year old girl with bronchial asthma requiring systemic steroids 39 year old dyspneic African American with bilateral hilar nodes 4Note: This material is copyrighted. All rights reserved. E (sarcoidosis, restrictive lung disease) ‘A 45-year old woman 24 hours post-cholecystectomy develops fever and dyspnea. Physical exam reveals decreased percussion, increased tactile fremitus, and decreased breath sounds i lower lobe. The diaphragm is elevated and there is inspiratory lag on the right side. The patient MOST LIKELY has. atelectasis a lung abscess bronchopneumonia 4 pulmonary infarction 4 spontaneous pneumothorax An afebrile 23-year-old man develops sudden onset of left-sided, stabbing chest pain with dyspnea. Physical exam of the left chest reveals hyperresonance to percussion, deviation of the trachea to the left, elevation of the diaphragm, decreased tactile fremitus, and decreased breath sounds. The MOST LIKELY diagnosis is. pleural effusion bronchopneumonia tension pneumothorax ‘a pulmonary infarction spontaneous pneumothorax A newborn child develops dyspnea, tachypnea, intercostal muscle retractions, and eyanosis 4 hours after birth. The mother developed gestational diabetes mellitus and was in poor glycemic control throughout the pregnancy. A chest x-ray reveals a “ground glass” appearance in both lungs. The primary mechanism for this patient's respiratory problem is. A. aspiration of amniotic fluid group B streptococcus pneumonia decreased production of surfactant Chlamydia trachomatis pneumonia heart failure from congenital heart disease C(RDS) ‘Which of the following describes a pneumonia due to Micoplasma pneumoniae rather than Streptococeus pneumoniae? A. High fever B. Insidious onset C. Productive cough D. Increased tactile fremitus E, _ Neutrophilic leukocytosis B (all other choices are those of typical pneumonia) A 58-year-old smoker presents with weight loss and cough. Physical exam reveals a mild lid lag on the left and a pinpoint pupil, scattered sibilant rhonchi throughout all lung fields that clear with coughing, and an increased anteroposterior diameter. Based on these findings, you suspect the patient has. A. aPancoast tumor a thoracic outlet syndrome the superior vena caval syndrome obstructive lung disease without primary cancer obstructive lung disease with metastatic cancer {tom another primary siteNote: This material is copyrighted. All rights reserved. A (Homer's syndrome also present) A 65 year old man with urinary retention secondary to prostatic perplasia, develops spikin fever, and tachypnea. Physical exam reveals intercostal muscle retractions crackles. A chest x-ray exhibits bilateral interstitial and alveolar infiltrates, ABGs demonstra severe hypoxemia, You expect the blood culture reveals. A. gram positive diplococci B. gram negative diplococci C. gram positive cocci D. _ gram negative rods E. gram positive rods D (Gram negative sepsis due to E. coli [gram negative rod] into an ARDS) Inspiratory stridor is commonly associated with A. arespiratory syncytial virus infection B. a parainfluenza virus infection C.aspirin-induced asthma D. —thinovirus infections E. choanal atresia B (croup or laryngotracheobronchitis due to parainfluenza virus, obstruct sign on lateral x-ray of neck) ion is in the trachea, "steeple Chlamydia trachomatis and the respirtory syneytal virus are BOTH commonly A. an interstitial type of pneumonia B. _laryngotracheobronchitis (croup) C. the respiratory distress syndrome D. typical community-aequired pneumonia E. _hospital-acquired (nosocomial) pneumonia A(RSV MCC of pneumonia and bronchiolitis in children) % Which of the followin aeruginosa Upper lobe cavitation Green-colored sputum Association with cystic fibrosis Association with respirators E. Productive cough A (choices B,C, D are features of P. aeruginosa, both r associated with, is more often associated with Klebsiella pneumoniae than Pseudomonas A B. c D. have productive cough [ehoice E]) {na 30 year old man who lives in Tennessee, you would expect a caleified solitary coin lesion in the lung to represent. A. a foreign body B. an old granuloma C. metastatic cancer D. aprimary lung cancer E, _ abronchial hamartoma B (histoplasmosis) and bilateral inspiratoryNote: This material is copyrighted. All rights reserved. F _A'55-year-old non-smoking coal worker has arthritis and nodular lesions in the lungs. His PPD skin testis negative. You suspect the patient has. A. systemic lupus erythematosus B. Caplan’s syndrome metastatic lung disease D. primary lung cancer miliary tuberculosis, B o In a 62 year old man who has been a roofer for 25 years and a smoker for 10 years, which of the prone to developing? following cancers would he be most likely A. Pleural mesothelioma B. Primary lung cancer C. Laryngeal carcinoma D. Oral cancer E. Pancreatic eancer B (asbestos exposure, same answer even if he wa not a smoker) oFNote: This material is copyrighted. All rights reserved, Gastrointestinal Common infection Organism Disease [Clinical Comments Coxsackievirus A | Herpangina Children between 3-10 yr. Fever, pharyngitis, cervical lymphadenopathy. Multiple vesicles and/or ulcers surrounded by erythema located on soft palate and pharyngeal tissue, Coxsackievirus A | Hand-footmouth Young children. Fever and vesicles located in mouth disease and distal extremities. | | Herpes simplex | Gingivostomatitis | Children gastric ulcer > esophageal varices Congenital pyloric stenosis: 1. vomiting 2-4 wks after birth of non-bile stained flui mass palpated in epigastrium multifactorial inheritance comparison with duodenal atresi A. latter disease has a Down syndrome relationship B. latter disease has vomiting of bile stained fluid at birth: atresia distal to ampulla of Vater C. latter disease lias double bubble sign on x-ray: air in stomach and proximal duodenum D. latter disease has polyhydramnios in mother NSAID uleers/erosions 1. usually superficial erosive gastritis 2; it PGE, which produces mucosal barrier— A. PGE; normally (2) increases blood flow to mucosa 2) _ increases secretion of mucous G) _ increases secretion of bicarbonate into mucous B. misoprostol, a PGE analog, is cytoprotective Chronic atrophic gastritis: 1. type A- A. body and fundus B. associated with autoimmune destruction of parietal cells in pernicious anemia C. —achlorhydria: (1) danger of adenocarcinoma @) problems with digestion @) high gastrin levels 2. type B- A. pylorus/antrum B. associated with H. pylori C. intestinal metaplasia predisposes to adenocarcinoma 3. Menetrier’s disease~ A. giant rugal hyperplasia with increased mucus secretion B. _hypoproteinemia A pylori: 1, gram negative rod 2. urease producer- urea converted to ammonia damages mucosal barrier 3. detected in Bx specimen 101‘Note: This material is copyrighted. All rights reserved, 4. serology excellent but not useful in detecting recurrent disease 5. complications A. gastric adenocareinoma B. type B atrophic gastritis €. low-grade malignant lymphoma A. metronidazole B. bismuth subsalicylate C. tetracycline "Comparison of gastric with duodenal ulcer: Characteristics | Gastric Uleer Duodenal Uleer Percentage of | 25% 75% PUD Epidemiology | Male/Female ratio 1/1 Male/Female ratio 2/1 AD pattern in some Pathogenesis Defective mucosal barrier due to- | Pathogenesis 1. HZ. pylori association 1. H. pylori (275% of cases), 2.|>90%: decrease bicarbonate in mucous mucosal ischemia (reduced PGE,), | barrier, 2. increased acid production. 3, 3. bile reflux. 4, COPD, 8. renal | blood group O relationship, 4. MEN I failure. relationship associated with Zollinger. Blood group A relationship. No | Ellison syndrome component MEN I of If relationship. Smoking delays healing but not a cause of PUD. Location Single ulcer on the lesser curvature | Single uleer on the anterior portion of the of the antrum, Same location for | first part of the duodenum (most common) | cancer. followed by single ulcer on posterior portion (danger of perforation into the pancreas). —_| Malignant Gastric ulcers do not predispose to [ No malignant potential. Not biopsied potential cancer. Cancer can be. ulcerative = and confused with gastvie ulcer. Cannot tell malignaney by the size of an ulcer. Must Bx to R/O cancer. Complications] Bleed and/or perforate (both less | Bleed (MC complication), perforate Gar common than duodenal ulcers). under diaphragm radiates to left shoulder) | astric outlet obstruction, pancreatitis Clinical Burning epigastric pain soon after | Burning epigastric pain 1-3 hours aller eating, Pain increases with food | eating. frequently relieved by antacids or (afraid to eat and lose weight). | food (do not lose weight). Pain wakes patient Relieved by antacids. at night, F ZE syndrome: 1, malignant islet cell tumor seereting gastrin 2. ulcers in usual place but can be multiple or in unusual plac 3. laboratory. ‘A. increased basal and maximal acid output B. increased gastrin C. increase in gastrin with IV secretin test 102Note: This material is copyrighted. All rights reserved, e 4 Re proton blockers can decrease gastrin B. surgery 5. _ other causes of hypergastrinemia. A. Heor proton blockers B. chronic atrophic gastritis of body and fundus C. renal failure D. gastric distention ‘Treatment for recurrent ulcers: vagotomy Heterotopic rests: benign pancreatic tissue in wall of stomach Patient with left supraclavicular nod 1. Virchow"s node~ associated with metastatic stomach cancer or any cancer arising in the abdominal cavity 2. right supraclavicular node drains the lung and upper neck Stomach cancer: 1, decreasing in incidence in United States 2. MC caneer in Japan— related to smoked foods 3. causes— A. H. pylori causally linked B. smoking C.nitrosamines D. adenomatous polyps E. — achlorhydria 4. linitis plastica— A. leather bottle stomach B. does not peristalse when barium is present 5. Krukenberg tumors- hematogenous spread to both ovaries Extranodal lymphoma: 1. stomach MC extranodal site~ Peyer's patches second MC site 2, most are high grade immunoblastic lymphomas 3. -H.pylori associated with low grade lymphomas Leiomyoma: 1, MC benign tumor in GI tract 2. MC location is stomach 3. bleed Malabsorption: 1, pathogenesis of fat malabsorption: ‘A. pancreatic disease: no lipase B, small bowel disease: no absorptive surface . bile salt deficiency: no emulsification and micelle formation (1) liver disease @) bile obstruction @) cholestyramine (4) bacterial overgrowth (8) terminal ileal disease 103Note: This material is copyrighted. All rights reserved. 2. lab Dx— A. stool for fat best screening test B. — D-xylose test evaluates small bowel ability to reabsorb: no increase in blood/urine indicates small bowel disease C. calcifications in pancreas presumptive evidence of chronic pancreatit 3. lab alterations A. hypoalbuminemia B, fat soluble vitamin (A, D, E, K) deficiencies €. combined anemias: iron, folate, Bys D. _ hypocalcemia from vitamin D deficiency: tetany and secondary hyperparathyroidism E, prolonged PT from vitamin K deficiency ____4.__ malabsorption disorders _ — Disease | Epidemiology/Pathogenesis_[ Gross and Micro | Clinical Diagnosis Celiac | Begins in infancy with expo- | Atrophy of villi in | Failure to thrive with abdominal disease sure to wheat gluten, Anti-| the duodenum | distention and diarthea in child- bodies develop against (ron deficiency) | ren. Adults have weight loss, din extract in gluten (best | and jejunum (fol- | diarthea, malnutrition. Risk of sereening test) immune | ate deficiency). | small bowel T cell Iymphoma. destruction of mucosal cells, Splenic atrophy. Gluten free diet Associations- HLA B8, -Dr3 gold standard Rx. Lab: abnormal and -DQ2 and dermatitis Deylose, anti-gliadin antibodies herpetiformis (vesicular skin (best test), anti-endomysial ant- disease), bodies. Whipple's | Systemic disease of middie | Blunting of vill in | Present with fever, diarhea, joint disease aged males, Infection by | the jejunum and | pains, emaciation, peculiar Trophermyma —whippleii.| ileum. Heavy inf- | brown skin pigmentation, ge Cannot culture. Only seen | iltrate of foamy | eralized lymphadenopathy. Lab: with electron microscope. In| macrophages in | abnormal D-xylose, RX with AIDS, MAI produces a| lamina propria | TMP/SMX Whipples-like syndrome: (contain the org. anisms) which blocks lymphatic | wos uptake of fat. | _ Diarrhea: 1. cause A. invasive (1) eg, Shigellosis @2) low volume diarrhea 8) _ positive stool for fecal leukocytes B. secretory: @) cAMP stimulation by toxins @) eg, cholera a, glucose added to orally administered hypotonic salt solutions in order to ensure sodium reabsorption b. no mucosal inflammation (3) _ traveler's diarrhea due to enterotoxigenic E: coli (4) high volume diarrhea with osmolality similar to that of plasma (5) _ negative stool for fecal leukocytes 104Note: This material is copyrighted. All rights reserved. C. osmotic: (Q) lactase deficiency: alias brush border enzyme deficiency, alias disaccharidase deficiency a. colon anaerobes degrade lactose to fatty acids (acid pH stool) and H, gas b. breath test for Hs best screen @) certain laxatives (3) high volume diarrhea with osmolality lower than that of plasma (4) negative sioo! for fecal leukocytes Microbial Pathogens Associated with Diarrhea Pathogen | Specific Pathogen Comments Virus Rotavirus (Reovirus) | MCC of childhood diarrhea. Winter months, Pecal-oral route. Infects small intestine mucosa and damages brush border enzymes and transport systems producing a watery, nonbloody diarthea. Rotazyme test on stool establishes Dx. | Norwalk (Picornavirus) | Common cause of both adult and childhood gastroenteritis vomiting/diarthea). Fecal-oral transmission. Cytomegalovines Common cause of diarrhea and biliary tract disease in| AIDS. Bacteria [Food poisoning from |S. aureus type (gram 7 coccus) occurs In 16 bs Gale preformed toxin limited). Culture food. B. cereus (gram positive rods noted in Staphylococcus aureus, | stool) associated with fried rice/tacos (self-limited). Adult C: Bacillus cereus, Clostri- | botulinum (gram positive rod) has heat labile exotoxin dium botulinum (adult) | (neurotoxin). Organisms proliferate in canned/preserved food. Toxin attaches to synaptic vesicles of cholinergic nerves, blocks the release of acetylcholine, and causes paralysis. Food poisoning after | Clostridia: gram positive rod. C. botulinum In infants trom colonization in bowel | eating spores in honey. Colonization first in bowel and then C. perfringens, C. botul- | toxin production. Salmonella: gram negative rod and MCC inum (infant), Salmon- | of food poisoning in United States. C. perfringens accounts ; ella enteritidis for 20% of cases of food poisoning. Clostridium difficile | Gram positive rod associated with pseudomembranous colitis. Administration of antibiotics (ampicillin #1, Cleocin) results in the overgrowth of toxin producing C. difficile in the colon. Fever and watery diarrhea, Enterotoxin-induced pseudomembrane covering the colon (creamy to greenish flat Plaques). Pseudomembranes also noted in shigellosis, enterohemorthagic E. coli, ischemic bowel disease. Toxin assay of stool best test. Rx: metronidazole (Flagyl) } Shigella species Gram negative rods. S. sonnei is the MCC of shigellosis followed by S. flexneri. S. dysenteriae produces severe disease, Oral-fecal route transmission. Produce endotoxin, No animal reservoir. No chronic carrier state. Targets the ileum and colon. Mucosal ulceration and pseudomembranous inflammation. Diarthea contains blood/mucus. Positive fecal smear for leukocytes. Association with HUS syndrome and HLA B27 positive ankylosing spondylitis, Usually produces a self-limited diarrhea. Rx: ciprofloxacin 105Note: This material is copyrighted. All rights reserved, | Gram negative rods. Py thogenie Salmonella species include Sieh, choleraesuis, “and phimurium (MCC at fmerocolits, self-limited). Animal reservoirs (poultsy furles, lizards). Oral-fecal transmission. ‘Typhoid. ferec {Gateic fever) caused by S. typhi chuman reservoir), Fie nade” invades Peyer's patches (longitudinal ulcers) ana | produces @ septicemia (best culture medium f solation), | Second week diarrhea (positive stool culture) and classic we neta aeveatdis, absolute neutropenia, hepan splenomegaly. Complications: osteomyelitis (sickle dines, Hundiee, renal filure, chronic carrier state (persistence of | peiettanism | year post infection, MC in gallbladdes Fositive fecal smear (mononuclear cells). Ceftriaxone is Rh of choice for typhoid and ampicillin for the chronie ears | Salmonella species State. Cholecystectomy may be necessary Mycobacterium Organisms swallowed ftom a primary focus Ihe Tung, tuberculosis Invade Peyer's patches in terminal ileum. Infections spreads sittin citcumferentially oriented lymphatics leading. te Stricture formation/obstruction. M. bovis MCC in third worla countries (unpasteurized milk) | Campylobacter jejuni | Gram (2) flageliated. curved Vibrio-like rod. MC invasive bacterial enterocolitis in United States. Contracted ne Fai Contaminated food (poultry) or drinking contaminated abscesses/ulcers resembling ulcerative colite, [rood/imucus present in stool. Positive fecal leukocyte sas Usually self-limited. Rx: erythromycin or ciprofionsnn | severe cases Escherichia col Gram negative rod. Produces toxin induced and vase diarrheas, Futeropathogenic strain: non-toxin type of mild diarrhea in infants and young children, Mucosa not inflamed. [aterotoxigenic strains: some strains produce heat labile (71) toxin stimulating cyclic AMP (secretory dianhes fimilar to cholera, normal mucosa). Other strains prodvce g heat stable (ST) toxin stimulates guanylate cyclase Producing TAT diarthea (MCC of traveler's diarrhea}, Rx wre TMP/SMX. | veeeaitvasive strain: invade large intestine producing mucosal necrosis/inflammation, falerohemorrhagic strain: O157:817 seroype in raw famburgers. May’ produce hemolytic uremic syndrome sot hemorrhagic or pseudomembranous colitis,Note: This material is copyrighted. All rights reserved. | Vibrio cholerae Curve ‘gram negative rods. Enterotoxin stimulates adenylate cyclase in small bowel. Severe secretory diarrhea ("rice | water stools”). Drinking contaminated water/eating contaminated seafood, especially crustacea (Gulf coast), Volume depletion, normal gap metabolic acidosis (lose bicarbonate), hypokalemia, Rx is fluid replacement. Glucose enhances if let | sodium uptake in oral supplements. Mortality ~ 40% | untreated Parasitic | Entameba histolytica | See table in the Hepatobiliary section - Cryptosporidium Contracted by ingesting oocysts (acid fast positive). Brush parvum (sporozoan) —_| border of intestinal epithelium. Diarrhea/abdominal pain 44 Biliary tract disease in AIDS. MC protozoal pathogen in AIDS diarrhea along with microsporidia species, Contaminates city water supplies producing a self-limited diarrhea in immune competent hosts (outbreak in Milwaukee, Wisconsin). Detected with the string test. Rx: paromomycin | is Rx in HIV positive patients Microsporidia species | Primarily occur in HIV positive patients, Diarrhea and wasting syndrome. Rx with albendazole. _ Giardia lamblia MC protozoal cause of diarrhea in United Stales. Contracted by ingesting cysts (mountain springs, etc.). Attach to small intestine mucosa (may involve biliary tract). Produces acute | and chronic diarrhea with malabsorption, Rx: metronidazole Amebiasis: 1. flask shaped ulcers in the cecum 2. afebrile, bloody diarrhea 3. trophozoites phagocytose RBCs ‘Traveler to Mexico who 1 week later develops a watery diarrhea with mucus and blood and colicky bowel movements: amebiasis Abdominal abscess: 1. MC Bacteroides fragilis A.B. fragilis below the diaphragm B, _B. melanogenicus above the diaphragm) 2. MC due to a perforated appendicitis nt diarrhea~?what organisms can be identified with the string test (Entero-Test): ‘Farmer and his wife are brought to the ER by their son because they are too weak to walk or drive and their vision is blurry and exam reveals ptosis, facial weakness, nonreactive dilated pupils, dry mucous membranes, and normal DTRs~? diagnosis: 1. C, botulinum food poisoning 2. Rx with botulism antitoxin 3. danger of respiratory paralysis Fecal smear for leukocytes: best screen for invasive diarrheas Bowel obstruction: 1. causes—Note: This material is copyrighted. All rights reserved. A. adhesions from previous surgery MCC: if no history of previous surgery, pick indirect inguinal hernia B. duodenal atresia: (1) association with Down syndrome @) vomiting of bile stained fluid after birth @) double bubble sign- air in stomach and proximal duodenum (4) polyhydramnios in mother C.— Hirschsprung: (2) absent ganglion cells in rectum Q) empty rectal vault on rectal exam 3) common in Down's syndrome (4) _ bowel proximal to defect is dilated and does have peristalsis and ganglion cells D. _ indirect inguinal hernia: 2nd MCC of bowel obstruction (MC type (2) superficial epigastric artery medial to finger in canal (artery is lateral border of triangle of Hesselbach) (3) USMLE: gross of infarcted bowel in weight tit a. incarcerated small bowel in an indirect inguinal hernia sac b. see picture on page 310 of review text ct inguinal herni (1) through posterior wall of triangle @) _ artery lateral to finger F. umbilical hernia: @) common in children @) common in pregnancy and ascites intussusception: (1) terminal ileum intussuscepts into cecum @) child with colicky abdominal pain and bloody dit H. volvulus: (1) MC due to sigmoid colon twisting around mesentery @)__ obstruction and infafction 1. gallstone ileu (1) elderly woman with chronic gallbladder disease @) fistula between gallbladder and small bowel (3) stone passes into small bowel and obstructs at ileocecal valve (4) _airin biliary tree meconium ileus: impacted meconium in eystic fibrosis in newborns KK, USMLE: X-ray with local dilated bowel (2) ileus (lack of peristalsis) of a small portion of bowel is called a sentine! loop @) due to bowel close to an area of inflammation (3) _ acute pancreatitis sentinel loop near duodenun (4) _retrocecal appendicitis sentinel loop of cecum 2. clinical A. colicky pain B, distended abdomen with no rebound tenderness C. constipation D. _ obstipation: no gas sav Aap E.%€ dilated small bowel with air/fluid levels in step-ladder appearance (04) \f rhea or transverse colon paid thew pain —Pe2 inet pay «pain “Ace inter / 108Note: This material is copyrighted. All rights reserved. + Sigmoid colon most common site for: 1, cancer in GI tract 2. diverticular disease polyps exception: polyps of Peutz-Ieghers syndrome, which are MC in the small bowel loss of bright red blood per rectum 2. diverticulgsis MCC followed by angiodysplasia / Vessel disorders: 1. small bowel infaretion~ / ‘A. thrombosis/embolism of the superior mesenteric artery with a transmural small bowel infarction (1) embolism is most often associated with heart disease and atrial fibrillation | 2) _ thrombosis most often associated with atherosclerotic plaque at orifice B. clinical: (1) sudden onset of diffuse abdominal pain, bowel distention, and bloody diarrhea in elderly patient 2) no rebound tenderness unless peritonitis is presi (3) absent bowel sounds (ileus) (4) "thumbprint sign” noted on barium enema: due to edema in bowel wall (5) amylase of bowel origin is often increased (6) bowel distention, air/fluid levels (7) profound neutrophilic leukocytosis ischemic col ‘A. severe pain in splenic flexure after eating B. overlap area between superior and inferior mesenteric arteries C. patient losses weight for fear of eating D. _ bloody diarrhea from localized infarction \ E repair with fibrosis leads to ischemic strictures angiodyspla: ‘A. dilated vascular'channels in submucosa of cecum (1) increased wall stress related to increased diameter of cecum increases tension on blood vessels causing dilatation @) second MCC of hematochezia 3) MC in elderly patients associated with: (1) von Willebrand's disease @) aortic stenosis F Diverticular disease: 1, small bowel divertieula— A. uncommon B, site for bacterial overgrowth (1) Biz deficiency | @) bile salt deficiency and malabsorption 2. Meekel’s diverticulum: A. vitelline duct remnant: 2 feet from ileocecal valve B. truediverticulum CC. MCC of iron deficieney in a newborn and young child (GI bleed) teliths ix hpetdle) Approdvote f ! 109Note: This material is copyrighted. Alt rights reserved, 3. sigmoid diverticula Ar diverticula are juxtaposed to a blood vessel, which isthe area of weakness: explains why diverticula are the MCC of hematochezia B. diverticulitis MC complication (2) _inbletedfeclith serves as nidus for nfecion/inflammation 2) clinically described as.a "eft sided" appendie @) __ danger of perforation and peritonitis C. _ diverticula are MCC of fistulas in GI wact: colovesical fistula MC fistula Comparison of ulcerative Colts (UC) and Crohn’ | Characteristic | Wleerative Colitis Disease | Extent of | Mucosal and submucosal | Transmural ~ disease | Location Primarily targets the rectum. May | Temminal “eum -aloow (G0%), ileumieoion SMtend up into left colon in eont- | (50%), colon alone (20%6). Anal involvement jnuous fashion (no skip lesions) or | 7596--fssures fistulas, abscesses. Involves imvalve entre colon. Does not | other areas of Gl wn (mouth to anus). | involve other areas of GI tract, Gross features “Inflammatory polyps pseadov Fat creeps around the serosa, Thick bowel wall polyps representing areas of | and narrow lumen. Skip areas (important fea- inflamed residual mucosa, Friable, | ture). Strictures fistulas (Very diagnostic) in re jucosa bleeds easily wen | areas other than ann Deep linear ulcers, cob- touched. Uleeration/hemorhage, blestone pattern, aphthoid ulcers (small mceea] {Colon shortened and mucosa fat | ulcers, origin of in uleers, early sign), in quiescent chronic disease. No _ | skip areas. Microscopic | Active disease: mucosal Infamuma ‘ets diagnostic features: noneasealing rami features hie) SPE abscesses (neutrop- | omas (60%), ‘transmural inflammation with hls), Dysplasiavcancer may be | subserossl lymphocytic infiltration, Present. Chronic disease: neutro- Phils replaced by lymphocytes! Plasma cells. Dysplasia/cancer may be present. | Complications | More common than CD: 1 toxle ‘More common than UC" 1. fistula Formation a megacolon- hypotoniv/distended obstruction, 3. disease in other areas of Gl init 7. cletosing. pericholan- | 4, calcium oxalate renal seria sits, 3. HLA B27 + ankylosing | Spondylitisiuveitis, 4. pyoderma gangrenosum, 5. adenocarcinoma %, greatest risks are pancolitis, early onset of UC, and duration of disease >10 years Left sided abdominal cramping | Right Tower Quadrant colicky pain (obstruction Gio" obstruction), diarrhea with | in area of tennant ileum) with diarrhea Plood/mucus, | rectal bleeding, | Bleeding iteolen involvement. fenesmus (painful straining at stool) Radiograph [Lead pipe appearance Ta Ghronle “String” sign inthe terminal Heum fom lnmnal Lies | diseas —————_Lnarrowing by inflammation, Fistulas. on! noNote: This material is copyrighted. All rights reserved. * Young woman with intermittent bouts of diarrhea and constipation associated with cramping right and left lower quadrant pai 1. irritable bowel syndrome intrinsic motility defect in bowel 2. flexible sigmoidoscopy is negative Melanosis coli: black colored colon due to laxative abuse 7 Polyps: 1. sigmoid colon MC site 2. hyperplastic polyps MC type— hamartomas 3. juvenile polyps— A. MC polyp in children B. only located in rectum @ 4. PJ polyps A. MC in small intestine B. hamartomas: very little risk for adenocarcinoma C. mucosal pigmentation 5. adenomatous polyps— A. precursors for cancer: (1) _ villous adenoma worst type: sessile polyp @) tubular adenoma MC type (looks like a strawberry on a stick) B. risk for cancer greatest: (1) polyp >2 om 2) _ has increased villous component vr Polyposis syndromes: 1, familial polyposis MC type~ A. AD disease involving (1) inactivation of APC suppressor gene on chromosome 5 (2) activation of ras oncogene (3) inactivation of p53 suppressor gene B. 100% penetrance: (1) all will develop cancer by age 40 (2) _ screen with flexible sigmoidoscopy in those affected beginning age 10-12 every L-2ys (3) genetic testing to confirm and to test first degree family members (4) congenital hypertrophy of retinal pigment is MC extraintestinal manifestation Gardner's syndrome~ A. variant of familial polyposis B. AD inheritance CC. benign osteomas in jaw D. — desmoid tumors in abdominal sheath 3. Tureot’s syndrome- only AR polyposis brain tumors tumor/syndrome: 1, tip of appendix MC overall site APUD tumor with neurosecretory granules B, $100 antigen positive ulNote: This material is copyrighted. All rights reserved, C. yellow color 2. all carcinoid tumors are malignant— \ A. size determines metastatic potential (22 Cm B. _appendiceal carcinoids rarely metastasize 3. * terminal ileum MC site for tumor that metastasi to liver to produce the carcinoid syndrome A. serotonin is fibrogenic and may cause bowel obstruction B. portal vein drains serotonin to liver where itis metabolized and excreted in urine as $< HIAA 4. carcinoid syndrome- A. metastasis tothe liver from a primary in the small intestine ( metastatic nodules. drain serotonin into hepatic vein tributaries: access to systemic circulation (2) flushing and diarrhea MC symptoms: due to serotonin 3) cardiac valvular lesions 8. tricuspid regurgitation. b. _ pulmonic stenosis B. measure S-HIAA (metabolite of serotonin) in urine: tryptophan often depleted from increased synthesis of serotonin C: bronchial carcinoids do not have to metastasize to produce carcinoid syndrome Colon cancer: 1, risk factors~ A. age B, tubular adenoma>2 em C. familial polyposis (100% penetrance) D. villous adenoma (villus component inereases the cancer risk) E, _ low fiber diet: increased exposure of mucosa to lithocholic acid F. smoking G. Lynch syndrome (family cancer syndrome) () AD disease @) type I limited to coton (3) type Il is family cancer syndrome a. colon cancer b. _breast/endometrial/cervical cancers © gastric cancer 2. screening- A; stool guaiac yearly after $0 years old with flexible sigmoidoscopy every 3-5 years aspirin has a protective effect B. second MC cancer and cancer killer in men and women 3. sites A. rectosigmoid 60% B. _cecum/ascending colon 25% j 4. clinical A. _ left side obstructs: change in bowel habits: annular configuration B. right side bleeds: (1) polypoid (2) found later than left sided typeNote: This material is copyrighted. All rights reserved. -Collin staging system for colorectal cancer Characteristics Prognosis Tumor limited to the mucosa. Negative Iymph 100% 5 year survival. nodes, | Tumor involves the submucosa and invades into | ~ 60% 5 year survivals but not through the muscularis propria, No lymph node involvement. Tumor penetrates through the muscularis propria | 55% 5 year survival. and extends into the serosa, No lymph node involvement Same as BI and B2, respectively, except lymph Cl; 30% 5 year survival. C2: 20% nodes are involved. | 5 year survival. Tumor with any level oF invasion with or without | <3% § year survival lymph node involvement but distant metastasis is | present 6. CEA- used to follow-up for potential recurrences Acute appendicitis 1 2, MC due to an obstructing fecalith in adults 3. clinical pain migrates from umbilicus to RLQ fever rebound tenderness at MeBumey's point Rovsing's sign: pain in RLQ when palpating LLQ psoas sign: pain when extending right thigh perforation MC complication Abdominal Pain 1. order for evaluating abdomen— A. inspection B. auscultation C. percussion D. palpation. causes of pain- A. hollow viscera: (1) distention of the viseus with fluid or air 2) forceful muscle contractions @) inflammation (ischemia solid viscera (1) stretching of capsule 2) inflammation of capsule visceral peritoneum and greater omentum are not sensitive to pain mesentery, parietal peritoneum and peritoneum covering posterior abdomen are sensitive to pain types of pain— A. visceral B. parietalNote: This terial is copyrighted. All rights reserved C. referred visceral pain— A. mediated by small unmyelinated afferent C fibers _ (1) poorly local the midline of the abdomen (2) pain usually dull, slow in onset, and of long duration (3) mid-epigastric visceral pain a. duodenum b. hepatobiliary system © pancreas (4) _periumbilical (mid-abdominal) pain: a. jejunum/ileum b. ‘cecum/appendix (S)_ mid-lower abdomen: a. colon b. intemal reproductive organs parietal pain A. mediated by both Cand myelinated A 8 nerve fibers B. _pain more acute, sharp, and better localized C. “causes of parietal pain involve irritation of parietal peritoneal surface by (pus @) bile @) urine (4) cyst fluid (5) Glsecretions example of appendicitis (pain begins in the periumbilical area when appendix becomes inflamed 2) shifts to RLQ (MeBumey’s point) when parietal peritoneum becomes inflamed referred pain— A. pain at a distant site owing to shared central pathways for afferent neurons from different sites B. right scapular pain in deute cholecystitis owing to afferents from the gallbladder centering the spinal cord from T6-T9 C. left shoulder pain with perforated duodenal ulcer and air under disphragm irritat pain onset- ‘A. explosive within seconds: e.g., perforated ulcer B. rapidly progressive within 1-2 hours: e.g, strangulated bowel C. gradual over several hours: e.g,, acute cholecystitis character of pain— A. colicky pain: (1) pain interspersed with pain free intervals of minutes to hours @) sign of obstruction in a viscus that has peristalsis a. small bowel obstruction b. terminal ileal disease in Crohn’s disease B. steady pain (2) dull and aching @) eg, ulcer pain C. stabbing pain (bowel infarction C4Note: This material is copyrighted. All rights reserved. @) acute pancreatitis 9. obstipation— A. absence of passage of both stool and flatus B. characteristic of mechanical bowel obstruction 10. rebound tenderness peritoneal i 11. increased bowel sounds (hyperp A. diaries B. carly obstruction 12. absent bowel sounds (ileus) A. intestinal obstruction due to inhibition of bowel motility (1) adynamic or paralytic ileus @) peritonitis B. mechanical obstruction (dynamic ileus): adhesions ‘Questions used during the board review: tems 1-3 Yersinia enterocolitica Staphylococcus aureus Enterotoxigenic E. coli A. Vibrio cholera B. Bacillus cereus C.Shigelta sonnei D. Salmonella typhi E, Campylobacter jejuni r G H ‘An afebrile 22 year old man and several other members of his family developed seve: without diarrhea ~1~6 hours after eating potato salad at a picnic. They all recovered 12-24 hours later. Answer: G TK vomiting ieventfully 23 year old man developed explosive, watery diarrhea with blood, leukocytes, and mucus ~3 days after eating chicken that was improperly cooked. Comma-shaped organisms are noted in the fecal smear of stool along with RBCs and leukocytes. Answer: E ‘FA febrile 10 year old child presents with severe right lower quadrant pain that is interpreted by the attending physician as acute appendicitis. At laparotomy, the surgeon notes that the appendix is normal. However, the mesenteric lymph nodes are markedly enlarged and have focal areas of microabscess formation on cut section. Answer: F + A 29 year old man develops watery diarrhea and volume depletion shortly after visiting the Gulf Coast states Answer: A. ‘* On atrip to India, a man develops a high fever associated with bradycardia, absolute neutropenia, and splenomegaly. A blood culture is positive for a gram negative organism, Answer: DNote: This material is copyrighted. AN rights reserved. Items 6-7 A. Yersinia enterocolitica B. Staphylococcus aureus C. Enterotoxigenie . coli D. Cryptosporidium parvum E, Mycobacterium avium-intracellulare @ A 28 year old man with AIDS presents with chronic, recurrent, profuse, nonbloody, watery diarrhea, An Entero-Test (string test) reveals oocysts that are partially acid-fast positive. Answer: D o A 25 year old medical student during Spring break in Tijuana, Mexico develops fever, vomiting, abdominal cramps, and watery diarrhea ~14 hours after eating a few tacos purchased from a street vendor, He recovers uneventfully in 48-72 hours, Answer: C Odynophagia in a HIV-positive 28 year old man with white plaque-like material on his tongue and buccal mucosa MOST LIKELY has an AIDS-defining lesion caused by A. Epstein-Barr virus B. Candida albicans C. — Kaposi’s sarcoma D. cytomegalovirus E. Herpes simplex B © An afebrile jear-old medical student presents with intermittent complaints of left and right lower quadrant abdominal pain and distention associated with altemating periods of mucoid diarrhea and constipation. He states that stooling relieves the pain. A flexible sigmoidoscopy and stool guaiac exam are both normal. The patient MOST LIKELY has... A. an intrinsic bowel motility disorder B. inflammatory bowel disease C. chronic appendicitis D. _ melanosis coli E. celiac disease A (irritable bowel syndrome) © Which of the following correctly describes a gastric rather than a duodenal ulcer? ‘A. Association with Helicobacter pylori B. Highest incidence of perforation C. Small risk for adenocarcinoma D. Pain awakens the patient at night E. Association with Zollinger-Ellison syndrome c ‘The MOST COMMON location for diverticula, polyps, and cancer in the gastrointestinal tract is the. ‘A. ascending colon B. sigmoid colon C. esophagus D. stomach BE. rectum B 16Note: This material is copyrighted, All rights reserved. C (lactas r Which of the following characterizes ulcerative colitis rather than Crohn's disease? Discontinuous spread Toxic megacolon Fistula formation Perianal disease Obstruction moop> A 38-year-old Asian woman has a long history of explosive diarrhea and abdominal distention aft ‘eating dairy products. The pathogenesis of this patient's diarthea is MOST CLOSELY related to. A. antigliadin antibodies B. activation of cyclic AMP C. intraluminal osmotically active solutes D. mucosal injury with increased permeability E. loss of the absorptive surface of the small bowel cy) ‘A 62-year old man smoker presents with weight loss, a dragging sensation in his right upper quadrant, and crampy left lower quadrant abdominal pain, He has alternating bouts of constipation and diarrhea. In addition, he states that blood coats and is mixed in with his stools. He sometimes has pain with defecation. There is mild hepatomegaly. ‘The rectal exam reveals non-thrombosed external hemorrhoids and a sentinel tag in the posterior midline. The stool is guaiac positive. A complete blood cell count (CBC) reveals a mild microcytic anemia. The MOST LIKELY cause for this patients condition is. A. angiodyspl B. ananal fissure C. diverticulitis D. hemorrhoids E, _ colon cancer E (also evidence of liver metastasis)Not is material is copyrighted, All rights reserved. Hepatobiliary/Pancreas © Liver function tests (LFTs L 4 Liver function tests (LFTs): cholestas 1 Wer necrosis indicators A. alanine transaminase: ALT B, Aspartate transaminase: AST C. Lactate dehydrogenase: LDH AST (formerly SGOT)- primarily a mitochondrial enzyme ALT (formerly SGPT) A. located in the cytosol B, _ more specific for liver disease than AST transaminases increased in hepatocyte injury/ne 2 A. alcoholic liver disease: <— «/ AS Rae, pcr (1) AST> ALT, since alcohol sa mitochondrial poison @) enzyme levels rarely >200-300 U/L B. _ viral hepatitis: (1) ALT> AST (2) ALT last enzyme to return to normal, 3) levels>1000 UAL in acute hepatitis LDH A. increased in cell necrosis B. non-specific marker of primary or metastatic tumor in the liver indicators enzymes— A. alkaline phosphatase (AP) B, _y-glutamyl transferase: GGT C. _S*-Nucleotidase cholestasis refers to intrahepatic or extrahepatic obstruction of bile flow- ‘A. APand GGT increase secondary to synthesis (not cell damage) B, GGT synthesis increases when drugs enhance the cytochrome P4S0 system (1) alcohol ri (2) phenobarbital rifampin Penyein C._APis present in (liver Q) bone @)_ placenta D. GGT primarily located in the liver in smooth endoplasmic reticulum obstructive jaundice A. APand GGT are markedly increased (1?) B. transaminases mildly increased (1) er disease— B. GGT disproportionately increased (111) du to induced synthesis by alcohol focal benign liver disease (granulomas) A. bilirubin, LDH, transaminases normal B. AP and GGT slightly increased (7) 18Note: This material is copyrighted. All rights reserved. 6. focal metastatic liver disease~ as above except LDH also increased (*) AP of liver versus bone or other tissue origin A. — both AP and GGT increased if AP is of liver origin B. only AP increased ifit isnot liver in origin Liver function tests (LFTs): excretory indicators, see schematic 1. total bilirubin (TB) with fractionation into conjugated (CB) and unconjugated : bilirubin (UCB), A. CB/TBx 100 =CB fractionation B. see schematic of bilirubin metabolism 2. CB<20%— primary increase in UCB (1) _ extravascular hemolysis 2) _ problem with uptake or conjugation B. CB 20-50%: mixed CB and UCB: hepatitis C. CB>50%: primarily CB: obstructive jaundice \ 3. urine bilirubin and urobilinogen relationship~ Urine bilirubin Urine urobilinogen Interpretation i Normal: absent trace CB 20%: absent tt extravascular hemoly CB 20-50%: tt 1 viral hepatitis CB >50%: tt absent obstructive jaundice Liver function tests (LFTs): index of severity of liver disease 1. severity index indicators~ A. serum albumin B, prothrombin time (PT): best indicator hypoalbuminemia and prolonged PT- | ‘A. indicate severe functional impairment of the liver B. _inccirthosis, the prolonged PT does not correct with intramuscular vitamin K transaminases decrease and PT is further prolonged~ indicates fulminant hepatic necrosis Liver function tests (LFTs): immune indices 1. serum protein electrophoresis in chronic liver disease A. polyclonal gammopathy due to an increase in IgG B, alcoholic cirrhosis has an increase in IgG and IgA producing a [-y bridge } C. in primary biliary cirrhosis (PBC) IgM is elevated. autoantibodies— ‘A. increase in anti-mitochondrial antibody in PBC B. increase in anti-smooth muscle antibody in autoimmune hepatitis Liver function tests (LFTs): tumor markers 1. alpha fetoprotein (AFP) A. hepatoblastoma in children B. hepatocellular carcinoma in adults 2. +1 antitrypsin (AAT)~ hepatocellular carcinoma * Anatomy: i 1. triads contain portal vein, hepatic artery, bile ducts— ] 2. hepatic artery and portal vein dump blood into sinusoids which drain into the hepatic vein back to the right heart neMacrophage Destruction RBC —eglobin split off —p amino acid poo! — Heme (protoporphyrin + iron) heme oxygenase Protoporphyria + iron Biliverdin + carbon monoxide (CO) } tiverta nose Peripheral Blood Unbound bilirubin (lipid soluble) rubin + albumin (unconjugated bilirubin; UCB) UCB then binds to ligandins vce } UDP elucuronyl transferases (conjugating enzymes) Conjugated bilirubin (CB, no acess to blood from bere on ia) Bile canalicular transport system (rate limiting step) CB in common bile duct Liver | uptake of UCB by carrier proteins Stored/concentrated in gallbladder (cholecystokin) Bowel CB in terminal ileum + colon bacterial reduction by B-glucuronidase Y (also present in breast milk) UCB t further reduction by bacteria Urobilinogen (colorless) oxidized to urobilin (color of stoa) Liver (90%) Urine (10%, urobilin gives color to urine) CB= conjugated bilirubin UCB = unconjugated bilirubin Normal Bilirubin Metabolismer ° Note: This material is copyrighted. All rights reserved. 3. zone around the central vein is most susceptible to hypoxia and alcohol damage 7 Summary of acquired/genetic causes of jaundice: 1. unconjugated (UCB) hyperbilirubinemia A. increased production: (1) _ hereditary hemolytic anemias with extravascular hemolytic anemias a. congenital spherocytosis b. sickle cell disease (2) acquired hemolytic anemias a. ABO hemolytic disease of newborn b. Rh hemolytic disease of newborn ©. _ autoimmune hemolytic anemia (3) _ ineffective erythropoiesis (RBC destruction in the bone marrow) a. severe B-thalassemia b, pernicious anemia/folate deficiency impaired uptake by hepatocytes: acute/chronic liver disease impaired conjugation by hepatocytes (1) Gilberts disease a. autosomal dominant b. second MCC of jaundice (hepatitis MCC) ¢. “increased production (mild hemolysis in 50%), decreased uptake, decreased conjugation d, jaundice exacerbated by fasting e. _ liver histologically normal f. fast the patient and note a doubling of bilirubin over the baseline g _noRx C CB <20%— oF (2) Crigler Najjar syndrome: genetic disease type I has total absence of UDPG transferase activity: incompatible with ! life b. type Il has reduced UDPG transferase activity (activity increased with phenobarbital) c. liver histologically normal Dx with enzyme assay (3) _ physiologic jaundice of newborn a. peaks on third day b. immature uptake and conjugation (4) breast milk jaundice a, occurs 3 days—3 wks b. fatty acids and hormones in breast milk inhibit conjugation ¢. increased bilirubin reductase in breast milk causes more UCB to be | reabsorbed in the bowel } 2, mixed type of jaundice with CB 20-50% ‘A. viral hepatitis: early phase of obstruction with light colored stools B. alcoholic hepatitis } 3. obstructive type of jaundice with CB >S0%— H A. Dubin-Johnson syndrome: (AR | (2) _ impaired canalicular transport system for CB ; (3) _ black pigment in hepatocytes 120Note: This material is copyrighted. All rights reserved. (4) _non-visualization of gallbladder with oral cholecystogram dye (3) abnormal clearance studies (6) benign disease B. Rotor'ss (@ aR @) pathogenesis same as Dubin-lohnson @) normal liver (4) normal visualization of gallbladder () abnormal clearance studies intrahepatic cholestasis (1) rug induced: see table @) primary biliary cirrhosis @)__ intrahepatic biliary atresia in children D. extrahepatic cholesta (1) extrahepatic biliary atresia in children @) _ stone in common bile duct: MCC in adults G) carcinoma of head of pancreas (4) _ primary sclerosing pericholangitis: associated with ulcerative colitis ‘@ Viral hepatitis: see schematics and tables HAV BY HCV DV HEV Type of virus [RNA® picorna- | DNA? hepadna~ | RNA: flavi- | Incomplete RNA | RNA? cals virus virus virus virus (requires | virus HBsAg). Prevalence [40% [35% 20% 5% <1% | [Transmission | Fecal-oral, Parenteral, close | Same as HBV. | Same as HBV. |Sameas HAV] food, water, | contact with an Coinfection (same anal intercour- | infected patient. needle has both se. 10% of infe- | Present in blood, viruses), Superine ctions in day | semen, saliva. fection (exposed care centers to HDV at later date) Tneubation [2-6 wks 2-6 mths 5-7 wks ‘Same as HBV [2-9 wks Clinical Traveler's hepa- | Serum sickness | MCC of post | Cytolytic to hepa- | Poor prog: associations | ttis (80%), drug | picture (5-10%): | transfusion he- | tocytes (rapid det- | nosis in pre- addicts (20%), | polyarthritis, urt- pattis (1/3300 | erioration with | gnant women homosexuals | icaria, nephritis, | chance). Com- | superinfections). | (20% mortal- (35%), inmates | vasculitis (PAN). | mon in alcoh- | Drug addicts and_| ity). in jail Virus is not cyto- | olic liver dise- | homosexuals. Iytic but CDs cy- | ase (25.60%), | totoxic T cells Kill hepatocytes Chronic earr- | None Yes: 10% in Yes: 40-60% | Yes: 10-40% ‘None ier state/chr- adults, 90% in | onic hepatitis newborns left untreated Massive necr- | Rare MCC of fiulmi- | Rare | Common ‘Common in sis nant hepatic nec- pregnant wo- tosis men.Say snfecTae pic hes Gy La foctin A Serviegic gap +> Jaundice Months atter exposureNote: This material is copyrighted, All rights reserved. is confirmatory HAV HBV [Hcv [DV ___ [HEV } Lab diagnosis | Anti-HAV-IgM: | See schematic | Anti-HCV: im | Anti-HDV-lgM or | Anti-HEV> active disease. dicates infect- | IgG: indicates in- | IgM or IgG: | Anti-HAV-IgG: ion, not protec. | fection, not prot- | IgM indicates inactive dise tive ELISA | ective. current infec- protective immunoassay Gin | | tests positive | in 2-6 weeks. ery and prote Recombinant ction immunoblot assy (RBA) | test along with pobmmenee Shp reaction (PCR) testing. AiwaTPas_| mune sam] assoe | mune see] HV Sons po Noe Sveimmuniz-| bin (pa Immune lobutn um oben, | rs spe ation sive). Vaccine | (passive). and hepatocellular [HBV | HBY serology facts: 1. anti-HBs protective 2. HBeAg and HBV DNA infective 3. _anti-HBe-IgM present in serologic gap when all other antigens are gone and anti-HBs is not yet present 4. vaccination protects against~ A. HBV B. HDV C, hepatocellular carcinoma from HBV postnecrotie cirrhosis, 5. recovery from HBV- anti-HBs and anti-HBc-IgG 6. vaccinated only anti-HBs 7. chronie HBV- A. HBsAg >6 mths B. infective cartier if have HBV-DNA or HBeAg: correlates with chronic active hepatitis with piecemeal necrosis and fibrosis "healthy carrier" if lacking HBV-DNA/HBeAg: correlates with chronic persistent hepatitis and portal triadtis 8. association of HBV with membranous glomerulonephritis and polyarteritis nodosa 9. summary of serologies HBsAg [HBeAg | Anti-HBc-IgM | Anti-HBe-IgG | AntHBs | Interpretation Gi [negative [negative | positive Tegative negative _| serologic gap Positive | positive | positive negative negative | acute infection or chronic IF >6 mth negative [negative | negative postive positive | recovered from HBV negative [negative | negative negative | positive _| immunized [positive [negative | negative negative | “negative | earliest phase of acute HBVNote: This material is copyrighted. All rights reserved, ‘Intravenous drug abuser in prison—2type of hepatitis: HBV * County jail with outbreak of hepatitis: 1, HAV most likely 2. if intravenous drug abusers, then HBV most likely Hepatitis most commonly chronic: HCV ‘© Hepatitis associated with urticaria, fever, arthralgias, and the nephrotic syndrome 1. BBY 2. serum sickness type of disease— type III immunocomplex mechanism 3. vasculitis associated with polyarteritis nodosa ‘Immunizations given at birth to 2 baby whose mother is positive for HBsAg: 1. Hep B vaccine (active immunization) 2. HIBIG (passive immunization) ‘Most commion infection from accidental needle stick: 1. BBV 2. greatest viral burden in blood of all hepatitis viruses _ 2 Summary of infectious diseases: Disease [ Comments Rickettsia Pathogenesis: Coxiella burnetii, Only rickettsia wansmitted without @ vector. | Ofever Inhalation. Contracted by people associated with the birthing process or fecal material of infected sheep, cattle and goats (handling of milk) or exposure to | pregnant cats, Clinieal/Pathology: interstitial pneumonia, granulomatous hepatiti (80%, anicteric), endocarditis. Rx: doxycycline Bacteria Pathogenesis: cholangitis from concurrent biliary infection and obstruction, the Acute ascending | latter either by a stone or a stricture from surgery (60% of cases). Mixed bacterial cholangitis flora (Escherichia coli MC). Clinical/Pathology: Charcot's triad (70%) with fever, jaundice and RUQ pain. MCC of multiple liver abscesses. } Liver abscesses | Pathogenesis: biliary tract disease MCC (acute ascending cholangitis). Escherichia coli MC organism. Clinical/Pathology: fever, jaundice (30%), hepatomegaly Usually multiple and located in the right liver. Granulomarous | Pathogenesis: hepatitis bacterial diseases include atypical Mycobacteria (M. avium-intracellulare, MCC AIDS), leprosy, brucellosis, syphilis (see below). Other non-infectious causes | include sarcoidosis (MC), drugs, primary biliary cirrhosis. Syphilis Pathogenesis: Treponema pallidum. Clinical/Pathology: in congenital infection | i there is diffuse fibrosis without nodularity. In tertiary syphilis there is a| granulomatous hepatitis, extensive scarring and gummas resulting in a contracted _ liver called hepar lobatum, | Fungus Pathogenesis: disseminated disease associated with histoplasmosis, coccidioido- € mycosis is MCC. Granulomatous hepatitis (caseous or non-caseating necrosis) aNote: This material is copyrighted. All rights reserved. Echinococcosis (Sheep —herder's disease) “cha hake Schistosomiasis Bitharziasis) Clonorchiasis Pathogenesis: fica, Ingestion of food/water containing cysts. Anal intercourse. Cyst walls are resistant to acid destruction. Excyst in the alkaline environment of small intestine with formation of infective trophozoites Clinical/Pathology: trophozoites favor cecum and right colon, They invade crypts and burrow into the lamina propria with cytolytic enzymes ("histolytica") produce "flask shaped ulcers". Bowel inflammation produces diarrhea containing blood and mucous. Afebrile (very characteristic). Trophozoites penetrate vessels t drain into the portal vein and into the right lobe of liver to form a single abscess (noted in 90% of patients who die of amebiasis). Abscess contains digested liver tissue resembling “anchovy paste". Complications: extension through diaphragm ht hung cavity and lung, hematogenous dissemination throughout the body (e.g., brain). Lab: identify trophozoites (usually diartheal stools) and/or eysts (usually more solid stool). Trophozoites have a small, centrally placed karyosome (nucleolus) and erythrophagocvtosis (important distinction from ‘other protozoal diseases). Cysts contain up to 4 nuclei and have blunt chromatoid bodies. Rx: metronidazol Pathogenesis: Echinococcus granulasis or multilocularis (cestode {tapeworm)). A sheep dog eats infected sheep meat containing the larva. Larva develop into adult worms in the dog (definitive host). Man (intermediate host) ingests eggs from infected dogs and the eggs develop into larvae but not adults. Larvae penetrate the duodenal wall, transmigrate across the peritoneum and penetrate the liver (75%) to produce single or multiples eysts. Clinical/ Pathology: in the liver, larva develop into hydatid cysts containing scolices with hooklets representing future heads of the adult tapeworm, Cyst walls have an outer layer (frequently calcified) and an inner germinal layer. Germinal layer develops vesicles (brood capsules) containing scolices that are referred to as "hydatid sand”. Rupture of cysts often produces fatal anaphylactic _shock, Lab: eosinophilia, Serologic tests are available, Rx: albendazole and surgery are used for therapy of the cysts if the patient is symptomatic or they are excessively large. Pathogenesis: Schistosoma mansoni (primarily). Trematodes (flat worms). Infection acquired by penetration of larvae from infected snails into the patient skin with subsequent entry into lymphatics and distribution to subcutaneous tissue (“swimmer's itch”) and mesenteric. veins. S_mansoni favors intrahepatic portal veins. Larvae develop into adult worms that mate and deposit eggs, to which the host develops a fibroinflammatory response (“pipe ste in the vessel wall. Complications: portal hypertension with hepatosplenomegaly, ascites and esophageal varices. Lab: embryonated eggs with a sharp lateral spine are noted in stool or ina liver biopsy. Eosinophilia. Rex: praziquantel. Pathogenesis: Clonorchis sinensis (Chinese liver fluke), Contracted by ingesting encysted metacercaria larvae in fish. Metacercaria enter the ampulla of Vater and ascend to the small bile ducts and gallbladder where they develop into adults. Egas are passed into the stool. Adults cause the bile duct epithelium to become hyperplastic and fibrotic leading to cholangiocarcinoma, Clinical/Pathology: hepatomegaly, jaundice, diarrhea. Lab: embryonated eggs are present in stool or duodenal aspirates. Eosinophilia. Rx: praziquantel 124Note: This material is copyrighted. All rights reserved. & SUSMILE\scenarios: hydatid cysts in liver in sheepherder (Basque, Greek) = Congestive hepatomegaly 1. MCCiis right heart failure~ nutmeg liver 2. transaminases elevated a Prehepatic obstruction to blood flow 1. portal vein thrombosis 2. ascites/varices 3. no hepatomegaly = Posthepatic obstruction to blood flow: 1, Budd-Chiai A. polycythemia rubra vera MCC B. _ birth control pills vein thrombosis 3. clinical A. liver painful and congested B. ascites C. portal hypertension Alcohol liver disease 1. types A. fatty change MC type: reversible B. alcoholic hepatitis: reversible (1) fever 2) neutrophil infiltration (3) _ neutrophilic leukocytosis (4) ascites ()_ Mallory bodies C. _ cirthosis: imeversible 2. pathogenesis— A. _ acetaldehyde-protein complex: B. fatty change C. stimulates collagen synthesis by Ito cells: normally, Ito cells store retinoic acid D. _perivenular fibrosis around central vein very characteristic E. _ immunologic damage to hepatocytes 3. see table of lab abnormalities ® Autoimmune hepatitis: 1. progressive type of chronic active hepatitis 2. commonly seen in women 3. _ serum antinuclear antibody commonly positive 4. autoantibodies against smooth muscle 5. Rx with corticosteroids r Obstructive jaundice: 1, intrahepatic and extrahepatic types stone in c 2. bile contains cholesterol and bile salts/acids 3. clinical eorrelations— mmon bile duct MCC A. fat soluble vitamin deficiencies from reduetion in bile salts leading to malabsorption B. _ hypercholesterolemia from backup of bile containing CHBOX 16-2, Laboratory Aspects of Alcoholic Liver Disease Aleoho! metabolism: alcohol dehydrogenase (cytosol) aldehyde dehydrogenase (mitochondria) ‘Alcohol —P acetaldehyde + NADH +H ———="-® goetate » NADH +H > weary! Coa lipvere: NADH over NAD" leads to an increase in the production of lace acid, very low density lipoprotein (VLDL) and B-hydroxybutyrie acid Lactic Acidosis NADH » NAD* Pyruvate ———__ Lactate > Metabolic acidosis T Lactate dehydrogenase Glucose-> Fasting hypoglycemia Sint how increased production of lactic acid produces metabolic acidosis (increased anion gap type) Since pyruvate is changed into lactate, there is less pyruvate available for gluconeogenesis, hence Patients commonly have fasting hypoglycemia, Increased VLDL (Hypertriglyceridemia) NADH > NAD" 13 Bisphosphoglycerate > glyceraldehyde 3-PO, —> Ditydroxyacetone PO, NADH y NAD* acetate Glycerol 3-PO, TG (VLDL) Note how the increase in NADH reverses the reaction between 1,3-bisphosphoglycerate and slyceraldehyde 3-phosphate in the glycolytic cycle in faver of glyceraldehyde 3-phosphate, which is carbone gitte ditydroxyacetone phosphate (DHAP) and from DAP nae elycerol 3-phosphate, the Sarbohydate backbone of triglyceride (TG). Acetate, a simple fatty acid, may be used in the process of Sinthesizing TG as well. An increase in VLDL in the liver results ta fatty liver, while in the peripheral blood, the increase in VLDL leads to hypertrighyceridemia, (type IV hyperlipoproteinemia) NADH whe: B-hydroxybutyric acid (ketoacidosis) Ace CoA, the end-product of alcohol metabolism, may be convenes by the liver into ketone bodies todos peetoseetate, B-hydroxybuty-rate). The increase in NADH drives ne reaction in favor of p. hdroxybutyrate, hence producing Ketoacidosis (increased amier Bap type). Since the nitroprusside reaction utilized in the laboratory to dé odes is only sensitive for acetone and acetoacetic acid, the ketoacidosis of aleoholics remains undetected. Hence, alcoholics have two types of increased same sab metabolic acidosis, mainly lactic and B-hydroxybutyric acidosis, Sine organic acids utilize the additional on, ie in the proximal tubules of the kidneys, the competition or uric acid with these additional acids often results in hyperuricemia and goutTh liver biath ccattio| pills Y fave Note: This material is copyrighted. All rights reserved. maboke stecids (Se C. generalized pruritus from bile salt deposition: Rx with cholestyramine D. CB>30% E colored stools: lack of urobilin pigment F. urine contains CB and no urobiliniogen G. AP and GGT primarily elevated Primary biliary cirrhosis: 1. female dominant 2. autoimmune, granulomatous destruction of bile ducts in triads 3. “elinical = A. early presentation with pruritus due to bile salt deposition in skin B. _ increased AP and GGT C. no jaundice until late in disease when most triad duets are destroyed D. increased anti-mitochondrial antibodies and IgM FE. association with Sjégren syndrome and renal tubular acidosis © Secondary biliary cirrhosis: commonly noted in cystic fibrosis ‘© Primary sclerosing pericholangiti 1, complication of ulcerative colitis 2. clinical A. jaundice B. danger of cholangiocareinoma C, ERCP gold standard for diagnosis: see beading effect of bile duct ‘7 Chemical and drug-induced liver disea: Morphologic | Chemical/Drug Patter: 1. isoniazid 10-20% liver damage, toxic metabolite acetylhydrazine 2. salicylates 3. halothane symptoms after 1 week, fever precedes jaundice, metabolites formed from P450 system 4, methyldopa positive Coombs test 5. acetaminophen— FR damage, Rx with N-acetyleysteine, MCC of drug-induced _ fulminant hepatitis Zonal necrosis | 1. zone I around triads— yellow phosphorous poisoning, ferrous sulfate poisoning 2. zone Il around central vein~ carbon tetrachloride poisoning (CCI, FR), ave- taminophen, Amanita mushroom poisonin, Intrahepatic 1. non-inflammatory fype- oral contraceptives (estrogen responsible, interferes cholestasis with intrahepatic bile excretion), anabolic steroids. 2, inflammatory type- erythromycin estolate, amoxicillin-clavulanic acid chlorpromazine, thiazides Fatty change 1, single droplet (nucleus peripherally displaced)- ethanol, corticosteroids, amiodarone (looks like alcoholic hepatitis including Mallory bodies and progression to cirrhosis) | 2. microvesicular (droplets without nucleus displacement)- tetracycline, valproic - acid | Fibrosis 1. methotrexate 2. hypervitaminosis A— eating bear meat, isotretinoin Rx for acne 126‘Note: This material is copyrighted. All rights reserved. Morphologic Chemical/Drug Pattern Vascular lesions “1. Budd-Chiari syndrome oral convacopuner 2. peliosis hepatis: oral contraceptives, anabolic steroid 3. angiosarcoma- vinyl chloride, arsenic, Thorotrast jimors or tumor- 1. benign tumors (hepatic or liver eel ade conditions | steroids, tendeney for rupture and intrope 2. malignant tumors— hepatocellular c steroids Granulomatous | 1. allopurinol hepatitis 2. hydralazine, 3. sulfonamides _ s intraperitoneal hemorrhage: y,_Bsume they are taking anabolic steroids leading to liver cell adenoma 2. _ spontaneous rupture of liver cell adenoma USMLE scenario ofa pregnant woman with intraperitoneal hemorrhage: efi Producing liver cell adenoma with tendency to rupture ‘7 Beth controt pitts estrogen component) and/anabotic Steroids effect on live 1, intrahepatic cholestasis 3 _ liver cell adenoma~ tendency to rupture during Pregnancy 3. hepatocellular carcinoma ‘ USMLE scenario with an athlete who presents with Jaundice, no previous health problems, zo history:of liver disease; and'ino previousitransfusions; seram transaminases are slightly. clevated and serum alkaline phosphatase 1s markedly elevared assume patient is taking tof estrogen on Hemochromatosis: 1. AR disease unrestricted reabsorption of iron from small bowel 3. clinical liver target organ: cirrhosis with 30% chance of hepatocellular carcinoma Pancreas: (1) malabsorption @) diabetes mellitus C. skin hyperpigmented: "bronze diabet. D. heart with restrictive cardiomyopathy E, iron overload findings: (1) increased serum iron @) decreased TBC (3) _ increased percent saturation (8) increased serum ferritin F, Rx with phlebotomy The Mast Common Crenchre Disease jw US. WeNote: This material is copyrighted. All rights reserved. <= Wilson’s disease: 1. AR 2 detect in copper secretion into bk ofistaileals a peoinesyet) A. chronic liver disease-> (1) low ceruloplasmin fevels with subsequent increase in free copper in blood—> Q) Kayser-Fleischer ring ineye wf le @)_ lenticular nuclei degeneration (chorea, rigidity) low total copper due to low ceruloplasmin /4,/ $ five cyyne lonls) pesults C. high serunvurine copper ob if D. Rx with penicillamine — @ AAT deficiency | 1. AR disease j 2. decreased liver synthesis of AAT-> panacinar emphysema | 3. defective secretion of AAT by hepatocytes-> chronic active hepatitiscirrhosis hepatocellular cancer in child~ AAT is PAS positive in hepatocytes ! 4. normal alleles MM 5. abnormal alleles MZ or ZZ Liver disease in pregnancy 1. viral hepatitis MC liver disease 2. benign intrahepatic cholestasis— A. estrogen related B. not dangerous to mother or baby 3. acute fatty liver of pregnancy- fatal unless baby delivered 4. pre-eclampsia A. HELLP syndrome (1) H=hemolytic anemia (2) EL=elevated transaminases, 3) LP=low platelets B. _ liver cell necrosis around triads o Liver disease in children: tl 1, neonatal cholestasis A. neonatal hepatitis MCC B. biliary atresia: (1) extrahepatic biliary atresia MC type 2) bile duct proliferation in triads (no proliferation i @) radioactive dye cannot get into the small intestine (4) jaundice in first week of life metabolic diseases: (1) eg, galactosemia 2) tyrosinemia Reye syndrome A. infection associations are chickenpox and influenza B. _ microvesicular fatty change in liver with increased ammonia and transaminases C. cerebral edema with encephalopathy | D. salicylates damage mitochondria in liver: disrupts urea cycle and metabolism of \ ammonia rahepatic atresia)Note: This material is copyrighted. All rights reserved. 7 Cirrhosis: 1. types A. micronodularmacronodular/mixed B. regenerative nodules lack norma liver architecture . _intrasinusoidal hypertension due to regenerative nodules: leads to portal hypertension 2. portal hypertension A. esophageal varices B. caput medusae €. ascites D. hemorrhoids 3. hepatorenal syndrome~ acute renal failure without any gross oF microscopic changes 4. hepatic encephalopathy A. due to build up of ammonia and false neurotransmitter like octopamine and y= aminobenzoie acid B. coma, asterixis, mental status abnormalities hyperestrinism: A. due to decreased metabolism of estrogen and 17-Ketosteroids (aromatized into estrogen) B. clinical (1) gynecomastia fy ——@, female secondary sex characteristics {co fowl?) spider angiomas (aeteiele-yernius Atala anal PEA (4) _ palmar erythema 6. Dupuytren's contractures in fingers- fibromatosis involving tendon sheaths contracts fingers 7. ascites A. pathogenesis () increased hydrostatic pressure in portal vein @2) decreased oncotic pressure 3) secondary aldosteronism decreased metabolism of aldosterone Bb. activation or renin-angiotensin-aldosterone system from decreased arterial blood volume B. danger of spontaneous peritonitis from E. C. —usealdasterone blacker rather than loop diuretics (1) produces a metabolic acidosis which increases the excretion of NHL" in stool (2) use of loop diuretics produces a metabolic alkalosis causing greater bowel production of diffusible NH: danger of precipitating hepatic encephalopathy ‘Cavernous hemangiomas: MC benign tumor in liver ‘© Hepatic adenoma (liver cell adenoma): 1, associated with estrogens/anabolie steroids 2. tendency to rupture and produce intraperitoneal hemorrhage ao ) Hepatocellular earcinoma: 1. causes A. HBV MCC in United States: MC cancer in Far East due to chronie HBV liver disease + exposure to aflatoxins (molds in food) HCV dvays eon aa brckRowd of cidehosiNote: This material is copyrighted. All rights reserved, C. hemochromatosis D. alcoholic cirrhosis 2. pathology— develops in a background of cirrhosis blood vessel invader neoplastic hepatocytes secrete bile ieal— weight loss abdominal pain due to rapid increase in bloody ascites increase in ALT is characteristic increase in AFP and AAT as tumor markers ectopic secretion of erythropoietin produces secondary polycythemia F. ectopic secretion of insulin-like factor produces hypoglycemia Metastasis is MC cancer of liver: lung cancer is MC primary site ® Gallbladder adenocareinoma 1. MC primary cancer of biliary tree 2 causes A. gallstones MCC B. porcelain gallbladder: dystrophic calcification of gallbladder Gallstones: 1. pathogenesis A, too much cholesterol (obesity) B. too litle bile sats/acids in bile (citthosis) 2. types A. most are ch B. black calcium bilirubinate stones suggest extravascular hemolytic anemia C. most stones do not caleify 3. Dx~ ultrasound is gold standard sereening test A. obstructive jatndice in common bile duct B. _ acute cholecystitis/pancreatitis C. gallbladder cancer Acute cholecystitis: 1. impacted stone in eystic duct 2. E.coli MC pathogen 3, AIDS patient with acute cholecystitis: cryptosporidium and/or CMV are MCC © Chronic cholecystitis: 1, stones are invariable 2. chemical inflammation Cystic fibrosis: 1. AR disease A. defect on chromosome 7 B. 3 nucleotide deletion which codes for phenylalanine leads to defective CF transport regulator for chloride ions: (1) decreased CI reabsorption in sweat glands (basis of sweat test) 130Note: This material is copyrighted. All rights reserved. @) increased Na’ reabsorption and decreased CI’ secretion into terminal bronchioles (infection) and pancreatic ducts (malabsorption: causes obstruction by thick mucus complications— A. respiratory infections/failure: «@ MCcop @) _P. aeruginosa MC pathogen @) MCC of bronchiectasis malabsorption: (1) pancreatic exocrine deficiency Q) diabetes meltitus secondary biliary cirrhosis total infertility in males(USMIE): (1) atresia of vas deferens 2) women have thick cervical mucus but can have children meconium ileus in newborn © USMLE scenario: mother states that child has a salty taste when kissed: 1. eystieiibrosis 2. dosweat test F Acute pancreatitis: 1. causes A. alcoholism «McC 2) _ causes thickening of pancreatic secretions leading to obstruction B. stone in common bile duct or accessory ducts in pancreas is a close second C. enzymatic fat necrosis clinical~ A. fever B. _ pain in epigastrium with radiation into back Jab— ‘A. increased serumvurine amylase: cleared quickly from serum in few days and is present in urine B. serum lipase is more specific than amylase complications~ A. pseudocyst MC complication: (1) persistence of elevated amylase beyond one week @) mass in abdomen abscess: high mortality unless drained left-sided pleural effusion: contains amylase ARDS with hypoxemia hemorrhagic pancreatitis: (1X) Gray-Tumer sign in flank @) Cullen's sign around umbilicus hypocalcemia from enzymatic fat necrosis a bad sign CT best test for pancreatie diseaseNote: This material is copyrighted. All rights reserved. Chronic pancreatitis 1, aleohotism MCC clinical— A. malabsorption B. severe pain C. diabetes mellitus D. _ predisposition to pancreatic cancer E. calcifications usually notes on x-rays © Panereatie cancer: 1. causes A. smoking MCC B. chronic pancreatitis, 2. clinical A. painless jaundice: head of pancreas MC location B. _ palpable gallbladder: Courvoisier sign C. clay colored stools D. weight loss E. superficial migratory thrombophlebitis: Trousseau's sign F. metastasis to umbilicus: Sister Mary Joseph sign 3. lab CA19-9 F Summary chart of laboratory abnormalities associated with select disorders of the liver: arrows represent the degree of magnitude. CB/TB % = conjugated bilirubin fraction of total bilirubin, AST = aspartate transaminase. ALT = alanine transaminase, AP = alkaline phosphatase. EHA = extravascular hemolytic anemia, GGT = gamma glutamyltransferase. LDH = lactate dehydrogenase. N = normal. Disease CBB [AST [ALT | AP |GGT [LDH | Urine | % Bilirubin Viral | hepatitis 20-50% | THt | tttt | tt tt cn tt tt ‘Alcoholic | hepatitis | 20-50% | 1 t t Mt | tt tt t Cholestatie T...|. liver disease |>s0% | tt | tt [ttt] str] tr | tot FHA <20% | Mt | N N + | Absent Mt RBC RBC (increased from bilirubin loa Granulomas_| N N at | tt | | Absent Metastasis | N n [wn | | tt Absent Note: AST is present in RBCsNote: This material is copyrighted, All rights reserved. ‘Questions used during the board review: ‘A febrile 12 year old boy with a viral infection lapses into coma. Physical exam reveals papilledema and hepatomegaly. The serum ammonia and transaminases are elevated and the PT is prolonged, The patient MOST LIKELY has. ‘A. viral hepatitis B. Reye's syndrome CC. salicylate intoxication D. acetaminophen toxicity E ‘a+ anttrypsin deficieney B 7 Which of the following serologic data best represents a patient who has recovered from hepatitis Br _ ee [HBsAg [HBeAg [Anti-HBe-IgM | Anti-HBeIgG | Ant-HBs A._| negative | negative | positive negative negative B. [ positive [ positive | positive [negative negative C. [negative [negative | negative | positive posi D. [negative [negative | negative negative | positive c serologic gap, B = acute or chronic HBV, D = vaccinated) ® An afebrile 42 year old migrant worker from Mexico presents with bloody diarrhea and right upper quadrant pain, The patient MOST LIKELY ha A. amebiasis B. echinococcosis C. acute cholecystitis D. ascending cholangitis E, metastatic colon cancer A A 48-year-old alcoholic with cirrhosis and chronic pancreatitis has steatorrhea and a prolonged PT The PT does not correct to normial after giving an intramuscular injection of vitamin K. You conclude thatthe patient MOST LIKELY has. A. vitamin K deficienc; B. acirculating anticoagulant C. an isolated factor deficiency D. inadequate synthesis of coagulation factors E, vitamin K deficiency secondary to malabsorption ‘A 45-year-old man presents with increased skin pigmentation, steatorthea, and diabetes mellitus The mechanism MOST LIKELY responsible for this constellation of findings is. amyloidosis alcoholic cirrhosis a defect in iron metabolism alphay-antitrypsin deficiency a defect in copper metabolism moomD> 133Note: This material is copyrighted. Al rights reserved. % In which of the following diseases would you expect a conjugated bilirubin >50% of the total bilirubin? A. Gilbert's syndrome B. Chronic viral hepatitis C. — Crigler-Najjar syndrome D. Stone in the common bile duet E, _ Extravascular hemolytic anemia D (choice A <20%, choice B 20-50%, choice C 0%, joice E <20%) An afebrile 62 year old man with a history of alcoholism and chronic pancreatitis presents with weight loss, a slow onset of painless jaundice, and a normocytic anemia, Physical exam reveals @ palpable gallbladder and a light-colored stool. The patient MOST LIKELY has A. hepatocellular carcinoma B. carcinoma ofthe gallbladder C. primary sclerosing cholangitis | D. _astone in the eommon bile duct | E, carcinoma of the head of pancreas E 134Note: This material is copyrighted. All rights reserved. Kidney, lower urinary tract, male reproductive: Syndrome: al disease: GN = | ‘Syndrome | Characteristics Nephritie 1. glomerular — diseases are | 1. type IV diffuse proliferative GN in SLE characterized by~ _oliguria | 2. post-streptococeal GN hematuria, RBC casts, | 3. rapidly progressive crescentic GN- e.g., Good: orbital puffiness (retention | pasture's syndrome salt), and mild to moderate | 4, IgA GN (Berger's disease)~ MC GN proteinuria, 5. Alport’s syndrome hereditary nerve deafness Nephrotie 1. glomerular diseases are | 1, minimal change disease— MCC in children | characterized by~ >3.5 gm/dL | 2. focal segmental glomerulosclerosis- MC type in of protein/24 hours, oval fat | AIDS, TV drug abusers | bodies, faty casts with Maltese | 3. membranous GN- MC type in adults, HBV crosses, generalized pitting | association edema, ascites 4. membranoprol with HCV 5. diabetic glomerulosclerosis~ be microalbuminuria 6. amyloidosis Rapidly progres- [1 formation of crescents | 1. end-stage disease for many discases~ Good sivecrescentic | (parietal cells) in Bowman's | pasture’s disease, Wegener’s granulomatosis, post GN space infectious GN 2, rapid loss of renal function with hematuria and proteinuria, 3. worst prognosis of all types tive GN type I associated of GN. ‘Acute renal 1. abrupt reduction in GFR 1 ischemic ATN= MCC is prerenal azotemia failure 2. oliguria (sometimes poly-| 2, nephrotoxic ATN- MCC is aminoglycoside uria) followed by radiocontrast dye used in IVP 3. proportionate increase in BUN¢creatinine (ratio <15/1) 4. tubular dysfunction— loss of concentration, FENa’ >1, renal tubular casts Chronic renal duction in GFR >3-6 mths | 1. chronic GN failure (CRF) | 2. waxy and broad casts 2, chronic pyelonephritis | | 3. proteinuria 3. end-stage diabetic nephropathy MCC of CRF 4, metabolic acidosis, 5. hypocalcemia vitamin D deficiency 6. hyperphosphatemia— cannot excrete 7. total loss of concentration’ lutionNote: This material is copyrighted. All rights reserved. yndrome Characteristies | Examples Renal tubular acidosis (RTA) 1. type I+ defect in proton/K™ pump in collecting tubule 2. type I~ lower threshold for reclaiming bicarbonate in proximal tubule 3. type IV- destruction of taglomerular apparatus, hypo- reninemic hypoaldosteronism, MC due to diabetes 1. normal anion gap metabolic acidosis 2. urine pH usually >5.5 3. all have hypokalemia except for type IV [Urinary tract infections 1. ascending infection from an \competent vesicoureteral valve. 2. fever, flank pain, lower urinary tract signs, WBC casts. 1, mean systolic pressure >140 mm Hg and diastolic pressure >90 mm Hg on 3 separate Hypertension acute and chronic pyelonephritis 1. essential hypertension~ MC type 2. secondary hypertension renovascular MC atherosclerosis in men, fibromuscular hyperplasia in women 3. nephrosclerosis— type of renal disease seen in all types of hypertension 1. decreased water intake 2. reduced urine citrate— norm. ally binds excess calcium 3. hypercaleiuria~ MC metabolic abnormality in urine, excess reabsorption of calcium in Gl tract 4, alterations ip urine pH favor- ing stone precipitation~ eg., alkaline pH with Proteus infections (urease producers) Renal stones 1. calcium stones MC type, radiodense, calcium ‘oxalate MC type, calcium ‘phosphate stones in children 2. magnesium ammoniun stones, due to urease producers 3. urie acid— urate nephropathy from chemother= apy, radiolucent stones phosphate struviteNote: This material is copyrighted, All rights reserved. « reactions in urinalysis [rest ents pH 1. pure vegans have an alkaline plI— citrate in fruts is converted Into bicarbonate 2. meat eaters have an acid pi1~ inereased excretion of organic acids 3. urine pH is manipulated to prevent stone recurrence- uri acd is insoluble in an acid pH but soluble in an alkaline pH 4. urine pH is manipulated in Rx of drug overdoses~ alkalinize the urine in salicylate intoxication to increase excretion . ammonium smell in an alkaline urine indicates a Proteus infection urease producer that converts urea into ammonia 6. ascorbic acid is the best agent for acidifying the urine 7. carbonic anhydrase inhibitor alkalinizes urine blocks reclamation of bicarbonate | 8 acidotic states have an acid urine pH— increased secretion of NaHi:PO, (titratable acidity) and NHJCI, exception is renal tubular acidosis where the pH is >3,3 9. alkalotic states generally have an alkaline urine pH exception of advanced metabolic alkalosis from vomiting, where excess reclamation of bicarbonate due to volume depletion causes a paradoxical aciduria _| Provein 1. proteinuria isthe first metabolic abnormality in renal disease 2. all positive dipsticks for protein are checked with sulfosalicylic acid (SSA) 3. SSA is equally sensitive to both albumin and globulins 4: if only albumin is present, the dipstick and SSA resul will parallel each other~ e.g, both +1 reactions 5. if albumin and globulins (e.g, Bence Jones light chains in multiple myeloma) are present, the dipstick may be only trace or +1, while the SSA is +4~ order a urine electrophoresis to R/O light chains 6. microalbuminuria (<30 mg/day) is the first indication of diabetic. nephropa ‘microalbuminuria dipsticks are more sensitive (I.5-8 mg/dL) than standard dipstic ACE inhibitors prevent progression of the disease Giucose 1. glucosuria is diabetes mellitus until proven otherwise o 2. non-DM glucosuria “pregnancy (renal threshold for glucose is lower than normal), benign glucosuria (low renal threshold), blood glucose is normal 3. Clinitest tests for reducing substances in urine~ glucose, galactose, fructose, lactose entoses— does not detect sucrose (not a reducing sugar) 2 4. urine Clinitest is used as a screen for children <2 years of age to R/O one of the { inborn errors of metabolism~ e.g. palactosemia, hereditary fructose intolerance Ketones 1. B-hydronybutyrate ketoacidosis (alcoholics) will have a negative nitroprasside reaction ("masked ketosis") 2. ketones are normal in pregnancy 3. pathologie Ketonuria fasting/starvation, ketogenic diets, diabetic ketoacidosis, isopropyl alcohol poisoning, von Gierke's glycogenosis Bilirubin 1. only water-soluble conjugated bilirubin (CB) enters urine bilrubinuria Is always a pathologic finding. 2. bilirubinuria is present in hepatitis or obstructive jaundice 3. bilirubinuria is not present in conditions with an excess in unconjugated bilirubin | (UCB) e.g. extravascular hemolytic anemia 137Note: This material is copyrighted. AM rights reserved, Test ‘Comments 1. increased urobilinogen indicates either extravascular hemolysis or hepatitis 2. false positive reactions with porphyrins e.g., acute intermittent porphyria 3. absence of urine urobilinogen indicates obstructive jaundice~ also absent in the stool Biood 1. dipstick is positive for either Hb and/or myoglobin 2. R/O myoglobinuria with serum creatine kinase 3. hematuria secondary to a lesion anywhere from the glomerulus down to the urethral meatus 4. always order a sickle cell screen when African-Americans have unexplained microhematuria— renal damage in both trait and disease Nitrite 1. detects nitrite produced by nitrate reducing bacteria— sensitivity 30%, specificity 90%) 2. E. colt is a nitrate reducer and the MC urinary pathogen. Teukoeyte | 1. leukocyte esterase reaction has a sensitivity/specificity of 80% fora UTI esterase 2. dipsticks for nitrite/esterase are a good urine screen for infection and whether to | culture urine or not | Classic urine casts: | 1. RBC casts A. nephritie syndrome } B. eg, post-streptococeal GN WBC easts— A. acute pyelonephritis B. acute interstitial nephritis due to drugs ! C. excludes a lower UTI renal tubular casts~ acute tubular necrosis waxy easts— chronic renal failure broad easts~ chronic renal failure hyaline casts A. ghost-like casts/non-refractile, smooth borders B, sign of proteinuria C. no clinical significance in the absence of proteinuria q 7. fatty casts with Maltese crosses— nephrotic syndrome Urine erystals: 1. calcium oxalate~ consider A. calcium oxalate stone x] B. Crohn's disease C. _ ethylene glyco! poisoning cystine ‘A. hexagonal crystal B. indicates cystinuria Renal dysplasia: 1. MC eystic disease in children 2. no inheritance pattern 3. abnormal development of one or both kidneys 4. present as unilateral flank mass in most eases. 4 138Note: This material is copyrighted, All rights reserved. ‘Juvenile polycystic kidney disease: LAR disease 2. bilateral disease 3. _sligohydramnios in mother: Potters facies due to cramped quarters 4 5 cysts in other organs incompatible with life Adult potyeystic kidney disease (APKD) I. AD disease with hypertension 2. association with CNS berry aneurysms— A. due to hypertension @ @ os &_ subarachnoid hemorrhage due to ruptured aneurysm , ideal Valve prolypse C. _ intracerebral bleed with hypertension also possivle 3. eysts not present at birth A. develop in early teens B. screen with renal ultrasound Renal agenesis: oligohydramnios Potter facies 1, child with eystic disease of kidneys 2. low set ears 3. parrot beak nose 4. hypoplasia of lungs due to oligohydramnios Retention cysts: 1. MC eyst in aduits 2. acquired cysts derived from obstruction of tubules 3. cysts also acquired with hemodialysis Glomerutonephri (nd 1. majority are immunocomplex (IC), type IIT hypersensitivity 2. nomenclature: A. if'itends in itis, itis type IN: exception is B. diffuse if all glomeruli abnormal C. focal ifonly a few glomeruli are abnormal D. isorders— syndrome, which is type I proliferative if >100 nuclei membranous if membranes thick membranoproliferative if membranes thick and hypercellular munofluorescence (IF) A. always linear if anti-basement membra syndrome B. always lumpy bumpy (granular) if Cs are present e.g, post-streptocoecal GN C. _cantell what is deposited in glomeruli .g,, IgA deposits in IgA ON A B. E. F ine antibodies are present: e.g, Goodpasture's electron microscopy (EM)- detects electron dense IC deposits detects fusion of podocytes (indicates nephrotic syndrome) and other structural abnormalities GBM made by visceral epithelial cells (have podocytes and slit pores) A. strong negative charge due to heparan sulfate: repels ne albumin B. negative charge is lost in minimal change disease ively charged proteins like 139Note: This material is copyrighted. All rights reserved. e Glomerular disea 1. es commonly presenting as a nephritic syndrome: post-streptococcal GN~ A. microscopic: diffuse proliferative pattern with neutrophil infiltration B. pathogenesis: (Q)_ post group A-streptococeal infection in a child (usually skin infection) with nephritic strains of streptococci @) IC GN with planted bacterial antigens ) activation of alternate complement pathway C. granular IF pattern D. EM with subepithelial deposits E. clinical (1) smoky colored urine (hemoglobin converted into hematin with acid pH) 14 wks following group A streptococcal infection: skin or pharyngeal 2) children fare better (95% recover) than adults (60% recover) @) high ASO titers, anti-DNAase B titers, low C3 systemic lupus erythematosus~ microscopic of type IV is diffuse proliferative GN (1) “wire looping” of capillaries (subendothelial deposits) @) neutrophilic infiltration with fibrinoid necrosis (3) hematoxylin bodies (altered DNA) B. pathogenesis: (1) DNAcanti-DNA ICs (2) activation of classical pathway C. granular IF D. _ EM with subendothelial deposits E. clinical ay an NA correlates with renal disease * @) decreased C3 correlates with disease aci (3) common COD in SLE Alport’s syndrome- ‘A. microscopic: foam cells in glomeruli B. _ pathogenesis: (1) sex-linked dominant @) common in Mormons ) abnormality of a5-chain type TV collagen (4) _ lack of a3-chain (Goodpasture antigen) (S)_ not an IC disease C. no IF pattem D. EM has no deposits E. clinical: (1) disease is worse in males than females (2) nerve deafness IgA glomerulonephritis (Berger’s disease)~ A. pathogenesis: (1) increased circulating levels of polymeric IgA and IC with IgA (2) activates altemate pathway ) similar findings in Henoch-Schénlein purpura B. granular IF: only way to Dx is to document IgA 140Note: This material is copyrighted. All rights reserved. C. EM with deposits in mesangium D. clinical: (1) MC glomeratonephritis (2) MC in children/young ad 3) children present with gross hematuria a few days after an URI (4) adults present with asymptomatic microscopic hematuria and (5) _ some cases become nephrotic (6) chronic in 30-50% (1) normal C3 5. of rapidly progressive erescentic GN (RPGN) A. microscopic: glomeruli compressed by crescents derived from parietal epithelium B. pathogenesis: (1) > Goodpasture’s disease (2) -»systemic diseases like SLE, polyarteritis, Wegener's (3) drugs . (4) _ infectious disease: e.g,, infectious endocarditis (5) _ antibody types a. anti-GBM (Goodpasture, type Il reaction) b. _anti-neutrophil cytoplasmic antibodies (Wegener's) Tt you've gf's... Came Wer fanulomatosis €. ICsinsome cases C. Goodpasture’s disease (1) anti-GBM: IgG antibody directed against non-collagen domain of a3 type TV collagen in GBM and pulmonary capillaries 2) linear IF @) EM with no deposits (4) clinical a. RPGN progresses to acute renal failure in a few weeks to months b. begins with hemoptysis and ends in renal failure )) ©. usually young adult males in 90% of cases = (5) plasmapheresis useful in removing antibodies Glomerular diseases commonly associated with nephrotic syndrome: > 3.54 jy / SL. minimal change disease (lipoid nephrosis, nil disease) : me i A. microscopic normal except for positive fat stains in the glomerulus and tubules 5 B, pathogenesis: > (1) T cells produce lymphokine that destroys negative charge barrier (polyanion 5 loss) Q) _ selective proteinuria (albumin) a C. negative IF a D. EM shows fusion of the podocytes: no deposits [s E. clinical (1) MCC of nephrotic syndrome in children ) 2) MC in boys between 6-8 ys old usually after = @) normal blood pressure = (4) associations: = a. atopic history = b. nodular sclerosing Hodgkin's disease (S) respond dramatically to corticosteroids 1Note: This material is copyrighted. All rights reserved. 2. membranous GN- mmo 3. focal segmental glomerulosclerosis (FS A. microscopic with diffuse thickening of membranes but no cell proliferation epimembranous spikes with a "hair on end appearance” noted with special correspond with subepithelial deposits of IgG and C3, pathogenesis: (1) in-situ IC deposition: resembles Heymans GN in rats with antibody directed against epithelial antigen (2) majority are idiopathic 3) drugs a. captopril b. NSAIDs (4) infections a. malaria b. hepatitis B (5) malignancy ZA + a. colon — A b. malignant lymphoma granular IF EM with subepithelial deposits: fus clinical: (1) MCC of nephrotic syndrome in adults 2) ~40-50% progress to end-stage disease (3) normal C3 of podocytes - pathogenesis: (1) part of minimal change disease spectrum in adults 2) NoIC deposits (3) associations a HIV b. renal transplant patients ¢. _intragenous heroin abuse EM with fusion of podocytes: no electron dense deposits clinical: (1) poor prognosis, (2) recurrence after renal transplantation. (3) normal C3 4. type and II membranoproliferative GN— A. microscopic has “tram tracks” in type 1 > type TI: ingrowth of mesangium between endothelial cell and GBM B. _ pathogenesis (1) type Lis an IC disease: associations with hepatitis C, cryoglobulins, neoplasms Jpne Jpg 27 9P5 HL as C3 nephritis factor losedimast/” 3 autoantibody against alterate pathway C3 convertase (C36Bb) dows? b,causes sustained activation of C3 . _intramembranous deposits are C3 C. —granular IF in type I and Ml D. EM: (1) type I has subendothelial depos (2) type IT has intramembranous deposits: called dense deposit disease 142Note: This material is copyrighted, All rights reserved. Pe E, clinical (Q) type I more common than type TT (2) always order HCV serologies in type T MPGN (3) _ poor prognosis (50% develop chronic renal failure in 10 years), (4) low C3 in both types (3) C3 nephritic factor in type IL Kimmelstie! Wilson disease (diabetic glomeruloselerosis)- A. B. c D. wae D> amyloidosi A microscopic: (Q) focal areas of glomerulosclerosis ("Christmas balls") due to proteir accumulation 2) afferent and efferent hyaline arteriolosclerosis © Ac hyaline arteriolosclerosis of afferent/efferent arterioles jo pathogenesis: (1) nonenzymatic glycosylation of GBM and tubule basement membranes increases vessel permeability to prot (2) glomerular hypertrophy from cytokine release from leukocytes (3) osmotic damage due 10 toxie effect of sorbitol on endothelial cells and GBM @ filtration damage to mesangium: increased GFR early in disease due to arteriole hyaline arteriolosclerosis negative IF EM with fusion of podocytes clinical: (1) MC disease invotving the glomerulus @) more common in type I than 11 DM 3) _microalbuminuria is first sign of nephropathy (begins after ~10 years) captopril slows onset of nephropathy by decreasing angiotensin Il: rel _— pressure on glomerulus (5) _ hypertension occurs when proteinuria is present (©) retinopathy parallels nephropathy (1) MCC of end-stage renal disease in United States (8) _ other renal problems with DM a. renal papillary necrosis, b. acute and chronic pyelonephritis microscopic: (1) thickening of GBM and mesangium 2) positive Congo red stain and apple green birefringence pathogenesis: deposition of amyloid derived from light chains in multiple myeloma ot serum associated amyloid in reactive amyloidosis negative IF EM demonstrates amyloid fibrils clinical: (kidneys most commonly affected in systemic amyloidosis in 80% of cases @) renal failure is MC COD in systemic amyloidosisRennl Note: This material is copyrighted. All rights reserved 7. pregnancy induced hypertension (preeclampsia/eclampsia)- A. microscopic shows diffusely swollen endothelial cells (“endotheliosis”) B. _ pathogenesis: (1) abnormal placentation results in decrease in perfusion (2) vasoconstriction from angiotensin II and endothelin overrides vasodilation of placental vessels (3) damage to endothelial cells in placenta and kidneys C. clinical (1) hypertension, proteinuria, pitting edema (convulsions is called eclampsia) usually in the third trimester @) molar pregnaney if the above occurs in first trimester BUN/Creatinine ratio in work-up of oliguria: 1. pormal ratio is 10/1 2. prerenal azotemin~ A. due to decrease in cardiac ou eft @) heart failure 2) _ hypovolemia B. ratio >15/1 (1) clearance of creatinine in urine decreases when Georeanes Ly Lie it cot Or Clegned faom bi @) BUN increases disproportionately due to reabsorption in the proximal tubule @) e.g, BUN 80 mg/dL, creatinine 2 mg/AL, ratio= 40/1 3. acute tubular necrosis— A. ratio remains <15/1 B. both creatinine and BUN are equally affected when there is tubular dysfunction co BUN 80 mg/dL, creatinine 8 mg/dL, ratio = 10/1 4. postrenal azotemia— ‘A. due to obstruction of urine flow behind the kidneys B. initially, the ratio is >15/1 but may become <15/1 if obstruction is not relieved and tubular damage occurs ® Ischemic ATN: 1. prerenal azotemia MCC 2. affects multiple parts of the nephron- A. basement membrane disrupted B. pigmented renal tubular casts C. thick ascending limb in medulla is most sensitive to ischemia 7 Nephrotoxic ATN: 1, aminoglycosides and IVP dyes MCC 2, damages the proximal tubule ‘A. basement membrane intact put: Carythio Jomerular, filtration, rate sguectly, due OLR B, _ better prognosis than ischemic ATNNote: This material is copyrighted. All rights reserved, Laboratory [Disorder ifferentiation of oliguri UOsm | Urinalysis mOsm/kg Prerenal azotemia ute glomerulonephritis Few hyaline casts, RBC casts, hematuria, fe tubular necrosis Postren Renal tubular casts, renal tabular cells, azotemia—_| 40 | Few WBCs, renal tubular cells, FENa = [Urine Na x Plasma ereatinine] + (Plasma Na x Urine creatinine] x 100 tubular function intact A. FENa 500 (kidney is concentrating) 3. tubular dysfunction A. FENa>I B. UNa>40 C. _UOsm <350 (kidney has lost its concentrating ability) indicate tubular dysfunction ronic renal failure (CRF): 1. causes in descending order- ‘A. diabetic nephropathy B. hypertension glomerulonephritis E (1) rapidly progressive crescentic GN @) focal nodular glomerulosclerosis 2. pathophysiology of CRF A. loss of concentration is first abnormality B. loss of concentration and dilution: fixed specific gravity of 1.010 indicating lack of concentration and dilution BUN/creatigine ratio <15/1 and Bead e at (tables dilahel) iormocytic anemia due to loss of erythropoietin vitamin D deficiency (2) 08s of 1a-hydroxylase enzyme and no second hydroxylation @) tow calcium with normal to high phosphorous @) _ secondary hyperparathyroidism renal osteodystrophy (1) osteoporosis (bone is a buffer for acidosis) @) osteomalacia from vitamin D deficiency @) osteitis fibrosa cystica from hyperparathyroidism and increased osteoclastic activity H, increased bleeding time (platelet dysfunction) hemorshagic pericarditis J. non-cardiogenic pulmonary edema 1 w ‘® Acute pyelonephritis (upper urinary tract infection) in females: 1. mechanism. A. ascending infection ns B. _vesicoureteral reflux 14sNote: This material is copyrighted. Ail rights reserved. C. E.coli MC pathogen 2. clinical A. fever B. flank pain C. WBC casts D. lower urinary tract signs E, danger of sepsis Chronie pyelonephritis 1. causes: ‘A. MC secondary to vesicoureteral reflux B. obstruction 2. Usshaped cortical sears with underlying calyeeal blunting © Acute drug-induced interstitial nephritis | 1. drugs~ A. methicillin is prototype drug B. sulfonamides C. NSAIDs D. diuretics 2. mechanism type IV cellular immunity 3. clinical abrupt onset of oliguria fever azotemia rash eosinophilia urinalysis: mild proteinuria @) hematuria ) @) WBC casts (4) eosinophituria 4. Rao withdraw drug and do not use again APoOR> ‘Analgesic nephropathy: 1, combination of aspirin + acetaminophen— A. aspirin inhibits synthesis of renal prostaglandins (vasodilator) leaving angiotensin II vasoconstrictive effects unopposed B. acetaminophen FRs damage tubules in medulla C. cumulative damage due to drugs D. danger of renal papillary necrosis 2. other causes of renal papillary necrosis— ‘A. diabetes mellitus B, acute pyelonephritis C. sickle cell traitidisease 3. x-ray finding- IVP shows ring defect where papillae used to be or | } Urate nephropathy: 1. causes A. Rx of disseminated neoplasms (e.g., leukemia, lymphoma): excess release of purines and synthesis of uric acid, which blocks tubular lumens | 46Note: This material is copyrighted. All rights reserved. B. lead poisoning: (1) increases reabsorption of uric acid @)__ produces an interstitial nephritis 2 Re A. allopurinol B. alkalinization of urine © Myeloma kidney: mechanisms include 1. Bence Jones protein precipitates in tubule lumen produces a foreign body giant cell reaction 2. _nephrocalcinosis due to hypercalcemia causes tubular dysfunction 3. light chains toxic to tubular epithelium = Pb poisoning: 1. lead produces proximal tubule damage— A. proximal renal tubular acidosis B. possible Fanconi syndrome (1) proximal RTA @) aminoaciduria @) _uricosuria (4) hypoglycemia (5) hypophosphatemia 2 il nephritis— A. increase in uric acid reabsorption B. urate nephropathy CC. _ hypertension D. gout - Nephroscleros L. kidney of hypertension A. cortical surface cobblestoned: due to hyaline arteriolosclerosis leading to tubular atrophy and glomerular sclerosis B. kidneys small (1) proteinuria @) hematuria 2. elinical- A. renal failure B. potential for malignant hypertension "Malignant hypertension: 1. develops in background of essential hypertension and benign nephrosclerosis 2. gross/miero— A. “flea bitten” kidney B, necrotizing arteriolitis with fibrinoid necrosis in glomerular capillaries bitten appearan C. _ onion skinning of arterioles (hyperplastic arteriolosclerosis) 3. clinical A. extremely high blood pressure B. cerebral edema with papilledema C. progress to acute renal failure D. potential for intracerebral bleed 4. Rxe nitroprusside (USMLF) uses flea M47Note: This material is copyrighted, All rights reserved. ‘Most common site to evaluate in a child with hypertensiot 1. kidneys A. Wilm’s tumor B. cystic kidney diseas adrenal medulla neuroblastoma Hyperplasia of JG apparatus with increased blood pressure: 1. renal artery stenosis 2. usually due to atherosclerosis of renal artery in elderly man 3. fibromuscular hyperplasia of renal artery in young women 4. high renin hypertension Kidneys with irregular white patches on the cortical surface: probable pale infarcts from embolization from the left heart Diffuse cortical necrosis 1. pale infaretion limited to renal cortex 2. seen in pre-eclampsia 7 Hydronephrosis: 1. MC due toa renal stone 2. dilated ureter and renal pelvis with compression atrophy of renal cortex 3. MC COD in cervical cancer r Renal stone: 1. see renal syndromes for pathogenesis at beginning of this section 2. calcium oxalate MC stone~ A. hhypercalciuria MC metabolic abnormality B. _hyperealciuria due to excess reabsorption of calcium from gut 3. - ‘A. colicky flank pain with radiation into ipsilateral groin B. hematuria C. spiral CT is best initial screening test D. routine x-ray often identifies calcium stones 4 rrease water intake B. _ hydrochlorothiazide increases calcium reabsorption Angiomyolipoma: 1. hamartoma of kidneys 2. most commonly associated with tuberous sclerosis o Renal adenocarcinoma: 1. causes A. smoking MCC B. von Hippel-Lindau disease 2, gross/micro— A. hemorrhagic mass >3 em: size determines malignant potential B. derives from proximal renal tubule: clear cells C. tendency for renal vein invasion 8Note: This material is copyrighted, Ail rights reserved. 3. elinieal— A. triad of (flank mass @) hematuria: MC @) pain ectopic secretion: (1) erythropoietin: secondary polycythemia (2) _ parathormone like peptide: hypercalcemia with low PTH! metastasis, (1) lungs: MC site "cannon ball" b. (2) bone (lytic) @) skin ‘© Wilm's tumor: 1, common childhood cancer 2 from mesonephric mesoderm— A. some cases are AD (1) relationship with chromosome 11 2) _aniridia and hemihypertrophy in genetic type B, abortive glomeruli C. primitive cells D. _thabdomyoblasts noted 3. clinical A. hypertension due to renin secretion B. unilateral palpable mass C. hematuria D. pain © (USMLE®\pathogenesis of hypospadias: faulty closure of urethral folds * USMLE: pathogenesis of epispa 1, defect in genital tubercie 2. associated with exstrophy of bladder ‘& SUSMLE# fetes draining from/umbilicussint day old: persistent umbilical (vitelline) sinus Urine draining from umbilicus in 4 day old: persistent urachal sinus Acute cystitis: 1. E.coliMCC 2. ascending infection 3. afebrile patient with increased frequency and dysuria 4. urinatysis— A. positive dipstick for nitrites/leukocyte esterase B. pyuria C. bacteria D. hematuria Rx- A. TMP/SMX B. ampicillin 6. hemorrhagic cystitis often due to adenovirus 149Note: This material is copyrighted. All rights reserved. e Sterile pyuria (WBCs in the urine) and negative culture (standard culture) after 24 hou 1. always think renal TB 2. could also be Chlamydia trachomatis non-specific urethritis ‘Complications of cyclophosphamide: 1, hemorrhagic eystiti 2. transitional carcinoma of the bladder cc: Diseases where E, coli upper/lower UTI sepsis in hospitalized patients spontaneous peritonitis in adults with ascites ute appendicitis in adults acute cholecystitis in adults traveler's diarrhea enterotoxigenic strain hemolytic uremic syndrome- enterohemorthagic strain with 0157:H17 serotype 1 2 3. 4 5, 6. ‘Transitional cell care 1. causes A. smoking MCC B. aniline dyes C. phenacetin D. cyclophosphamide E. _ benzidine 2. clinical~ ‘A. painless hematuria B. usually papillary tumors CC. tendency for recurrence and multifocality joma of bladder: Bladder cancer associated with parasitic disease: 1, squamous cancer of bladder ‘Schistosoma hematobium- egg has a nipple at the end Epididymi " 1, -<38 ys old— A. GC B. Chlamydia trachomatis 2. >38yys old AL Ecoli B, Pseudomonas aeruginosa Varicocel 1. left side A. "bag of worms" B. spermatic vein comes off the left renal vein 2. very common cause of infertility Gross of torsion of the testicl 1. testicle has a bluish black color, 2, absent eremasteric reflex 3. testicle drawn up into the inguinal canal 4. surgery imperative 150Note: This material is copyrighted. All rights reserved. 7 Orchitis: 1. mumps. . infertility uncommon B. — mostare unilateral C. older child or adult 2. syphilis 3. HIV 7 Hydrocele: 1. scrotal mass that transilluminates 2, persistent tuni a vaginalis Prostatic hyperplasi: 1. develops in transitional zone around the urethra prostate cancer is in peripheral zone (outside) and detected by rectal exam 2. dihydrotestosterone and estrogen mediated 3. clinical A. dribbling B. urinary retention is more likely benign than malignant C. PSA does not distinguish hyperplasia from cancer D. PSA isnot increased after a rectal exam F Prostate cancer: 1. age is greatest risk factor A. increased risk with first-degree relative B. smoking €. MC cancer in men D. _ second MC cancer killer in men dihydrotestosterone-mediated 3. clinical detected by rectal exam perineural spread and extension into seminal vesicles is common sereening testis rectal éxam + PSA. confirmatory testis transrectal ultrasound with Bx osteoblastic metastasis with elevated alkaline phosphatase © USMLE: elderly mate with low back pain: 1. do‘ rectal exam to R/O prostate cancer before any other test 2. sifithey-state that the serum alkaline phosphatase is elevatedsitis osteoblastic metastasis Testicular cancers: 1. painless mass that does not transilluminate 2. seminoma MC testicular eancer— A. cryptorchid relationship: risk extends to normal B. most radiosensitive C. para-aortic lymph node metastasis 3. chorioearcinoma most malignant— ‘A. increased f-hCG from syncytiotrophoblast. B. may produce gynecomastia C. lung metastasis olk sac tumor MC in children— endodermal sinus tumor PoOR> 151Note: This material is copyrighted. All rights reserved. B. Schiller Duval bodies C._ inereased AFP 5, malignant lymphoma MC in elderly man (metastatic) 6. teratocarcinoma MC associated with increase in AFP and B-hCG: embryonal carcinoma + teratoma * Penis squamous cancer: causes include 1. Bowen's disease 2. erythroplasia of Queyrat 3. lack of circumcision Pure seminiferous tubule dysfunction: 1. no sperm 2. increased FSH- loss of inhibin synthesized in Sertoli cell 3. normal LH- ‘A. acts on Leydig cells B. normal testosterone Pure Leydig cell dysfunction: 1. no sperm testosterone also necessary for spermatogenesis 2. normal FSH 3. high LH- low testosterone w Nocturnal penile erections: presence R/O any organic cause for impotence ‘Questions used during the board review: ® An 82 year old man presents with lower back pain and complaints of problems with voiding wi ‘There is point tendemess over the lower lumbar vertebra, His bladder is percussed at the level of the umbilicus. Which of the following tests or procedures is indicated as the first step in the management of this patient? Radionuclide bone scan Prostate specific antigen Digital rectal examination Serum alkaline phosphatase Transtectal ultrasound with biopsy C (metastatic prostate cancer) moop> % A 28-year-old man with a history of removal of a right cryptorchid testis as a child is noted to have 4 painless enlargement of the remaining testicle in the left scrotal sac. The testicle is enlarged and does not transilluminate, The patient most likely has a... A. hydroeele B. seminoma C. varicocele D. yolk sac tumor E. choriocarcinoma B 152Note: This material is copyrighted, All rights reserved. 7 A 66 year old man with a 45 pack year history of smoking presents with hematuria, fever, and a palpable mass in the left lower quadrant. A chest x-ray reveals multiple nodular masses in the lungs. These findings most strongly suggest which of the following diagnoses? A. Miliary TB involving the kidneys B. Renal cell carcinoma with lung metastasis C. Primary lung cancer with metastasis to the kidney D. _Choriocarcinoma with metastasis to lungs and kidneys E. Acute pyelonephritis with metastatic abscesses in the lung B ‘FA febrile 23 year old woman presents with an acute onset of right flank pain, suprapubic discomfort, dysuria, and increased frequency of urination. The urinary sediment examination reveals clumps of leukocytes, WBC casts, occasional RBCs, and numerous motile bacteria. The mechanism of this patient's urinary condition is most closely related to A. arenal stone B. ascending infection CC. immunocomplex disease D. drug-induced interstitial nephritis E. _ hematogenous spread of infection to the kidneys B (acute pyelonephritis) 7 A 25 year old male presents with a history of hemoptysis and malaise, His blood pressure is 140/90 mm HG. He has periorbital edema and smoky colored urine, Pertinent laboratory data include a serum urea nitrogen of 40 mg/dL. (7-18 mg/dL) and a creatinine of 4.0 mg/dl. (0,6-1.2 mg/dL), Urinalysis shows 2+ protein, 3+ blood, RBCs too numerous to count, and RBC casts. A chest radiograph demonstrates opacities in both lung fields. The mechanism of this patients lung and renal disease is most closely related to a A. type I hypersensitivity reaction B. type Il hypersensitivity reaction C. type Ill hypersensitivity reaction D. type IV hypersensitivity reaction E. type land Ill hypersensitivity reaction B (Goodpasture) Items 6-7 IgA glomerulonephritis Membranous glomerulonephritis Focal segmental glomerulosclerosis Rapidly progressive crescentic glomerulonephritis ‘Type I membranoproliferative glomeruloneplhritis type I ronp> ‘FA 74 year old man with a 80 pack history of cigarette smoking presents with hemoptysis and shortness of breath. Radiographs of the chest demonstrate a let hilar mass. He also has generalized anasarca with 4+ proteinuria, hypercholesterolemia, and fatty casts in the urine. Answer: B (assoeiation of lung cancer with membranous GN) 7 A 34 year old male who is a known drug seeker and heroin addict comes to the emers department in an agitated state. He is restrained and you note multiple needle tracks on both arms He also has severe pitting edema of the lower extremities. Urinalysis is positive for protein and shows fatty easts on urine sediment. Answer: CNote: This material is copyrighted. All rights reserved. A 10 year-old-adolescent boy presents with a unilateral, tender subareolar mass in the left breast. Physical exam is otherwise unremarkable, Which of the following would you recommend for this patient? A. Serum gonadotropins B. Chromosome analy C. Serum B-hCG - D. Surgical consult . No treatment E (pubertal gynecomastia) 154Note: This material is copyrighted. Aul rights reserved. Female reproductive, breast: e Sexually transmitted dis L Herpesvirus type 2~ A B. D. human papillomav A genital herpes MC due to herpesvirus, type 2 (HSV 2): sexually transmitted primary infection (1) systemic signs and symptoms 2) _ painful vesicles that ulcerate ©) _ vesicles located on pe (4) _ lesions on labia, vulva, cervix: erosive c ) proctitis: anal intercourse (6) vesicles heal within 3 wks and may recur every 4~6 wks (7) most infectious phase for congenital infections recurrent herpes without systemic signs or symptoms Tzanek preparation (1) _ scrapings at base of vesicles 2) multinucleated squamous cells with intranuclear inclusions Rx: (1) acyclovir decreases the frequency of recurrences @) nocure pregnancy, (Q) viral shedding may occur without visible lesions (2) _ presence of viral shedding, babies must be delivered by Cesarean section us (HPV) types 6 and 11 associated with condyloma acuminata: ) venereal warts 2) _ located in moist areas in the anogenital region and on cervix (3) _ fern-like appearance (4) confused with condyloma latum in secondary syphilis (8) _ keilocytie ehange/in squamous epithelium: wrinkled pyknotic nuclei surrounded byahalo (6) _ Rx: topical podophyllin HPV types 16 (most common), 18 and 31 other HPY squamous cancer associations: citis with dise! () cervical @) vulvar 3) vaginal (4) anal squamous cell carcinoma (homosextil males) Chlamydia trachomatis A B, MCC of sexually transmitted disease (STD) in males/females: Chlamydia and GC infections frequently coexist males (1) nonspecific urethritis (NSU) a. incubation period is 2 b. dysuria thin watery exudate 4. numerous neutrophils without bacteria on gram sta sterile pyuria weeks post-sexual exposureNote: This material is copyrighted. All rights reserved. f£ Rx © single dose erythromycin * doxycycline 2) epididymitis in men < C, Chlamydial urethritis in women: (1) acute urethral syndrome @) _ mucopurulent cervicitis: fears of age a. source for conjunetivitis in newborns b. MCC of ophthalmia neonatorum ¢. erythromycin eye drops have reduced this comy ication: usually occurs after 1 wk d. cervical Pap smear: Chlamydia produce red inclusions in endocervical cells (3) 50% of PID due to Chlamydia machomatis, 4. lymphogranuloma venereum (LGV)— A. — due to Chlamydia trachomatis subspecies B. tiny papules in the genital region associated: (1) reactive lymphadenitis with granulomatous microabscesses and multiple draining @) fibrous stricture formation: a. localized lymphedema of serotum/vulva b. women may have rectal strictures C. Rx: doxyeycline Neisseria gonorrhoeae (GC) A. gram negative diplococeus B. _ women more likely to be asymptomatic carriers than men (2) men more likely to transmit to women after each sexual exposure @) drug resistance a. chromosomal mutations b. —Prlactamase production (plasmid mediated) C. clinical presentation in men: () GC urethritis MC presentation 2) creamy, purulent penile exudate within 2~$ d of exposure @) stricture (4) epididymitis (8) _ proctitis (homosexuals) (6) prostatitis (2) sterility D. Rx inmen: () Rx with ceftriaxone 2) _ spectinomycin for Rx failures E. clinical presentation in women: (1) GC primarily infects glandular epithelium a, estrogen protects squamous epithelium from bacterial adherence b, _prepubescent female lacking estrogen may have vulvovaginitis 2) urethritis (dysuria) @) cervicitis: a. MCsite b. cervical discharge 156 Pp 2 = = oo = = = = = i. oo = = - = & - = = = = . :Note: This material is copyrighted. All rights reserved. 8 (4) Bartholin gland abscess PID: a. during or shortly after menses b. lower abdominal pain ©. adnexal tenderness on movement of the cervix (chandelier sign) a. fever f. elevated neutrophil count perihepattis results in Fitz-Hugh-Curtis syndrome: + adhesions + RUQpain 8. Rx with ceftriaxone (for GC) and doxycycline (Chlamydia) (©) complications of GC a. sterility b. ectopic pregnancy fr ym tubal scarring (MCC of ectopic) ©. disseminated gonococcemia: © dermatitis * tenosynovitis © septic arthritis (1) _ birth control pills protect against GC but not Chlamydia F. other GC infections: (1) pharyngitis (result of fellatio) (2) _ proctitis (anal intercourse): recurrent disease unless patient with GC proctitis is treated (USMEE) )__ ophthalmia neonatorum: bilateral conjunctivitis in first week (USMILE) Hemophilus ducreyi ‘A. chaneroid caused by the gram negative rod: gram stain shows a classic "school of fish orientation of the bacteria B. painful genital and perianal ulcers: suppurative inguinal nodes €. Rx: ceftriaxone or azithromycin or erythromycin Calymmatobacterium (Donovan's bacillus) granulomatis— A. granuloma inguinale is caused by a gram negative coccobacillus B. organism is encapsulated: phagocytized by macrophages (Donovan bodies) C. creeping, raised, sore that heals by scarring D. _ no lymphadenopathy E Rx: doxycycline Gardnerelta vaginalis A. bacterial vaginosis is caused by gram negative rod Gardnerella vaginalis often associated with other anaerobes like Mobiluncus and some Bacteroides species does not produce an inflammatory exudate (no neutrophils or erythema) commonly noted when vaginal pH between 5~5.5: reduction in Lactobacilli Gardnerella adheres to surface of squamous cells: characteristic "clue cells" potassium hydroxide added to discharge produces a fishy, amine-like smell G Rx D. E. FE (1) Rx patient (not the partner) with metronidazole @) avoid metronidazole in first trimesterNote: This material is copyrighted. All rights reserved. a 9. syphilis— A B, caused by the spirochete Treponema pallidum: (2). primarily contracted by sexual contact 2) organism produces a vasculitis called endarteritis obliterans a. localized ischemic necrosis b. heavy plasma cell infiltrate primary syphilis: (1) solitary painless, indurated chancre (2) 3-4 weeks after exposure (3) _ shaft of penis (4) labia (5) _chancre persists for 1-5 wks: spontaneously resolves secondary syphilis: (0) occurs 6 wks to 6 mths later (2) most contagious stage of syphilis (3) _ diffuse maculopapular rash: commonly involves palms and soles (4) generalized lymphadenopathy (©) condyloma latum: a. raised white lesions b, located around moist areas of anogenital region (©) pericholangitis (meningitis (8) _ nephrotic syndrome (9) lesions heal in 412 wks (10) disease may enter latent phase latent syphilis: (2) usually asymptomatic Q) positive serology (3) considered noninfective when duration >4 ys: a. exception is pregnancy b. disease can be transmitted to fetus (4) _ ~one-third of patients left untreated with syphilis will enter tertiary phase tertiary syphilis: (1) CNS disease (MC): see CNS notes @) locally destructive disease due to gummas @) cardiovascular disease: a. aortic arch aneurysm b. see cardiovascular notes congenital syphilis: see genetics notes dark field microscopy: (1) considered gold standard for primary and secondary syphilis 2) direct fluorescent tests just as accurate nonspecific serologic tests (1) reagin antibodies react with cardiolipin antigens from beef heart: basis for the RPR (Rapid Plasma Reagin) and VDRL (Venereal Disease Research Laboratory) tests (2) sensitivity 75% in primary syphilis, 99% in secondary syphilis, 70% in latent syphilis, ~ 50% in tertiary syphilis: a. false positives in SLE due to anticardiolipin antibodies 158Note: This material is copyrighted, All rights reserved. b. false negatives in secondary syphilis due to antibody excess (prozone Phenomenon): must dilute serum until an agglutination reaction occurs (2one of equivalence) © __RPR/VDRL become nonreactive after 1_yr in primary, 2 yrs in secondary, 2-s yrs in latent syphilis (4) VDRL test of choice on CSF in diagnosing neurosyphilis 1. specific tests for syphilis: (1) Fluorescent treponeme antibody-absorption test (FTA-ABS) a treponemal test with highest sensitivity/specificity for Dx of syphilis in al stages b. remains positive after Rx © _ positive FTA-ABS either represents active or inactive syphilis (2) microhemagglutination-Treponema pallidum (MHA-TP); sim specificity to FTA-ABS ar in sensitivity de Rx (2) syphilis is only bacterial STD that has not changed its antibiotic susceptibility (2) exquisitely sensitive to penicillin (3) Jarisch-Herxheimer reaction (not a pen a few hs of Rx of secondary syphilis: lin allergy) commonly occu a, fever b, headache ©. intensification of rash 10. Candida albicans— A. Candida vaginitis: a) uncommonly transmitted sexually b. diabetes mellitus ©. systemic antibiotics @. pregnancy @) _ intensely prurtie vaginitis with a "cottage cheese” discharge G) KOH preparation feveals budding yeasts with pseudohypha (4) Rx: fluconazole single dose 1. Trichomonas vaginalis A. flagellated protozoan (1) locates in the urethra (males and females), prostate, seminal v 2) pear shaped B. vaginitis: (1) intense pruritus @) strawberry colored mucosa G) _leukorthea (discharge) (4) urethritis (5) tumbling motility of trophozoites in a han; © Rx: a. _patient/partner Rx with metronidazole b. metronidazole contraindicated in first trimester yyphilis and HIV (USMLE) icles, vagina ing drop prep of discharge ‘Condom: best protection againstNote: This material is copyrighted, All rights reserved. Vulvar leukoplakia: 1. possible precursor for squamous cancer or Paget's disease 2. do Bx @ Lichen selerosis et atrophicus: 1. atrophy of epidermis of vulva 2. parchment like appearance of skin 3. no risk for squamous carcinoma Squamous hyperplasia of vulva: 1. precursor for squamous cancer 2. leukoplakic lesion & Squamous cancer of vulva: 1. MC eancer of vulva 2. labia majora MC location 3. HPV relationship ® Vulvar Paget's disease: 1. intraepithelial adenocarcinoma 2. confused with malignant melanoma © Gartner's duct cyst 1. remnant of wolffian duct 2. cyston lateral wall of vagina * Young girl with grape-like masses protruding from the vagina: 1. embryonal rhabdomyosarcoma 2. MC sarcoma in children 3. not related to DES Clear cell adenocarcinoma of vagina: 1, associated with DES exposure during pregnancy 2. vaginal adenosis is the precursor— A. located at junction of Millerian epithelium with that of urogenital sinus B. _ DES inhibits Milllerian differentiation: (Q) tubes, uterus, cervix, upper one-third of vagina are all affected @)__ cervical stenosis and incompetence leads to repeated abortions 3. recent USMILE' scenario: woman with multiple spontaneous abortions A. showed a picture of endometrial biopsy: probably showed clear cells B, _ probable clear cell adenocarcinoma not gonorrhea, endometrial cancer, or HPV e Cervieal Pap smear: 1, must be endocervical cells (gold standard)~ indicates proper sampling of the endocervical canal where dysplasia occurs superficial squamous cells indicate adequate estrogen intermediate squamous cells~ indicate adequate progesterone parabasal cells— hormonally unstimulated squamous cells normal non-pregnant adult woman— ‘A. 70% superficial B. 30% intermediate pregnancy/prepubertal~ 100% intermediates from progesterone effect . elderly woman not on estrogen- atrophic smear with predominantly parabasa ‘woman on unopposed estrogen- 100% superficial 160Note: r 3 ‘This material is copyrighted. All rights reserved. Cervieal polyp: 1. non-neoplastic 2. hangs out of cervieal os 3. posteoital bleeding Nabothian cysts: blocked endocervical glands with mucous retention (USMIEE) Koilocytosis: 1. HPVeffect in squamous cells, 2. pyknotic nucleus surrounded by a clear halo Cervical intraepithelial neoplasia (CIN) 1. related to HPV 2. CIN F-mild dysplasia that involves lower one/third 3. CIN H- moderate dysplasia that involves lower two thirds 4. CIN III- severe dysplasia to carcinoma in situ that is full thickness dysplasia 5. requires 10 yrs to move from CIN I to CIN TIT 6. requires another 10 yrs to move from CIN III to invasi fe cancer Cervical squamous cancer: 1. causes A. HPV 16, 18: early onset of sexual activity with multiple parmers increases exposure risk B. smoking . birth control pills D. _immunosuppression 2. develops in transformation zone 3. death due to renal failure from extension into the retroperitoneum and blocka ureters 4. average age ~45 ys old Gynecology cancers by decreasing incidence; endometrial > ovarian > cervical Gynecology cancers by decreasing mortali ovarian > cervical > endometrial Gynecology cancers by age: cervical 45, endometrial 55, ovarian 65 Sequence to menarche 1. breast budding—> 2. growth spurt 3. pubic hair—> 4 5. axillary hair—> menarche (mean age 12.8 ys) Proliferative phase: 1. estrogen mediated proliferation of glands 2. estrogen surge 24-36 hs prior to ovulation has positive feedback of LH and negative feedback on ESH-> A. LH surge> B. ovulation Ovulation: 1, usually on day 14 2. indicators of ovulation ‘A. increase in temperature due to progesterone 161o Note: This material is copyrighted, All rights reserved. e 4q subnuclear vacuoles in cells ferning of cervical mucus presence of secretory endometrium on day 21 confirms ovulation has occurred mittelschmerz may occur: blood from ruptured follicle causes peritoneal irritation rth control pills~ mixture of estrogen + progestins baseline levels of estrogen prevent midcycle estrogen surge preventing LH st progestins arrest proliferative phase and lead to gland atrophy progestins inhibit LH cervical mucus is hostile to sperm alters fallopian tube motitity progestins produce lipid abnormalities Secretory phase: 1. progesterone-mediated~ A. increase in gland tortuosity and secretion B. development of pseudodecidua C. most fixed stage of eycle 2. Arias-Stella (exaggerated secretory phase) indicat s pregnancy Menses: 1, initiated by drop off in estrogen and progesterone 2. plasmin prevents menstrual blood from clotting excessive clots indicates menorrhagia Implantation on day 21: 1, 3 days in the tube 2. 2 days in uterus Functions of FSH: 1. prepare follicle of month 2. increase aromatase synthesi 3. synthesis of LH receptors Funetions of LH 1, proliferative phase A. increase synthesis of 17-ketosteroids (DHEA and androstenedione) in theca inte B. DHEA converted into androstenedione C. androstenedione converted into testosterone D. testosterone enters granulosa cells and is aromatized into estradiol 2. Lif surge= induces ovulation 3. seeretory phase- theca interna primarily synthesizes 17-hydroxyprogesterone in granulosa cells Estrogens: 1. estradiol- ‘A. main estrogen in non-pregnant woman B. derived from aromatization of testosterone in granulosa cells of developing follicle 2. estrone- weak estrogen in menopause derived from adipose cell aromatization of androstenedione from adrenal 3. estriol A. end-product of estradiol B, primary estrogen of pregnancy 162Note: This material is copyrighted. All rights reserved. ® Androgens in women: 1, androstenedione A. B. 50% adrenal cortex 2. DHEA- A. 80% adrenal B. 20% ovary 3. DHEA-sulfate A. 95% adrenal cortex B, _ best test for adrenal origin of hirsutism/virilization J. testosterone— A. 50% from peripheral conversion of androstenedione into testosterone (oxidoredu reaction) B, 25% in ovaries C. 25% in adrenal cortex © Sex hormone binding globulin (alias androgen binding globulin): 1. _ binding protein for testosterone and estrogen higher affinity for testosterone 3. high levels of SHBG decrease free testosterone levels 4. synthesized in liver in women and liver and Sertoli cells in men estrogen and thyroid hormone increases synthesis of SHBG: reason for gynecomastia in men with hyperthyroidism androgens and insulin decrease synthesis of SHBG m have decreased SHBG: reason for hirsutism in these — 1, mean age 52 yrs 2. elevated gonadotropins~ + FSH best marker 3. ical A. secondary amenorrhee B. hot flushes C. decreased vaginal secretions D. night sweats 4. Rx estrogen = Menstrual dysfunction: 1. menorrhagia— A. loss >80 mL per period B. MCC of iron deficiency in women 2. metrorrhagia— interval blee 3. oligomenorrhea A. infrequent bleeding B. polycystic ovarian syndrome 4. dysmenorrhea~ A. painful bleeding B. primary type due to prostaglandin F2a. C. _ Carboprost tromethamine is analogue of PGF2 (1) abortifacient that iner uterine contractility 163Note: This ca iaterial is copyrighted. All rights reserved. 2) control postpartum bleeding D. secondary type MC due to endometriosis Dysfunctional uterine bleeding: 1, bleeding unrelated to an anatomic eause~ hormonal imbalance 2, anovulatory bleeding— A. MCC of bleeding after menarche B. estrogen increases mucosal thickness and then tissue sloughs C. inadequate amounts of progesterone D. Rx with progesterone or birth control pills 3. ovulatory types A. inadequate luteal phase: poorly developed secretory endometrium B. irregular shedding of endometrium: persistent luteal phase with mixed proliferative/secretory glands in menstrual effluent Primary amenorrhea: 1. definitions A. no menses by 14 ys of age in an adolescent with poor secondary sex characteristics B, no menses by 16 ys of age in an adolescent with good secondary sex characteristics 2. no bleeding post administration of progesterone- 6— /RogessROVE Clu/lerge tes A. _ indicates that the uterus is not estrogen primed, or 1 bleeding, tee B. _ end-organ defect prohibiting exit of the menstrual blood PReyesteateare. level 3. hypothalamic/pituitary defect- Grom Peyesheaw A. decreased FSH/LH: B. _hypogonadotropic hypogonadism C. causes: (1) anorexia nervosa or weight loss syndrome @) pituitary tumor @) Kallman syndrome: a. absent GnRH b. —_anosmia and color blindness (4) constitutional delay 4. ovarian defect in synthesis of estrogen— A. increased FSH/LH: B. _ hypergonadotropic hypogonadism . probable Tumer’s syndrome (2) MC genetic cause of primary amenorrhea (2) poor secondary sex characteristics, 5. end-organ defect: A. normal FSH/LH B, _ imperforate hymen CC. Rokitansky-Kuster-Hauser: no vagina jecondary amenorrhea: definition no menses for 3 mths pregnancy MCC hypogonadotropic hypogonadism— A. prolactinoma B. _ anorexia nervosa/weight loss syndrome C. stress Se 1 2, 3 164Note: This material is copyrighted. All rights reserved. D. hypopituitarism 4. hypergonadotropic h A. surgical remo pogonadism— al of ovaries B, autoimmune disease 5. end-organ disease- A. Asherman syndrome B. removal of stratum basalis owing to repeated dilatation and curettage © Endometritis: _ 1. plasma cells present A. group B streptococcus (Streptococcus agalactiae) in pregnancy 5 B. Neisseria gonorrhoeae A C. IUD with Actinomyces israeli = Endometrial polyp: ° 1. nomalignant potential 2, menorrhagia * Endometrial hyperplasia > L. precursor for endometrial cancer S 2. simple and complex types 3. due to unopposed estrogen— 7 A. — taking estrogen without progesterone > B. obesity C. polycystic ovarian syndrome SF Adenomyosis: 1. glands and stroma in myometrium— A. not endometriosis B. coarse, thickened myometrial tissue clinical A. menorrhagia B. _ pelv €. — dysmenorthea Endometrios 1. glands and stroma outside confines of the uterus A. MC due to reverse menses B. metaplasia C. _hematogenous/ymphohematogenous spread ay mney i D. only occurs in reproductive life donbhiises = 2. clinical ; ; A. MCC of secondary dysmenorthea Ly bk Wed cantees B. ovaries most often involved (chocolate cysts) f : “ C. induration in pouch of Douglas tel of 5 Ailey D. dyspareunia menses / E. intestinal obstruction 3. laparoscope best for Dx and Rx » ‘% Endometrial carcinoma: 1. due to unopposed estrogen— A. woman on unopposed estrogenNote: This material is copyrighted. All rights reserved. carly menarche/late menopause nulliparity polycystic ovarian syndrome obesity F. Hx of breast cancer bleeding in postmenopausal woman spreads down into endocervix and out into Leiomyoma: 1, MC benign tumor in women~ ‘A. sometimes called "fibroids B. MC tumor of Gi tract: MC in stomach clinical A. cause of menorrhagia B. obstructive delivery Leiomyosarcoma: MC uterine sarcoma ic pregnancy: MCC is previous PID ruptare MC COD in early pregnancy B-hCG best initial test A. vaginal ultrasound to check for amniotic sac B. _unclotted blood in pouch of Douglas 4. sudden onset of lower abdominal pain Polycystic ovarian syndrome: 1, pathogenesis— A. increased LH stimulates ovary to produce testosterone and 17-ketosteroids (androgens leading to hirsutism)-> B. increased adipose aromatizes androgens. to estrogens (endometrial hyperplasia/cancer)—> estrogen inhibits FSH and enhances LH release-> continued eycle of LH stimulation—> E. _ lack of FSH causes atresia of follicles and large ovaries with subcortical cysts linical- obesity hirsutism irregular menses infertility endometrial carcinoma LIVFSH ratio >3/ increased 17-ketosteroids incteased free testosterone increased weak estrogens A. * birth control pills suppress LH B. * clomiphene if patient wants to become pregnant Follicular eyst: MC overall ovarian massvr ‘This material is copyrighted. All rights reserved, Ovarian tumors: 1, most ovarian tumors are benign in women <45 ys old serous cystadenoma MC type 2. most are malignant in women >45 ys old— A. serous cystadenocarcinoma MC type B. should not be able to feel an ovary in postmenopausal women (presumptive evidence of cancer) risk factors. A. increa B. _ hereditary ovarian cancer syndromes: ¢.g C. — Turmer's syndrome: dysgerminoma 4. most malignant tumors spread by seeding- fee! induration in pouch of Dou, :d ovulation: birth control pills decrease incidence of ovarian cancer Lynch syndrome Surface derived ovarian tumors: 1. benign A. serous eystadenoma with cysts lined by cilia (1) MC overall benign tumor @) MC bilateral benign tu mucinous cystadenoma: cysts lined by mucous secreting cells Brenner’s tumor: Walthard’s rests nant~ classification scheme also lists borderline types serous eystadenocarcinoma: (1) MC primary cancer of ovary Q) MC bilateral ovarian tumor @) MC ovarian cancer with psammoma bodies B. _ mucinous eystadenocareinoma: (1) largest ovarian tumor @)__ most often associated with pseudomyxoma peritonei C. endometrioid carcinoma: (1) greatest association with endometriosis @) greatest association with endometrial carcinoma Germ cell tumors of ovai 1. eystie teratoma MC (USMLE pictur) ‘A. undergoes torsion in adolescent B. x-ray shows calcifications CC. struma ovarii is a teratoma with a component of functional thyroid tissue 2. dysgerminoma MC malignant tumor association with Turner syndrome 3. yolk sae tumor- — A. MC tumor in girl B. increased AFP Sex cord stromal tumor: 1. fibroma MC type- A> benign tumor B. Meig syndrome (USMLE): (1) fibroma 2) ascites (3) right sided pleural effusion 167Note: This material is copyrighted, All rights reserved granulosa cell tumor— ‘onkins Akamakse ) A. feminizing tumor B. low grade malignancy C. Call Exner bodies thecomas. A. benign estrogen secreting tumors B. yellow color Sertoli Leydig cell tumor— A. benign masculinizing tumor B. _ alias androblastoma or arrhenoblastoma Leydig cell tumor— A. benign masculinizing tumor B. alias hilar cell tumor C. contains crystals of Reinke totost 6. gonadoblastoma— A. — germ cell and sex cord stromal tumor combined B. calcifies C. association with Turner's ‘Krukenberg tumor (USMLE): 1, hematogenous spread of gastric cancer to both ovaries 2. signet ring cells 1 Chorionic villus/umbilical cord: lined by trophoblastic tissue A. syncytiotrophoblast (synthesizes hCG @) LHanalogue 3) _ keeps corpus luteum functional for 8-10 wks in normal pregnancy (4) _ synthesizes human placental lactogen: growth hormone of pregnancy B. cytotrophoblast villus contains myxomatous appearing stroma with blood vessels two umbilical arteries and one vein (oxygenated blood)~ single artery has an increased incidence of congenital anomalies Placenta abnormalities: placenta previa— A. implants over cervical os B. painless bleeding abruptio placenta— A. retroplacental clot B. _ painful bleeding C. association with smoking/cocaine/hypertension placenta accreta~ direct implantation into muscle without intervening decidua enlarged placents diabetes mellitus B. Rh hemolytic disease of newbom syphilis 168Note: This material is eopyrighted, All rights reserved. o placenta— A. monochorionie are associated with identical twins whether monoamniotic or diamniotic (1) ‘Siamese twins (USMLE) in monochorionic monoamniotie placenta (2) _ fetal to fetal transfusion in monochorionic mono or diamniotic (3) _ tangle in umbilical cord only in monochorionic monoamniotic B. dichorionic can be either fraternal or identical twins bleeding 8-10 wk gestation— A. cottesponds with drop in progesterone due to involution of corpus luteum of pregnancy maintained by B-hCG B. _ not enough progesterone being synthesized by placenta Chorioamnionitis: usually Streptococcus agalactiae Preeclampsia/eclampsi 1 2. usually occurs in third trimester~ think hydatidiform mole if in first trimester pathogenes ‘A. abnormal placentation causing mechanical or functional obstruction of spiral arteries leading to decreased perfusion in placenta 1) 7 increase in angiotensin Il, a vasoconstrictor @) ¥ decrease in prostaglandin E;, a vasodilator @) 7 increase in TXAs, a vasoconstrictor (4) decrease in nitric oxide, a vasodilator B. placenta exhibits premature agi clinical A. preeclampsia: () * hypertension Q) Aproteinuria @) pitting edema eclampsia: (1) seizures @) Rx with magnesium sulfate renal disease: swollen endothelial cells in glomerulus liver disease: see Hepatobiliary notes, y increase in serum BUN increase in uric acid increase in serum creatinine decrease in glomerular filtration rate increase in serum transaminases schistocytes/anemia/thrombocytopenia: consider HELP syndrome mESOePESO Gestational neoplasms: L hydatidiform mole (USMLE picture)- ‘A. looks like a bunch of grapes B. complete mole: (1) - 46 XX (90%) a, both chromosomes of paternal origin (androgenesis) chromosomes or the chromosomes are inactive 169Note: This material is copyrighted, All rights reserved. egg is fertilized by one haploid X sperm that duplicates itself after fertilization ‘#25 without chromosomes are fertilized by 2 haploid sperm that are either X or Y, resulting in either a 46 XX or 46 XY genotype (3) most often associated with choriocarcinoma clampsia in frst trimester Uterus too large for gestational age increased B-hCG C. partial mote: (1) triploid (69 XxY) a. haploid egg with 23 X may be fertilized by 1 or 2 sperms b, diploid 46 XY sperm +23 X = 69 XXY © one haploid 23 X sperm + one haploid 23 Y sperm XXxY 2) embryo present G) does not transform into choriocarcinoma invasive mole- benign but does metastasize gestationally derived chorioearcinoma- A. syncytiotrophoblast and cytotrophoblast B. no chorionic villi C. metastasizes to lungs D. responds dramatically to methotrexate Amniotic fluid 1. composition A. fetal urine B. alkaline pit C. high salt content causes ferning when allowed to dry on a slide D. swallowed and recycled by the fetus polyhydramnios Q) too much fluid Q) TE fistula @) duodenal atresia oligohydramnios: (1) too little fluid @) fetal renal abnormalities AFP- A. high AFP: (1) open neural tube defects @) related to folate deficiency (3) should be on folate before pregnancy B. _ low AFP: Down syndrome lecithin/sphingomyelin ratio- A. _ lecithin is synthesized by lamellar bodies in type II pneumocytes in fetal lungs during 34th-36th week: (1) _ lecithin is phosphatidylcholine @) decreases alveolar surface tension >2/1 in amniotic fluid indicates adequate pulmonary surfactant surfactant increased by cortisol and thyroxineNote: This material is copyrighted. All rights reserved. D. surfactant nhibited by insulin: sce respiratory for RDS discussion Urine estriol: 1. derived from fetal adrenal, placenta, maternal liver 2, low levels indicate fetal, placental or maternal problem Breast * Breast masses: 1. fibrocystic change swe YORE A. MC breast mass <30 years pepte u cysts with apocrine metaplasia (red epithelial cells) ducing | C. duct hyperplasia: (1) estrogen mediated @) atypical ductal hyperplasia only risk factor for cancer D. fibrosis E. sclerosing adenosis in terminal duct lobules: small risk for eancer 2. bloody nipple discharge— A. <50 ys old: benign intraductal papilloma in lactiferous duct B, _>50 ys old: consider malignancy 3. tumor <35 ys old A. fibroadenoma: (1) frcely movable mass @)__ stroma is neoplastic component @)__ stroma compresses ducts forming sit like spaces, (A) estrogen-sensitive 4. breast mass >50 ys old- infiltrating ductal cancer Breast lesions by location: 1, nipple/areota complex— A. Paget's disease of breast (1) rash-like lesion @) _ indicates underlying breast cancer infiltrating nipple epithelium B. breast abscess (1) usually associated with lactation Q) Staphylococcus aureus lactiferous duct/sinus~ A. intraductal papilloma in lactiferous duct | B. galactocele C. plasma cell mastitis 3. major ducts. A. fibrocystic change B. ductal cancer 4, terminal duet tubular carcinoma 5. terminal lobule- A. sclerosing adenosis B, lobular carcinoma: (1) _ bilaterality: does not have to be the same type of cancer in other breast Q) _ slow progression into invasion @) "Indian filing” of cancer cells throughout the stromaNote: This material is copyrighted. All rights reserved. (4) not palpable 6 stroma— A. fibroadenoma B. _cystosarcoma phyllodes: (2) malignant, bulky, fungating tumor @) rarely metastasizes ® Breast cancer risk: 1. >80ys old~ most important risk 2. family history- A. first generation relatives most important (2) overrides age as most important risk factor @) mother andlor sister B. | young woman witha family Hx should get genetic counseling to R/O BRCAI/BRCA2 connection (USMLE): (1) mammography should begin 10 yrs earlier than age of affected relative having the cancer @) eg, mother had cancer at age 45, mammography in daughter should start at age 35 3. Hx of contralateral breast cancer— overrides age as major risk factor 4. unopposed estrogen— A. _ early menarche/late menopause B. _ nulliparity . Hx of endometrial cancer 6. radiation exposure Mammography: 1, purpose is to detect non-palpable masses 2. screening should begin at age 40 ys~ A. every other year until 49 ys B. yearly from 50 ys on & Breast cancer types: > 1. intraductal carcinoma~ comedocarcinoma with central duct necrosis 2. infiltrating ductal carcinoma: ‘A. simple type: MC overall type B. medullary carcinoma: (bulky @) younger age bracket @)__ pushing borders (4) large malignant cells with a lymphocytic infiltrate ©) _ better prognosis than infiltrating ductal cancers C. colloid (mucinous) carcinoma: () elderly @) tumor nests in lakes of mucus L the orect, @) good prognosis, ys BN Adsaiaeniorn D. Paget's disease: (ul)l m don CP) — lncaceinirm +avvklyitg (1) nipple rash with underlying cancer invading epidefinis causing the rash 24 2) poor prognosis E. inflammatory carcinoma: clinical tumor (1) worst breast cancerNote: This material is copyrighted. All rights reserved. 4q (2) _ peau du orange appearance due to plugging of subepidermal |ymphaties 3. lobular carcinoma A, MC terminal lobule can B. bilateral 4. stromal tumors ‘A. cystosarcoma phyllodes B. sarcomas: angiosarcoma MC type Clinical presentation of breast cancer: 1. presentation A. MC presentation is a painless mass in upper outer quadrant B. _skin/nipple retraction €. peau du orange: inflammatory type investigative tools A. mammography B, fine needle aspiration: most often used for sampling palpable mass (2 Shep i mer gael sy ead to Melek pow -palplte masse Prognostic tools: 1, estrogen receptor assay (ERA) and progesterone receptor assay (PRA)- A. if positive, indicates that ablative Rx is indicated (1) tamoxifen is an anti-estrogen that blocks estrogen receptors @)* protects against coronary artery disease and osteoporosis (3) can produce endometrial cancer B. less likely to be positive in women in reproductive period of life: down receptors from estrogen C. more likely to be positive in postmenopausal women: (1) up-regulation of estrogen receptors @) better remission rate 2. § phase fraction determines number of neoplastic cells in proliferating in the cell cycle: less the S phase fraction, the better the prognosis 3. diploid (even number of chromosomes) vs aneuploid (odd number of chromosomes)- diploid is better than aneuploid 4. erbB, oncogene- poor prognosis if present 5. grading of cancer A. nuclear chromatin pattem B. necrosi lation of Rx of breast cancer: 1, modified radical mastectom: A. all breast tissue including n pple B. axillary lymph nodes below axillary vein C. _pectoralis minor in most cases lumpectomy with low axillary nodes (for staging) followed by radiation similar statistics as for modifiedNote: This material is copyrighted. All rights reserved. Questions used in the board review: Items 1-3 A. Infltrating ductal carcinoma B. Lobular carcinoma C. Fibrocystic change D. Intraductal papilloma E. Intraductal carcinoma ar-old woman during her breast exam is noted to have a bloody discharge. No masses are palpable. Answer: D © A 65 year old woman with a history of breast cancer in her mother is noted to have retraction of skin in the right upper outer quadrant when abducting her right arm during her annual clinical exam, An indurated 3-om mass is palpated directly beneath the skin retraction. Non-tender, firm right axillary lymph nodes present in the lower axillary chain Answer: A o A 26 year old woman without any family history of breast cancer complains of pain lumpiness" in her breasts that progressively increases throughout her menstrual cycle and is relieved after menses is completed. Physical exam reveals a painful, ill-defined mass in the left upper quadrant. No palpable axillary lymph nodes are present. Answer: C o A 58-year-old woman with a 20-year history of smoking has a history of breast cancer in her mother. Her diet is poor in fiber and rich in saturated fats. Menarche occurred at 13 years of age and menopause began at 52 years of age. She has had 3 children, She had a cervical conization at 28 years of age for severe cervical dysplasia and has since had normal cervical Pap smears. Which of the following is her greatest risk factor for breast cancer? A. Age B. Family history C. Smoking history D. Severe cervical dysplasia E, Low fiber, high saturated fat diet B (first generation relatives overrides age) ‘During her monthly self-breast exam, a 19-year-old woman notes a moveable, firm, slightly tender mass in the left upper outer quadrant, There is no skin retraction or nipple discharge. She is currently taking birth control pills. Her older sister was recently given a diagnosis of breast cancer for which she opted for breast conserving therapy. You would expect a fine needle aspiration of the mass to reveal A. an infiltrating ductal cancer B, an intraductal papilloma C. benign cyst fluid D. afibroadenoma E. lobular cancer 174Note: This material is copyrighted. All rights reserved. + o The incidence of breast cancer has been increasing in the U A. B. a D. E. A 22 year old woman, gravida 1, para 0, presents to the o at 34 id States primarily due to smokin poor diet ‘mammography breast self-exam clinical breast exam tpatient office for a routine prenatal visit weeks’ gestation. Her blood pressure is 150/95 mm HG. On urine dipstick, she has 1 glucose and 2+ albumin. Her blood pressure on the initial prenatal visit at 14 weeks’ gestation was 120/75 mm HG. Her maternal grandfather has adult explanation for the findin A. B. nset diabetes, Her mother and mater: other both have chronic hypertension. Which of the following is the most likely s in this patient? Preeclampsia Molar pregnancy Abruptio placenta Gestational diabetes Primary renal disease A 17 year old gitl presents with a sudden onset of abdominal pain, Physical examination reveals a tender left ovary with focal areas of calcification. Which of th D. E mass in the left adnexa. A pregnancy test is negative. An x-ray exhibits a mass lesion of the following best characterizes the ovarian Benign surface-derived tumor Malignant surface-derived tumor Follicular cyst of the ovary Benign germ cell tumor Malignant germ cell tumor D (cystic teratoma) c A 66 ye underwent menopause 17 years ago. A rectal exam reveals induration in Dougl shows clumps of malignant cells that stain posit likely old nulliparous woman presents with abdominal distention despite a poor appetite. She he rectal pouch of ie has a fluid wave in the abdomen and a left-sided pleural effusion. A thoracentesis for CA 125.Which of the following is the most diagnosis? Metastatic uterine leiomyosarcomas Metastatic endometrial cancer Metastatic ovarian cancer Metastatic cervical Metastatic stomachNote: This material is copyrighted. All rights reserved. ‘FA 28 year old woman, gravida 1, para 0, at 12 weeks’ gestation presents with painless vaginal bleeding, Her blood pressure is 160/95'mm Ha, there is 3+ proteinuria, and the uterus is large for gestational age, Which of the following is the most likely diagnosis? A. Gestational diabetes B. Placenta previa CC. Abruptio placenta D. Molar pregnaney E, Twin placenta D ‘F Place the following neoplasms of the female genital tract in decreasing incidence (morbidity) and in decreasing mortality L Cervix 2 Ovary . 3. Endometrium Morbidity Mortality A. 213 [321 B 13,2 2.3.1 c 3,2,1 213) D. 3.2.1 $12 [z. 3.21 3.21 é A 51 year old woman with a long smoking history is hospitalized for treatment of right pyelonephritis. An intravenous pyelogram shows right-sided hydronephrosis and a dilated ureter. During pelvic examination, you detect a malodorous vaginal discharge. A firm, irregular right adnexal mass extends to the pelvic side wall. The patient experiences vaginal bleeding after examination. What is the most likely diagnosis? A. Perinephric abscess due to acute pyelonephritis B, Endometriosis involving the right ovary C. Invasive cervical carcinoma D. Invasive endometriaLadenocarcinoma E. _ Invasive ovarian adenocarcinoma c + ear-old moderately obese woman presents with infertility problems. She has a long history « of oligomenorrhea. Physical exam reveals hirsutism on the face and anterior chest. Pelvic exam @ exhibits bilaterally enlarged ovaries. The following laboratory tests are available: serum LH gg increased, serum FSH low, LH/FSH ratio >3/1, serum total testosterone slightly increased, serum free testosterone increased, serum DHEA-sulfate normal, serum prolactin normal, and the serum - TSH is normal. Based on these findings, you strongly suspect that the patient as = A. bilateral androgen-secreting tumors of the ovaries ‘ B. deficiency of gonadotropin-releasing hormone C. polycystic ovarian syndrome D. adrenal Cushing's syndrome a E, a gonadotropin-secreting pituitary tumor - cNote: This material is copyrighted. All rights reserved. Endocrine: © Examples ofs 1 imulation tests hypopituitarism: Gonadotropin releasing hormone (GnRH) stimulation test A. lack ofan increase in gonadotropins over the baseline indicates an anterior pituitary disorder B. eventual rise in gonadotropins indicates a hypothalamic releasing factor disorder hypopituitarism: growth hormone (GH) deficieney- A. stimulation with sleep: (1) best test @) GH and insulin-like growth factor 1 (somatomedin) are released around 5 A @) _IGF-1 is more sensitive test B. dopa and arginine: lack of an increase in GH or somatomedins indicates an anterior pituitary or hypothalamic disorder hypopituitarism: thyrotropin releasing hormone (TRH) stimulation test A. lack of an increase in TSH indicates an anterior pituitary disorder B, eventual rise indicates a hypothalamic problem hypopituitarism: pituitary/adrenal axis A. \etyrapone test evaluates the integrity of the pituitary and adrenal axis for ACTH and cortisol: (1) metyrapone blocks 1 -hydroxylase enzyme in the adrenal cortex a. reduces synthesis of cortisol—> b. stimulates ACTH ©. proximal build-up of 11-deoxyeortisol 44? ACTH in pituitary TIT 11-deoxycortisol 11-OFfase blocked by metyrapone T1-hydroxylase 14 cortisol d. lack of an increase in ACTH and deoxycortisol indicates a hypothalamic. anterior pituitary problem €. increase in ACTH and decrease in deoxycortisol indicates an adrenal of hypocortisolism B, _ insulin tolerance test: hypoglycemia stimulates the release of both GH and ACTH hypopituitarism: TRH stimulation test for prolactin A. TRHis a potent stimulator of prolactin B. good test for Sheehan's postpartum necrosis posterior pituitary: diabetes insipidus— A. differential for polyuria: (1) central/nephrogenic DI @) due to glucosuria in diabetes mellitus @) @ rcalcemia: metastatic calcification of kidney tubules (nephrocalcinosis, dilution and concentration of urine (8) psychogenic polydipsiaNote: This material is copyrighted, All rights reserved. o B. water deprivation test for central or nephrogenic DI (2) _ ina normal person, water deprivation should: a. increase serum Na’ (POsm) to upper limit of normal b. increase UOsm due to concentration of urine (2) ina patient with DI, water deprivation will a, increase the POsm: T serum Na’ (POsm) = TBNa’/LUTBW, due to loss of free water in the urine b. decrease the UOsm due to loss of free water in the urine @) _ if intramuscular vasopressin (ADH) increases UOsm >50% from the baseline UOsm, the patient has central DI (4) _ if'intamuscular vasopressin incr patient has nephrogenic DI (8) _ in psychogenic polyuria (compulsive water drinker), water deprivation resembles anormal person primary hypocortisolism (Addison’s A. short ACTH stimulation test: GQ) does not distinguish hypopituitarism/hypothalamic cause of hypocortisolism from primary hypocortisolism (Addison’s disease) 2) cortisol remains decreased in both B. prolonged ACTH (Q) stimulation (3 days) and measurement of urine 17-hydroxycorticoids (17-OH) (2) no increase in 17-OH and increase in plasma ACTH indicates Addison's disease ) increase in 17-OH and decrease in plasma ACTH indicates a hypothalamic pituitary cause of hypocortisolism s UOsm <45% from the baseline, the isease)- Suppression tests: L majority of hormone excess conditions are due to benign adenomas~ primary endocrine gland hyperplasia or carcinoma are sometimes responsible for hormone access in general, overactive endocrine disorders cannot be suppressed~ exceptions include A. prolactinomas are suppressed with bromocriptine (dopa analogue) B. pituitary Cushing's suppressed with high dose dexamethasone oral glucose tolerance test for acromegaly lack of suppression of GH or IGF-I indie: functioning pituitary adenoma Cushing's syndrome— A. hypercortisolism: (1) patient taking corticosteroids 2) pituitary Cushing's 3) adrenal Cushing's (4) ectopic Cushing's B. dexamethasone suppression test: (1) dexamethasone is a cortisol analogue: should suppress ACTH in a normal person and reduce cortisol (2) low dose dexamethasone suppression test: no suppression of a high baseline cortisol in pituitary/adrenal/ectopic Cushing's syndrome (8) high dose dexamethasone suppression test: suppresses cortisol in pituitary Cushing's but not adrenal or ectopic Cushing's C. metyrapone test: (1) normally blocks 11-hydroxylase in adrenal cortexNote: This material is copyrighted. All rights reserved. (2) no change or increase in 11-deoxycortisol levels in pituitary Cushing’: indicates that pituitary tumor is responsive to a drop in cortisol induced by metyrapone @) nochange in plasma ACTH or 11-deoxycortisol levels in adrenal or ectopic Cushing's pheochromocytoma~ A. catecholamine excess: usually a benign adenoma in adrenal medulla B. clonidine suppression test (2) suppression tests are not usually performed @) clonidine, an a3 agonist, normally decreases efferent sympathetic outflow: does not decrease catecholamines in pheochromocytoma 6. primary aldosteronism (Con's syndrome)~ A. mineralocorticoid excess from benign adenoma of zona glomerulosa B. isotonic saline infusion: (Q)__ isotonic saline should normally suppress aldosterone release by decreasing renin release (2) _ in primary aldosteronism, there is a lack of aldosterone suppression = Hypopituitarism: 1, adult non-functioning pituitary adenoma MCC of hypopituitarism (2) MENT(AD inheritance) association: a. pituitary tumor b. parathyroid adenoma & — ZEsyndrome d. peptic ulcers @) order of succession of trophic hormone deficiency: a. gonadotropins-> b. GES © TSH> a. ACTH prolactin B, Sheehan's postpartum necrosis: (1) sudden cessation of lactation (2) hemorrhagic infarction of pituitary usually related to hypovolemic episode during delivery 3) normally, pituitary doubles in size during pregnancy 4, estrogen‘progesterone inhibits prolactin release b. delivery of placenta removes inhibition and lactation begins 2. children A. craniopharyngioma MCC of hypopituitarism B. derives from Rathke's pouch C. visual disturbances common: presses against optic chiasm D. cystic and calcified % Addison’s disease versus secondary hypocortisolism: differences are in ACTH levels and electrolytes Addison's disease (primary hypocortisolism) (1) increased ACTH with hyperpigmentation @) _mineralocorticoid deficiency from destruction of adrenal cortex: a, severe hyponatremia 179 :Note: This material is copyrighted. All rights reserved. b. hyperkalemia © metabolic acidosis d. 20 response to prolonged ACTH stimulation (3) hypoglycemia due to lack of gluconeogenic effect of cortisol B. secondary hypocortisolism: (1) decreased ACTH @) no mineralocorticoid defi (3) mild hyponatremia due to mild inappropriate ADH from lack of thyroxine and cortisol effect on inhibiting ADH (4) hypoglycemia from loss of cortisol and GH (S) adrenal response does occur to prolonged ACTH stimulation Diabetes insipidus: 1. central DI- A. hypernatrem B. causes: (1) CNS trauma with severance of pituitary st @)_ hypothalamic disease a. Hand-Schuller-Christian disease (histiocytosis X) b. sarcoidosis C. water deprivation: UOsm increases >50% with injection of ADH 2, nephrogenic DI- (increased POsm) with very low UOsm: lack of concentration of urine A. same lab findings as central DI except UOsm is <40% increased after ADH administration B. causes: (Q) drugs: b. (2) _ severe hypokalemia: damages kidney tubules so they become refractory to ADH (called vacuolar nephropath ‘Clinical signs and symptoms and laboratory abnorm: 1, gonadotropins (FSH/LED deficienc A. adult women: (@) secondary amenorrhea @) decreased libido @) diminished secondary sex characteristies B. adult men: (1) impotence (failure to sustain an erection) @) diminished secondary sex characteristics C. children (1) growth and sexual maturation retardation (2) delayed fasion of epiphyses D. laboratory Q) low FSH and LH 2) low estradiotitestosterone 2. growth hormone (GH) deficiency- A. adults: no effect on growth B. children: (dwarfism ies of hypopituitarism: 180Note: This material is copyrighted. All rights reserved. (2) delayed fusion of epiphyses C. laboratory (1) low GH and IGF-1 a. insulin-like growth factor (IGF-1) is synthesized in the live b, GH stimulates IGF @) hypoglycemia: GH is a gluconeogenic hormot (3) _ no increase in GH or IGF with oral glucose tolera 3. thyroid stimulating hormone (TSH) deficiency AL adult (1) dry, brittle hair (2) cold intolerance @) weight gain (4) periorbital and facial puffiness () impaired memory (6) delayed Achilles reflex recovery (7) muscle weakness (proximal muscle myopathy) (8) _ yellowish skin: decreased conversion of f-carotene to retinoic acid in intestinal cells (9) constipation B. child: (1) mental retardation: brain requires thyroxine for maturation by 2 ys of age (2) increased weight but decreased height C. laboratory @ lowT (2) low TSH: key distinction from primary hypothyroidism (3) increased CK (myopathy) (4) increased LDL and cholesterol: decreased synthesis of LDL receptors (5) _ mild hyponatremia: mild inappropriate ADH, owing to the normal inhibitory effect of T; on ADH 4. adrenocorticotropic hormone (ACTH) deficieney— A. clinical (1) fatigue/weakness @) postural hypotension B. laboratory (1) low ACTH: distinguishes it from Addison’s disease @)_ low cortisol @) fasting hypoglycemia: cortisol is gluconeogenic (4) mild hyponatremia: mild inappropriate ADH owing to the inhibitory cortisol on ADH (S) eventual increase in 17-OH with prolonged ACTH stimulation test (6) eosinophilia: due to the decrease in cortisol prolactin deficieney— sudden cessation of necrosis 6. antidiuretic hormone (ADH) defi lactation in a woman with Sheehan's postpartum ey see previous discussion Pituitary apoplexy: refers to hemorthage/infarction of pituitary adenoma leading 10 hypopituitarism Nelson's syndrome: refers to enlargement of a preexisting pituitary adenoma secreting ACTH after both adrenal glands are removedNote: This jaterial is copyrighted. All rights reserved. Afriean pygmies 1. GH levels normal 2. low IG! Laron dwarfism: 1. end-organ unresponsiveness to GH effect normal to increased GH 3. low IGF- GH excess: 1. GH funetions~ A. increase amino acid uptake in muscle B, gluconeogenesis C. stimulates synthesis and release of IGF-I in liver 2. IGF-1 funetions~ A. linear and lateral bone growl B. chondrogenesis C. growth of soft tissue D. _ best screening test for hyper- or hypofunction states 3. gigamtism— occurs in children where epiphyses have not fused 4. acromegaly A. occurs in adults B. no linear growth in bones but lateral growth due to IGF-1 (1) jaw widens: gaps in teeth @) hand/feet enlarged (3) _ enlarged frontal sinuses increases hat size (4) _visceromegaly (5) cardiomyopathy: heart failure MC COD (© hyperglycemia @ — Galactorrhea/vaginal bleeding in newborn girl: influence of maternal estrogen © Prolactinoma LMC pita 2. clinical A. secondary amenorrhea: prolactin inhibits GnRH B. — galactorthea ‘ary tumor C. impotence in males: no galactorthea 3. other causes of prolactinemia~ A. drugs (1) birth control pills @) hydralazine @) Fe blockers B. primary hypothyroidism (1) low 7; increases TSH and TRH @) TRH isa stimulator of prolactin 4. Rxof prolactinoma~ ‘A. bromocriptine in most cases: dopamine analogue (inhibits prolactin) B. f sella enlarged 182Note: This material is copyrighted. All rights reserved. Thyroid function studies: 1. see schematics 2. measured total serum T, (and T))~ A. reflects hormone that is: (1) _ bound to thyroid binding globulin (TBG) @) free, or metabolically active B, changes in either the free hormone level (hypo- or hyperthyroidism) or TBG concentration alter the total serum T, without affecting free T. level (1) estrogen increases synthesis of TBG a. increased total Ty b. normal TSH androgens decrease synthesis of TBG: a. decreased total b. normal TSH 3. resin Ts uptake (RTU)- A. reflects TBG concentration: reported as a percentage (25 B, preset amount of radioactive Ts is added to a sample of patient serum (1) radioactive T; binds to all available binding sites on TBG @) leftover is bound to a resin and measured @) _RTU is converted into a T; binding ratio (T; BR), by dividing measured RTU by reference serum mean RTU, which is 30%: e.g, patient RTU 30%, T, BR = 30/30=1 (4) RTUand T, BR are low and high in hypo- and hyperthyroidism, respectv a. in hypothyroidism, more binding sites available on TBG, hence less is left over b. in hyperthyroidism, less binding sites available on TBG ( T,), hence more is left over (8) RTU and T; BR are both increased when TBG is decreased: less binding sites available on TBG, hence more is left over (© RTU and T, BR are both decreased when TBG is increased: more binding sites available on TBG, hence less is left over 4, free Ty index (FT-1)- calculated free T; hormone concentration calculated by multiplying the total serum T, by the T, BR Lis low and high in hypo- and hyperthyroidism, respectively is normal when the TBG concentration is high: increased total T, x decreased jormal FT 1 E, FT rl is normal when the TBG concentration is low: decreased total T, x in T,BR = normal FT, serum TSH ‘A. TSH has a negative feedback relationship with circulating Ty and Ts B, _TSHis single best test for Dx of primary hypothyroidism and hyperthyroidism (1) primary hypothyroidism: TSH increased @) secondary hypothyroidism: TSH decreased (3) hyperthyroidism: TSH decreased turated with A B. c. D. C. TSH is always normal with altera are normal ins in TRG concentration since free T, levelsTBG BG TRG TBC ‘TBG (Estrogen Rx) ‘Thyroid gland Free Total Ty =15 TSH = normal TSH = normal Primary Hypothyroidism Hyperthyroidism TBG (Anabolic steroids) TBG TBG TBC TB eee eee FreeTs=6 Total T= 9 TSH = high ‘TSH = normalNote: This material is copyrighted. All rights reserved. 6. radioactive Is; uptake AL lis: uptake is used to: (1) detect nodules (2) _ provide an index of thyroid activity B. thyroid hormone is tyrosine with iodides attached to it (1) tue hyperfunetionng ofthe gland (eg, Grave’ disease) inereases In uptake (2) _hypofunetioning land has a decreased yy uptake C. hot nodules: (Q) functionally active e @) preferentially take upp: 1 suppressed D. cold nodules: (Q) inactive (2) donot take up the ly (lear space): normally functioning gland takes up the ny nainder of the gland is not visualized, since it is Thyroglossal duct eyst: midline cystic mass Branchial cleft cyst: cyst in anterolateral neck Thyroiditis 1, acute thyroiditis A- infection caused by Staphylococcus aureus, Streptococcus pneumoniae or Streptococeus pyogenes B. _signs/lab of thyrotoxicosis but I, uptake is decreased 2. subacute granulomatous thyroiditis (de Quervain thyroi A. MCC of painful thyroid gland B. follows a viral infection (e.g., coxsackievirus) C. granulomatous inflammation with multinucleated giant cells 3. Hashimoto's thyroiditis ‘A. autoimmune thyroiditis B. pathog (MCC hypothyroidism 2) _amtibodies against“peroxidase (anti-microsomal antibodies) and thyroglobulin (anti-thyroglobulin antibodies) @) cytotoxic T cell damage (4) _ inhibitory autoantibodies against TSH receptor that prevent CC. gross/micro: (1) enlarged gland with heavy lymphocytic infiltrate, germinal follicles (2) predisposes to primary malignant lymphoma of thyroid thyroiditis intense fibrous tissue replacement of the gland tis) jormone synthesis 4. Reid Thyroid hormone exces 1. hyperthyroidism~ A. excess synthesis of hormone: e.g., Graves’ disease, toxic nodular goiter 2. thyrotoxicosis: ‘A describes the end-organ effects excess thyroid hormone, regardless of the etiology e.g. thyroiditis, taking excess hormoneNote: This material is copyrighted, All rights reserved. F Graves’ disease 1. MCC of hyperthyroidism and thyrotoxicosis A. female dominant autoimmune disease B. due to synthesis of an autoantibody against the TSH receptor called thyroid stimulating antibody (TSI): type II hypersensitivity 2. gross/micro~ ‘A. symmetrical, nontender thyromegaly B. _ microscopic features of overactivity (1) scant colloid 2) _ papillary infolding of the glands lab features unique to Graves? disease A. infiltrative ophthalmopathy often associated with exophthalmos B. pretibial myxedema: excess glycosaminoglyean deposition C. _antimicrosomal and thyroglobulin antibodies present D. other features of thyrotoxicosis commen to all types: (1) sinus tachycardia 2) atrial fibrillation: always order TSH when this arrhythmia is present 3) _ systolic hypertension (4) anxiety (5) weight loss (6) heat intolerance (7) muscle weakness/increased reflexes activity (8) diarrhea (9) low cholesterol: increased synthesis of LDL receptors (10) hypercalcemia: increased bone tumover 4. laboratory profile- see table 5. Rx of Graves disease A. Brblockers: block adrenergic effect of thyroid hormones on target organs B, drugs that decrease hormone synthesis: propylthiouracil only one that can be used in C. if above does not correct in ~Lyr, radiation ablation is used ‘Toxic nodular goiter (Plummer’s disease): develops in the setting of a multinodular goiter Hypothyroidism: 1. reduction in secretion of thyroid hormone— ‘A. primary disease: MCC is Hashimoto's thyroiditis B. _pituitary/ hypothalamus dysfunction eal A. muscle weakness: (1) MC symptom 2) due to myopathy: increased serum creatine kinase coarse skin periorbital puffiness/pretibial myxedema: due to deposition of glycosaminoglycans brittle hair constipation cold intolerance weight gain delayed recovery of the Achilles reflex FOmmSopNote: This material is copyrighted, All rights reserved. I. diastolic hypertension J. yellow skin: increase in B-carotenes from decreased conversion into retinoic acid 3. Iab- A. see table B. _ hypercholesterolemia 4 Re A. levothyroxine B. follow patient with TSH levels until they become normal Goiter: 1, enlargement of thyroid gland 2, due to an absolute or relative deficiency of thyroid hormone~ most often associated with iodide deficiency recurrent episodes of TSH stimulation (hyperplasia) and involution (colloid stage) A. causes gland to enlarge: (1) initially diffuse enlargement 2) eventually multinodular B. hemorrhage into cyst is MCC of sudden gland enlargement ‘© Solitary thyroid nodule (usually cold nodule) 1. adult woman- A. 60% due to cysts in goiter B. % benign follicular adenoma C. 15% malignant 2. adult man/ehild— usually cancer 3. Hx of radiation to head and neck cancer in majority of cases Follicular adenoma: MC benign thyroid tumor Papillary adenocarcinoma: 1, MC thyroid cancer in adults and children 2. multifocal tumors A. papillary fronds lined by empty appearing nuclei (Orphan Annie nuclei) B. _psammoma bodies C. lymphatic invasion with focal cervical lymph node involvement is the rule 3. exeellent prognosis Follicular carcinoma: 1. gross/micro— A. well circumscribed encapsulated tumor with capsular and/or blood vessel invasion B. invasive cancer without a capsule C. blood vessel invasion without lymph node metastasis is the rule D. more likely to have distant spread than papillary cancer: () lungs @) bone 2. commonly takes up Is, e Medullary carcinomas: 1. sporadic (80%) 2. familial (20%)~ ‘A. autosomal dominant MEN Ila and Ilb syndromes: (1) MEN Tia syndrome: 186Note: This material is copyrighted. All rights reserved. a. medullary carcinoma b. primary hyperparathyroidism pheochromocytoma 2) MEN Mb variant: a. medullary carcinoma b, mucosal neuromas involving the lips and to ¢. pheochromocytoma d.— Marfanoid habitus 3. derive from parafollicular C cells: A. synthesize calcitonin B. calcitonin is a tumor marker for the can C. calcitonin is changed into amyloid in the tumor ‘Summary of thyroid profile and Is; uptake in thyroid disorders: bolded areas are short cuts to making the Dx Disorder Total Serum | RTU/T,BR a Tox T% Grave's | Tnereased_|Tnereased | Inereased | Suppressed | Increased Factitious thyrotoxicosis Increased | Increased | Increased _| Suppressed _| Decreased [Thyroiditis (acute, subacute) [Tmereased | Increased | Increased _| Suppressed | Decreased Primary hypothyroidism Decreased | Decreased | Decreased | Increased | Decreased (Hashimoto) _ Secondary hypothyroidism | Decreased | Decreased | Decreased | Decreased | Decreased } (hypopituitarism/ | hypothalanni | Increased TBG Tnereased | Decreased | Nommal | Normal | Normal (increased estrogen) Decreased TBG Decreased | Tncreased | Normal | Normal | Normal (increased androgens) RTU = resin T; uptake, FTI = free Ty index, T,Bl hormone, | 131 = radioactive iodine 1 131 uptake, TBG = T4 binding ratio, TSH = thyroid stimulating hyroid binding globulin = Total serum calcium (see schematics): 1. measures calcium bound (40% albumin, 13% phosphate, citrates) + free (47%, ionized fraction, metabolically active fraction) 2. hypoalbuminemia— A. decreases total calcium without altering the free ionized level B. correct for hypoalbuminemia with formula: corrected calcium = (serum serum albumin) +4 3. alkalosis— ‘A. increases negative charges on albumin B. binds more calcium: e.g., 60% bound vs normal of 40% C. lowers ionized calcium level without altering the total caleium D. clinical evidence of tetany jeal fim A. tetany B. clinical eium ~ igs with hypocalcemia due to decreased ionized levels (2) carpopedal spasm: Trousseau’s sign with blood pressure cuff, thumb flexes into palmNote: This material is copyrighted. All rights reserved. ¢ Pri (2) Chvostek’s sign: facial nwitch after tapping the facial nerve ary hyperparathyroidism (HPTH): MCC hypercalcemia in the ambulatory population MC due to a benign parathyroid adenoma- composed of sheets of chief cells with no intervening f PTH functions- A. increase reabsorption of calcium in kidneys: Na'/CI pump in early distal tubule in cortex decrease bicarbonate reclamation in proximal tubule: proximal renal tubular acidosis decreases phosphate reabsorption in proximal tubule increase synthesis of I-a-hydroxylase enzyme in proximal tubule for second hydroxylation of vitamin D: vitamin D reabsorbs calcium and phosphorous from the all bowel E. ntains ionized calcium levels: (1) receptor on the osteoblast Q) PTH causes release of IL-1 (osteoclast activating factor) (3) IL-1 activates the osteoclast to break bone down and maintain ionized calcium levels (4) estrogen has inhibitory effect on IL-1 in women (8) _ testosterone has inhibitory effect on IL-1 in men clinical A. most cases are asymptomatic and are discovered incidentally B. renal stones MC symptomatic presentation: (1) due to hypercaleiuria @) more calcium is released from bone than is reabsorbed back by PTH in the kidneys C. peptic ulcer disease: hypercalcemia stimulates gastrin release D. acute pancreatitis: hypercalcemia activates phospholipase in pancreas constipation polyuria (1) metastatic caléification of kidney tubules @) called nephrocalcinosis G. short QT interval H. diastolic hypertension L bone disease (1) osteitis fibrosa cystica @) cystic lesion with hemorrhage (brown tumor) @) usually involves the jaw Inb: A. elevated serum PTH B. hypercalcemia C. _hypophosphatemia D. normal anion gap metabolic acidosis: loss of bicarbonate in the urine is counterbalanced by an equal gain in chloride E. increase in serum alkaline phosphatase: bone formation counteracts bone resorption ". _ hypercalciuria/hyperphosphaturia G. _chloride/phosphate ratio >33 188Note: T q is material is copyrighted. All rights reserved. Malignancy-induced hypercalcemia: pathogenesis includes 1, bone metastasis with activation of osteoclasts: A. McC B. _ secretion of interleukin-I/prostaglandins by cancer cells 2. _ ectopic secretion of a PTH-like peptide: A. primary squamous cell ear B. renal adenocarcinoma C. breast cancer D. _ PTH-like peptide increases calcium reabsorption in the kidneys (hypercalcemia) and decreases phosphorous reabsorption (hypophosphatemia) 3. hypercalcemia suppresses the patient’s PTH as it does with all the other causes of hypercalcemia not related to primary HPTH Other 1. sarcoidosis 2. thiarides 3. min D toxicity 4. multiple myeloma Secondary HPTH 1 erplasia of all of the parathyroid glands as compensation for hypocalcemia 2. MCCis hypovitaminosis D from chronic renal failure ‘Tertiary HPTH. 1. hypercalcemia that has developed from secondary HPTH 2. usually associated with chronic renal failure inoma of the lung uses of hypercalcemia’ Primary hypoparathyroidism: 1. hypofunction of the parathyroid glands leading to hypo 2. causes- A. previous thyroid surgery MCC B. autoimmune hypoparathyroidism: usually associated with polyendocrine deficiency syndromes (multiple endocrine gland deficiencies) C. DiGeorge syndrome 3. clinical A. reduction in total and ionized calcium Jevel results in tetany’ (1) circumoral paresthesias (numbness and tingling) @) positive Chvostek’s sign (3) _carpopedal spasm due to muscle spasms (Trousseau's sign) when taking a blood pressure B. _caleification of basal ganglia 4. Iab- A. lowPTH B. hypocalcemia CC. hyperphosphatemia D. prolonged QT interval Pseudohypoparathyroidism: 1. SXD inherited disease characterized by end-organ resistance to PTH. A. type I disease: Q) defect proximal to the generation of CAMP 2) receptor problem 189Note: This material is copyrighted. AN rights reserved. 3 B. c acute pane! (8) _no cAMP response to infused PTH type Il disease (1) defect distal to the generation of cAMP 2) post-receptor problem @)_ cAMP response to infused PTH ; mild mental retarda A. ion B, short 4th and Sth metacarpals (USMLE) Jab ‘A. hypocalcemia B. _hyperphosphatemia CC. normal to high PTH Other causes hypocalcemia hypomagnesemia A. magnesium is a cofactor for adenylate cyclase, which generates cAMP (required for PTH activation), hence inhibiting PTH activity inhibits synthesis and release of PTH causes hypomagnesemia: (1) alcoholic @) diarrhea @) diuretics (4) aminoglycosides () cisplatin itis calcium used up in enzymatic fat necrosis hypoalbuminemia~ MCC of hypocalcemia iGeorge syndrome- see Immunopathology notes failure of 3rd and 4th pharyngeal pouches to develop hypoparathyroidism truncus arteriosis: cyanotic CHD povitaminosis D. B. C. absent thymus: T cell deficiency D. hyp Poop chronic renal failure: MCC malabsorption cirrhosis lack of sunlight type I vitamin D-dependent rickets: (1) decreased la-hydroxylase @) hypocalcemia and hypophosphatemia @) high PTH (4) normal 25(0H)D; ©) low 1,25(08),D, type II vitamin D-dependent rickets: (1) absent vitamin D receptor (2) _ hypocalcemia and hypophosphatemia 3) high PTH (4) normal 25(OH)D; (©) high 1,25(0H),D, 190OF = ,,8 pazuoy uqumngry ss eds Bequoy 4 Tato ri ST= 8D IGOL £= 8D pazquoy 9= 8D [eo], ; ec0c5e eecce eco eco eccc6e unungy upungqiy 1 uyungty (09 TVWON v AWTVOdAH = NOLLIGN VINGOTVONIEAH WSIMIOWAHLLVUVaOdAH QLVIS OLLOTVNTY —-VIWANINLNote: This material is copyrighted. All rights reserved, 6. hypoparathyroidism Summary of calcium, phosphorous and PTH related disorders: der Caleium Phosphorous [PTH [Hyperealcemia [Primary HPTH Increased | Decreased [Increased | Malignancy (PTF-like peptide) | Increased [Decreased | Decreased [Hlypocalcemia : Primary Hypoparathyroidism Decreased Tnereased Decreased | Pseudohypoparathyroidism Decreased Increased Normal to. Increased [Seconda HPTH (Malabsorption) Decreased | Decreased Increased | Secondary HPTH (Renal Failure) | Decreased Increased | Increased Hypoalbuminemia Decreased normal ionized | Normal Normal calcium alkalosis Normal decreased fonized | Normal Tnereased calcium Lo HPTH = hyperparathyroidism ® Graphic representation of PTH/caleium disorders: PTH Serum calcium 1. group A ‘A. low calcium and low PTH B. _ primary hypoparathyroidism C. DiGeorge syndrome D. hypomagnesemia 2. group B- A. low-caleium and high PTH B. _ secondary hyperparathyroidism: (1) chronic renal failure leading to hypovitaminosis D MCC @) malabsorption leading to hypovitaminosis D group C- A. high calcium and high PTH B, _ primary hyperparathyroidism 4. group D- ‘A. high calcium and low PTH B. all other causes of hypercalcemia: Q) malignancy induced @) sarcoidosis 191is copyrighted. All rights reserved. ® Adrenal gland: 1. zona glomerulosa produces aldosterone A B. activation of the renin-angiotensin-aldosterone system enzymes present. (2) 2I-hydroxylase @) LU Lhydroxylase @) 18+hydroxylase a, activated by angiotensin TI b. _ deoxycorticosterone converted into aldosterone enzyme not present in other zones 2. zona fasciculata produces glucocorticoids- A B. Ci deoxycortisol cortisol enzymes present: (1) 17-hydroxylase: not present in zona glomerulosa @) 21-hydroxylase (3) 1-hydroxylase 3. zona reticularis produces sex hormones- A. estrogen: (1) aromatization of androstenedione @) aromatization of testosterone B. androgens: (1) 17-ketosteroids DHEA and androstenedione Q) testosterone C. enzymes present: same as fasciculata 4. urine for 17-hydroxycorticoids (17-OF)- metabolites of 11-deoxycortisol (compound S| and cortisol 5. urine for 17-ketosteroids (17-KS)- A. dehydroandrosterone (DHEA) B, androstenedione 6. adrenal medulla A. neural crest origin B. synthesizes the catecholamines epinephrine (EPI) and norepinephrine (NOR) €. EPI and NOR: metabolized into biologically inactive metabolites by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT), respectively, and into the urinary metabolites metanephrine and vanillylmandelic acid (VMA), respectively D. _ metabolite of dopamine is homovanillic acid (HVA) = Cushing's syndrome: 1. causes ‘A. long-term glucocorticoid therapy MCC: zona fasciculata and reticularis atrophied B. pituitary Cushing's: sometimes called Cushing’s disease (1) tumor produces excess ACTH @) hyperplasia of zona fasciculata and reticularis C. adrenal Cushing's (2) adenoma produces exeess cortisol (2) suppressed ACTH (3) adrenal tissue surrounding the adenoma is atrophic and contralateral zona fasciculata/reticularis is atrophied 192auosasorsaospsyia, sprosnioasxospsy aseyonpas—n$ (o1Pe:)534-< 619) auds0}s0)s0, dseyvmrore ‘asekxoaphy-17 ssersxoups-1z | aseyompasoprxo—> I | (omnoueudaxd) wowospuy €— ouose}so¥osdéxoupsyy-z) (1:5) auosajsodoag asepdxoupsy-2y 4 aswsswosyastuadoapsyap plosaysxospiy-ie p> (69) suossrsospaerdsoapéyaq <¢—— auojousudoadssoupsyy-z <———____ suoyousuaaug aseSxouphy-zp A asejousop p> aurkzua aBeaeaq9 wyeqo ap} J043)89[049 —p (9) tosa1s9}045,Note: This material is copyrighted, All rights reserved. S D. ectopic Cushing’s: (1) cancer ectopically secreting ACTH @) _ zona fasciculata/reticularis exhibit hyperplasia 2. pituitary Cushing's A. MC type: also called Cushing's disease B. benign adenoma secreting ACTH 3. adrenal Cushing's— A. excess production of cortisol secondary to neoplasia (adenoma, carcinoma) or hyperplasia) B. ACTH is suppressed 4, ectopic Cushing’s- A. small cell carcinoma of lung MCC B. highest ACTH levels (hyperpigmentation) clinical- A. weight gain: (1) fat deposition in face (“moon faci @) upper back (“buffalo hump”) (3) _ trunk (truncal obesity) with sparing of the extremities (4) due to hyperinsalinism B. diastolic hypertension: due to increased synthesis of weak mineralocorticoids C. glucose intolerance: due to increased gluconeogenesis D. hirsutism: due to increased 17-KS E. purple abdominal stria: (1) ruptured blood vessels in stretch marks @) cortisol weakens collagen F. osteoporosis, G. thin extremities: due to excess cortisol breaking down muscle to get alanine for aluconeogenesis 6. screening tests A. plasma ACTH B. _ low dose dexamethasone (cortisol analogue) test: cannot suppress cortisol C. 24 hour urine for free cortisol: (1) best screen (2) measures excess unbound cortisol 7. confirmatory test A. high dose dexamethasone test: suppresses cortisol in pituitary Cushing's but not the other typesNote: This material is copyrighted, All rights reserved. Labi studies in Cushing's Syndrome _ [Laboratory Test Pituitary Cushing's Adrenal Cushing's | Eetopie Cushing { Serum Cortisol Increased [increased Urine for free cortisol | Increased Increased Increased Low dose Cortisol not suppressed | Cortisol not suppressed | Cortisol not suppressed dexamethasone High Cortisol suppressed | Cortisol not suppressed | Cortisol not suppressed dexamethasone 7 Plasma ACTH. | “Normal” to Increased | Low Markedly Increased Metyrapone Deoxycortisol normal _| Deoxycortisol not Deoxycortisol not to increased tumor is_| inereased increased not autonomous, hence itcan increase ACTH synthesis in response to ____| hypocortisolism ‘Normal: a plasma ACTH in the normal range cortisol. Primary aldosteronism (Conn's syndrome): see Fluids and Hemodynamics notes ® Pheochromocytoma: 1. associations A. neurofibromatosis B, MEN Ila and Ilb, C. _ von Hippel Lindau disease clinical A. key features: (1) unilateral (2) benign adenomas (3) majority arise in adrenal medulla B. hypertension C. episodic palpitations D. drenching sweats E, excessive anxiety F. headache 3. screening tests A. 24 hour urine for vanillylmandelic acid (VMA) and metanephrines (best overall screen) B. _ neutrophilic leukocytosis: decreased adhesion molecule synthesis by catecholamines CC. hyperglycemia: (1) alycogenotysis @) gluconeogenesis 4. Rx by surgery A. phenoxybenzamine an q-adrenergic blocker used preo hypertension B. _ -blockers to control tachycardia afier hypertension controlled C. phentolamine, an o-blocker used in hypertensive crisis tively to control 194Note: This material is copyrighted. All rights reserved. = Neuroblastoma: 1, malignant tumor of neural erest origin— A. MC site of origin is adrenal medulla B. posterior mediastinum 2. deletion or rearrangement of the short arm of chromosome 1 leading to amplification of the N-mye oncogene 3. clinical A. “small cell” tumor composed of neuroblasts and Homer-Wright rosettes, B. neuroblasts are $100 antigen positive: contain dense core neurosecretory granules C. palpable abdominal mass with abdominal distention D. diastolic hypertension E. metastasis: bone MC site 4. Iab- elevated urine VMA, metanephrines, HVA 5. prognosis— A. age of the patient isthe single most important factor determining prognosis: B. cure rate is 85-90% under | year of age C. 15-40% cure rate in older children ‘Adrenal hypofunction 1. causes— autoimmune destruction MCC chronic insufficiency (Addison's disease) abrupt withdrawal of corticosteroids: MCC of acute adrenal insufficiency miliary TB: MCC worldwide disseminated meningococcemia: (1) Waterhouse-Friderichsen syndrome (2) DIC with bilateral adrenal hemorrhage E, _ congenital adrenal hyperplasia: alias adrenogenital syndrome (see Genetics notes) pope 2. I~ A. weakness B. _ hypotension: salt loss C. diffuse hyperpigmentation: increase in plasma ACTH 3. lab. A. no detectable increase in urine 17-OH in both a short and prolonged ACTH stimulation test B. elevated plasma ACTH C. hyponatremia: hypertonic loss of salt inthe urine D. hyperkalemia: no exchange of sodium for potassium or hydrogen ions for p owing to hypoaldosteronism E. _ fasting hypoglycemia: loss of gluconeogenic activity of cortisol F. normal anion gap metabolic acidosis: retain H’ ions owing to loss of aldosterone its normal maintenance of the proto/K" ATPase pump in the collecting tubules G. eosinophilia: loss of the cortisol effect on eosinophils F Jstet cell tumors: 1. insulinoma— A. benign tumor arising from the B islet cells that produces fasting hypoglycemia B. 80% have MEN I syndrome C. MC islet cell tumor (70%) (1) secrete excess insulin and C-peptides 195Note: This material is copyrighted. All rights reserved. 2) _ fasting hypoglycemia: a. insulin inhibits gluconeogenesis b. prolonged fast isthe best test D. clinical (1) neuroglycopenia (brain without glucose) from fasting hypoglycemia (2) forgetfulness (3) mental status abnormalities E. laboratory (2) hypoglycemia in the presence of an increased insulin and C-p 2) C-peptide is the best test for endogenous insulin release factitious hypoglycemia from injection of insulin (1) _ increased serum insulin and hypoglycemia 2) decreased C-peptide: suppression of endogenous insulin release by hypoglycemia gastrinoma (Zollinger-Ellison Syndrome) A. malignant islet cell tumor arising from G cells in pancreas MC site: excess of gastrin leads to hyperacidity and peptic ulcer disease duodenum second MC location association with MEN I syndrome clinical (2) single ulcers in the usual locations for peptic ulcers in most cases 2) multiple ulcers can also occur 3) suspect ZE if any ulcer is in an unusual site (4) abdominal pain from PUD (5) diarrhea: malabsorption, since the enzymes cannot work in an acid pH E, laboratory. (1) _ basal acid output (BAO) is best screening test a. markedly increased BAO b, maximal acid output (MAO) also increased and at its maximum 2) BAO/MAO ratio > 0.60 @) intravenous secretin test is confirmatory: see paradoxical increase in gastrin (4) serum gastrin levels usually >600 pg/ml (8) _ other causes of hypergastrinemia: Por a, Hy blockers (decreased acid, increases gastrin) b, atrophic gastritis involving the body and fundus (decreased acid, increases gastrin) pyloric obstruction (antral distention is a potent stimulus for gastrin) glucagonoma- A. malignant tumor of islet cells (a cells) with excess secretion of glucagon B. clinical: (1) diabetes mellitus (glucagon is gluconeogenic) @) characteristic rash called necrolytic migratory erythema somatostatinoma— A. malignant tumor of islet cells (6 cells) secreting excess somatostatin B. clinical: (1) achlorhydria: inhibits gastrin (2) cholelithiasis: inhibits cholecystokinin G) diabetes mellitus: inhibits gastric inh insulin release FY Peptide, which normally stimulates 196Note: This material is copyrighted. All rights reserved. (4) _ steatorrhea: inhibits secretin and cholecystokinin \ViPoma or pancreatic cholera or Verner Morrison syndrom A. — malignant tumor of islets with excessive secretion of vasoactive intestinal peptide B. clinical: (1) severe secretory diarhea: VIP acts by stimulating cAMP similar to toxin in cholera and toxigenic E. coli @) hypokalemia and normal gap metabolic acidosis, @) achlorhydria mary of type I and type IT diabetes mellitus (DM): prevalence type 15-10% type 11 90-95% type [<20 years (80%) type Il >30 years of age y habitus— type [ usually thin type II majority are obese ly Hx— type I family Hx uncommon: ~$0% concordance rate with identical twins type II family Hx is common: (1) multifactorial inheritance 2) ~90% concordance rate with identical twins. G) _ increased in native Americans and African Americans pathogenesis— ‘A. type I insulin lack: (1) _ presence of HLA-DR3 and -DR4 (90-95%): a. Brislet cell destruction by viruses: coxsackie B virus, mumps, EBV rubella, rubeola 1b. _Bsislet cell destruction by autoimmune disease: cytotoxic T cells producing “insulitis” B-islet cell destruction by environmental factors: streptozotocin (drug used in treating malignant islet cell tumors) alloxan pentamidine children exposed to cow’s milk (antibodies against bovine albumin cross-react against the islet cells) (2) _ pancreas is devoid of f cells (3) _ islet cell antibodies in 80% type Il has no HLA relationshi (1) relative insulin deficiency: ‘4, not enough insulin to handle glucose load b. peripheral tissue insulin resistance secondary to a receptor deficiency: ‘© direct relationship with obesity + more fat causes down-regulation of insulin recep postreceptor defects: * tyrosine kinase abnormalitiesNote: This material is copyrighted. All rights reserved. * problems with translocation of GLUT-4 receptors to facilitate glucose absorption 2) Becells are fibrosed and often contain amyloid 6. initial symptoms. A. typeI rapid onset of polydipsia, polyuria, weight loss B. _ type Il insidious onset, symptomatic or asymptomatic ketoacidosis A. typeI may occur owing to insulin lack B. type Il has no ketoacidosis: (1) susceptible to hyperosmolar nonketotic coma: @) enough insulin to prevent ketosis but not hyperglycemia (3) _ increased anion gap from lactic not ketoacidosis 8. treatment ‘A. type I requires insulin B. type Il requires: diet a. losing weight most important Rx b. lose adipose causes upregulation of insulin receptors @) oral glucose lowering agents. @) _ insulin necessary in some cases @ Pathology of DM: 1. pathogenesis A. nonenzymatic glycosylation (NEG): (1) glucose combines with amino groups in proteins (e.g., glycosylated Hb AIC) @) forms advanced glycosylation products (AGE) that alter vessel permeability and increase atherogenesis (3) _ hyaline arteriolosclerosis: a. main cause of microvascular disease in DM b. diabetic nephropathy (4) macrovascular disease: a. coronary artery disease b. peripheral vascular disease ©. cerebrovascular disease B. osmotic damage: (1) conversion of glucose into sorbitol and fructose by aldose reductase and sorbitol dehydrogenase, respectively (2) draw water into tissue leading to permanent damage (3) _ peripheral neuropathy due to destruction of Schwann cells (8) cataracts (5) _ microaneurysms in diabetic retinopathy: damage to pericytes weakens the vessel wall duration and severity of disease- A. key factors determining organ damage B. tight control of glucose reduces the onset and severity of complications related to retinopathy, neuropathy and nephropathy in descending order diabetic ketoacidosis (DKA)- see schematics A. complication of type I DM 198Note: This material is copyrighted, All rights reserved, B. pathogenesis of hyperglycemia: (1) reduced uptake of glucose by adipose and muscle @) increase in glycogenolysis due to glucagon and counterregulatory hormones (3) _ increase in gluconeogenesis: 2. primarily a glucagon effect b. most important factor pathogenesis of ketone bodies: (1) _ increased lipolysis in adipose: a. glucagon enhances hormone sensitive lipase-> b. increased release of fatty acids and glycerol—> increased amount of fatty acids for B-oxidation> increa dation of fatty acids leading to an excess of acetyl CoA» converted into acetoacetate and BHB: AcAc also forms acetone giving fruity odor to breath severe volume depletion: due to osmotic diuresis and loss of salt in hypotonic proportions dilutional hyponatremia: osmotic effect of hyperglycemia draws water into the E from the ICF potassium and phosphate ion loss in the urine: osmotic diuresis pathogenesis of hyperlipidemia: reduced capillary lipoprotein lipase degradation of chylomicrons and VLDL fate of glycerol from lipolysis: (J) converted in the liver to glycerol 3 phosphate: liver is the only organ that can andle glycerol since it has glycerol kinase @) glycerol 3P converted into dihydroxyacetone phosphate (3) DHAP is used as a substrate for gluconeogenesis hyperosmolar non-ketotic coma (HNKC)~ A B. primarily seen in type IDM: presence of enough insulin to prevent ketogenesis but not hyperglycemia accelerated atherosclerosis A B. c D. ischemic injury to the extremities: DM is MCC non-traumatic amputation of limbs increased incidence of abdominal aortic aneurysms acute myocardial infarction: MC COD. atherosclerotic strokes diabetic nephropathy— see renal notes retinopathy~ A. B, C DM is the MCC of blindness in United States microaneurysms rupture neovascularization peripheral neuropathy— A B, DMis the MCC of distal symmetrical polyneuropathy in United States peripheral neuropathy is the MCC of pressure ulcers on bottom of feet autonomic neuropathy— A B. ie cardiac arrhythmias gastroparesis impotence mucormycosis of the frontal sinuses leading to frontal lobe brain abscesses malignant external otitis from Pseudomonas aeruginosaSUMMARY OF INSULIN ACTIVITY GLYCOGENESIS/FATTY ACID SYNTHESIS Glucose HMP shunt- DNA Glucose 6-PO, Glycogen synthesis v (glycogen synthase) DHAP > Glycerol 3-PO, > VLDL (liver) y Pyruvate <—____ Malate malate dehydrogenase Pyruvate OAA Acetyl CoA citrtg syythase Citrate OAA Citrate lyase “Acetyl CoA —> Malonyl CoA ~-> Fatty acids inhibits B-oxidation transferase (mitochondria) Citrat Carnitine acy!SUMMARY OF INSULIN ACTIVITY « ST NELIN ACTIVITY LIPIDS Chylomicrons VLDL ‘apillary lipoprotein lipase, (insulin enhances) - Glycerol + Fatty acids fiver glycerol kinase 4, Glycerol 3-PO, VLDL (stored in liver) ADIPOSE | Glucose +> Glucose 6-PO, > Glycerol 3-PO,—» TG (insulin +) a Hormone sensitive lipase (insulin inhibits)DIABETIC KETOACIDOSIS HYPERGLYCEMIA Muscle Adipose TG Glycogenolysis v (+ gluca/eat) = Alanine hormone|sensitive lipase (+ glucagon/catecholamines) transaminase =i Glycerol + Fatty acids Pyruvate liver glycdrol kinase Glycerol 3-PO, v DHAP GLUCONEOGENESIS HYPERGLYCEMIADIABETIC _ KETOACIDO: Ss LE ME TOACIDOSIS KETOGENESIS Adipose TG hormone sensitive lipase (+ glucagon/eatecholamines) Liver¢— Glycerol + Fatty acids nn Ae | Carnitine acyltransferase | Mitochondria B-Oxidation v Acetyl COA me Ketogenesis (liver)Note: This material is copyrighted. All rights reserved. 12. lab Dx of DM— A. fasting glucose >126 mg/dL. on 2 separate occasions B. 2 hr blood glucose level >200 mg/dL after 75 gm glucose challenge on 2 C. random glucose >200 mg/dL. with symptoms on 13, home monitoring of blood glucose is mandatory 14, Hb AIC evaluates long-term glycemic control- A. represents mean glucose value for the last 3~4 mths B. 6-7%is ideal 15. sweeteners have no deleterious effect in DM parate separate occasions Impaired glucose tolerance: patient who does not fit the established criteria for DM but who does have an increased risk for macrovascular disease and neuropathy ‘* Gestational diabetes (GDM): 1, refers to glucose intolerance that first develops during pregnancy~ due to an A. increased placental size B. _anti-insulin effect of human placental lactogen 2. screening: A. all pregnant women between 24~28 wks gestation B. screened with a 50 gram glucose challenge followed by 1 hour glucose level C. _>140 mgldL. is a positive screen 3. confirmatory test A. 3 hr 100 gram glucose tolerance test B. _ limits ofthe test set for highest sensitivity 4. newborns complications A. macrosomia: insulin increases adipose stores of fat and muscle mass B. respiratory distress syndrome: insulin inhibits surfactant production C. open neural tube defects D. neonatal hypoglycemia: (1) hyperglycemia in fetus causes fetal release of insulin 2) delivery of the baby decreases glucose level from mother but fetal insulin is still present E. transposition of the great vessels 7 Hypoglycemi 1. types- ‘A. reactive type: adrenergic symptoms in fed state hypoglycemia (sweating 2) trembling @)_ anxiety B. fasting type: (1) neuroglycopenic (brain without glucose) in fasting state hypoglycemia: a. dizziness b. confusion headache d. inability to concentrate 2. patient on insulin or oral sulfonylurea compounds is MCC of hypoglycemia 3. aleohol ‘A. primarily produces a fasting hypoglycemia 200Note: This material is copyrighted. Alt rights reserved, B. increased NADH produced in C. less pyruvate for gluconeogenesis D. decreased glycogen stores in severe netabolism converts pyruvate into lactate liver disease 4. carnitine deficiency A. camitine is cofactor in the transport of fatty acids (camitine acyhtransferase) into the mitochondria B. deficiency of carnitine decrease: C. all tissues are glucose dependen: D. absence of ketone bodies, owii acetyl CoA as substrate Ketotie hypoglycemia in childhood MCC of hypogiycemia from 18 months to mid-childhood B. usually occurs in fasting state C. multiple etiologies: (1) maple syrup urine disease @) galactosemia (3) _ hereditary fructose intolerance 6. liver disease A. decreased glycogen stores B. decreased gluconeogenesis Von Gierke’s glycogen storage disease~ see genetics notes S the use of fatty acids for fuel t leading to hypoglycemia g 10 reduced p ‘xidation of fatty acids and lack of 2 Questions used during the board review: ‘[RnumnaR) FT index ] Tia | A. Increased | Tnereased | Tacreased | Decreased [Increased |B. [increased | Decreased LC. [increased [Increased formal Not indicated Decreased | Decreased D._| Decreased [Increased | Normal [Normal _[ Not indicated LB._| Decreased | Decrease | Decreased T Increase Not indicated RTU= resin Ts uptake, TBI Ts binding ratio | aas. ‘year-old obese woman Presents with a history of we igl keep her awake at ight. She states that she has lost over attending a weight loss clinic. deep tendon reflexes, systolic Prescription medications other Answer: C (taking excess hormone) F an gland, brisk ¥ Iregular pulse, She isnot taking any given to her by the clinic, “year-old woman complains of intermittent Altering in her chest. Physical exam rey tenden ytoid, no lid stare or exophthalmos, a regular hac J#te of 108 beats/minute, normal deep tendon reflexes, and blood pressure of 100/80 mn He, A mid-systolic click and murmur is heard the apex that increases with expiration. She is currently taking birth control pills Answer: B (estrogen effect, MVP is incidental finding) 7 A 28-yearold woman presents wi reals @ tipation and progressive weight She is currently on no Ysical exam exhibits a pale young woman win OOO oad gpNote: This material is copyrighted. All rights reserve, periorbital puffiness, dry, yellow-colored skin, normal sclera, a normal cardiovascular. and creaiory exam, delayed deep tendon reflexes, and Proximal muscle weakness in her lower extremities ‘Answer: E (primary hypothyroidism) A'= Graves disease, D = Androgen effect Items 4 PTH ‘A Sseyearold woman with diastolic hypertension Jresens with a sudden onset of right flank pain With radiation of pain into the right groin. A utinainen reveals a positive dipstick for blood and 4 cguare atic for nitrite and leukocyte esterase, Sediment ne” exhibits numerous RBCs and tals resembling the back ofan envelope. Answer: C (renal stone in primary HPTH) 2 _Anewbom presents wit tetany, heart failure, and an absent thymic shadow Answer: A (DiGeorge syndrome, could also be Fanaty bypoparathyroidism), B = secondary hyperparathyroidism, D = malignancy induce and all other types of hypercalcemia ‘Which of the following clinical and 'shoratory abnormalities cecur in BOTH Addison's disease and Panhypopituitarism? B Low I-deoxycortisol post-metyrapone test B. Normal urine for 17-ketosteroide C. Hypematremia D. Hyperkalemia E. Low TSH fay Heites B and C occur in neither condition: 17 KS ‘would be low in both of them and both would have hyponatremia; choice D is. only Present in Addison's, choice E is only present id Panypopituitarism) ‘Which of the following alterations in Nid metabolism is expected in a patient with diabetic ketoacidosis? A Activation of capitiary lipoprotein lipase B. Increased B-oxidation of fatty acids c D. Decreased production of acetyl-CoA Increased fatty acid synthesis Eq lthibition of hormone sensitive lipase B (choice A occurs in the presence of insulin sad is inhibited in DKA, choice C oceurs when insulin is Mon rent COA shouldbe increased in DKA due toincreares B-oxidation of FAs; choice D occurs pp insulin is present; itis inhibited in DKA, chore occurs when insulin is present; itis activated in DKA due to glucagon and catecholamines)Note: This material is copyrighted. All rights reserved. ‘FA 22-year-old woman has been amenortheic for the last 6 months. She complains of a milky discharge from her nipples that has béen present for the last 7 months. The pregnancy test is negative and the serum TSH is normal, Which of the following additional tests should you order on this patient? A. Serum prolactin B. — Metyrapone test C. Serum Ty D. Serum cortisol E, _ Serum gonadotropins A (prolactinoma) ‘Which of the following tests distinguishes pituitary Cushings from both adrenal and ectopic Cushings? A. 24-hour urine for 17-ketosteroids B. Low dose dexamethasone test ©. Serum cortisol level D. High dose dexamethasone suppression test E, 24-hour urine for free cortisol D (cortisol in pituitary Cushing's is suppressed with the high dose dexamethasone test and not in other types of Cushings; all the other choices are the same in all of them) @ A 35-year-old pharmacist presents to your office with recurrent episodes of forgetfulness and tiredness. A serum glucose is reported to be 20 mg/dL. (70-110 mg/dL), Additional studies on the same sample reveal a high serum insulin and high C-pepide level. Based on these findings, you suspect the patient has. A. a benign tumor involving B-islet cells B. nearly phase of type I diabetes mellitus C. a benign tumor involving c-islet cells D. ectopic secretion of an insulin-like factor E, surreptitiously injected human insulin A (high C-peptide proves it is an insulinoma, would be suppressed if choice E was correct) old type I insulin dependent diabetic has a burning sensation around his ankles and on the bottoms of both feet. Neurological examination reveals depressed Achilles and knee jerk reflexes bilaterally and decreased light touch sensation in both lower extremities. The mechanism for this is most closely associated with. A. osmotic damage B. thiamine deficiency C. pernicious anemia D. syringomyelia E. lumbar disk disease A (osmotic damage of Schwann cells produces a sensorimotor peripheral neuropathy) o Water deprivation test for poly POsm post water sm past UOsm post deprivation _| water deprivation vasopressin normal 292 750. 760 A 312 98 120, B. 319 110 350 Le. 288 __ 760 ___780 ie Giabetes melius, eg lum, B= cenaldabeis insipidus, ep ed injury, C= Shogenie polydipsiaNote: This material is copyrighted. Al rights reserved. Musculoskeletal, soft tissue: w Synovial fluid (SF) analysis: 1, secreted by synoviocyte- A. B. A. B. c D. joint lubricant that is rich in hyaluronic acid provides nourishment for articular cartilage routine studies gross appearance: e.g., normally pale yellow WBC count and differential (1) normally <200 cells/uL. (2) neutrophils <25% of the total count crystal analysis culture and gram stain if infection is suspected 3. crystal identifieation— A, F Osteoarthritis (OA) monosodium urate (MSU) crystals are needle shaped (monocli (1) _ using special red filter, slide background becomes red (2) crystals are aligned parallel to the slow ray (axis) of the compensator (3) _ yellow crystal when parallel to the slow ray is a negatively birefringent MSU crystal ———— sellow = negatively birefringent +> direction of slow ray of compensator caleium pyrophosphate crystals (CPPD): (1) can be needle shaped or chunky (2) blue crystal when parallel to the slow ray indicates a positively birefringent calcium pyrophosphate crystals (CPPD) ——— blue = positively birefringent +> rection of slow ray of compensator 1. MC rheumatic disease and cause of joint disability in the United States 2. pathogenesis A progressive degeneration of articular cartilage: (1) age dependent process that is universal after 65 years of age 2) 10 times more common in women than in men @) primarily targets weight bearing joints (hips, knees) and hands (distal interphalangeal) chondrocytes in articular cartilage require glucosamine in order to maintain the ‘macromolecular structure of cartilage: (1) glucosamine stimulates the synthesis of glycosaminoglycans,(Gé the primary components of cartilage (2) most important factor predisposing a joint to OA is abnormal load placed on a ight bearing joint articular surface reveals erosions and cleft formation: clefts penetrate into the underlying subchondral bone (fibrillation) bbone rubs on bone: dense sclerotic bone resembling ivory (eburnation) Gs which are 204Note: This material is copyrighted. All rights reserved. subchondral bone cysts develop beneath the articular surface reactive bone formation occurs at the margins of the joints: (1) _ produce osteophytes (bony spurs) @) “lipping" found in the vertebral bodies @)_Heberden's nodes found at base of the DIP joints of the fingers (4) Bouchard’s nodes in the proximal interphalangeal (PIP) 3. secondary types due to~ ‘A. congenital hip dislocation B, trauma C. obesity D. _ hemochromatosis 4. clinical A. non-inflammatory joint disease B. _ pain with passive motion of the joint: secondary synovitis C. joint stifiness/entargement D. ‘harrow joint space E. _ no joint fusion 5. no specific lab alterations Neuropathic arthropathy (Charcot's joint) 1. joint disease that develops secondary to a neurologic disease A. diabetes mellitus (MCC) B. syringomyelia CC. tabes dorsalis * Rheumatoid Arthritis (RA): 1. deseription~ female-predominant chronic, systemic inflammatory disease occurt 30-50 ys of age 2. pathogenesis— ‘A. microbial infections: ? Epstein-Barr virus B. HLA-DR, C. injury () influx of CD, T cells‘macrophages into synovial tissue—> @) local stimulation of B cells to produce IgM autoantibodies directed against the Fe receptor of IgG (rheumatoid factor~ RF)» 3) _ RF aggregates into immunocomplexes that activate complement system—> (4) chemotaxis of neutrophils into joint space—> () phagocytosis of immunocomplexes (ragocytes) > (6) release of inflammatory mediators—> (7) macrophages release interleukin-1 (IL-1) and tumor necrosis factor (TNF)-c —> (8) induce synovial cells to release inflammatory mediators that destroy connective tissue, cartilage and bone—> (9) chronically inflamed synovial tissue containing numerous plasma cells begins to proliferate (pannus formation) and destroy the articular cartilage (10) reactive fibrosis and fusion (ankylosis) of joint 3. clinical- see table 4. Iab- see tableNote: This material is copyrighted. Ail rights reserved. o 1 2. 3, 4 Comparison chart of Characteristic _| Osteoarthritis Juvenile Rheumatoid Arthritis (JRA): definition chronic synovi jal inflammatory condition that frequents patients under 16 years phadenopathy, polyarthritis of age girls > boys types of FRA- A. Stills disease (2026): systemic disease with fever, rash, lym B. polyarticular (40%): disabling arthritis predominates C. _ pauciarticular (40%) @ @) lab~ RF negative (seronegati arthritis in few joints teoarthy uveitis withthe potential for blindness e) in most cases (OA) and rheumai oid Arthritis (RA): Rheumatoid Arthritis Classification Group I noninflammatory Group Il inflammatory Sex/Age Female dominant. Middle to late | Female dominant. All ages, | decades of if HLA Possible HLA Al, BS HLA Det relationships [Pathogenesis Degenerative Immunologie destruction Initial site of | Articular cartilage Synovial tissue involvement Key abnormal: ] Carilage “fibrillation, subchondral | Tallamed synovial Usaue Grows over articular ities bone cysts, osteophytes, secondary | cartilage (pannus) and releases degradative | are ties wauding. © reduced joint | enzymes that degrade bone and cartilage mobility without fusion Reactive fibrosis leads to fusion (ankylosis) of the joint and immobility Clinical Asymmetric involvement of weight | Symmetric joint involvement. Involves bearing joints and small joints of hands (DIP and PIP), Mild morning stiffness, Heberden’s nodes (DIP) and Bouchard’s nodes (PIP), Compression neuropathies in vertebral column disease. smaller joints ‘and knee. Morning stiffness >| hr, Targets MCP and PIP joints in hands, Ulnar deviation, Baker's eysts (synovial cyst) in popliteal fossa (confused with popliteal artery aneurysms). Extraarticular disease: vasculitis (fingers, ankles; correlates. with high RF titers), subcutaneous (theumatoid) nodules (fibrinoid necrosis), pulmonary disease (restrictive lung disease), Caplan’s syndrome (coal worker's pneumoconiosis ot silicosis + RA lung disease), ftbrinous Pericarditis, hematologic disease (anemia chronic disease, iron deficiency anemia, autoimmune hemolytic anemia), reactive (secondary) amyloidosis, Sjogren's syndrome (RA + dry eyes and dry mouth), Felty’s syndrome (RA + autoimmune neutropenia and splenomegaly), uveitis, carpal tunnel syndromeNote: This material is copyrighted. All rights reserved. Characteristic | Osteoarthritis Rheumatoid Arthritis Laboratory Slight elevation of alkaline phospha- [ Positive cheumatoid factor (RF; [gM antibody tase from osteophyte formation. against IgG; positive in 70%). High RF titers correlate with increased severity of disease theumatoid nodules, greater frequency of systemic complications, vasculitis, poorer Prognosis. Normal to increased serum complement (C3). Increased erythrocyte sedimentation rate (ESR). Polyclonal gammopathy. Positive serum ANA (30%), Narrowing — of joint space. | Narrowing of joint space from destruction oF Osteophytes. Dense, sclerotic bone. | articular cartilage, Marginal bone erosions | Subchondral bone eysts Fusion (ankylosis) of joint. = MCP = metacarpophalangeal joint PIP = proximal interphalangeal joint DIP = distal interphalangeal joint tion— male dominant disease with hyperuricemia, recurrent attacks of acute arthritis, deposits of MSU (tophi) in soft tissue types A. primary gout: () disorder in uric acid metabolism @) _underexcretion of urie acid MC (3) _ overproduction less common B. secondary gout: (1) diabetes meltitus @) polycythemia vera @) leukemia @ diuretic therapy (S) Rx disséminated carcinomas attack A. usually involves metatarsophalangeal joint (big toe): called podagra B. inflammation due to an interaction of MSU crystals with mononuclear phagocytes-> (1) stimulates macrophage production of interleukin | (IL-1)-> 2) IL-1 initiates inflammatory reaction (e.g, fever) > 3) MSU crystals tyse neutrophils» (4) neutrophils release lysosomal enzymes and free radicals» (S) contribute to the inflammatory reaction chronic gout— A. presence of tophi B. _ tophi develop after 10 years of poorly controlled disease C. _ tophi represent deposits of MSU: (2) MC occur around affected joints @) granulomatous reaction with foreign body multinucleated giant cells surrounding central core of amorphous MSU erystals complications— A. deforming arthritis with erosion of cartilage and boneNote: This material is copyrighted, All rights reserved. B. renal disease: (1) chronic interstitial nephritis @)_uroithiasis 6 lab- A. demonstration of MSU crystals in the SF is confirmatory, not hyperuricemia B. absolute neutrophilic leukocytosis Rx A. acute attacks: reduce inflammation with: (1) _ indomethacin (MC drug) @) colchicine 4. inhibits release of leukocyte-derived crystal induced chemotactic factor b. chemotactic factor initiates the inflammatory reaction in the joint when neutrophils phagocytose MSU crystals B, most are underexcretors: determine this by a 24-hr urine collection (1) Rx with uricosurie agents like probenecid or sulfinpyrazone @) _overproducers Rx with allopurinol: inhibits xanthine oxidase C. chronic disease: Rx with allopurinol = Calcium pyrophosphate dihydrate crystal deposition arthropathy (CPPD disease), or pseudogout: 1, definition degenerative joint disease with deposition of CPPD crystals in joints: knee MC site 2. clinical A. crystals deposit in articular cartilage: called chondroealeinosis, B. linear densities on radiographs Ankylosing spondylitis (AS): 1, definition seronegative (rheumatoid factor negative) spondyloarthropathy that targets young men between the ages of 15~30 years who are HLA-B27 positive (95% of cases) associ A. Reiter syndrome B. psoriasis C. ulcerative colitis D. microbial pathogens: ()Fersinia species @) Shigetia species 3. clinical ‘A. targets the sacroiliac joint: (1) sacroilits is first manifestation @) stiffness upon wakening in AM 3) _ subsides with activity B. _ vertebral column becomes imm (1) “bamboo spine” @) fusion of the vertebra CC. sorttis: aortic regurgitation D. uveitis: blurry vision © Reiter syndrome: 1, definition A. male dominant seronegative spondyloarthropathy 208This material is copyrighted. All rights reserved. (Q) urethritis (usually Chlamydia trachomatis) 2) non-infectious conjunctivitis (3) HLA B-27 positive arthritis B, inflammation at insertion of Achilles tendon is characteristic (USMLE) Psoriatic arthritis 1, definition- HLA B27 positive seronegative spondyloarthropathy that occurs in <10% of patients with psoriasis: pencil in eup deformity in fingers noted on x-ray Enteropathic arthritis: 1, definition— HLA B27 positive arthritis associated with inflammatory bowel disease 2. associations~ post-gastroenteritis with Shigella, Campylobacter, Salmonella, ot Yersinia species Bone/soft tissue infections: 1. osteomyelitis in HbSS- Salmonella is MC in patients with sickle cell disease 2. osteomyelitis A. metaphysis MC site: most vascular part of bone B. Staphylococcus aureus MCC: (Q) neutrophils enzymatically destroy bone and leave behind devitalized portions of bone called sequestra @) chronic disease has extensive reactive bone formation in the periosteum called involucrum (@) _Brodie’s abscess is a type of osteomyelitis that becomes encapsulated and surrounded by dense sclerotic bone due to hematogenous spread to bone radionuclide bone scan best for detection complications Q) raining sinus tracts to the skin 2). (squamous cell earcinoma developing within the sinus tract (USMLE) 3. tuberculous osteomyelitis MC secondary to hematogenous extension from a primary focus in the lung B.__ primarily targets the vertebral column (called Pott's disease) 4. USMLE scenario: peripheral smear of sickle cells in patient with osteomyelitis~ >80% of osteomyelitis in sickle cell disease is due to Salmonella, not Staphylococcus aureus 5. USMLE scenario: diabetic with wet gangrene of the foot followed by stiffening of the jaw, neck stiffness, and inereased irritability and increased hyperreflexia--? diagnosis A. patient has'tetamus rpo BR: (2) tetanus immune globulin 2) penicillin (3) _ give full immunization with toxoid when the patient recovers: infection does not produce high enough titers of protective antibodies 6. (USMY scenario: patient steps on nail with rubber shoes on- Pseudomonas aeruginosa infection may occur with underlying osteomyelitis, 7. cat bite- ‘A. Pasteurella multocida infection likely: B. potential for septic arthritistendinitis 209Note: This material is copyrighted. All rights reserved. disseminated gonococcemia— A. decteased C5-C9: (2) _ final common pathway complement components required for phagocytosis of the organism (2) GCis the MCC of septic arthritis B. knee MC large joint involved C. pustules on wrists/feet D. tenosynovitis wrists/feet Lyme disease— A. pathogen— Borrelia burgdorferi transmitted by Ixodes tick B. early disense— (1) erythema chronicum migrans: Q) Rx with doxye; C. late disease (1) bilateral Bell's palsy a. Vil cranial nerve MC involved b. «bilateral Bell's palsy is highly predictive of Lyme's disease @) arthritis @) myocarditis (4) Rx with ceftriaxone ‘Osgood Schlatters: a 2 3 inflammation of proximal tibial apophysis at insertion of patellar tendon propensity for active boys permanent knobby appearing knees Osteogenesis imperfecta: usually AD inheritance A. brittle bone disease B. MC genetic bone disease pathogenesis— defective synthesis of type I collagen clinical A. pathologic fractures B. blue sclera due to visualization of choroidal veins under sclera devoid of collagen (USMLE picture) C. deafness Achondroplasia: ih AD inheritance impaired enchondral ossification and premature closure of the epiphyseal plates of long bones: A. normal sized head and vertebral column B. shortened arms and legs ‘marble bone disease” B. secondary to an overgrowth and sclerosis of cortical bone ("too much bone"): defect in osteoclasts clinical- A. gradual replacement of the marrow cavity by bone: severe anemia 210Note: This material is copyrighted. All rights reserved. B. pathologie fractures C. cranial nerve compression: visual and hearing loss D. hydrocephalus 3 Rx= bone marrow transplantation has been helpful owing to the introduction of normal osteoclasts, Osteoporosis: 1. MC metabolic abnormality of bone in the United States 2. pathogenesis A; reduction in normal mineralized bone (decreased bone mass): bone subject to pathologie fractures, B. types: ) primary (e.g,, postmenopausal) @) secondary to an underlying disease (¢ heparin) 3. postmenopausal osteoporosis A. secondary to estrogen deficiency CH) “eatogen serves t0 dampen the release of interleukin-l (osteoclast activating factor) from osteoblasts (2) deficiency leads toa greater breakdown of bone by osteoclasts than formation of bone by osteoblasts B. clinical: (1) MC see compression fractures of the vertebral bodies 2) Colles fractures of the distal radius | C. Dx of osteoporosis: | (1) dual photon absorptiometry (evaluates bone density) (2) _ tests for bone tumover: a. increased urinary concentration of osteocalcin b. increased pyridinium collagen crosslinks D. prevention of postmenopausal osteoporosis (USMLE): (1) estrogen is gold standard for its prevention. 8. also a 50% reduction in incidence of ischemic heart disease b. _unogposed estrogen increases the incidence of endometrial carcinoma Prevented by addition of progesterone | @) calcium (1500 mg) (3) _ vitamin D 400-800 U (weight bearing exercise: walking, not swimming (USMLE) E. Rx of postmenopausal osteoporosis: (1) _ bisphosphonates: potent inhibitors of bone resorption 2) _caleitonin-salmon: inhibits osteoclasts hypercortisolism) or medication (e.g / Bone fractures: 1. femoral neck fracture A. bleeds into the capsule B. _may compromise medial femoral circumflex artery leading to avascular necrosis (USMLE) C. posterior dislocations are most dangerous 2. pelvic fractures— usually involve the symphysis, rami of the pubis, and ischium B. _ bladder rupture and urethral tears are MC soft tissue injury 21Note: This material is copyrighted, AU rights reserved. €. associated with the greatest amount of blood loss of all fractures 3. scaphoid (navieular) bone~ A. MC fracture of carpal bones B, _ very susceptible to avascular necrosis and non-union 4. Colles! fracture A. person falls on an outstretched hand B. distal end of the radius at the suprastyloid level C. fracture of styloid process of the ulnar D. “dinner fork” deformity: radial supracondylar fracture A. distal fracture of humerus B. compromises brachial artery with danger of Volkmann's: ischemic-contracture,of forearm muscles (USMILE), C. median nerve injury ment is displaced upward and backward Avaseular (aseptic) necrosis of bone: 1. pathogenesis occurs when the microcirculation within bone is disrupted leading to bone MC in a femoral head fracture in the elderly SLE patients on long-term corticosteroid therapy C. sickle cell disease 3. wray- ‘A. bone has increased density on x-ray B. MRI has highest sensitivity Osteochondrosis: 1, aseptic necrosis involving the ossification centers of various bones in children 2. Legg-Perthe’s disease- A. involves the femoral head B. males > females C. 3-10 years of age D. pain in knee or limp E, secondary osteoarthritis common Paget's disease of bone (osteitis deformans): 1, increased thickness of abnormal bone 2. pathogenesis A. primari B. in decreasing order it targets: pelvis > skull > femur C. carly phase of excessive osteoclastic resorption of bone D. _ late phase of excessive bone formation: (D) increased alkaline phosphatase (2) production of thick, weak bone (mosaic bone) without a normal lamellar structure occurs in elderly males: unknown etiology (2slow virus) clinical A. pathologie fractures B. head enlargement C. increased risk for osteogenic sarcomas D. high output heart failure: arteriovenous connections in vascular boneNote: This material is copyrighted, All rights reserved. Fibrous dysplasia: 1. definition A. benign, nonneoplastic process of bone that primarily targets children and young adults B, replacement of marrow by woven bone that lacks the normal lamellar pattern: subject to pathologic fractures single bone (monostotic) type 3. polyostotic type associated with Albright's syndrome~ A. abnormal skin pigmentation (café au lit spots) B. precocious sexual development due to midline hamartoma in hypothalamus sites: ribs/femur/cranial bones Fibrous cortical defeets/nonossifying fibromas: 1. essentially the same disease except for a difference in size A. fibrous cortical defect B. _ nonossifyi 2. clinical A. children B. involve cortical aspect of metaphysis of long bones: femur, tibia and fibula in descending order of frequency C. irregular, sharply demarcated radiolucent defect in the metaphyseal cortex ‘= Neoplastic disorders of bone: 1, MC primary bone tumors in order of increasing age~ Ewing's sarcoma > osteozenie sarcoma > chondrosarcoma > multiple myeloma 2. MC primary malignant tumors of bone in descending order of frequency— multiple myeloma > osteogenic sarcoma > chonidrosarcoma > Ewing's sarcoma > giant cell tumor of bone 3. metastasis is the MC malignaney of bone- breast cancer is MC primary site of origin o Cartilaginous bone tumors: 1, osteochondroma- A. children and adolescents B. metaphysis of iong bones C. MC benign bone tumor: (Q) lobulated outgrowth of bone (exostoses) capped by benign proliferating cartilage @) solitary (3) multiple called osteochondromatosis a. AD disease b. — chondrosarcoma risk greatest with multiple tumors 2. enchondroma~ A. children and adolescents B. tubular bones in hand C. benign tumor: (1) solitary @) multiple called enchondromatosis (Ollier’s disease): chondrosercoma risk greatest with multiple tumors 3. chondroblastoma A. 10-20 yrs old B. _ epiphysis of distal end femur, proximal tibia, humerus C. benign tumor:Note: This material is copyrighted. All rights reserved. Bone 1 (1) “popcorn” appearance on radiographs @) extends into metaphysis chondrosarcoma— A. >30,years old B. pelvic bones > upper end femur and humerus C. MC primary malignant cartilaginous tumor (1) denovo @) secondary to osteochondromatosis or enchondromatosis D. grade determines biologic behavior E. _ metastasize to lungs forming tumors: osteoma— A. >40 years old B. sites: (1) simuses (MC) 2) facial bones C. benign tumor: association with Gardner's syndrome osteoid osteoma~ A S years B. proximal femur: cortex of bone C. benign tumor: (1) radiograph exhibits small radiolucent focus (nidus) surrounded by densely sclerotic bone (2) nocturnal pain relieved by aspirin osteoblastoma: A. <30years old B. _vertebra> long bone C. benign tumor: (1) “giant osteoid osteoma” @) pain not worse at pight and not relieved by aspirin osteogenic sarcoma— A. 10-25 years old B. metaphysis distal end femur > upper end tibia (1). second MC primary malignant tumor of bone @) arises de novo or secondary to other conditions @) _ risk factors: a. Paget's b. radiation bone infarct 4. inactivation of Rb suppressor gene on chromosome 13 (4) destruction of metaphysis and invasion of subjacent soft tissue: a. elevation of periosteum producing a Codman's triangle on x-ray b. "sunburst" appearance from calcified osteoid extending into soft tissue (S)_ metastasize to lung highty malignant primary bone tumor of marrow origin A. most frequently targets children in the first and second decades of life B.Note: This material is copyrighted, All rights reserved. C. sites: femur, flat bones of pelvis and tibia D. “round cell” tumors: differential diagnosis includes (1) metastatic neuroblastoma 2) metastatic malignant lymphoma (3) _ acute lymphoblastic leukemia 2. elinieal- A. fever with localized heat over the tumor B. anemia C. onion skinning noted around bone on x-rays Giant cell tumors: 1. benign bone tumors that arise in the epiphysis and extend into the metaphysis of bone 2. favored locations in descending order— distal end of the femur > proximal end of the tibia 3. pathology— A. nonneoplastic component consisting of multinucleated giant cells, B, neoplastic mononuclear fibroblast-like cell that determines the biol tumor behavior of the Muscle disorders: 1. type Ifibers- A. slow-twitch fibers (red muscle) B. rich in mitochondria and oxidative enzymes C. capacity for long, sustained contractions without fatigue: e.g., soleus muscle | 2. type Il fibers: A. fast-twitch fibers (white muscle) i B. _ poor in mitochondri } C. geared for anaerobi ly D. _ react to training with hypertrophy: e.., biceps muscle muscle weakness— causes include diseases involving: ‘A. motor neuron pathways: e.g., amyotrophic lateral sclerosis B. neuromuscular synapse: e.g., myasthenia gravis, C. muscle: e.g., Duchenne's muscular dystrophy neurogenic atrophy motor neuron or its axon degenerates leading to atrophy of both type | and UI fibers Mi 5. muscular dystrophy (MD)- peok < A. _ inherited progressive primary muscle disease that MC presents in early childhood y B. Duchenne’s: i (@ SXR(70%) @) MC and severe MD. oe (3) deficiency of dystrophin: dystrophin normally anchors actin to the membrane glycoprotein (4) Becker's type is milder: defective dystrophin (USMILE) | (5) progressive degeneration of type I and Il fibers: progressive fibrosis and infiltration of muscle tissue by fatty tissue (pseudohypertrophy of calf muscle) (© presents in second to fifth year of life a. weakness and wasting of proximal pelvic muscles, b. — “waddling gait” with difficulty in standing up ¢. place hand on the knee to help stand (Gower d. death by twenty years of age e. may affect cardiac muscle sign) 215Note: This material is copyrighted, All rights reserved. (7) laboratory a, antenatal diagnosis (dystrophin defect) u: technology b. serum CK/aldolase increased at birth ‘* noclinical signs of disease ng recombinant DNA. © serum CK declines as muscle tissue is progressively replaced by fat and fibrous tissue ¢. female carriers have elevated serum CK activity C. myotonic dystrophy: (1) AD disorder: MC adult MD @) triplet repeat of CTG on chromosome 19. a. codes for a protein kinase b. anticipation: disease worsens in future generations @) selective atrophy of type I fibers (4) initial presentation in adolescence with facial weakness: a. mouth hangs open b, distal extremity muscle weakness myotonia’ * inability to retex muscles (sustained grip) ‘© cannot release grip on a golf club (SMILE) frontal balding cataracts testicular atrophy facial muscle wasting cardiac involvement i. increased serum CK 6. congenital myopathies— primary non-progressive muscle diseases that present at birth with poor muscle tone A. central core disease B. _ nemaline rod myopathiy 7. myasthenia gravis (MG). A. autoimmune disease: reduction in acetyicholine-receptors due to (1) presence of an autoantibody against the receptors (2) _ type Il hypersensitivity reaction B. afflicts women in the second and third decades C. afflicts men in the sixth and seventh decades of life D. ~85% have thymic hyperplasia with germinal follicles representing B cell proliferation: site of antibody synthesis remo E, 15% may have thymomas F. ical (1) ptosis (first sign) @) diplopia (3) muscle weakness improved with rest (4) dysphagia for solids and liquids G. Dx (1) Tensilon (edrophonium) test: a. inhibits acetylcholinesterase, which increases acet b. reverses muscle weakness 2) assays for anti-acetyleholine receptor antibodyNote: This material is copyrighted. All rights reserved, (3) _anti-striated muscle antibodies H. Rx: (1) anticholinesterase drugs: pyridostigmine (2) surgical thymectomy (improvement in most cases) 3) immunosuppression (corticosteroids) (4) plasmapheresis to remove the antibody & Fibromatosis: 1, non-neoplastic, proliferative connective tissue disorders~ A. infiltrate tissue (usually muscle) B. commonly recur after surgical excision Dupuytren's contracture A. MC fibromatosis B. involves palms of hands: contraction of fingers (usually the 4th and Sth) €. MC inalcoholies 3. desmoid tumor- ‘A. fibromatosis of anterior abdominal wall in women B, associated with: (1) previous trauma @) multiple pregnancies @) Gardner's syndrome ‘Soft tissue tumors: 1. lipomas- A. MC benign soft tissue tumor: (1) arise in subcutaneous tissue (2) _ trunk, neck, proximal extremities B. noclinical significance iposarcoma— A. thigh, retroperitoneum: second MC sarcoma B. MC occur in.men >$0 years of age C. _lipoblasts identified with fat stains 3. fibrosarcoma A. thigh, upper limb B. may arise after radiation } 4. dermatofibroma— } ‘A. lower extremities: elevated, ted nodule that umbilicates (central dimple) when squeezed B. _ benign nonencapsulated proliferation of spindle cells confined to the dermis, 5. malignant fibrous histiocytoma | A. MC adult sarcoma B. thigh, retroperitoneum C. associated with radiation therapy or surgical scars 6. rhabdomyomas— A. heart tumors in children associated with tuberous sclerosis B. also located in tongue and vagina 7. embryonal rhabdomyosarcoma A. MC sarcoma in children B. _ grape like masses protruding from the vagina or male urethra (2) shabdomyoblasts have cross-striations 217Note: This material is copyrighted. All rights reserved. @) _ stain positive for desmin Jeiomyoma- ‘A. MC benign tumor in women: myometrium of uterus B. MC benign GI tumor: MC in stomach C. uncommon outside the organs Ieiomyosarcoma— A. MC sarcoma in the GI tract and uterus B. uncommon outside organs 10, neurofibrosarcoma- ‘A. major nerve trunks (sciatic B, most arise in conjunction with type I neurofibromatosis, Autoimmune diseases: 1. organ-specific A. Addison's disease B. pernicious anemia C. Hashimoto's thyroiditis systemi A. SLE B, rheumatoid arthritis (RA) C. progressive systemic sclerosis (PSS) Laboratory testing in autoimmune disease: 1, serum antinuclear antibody (ANA) test- ‘A. nuclear antibodies directed against: (DNA a. double-stranded (ds): specific for SLE b. single-stranded (ss) @) histones: specific for drug-induced lupus (3) _ acidic proteins: a. anti-Smith (Sm): 100% specificity and PV’ for SLE . _anti-ribonucleoprotein (RNP): specific for mixed connective disease (4) nucleolar antigens pattern of nuclear fluorescence: (1) speckled 2) rim: usually anti-ds DNA in SLE with glomerulonephritis (3) homogeneous (4) nucleolar: specific for PSS C. antibody titer >1/80 is usually significant lupus erythematosus (LE) cell~ ‘A. neutrophil with phagocytized DNA previously altered by IgG antibodies B. not specific for SLE autoantibodies in autoimmune disease- A. anti-acetylcholine receptor antibody: myasthenia gravis (90%) anticentromere antibody: (1) CREST syndrome (60%) @) PSS (10%) anti-endomysial antibody: celiac disease anti-gliadin antibody: celiac disease (95%) anti-glomerular basement membrane antibody 218Note: This material is copyrighted. All rights reserved. a (1) Goodpasture’s syndrome @) against an epitope from type TV collagen in the basement membrane of the glomerulus and pulmonary capillaries F, anti-insulin and anti-islet cell anti-bodies: GQ) _anti-insulin antibodies develop in pre-type I diabetes mellitus @)__anti-islet cell antibodies in type I diabetes mellitus (60-90%) (3)__ antibodies not present in type II DM G. _anti-microsomal antibody: (1) Hashimoto's autoimmune thyroiditis (97%) Q) Graves disease 1H. _anti-mitochondrial antibody: primary biliary cirrhosis (90-100%) I. _anti-neutrophil eytoplasmic antibody (ANCA) (@) C (cytoplasmic) ANCA in Wegener's granulomatosis (> 90%) 2) P (perinuclear) ANCA in polyarteritis nodosa (>80%): antibody against myeloperoxidase J. anti-parietal cell and intrinsic factor antibodies: « (1) _ parietal cell antibodies present in 90% of pernicious anemia (PA) = (2) antibodies to intrinsic factor (IF) more specific for PA K. _anti-thyroglobulin antibody (1) Hashimoto's autoimmune thyroiditis (85%) . | Q) Grave's disease (30%) Systemic lupus erythematosus (SLE): 1. definition— / A, — female dominant disorder: (1) _ polyclonal activation of B cells, @) hormonal: increased estrogen activity (3) environmental triggers: a. sunlight b. procainamide (1) immunocomplex (IC) deposition of anti-DNA antibodies along the basement membrane: called band test (2) IC restricted to the area of the rash in discoid lupus (3) _ ICs in both normal and involved skin in SLE (4) classic malar butterfly rash @Q) arthritis or arthralgias involving small joints (e.g., hands) @) MC presenting symptom (3) _-moming stiffness resembling RA C. avascular (aseptic) necrosis of the femoral head: complication of long-term corticosteroid therapy D. cardiovascular: (1) fibrinous pericarditis/effusion MC cardiovascular manifestation of SLE @) Libman-Sacks endocarditis: sterile vegetations on mitral valve pulmonary disease: (1) pleuritis/effusion MC (2) interstitial lung disease with a restrictive pattem 219Note: This material is copyrighted. All rights reserved. F Progressive systemic sclerosis (P! L F. _hematologie: autoimmune hemolytic anemia/thrombocytopenia/leukopenia G. _anti-phospholipid antibodies (1) lupus anticoagulant and anti-cardiolipin antibody @) mid-rimester fetal loss @) _ strokes H. renal disease (1) diffuse proliferative GN MC type @) correlates with presence of anti-dsDNA @) common COD L_anti-SS-A (Ro) antibodies in pregnancy: newboms with complete heart block J. infection MC COD laboratory- A. positive serum ANA (99%) B. anti-dsDNA (70%) €. _ anti-Sm (30% sensitivity, 100% specificity) D. _anti-SS-A (Ro, 30%) E, complement C3 levels are low in active disease F. _ biologic false positive syphilis serology: due to anticardiolipin antibodies drug-induced SLE- A. MC due to procainamide: hydralazine also common offender B, differs from SLE (1) abrupt rather than slow onset (2) _ very low incidence of renal/CNS involvement (3) absent anti-dsDNA/anti-Sm antibodies (4) normal complement levels (5) _ elevated anti-histone (95%) antibodies (©) disappears with discontinuance of the drug 5): definition— A. female dominant B. _ initially involves small vessels C. _ followed by excessive deposition of normal collagen in multiple organ systems clinical A. : parchment-like appearance swelling of fingers/hands tight facial features ‘multiple, punctate blood vessel dilatations (telangiectasias) () Raynaud's phenomenon: MC initial sign of PSS B. joints: polyarthritis c Gk (2) dysphagia for solids/liquids (lack of peristalsis) @) malabsorption @) _ wide-mouthed diverticula D. renal: (1) glomerulonephritis (2) _ severe hypertension @) renal failure 220Note: This material is copyrighted. All rights reserved. pulmonary (1) diffuse interstitial pneumonitis with fibrosis @) Mccop F, _ heart: left ventricular dysfunction c A. calcinosis (fingertips) and anti-centromere antibodies B. Raynaud's phenomenon c. sal motility dysfunction D. _sclerodactyly E. felangiectasias laboratory— ‘A. positive ANA (70-90%) B. anti-Scl-70 (70%): topoisomerase i (USMLE) CC. anti-centromere antibodies (30%) ‘Dermatomyositis (DM) and polymyositis (PM): Mixed connective ti 1 2 definition both associated with an inflammatory myopathy with or without involvement of the skin clinieal- A. muscle pain and atrophy: shoulders commonly involved B. dysphagia for solids/liquids: involves striated muscle of upper esophagus C. puffy eyelids with a purple-red discoloration (heliotrope eyelids) D. E. Gottron’s patches over dorsum of PIP joints increased risk for malignant neoplasms (15-20%): particularly lung cancer laboratory— A. elevated serum creatine kinase B. positive anti-Jo-1 antibodies C. Bx of muscle shows lymphocytic infiltrate we disease (MCTD): features of SLE, PSS, and polymyositis ‘A. follows a more benign course than the autoimmune diseases B. rarely involves the kidney anti-ribonucleoprotein (RNP) antibodies are present in most cases Sjogren's syndrome: definition. ‘A. female dominant disease B. associated with rheumatoid arthritis clinical A. immune destruction of lacrimal/minor salivary glands (1) dry eyes (keratoconjunetivitis) @) dry mouth (xerostomia) B. _ increased incidence of malignant lymphoma C. renal: tubulointerstitial disease leads to distal renal tubular acidosis (type 1) laboratory— ‘A. positive serum ANA (50-80%) B. _anti-SS-A/Ro (70-80%) C. _ anti-S$-B/La (50-70%: more specific than anti Ro antibodies D. _ positive rheumatoid factorNote: This material is copyrighted. All rights reserved. E. confirmatory test: lip biopsy of # minor salivary gland demonstrating lymphocytic destruction of the glands ‘Questions used during the board review: ‘FA sexually active 30 year old man presents with fever and pain in his right big toe that woke him up at night. He has been taking aspirin to relieve the pain without relief. His osteoarthritis. The right toe is swollen, hot and exquisitely sensitive to touch. Laboratory studies reveal a neutrophilic leukocytosis and left shift. A synovial tap was performed. Based on the above history, his problem is most likely elated to A. joint inflammation secondary to a positively birefringent crystal B. disseminated gonococcemia with septic arthritis CC. underexcretion of urie acid in the urine D. osteomyelitis secondary to hematogenous spread of Staphylococcus aureus E. an HLA B27 positive spondyloarthropathy C (gout, MC due to underexcretion rather than overproduction) ither has severe ‘Which of the following characterizes joint disease associated with rheumatoid arthritis rather than osteoarthritis? A. Cartilage fibrillation B. —Subchondral bone cysts C. Osteophytes D. —Ankylosis of the joint E. Bouchard's nodes D (all the other choices are findings in OA) F428 year old man who works in @ summer camp in upstate New York presents with bilateral facial ‘weakness involving both the upper and lower facial muscles. He also complains of joint pains in both knees. He has a history a few weeks ago of having had a peculiar rash on his right thigh that was circular, red colored and had a central area of clearing. The patient's disease is most likely caused by a A. gram negative diplococcus B. spirochete C. gram positive coccus D. virus E, _ immune complex reaction B (classic Lyme disease, due to the spirochete Borrelia burgdorferi) e A febrile, sexually active 23 year old woman presents with a hot, swollen right knee and pustular lesions on the palm of her left hand. She recently retumed from a camping trip in Colorado. A gram stain of the synovial fluid in the knee and from an aspirate of one of the pustules revealed a gram positive diplocoecus ‘gram negative rod spirochete gram negative diplococcus intranuclear inclusion (disseminated gonococcemia due to Neisseria gonorrhoeae, a gram negative diplococcus) moowpeNote: This material is copyrighted, AU rights reserved. 7 Septic arthritis and tenosynovitis is most often associated with which one of the following complement abnormalities? A. Cl esterase inhibitor deficiency B. C2 deficiency CC 3deficieney D. CSa deficiency E. C5-C9 deficiencies E (associated with disseminated gonococcemia) F A veterinarian develops tenosynovitis within 24-hs of an animal bite. You suspect the offending organism is. A. Yersinia pestis B. Eikenella corrodens C. Fusobacterium D. Pasteurella multocida E. Staphylococcus aureusNote: Skin eo ‘This material is copy: hed. All rights reserved. ‘Normal skin/dermatology terms: 1. epidermis A. stratum basalis: actively dividing stem cells along the basement membrane B. stratum spinosum: prominent desmosome attachments C. stratum granulosum: granular layer with keratohyaline granules D. stratum corneum: anucleate cells with keratin: site for superficial dermatophytes 2. dermis~ papillar 3.___dermatology terms~ — _ Term Definition Examples Hyperkeratosis Increased thickness of the stratum | Chronic dermatitis, Tichen planus corneum. Clinically, it is | psoriasis, ichthyosis, verruca vulgaris manifested as a scaly appearance | (wart) of the skin, Acanthosis Tnereased thickness of the | See above examples epidermis that is most commonly due to hyperkeratosis, Parakeraiosis Persistence of nuclei in the | Psoriasis stratum comeum layer, Papillomaiosis Spire-like projections from the surface of the skin often associated with similar projections downward into the papillary dermis, Vernuca vulgaris, Acantholysis Loss of cohesion between squamous cells, Most commonly due to immunologic destruction of the intercellular bridges. Pemphigus v igaris. Macule Pigmented .or erythematous flat | Lentigo maligna, frecKles (ephelides), lesion on the epidermis lentigo simplex. Papule Peaked or dome-shaped surface | Acne vulgaris, pityriasis rosea. elevation <10 mm in diameter. Nodule Elevated, deep dome-shaped | Epidermal inclusion cyst, basal cell | uses that extends into the | carcinoma, erythema nodosum. dermis. [Plaque | Flattened, elevated area on the | Psoriasis, 7 epidermis >5 mm that is often associated with erythema and sealing. [Vesicle Fluid filed blister 3 mm in | Bullous pemphigoid, scalded skin I diameter. syndrome. Pustule Fluid filled blister with | Impetigo, folliculitis, inflammatory cells. Umbilication Central crater or indentation in a | Molluscum contagiosum, basal cell. papule or nodule. carcinoma,c Note: This material is copyrighted. All rights reserved. = Fexema: n~ skin lesions characterized by pruritus and distinctive gross and micro 2. acute eczema ‘A. weeping, erythematous rash with vesicle formation B. _spongiosis (intercellular edema) in the epidermis 3. subacute eezema~ A. crusts developing over ruptured vesicles, erythema and some scaling of the epidermis B. hyperkeratosis with increased thickness of the stratum comeum chronic eczema— A. lichenification: thickening due to hyperkeratosis from constant soratching B. scaling C. _hyperpigmentation atopic dermatit A. type TIgE mediated disease B. presents in neonates as a rash on the cheeks, trunk, and extensor surfaces: moves to the flexor creases as the child grows older 6. contact dermatitis A. inflammatory disorder of skin associated with exposure to various antigens and irritating substances B, allergic contact dermatitis: (1) cell mediated type IV hypersensitivity reaction 2) _ poison ivy-oak-sumac @) nickel (4) chemicals: a. household cleaners b. medications (5) QUSMLE scenario’ child develops a rash while running through bushes: poison C. irritant contagt dermatitis: () MC type @) nonimmunologic reaction due to a local toxic effect of a chemical on the skin (B) detergents present in soaps D. contact photodermatitis: (Q) type of allergic contact dermatitis that is dependent on ultraviolet (UV) light reacting with drugs that have a photosensitizing effect a. tetracycline b. sulfonamides c. _ thiazides 2) USMLE seenarios: a. girl playing’ soccer is on tetracycline and distribution of rash is face, neck, forearms, and legs (shorts) . same question asked with a baseballplayer (legs would not be involved) contact urticaria: (1) wheal and flare reaction: @) IgE mediated (3) _non-immunologic reactionNote: This material is copyrighted. All rights reserved. @ Seborrheic dermat 1, definition scaly, often greasy type of dermatitis: 2. locations— A. scalp: Q) dandruff @) cradle cap in infants B. face: (1) eyebrows (2) nasal creases 3. due to a Pityrosporum species (Malassezia furfur)~ disseminated in AIDS F Superficial mycoses (dermatophytoses): 1. definition group of fungi confined to the stratum comeum or its appendages (1) circular, or ring-shaped patches (" erythema and scaling @) MCC is Trickophyton tonsurans: negative Wood's lamp, since the pathogen infects the inner hair shaft pathogen () Microsporum canis second MC pathogen: Wood's lamp positi pathogen infects the outer hair shaft 3. other types of tinea— A. MC cause is Trichophyton rubrum B. KOH preparation for yeasts and hyphae 4. tinea versicolor— A. caused by Malassezia furfur B. associated with areas of hyper- and hypopigmentation after exposure to the sun scrapings reveal the classic “spaghetti (hyphae) and meatball (yeast)” appearance 5. Rx of dermatophytes- ‘A. topical imidazoles for body fungi B. griseofulvin for hair/nails Candida albicans. 1. commonly produces cutaneous disease involving the skin~ 2. MCC of diaper rash 3. MCC of onychomycosis (nails) ingworm”) of alopecia (hair loss) with since the © Maculopapular disorders: 1. definition combination of macules (lat, pigmented lesions) and papules (peaked lesions <1 cm) 2. human papillomavirus (HPV)~ ‘A. condyloma acuminata: venereal warts (HPV 6, 11) B. common warts: verruca vulgaris 3. molluscum contagiosum— A. poxvirus family B. bow! shaped lesion 2) central area of umbilication filled with keratin @)_ viral particles in keratin debris C.-MC in children 226Note: This material is copyrighted, All rights reserved. 6 D. disseminated in HIV measles (rubeola)- A. clinical: (1) fever 2) conjunctivitis @)_coryza (excessive mucous production) (4) Koplik spots in the mouth: followed by maculopapular rash that begins at the hairline and extends down over the body (5) not teratogenic (©) otitis media common (@) pneumonia: Warthin-Finkeldey giant cells () subacute sclerosing panencephalitis German measles (rubella) “three day measles" fever arthralgias (characteristic) painful postauricular lymphadenopathy (characteristic) 1 to 2 days prior to the onset of 4 maculopapular rash: begins on the head and spreads downward E, teratogenic: see genetics notes parvovirus B19- ‘A. erythema infectiosum (Fifth disease): (1) confluent maculopapular rash @) usually beginning on the cheeks (‘slapped face” appearance) 3) _ extends centripetally to involve the trunk B. other parvovirus associations: (Q) pure RBC aplasia @) chronic arthritis @) _ repeated abortions roseola (exanthem subitum)— A. caused by herpesvirus 6 B. sudden onset of @ high fever that falls by erisis on the 3rd to 4th day C. _ followed by a maculopapular rash that begins on the trunk and spreads centrifugally ‘toxie shoek syndrome (TSS) A. due to a toxin producing strain of Staphylococcus aureus: most frequently associated with tampon wearing menstruating women B. 1-4 day prodrome: (1) high fever (39°C) Q) mental confusion ope 3) diarthea (4) hypotension (5) pharyngi (6) erythematous rash that occurs during or soon after menses: a. diffuse, blanching, sunburned appearance b. occurs predominantly on the hands/feet © resolves with desquamation in 7-10 d C. Rx withmafeillin(USMLE)Note: This material is copyrighted. All rights reserved. searlet fever~ A. Streptococcus pyogenes that generates an B. erythematous rash (sandpaper consistency): (1) begins on the trunk and limbs @) resolves with desquamation C.circumoral pallor D. tongue initially has a “white strawberry” appearance: followed by a “red strawberry appearance when desquamation occurs E. association with post-streptococcal glomerulonephitis 10. drug reactions- A. MC skin lesion associated with drugs B. eg, penicillin, sulfa drugs © Papulosquamous disorders: 1. actinic (solar) keratosis— ‘A. pre-malignant skin lesion: (1) may progress to squamous cell carcinoma 2) _ hyperkeratotic, pearly gray/white appearance B, _ induced by UVB light damage on sun exposed areas like the face, hands, and forearms C. also associated with arsenic poisoning 2. lichen planus: ythrogenic toxin A. _ intensely pruritic, scaly, violaceous, flat-topped papules: () wrists @) scalp B. oral mucosa (50%): (1) fine white net-like appearance called Wiekham's striae @) precursor for squamous cell carcinoma 3. psoriasis A. chronic disorder characterized by erythematous plaques secondary to an unregulated proliferation of keratinocytes: hyperplasia pathogenesis: (1) genetic factors @) environmental factors: e.., infection due to streptococcal pharyngitis @) _ unregulated epidermal proliferation (4) microcirculatory changes in the superficial papillary dermis (5) associated with destructive arthritis if patient is HLA-B27 ©. plagues: (1) located on sealp: MC location (2) _ pressure areas like the elbow 3) well-demarcated, fla, elevated salmon colored lesions (8) covered by silver-white scales: reveal pinpoint areas of bleeding (Auspitz sign) when picked off (8) _ rash develops in areas of skin trauma: called Koebner's phenomenon 5 © pitting of the nails D. microscopi (1) hyperkeratosis 2) _parakeratosis: persistent nuclei in the stratum comeurn @) focal absence of granular layer© ‘Note: This material is copyrighted. All rights reserved. (4) regular pattern of elongation of the rete pegs: downward extensions of the basal layer (5) _ extension of papillary dermis close to the surface epithelium: a. blood vessels located just below surface epithelium b. rupture when scales are picked off (Auspitz sign) (6) collections of neutrophils in the stratum comeum: called Munro microabscesses B Rx (1) topical steroids @)__ methotrexate in resistant cases F. (USMUE)scenario: picture of psoriatic plaques on elbow of Afic 4% pityriasis rosen— A. presents initially as a single, oval shaped, scaly, pink plaque on the trunk: called a “herald patch” B, followed in a few days to weeks by an eruption of papules on the trunk: rash follows the lines of cleavage in a “Christmas tree” dist American Vesiculobullous disorders: 1. herpesvirus type I and IT infections~ see gynecology notes, 2, chickenpox (varicella) ‘A. presents with a rash: (1) macules vesicles-> pustules (2) _ lesions at different stages of development (3) _ begins on the trunk and extends centrifugally to involve the face and extremities, B. Tzanck prep of vesicles has multinucleated squamous cells with intranuclear inclusions like Herpes C. _cerebellitis is common: self-limited D. association with Reye's syndrome if patient takes aspirin 3. Herpes zoster (shingles) A. reappearance of the varicella-zoster virus B. _ remains dormant in sensory dorsal root ganglia after the primary infection C. presents as an“eruption of painful vesicles: rash follows along the dermatome of a sensory nerve D. Rx with acyclovir 4. impetigo A. Streptococcus pyogenes B. rash begins on the face: (1) erythematous macules and progresses into vesicles and pustules that rupture to form honey colored, crusted lesions @) sometimes superinfeeted with Staphylococcus aureus: adds a bullous component to the lesions C. associated with post-streptococeal glomerulonephritis 5. scalded skin syndrome— A. neonatal disease B, development of bulla (blisters >1 cm) that rupture and leave large, red areas of denuded skin C. caused by a toxin producing Staphylococcus aureusNote: This material is copyrighted, Ail rights reserved. 6. pemphigus vulgaris~ A. autoimmune skin disease (Q) 1G antibodies directed against the intercellular attachment sites (desmosomes) between keratinocytes @) type IT eytotoxic antibody hypersensiti B. produces vesicles (blisters <5 mm) and bull (1) lesions occur on skin and of oral mucosa Q) vesicles are intraepidermal @) —suprabasal location 8. just above the basal cell layer bb, basal cells intact and look like a row of tombstones (4) detachment of individual keratinocytes from each other: a, called acantholysis b. keratinocytes are present within the vesicle fluid (5) _ bulla exhibit the Nikolsky sign: outer epidermis separates easily from layer with minimal manual pressure C. Rx with systemic corticosteroids bullous pemphigoid A. autoimmune vesicular disease: IgG antibodies directed against the basement B. vesicles are in a subepidermal location (1) negative Nikolsky sign Q)__acantholysis is not present 8. dermatitis herpetiformis— A. autoimmune vesicular disease: (1) "IgA immunocomplexes (type IIT immunocomplex reaction) located at the tips of the dermal papilla (2) subepidermal vesictes with neutrophils B. strong association with celine disease C. _ anti-reticulin antibodies 9. erythema multiforme- A. immunologic reaction? B. skin: (vesicles @) _ bullae with bull’s eye lesions: "target cell” of the skin . involves mucous membranes: (1) called Steven's Johnson syndrome @) response to an infection: e., Mfvcoplasma pneumoniae @) response to drugs: a. penicillin b. sulfa drugs (4) response to various autoimmune diseases (SLE) or pregnancy ‘ty reaction F Pustular disorders: 1. Staphylococcus aureus A. gram positive coccus associated with (Q) furuncles (boils) (2) carbuncles (furuncle with multipl (3) _ bullous type of impetigo (4) scalded skin syndromeNote: This material is copyrighted, All rights reserved. (8) _ toxic shock syndrome (6) hidradenitis suppurativa: a. abscess of apocrine glands b. usually in the axilla (7) paronychial infections (8) postoperative wound or stitch abscesses (9) postpartum breast abscesses 2, acne vulgaris— A. chronic inflammatory disorder involving the pilosebaceous unit in the skin B. obstructive type: (1) closed comedones (whiteheads) (2) _ open comedones (blackheads) inflammatory type: (2) _ papules/pustules/nodules/eysts/scars 2). candidate for isotretinoin acid | D. pathogenesis of obstructive type (comedones): plugging of the outlet of a hair follicle | by keratin debris pathogenesis of inflammatory type: () abnormal keratinization of the follicular epithelium 2) _ increased sebum production (androgen controlled) | (3) bacterial lipase (Propionibacterium acnes): production of irritating fatty acids that produce an inflammatory reaction aggravating factors: (Q)__ hormones (e.g, testosterone, progesterone, glucocorticoids) Q) drugs (e.g, lithium) 3) occupational factors (e.g, grease) (4) dietary factors do not contribute to acne (e.g, chocolate, nuts) 3. acne rosacea~ inflammatory disease of the pilosebaceous units on the face in middle aged individuals Urtieai 1. definition urticaria (hives) refers to the presence of pruritic elevations of the skin 2. causes— A. secondary to histamine release and other chemical mediators (type I IgE reaction) from exposure to: (2) _ foods (shellfish, peanuts) (2) drugs (eg,, penicillin) (3) _ insect bites (e.g., bee sting (4) _radiocontrast dyes B. _ may be immunocomplex (type TI} induced: serum sickness like syndrome in HBV angioedema— A. unlike urticaria, it is edema within the deeper subcutaneous tissue B. produces diffuse swelling of the involved tissue: (1) Cl esterase inhibitor deficiency 2) _ bradykinin effect of ACE inhibitors or IV vancomycin ("red man' syndrome) = Cellulitis: 1, cellulitis with lymphangiitis ("red streaks") A. characteristic of Streptococcus pyogenes infections B. elaboration of hyaluronidase: allows exudate to spread through the subcutaneous tissue 231Note: This material is copyrighted. All rights reserved. 2. erysipelas— A. due to Sireprococcus pyogenes: B. raised, erythematous (""brawny edema’): hot cellulitis C. usually on the face ® Atrophy of skin: 1. SLE and chronic discoid lupus~ A. produce skin lesions associated with epidermal atrophy B. pathogenesis (1) anti-DNA antibodies directed against DNA trapped in the basement membrane (planted antigen) @) DNA-anti-DNA immunocomplexes that deposit in the basement membrane of the skin 8. deposits noted in involved and uninvolved skin in SLE b. deposits only present in involved skin in chro CC. microscopic: (2) immune reaction leads to degeneration of the basal cells along the dermal epidermal junction and hair shafts: basis of the band immunofluorescent test 2) lymphoid infiltrate in the same areas as well as around vessels in the papillary dermis @) epidermis atrophic (4) follicular keratin plugs along the surface ® Benign nodular and cystic disorders: 1, subcutaneous mycoses~ A. acquired by puncture wounds (traumatic implantation) of the skin B, _ may also extend into the underlying bone chromoblastomycosis— A. verrucous (wart like) dermatitis associated with several pigmented fungi (USMLE): elicit a granulomatous reaction B, commonly occurs in carpenters that get wood splinters 3. sporotrichosis (USMLE)—) - ‘A. caused by Sporothric schenckii (1) acquired from traumatic implantation of the fungus growing in th 2) commonly occurs in rose gardeners B. clinical: (1) lymphocutaneous disease: chain of suppurating subcutaneous nodules 2) Rx with oral potassium iodide 4. Mycobacterium leprae~ A. acid fast organism: (1) cause of leprosy @) transmitted by direct contact or droplet inf B. _ tuberculoid type Q) intact cellular immunity: granulomas can develop ie discoid lupus soil tion (2) _ positive lepromin skin test (test of cellular immunity) (3) _ causes localized skin lesions with nerve involvement leading to: a, skin anesthesia b. muscle atrophy ©. autoamputation of digits (4) no organisms in lesionsNote: This material is copyrighted. All rights reserved. C. _lepromatous type: (1) lacks cellular immunity (2) negative lepromin skin test @) _ organisms easily identified in tissue within macrophages (lepra cells) (4) associated with the classic leonine facies (8) _ skin biopsies: & narrow zone bertcath the epidermis that is free of organisms called Grew zone (USMLE) b. underlying Grenz zone contains foamy macrophages with organisms (©) neural involvement is a late feature of the disease 5. keratoacanthoma~ A. rapid growth of a crateriform lesion B. _regresses and involutes with scarring C. _ histologically confused with a well-differentiated squamous cell carcinoma 6. erythema nodosum— 4. MCC of inflammation of subcutaneous fat (panniculitis) B. raised, erythematous, painful nodules usually on the anterior portion of the shins C. associations: (1) _ coccidioidomycosis/histoplasmosis\(USMIEY (2) _ streptococcal infections @) sarcoidosis (® TBAeprosy (©) drugs (e.g, sulfonamides) ‘Skin cancers associated with UV light damage (exeluding malignant melanoma): 1, basal cell carcinoma (BCC) A. MC malignant tumor of the skin oceurs on sun-exposed, hair-bearing surfaces locally aggressive, infiltrating cancer. (1) arises from the basal cell layer of the epidermis @) multifocal @) do not metastasize A) locations: of a, inner aspect of the nose b. around the orbit upper lip D. appearance: (1) raised nodules containing a central crater 2) _ external surface of nodule is pearly-colored and has prominent vascular channels visible beneath the surface E, microscopic: (1) cords of basophilic staining cells originating from multiple locations along the basal cell layer infiltrate into the underlying dermis @) form neatly arranged nests of malignant, basophilic staining cells with peripheral palisading 2. squamous cell carcinomas (SCC) of the skin— A. low but significant potential for metastasis: B. located on the face: ears, nose, lower lip C. predisposing causes:Note: This material is copyrighted, All rights reserved. (1) _arsenie poisoning (2) chronic skin uleers (3) sinusitracts (particularly chronic osteomyelitis SMILE)" (4) _ sites of previous radiation/burn scars (5) MC cancer associated with immunosuppressive therapy (USMLE scenario: ulcer at orifice of chronically draining sinus that does not go away with antibiotics, ete ‘Epidermal inclusion cyst 1, derived from the epidermis of a hair follicle 2. contains lipid-rich debris intermixed with laminated keratin material Pilar cyst (wen): scalp lesion similar to epidermal inclusion cyst except for the absen 1, stratum granulosum layer in the cyst wall 2. laminated keratin in the eyst ® — Melanocytic disorders: 1. vitiligo- A. autoimmune destruction of melanocytes resulting in areas of depigmentation B, common in African-Americans C. usually associated with other autoimmune diseases D. compare with albinism: (1) melanocytes present in albinism (2) _ both have absence of melanin pigment 2, seborrheic keratosis ‘A. benign epidermal tumor: B. presents on the skin of middle aged individuals C. raised, pigmented lesions with a verruca-like surface D, rapid increase in number called Leser-Trelat sign: possible gastric adenocarcinoma 3. acanthosis nigrieans~ ‘A. pigmented skin lesion commonly present in the axilla B. _ phenotypic marker for an underlying adenocarcinoma of the stomach 4. freckles (ephelides)~ ‘A. pigmented macular lesions that occur in sun-exposed B, not premalignant €. normal number of melanocytes along the basal cell layer: increase in melanin within individual melanocytes ‘chloasma/melasma (USMLE)- A. flat, hyperpigmented lesions on the forehead and cheeks B, occur in Women on oral contraceptives or who are pregnant: "preganeyimask" 6. — nevocellular nevus— A. benign tumor of neural erest-derived cells: contain modified melanocytes of various shapes (nevus cells) B. begin in early childhood as junctional nev as of the skin (1) nests of pigmented nevus cells along basal cell layer @) flat, pigmented lesions (3) _ junctional nevi develop into compound nevi compound nevus: (1) nevus cells extend into underlying superficial dermis @) both a junctional and intradermal component @) raised, pigmented, verruca-like lesionsNote: This material is copyrighted. All rights reserved. (4) usually children/adolescents D. intradermal nevus: (1) develop around puberty @) compound nevus loses its junctional component (3) _ pigmented nevus cells only within the dermis (4) MC nevi in adults E. dysplastic nevus: (1) more likely to develop in patients who have numerous nevi spread over the entire body: called the dysplastic nevus syndrome (2) predispose to malignant melanoma 7. malignant melanomas. A. derive from melanocytes B. epidemiology: (1) affect both sexes equally ] 2) more common in whites than African Americans 3) _ predilection for fair skinned, blue eyed persons with red or blond hair C. risk factors: (1) exposure to excessive sunlight at an early age single most important predisposing risk factor 2) Hx of severe sunburn (3) dysplastic nevus syndrome (4) melanoma in first/second degree relative (5) _ xeroderma pigmentosum: AR disease with a lack of DNA repair enzymes (6) congenital nevus (1) lentigo maligna D. radial growth phase: (1) initial phase where melanocytes proliferate laterally within the epidermis, along the dermoepidermial junction, or within the papillary dermis (2) they do not metastasize while in this phase E, _ vertical growth phase: malignant cells penetrate into the underlying reticular dermis F. superficial spréading melanoma: (1) MC type (70%) @) primarily affects women >50 years of age (3) lower extremities/back MC sites (4) black, irregular, raised lesions (5) focal brown and/or red areas of discoloration (©) foci of depigmentation and ulceration Jentigo maligna melanoma (4~10%): (1) extension of a lentigo maligna (intraepidermal lesion) into dermis 2) _ primarily occur on the sun exposed face in elderly people H, nodular melanomas (15-30%): (1) lack radial growth phase @) directly invade into dermis 3) _ poor prognosis 1. Saeral lentiginous melanomas (2-82): (1) _ located on the palms/soles/subungual regions @) MC type in African Americans 8) @USMILE'tried to pass off a picture of a subungual hematoma for an acral lentiginous melanoma 235Note: This material is copyrighted. All rights reserved. K. L. Breslow system: (1) _ best staging system (2) measures depth of invasion from the outermost granular layer to the deepest margin of the tumor 3) _ lesions with <0.76 mm of invasion do not metastasize (4) _ lesions with >1.7 mm of invasion have the potential for lymph node metastasis Clark system: subdivides invasions into levels I through V overall 5 year survival regardless of type is ~80% Acute intermittent porphyria (AIP): 1, porphyrin synthesis A B. c 2. enzyme defici drugs produce SER hyperplasia lead to a decrease in heme (part of cytochrome system (QD) barbiturates (2) alcohol heme has a negative feedback on activity of 6-aminolevulinie acid synthase (rate limiting enzyme in porphyrin synthesis): see schematic drugs lowering heme, cause an increase in ALA synthase activity cy in AIP is uroporphyrinogen synthase— ‘A. AD disease: uncommon for an enzyme deficiency B. accumulation of porphobilinogen and 8-ALA proximal to the enzyme block occurs precipitates an acute porphyric attack 3. clinical A. abdominal pain simulating acute abdomen: (1) mistaken as a surgical abdomen (2) end up with a "bellyful of sears" B. intermittent exacerbations of neurologic dysfunction (psychosis 2) neuropathies (8) eventual dementia 4. Iab- * ‘A. increase in urine porphobilinogen: (1) must be oxidized to porphobilin before wine-red color produced (2) _ basis of the "window sill” test: sunlight oxidizes porphobilinogen to porphabilin B. increase in urine 6-aminolevulinic acid C.-measure enzyme at any time Rx- A. periodic infusions of heme reduce the number of attacks B. avoid drugs that rev up the cytochrome system © Porphyria cutanea tarda (PCT): 1. acquired disease~ A. decreased activity of uroporphyrinogen decarboxylase: see schematic B. net result (1) increased excretion of uroporphyrin I (urine is wine-red color on voiding) (2) slight increase in the formation of coproporphyrins (3) _ normal porphobitinogen levels 2. clinical A. photosensitive bullous skin lesions B. _ hyperpigmentationGlycine + succinyl CoA | ALA synthase (rate limiting) 8-Aminolevulinic acid } ALA dehydrase Porphobilinogen > Porphobilin (color) Hydroxymethylbilane Uroporphyrinogen I | Uroporphyrinogen synthase (1 in AIP) t Coproporphyrinogen 1 Uroporphyrinogen IIL Uroporphyrinogen decarboxylase (1 in j PCT) Coproporphyrinogen III Protoporphyrinogen IX Y Protoporphyrin IX + iron | Ferrochelatase Heme 4 Heme = ¥ ALA synthase activity ¥ Heme = 4 ALA synthase activityNote: This material is copyrighted. All rights reserved. C. fragile skin D. increased amounts of vellus type hair (hyper E. can be precipitated by alcohol ichosis) 7 Alopecia 1. genetic predetermination MCC- MC in males 2. telogen effluvium- when all the hairs enter the resting phase at once A. postpartum B. birth control pills C. high fever D. crash diet Irregular patches of hair loss in child: 1. trichotillomania 2. pulling out of one’s own hair 3. relationship to the dominant hand USMIL'seenaFi6? patient has hyperpigmented spots on the skin which when scratched become intensely pruritic and red 1. patient hasweticaria pigmentosa 2. smastieelhdisense- pressure causes the release of histamine setting up an urticarial reaction ‘Questions used during the board review: ar-old man with congestive heart failure develops cough and swelling in the deep subcutaneous tissue. He is most likely taking A. athiazide diuretic B. an ACE inhibitor C. aphenothiazine D. digitalis E, _acalcium channel blocker B (mechanism is the release of bradykinii) '‘% The most common fungal cause of tinea capitis with a negative Wood's lamp is. A. Trichophyton tonsurans B. Microsporum canis C. Trichophyton rubrum D. Candida albicans E. Malassezia furfur A (M. canis is Woods lamp positive, MCC of tinea capitis) % A 43-year-old woman presents with joint pains and a butterflyclike rash on the face. She is most likely taking A. thiazides B. oral contraceptives C. hydralazine D. doxycycline E, _ barbiturates (procainamide is another drug that is associated with drug-induced SLE)Note: This material is copyrighted, All rights reserved FA 42-year-old man has recurrent development of vesicular and bullous lesions in sun-exposed areas, He has had to avoid alcohol, because it seems to coincide with these episodes. You would expect this patient to have. A. ahistory of abdominal pain B. an increase in 8-aminolevulinic acid in his urine C. an increase in porphobilinogen in his urine D. colorless urine during these attacks | E. _ adecrease in red blood cell uroporphyrinogen decarboxylase ) E (porphyria cutanea tarda) ‘4 30-year-old female with a long history of alcohol and barbiturate abuse presents with diffuse | colicky abdominal pain. Examination reveals numerous surgical scars on the abdomen. There is no | history of photosensitivity. You suspect that her urine would A. contain an increase in uroporphyrin B. contain an inerease in coproporphyrin €. be positive for blood D. have an excess amount of urobilinogen E, tua port wine color after exposure to light E (acute intermittent porphyria)Note: This material is cop: ‘ighted. All rights reserved. ‘Central Nervous System/Special Senses r Increased intracranial pressure: 1 ses noncommunicating hydrocephalus (see below) space occupying mass (e.g., metastatic tumor) cerebral edema: (2) _ intracellular (hyponatremia, ischemia) @) extracellular: increased vessel permeability from tumor, inflammation, trauma, or lead poisoning OF rs 2, clinical ‘A. uncal herniation: (2) medial portion of the temporal lobe hemiates through tentorium cerebelli (2) compression of midbrain: produces Duret’s hemorrhages @) oculomotor nerve palsy a. eye down and out b. pupil mydriatic (4) compression of posterior cerebral artery: hemorrhagic infarction of the lobe B. cerebellar tonsils into the foramen magnum: cardiorespiratory arrest Hydrocephalus: 1. defiition- 2 CSF fluid ‘A. primarily produced by choroid plexus in lateral ventricles» Bets the fourth ventricle through the foramina of Luschka enters the subarachnoid space -> D. _ reabsorbed by the arachnoid granulations into the dural venous sinuses 3. communicating hydrocephalus— Aopen communication of CSF between ventricles and subarachnoid s B. causes (GQ) increased production of CSF: e.g, choroid plexus papilloma (2) block in the reabsorption of CSF by the arachnoid granulations: e.g post-meningits 4. noncommunicating hydrocephalus 4 obstruction to CSF flow out of ventricles B. causes (@) stricture of the aqueduct of Sylvius! MCC in newborns (2) tumors inthe fourth ventricle: eg, ependymoma (8) _Armold-Chiari syndrome (Dandy Walker syndrome (S) blockage of CSF flow out of foramina of Luschka and Magendie: e.g, inflammation, blood elt C.USMLE scenario: (1) _ gross of a colloid cyst in the third ventricle (@) round object in third ventricle and ease of non-communicating hydrocephalus 5 elinical- ‘a newboms: ventricles dilate and enlarge the head cireumference crease in CSF volume with distention of the ventricles id Magendie->Note: This material is copyrighted. All rights reserved. B. adults: (1) progressive dementia @) gait disturbances @) urinary incontinence hydrocephalus ex vacuo~ A. appearance of the ventricles when the brain mass is decreased B. eg,, Alzheimer's disease Open neural tube defects: 1, definition failure of fusion of the lateral folds of the neural plate or 10 rupture of a previously closed tube: 2. increase in maternal a-fetoprotein in serum or amniotic fluid- folic acid teken before pregnancy protects the fetus from these defects 3. anencephaly— complete absence of the brain absence of the fetal adrenal cortex frog-like appearance polyhydramnios bifida failure of the posterior vertebral arches to close on the 26th day of gestation spina bifida occulta; dimple or tuck of hair in the overlying skin of Le-S, meningocele: spina bifida and a cystic mass containing dura and arachnoid ‘meningomyelocele: cystic mass including the spinal cord Syringomyel 1. definition fluid filled cavity (syrinx) within the ce 2. clinical = A. may be acquired later in life from ischemia, inflammation or trauma B, cervical cord enlargement C. associated with Amold-Chiari syndrome D. neurologic deficits: (1) Joss of pain and temperature sensation: disruption of the crossed lateral spinothalamic tracts 2) atrophy of intrinsic muscles of the hands: a. — destruction of anterior horn cells b. confused with amyotrophic lateral sclerosis (no sensory changes in ALS) (3) burn hands and do not know it (USMLB) Arnold-Chiari malformation: malformation associated with elongation of the medulla and cerebellar tonsils through the foramen magnum hydrocephalus platybasia meningomyelocele syringomyelia Jandy-Walker syndrome: syndrome includes— hypoplasia of the cerebellar vermis cystic dilatation of the fourth ventricle hydrocephalusNote: This material is copyrighted. All rights reserved. * Phakomatoses: definition A neurocutaneous syndromes: (1) disordered growth of ectodermal tissue (2) malformations or tumors of the CNS examples: (1) neurofibromatosis (see genetics notes) (2) Sturge-Weber (see cardiovascular notes) (3) tuberous sclerosis tuberous selerosis— A. B. AD disease clinical: (1) mental retardation @) skin lesions a. adenoma sebaceum b. shagreen patches that are hypopigmented (USMLE) © periungual fibromas @. hamartomas: ‘+ proliferations of astrocytes located in subependymal portions of the brain —» "candlestick drippings" within the ventricles + angiomyolipomas in kidneys (3) thabdomyoma in the heart (USMLE) ‘F Infections of the CNS: 1. general comments A. secondary to: (1) hematogenous spread (MCC) @) traumatic implantation (3) _ local extension from nearby infections (4) _ ascent up the peripheral nerves: rabies (S)__ ascent up olfactory bulb: herpes types: (1) leptomeningitis: a. MC type b. hematogenous 2) encephalitis: inflammation of brain @) cerebral abscess leptomeningitis: (1) acute purulent (bacterial) @) lymphocytic (viral) @) chronic granulomatous types: a. primary TB 1b. systemic fungi symptoms associated with leptomeningitis: (fever (2) headache @) nuchal rigidity: positive Brudzinski and Kemig's test (4) altered sensoriumNote: This material is copyrighted. All rights reserved ___E._ CSF findings in bacterial/ — CSF characteristics | Bacterial [Vira | Total Cell Count | 1,000-20,000 celistu. | <1,000 celisiul Differential Count | >90% polys First 24-48 hours, neutrophils, then switches to lymphoeytes/monocytes after 48 hs. CSF glucose Decreased ‘Normal: exceptions mumps, herpes. CSF protein Tnereased Increased Gram Stain Frequently positive (en- | Negative sitivity 75 t0 80%) F. S/S of encephalitis (1) impairment of mental status @) drowsiness (3) _ intracytoplasmic Negri bodies in Purkinje cells in cerebellum in rabies (4) _ intranuclear/intracytoplasmic inclusions: a. CMV: MC CNS viral infection in AIDS b. subacute sclerosing panencephalitis (SSPE) in measles (5) intranuclear inclusions: a. HSV infections: hemorrhagic necrosis of the temporal lobes b. Herpes zoster progressive multifocal leukoencephalopathy (PML) cerebral abscess: (adjacent focus of infection: a. sinuses b. middle ear usually solitary @) hematogenous spread a. cyanotic heart disease b. bronchiectasis ¢ usually multiple 2,__ summary of viruses associated with CNS infections Pathogen | Specific Organism | Disease/Comments 7 Viruses Enteroviruses (85%): | Meningitis: Viral meningitis peaks in late summer coxsackievirus (#1), | and early autumn, It most. commonly. involves echoviruses, | patients <40 years of age. CSF with increased polioviruses protein and lymphocytes, and normal glucose | arborviruses Encephalitis: Mosquitoes are the vector and vertebrates the natural host. Infections primarily occur in humans, St. Louis encephalitis is MC encephalitis. English sparrows are the natural host. Easter equine encephalitis has the greatest momslty. Wild birds are the natural hos. . Herpes Encephalitis/Meningitis/Meningoencephalitis and if HSV-1 produces meningoeneephalitis with hemorrhagic necrosis of the temporal lobes Intranuclear inclusions occur in neurons and glial cells. HSV-2 produces meningitis in adults and | encephalitis in infantsNote: This material is copyrighted. All rights reserved. E.__ CSF findings in bacterial/viral meningitis: see Table CSF characteristics | Bacterial Viral Total Cefl Count | 1,000-20,000 celis/ul. | <1,000 celis/ul Differential Count | >90% polys First 24-48 hours, neutrophils, then switches - to lymphocytes/monocytes after 48 hs. CSF glucose Decreased Normal: exceptions mumps, herpes. [CSF proiein Increased Increased | Gram Stain Frequently positive (Gen- | Negative sitivity 75 to 80%) of encephalitis impairment of mental status drowsiness intracytoplasmic Negri bodies in Purkinje cells in cerebellum in rabies intranuclear/intracytoplasmic inclusions: | a. CMV: MC CNS viral infection in AIDS b. subacute sclerosing panencephalitis (SSPE) in measles ! () _ intranuclear inclusions: a, HSV 1 infections: hemorrhagic necrosis of the temporal lobes b. Herpes zoster c, _ progressive multifocal leukcencephalopathy (PML) cerebral abscess: (1) adjacent focus of infection: a. sinuses b. middle ear usually solitary q (2) hematogenous spread: ! a, cyanotic heart disease b. bronchiectasis ¢. _ usually multiple 2.__summary of viruses associated with CNS infections— Pathogen | Specific Organism | Disease/Comments — Viruses Enteroviruses (85%): | Meningitis: Viral meningitis peaks in late summer coxsackievirus (#), | and early autumn. It most commonly involves echoviruses, patients <40 years of age. CSF with increased polioviruses protein and lymphocytes, and normal glucose. Arborviruses Encephalitis: Mosquitoes are the vector and vertebrates. the natural host. Infections primarily occur in humans. St. Louis encephalitis is MC ! encephalitis. English sparrows are the natural host Eastern equine encephalitis has the greatest mortality. Wild birds are the natural host | Herpes simplex type T| Encephalitis/Meningitis/Meningoencephalitis and IT HSV-1 produces meningoencephalitis with hemorrhagic necrosis of the temporal lobes Intranuclear inclusions occur in neurons and. glial cells. HSV-2 produces meningitis in adults and encephalitis in infants. 242Note: This material is copyrighted. All rights reserved. Pathogen | Specific Organism mn | Varicelta/zoster ranial nerve inflammation/Meningoencephalitis) | Cerebellar inflammation: Herpes zoster (latent | virus) may involve the trigeminal (V) nerve with painful vesicular lesions (shingles) or the VIIIth | nerve (Ramsay-Hunt syndrome, lesions in outer ear canal). Varicella (chickenpox) may produce self limited cerebellar inflammation Rabies virus Encephalitis: In the United States, humans contract rabies by the bite (virus in saliva) of a rabid skunk (Midwest, Southwest, California), fox (New England, Southwest, Alaska), raccoon (East, New England), or bat (bite or aerosolization). Rodents (eg. rabbits, squirrels) may contract rabies but not transmit it to humans, In third world countries, most cases are due to rabid dog bites (includes Mexican border with USA). Viral incubation is 30 to 90 days. Virus enters the CNS by ascending along peripheral nerves. Clinical: prodrome of fever, headache, excitability and paresthesias around the wound site. ~ 80% enter into a CNS excitability stage with pain, convulsions, autonomic excitability, frothing of the mouth Patients avoid water (hydrophobia). Eventually flaccid paralysis progresses to coma and respiratory center failure. Neurons (particularly Purkinje cells) contain intracytoplasmic Negri bodies Diagnosis: serologic tests, culture of infected material (brain biopsy), or direct immunofluorescent techniques on comeal smears, saliva, or skin Quarantine dogs for 10 days (no signs of rabies, no need to immunize the patient). All patients with wild animal bites (listed above) should receive passive (buman rabies immune globulin 1/2 into wound site) and active immunization (human diploid vaccine). Wound must be thoroughly washed out with quaternary ammonium compound soaps. Chtamegalovirus Encephalitis: MC viral CNS infection in AIDS. Intracytoplasmic and intranuclear basophilic inclusions. MC congenital infection in children (encephalitis with periventricular calcification). 243Note: This material is copyrighted, Al rights reserved. Pathogen Specific Organism | Disease/Comments a Poliovirus Myelitis/Encephalitis: Enterovirus that specifically attacks lower motor neurons, particularly the anterior hom cells of the spinal cord (rarely, it can produce an encephalitis as well). Outbreaks occur in summer. Paralysis in children is less severe than adults. Only permanent neurological residual is lower motor neuron paralysis. Post-polio syndrome cur 25-35 ys later. Sabin vaccine is live is a killed vaccine. Cannot use live vaceine in an immunocompromised host (AIDS), but SALK _ vaccine can be used. 3.__ summary of bacteria, fungal and parasit [Pathogen pecifie Organism Bacteria | Neonatal meningitis (<1 | Meningitis: All the infections are maternally | mth): © MCC is group B | transmitted. Group B streptococeus is MCC of streptococcus (Streptococcus | neonatal meningitis (E. coli #2, Listeria ), gram positive | monocytogenes #3). Group B strep may produce E.coli: gram| infection in the first week or up to 4 months negative rod, 2nd MCC, « | later. Women should-avoid. goat's milk'cheese: Listeria monocytogenes, 3rd | tovavoid Listeriosis McC | 1 mth to 18 years of age: « | Meningitis: Hemophilus influenza was once the Neisseria" meningitidis—| #1 cause before immunization against the gram negative diplococcus, | bacteria. N. meningitidis now accounts for the #1 cause, © Streptococcus | majority of child/adolescent/young adult pneumoniae gram positive | meningitis. Usually results in sepsis and may | diplococeus, #2 MCC cause the Waterhouse-Frederickson syn- >18 years of __age: | drome. Petechial lesions are commonly present. ! Streptococcus pneumoniae | Particularly common in crowded conditions (boot camps). All elose contacts must receive ritapin Wo eradicate the arvirstate. | Mycobacterium tuberculosis | Meningitis/Mass lesion: TB — meningitis | (acid fast) generally involves the base of the brain and produces an obliterative vasculitis with associated cerebral infarction, Most commonly 4 complication of primary TB in children. | Associated with post inflammatory scarring with noncommunicating hydrocephalus. CSF has <500 cells/ul. (lymphoeytes/mononuclear celts), high protein (forms # pellicle), normal to low glucose levels, and very low chloride levels. Treatment: Systemic corticosteroids are frequently used along with the anti-tubereulous drugs to combat the vasculitis and the potential for strokes and hydrocephalus. A tuberculoma is 4 granuloma that most commonly locates in the | cerebellum as a mass lesion, | 244Note: This material is copyrighted. All rights reserved. Pathogen | Specifie Organism Disease/Comments Treponema pallidum (spirochete) Myelitis/Encephalitis/Meningoencephalits Neurosyphilis is the tertiary stage of syphilis (10% of patients) and is the MC overall manifestation of tertiary syphilis, Three types meningovascular (25%), paretic, and tabes dorsalis. Meningovascular: chronic low grade meningitis with vasculitis (increased plasma cells around vessels) that frequently presents as a stroke in a young patient in the absence of hypertension; no visible spirochetes. Paretie form: has generalized atrophy (neuronal loss) of the frontal cortex (organisms present), dementia, and an Argyll-Robertson pupil. Tabes dorsalis. spirochetes atlack the posterior root ganglia or their afferent sensory axons between the Posterior root ganglia and the cord producing impaired joint position sense leading to a broad based ataxia and @ positive Romberg’s test (lose balance with eyes closed, but restore balance with eyes open), loss of pain and vibration sensation, joint damage (Charcot sensory disturbances with "lightening absent deep tendon reflexes, Argyll- Robertson pupil: pupils constrict with a near stimulus (accommodates) but fail to react to direct light. No spirochetes present, Laboratory findings in neurosyphilis: positive VDRL (25-50%, best initial test), positive CSF FTA-ABS (80-95%), oligoclonal__ bands (demyelination), mild lymphocytosis, increased protein, normal glucose, Systemic Fungus Cryptococcus neoformans Meningitis/Abscess: MC systemic fungal infection in immunocompromised hosts (e.g AIDS). Numerous budding yeasts (narrow based bud) with absence of an inflammatory response CSF India ink preparation (75% sensitivity) May produce cystic lesions in the brain. Other systemic fungi involve the CNS as well. Candida (multiple abscesses), Histoplasma, Blastomyces, Coccidioides, Mucormycosis (frontal lobe absceNote: This material is copyrighted, All rights reserved. Pathogen Specific Orga Disease/Comments Parasites Taxoplasmagondll (ep oma} ~oro- | Encephalitis: MCC of a space occupying CNS lesion in AIDS. Congenital toxoplasmosis produces basal ganglia calcification Plasmodium falciparum (spo rozoan) Encephalit numbers of RBCS that block capillaries and Produce small necrotic and hemorrhagic. foc usually within the cortex and cerebellum ?. Jelvparun yaraiiinas lage] ‘Naegleria fowleri (free living amoebae) Trypanosoma brucei ga ense or rhodesiense (let flagellate) (Meningoencephalitis. (USMLE): Prowzoal infection contracted by swimming in fresh water lakes. Infects the frontal lobes through the cribriform plate. Encephalitis: Transmitted by tsetse fly. Diffuse neuronal degeneration. Produces sleeping sickness (die of starvation). Trypanosomes in the blood. leM elevated. imb- m0 ~4.__ slow virus diseases of the CNS- [ype Taenia solium (tapeworm) Disease Cyst —formation/Meningitis: _ \Gysticercosis (WSMEE)is contracted when an individual (intermediate host) ingests food or water contaminated with the feces of a person (definitive host) harboring the eggs of 7. solium. There is subsequent development of the cysticerci (larva) in host tissues (subeutaneous tissue, brain, eye, muscle) with cyst formation. Caleified cysts are frequent sites for Jacksonian seizures. Hydrocephalus may occur, ‘omments | Conventional Agent | (PML) ‘Subacute sclerosing panencephalitis (SSPE) Progressive multifocal leukoencephalopathy ‘SSPE is associated with the measles (rubeola) virus cither as a primary infection or as a complication of immunization against measles (live attenuated vaccine). Progressive disease with extensive brain damage leading to death within one to two years. _ PML, due to a papovavirus (JC virus, SV40 virus), infects and destroys oligodendrocytes (intranuclear inclusions) leading to primary demyelination. It is commonly observed in immunocompromised patients (AIDS). 246 °Note: This material is copyrighted. All rights reserved. [Type | Disease Comments senepivent | Creuifelat-Jakob’ (CD)| CI presents as a rapidly prograsive dementia a ‘onal Agent | disease (subacute spong. | subviral transmissible agent" known ce prion | | iform encephalopathy) "| (extracellular protein with no nucleic ac) hae aoe identified. Transmitted by corneal transplantation, improperly sterilized cortical electrodes (neuro, Surgery), contaminated pituitary. growth hormone (no longer used), or eating human brains (called. kure confined to New Guinea head hunters). It is not transmitted person to person and isa health hazed those working with brains (neuropathologists), A fecent outbreak occurred in England (“mad cow” disease). Microscopically, it has a characteristic “bubble and holes” spongiform change in the cerebral cortex with little or no inflammatory reaction, Death SNS trauma; eeswithin ty, 9. CNS trauma: 1, cerebral concussion ‘A. transient loss of consciousness immediately following a nonpenetrating blunt impact to the head: e.g., boxing B. no histologic evidence of damage to the brain 2 cerebral contusions— A+ Permanent damage to small blood vessels and the surface ofthe brain {) most commonly secondary to an acceleration-deceleraton injury @) eg, car accident B. contusions occurring at the site of impact are coup injuries C. contusions occurring on the opposite side of the brain are called contrecoup injuries more damage than coup injury = D. contusions and lacerations usually occur at the tips ofthe frontal and temporal lobes . ++ diffuse axonal injury— shearifg of axons located in the white matter tacts fe the brain - and/or brain stem 4. meningeal tears = A. occur with basilar and orbital skull fractures = B. frequently results in loss of CSF fluid through the nose (chinorthea) and/or ears 4 (otorrhea) C. CSF hias a lower protein and glucose and higher ehloride than serum 5. acute epidural hematoma— A. definition (1 Bacture ofthe temporoparietal bone with severance ofthe middle meningeal artery (2) _ artery lies between the dura and inner table of bone initially unconscious but then becomes lucid arterial bleeding creates a blood filled space between the calvarium and dura intracranial pressure increases leading to herniation and death unless the removed 6 subdural hematoma— A. definition: () collection of venous blood between the dura and the arachnoid m 247‘This material is copyrighted, All rights reserved. 2) _ most often the result of blunt trauma @) MC in patients with cerebral atrophy a. elderly patients b. chronic aleoholies (4) bleeding due to tearing of bridging v convexities of the cerebral hemispheres (©) _ organized blood clot over convexity of brain B. fluctuating levels of consciousness C. CT scans best examination for demonstrating intracranial hemorrhages in the first 48 hs: MRI is best after 48 hs ‘Vascular injuries in the CN: 1, neurons and neuroglial cells susceptible to oxygen deprivation (hypoxia) or hypoglycemia— A. neurons most sensitive in descending order: () hippocampus (2) cerebellum (Purkinje cells) (3) _ layers 3, 5, 6 in cerebral cortex (4) neurons are permanently differentiated B. _neuroglial cells most sensitive in descending order: (1) oligodendrocytes: synthesis of myelin (analogous to Schwann cell in peripheral nervous system) (2) astrocytes: a. blood-brain-barrier b. —repaircell €. analogous to fibroblast, except collagen is not produced (3) neuroglial cells are stable cells and can divide 2. chronic ischemia— A. MC secondary to atherosclerosis involving internal carotid artery B. laminar necrosis secondary to apoptosis of neurons in layers 3, 5, and 6 of the cerebral cortex: cerebral atrophy C. watershed infarcts: junctions between overlap of major arterial territories, D. cerebrovascular accidents (strokes) Cerebrovascular accidents (strokes): 1. types A. ischemic (80%): (1) majority due to atherosclerosis, 2) infarction due to liquefactive necrosis B. hemorrhagic (20%): (1) majority due to embolism (embolic stroke) from the left heart @) _ infarction due to liquefactive necrosis C. intracerebral bleed (10%): (1) intracerebral hemorthage most often due to hypertension @) intracerebral hematoma D. _ subarachnoid hemorrhage (10%): MC due to a ruptured congenital berry aneurysm 2. atherosclerotic strokes— A. AMC due to platelet thrombus overlying an atheromatous plaque in the internal carotid near the bifurcation B. 80% are pale infarets (liquefactive necrosis) between venous sinus located over the 248 oNote: This material is copyrighted. All rights reserved. (1) _ usually in distribution of the middle cerebral artery (MCA) @) _ pale infarct because there is usually no reperfusion (3) hemorrhagic if they do reperfuse (20%) C. microscopie: (1) reactive astrocytes (gemistocytes) proliferate a the margi (2) microglial cells (macrophages of CNS) remove lipid debris (3) response to injury is called gliosis (4) cystic area after 10 days to 3 weeks D. majority preceded by transient ischemic attacks (TIAs): (1) due to embolization of platelet or cholesterol plaque material into the periphealvessls— (2) results in transient neurologic deficits lasting <24 hours > {ej G) _ deficits not resolving within 24 hours are called strokes fXe/ E. _ clinical manifestations of MCA occlusion; x 7 (1) contralateral hemiparesis and sensory loss Stroke (2) expressive aphasia if Broca’s area is involved in the dominant (left) hemisphere (3) amaurosis fugax: a, fleeting blindness b. cholesterol embolus seen in retinal vessels: called Hollenhorst plaque (4) visual field defects: a. contralateral inferior quadrantanopsia or b. homonymous hemianopsia (©) deviation of the head and eyes toward the side of the lesion F. _ vertebrobasilar arterial system strokes: (1) vertigo @Q) ataxia (3) _ ipsilateral sensory loss in face and contralateral hemiparesis and sensory loss in the trunk and limbs G. _ majority of patients survive and recover some function 3. embolic stroke- A. thromboemboli originating in left heart or plaque material from internal carotid B. MC associated with a hemorrhagic infarction in the distribution of MCA: (1) area of infarction usually limited to the gray matter at the periphery of the brain 2) hemorrhagic because of reperfusion of the occluded vessel ) mortality ~30% 4, intracerebral hemorrhage- ‘A. MC secondary to vascular changes related to hypertension: (1) vascular changes occur in penetrating branches of lenticulostriate vessels: (2) formation of Charcot-Bouchard macroaneurysms—> (3) rupture of aneurysms—> (4) intracerebral hemorrhage (clot, not infarct) B. _ locations: = (1) basal ganglia (35-50% in the putamen) (2) thalamus (10%) (3) pons (10%) (4) _ cerebellar hemispheres (10%) C. 30-40% mortality D. effective Rx of hypertension has its greatest benefit in preventing strokes of infarct, layreng, 249Note: This material is copyrighted, AU rights reserved. subarachnoid hemorrhages~ ‘A, majority secondary to rupture of a congenital berry aneurysm (80%): arteriovenous malformations less common cause B. patients (usually women) between the ages of 40~65 ys old C. congenital aneurysms (2) absence of internal elastic lamina and smooth muscle in the media of ce vessels 2) particularly occur at branching points in the vessels (3) _ above histologic changes are present in all people (4) aneurysms are not present at birth: a. “develop with normal hemodynamic stress or b. presence of hypertension: * essential hypertension * due to adult polycystic kidney di * due to increased pressure in a postductal coarctation of the aorta ‘* due to renovascular hypertension (4) MC aneurysm site is junction of anterior communicating artery with ACA D. clinical: (1) sudden onset of severe occipital headache ("worst headache I have ever had") followed by a loss of consciousness (2) _ blood in subarachnoid space covers entire surface of brain (3) ~25% die from first bleed (4) additional 25-35% die by end of first year owing to rebleeds 6. lacunar infarets A. small ( men B. associations: (1) neurofibromatosis (2) deletions on the long arm of chromosome 22 @) _ previous Hx of radiation C. locations (1) convexities of brain: parasagittal MC site Q) olfactory groove (3) _ lesser wing of the sphenoid (4) _ spinal cord (thoracic segment) D. _ gross/micro: () firm tumors 2) may indent (not invade) the surface of brain (3) common cause of new onset seizure activity in adults (4) infiltrate overlying bone: a. nota sign of malignancy b. visible hyperostosis on a skull x-ray () swirling masses of meningothelial cells encompassing (caleified bodies): only benign tumor with psammoma bodies 9. CNS lymphomas- oe A. MCC are metastatic high grade non-Hodgkin's Iymphomas of B lymphocyte origin meningeal spread and spare parenchyma primary CNS lymphomas: (1) multifocal in their distribution @) most often associated with AIDS: HIV and EBV mediated 3) _ also associated with immunosuppression in renal transplant patients (4) _ incidence increased over the last decade due to AIDS sammoma bodies 256Note: This material is copyrighted. All rights reserved. 10. schwannomas (neurilemomas)~ A. benign tumors derived from Schwann cells: (1) cranial nerves @) spinal nerve roots (3) __ peripheral nerves B, MC intracranial site is the cerebellopontine angle (1) involvement of the Vilith cfanial nerve: called acoustic neuroma . acoustic neuroma: (1) _ tinnitus (MC symptom) @) sensorineural deafness (3) _ sensory changes in trigeminal nerve distribution oscopi "zebra tumor" ‘compact Antoni type A areas interspersed with loosely structured my appearing areas designated Antoni type B areas E, WSMLEséenarios CT with enlarged internal ac: tinnitus, nerve deatnes 11. metastasis is MC CNS cancer ‘A. lung cancer MC primary site B. women non-smoker: consider breast CNS and PNS abnormalities in AIDS: 1. HIV enters the CNS via macrophages/monocytes (reservoirs of HIV) and astrocytes microglial cells are the reservoir for HIV in the CNS 2. € primary CNS lymphomestee previous discussion 3. ‘meningitis 4. encephalitis ‘A. AIDS dementia complex (ADC): (1) motor impairment (e.g., spasticity) (2) cognitive deficits (3) neurological deficits (¢.g., memory loss) (4)__ behavioral or neuropsychological impairment (e.g., hallucinations) B. multinucleated microglial cells is « characteristic feature fomatous © meatus in a patient with 5. vacuolar myelopathy. A. subacute combined degeneration of spinal cord B. similar to Byz deficiency but not due to Bip deficiency 6. peripheral neuropathy 7. opportunistic infections A. CMV: MC CNS virus B. toxoplasmosis: (1) MC parasite @) MCC space occupying lesions C. C.neoformans: MC fungal CNS infection © Peripheral neuropathies: 1. types- A. demyelination (often segmental): (1) sensory changes @) symmetrical "glove and stocking" distribution of sensory loss (3) _ burning foot” syndromer & Note: This material is copyrighted. All rights reserved B. axonal degeneration: muscle atrophy and fasciculations C. combinations of the two 2. causes— A. diabetes mellitus: «McC @2)__ osmotic damage of Schwann cells, B. toxins: (1) alcohol @) heavy metals (e.g., Pb) @) diphtheria C. amyloidosis D. drugs: (1) isoniazid (B, deficiency) 2) __ vincristine E. nutritional deficiencies: @) thiamine Q)_ pyridoxine 3. Guillain-Barré syndrome— A. MCC acate peripheral neuropathy: autoimmune demyelination syndrome B, presents with an ascending or descending paralysis, C. high CSF protein levels + few lymphocytes D. _ Rx: plasmapheresis (USMILE) 4. Charcot-Marie-Tooth disease~ ‘A. MC genetic (AD) peripheral neuropathy B. peroneal nerve C. atrophy of muscles of lower legs D. _ inverted bottle appearance 5. Wallerian degeneration see cell injury notes 6. idiopathic Bell's palsy- A. acute onset of unilateral factal nerve (VIIth nerve) paralysis ! B. HSV I may be implicated C._Lyme's disease if bilateral: Vilth nerve MC cranial nerve involved D. clinical: (1) drooping of the comer of the mouth @) difficulty with speaking 3) _ inability to close the eye (4) drooling ‘F Orbital cellulitis vs cavernous sinus thrombosis: ! 1. both have proptosis of the eye and poor eye movements 2. cavernous sinus thrombosis has papilledema ‘Treatment of CMY retinitis in AIDS if ganciclovir does not work: 1. foscarnet (renal toxicity) 2. CMV retinitis MCC of blindness in AIDS % Menetrier disease: 1, inereased endolymph in inner ear 2. dizziness 3. vertigo 4. sensory hearing lossNote: This material is copyrighted. All rights reserved. 5. horizontal nystagmus Benign positional vertigo: 1. MCC recurrent vertigo 2. no hearing loss or tinnitus 3. nystagmus 4. due to dislocation of otoliths Conjunctivitis: 1. bacterial A. Staphylococcus aureus B. Hi. influenzae C. Streptococcus pneumoniae 2. viral- A. adenovirus B. HSV I: dendritic ulcers 3. _allergie~ seasonal * Glaucoma: 1. increase in intraocular pressure— fluid cannot exit canal of Schlemm 2. clinical A. pain B, blurry vision C. pupil fixed and mid-dilated D. optic atrophy and blindness if not treated © Sudden unilateral loss in vision: 1, amaurosis fugax— A. embolism of atherosclerotic plaque to retinal vessel B, “curtain down and then up" 2. retinal artery occlusion— embolism MCC 3. retinal vein ocelusion— polycythemia MCC uveitis! » 1, inflammation of uveal tract (choroid, ciliary body, iris)— A. clinical: (pain @) blurry vision 3) severe photophobia (4) congestion of ciliary vessels around comea (8) miotic pupils (6) poor light reflex (7) normal pressures 2. veatises (USMLE)- A. ankylosing spondylitis B. rheumatoid arthritis C. sarcoidosis D. juvenile rheumatoid arthritis r 1, inflammation of optic nerve 2. causes— 259Note: This material is copyrighted. AM rights reserved. ‘A. multiple sclerosis MCC B, _ methyl alcohol poisoning 3. clinical— pain blurry vision flame hemorrhages around nerve danger of optic atrophy (1) cupping of disk margin 2) pale disk due to absence of disk vessels, Macular degeneration: MCC of blindness in elderly F Weber test/Rinne test: 1. Weber test reveals tuning fork sound lateralizing to affected ear in conduction deafness Rinne test shows bone conduction > air conduction in that ear 2. Weber test reveals lateralization of sound to normal ear in sensorineural hearing loss~ Rinne test shows preservation of air > bone conduction in both normal and abnormal ear which means that the opposite ear is affected ear © Presbyeusis: MCC of sensorineural hearing loss in elderly o Otosclerosis: 1. MCC of conduction deafness in elderly 2. middle ear ossicles fuse F Otitis media: 1, MC conduction deafness in children— pathogens in descending order: A. Streptococcus pneumoniae B. — Hemophilus influenzae C. Moraxella catarrhalis 2. Rx with amoxicillin Absence seizures: 1, abrupt onset of impaired consciousness (stare into space) 2. 3-Hz spike and wave activity on EEG 3. ethosuximide Rx of choice ‘Questions used during the board review: Cognitive abnormalities, ataxia, nystagmus, ophthalmoplegia, and foot drop are all associated with ‘A. folate deficiency B. multiple sclerosis C. Alzheimer’s disease D. alcoholism E. Parkinson's disease D (all of the S/S are due to thiamine deficiency and Wernicke’s encephalopathy) 260 « « « « « « « « « « « « « « « « « = = = « = * = « « « « = =Not : This material is copyrighted. All rights reserved A family history of chronic liver disease beginning at an early age and a movement disorder developing later in life characterizes a disease associated with A. atriplet repeat mutation B. low ceruloplasmin levels C. thiamine deficiency D. excess alcohol intake E. vitamin B)2 deficiency B (Wilson's disease) FA 40-year-old neuropathologist developed a rapidly progressive dementia and died. ‘The pathogenesis of his disorder is related to A. a decrease in acetylcholine levels B. _adeficiency of dopamine C. neuronal damage by amyloid D. a slow virus disease involving prions E. subacute sclerosing panencephalitis DK disease) ‘FA 15-year-old boy develops fever, nuchal rigidity, and petechial lesions. A spinal fluid reveals increased protein, decreased glucose, increased neutrophils, and a positive gram stain. You would expect the CSF gram stain to reveal. ‘A. gram positive diplococci B. _ gram negative coccobacilli C. gram positive rods D. gram negative diplococei E, gram positive cocei D (Neisseria meningitidis) ‘F Which of the following represents a primary brain tumor that would more likely develop in a cl rather than an adult? ‘A. Glioblastoma multiforme B. Medulloblastoma C. Malignant lymphoma 2 D. Acoustic neuroma E. Meningioma q@ An afebrile $2 year old smoker with weight loss, cough, and hemoptysis, develops a severe hheadache associated with unilateral lid lag, ophthalmoplegia, and mydriasis. An MRI reveals multiple densities in the cerebral cortex. The pathogenesis of this patient's neurologic condition most closely relates to... A. ademyelinating disease B. primary CNS tumor C. embolic stroke D. cerebral edema with uncal herniation E. _ cerebellar herniation into the foramen magnum D (patient has metastatic lung cancer to the brain) 261Note: This material is copyrighted, AM rights reserved. ‘An autopsy is performed on a 40-year-old man with Down syndrome, Examination of the brain reveals atrophy of the frontal and temporoparietal lobes. The pathogenesis of the CNS disease in this patient is most closely related to. A. Bramyloid protein B. lacunar infarets C. decreased dopamine levels D. alow virus disease E. _atriplet repeat disorder A (classie Down syndrome-Alzheimer's disease question) Recurrent episodes of blurry vision, scanning speech, and paresthesias is most closely associated with. ‘A. multiple sclerosis B. — Wemicke's encephalopathy CC. slow virus disease D. Huntington's disease E. Wilson's disease A = ‘An encapsulated mass is removed from the right cerebellopontine angle of a 32-year-old male with right-sided sensorineural hearing loss and facial numbness in the distribution of the trigeminal nerve. The patient most likely has a/en. A. ependymoma B. medulloblastoma C. demyelinating disease D. meningioma E. acoustic neuroma E (sensory changes are due to VIlIth nerve tumor in cerebellopontine angle impinging on the Vth CN) © 4 45-year-old woman with a history of mitral stenosis and a chronic arrhythmia died suddenly at home, At autopsy, a hemorrhagic lesion was noted at the periphery of the temporal lobe. The patient most likely has aan... A. atherosclerotic stroke B. intracerebral hematoma C. embolic stroke D. glioblastoma multiforme E, AV malformation (atrial fibrillation is the MC arrhythmia) F Ae, fear-old man complains of weakness in his left arm and tremor in his hands that prevents him from writing legibly. He has a shuffling gait when he enters the examining room. His deep tendon reflexes are normal. The patients clinical findings most closely relate to.. amyotrophic lateral sclerosis atherosclerotic stroke pure motor stroke Parkinson's disease post-poliomyelitis syndrome roOm>Note: This material is copyrighted. All rights reserved. F 4 30-yearold woman states that she bums her hands without feeling any pain, Physical exam reveals decreased pain and temperature sensation in the upper extremities, atrophy of the intrinsic muscles of his hand, and abnormal deep tendon reflexes in the upper extremity. The patient most likely has... A. syringomyelia B. multiple sclerosis C, amyotrophic lateral sclerosis, D. spinal cord tumor E. Bp deficiency A (classic question between syringomyelia and ALS) FA febrile 28-year-old man with AIDS and a CD, T helper count of 50 cells/uL. develops focal epileptic seizures. A CT scan reveals multiple ring enhancing lesions in the brain. The pathogenesis of this patient's CNS disorder is most closely related to. A. cytomegalovirus B. cryptococcosis C. toxoplasmosis D. Epstein-Barr virus E. disseminated MAI c F Which of the following is more often associated with Escherichia coli than Pseudomonas aeruginosa? ‘A. Osteomyelitis from puncture wounds through rubber footwear B. Malignant otitis externa in a diabetic patient C. Pneumonia in an intensive care unit D. Death in a patient in a burn unit E. Meningitis in a newbom E F A '55 year old man has broad-based ataxia and loss of pain and temperature sensation in the lower extremities. Both pupils accommodate but do not constrict with direct light stimulation. You would expect the spinal fluid to exhibit. ‘A. encapsulated yeast with narrow-based buds B. neutrophil dominant cell count C.apositive VDRL D. spirochetes E, _ xanthochromia C (tabes dorsalis) 263Note: This material is copyrighted. All rights reserved, Anatomy Questions: 17, 18, 19, 20. 21 23 24, 25 26. Gap junetion: dye passes from one cell to the next Derivation of adrenal medulla: neural crest origin ($100 antigen positive); neuroblasts develop into ganglia; know the layers of the adrenal gland from outside in: cortex: glomerulosa, fasciculata reticularis: medulla Tibial nerve function; plantar flexion of toes; injury: loss of plantar flexion, foot dorsiflexed and everted (calcaneovalaus-cavus), sensory loss on sole of foot, ‘Composition of aortic valve (also pulmonic valve): lined by endothelium and have abundant fibroelastic tissue plus a dense collagenous core; avascular. MV and TV have a loose connective tissue core which is increased in mitral/tricuspid valve prolapse (myxomatous degeneration) Break humerus, wrist drop: radial nerve injury Post-radical mastectomy--winged seapula: indicates injury to the long thoracic nerve; paralysis of the serratus anterior muscle Patient with a nosebleed and rhinorrhea: fracture of cribriform plate in ethmoid sinus Medial longitudinal fasciculus demyelination in MS: bilateral internuclear ophthalmoplegia Parathyroid derivation: third and fourth pharyngeal pouches Aortic arch derivatives: review in embryology book or First Aid for Boards What runs along the radial artery: median nerve Artery affected in femoral neck fracture: medial femoral circumflex artery~ damage leads to aseptic necrosis of the femoral head EM of egg: where does sperm penetrate (zona pellucida) Where is metaphase II completed: in uterus ‘Types of collagen: I (bone, tendon, skin; greatest tensile strength), III (initial collagen of wound repair; replaced by type I [collagenase with Zn as a cofactor]), IV (basement membrane), X (epiphyseal plate; picture of bone on the exam and had to label where X was located) ‘Wallerian degeneration: Schwann cells begin to proliferate and form a tube that will serve to guide axon sprouts in the regeneration process; regeneration of the nerve occurs by the outgrowth of multiple axon sprouts from the proximal surviving segment of the axon; sprouts are directed distally (growth rate of 1-3 mm/day) down the tube established by the proliferating Schwann cells; sprouts are remyelinated and reestablish continuity with the motor end plate of the muscle. Cirele of Willis diagram: name arteries CT liver: show where the hepatic vein drains into the inferior vena cava Nerve injured in midshaft humerus fracture: radial nerve Know the layers of the gastric mucosa Oligodendrocytes: myelinate in the CNS, while Schwann cells myelinate in the PNS. Stage of eggs post-partum: meiosis I arrested in prophase closed cannot open and eye deviated down and out: oculomotor nerve palsy; eye down and rochlear nerve palsy Child with a popsicle stick in his mouth falls down causing the popsicle stick to hit the back of his throat and develops ptosis and meiosis of the right eye: injury to the cervical sympathetic ganglion ‘Vertical diplopia is associated with: cranial nerve IV palsy Patient with headache and physical findings of mydriasis in the right eye in association with id lag, and deviation of the eye down and out: an aneurysm compressing cranial nerve II] (headache is the giveaway for aneurysm) Patient with a recent history of bacterial meningitis has horizontal diplopia in the left eye, which is worse on gaze to the left: cranial nerve VI palsy (lateral rectus weakness from VI nerve palsy) 264Note: This material is copyrighted, All rights reserved. 28. 32. Patient with bilateral lateral reetus muscle weakness: increase in intracranial pressure (classic sign; papilledema usually present) Paralysis of upward gaze in an infant: hydrocephalus secondary to stenosis of the: aqueduct of Sylvius (this is called Parinaud’s syndrome) Multiple ocular motor nerve disorders: diabetes mellitus (common cranial nerve palsies from osmotic damage to nerves) Weakness of the quadriceps muscle and an absent knee jerk reflex: herniated L:-Ls disk Pain in the hip and lateral quadriceps, numbness of the anterolateral leg and the webbed space between the great toc, weakness of dorsiflexion of the foot, and normal knee and ankle Jerk reflexes: herniated Ly-Ls disk (note the normal DTRs) Numbness along the lateral and posterior aspect of the calf and plantar aspect of the foot, and an absent ankle jerk reflex: herniated Ls-S, disk ‘Young child falls on his outstretched arm and has pain in the middle and lateral portion of his clavicle; upper extremity remains in abduction, extension, and internal rotation: nerve injured is C:~Ce (Erb-Duchenne syndrome, or superior brachial plexus injury due to a clavicular fracture; these are also the most common fractures in newborns; Cy~T; are inferior brachial plexus injures or Klumpke’s syndrome) Patient has paralysis of the oculomotor nerve after a head injury: uncal herniation with compression of the IlIrd nerve (ptosis of eye, mydriasis) Numbness of the thenar aspect of the hand: median nerve (carpal tunnel) Wrist bone with greatest incidence of aseptic necrosis: navicular bone (scaphoid) Supracondylar fracture: injury to brachial artery and median nerve; danger of ischemic contractures in forearm muscle (Volkmann’s ischemic contracture) Know the fetal circulation: ductus venosus and umbilical vein have the highest oxygen content EM of alveolus with macrophage, type I pneumocytes (lamellar bodies [surfactant]) EM of small bowel with microvilli on the surface Histologic section of seminiferous tubule: identify cell that makes sex hormone binding globulin (Sertoli cell); Sertoli cell also synthesizes inhibin (negative feedback with FSH) Know the bands in skeletal muscle: A band has myosin ATPase story bronchiole: last airway structure with cilia, J bronchioles: cilia but nb goblet cells; site of obstruction in asthma, CF, chronic bronchitis EM: know normal organelles in a cell--see picture in First AID for Boards Know normal structures CT exams of the chest, abdomen, leg, arm, CNS Voice hoarseness post thyroid surgery: injury to laryngeal nerve MRI of orbit: find superior oblique muscle MRI of abdomen: identify splenic artery above the pancreas Chest x-ray: fluid in the costophrenic sulcus in CHF Barium study of small intestine: need to know how to separate from large bowel; superior mesenteric artery supplies small bowel X-ray showing enlargement of the posterior heart: enlarged left atrium in a patient with mitral stenosis; most posteriorly located chamber in the heart; see best with transesophageal ultrasound Neuroanatomy: emphasis on blood supply and lesions of the brainstem and cortex, all of the cranial nerves and their functions MRI of the carotids with occlusion of the anterior cerebral artery: would effect the contralateral leg Schwannoma in jugular foramen: weakness of palate/loss gag reflex/laryngeal paralysis (X), trapezius/stemocleidomastoid (XI), loss taste sensation posterior third of tongue (IX) Weber syndrome: lesion of oculomotor nerve and UMN signs with a midline, midbrain lesion 265Note: This material is copyrighted. All rights reserved. 58, 59. 60, 61 62 63 64 65 66, 67 68. 69. 70. n Horner's syndrome: diagram of vertebra and sympathetic trunk; pick cervical sympathetic ganglion Pupil light reflexes with eye diagrams of pupils: one set is an oculomotor nerve lesion ss of brainstem anterior view—find area of oculomotor nerve Frontal lobe lesion: affects personality Bitemporal hemianopsia: lesion at the optic chiasm; commonly 2 craniopharyngioma (derived from Rathke’s pouch) Inferior quadrantanopia: defect in the superior fibers in the parietal lobe Loss of sensation in the hands, history of burns without know cord and involvement of crossed spinothalamics: syringomyelia C2 transection of fasciculus gracilis: effects vibration and fine touch of lower extremity only CN ILL and UMN signs on opposite side: midline midbrain lesion Loss of pain and temperature and UMN signs on opposite side: mid pons lesion Horner's syndrome with localization of lesion on a diagram: lateral medullary syndrome with associated cranial nerve palsy in the medulla and hypothalamus with associated temperature regulation problems Parkinson’s disease: MPTP drug of abuse association Cross-section of an embryo: identify neural crest tissue Blood production prior to birth: liver, bone marrow Bochdalek hernia in posterolateral part of diaphragm on left: present early in life; visceral contents extend into the chest cavity causing severe respiratory distress at birth; parasternal diaphragmatic hernias extend through the foramen of Morgagni beneath the sternum and do not usually develop symptoms until later in life. Artery associated with foregut: celiac; midgut: superior mesenteric; hindgut: inferior mesenteric Damage to hearing in a rock and roll band player: injury to cochlea Know normal histologic appearance of small bowel and stomach Argyll-Robertson pupil: accommodates when patient follows finger moving towards the nose but does not react to direct light; neurosyphilis MERI of liver: had to identify the hepatic vein~ vessel emptying into the inferior vena caya Pathogenesis of hypospadias: faulty closure of urethral folds Pathogenesis of epispadias: defect in genital tubercle, associated with exstrophy of bladder Feces draining from umbilicus in 4 day old: persistent umbilical (vitelline) sinus Urine draining from umbilieus in 4 day old: persistent urachal sinus cervical Femoral neck fracture: bleeds into the capsule, may compromise medial femoral circumflex artery leading to avascular necrosis, posterior dislocations are most dangerousNote: This material is copyrighted. ll rights reserved. “Microbiology Questions: 16 17. 18. 19, 20, Mechanism of action of Streptococcus agalactiae (group B_ streptococeu phagocytosis Cause of an immunodeficiency with a high IgM: defect in isotype switching Cyclosporine necessary in identical twin transplant~why: there is still some difference in MHC sites from crossover of chromosomes duriag meiosis Major drift with influenza: major changes in the reassortment of genome pieces indicating a need for a new vaccine; only protects against influenza A; egg based vaccine; killed virus vaccine Receptor for HIV: CD, molecule on helper T eells (also macrophages, dendritic cells) Tetany at birth: DiGeorge syndrome, a pure T cell deficiency due to absence of the third and fourth pharyngeal pouches (3rd inferior parathyroids + thymus; 4th superior parathyroids); absent thymic shadow Graft versus host reaction: common in T cell deficienci destroy lymphocytes (also destroys CMV) CD common to both B and T cells: CD,sis present in all leukocytes Complement fixation reactions: read Jawitz section in Medical Microbiology on immunologic tests Hanta virus: carried in rodents (deer mice); ARDS, hemorrhage, renal failure; viral RNA in lung | tissue (PCR test) | Staphylococeus aureus: protein A attaches to Fe receptor of macrophages, hence blocking | ‘opsonization of bacteria Proteus mirabilis: moves with flagella; urease producer | . diphtheria: toxin inhibits elongation factor 2 by ADP-ribosylation, hence blocking protein synthesis Mycoplasma pneumoniae: requites sterols Pacumonitis (larval transmigration) + ova in stools: Ascaris or hookworm; not Strongyloides (shabditform larvae in the stool not eggs) Latex agglutination reactions: antibody to capsular antigens js attached to the beads Locations of cells in lymph node: B (follicles), T (paracortex), histiocytes (sinuses) Cells that attack protozoans: CD, T cells What gives bacteria their shape: peptidoglycan layer in the cell wall ing motility, Gram positive rod: Listeria monocytogenes; invades mononuclear cells, beta-hemolysis in blood ager, transplacental infection in fetus or occurs in renal transplant patients, ‘mainly contracted from eating unpasteurized cheese (goat's milk cheese) Gray membrane that bleeds when removed: Diphtheria Dengue: transmitted by mosquito (Aedes aegypti; same mosquito as in yellow fever); “breakbone fever”; may be hemorrhagic Infection associated with premature rupture of the membrane: group B streptococcus (S. agalactiae), CAMP test IL-1 function on B lymphocytes: activates B cells Location for Staphylococcus aureus carriers: anterior nares Onchocerca, bite of blackfly, do skin biopsy, ivermectin : common cold occurs more often in fall and winter; person to person droplet infection and contamination of hands; acid-labile (does not cause gastroenteritis because of this) Virus responsible for a cold in spring and summer: adenovirus Lactobacillus : responsible for the acid pHT Influenza vaccine: killed; ega-based Pruritic skin lesion in Gulf War veteran: cutaneous leishmaniasis due to bite of sandily s; must irradiate the donor blood to 267Note: This material is copyrighted. All rights reserved. 34 39, 40, 4 42. 4B 44 45 46, 47. 48, 48, 50. 37. 58, 60. 61: 62. 63 64, 59, Hib vaccine: antibody against capsular polysaccharide In addition to the normal childhood. immunizations, what additional immunizations are recommended in sickle cell disease and cystic fibrosis: Pneumococcus and influenza (Pneumovax is given after 2 years of age) ‘Which live vaceine can be given to a patient with AID: natural infection for measles attenuated virus) List the live vaceines: MMR, varicella, OPV, BCG, smallpox, and yellow fever List the polysaccharide vaccines: Pneumococcus and Hib (meningococcal vaccine is another example) List the killed virus vaccines: influenza, rabies, SALK vaccine List the immunizations that are contraindicated in patients with anaphylactic reactions against eggs: MMR, influenza, yellow fever List immunizations that are contraindicated in patients with anaphyla neomycin: MMR, varicella (neomycin is used as a preservative) Verrueoid lesion in lower extremity in a patient returning from South America: South American blastomycosis, yeast with a ships wheel appearance; North American blastomycosis has wide based buds AIDS patient with 2 peaks in the natural history of his disease: p24 antigen ELISA test for HIV: anti-gp 120 antibodies, confirm with western blot Best test for detecting HIV viral burden in blood: HIV RNA by PCR Newborn baby in HIV positive mother: newborn has anti-gp 120 in the serum (IgG antibody); prevent HIV in newborn by giving mother AZT. Animal association with toxoplasmosis: cat Most common cause of diarrhea in children: rotavirus E. coli: attaches to the urogenital epithelium, hence its #1 status for urinary tract infections Bruton’s agammaglobulinemia: SXR; defect in pre-B to B cells; prone to respiratory infections; need IV gamma globulin SCID: first immunodeficiency treated with gene therapy (replacement of adenosine deaminase) Wiskott Aldrich: SXR; triad of sinopulmonary infections, eczema, thrombocytopenia; B and T cell deficiency; increased incidence of leukemia/lymphoma Part of a vaccine that is antigenie: polysaccharide capsule Person working with animal hides develops lung disease: Bacillus anthrax (woolsorter's disease) Cryptococcus: evades host destruction via its polysaccharide capsule Child with anemia and diarthea~? parasite: hookworm produces iron deficiency Lymphocutaneous nodules in a rose gardener: sporotrichosis; treat with potassium iodide Elderly male smoker with non-productive cough, bacteria fails to grow on ordinary medi (must be supplemented with iron and cysteine), need Dieterle silver stain to identi Legionella; treat with erythromycin ‘Macrophage activation: y-interferon secreted from helper T cell Know examples of all the hypersensitivity reactions: see immunopathology chapter IgA deficiency: sinopulmonary disease; most common genetic immunodeficiency AIDS: most common acquired immunodeficiency HLA system coded on chromosome 6 MMR (MMR is given only because the js worse than the one that potentially could happen with the ic reactions against Hyperacute rejection of a transplant: ABO incompatibility or patient had anti-HLA antibodies against an HLA antigen in the graft, type II hypersensitivity reaction HLA-A, B, C code for class I antigens: CDs cytotoxic T cells recognize HLA-D loci code for class If antigens: CD, helper T cells, macrophages recognize‘his material is copyrighted, All rights reserved. Graft vs host reaction: NK cell mediated; common in bone marrow and liver transplants; res, Jaundice (necrosis of bile ducts), diarrhea, danger in T cell deficient patients Receptor for EBV: CDs, on B cells; polyclonal stimulator causing increased synthesis of immunoglobulins“ reason for hypergammaglobulinemia in AIDS; increased divisions increase risk for t;8:14 and Burkit’s lymphoma CD type for histiocytes: CD,; positive in patients with histiocytosis X (Hand-Schuller-Christian Letterer-Siwe, eosinophilic granuloma) Destroy C. difficile in bedpan: autoclave Hanta virus: carried in rodents (deer mice); ARDS, hemorrhage, renal failure; viral RNA in lung tissue (PCR test) Blastomycosis: spores associated with beaver dams and inland water ways; broad-based-bud: shipwhee! appearing yeast is South American blastomycosis, Impetigo: most commonly caused by group A streptococcus D5: antigen recognition site for T cells Antigen that binds to CD, on T cells in HIV: gp120 Risk for HIV if accidental needle stick from an HIV positive patient: 1/330; Rx with triple therapy for 6 months and get ELISA test at repeated intervals Fever in malaria: coincides with rupture of RBCs Malaria: treat with primaquine and develop acute intravascular hemolysis in G6PD deficiency 269Note: This material is copyrighted. All rights reserved. Biochemistry Questiot Rate limiting reaction in cholesterol synthesis: HMG Co reductase Findings in PKU: mousy odor; tyrosine missing, hence it must be supplied in the diet, « diagnose by amniocentesis and finding the abnorma} gene; eliminate phenylalanine from diet (Nutrasweet is aspartate and phenylalanine, so cannot use it) 1 cell disease: inability to phosphorylate the mannose residues of potential lysosomal enzymes located in Golgi apparatus, hence they cannot be taken up by the lysosomes to degrade complex. substrates Number of glucoses necessary to build palmitic acid a 16 carbon compound: 4 glucoses, each glucose run produces 2 acetyl CoA, the latter containing 2 carbons each Insulin lack in DKA: decreased glycolysis, glycogenesis, fatty acid synthesis, storage of adipose Uncoupling agents (e.g, alcohol, salicylates): produces brown fat from increased heat from reactions trying to increase the generation of more protons to make ATP Von Gierke's: decreased glucose 6-phosphatase (gluconeogenic enzyme) with decrease in glucose (fasting hypoglycemia) and increase in glucose 6-phosphate with production of normal glycogen in the liver and kidneys; stimulation tests with glucagon, fructose, ete. cannot increase the glucose levels owing to the missing enzyme Biochemical processes in both cytosol and mitochondria: urea cycle, heme synthesis, gluconeogenesis Female with pheochromocytoma: what dietary alteration: probably decrease phenylalanine (essential A) and tyrosine (not an essential AA) in the diet Pregnant female with PKU: what diet: low in phenylalanine and high in tyrosine; avoid Nutrasweet since it contains aspartate and phenylalanine Lesch Nyhan: SXR with absent HGPRT, self-mutilation, hyperuricemia, mental retardation Glucokinase: only in liver, high Vm and high Km, not inhibited by glucose 6-phosphate, hexokinase: in all tissues; inhibited by glucose 6-phosphate; low Vm and low Km Branched chain amino acids and maple syrup urine disease: only muscle can metabolize branched chain amino acids Glycogenolysis: review biochemistry Key enzyme in gluconeogenesis: fructose 1,6 bisphosphatase (catalyzes the conversion of fructose 1,6-bisphosphate to fructose 6-phosphate) Locations of glucose 6-phosphatase (gluconeogenic hormone): liver, kidney, intestinal epithelium (lesser extent than others); absent in von Gierke’s disease Shuttles and what they carry: carnitine (even chained fatty acids), malate (NADH) Functions of LDL: vitamin D synthesis, other steroid synthesis, cell membranes, synthesis of bile salts/acids ‘Acetyl CoA uses: how many times used in FA synthesis, CH synthesis, ketone body synthesis; not a substrate for gluconeogenesis Km and Vmax Lineweaver Burke: competitive vs non-competitive inhibitors, competitive (c.2, alcohol dehydrogenase binding ethanol, methanol, ethylene glycol at the same binding site) has no change in Vm but an increase in Km (lower affinity for ethanol, increasing ethanol reverses the inhibition), non-competitive inhibitor (e.g., organophosphates and effect on acetylcholinesterase does not bind to the same site as acetylcholine, binds to another site on the enzyme that decreases velocity of the reaction) has a decrease in the Vm, but the Km remains the same, since the substrate still binds to the normal site Question on fatty acid length and energy production Urea cycle: method of eliminating ammonia, located in the hepatocyteNote: This material is copyrighted. All rights reserved. Epinephrine given and only small branched chains found: debrancher deficiency Know cholesterol synthesis: review Harvey/Champe, note that first few steps are similar to ketone body synthesis except HMG CoA lyase is used instead of HMG CoA reductase Origin of apolipoproteins 100 (liver) and 48 (intestine) Rate limiting step in glycogenolysis: glycogen phosphorylase Reason why liver can not use ketones for fuel: liver cannot activate acetoacetate in the mitochondria, which requires succinyl CoA: acetoacetate CoA transferase (a thiotransferase enzyme) in order to convert Acc into acetoacetyl CoA. 28. McArdles disease: absent muscle phosphorylase: increased glycogen in muscle; no increase in lactic acid afier exercise 29. Pregnant woman is a beer drinker--what supplements does she need: still needs folate because alcohol increases loss of folate in urine and stool which offsets the amount of folate present in beer; furthermore, she would probably be taken off beer because of fetal alcoho! syndrome and ‘would need folate; iron is not affected by beer drinking 30. Insulin: key hormone of the fed state; glucagon: key hormone of the fasting state 31. Mannose 6-phosphate: involved in transfer of dolichol (lipid) in the RER in the synthesis of O- linked glycosides 32, Know all the lysosomal storage diseases: see Genetics notes; two SXR diseases are Fabry’s and Hunter's syndrome 33. Know all the reactions involving NAD/NADH and NADP/NADPH: see Nutrition notes, 34. Major source of NADPH: HMP shunt; malate dehydrogenase reaction to a lesser extent; NADPH supplies reducing equivalents 35, Mutation changes an amino acid sequence-which one would have the greatest effect on migration in a serum protein electrophoresis: one with the most negative charges (most acidic) glutamine; one that would remain closest to the anode (- pole) is the most basic amino aci arginine 36. Mechanism of ketoacidosis in DKA: increased B-oxidation of fatty acids and production of acetyl CoA, which is used by the liver to synthesize ketone bodies 37, Promoter location: linear gene drawing with labels: pick upstream location 38. Energy source for protein synthesis: GTP 39. Isoenzyme with 2 genes, 4 subunits: LDH isoenzymes; 5 isotypes: LLL, LLLH, LLHH, LHHH, HHH 40. Second messengers: atrial natriuretic peptide: cGMP, insulin: tyrosine kinase, nicotinic: ion channels; see Katzung/Trevor pharmacology for more second messenger relationships 41, Best method of detecting relatedness of a new bacteria: restriction fragment length polymorphism 42. Enzyme used for PCR: DNA polymerase 43. Source of glucose in a brain in starvation: alanine (transaminated into pyruvate) 44, Glutamine: most abundant amino acid, carries ammonia in nontoxic form 45. ‘Tyrosine: thyroid hormone, synthesis of melanin, synthesis of neurotransmitters (dopamine, Nor, Epi), decreased in PKU (must supply tyrosine in diet) 46. Glycine: inhibitory neurotransmitter blocked by tetanus toxin, synthesis of 5 aminolevulinie acid in heme synthesis, synthesis of bile acids/salts 47, Biochemistry of hepatic encephalopathy: increase in aromatic amino acids~ phenylalanine, tyrosine, tryptophan (mnemonic PTT) leads to increased synthesis of false neurotransmitters (GABA, octopamine) in hepatic encephalopathy; branched chain amino acids inhibit synthesis of false neurotransmitters— reason Why they are given for RxNote: Thhis material is copyrighted. All rights reserved. Pharmacology Questions: 1. Pharmacology general: heavy emphasis on antimicrobials and mechanisms of action and resistance to the drug, cardiovascular drugs, asthma drugs, NSAIDs, endocrine drugs, CNS drugs; know the class of drug, mechanism of action, and significant side effects ‘Treatment of benzodiazepam overdose: flumazenil Arachidonic acid metabolism: review inflammation chapter ‘Cause of cough/angioedema in patient on an ACE inhibitor: bradykinin Use of epinephrine in shock: 1:1000 difution subcutaneously Dantrolene: used in the treatment of malignant hyperthermia after halothane Treatment of acetaminophen overdose: acetylcysteine to replace used up GSH (neutralizes acetaminophen free radicals formed in the liver cytochrome system) 8. Mechanism of loop diuretic: blocks Na-K-2C! cotransport pump in the thick ascending limb in the renal medulla; also blocks calcium reabsorption 9, Cyanide poisoning treatment: review in environmental pathology chapter; amyl nitrite and thiosulfate 0. Thrush: may be a complication of a corticosteroid inhaler 1 Isotretinoin: always do a pregnancy test in females; put them on BCP Mechanism of propylthiouracil: blocks iodination of the tyrosine residues of thyroglobulin; also blocks coupling of DIT and MIT: only drug that can be used in pregnancy but may produce goiter in the newborn and nail defects 13, 450 system in the liver: makes drugs water soluble 14. Angioedema and renal failure: ACE inhibitor relationship 15. Mechanism of action of retinoic acid: behaves like a steroid in that it binds to receptors in the nucleus with subsequent transcription of genes; proteins produced by this action are important in growth, differentiation, reproduction, and embryonic development; also used in treatment of acute progranulocytic leukemia 16, Allopurinol action in purine synthesis: blocks xanthine oxidase (schematic of purine metabolisin ‘was provided and had to identify the reactions (hypoxanthine to xanthine and xanthine to uric acid]), mercaptopurine degradation is inhibited as well Most common antibiotic used to prevent endocarditis in patients with valvular disease: amoxicillin is the drug of choice; all valvular diseases except asymptomatic MVP and all congenital heart disease except asymptomatic ASD) 18, Yellow coloration of the skin that can be mistaken for jaundi chlorpromazine and arsenic produce a blue-gray color to the skin 19. Diffuse erythema followed by separation of the skin (scalded skin syndrome or toxic jermal necrolysis)--2drug: barbiturates, sulfonamides, phenytoin, NSAIDs 20. Hair loss in a woman~2drug: oral contraceptives (predictable side effect; estrogen causes hair to be at same stage of development; may also occur after delivery) } 21. Erythematous, hyperpigmented plaque-like lesion that recurs at the same site every time: fixed drug eruption (phenolphthalein, NSAIDs, tetracycline, Bactrim, and barbiturates are the most common cause of these reactions) 22. Group of drugs has the highest association with urticarial and maculopapular lesions: amoxicillin, TMP/SMX, ampicillin/penicillin (rashes are the MOST COMMON adverse reaction to drugs, with maculopapular rashes leading the list; most drug reactions involving skin are NOT type I hypersensitivity histamine-related) 23. Elderly woman on thiazides is most at risk for developing: gout 24. Tardive dyskinesia, malignant syndrome (sweating, hyperpyrexia, autonomic instability): neuroleptics i 2 drug: quinaerine;Note: This material is copyrighted. All rights reserved. Antipsychotic drug requiring visual examin: defects) 26. Nephrogenic diabetes insipidus~? drug: lithium for bipolar disturbances 27. Drug contraindicated with MAO inhibitors: epinephrine 28. Use of phentolamine: non-selective c-blocker that lowers blood pressure during surgery for a pheochromocytoma + thioridazine (also produces heart conduction 29, Mechanism of AZT: inhibits reverse transcriptase; produces @ macrocytic anemia unrelated to folate/B 12 30. Treatment of Pb poisoning: BAL and EDTA Drugs involved in folate metabolism: phenytoin blocks intestinal conjugase (polyghutamate to monoghitamate, BCP blocks uptake of monoglutamate, methotrexate/IMP-SMX block dihydrofolate reductase 32. Cromolyn sodium: stabilizes mast cell membrane preventing release of preformed mediators and release of prostaglandins/leukotrienes after the release reaction 33. Methotrexate: blocks dihydrofolate reductase and the conversion of dihydrofolate to tetrahydrofolate 34, Glucuronyl transferase in liver renders compounds water soluble 35. Cyclooxygenase: aspirin inhibits irreversible, NSAIDs reversible 36. Thromboxane A: synthesized in platelet; vasoconstrictor and increases platelet aggregation, also ‘a bronchoconstrictor 37. Effect of proton blockers: blocks H’-K’-ATPase proton pump in parietal cell; not a receptor mediated event; H; blockers: blocks H; receptor, which normally activates adenylate cyclase producing cAMP which stimulates protein kinase; acetylcholine: activates cholinergic receptor causing the release of calcium, which stimulates protein kinase; misoprostol: prostaglandin receptor, which normally inhibits adenylate cyclase and cAMP production 38. Treatment of schistosomiasis and clonorchiasis: praziquantel 39, 7-fold membrane spanning protein-? drug: propranolol a B-blocker 40, Phase 3 clinical trials: double blind 41 substitute for aspirin in preventing strokes, CAD if the patient is allergic to aspirin: causes neutropenia 42. Drug induced SLE: procainamide and hydralazine 43. Overdose of suecinylcholine: use acetylcholine blockers 44, Finasteride: blocks S-a reductase, which converts testosterone into dihydrotestosterone, hence testosterone would increase proximal to the block and dihydrotestosterone would decrease; increases hair growth 45, Flutamide, cyproterone, spironolactone: block androgen receptor, hence testosterone! dihydrotestosterone increase but have not physiologic effect 46, Ketoconazol testosterone synthesis (suppresses adrenal steroid synthesis) 47, Leuprolide: GnRH analogue, which when given in sustained fashion, inhibits FSH and LH, hence lowering testosterone and estrogen levels 48. ACE inhibitors: increase in renin and ATT, but a decrease in ATII and aldosterone; aldosterone eventually increases, hence the addition of spironolactone to keep aldosterone suppressed! increases longevity in CHF Arsenic poisoning: dimercaprol 50. Chloroquine in treatment of malaria~-malaria recurred-why?: exoerythrocytic/hepatic stage (e2,, P. vivax, P. ovale); drug kills active disease but does not eradicate hepatic stage 51, Primaquine in treatment of malaria: not good in the active stage but does kill the hepatic stage of vivax and ovale 22Note: This material is copyrighted. All rights reserved. 54 58 59. 60. 61 62 63 64, 65 66, 67 68, 69. 70. 74, 45. 76 Dantrolene: reduces the release of calcium from the sarcoplasmic reticulum of skeletal muscle: antispasmodic drug: also used in treating malignant hyperthermia Methanol: increased anion gap metabolic acidosis due to conversion of methanol into formic acid; optic nerve degeneration and blindness; treat with alcohol infusion to block metabolism of methanol by alcohol dehydrogenase Botulism toxin: blocks the release of acetylcholine (diagram of neurotransmitter synthesis and must locate the block); good diagram in Katzung/Trevor pharmacology book; used to treat LES spasm in achalasia Ribavirin: used in severe RSV infections in children Asthma: albuterol (fi-selective agonist; bronchodilator); albuterol may cause hypokalemia drives K’ into cells Acetylcholine breakdown: occurs in the synapse into choline and acetate by acetylcholinesterase in the cleft; products are recycled and not excreted Know the graph of NOR/EPLisoproterenol and effects on blood pressure and heart rate, plus the effect of a;-blockers: see graph in Katzung/Trevor book Amphotericin: disrupts cell membrane permeability; binds to ergosterol in the membrane Ketoconazole: inhibits the metabolism of nonsedating antihistamines like Seldane leading to cardiac arrhythmias Be very familiar with second messengers: see Harvey/Champe biochem book page 80 Opioid toxicity: naloxone (opioid receptor antagonist) Opioids: no tolerance to miosis and constipation Codeine: metabolized into morphine in small amounts owing to significant first pass metabolism of morphine in the liver Delirium tremens: use benzodiazepines Lovastatin: inhibits HMG CoA reductase Patent ductus arteriosus: keep open with PGE Peni -lactam antibiotic that inhibits cell wall synthesis; bind to specific receptors in cytoplasmic membrane; inhibit transpeptidase enzymes that cross-link linear peptidoglycan chains that form part of the cell wall; activate autolytie enzymes in the cell wall Cephalosporins + aminoglycosides: synergistic effect of enhancing nephrotoxicity Erythromycin: interacts with the 50S subunit of bacterial ribosomes leading to inhibition of protein synthesis; inhibits the formation of the initiation complex and interferes with translocation reactions; resistance develops secondary to plasmid-mediated formation of enzymes that methylate the receptor that erythromycin binds with; coliforms produce a transmissible plasmid that produces an esterase that hydrolyzes the lactone ring of erythromycin Chloramphenicol: gray baby syndrome (dose related aplastic anemia) Sulfonamides, dapsone: may precipitate hemolysis in G6PD deficiency ‘TMP: inhibits dihydrofolate reductase; plasmid-mediated resistance; TMP -+ SMX has a synergetic effect from the sequential blockade of folate synthesis, since SMX blocks dihydropterate synthase, which is an enzyme that converts paraaminobenzoic acid into dihydrofolic acid Metronidazole: produces a disulfiram-like reaction Fluconazole: treatment of esophageal candidiasis in AIDS Ganciclovir: first drug used in treating CMV retinitis, the most common cause of blindness in AIDS; foscarnet is used if ganciclovir does not work Cholinomimetic used in treating open angle glaucoma: pilocarpine, physostigmine Dobutamine: inotropic (increase contractility) vasodilator (decreases afterload) that activates at and B1>B2activity without much chronotropic effect: used in the treatment of shock (cardiogenic) associated with hypotension, hypotension associated with renal failure or CHF‘his material is copyrighted. All rights reserved. 79. Dopamine: stimulates cardiac BI receptors, peripheral c-receptors, and dopaminergic receptors in vessels in the renal and splanchnic bed; at low. doses, it is primarily a vasodilator that increases renal and splanchnic blood flow; at high doses, it increases cardiac contractility (inotropic) and cardiac output via its activation of cardiac BI receptors 80. Benzodiazepines: via its own receptors in the thalamus, limbic structures, and cerebra cortex which are part of the GABA receptor-chloride ion channel macromolecular complex. benzodiazepines facilitate the inhibitory action of GABA via increased conductance in the ehloride ion channels (flumazenil blocks this effect by blocking the receptor for benzodiazepines and is the treatment of choice for benzodiazepam overdose) 81. Anelderly woman on thiazides is most at risk for developing A. diabetes mellitus B. gout C.arenal stone D, _ metabolic acidosis E. hyperkalemia 82. A child who ingests 30 adult aspirins will most likely develop A. anormal anion gap metabolic acidosis B. _amixed respiratory and metabolic acidosis C. profound respiratory acidosis D. an increased anion gap metabolic acidosis E, metabolic alkalosis from vomiting Answer: D (children, unlike adults, do not commonly develop @ mixed metabolic acidosis and respiratory alkalosis. Rx is to perform gastric lavage and add activated charcoal and to produce an alkaline urine for increased excretion of the acid) 83. Open angle glaucoma is best treated with ‘A. a-adrenergic blocking agent B. topical corticosteroids C. topical antihistamines D. furosemide E. intravenous acetazolamide Answer: A (timolol is a favored agent; pjlocarpine may also be used; most common type of glaucoma produces gradual loss of peripheral vision (tunnel vision) and optic atrophy) 84, Trazodone: second generation anti-depressant; inhibition of serotonin reuptake; sedation; may cause priapist 85, Thioridazine: retinitis pigmentosum may be a complication 86. Tamoxifen: anti-estrogen; estrogen receptor partial agonist that blocks the binding of estrogen to their receptors in ERA-positive breast cancer cells; also protects against osteoporosis and CAD; risk factor for endometrial cancer; can be used in treating progestin-resistant endometrial cancer 87. Acetaminophen: analgesic and antipyretic but not an anti-inflammatory agent; inhibits prostaglandin synthesis in the CNS; very weak cyclooxygenase inhibitor; most common drug causing acute fulminant hepatitis; converted into free radicals in the liver; glutathione inactivates the FRs (acetyleysteine treatment replaces GSH) 88. Digitalis toxicity: treat with digoxin antibodies (FAB fragments) 89, Cephalosporins: first generation: drug of choice for surgical prophylaxis in many cases; second generation: sinusitis (cefuroxime), mixed anaerobic infections; third generation: meningitis, GC (ceftriaxone) 90, Cromolyn sodium in asthma: only for prophylaxis; blocks early and Iate asthmatic responses to allergens‘Note: This material is copyrighted. All rights reserved. 1 92 93 ‘Omeprazole: inhibits the proton pump located on the luminal membrane of the parietal cell; useful in the treatment of ZE syndrome, GERD, and H. pylori infections Clozapine: blocks D. (dopamine) and 5-HT2, receptors moreso than D3 receptors Fever in a patient on a loop diuretie: do not use any type of NSAID (including aspirin) since it blocks renal synthesis of prostaglandin, which vasodilates the afferent arteriole. Use acetaminophen to lower fever, since it does not interfere with prostaglandin synthesis. Loop diuretics lead to volume depletion, hence angiotensin II will be elevated (vasoconstricts efferent arteriole), Loss of prostaglandin effect predisposes the patient to renal failure. Pathogenesis of cough and angioedema in ACE inhibitors: increase in bradykinin Red man syndrome: IV vancomycin Drug for bacterial carrier states (S. aureus, N. meningitidis, H. influenzae): rifampin Single dose drug for GC and Chlamydia: azithromycin Rx of malignant hypertension: nitroprusside Patient on Lasix who develops fever and needs antipyretic: use acetaminophen, do not use NSAIDs since they block prostaglandin production in the kidneys Antibypertensive and antiarrhymie drug that lowers blood pressure and increases heart rate calcium channel blocker, ¢.g., nifedipineNote: This material is copyrighted. All rights reserved. Physiology Questions: NOTE: a lot of graphs are used; know the classic cardiac cycle graph very well; review Yarrow diagrams on fluid alterations in my fluids and hemodynamics chapter 1. Major site of water reabsorption in the GI tract: in descending order: jejunum, ileum, colon Most effective nephron site for acid excretion: proximal tubule of the kidney 3. Nephron site for ADH effect: collecting tubule 4. Nephron site for greatest generation of free water/most susceptible to ischemia: thick ascending limb in the medulla 5. Compression of the thorax under water: produces a restrictive pattern on PFT 6. — Constriction of the efferent arteriole: increases the GFR and decreases renal plasma flow 7. Know Starling equation for GFR ml/min: GFR = Kf {(Pge - Pas) - Rec], where Kf hydraulic conductance in mV'min . mm Hg or filtration coefficient in mlimin . mm Hg, Pac = hydrostatic pressure in the glomerular capillary in mm Hg (pushes fluid out of the capillary; e.g., +45 mm Hg; it is inereased if the efferent arteriole is constricted and decreased if the afferent arteriole is constricted), Pps = hydrostatic pressure in Bowman’s space in. mm Hg (pushes fluid into the capillary; e.g,,-10 mm Hg), and toc = the oncotic pressure in the glomerular capillary in mm Hg (brings fluid back into the capillary; e.g.,-19 mm Hg); the net filtration isthe algebraic sum of the above 3 parameters (in the above example, the net pressure would be -10-+ 45 -19 = + 16 mm Hg)- fluid should move out of the glomerular capillaries; question: what Starling force changes to produce a net ultrafiltration of zero (answer: gc, which becomes increased {pulls fluid back into the glomerular capillary; using the above example-— 10 + 45 - 35 = 0 net pressure]; itis the only factor that does not remain constant along the length of the capillary owing to differences protein concentration; the high moc at the end of the glomerular capillary extends into the peritubular capillaries that surrounds the nephrons and allows for the reabsorption of solutes) 8. Filtration fraction in the glomerulus: FF = GFR/RPF; constrict afferent arteriole, no change in FF (J GFR/ RPF), constrict efferent arteriole increases FF (1? GFR/Y RPF), increase plasma protein concentration, hence increasing mgc, decreases the FF (1 GFR/no change RPF); decreasing plasma protein concentration, hence decreasing zac, increases the FF (T GFR/no change RPF): constricting the ureter, decreases PBS, hence decreasing GFR and the FF without affecting RPF (¥ GFR/no change RPF) > 9, _ Negative charge of GBM: heparan sulfate 10. SI heart sound correlates with C wave in the jugular venous pulses (C wave is closure of the tricuspid valve); Know the jugular venous pulses: see box in cardiovascular chapter on physical diagnosis 11, Carotid massage: decreases heart rate and increases vasodilatation (carotid sinus baroreceptor innervated by the IX and Xth nerve; impulses generated in this receptor inhibit tonic discharge of the vasoconstrictor nerves and excite vagal innervation of the heart producing vasodilatation vvenodilation, drop in blood pressure and heart rate, and a decrease in cardiac output) 12. 3% Hypertonic saline and effect on POsm and ADH levels: 3% hypertonic saline increases POsm, Increased POsm stimulates the release of ADH (increases). Atrial natriuretic peptide is also stimulated and normally does inhibit ADH release, however, hypertonicity overrides ANP. 13. Patient walking briskly on a hot day: question was put in a chart form; no increase in body temperature, vasodilatation of vessels in skin 14. Marathon runner on a hot day: question was put in @ chart for vasodilatation of vessels in skin increase in body temperature,

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