PATHOLOGY NOTES DR. GOLJAN SYSTEMIC PATHNote: This material is copyrighted. All rights reserved. TABLE OF CONTENTS FOR SYSTEMIC PATHOLOGY NOTES Prepared by Edward Goljan, M.D. Subject Pages | Hematology: RBC disorders rT Hematology: WBC disorders 1-14 | Hematology: Lymph node/ plasma cell 15-18 Hematology: Coagulation disorders 19-26 Hematology: Immunohematology 27-31 Cardiovascular pathology 32-77 Respiratory pathology | 78-97 —_ . Gastrointestinal pathology 98-117 Hepatobiliary/pancreas pathology 118-134 ] Kidney/LUT/Male pathology 135-154 | Female/Breast pathology 155-176 Endocrine pathology 177-203 ] Musculoskeletal/Soft tissue pathology 204-223 | Skin pathology 224-238 ‘Central nervous system pathology 239-263, [Anatomy USMLE topies 264-266 | Microbiology USMLE topics 267-269 ‘Biochemistry USMLE topies 270-271, | Pharmacology USMLE topics 272-276 Physiology USMLE topies 277 [Comprehensive pathology exam/answers 1-48? SD 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, = partial pressure of oxygen in arterial blood, PB = peripheral blood, Rx = treatment, SaO3 = oxygen saturation of arterial blood, SXR = sex-linked recessive Systemic Pathology RBC disorders © Peripheral blood pictures om USMLE: 1, hypersegmented neutrophil- folate/B deficiency 2. microcytic hypochromic cells— ‘A. RBCs that have increased pallor can be assumed to be microcytic B, iron deficiency C. anemia of chronic disease (ACD) D. thalassemia E. _ sideroblastic anemia 3. sickle cells sickle cell anemia not trait have sickle cells in the peripheral blood 4. target cells— A. bullseye . B. alcoholic liver disease C. _hemoglobinopathy 5. spherocytes~ A. _n0 central area of pallor B. congenital spherocytosis C. ABO hemolytic disease of newborn 6. tear drop~ A. myelofibrosis B. thalassemias . Howell Jolly body- spleen surgically removed or dysfunctional spleen as in HBSS disease, 8. _ platelet— small, red, anucleate cell 9. lymphocyte black dot with a thin rim of cytoplasm 10, Auer rod~ myeloblast with immature nucleus and splinter-like structures in the cytoplasm 11. atypical lymphocyte A. big cell with abundant sky blue eytoplasm 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 I hypersensitivity . invasive helminthic infectionsNote: This material 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: 15. schistocytes~ A. fragmented RBCs sen 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 (Q) hemolytic anemias @) S=7 days after blood loss, ¢ « (3) _ after Rx of iron deficiency (4) Buyfolate deficiency 17. Heinz bodies ‘A. special stain: large blue inclusions with involvement of the RBC membrane _—® increased sedimentation rate B. GOPD deficiency 18. coarse basophilic stippling~ A. routine stain: persistent ribosomes B. Pb poisoning all the cells appear big due to large, immature nuclei: e.g., giant band neutrophils B. _B),/folate deficiency 2. myelofibrosis~marrow is composed of fibrous tissue: large cells represent megakaryocytes 3. aplastic:anemia— empty marrow with predominantly fat, and islands of lymphocytes 4. multiple:myeloma— plasmablasts with bright blue cytoplasm, eccentric nuclei, perinuclear halo “ringed siderobiast— 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 g/dL C. left shifted oxygen dissociation curve (ODC) 3. peripheral blood (PB) retiewlocytes A. manifestation of EPO stimulated marrow B. reticulocytes require 24 hours to become mature RBCs C. reticulocytes have RNA filaments: identified with supravital stainse Note: This material is copyrighted. All rights reserved. FE reticulocyte count is the most cost eff tive method of determining wh marrow is responding appropriately to anemia: called effeetive erythropoiesis reticulocyte count is normally reported asa percentage: normal 0.5—1.5% reticulocyte count is first corrected for the degree of anemia (if present) with the following formula: her the (1) corrected reticulocyte count = (patient Het represents the normal Het (2) example: patient’s Het = 15% Ret (15/45 x 9% = 3%) corrected count >3% is considered a good response to anemia: (1) blood loss >7 days (takes marrow ~5~7 days to respond) 2) hemolytic anemias (3) Rx of iron deficiency with iron (@ Rx of By deficiency with Bi» (5) Rx of folate deficiency with folate corrected reticulocyte count <2% is considered a poor response (something is wrong in the bone marrow): (1) iron deficiency 2) _ anemia of chronic disease (ACD) @)Biy/folate deficiency (4) aplastic anemia (5) blood loss <1 week 45) x reticulocyte count, where 45 locyte count = 9% Corrected count Signs and symptoms of anemias: Bi,/folate deficiency Bi: deficieney- posterior column/lateral corticospinal tract signs exercise intolerance dyspnea high output failure decreased viscosity of blood lowers total peripheral resistance koilonychia (spoon nails)-iron deficiency glossitis3 HuxKousop st Dery a4 2prsno Sunowos ynq eww Kyesmonas 5} Sqn seruowe andfoursy aysusayay DERE HT hes Sou SeoqwNoyD0¥q 40 Kpeamonas st SunyFoWOS :eIWaUE pySjoulDy >ISULAVUL Adua!oyop aseury >yeandg (wounios sou) Aousrayap aseuaBoupsyap ayeydsoud 9 asoansy seuidzud juoroysq © stunisea/aseasip jJ20 914915 258254p jouay Sugoyowy youuougy « ——_aseasip aiuosyo Jo e1wuouy 39M 1< $50] Poole ¢ (HINA) eunugo|SouDY yeusnjoou jewsKeorey Rjuraue onseidy ejwoUR onéjouigy 91 OND « sisordaoidi|9/s1S01420104ds joueduo> Aauayayjap wow £103 suluioue snfjoway oununuto;ny » StoQjap oUMIqUIOTT © — (skep 1~¢>) sso} poojg ajnoy APP Dee supp (GVW) 2932p Dam osuL ay t Wee = UH IAT PHT TAAGT WE TMH IST PIII Tats TMNET THAT {5 dnayk Skye My 2 1 to s ay a vagopg < (U 001-08 ADW) sermBUY appss0uz0N Yh) 2642. payz22—) Aduatoijap (ttuejeqo0) zig « (wounuos sow) Koua!oyjap ayejou (unt 001< ADW) sewany ay Koo19¥ yy (uoumos va ejuassopeyy « SeaSIp 1UOIYD Jo BIMiUY & (vounuuos ysou) Aouatayap uos} (cunt 08> AD) stimauy ap fo0291,y ste (ADIN) stun]04 seqaosnds0; weayy Jo seq 24) uo epuaUy Jo uonEDYSsE1>Note: This material is copy ighted. All rights reserved. Microcytic anemias: see Tables/schematics A B c D 1. serum iron— A. bar A represents the normal B. area in black is iron bound to transferrin: arrow with solid line C. height of the bar is the 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 2. TIBC is measured by adding iron to the patient specime: 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 in the bone marrow (1) decreased ferritin’stores, increases liver synthesis of transferrin: increases TIBC (2) increased ferritin stores, decreases liver synthesis of transferrin: decreases TIBC order to fill up all available 3. saturation is a calculation: % saturation of iron = iron/TIBC x 100 = 100/300 x 100 = 33% , le hy » 4. serum ferritin sind hesticon Study ‘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, _TIBC high: ~500 (iron stores are decreased) hies/ C.-Y saturation tow: 4% 6. anemia of chronic disease— bar C serum iron low: ~20 TIBC low: ~200 (iron stores are increased in ACD) °% saturation low: 20% serum ferritin is high popPaseqnuts WFy ¥ J omay asvanuas WIV V > amay | :oron C202) aH (9292) °v aH (dz70) v aH uqordowaH 4 omayy + }oudsodosdo:) «—_ uadonyqoudiodosy ¢——_ uyskydrodojorg + Sujuosyod poay woay aseyejayoouay atopy Suey wIqOHT Lg ‘ef Sy 1050)49 ysejqousoy sussquiom s¥jqousoy, HoneWUEyUr >3H0A49,0 eIMoHE— azy aupopudd = %q 9196 prow aydxoquvaisy = yy, uatouyqoydiog aapourary y (IV) ppe (omar 2% asequds poe oyu (aie aust . 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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 Macroeytic anemias: see Nutrition notes, see Tables and schematic ‘Sites for reabsorption or iron, folate, By: 1. duodenum= iron A. Billroth TI (distal stomach to jejunum, duodenum blind loop) associated with iron deficiency B. _ malabsorption syndromes decrease iron reabsorption: e.g, celiac disease jejunum folate ‘A. malabsorption syndromes decrease reabsorptionNote: This material is copyrighted. All rights reserved. (0) DHT is converted by dihydrofolate reductase back into THF (reduced form) 9. causes of Biz deficieney— As pernicious anemia (PA): (ce @) autoimmune destruction of parietal cells (3) autoantibodies against IF and parietal cells (4) loss of IF leads to By deficiency (8) _achlorhydria: increases serum gastrin levels () chronic atrophie 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 By>-IF complex @)_also destroy bile salts leading to malabsorption of fats Fe eeciminal ileal disease (normal site for Bi>-IF reabsorption): eg., Crohn's disease 10. causes of folate deficiency A. alcoholism: () MCC of folate deficiency @) _notdeficient in folate in a beer drinking aleoholic B. poor diet: elderly CC. pregnaney/lactation: uses up folate D. disseminated cancer: uses up folate phenytoin: blocks intestinal conjugase birth control pillsalechol: block uptake of monoglutamates in jejunum - inhibition of dihydrofolate reductase: (1) methotrexate Q) trimethoprim 11. S/S of Byy/folate deficieney A. macrocytic anemia: delayed nuclear maturation of hematopoietic cells B. glossitis C. diarrhea: Q) malabsorption @) affects duplication of stem cells in the intestine 12. S/S unique to By: deficiency- A. subacute combined degeneration B. posterior column demyelination (1) lack proprioception 2) lack vibratory sensation G) positive Romberg’s test C. lateral corticospinal tract demyelination (1) positive Babinski (2) upper motor neuron disease 3) spasticity D. dementia ern achlorhydria chronic atrophic gastritis body/fundusNote: This material is copyrighted. Al rights reserved, C. gastric adenocarcinoma D. autoantibodies E. _ correction of Shilling’s test with addition of IF lab findings in By/folate deficieney— A. large nucleated cells with immature nuclear features: cells are called megaloblastic B. pancytopenia: megaloblastc cells in the bone marrow are destroyed by macrophages before they enter the sinusoids C. _hypersegmented neutrophils: (1) >5 nuclear lobes 2) excellent marker for B)y/folate deficiency D. increased plasma homocysteine levels: no methyl group to transfer to homocysteine to produce methionine if either By, or folate deficient lab findings unique to folate deficiency- A. increased formiminoglutamie acid (FIGu): usually metabolized by THF decreased serum folate C. _ decreased RBC folate: best test for folate deficiency lab findings unique to B,; deficiency— ‘A. decreased serum By: B. increased urine methylmalonic acid: build-up methylmalonyCoA proximal to the block C. increased propionates (odd chained fatty 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 By: from binding to transcobalamin (2) forces it to be excreted in the urine radioactive Biz given by mouth followed by 24h urine for % radioactive Bis reabsorbed: no radioactive Biz in 24-h urine confirms By» deficiency, if corrected with addition of IF to oral radioactive B;: patient has pernicious anemia if corrected after antibiotic therapy: patient has bacterial overgrowth if corrected 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 Biz deficiency but not the neurologic abnormalities Rx of By: deficieney- 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 MC Tnereased Tnereased | Tnoreased Pancytopenia Present Present Present Hypersegmented neutrophils | Present Present Present = Megaloblastic bone marrow | Present Present Present Autoantibodies against IF and} Present ‘Absent ‘Absent parietal eells Chronic atrophie gastritis Present ‘Absent ‘Absent (body and fundus) ‘Achlorhydria Present Absent ‘Absent Serum gastrin levels Increased ‘Normal Normal Risk of stomach Increased ‘None None’ | adenocarcinoma Plasma homocysteine increased Increased | Tnereased Urine methyimalonie 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 add- ing intrinsic factor -ytic anemias: see Tables ®” USMLE scenarios: 1, janemia’since birthy splenomiegaly= probable congenital spherocytosis: do splenectomy 2. cause of Pneumococeus infection in HbSS= autosplenectomy or functional asplenia 3. (Howell Jolly body;- indicates absent or dysfunctional spleen 4, (primaquine~ often precipitates hemolysis in G6PD deficiency 5. patient with hemolytic anemia post dapsone (sulfur drug, used in leprosy) and:aspirin GOPD deficiency peripheral smear with sickle cells in patient with osteomyelitis: Salmonella species ‘Summary chart of mechanisms of hemolysis in the hemol 1, extravascular— A. macrophage removal and destruction of RBCs: (Q) abnormally shaped RBCs (e.g., spherocytes, sickle cells) @) IgG and or C3 coating RBCs (e.g., autoimmune hemolytic anemia) B. increase in unconjugated bilirubin 2. intravascular— A. intravascular destruction of RBCs B. 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All rights reserved. C- haptoglobin levels decreased: haptoglobin binds to free Hb in plasma and is removed ‘macrophages 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), iniravascular (minor) Glucose 6-phosphate dehydrogenase Intravascular (major), extravascular (minor) deficiency _| Autoimmune hemolytic anemia (warm [eG] Exiravascular | type) Autoimmune hemolytic anemia (eold IgM | Intravascular type) “Microangiopathic anemia Questions used during the board review: ‘FA 19-year-old African American woman presents with fatigue and exercise intolerance, She has a history of menorrhagia. A CBC reveals a mild microeytic anemia, alow normal WBC count and a Hneenal Platelet count. A corrected reticulocyte count is <2%. Which of the following sets of laboratory data best represents the hematologic findings in this patient? [Serum Iron [ TIBC | % Saturation [ RBC Count Ferritin | A. [normal normal |" normal high normal | B. Tow low Tow low high c. Dow: high low low low | D. [high low high normal high | E. [normal normal | normal To normal | A= thalassemia, B = ACD, D= iron overload, E = Blood loss ‘% Which of the following charactetizes pernicious anemia rather then Bh deficiency from other causes? . ‘A. Increased plasma homocysteine levels B. Increased urine methylmalonie acid C. Decreased vibratory sensation D. _Hypersegmented neutrophils E. High serum gastrin levels E (other differences include achlorhydria, autoantibodies against intrinsic factor and parietal cells, correction of Schilling's test with intrinsic factor) FA 28-year-old man has a motorcycle accident outside the emergency room. Physical exam in the emergence room reveals a weak, thready pulse, cold, clammy skin, and a blood pressure of 60/40 Wie: An open right femoral fracture is present as well as tenderness over the left lower rite Which of the following would you expect in this patient if a blood sample was dav prior to insertion of an IV line with 0.9% normal saline? SELECT 3 Normal hemoglobin and hematocrit Normal effective arterial blood volume Increased central venous hydrostatic pressure Decreased mixed venous oxygen content Decreased pulmonary capillary wedge pressureNote: This material is copyrighted. All rights reserved. 4 year old African American child with sickle cell anemia presents with a high fever and nuchal ‘igidity. Scleral icterus and hepatosplenomegaly are present. A CBC reveals moderately severe somurestic anemia and a WBC count of 21,000 cells/uil. with let shit. A urinalysis is normal, A Far aiP teveals turbidity, increased protein, and neutrophils. You would expect a gram stein of CSF and a blood culture to reveal A. gram positive diplococei B. gram negative diplococci C. gram positive cocci D. gram positive rods E, gram negative coccobacilli A (Streptococcus pneumoniae) WBC disorders: see Tables 2 Test for fectious mononucleosis: heterophile antibody, which detects antibodies against horse RBCs ‘* _ Classification of polycythemia: _ Subtype of Polyeyth- | Causes/Discussion emia | Absolute polyeythemia: | Chronic obstractiv © pulmonary disease: 1.MCC in this category low Appropriate: stimulus of | PaO, tissue hypoxia High altitude residents: I.percentage of oxygen i 21% bur the atmospheric pressure is decreased low PaO, Cyanotic congenital heart disease: L.right to left shunt= low Pay Hypoventilation syndromes (sleep apnea, Piekwickian syndrome): | L.respiratory acidosis— low PaO. Left shifted oxygen dissociation curve: I.decreased release of oxygen tissue— A. CO poisoning: (1) low Sa0:, (2) normal PaO. B.| nethemoglobinemia: (1) low SaO;, 2) normal PaO, C. increased Hb F Polyeythemia rubra vera: normal PaO3/Sa0; and low e increased erythropoietin A. normal PaQ:/Sa0., B. hypoxic stimulus normal PaQ/SaQs, (1) renal adenocarcinoma/Wilm’s tumor, (2) cysts __| Endocrine disorders: Cushing’s syndrome cortisol and 17-ketosterolds stimulate erythropoiesis Miscellaneous: L.uterine leiomyomas- compression of weit cerebellar hemangioblastoma— | incidence of renal adenocarcinom: erythropoietin production Relative polycythemia: Smoker’s polycythemia; unexplained eliecis oF carbon monoxide in due to decreased plasma | smoke increases RBC mass— nicotine decreases plasma volume by | pl pl | volume, norntal RBC vasoconstriction mass Absolute polycythemia: Inappropriate no Part of von Hippel disease: increased a, 3.hepatocellular carcinoma~ ectopic Stress polycythemia (Gaisbock’s syndrome): individuals under constant | siress— typically males with hypertension and obesity Volume depletion: volume contraction hemoconeentrates RBCsSISIITISISISIIIIF IIE Splovaysoairioa ~ejuadouisog » | \douysoosod4y ~aseasyp Aasuowng « esopou siuauesjod -asvasyp aunumoyny « ‘2882SIp s,uosippy —ausz0pug jydoussoa aapusayyosdoyasyy « 9 180 osvasip s,urySpoH] + ‘et | _gruadoussog swauus e19 1oysopAoue 's iuod & uo sjrydouy ~ABuoys ‘syseisease Jo aseyd [ease] “ 809 Jo aouasqe 21qu —sqdouysoo 205 avaus jeseN © Pred J0 1904J9 :owospucs 5,8u1ysn> -oupsopITg & aanjye} ueay o}uosyD Woy “809 + oayJa Au aunssaid sneyduus| | ¢ -orkooyduss| + sapou sapio -ouduuky Jo S507 © somneydinsy U0 ~4yuAs 9jn99}0u1 uoIs “aja u ¢ | oog> ~was -sysovko0yna] “d+ | S9pou yd an jansysap aununujoyny « | wosy aseajy | — yosi>-suMpy« + SOG wo syaya tunsas 214204 nIseG | © wquad Spjoa9ys0911407) « Ope | :sproieysoon00 + —s8usqe | woponporg 7 «payoodsns SeydsKpojaktu 10 e1twayn9| ~euuouraie> -2S1p SUMMON + —HoHEWMEYUY UCL ‘smpaeoopua jesai2eq ainseqns + ‘sjsojnaioqn) + —wonyaayuy aquoay-y uoyeu -ameyuy 2]u0ay> 0) asuodsay « TH/s11°2 008 <* sis0)4a0n0\y ‘uy pue auruneysiy jo asvojas yay siomoys suas ye ~sB9p —upys a ‘BuHo¥ND] snousFojacus 21039 uv waa exqns e1uoyp-ppng JO DOW) isoquuosyy ui9s anedoy @ amoge ax0N1S © puBd0KUH apna» ‘Suypnjout (GOD DW) sepostda dnoquiony 0} Sasodsipaid sseu DEY | + —Ansoosyas0d ep exuianposjod qunos De yum quopeanba you st sseu Jey sso Day 24X9 49550} # 0} stojorejd pur saxo ques pur ‘oun dW 405 Stoyeur ju9jj20x2 aeawus pay Jou samen suqdoaynayy syoyorejd querd —sys -ohooqumo.yy © wroqaou UL %S9< PH 000°00r< wnod yajaye/d ¥ KM sISOAo0quIO.ID —[E wars Jo-sasnea sa1j0 ow ‘apeuiay ympe 219 gq K108998-) | -yop uo, «seu | pue Aygo} onbiun s} aUinjor ue Uy %68F< DH © jeBowouajds gy Deu eonpar | euisejd wy | —vpuajoarod cy ayour ype %4Z6< wonIMes WaAKx0-zy ¥| —_« ‘ao1049 Jo xy Plo six24 99J0} projadw afeamjin | we my %7S< PH & ssew OEY | -1Ve| suoye Awoyogayyd | oe weipau —woutom meq wou | a4 jo wojsuedxa (arta) #12 + Awoyoqapyd ¢ | _ wf womutos ax0u Kjpydug « | jeu} « -syMpy « | very epMoyrAoAjog waouneaT, ‘shanatowped wontuys: ‘yioads ¢%001 TOU [ ang WN 405 -suiosouoaga eqydyape Me 8} ZZ PuOSOWIOIY © sisoyfo0yn9] (sasea Jo %0¢- sepa wd UNG Seas $7) s9s119 ysu1q proydurdy] « 38 OSBUTY BUISOIAG | pee pe siseiqou =quoo <= ata woIsny ¥ WLIO} 4001 wr Apmis aua8 HOE pur sisejgojosw But | 04 (199) worBas sa}snJo yoOsq uur 2anysod awiosou tuouajsaquy | -quasaudas siseg Jo 90L ya | 94 ye worsny yplAs Zz aos

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Hemoglobin electrophoresis | Gold standard test for identifying an increase in normal Hb (ey Hb Ay and F in B-thalassemia) or an increase in an abnormal Hb (e.g., Hb SS, Hb SC). Enzyme assays Confirmatory test in glucose 6-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.g., lead poisoning) and iron overload conditions (e.g, hemosiderosis, hemochroma- tosis).Note: This material is copyrighted. All rights reserved. Total iron binding capaci Correlates with transferrin levels. Increased in iron deficiency (IBC) Decreased in ACD and iron overload disease Percent saturation of Decreased in iron deficiency and ACD. Increased in iron overload transferrin states Serum ferritin Iron stain Free RBC protoporphyrin levels (FEP) Serum By Decrease in iron defi diseas Prussian blue stain, Absent iron in iron deficiency. Increased iron in ACD, sideroblastic anemia (idemtfies the ringed sideroblast) and iron overload states ofie | 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 sney. Increased in ACD and iron overload Serum folate/RBC folate Urine forminoglutamie acid Decreased in folate deficiency i} Increased in folate deficiency. Urine methylmalonic acid Increased in Bis deficiency. Serum homocysteine Increased in By» and folate deficiency (MCC). ‘Serum lactate dehydrogenase (LDH) Unconjugated bilirubin Increased in any condition with RBC hemolysis (eg intravascular/extravascular hemolytic anemia, ineffective erythropoiesis in Bi/folate deficiency) or with massive breakdown of cells (eg. leukemia). Increased in extravascular hemolytic anemias (eg, congenital spherocytosis, autoimmune hemolytic anemia), ‘Serum haptoglobin Urine hemosiderin Sickle cell screen Donath-Landsteiner antibody Direct/Indirect Coombs test Decreased in intravascular hemolysis and severe extravascular hemolysis (Hb leaks out of phagocytosed RBCs). Increased in chronic intravascular hemolysis (e.g., microangio- | pathic hemolytic anemia, paroxysmal nocturnal hemogiobinuria) ‘Solubility test and metabisulfite test. Positive in Hb AS, Hb SS, Hb SC, Hb Sithalassemia _| Bithermal antibody. Positive in paroxysmal cold hemoglobinuria Detect IgG, leM or C3 on the surface of RBCs (direct Coombs) or detect 1gG_ 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 newborn, | Reticulocyte count Heinz body preparation 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) or in primary diseases of the marrow that push reticulocytes ‘out (e.g., acute/chronic leukemia). Decreased <2% in most of the microcytic anemias (exceptions: lead poisoning, severe & and (- | thalassemia), Bj» 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 damage in glucose 6-phosphate dehydrogenase deficiency.Note: This material is copyrighted. All rights reserved. Total iron binding capacity | Correlates with transferrin levels. Increased in iron deficiency «rrBC) Decreased in ACD and iron overload disease Percent saturation of Decreased in iron deficiency and ACD. Increased in iron overload i transferrin states [Serum ferritin Iron stain | Free RBC protoporphyrin Levels (FEP) [Serum By Decrease in iron defi | diseas a se _| Prussian blue stain. Absent iron in iron deficiency. Increased iron in ACD, sideroblastic anemia (idemtfies the ringed sideroblast) and iron overload states ‘ | Increased in iron deficiency, ACD, and lead poisoning. Decreased | in pyridoxine (B6) deficiency __ | Decreased in Byz deficiency and increased in polycythemia rubra vera and chronic myelogenous leukemia sney. Increased in ACD and iron overload Serum folate/RBC folate Urine forminoglutamic acid Decreased in folate deficiency | Increased in folate deficiency Urine methylmalonic acid Increased in Bis deficiency. Serum homocysteine Increased in By» and folate deficiency (MCC). ‘Serum lactate dehydrogenase (LDH) Unconjugated bilirubin Increased in any condition with RBC hemolysis (eg. intravascular/extravascular hemolytic anemia, ineffective erythropoiesis in Biy/folate deficiency) or with massive breakdown of cells (e.g., leukemia). Increased in extravascular hemolytic anemias (eg. spherocytosis, autoimmune hemolytic anemia). ‘congenital Serum haptoglobin Urine hemosiderin Sickle cell screen Donath-Landsteiner antibody Direct/Indirect Coombs test Decreased in intravascular hemolysis and severe extravascular hemolysis (Hb leaks out of phagocytosed RBCs). Increased in chronic intravascular hemolysis (e.g., microangio- | 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, leM or C3 on the surface of RBCs (direct Coombs) o detect 1gG_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 newborn, Reticulocyte count ‘Heinz body preparation 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, | By,/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 (e.g., acute/chronic leukemia). Decreased <2% in most of the microcytic anemias (exceptions: lead poisoning, severe a and (i | thalassemia), Bj» 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 damage in glucose 6-phosphate dehydrogenase deficiency.Note: This material is copyrighted, All rights reserved. | Leukocyte alkaline phospha- | Stain oF neutrophils and score based on the intensity of the slain] | tase (LAP) score Marker (of ‘mature neutrophils. Increased in benign neutrophil disorders but decreased in chronic myelogenous leukemia, Immunophenotyping of Gold standard test to subclassify the type of cell involved in acute) lymphocytes lymphoblastic leukemia, >. Tartrate resistant acid Key stain for identifying neoplastic B cells in hairy cell leukemiar 7 | phosphatase (TRAP) stain Philadelphia chromosome 1:22) located “on “chromosome 22 in chronie myelogenous | leukemia, | Heterophile antibody test ‘Test to identify the unique heterophile antibody Ta Tnisolous mononucleosis. Heterophile antibodies in mono are against horse | | RBCs (most sensitive antigen, used in slide test), sheep RBCs, and Povine RBCs. IM antibodies do not react against guines pig kidney | (GPK), Blood mixed with GPK does not clump, but when hone RBCS added it does clump. Epstein-Barr body titer Anti viral capsid antigen-IgM and 1gG, anti early antigen, anti | Epstein-Barr nuclear antigen in the evaluation. of heterophile i _ antibody negative infectious mononucleosis, x! ‘Questions used during the Board review: ‘SA febrile 23 year old college coed presents with fatigue and difficulty with swallowing. Physical © hepatosplen ckuative tonslltis, palatal petechia, cervical lymphadenopathy’ end tender hepatosplenomegaly. A CBC reveals a mild microcyti¢ anemia lymphocytic leukocytosis with ~ 20% of the lymphocytes exhibiting atypical features, and a mild thrombocytopenia. You would expect this patient to have. A. alow TIBC B. anormal serum ferritin C. an elevated total bilirubin " D. _heterophile antibodies E, normal serum AST auid ALT titers o ‘A 65-year-old man with an elevated RBC count has a history of gout, frequent headaches, and Wns attr bathing. He presents with a sudden onset of abdominal pain and bloody diarrhea. ‘Which of the following sets of laboratory data best represent this patient's hematologic disease? RBC Mass_[Plasma Volume _ | Sa0z Erythropoietin A. [Increased [Normal Decreased | Ihereased B. [Increased | Normal Normal | Increased C. [Increased [Increased Normal [Low D.__ [Normal | Decreased Normal [ Normal Sa02 = oxygen saturation CA polycythemia (volume depleted) ‘OPD, cyanotic CHD, B = ectopic EPO production, DNote: This material is copyrighted. All rights reserved. Lymph nodes/Plasma cells/Histiocytes/Spleen Reactive lymphadenopathy Z 1. clinieal— A. painful lymph node B. localized in localized disease: e.g., tonsillitis C. generalized in systemic disease: e.g., HIV, infectious mono lymph node relationships A. germinal follicle contains B cells: absent in Bruton's agamm 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 (3) _ histiocytes are CD, positive obulinemia: also no Malignancy 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 (2) non-Hodgkin's lymphoma r 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 ‘F Burkitt’s lymphom: 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 malignancy A. EBV relationship B, 8:14 translocation of c-myc oncogene F Mycosis fungoides: 1. CD, T helper cell malignancy 2. skin invasion produces nodular lesions and Pautrier's microabscesses ( cells) 3. systemic disease 4. called Sezary syndrome when PAS positive T cells are present in blood F Histiocytosis X: 1. mainly childhood disease histiocytes are CD, positive 2 types- A. eosinophilic granuloma: (1) benign histiocytes (2) lytic lesions in bone with pathologie fracturesrpop with the least number to the greatest number of RS cells, from best prognosis to poorest subtype prognosis, and from a young age to an older age Lymphocyte 3% HD. Male dominant. Asymptomatic young male with isolated node or node predominant ‘group (cervical or supraclavicular). Hard to identify RS cells. Usually stage 1 Best survival (90% 5 year survival). Increased incidence of second malignancy (NHL) due to alkylating agents used in Rx of HD. Nodular sclerosing | 60% HD. Female predominant. Stage IA MC presentation Yanierior mediastinal nodes_and_cervical/suprack laviouée), 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 Sternberg 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 2. summary of monoclonal gammopathies (includes amyloidosis)~ 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. % 5 year [Multiple myeloma (MM) | ~20% of all cases of MG. MC primary malignaney of bone. More common in African-Americans than whites (2:1). Rare under 40 years old. Increased risk with radiation exposure. M-spike in 80-90% and urine BI protein (light chains) in 60-80%. M-spike usually 1gG. Note: This material is copyrighted. All rights reserved. “ay names .. D® @ 2, 5 ynptens B. Hand-Schuller-Christian disease (1) malignant & (2) _trind of exophthaimos, diabetes insipidus, Iti lesions in the skull CC. _Letterer-Siwe disease (1) malignant: infants and young children @) diffuse eczematous rash (3) _ organ involvement (4) _ lytic lesions in bones 3. USMBE'stenario— two year old with eczematous rash and organomegaly and biopsy of skin revealed CD; positive cells, @ Hodgkin's disease (HD): 1, clinical ‘A. RS cell is the neoplastic cell: see question #1 p. 186 of Review book for picture (Q) can beaBorT cell (2) _ must be present to Dx Hodgkin's . nodular sclerosing MC type "fever, night sweats, weight loss often confused with TB prognosis corresponds with number of RS cells and type of Hodgkin's 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 Hodgkin's disease | Comments = = = = = - « _ = - = « 16 « = ©Note: This material is copyrighted. All rights reserved. Sheets of malignant plasma cells >10% of cells in marrow. Increased 8-y microglobulin portends a poor survival (correlates with degree of plasma cell proliferation). Suspect MM in any. middle aged to elderly patient with unexplained anemia, bone pain, pathologic fracture, recurrent infection, unexplained _hyperealcemia,_or_renal_failure without hypertension. Skeletal system: Ivtic lesions (‘punched out”) bone pain, pathologic fractures Hematologie system: anemia, rouleaux, increased sedimentation rate, thrombocytopenia Urinary system: nephrocalcinosis (from hypercalcemia) MCC of acute renal failure. Light chains are toxic to tubules and produce a giant cell reaction, Prone to primary amyloidosis involving kidneys. Endocrine system: hypercalcemia due to local release of osteoclast activating factor by plasma cells. Infection MC COD. ____t Waldenstrom’s Chi monoclonal proliferation of Iymphoplasmacytoid cells macroglobulinemia secreting excessive IgM. Clinical: hyperviscosity syndrome (85 lymphadenopathy, anemia. BJ protein in ~80' Heavy chain diseases (a, | M protein part of heavy chain devoid of light chains located in serum Y.types) and urine. Amyloidosis ‘Amyloid is a fibrillary pro resulting in organ dysfunction. Properties of amyloid: twisted B- pleated sheet (B-fibrilloses). Congo red positive and demonstrates apple green birefringence (like a Granny-Smith apple) under polarized light. Electron microscopy linear, non-branching fiber with hollow cores. Derived from different proteins: light chains (association with MM), serum associated amyloid (SAA, an acute phase reactant in inflammation), prealbumin, i amyloid p and peptide hormones like calcitonin. Two main types of amyloidosis: primary amyloidosis (light chain | derived) and secondary (reactive) amyloidosis (SAA derived, rheumatoid arthritis, TB, leprosy, renal adenocareinom: ‘Common sites of involvement: heart, spleen, tongue and kidneys. Cardiovascular system: restrictive cardiomyopathy local in the elderly due to prealbumin-derived amyloid Gastrointestinal system: macroglossia, malabsorption, hepatomegaly with increased alkaline phosphatase Musculoskeletal system: carpal tunnel syndrome common. Renal system: renal failure is MC COD (nephrotic syndrome) CNS: Alzheimer's disease (f-amyloid protein coded by chromosome hepatosplenomegaly, that deposits into interstitial tissue | 21. Amyloid toxic to neurons. MC COD in Down’s syndrome patients | S40. Diagnosis: Bx of rectal mucosa, gingiva, omental fat pad, or the organ involved. Other types of amyloidosis: medullary carcinoma of thyroid (calcitonin derived amyloid) 7Note: This material is copyrighted. All rights reserved. e [Border Systemic infections! inflammation Neoplastic disorders Hypersplenism Sickle cell disease Portal hypertension eH) | Splenic infaretion Congenital asplenia Splenectomy ‘Summary chart of important disorders of the spleen: 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). Myeloproliferative disease: splenomegaly invariably present (massive in agnogenic myeloid metaplasia). Extramedullary hematopoiesis common (trilineage hematopoiesis in sinusoids) Leukemia: splenomegaly invariably present often massive (chronic lymphocytic 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 cirthosis 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 infarcts secondary to emboli originating in the left side of the heart (¢.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). Streptococcus 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 ferial is copyrighted. All rights reserved. Coagulation: see schematic et Factors preventing small vessel clotting: 1, heparin— enhances antithrombin Ill (ATID), which neutralizes most serine protease coagulation factors: XII, XI, IX, X, prothrombin (II), thrombin s ‘A. synthesized by endothelial cells B. vasodilator C. inhibits platelet aggregation 3. protein Cand S—(Y/taininy Keeper ‘A. inactivate factors V and VIII B. enhance fibrinolysis 4. tissue plasminogen activator— A. release of plasmin B. destroys coagulation factors and clots * Factors acting as procoagulants (form clots) in small vess 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. VILWWF B. synthesized by endothelial cells and megakaryocytes: platelet C. platelet adhesion factor: platelets have receptors for VIII:vW der) carry some VIIL:v WF 3. extrinsic and intrinsic coagulation system ‘= Normal events with 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 IX in the intrinsic system)—» 3. platelets stick to VII:vWF in damaged endothelial cells via their receptors (platelet adhesion) —> 4. stimulus for platelet release of ADP from dense bodies causing platelet aggreg: synthesis of TXA: —> 5. temporary platelet plug with fibrinogen draped over it (fibrinogen receptors on platelets) stops bleeding (end of the bleeding time)~» thrombin generated by coagulation pathway stimulation converts fibrinogen into fibrin and forms a stable platelet plug ~> plasmin destroys the plig and reestablishes blood flow 1 , Bledingtine (BT): Digs mlest Zoe. Coayalthcn) actor detiets 1, detects platelet abnormalities up to the formation of the temporar; 2. causes of a prolonged BT- Vv ‘A. thrombocytopenia S B. no VIILvWF for platelet adhesion jon and / platelet plug ae J oct ©: Patient on aspirin: MCC, due to no TXAy for aggregation 1A fowl. renal failure Biol wea pat,Note: This material is copyrighted. ANI rights reserved. o (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 2. iormal platelets clump when ristocetin is added to a test tube 3. platelets without VITI:vWF or the receptor for VITI:vWF- Bernard-Soulier diseas (thrombocytopenia and giant platelets) do not clump Summary of platelet tests 1. platelet count: normal numbe aspirin 2. bleeding time- tests platelet function 3. ristocetin cofactor assay— detects VIII:vWF or its receptor on platelets Prothrombin time (PT): 1 detects extrinsic coagulation system factors down to formation of a clot- VII (extrinsic system) —> X > V > Il (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 PT does not always mean they are functional~e.g., patient on Extrinsic system” vo Partial thromboplastin time (PTT): see above schematic 1. detects intrinsic coagulation system factors (XII, XI, IX, VII) down to formation of a elot— XII -> XI + IX > VII > X > V > Il (prothrombin) + | (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 fibrinogen ora fibrin clot 2._, D-dimers- Tf A. — measures cross-linked fibrin monomers in a fibrin clot B. cross-links indicate factor XII activity in forming a stable clot USMLE picture of an elderly patients hands with senile purpura: norma finding and not a sign of patient abuse age-dependentNote: This material is copyrighted, All rights reserved. Signs and symptoms of vessel instability and platelet problems: epistaxis— nosebleeds (MC symptom) bleeding from superficial scratches no temporary platelet plug easy bruising petechia and ecchymoses— A. these do not blanch since they represent bleeding into subcutaneous tissue B. capillary hemangiomas and spider angiomas blanch with pressure 3. mucosal bleeding @ USE scenario: 1. URVin-wehild followed by epistaxis and petechia 2, idiopathic thrombocytopenic purpura~ MCC of thrombocytopenia in children IgG antibody against platelets: type TI hypersensitivity no splenomegaly D. megakaryocytes are present in marrow E. responds well to corticosteroids Autoimmune thrombocytopenia in adults 1, most commonly associated with SLE- A. IgG antibody against the platelet: type IT hypersensitivity B, splenomegaly usually present unlike ITP in children Cc Rx (1) corticosteroids» @) _splenectomy—> (3) _ alkylating agents (4) IV y-globulin if bleeding cannot be controlled: blocks Fe receptors for IgG on macrophages 2. other causes of autoimmune thrombocytopenia— A. drugs: (1) quinidine (type I hypersensitivity) (2) heparin (antibody against heparin attached to platelet membrane) B. viruses: HIV (MC hematologic abnormality) Thrombotic thrombocytopenic purpura: 1. small vessel damage (unknown plasma factor) with consumption of platelets~ ‘A. possible causes of endothelial cell damage: (1) infectious diseases (2) diseases: progressive systemic sclerosis, hypertension 3) drugs~e.g., mithramycin, birth control pills (4) _anti-phospholipid antibodies (8) _ preeclampsia B. platelet thrombi (1) not DIC, since coagulation factors are not consumed @) only platelets are consumed (3) abnormal VIIL-vWF in endothelial cells may contribute to platelet aggregation C. vasoconstriction (1) endothelin (vasoconstrictor) released in dam: endothelial cells (2) decrease in nitric oxide and PGI2 normally, they are vasodilatorsNote: This material is copyrighted, All rights reserved, e 2. microangiopathic hemolytic anemia— A. RBCS hit platelet plugs—> schistocytes: must be present to secure the Dx 3. 4 'S problems 5. renal failure 6. Rx with plasmapheresis 7. hemolytic uremic syndrome in children similar except kidney is worst hit while in TTP the brain is worst hit O157:H7 serotype of E. coli: 1. hemolytic uremic syndrome— A. renal failure B. _ anemia with schistocytes €. thrombocytopenia, D. _ CNS findings: less common than TTP 2. organism proliferates in undercooked beef or produce contaminated with E. coli— e.g unpasteurized apple cider 3. Shigella toxin can also produce HUS ‘Thrombocytosis: causes— chronic iron deficiency: common malignancy: common splenectomy infections myeloproliferative diseases: e.g., polycythemia vera Signs and symptoms of coagula late 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 2. _ bleeding into joints (hemarthroses) and closed spaces only severe types like hemophilia A and B with very low factor levels 3. mucous membrane bleeding GI and GU bleeds in disorders: Hemophilia A: 1. SXR 2 lab- A. prolonged PTT B. normal PT C. low VII:C D. normal Villantigen and VII: vWF 3. clinieal- see previous diseussion 4 Ree ‘A. recombinant factor VIII for severe cases B. DDAVP (vasopressin) for mild cases: increases synthesis ofall factor VIN molecules Classical VWD: 1 AD 2. Iab- A. prolonged bleeding time B. normal PTNote: This material is copyrighted, All rights reserved. C. prolonged PTT D. low VIC E. low VII: antigen F. low ristocetin cofactor assay: decreased VIILvWF 3. MC genetic coagulopathy 4, clinical~ A. menorrhagia B. — mucous membrane bleeding SOR A. DDAVP (desmopressin) B. birth contro! pills in women with menorthagia: estrogen increases synthesis of all VIII molecules C. cryoprecipitate: (1) _ blood product containing VIIL, fibrinogen, XIII Q) rarely used Patient with antibody against factor VII:coagulant (circulating ant prolonged PTT: lab findings 1. normal PT 2. prolonged PTT 3. after mixing 0.5 cc of normal plasma with 0.5 cc of patient plasm, the PTT is repeated and is still prolonged: antibodies inhibit VItl:coagulant in the normal plasma as well ‘4 true 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 biologie false positive syphilis serology 2) seen in SLE, HIV, other disorders (3) causes thrombosis 3. clinical syndromes— A. repeated abortions: placental bed clots B. strokes C. thromboembolism D. hepatic vein thrombosis Vitamin K deficiency: 1. causes bleeding- A. vitamin K y-carboxylates Il, VII, IX, X, protein C and § B. _ }-carboxylation allows calcium to bind to these factors in a clot C- absence of y-carboxylation leaves vitamin K dependent factors non-functional: patient is anticoagulated 2. causes of K deficiency— ‘A. newborns lack bacterial colonization for vitamin K synthesisNote: This material is copyrighted, All rights reserved. (1) require IM injection of vitamin K at birth: no vitamin K in breast @) vitamin K levels normally decrease between days 2-5 (@) danger of intracerebral hemorrhage if newborn is not protected: called hemorshagie disease of the newborn B, malabsorption C. antibiotic Rx sterilizes bowel: MCC in a hospitalized patient D. _ warfarin blocks epoxide reductase (normally keeps vitamin K in functional K1 state) (1) vitamin K non-functional Q) rat poison 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 USMLE question of child taking rat poison: 1. contains warfarin— will cause bleeding 2. Rx with IM vitamin K if not medically significant bleeding- use fresh frozen plasma if a medically significant bleed 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 "Patient on warfarin: 1. mechanism— ‘A. blocks vitamin Ks ability to y-carboxylate factors II, VII, IX, X, protein C and S B. _ blocks epoxide reductase: normally keeps vitamin K in its active K1 state prolonged PT and PTT- PT is better test for following patients than PTT bleeding MC complication ‘A. if overanticoagulated and seriously bleeding give fresh frozen plasma B. IM vitamin K, if bleeding not serious 4, previously y-carboxylated vitamin K dependent factors must 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 34 d 5. hemorrhagic skin necrosi 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 pear before patient ‘@ 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 thrombocytopeni 4, prevents venous clot formation— ‘A. does not dissolve the clot in the hospital 24Note: This material is copyrighted. All rights reserved. B. can be used in pregnancy C. complications: (bleeding @) thrombocytopenia (3) _ osteoporosis = pic 1. pathogenesis. A. intravascular consumption of clotting factors B. _ consumption of fibrinogen, V, VIM, prothrombin, platelets 2. clinical~ diffuse oozing of blood from all breaks in the skin plus mucous membranes 3. causes: A. endotoxic shock: MC B. _ infections: meningococcemia C. rattlesnake envenomation D. amniotic fluid embolism A. prolonged PT and PTT B. low fibrinogen C. imereased split products and D-dimer: best tests for DIC (USMEE) A. Rx underlying disease causing DIC B. _ use blood components to keep the patient alive: basically adding more fuel to the fire €. hepgrin; blocks, thrombin, hence preventing clots and consumption of coagulation factors (1 ‘Hereditary thrombosis syndromes: 1. linical- A. yenous thrombosis and pulmonary emboli at early age B. clots in unusual placesye.g., dural sinuses 2. eauses~ A. factor V Leiden: (1) MC hereditary thrombosis syndrome 2) _ protein C and § cannot degrade factor V B, ATIII deficiency (1) no prolongation of PTT after start (2) _ give massive doses of heparin and the (3) send home on warfarin eparin PTT will eventually prolong (4) birth controt pills is MC acquired cause protein C and S deficiency (1) cannot inactivate V and VIIL @) start with heparin and very low doses of warfarin so that hemorrhagic skin necrosis does not occurNote: This material is copyrighted. All rights reserved: & — Examples of hemostasis abnormalities: [Bleeding time | Platelet count | PT PIT Jinterpretation iy Prolonged Normal Normal [Normal ‘Agpinn or NSAIDS | b Prolonged ‘Normal Normal [Prolonged | von Willebrand's __| © Normal Normal ‘Normal [Prolonged | Flemophilia A fa Prolonged Low [Normal | Normal rrp, TTP, HUS | le ‘Normal ‘Normal [Prolonged [Prolonged | Warfarin or heparin _| |(aby | Protonged Low Prolonged [Prolonged | DIC (ae) ‘Normal ‘Normal. [Normal___[Normal Blood loss. | Questions used during the board review: =F Which of the following is more often associated with mild hemophilia A than classical von Willebrand's disease? A. Normal PT B. Prolonged PTT C. Low VILAg levels D. Normal bleeding time E. Treatment with desmopressin acetate qv A febrile 65-year-old man with urinary retention secondary 10 prostate hyperplasia develops ‘ARDS complicated by endotoxic shock. Within 24 hours he has oozing of ‘plood from all puncture eae emive eechymoses, and mucosal bleeding. Which of the following tests \S MOST USEFUL as an initial screening test? A. D-dimer assay B. Prothrombin time C. Bone marrow aspirate D. Partial thrombopTastin time E. Examination of the peripheral blood AIC) Vitamin K deficiency is MOST LIKELY present in a patient Jari liver disease who i being treated with a broad spectrum antibiotic B. with traveler's diarrhea who is being treated with ciprofloxacin €._onheparin therapy for prevention of a pulmonary embolus D. with lactase deficiency who eurrently has watery stools E. who has taken warfarin 3 hours agoNote: This material is copyrighted. All rights reserved. Immunohematology ® Glycoproteins: 1, proteins to which are attached short, branch-chained oligosaccharides 2. fumetions include— A. cell surface antigenicity: e.g,, blood group antigens on RBC B. components of mucin: e.g., mucous layer covering the stomach mucosa C. tumor markers: e.g,, prostate specific antigen ® ABO blood groups: 1, Higene~ codes for a transferase that attaches fucose to a glycolipid to form H antigen 2, A gene transferase product attaches N-acetylgalactosamine to H antigen to produce A antigen 3. B gene~ transferase product attaches galactose to H antigen to form B antigen 4. Ogene- A. inactive B. _ORBCsare 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: (2) anti-A IgM Q) antiBigt @) _anti-A,B IgG (can cross 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 gastric cancer 9. blood group B- has anti-A IgM Poomp 10, ABO typing of mother and father to see if the child is theirs~ A. AB parents cannot have an O child B. O parents cannot have an AB, A, or B child‘Note: This material is copyrighted, All rights reserved. @ ABO blood group summary: _ Type | Antibodies | Whites | Blacks | Asians | Native Comments Americans 0 anti-A TgM, [45% [49% [40% | 79% Universal donor (no | antigens on the surface), Anti-A,B IgG is respon (can cross the sible for ABO incompa- placenta) tibility. Can only receive © blood —(antibodis would destroy A, B, or AB blood). Predisposi- tion for duodenal uleer | disease. A antiBigM [40% [27% [28% | 16% Predisposition for gastric | carcinoma, : B anti-A IgM 11% | 20% [27% 4% AB none present [4% [4% [5% |<1% Universal recipient (no antibodies) * Rh positive 1, means the patient has D antigen 2. other Rh antigens~ C, c, E, e,d (does not exist) Lewis antibodies: 1. naturally occurring IgM antibodies 2 no I significance 3. no risk of hemolytic disease of newborn (HDN) © Duffy antigens: 1. uncommon in African-Americans 2. surface receptor for P. vivax- African-Americans lacking the antigen have protection against malaria © Lantigens: 1. anti-Tis 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— indirect Coombs test 2. major crossmateh: A. purpose is to see if the patient has antibodies that will destroy donor RBCs B. patient serum against donor RBCs C. good quality control on whether patient had any antibodies reacting against donor RBC antigens D. type Il hypersensitivity reaction E. does not prevent patient from: (1) developing antibodies against donor RBC antigens :r rc This material is copyrighted. All rights reserved. (2) _ patient from getting infection: CMV MC, HCV, HIV, HBV MC antibodyin'U:Si(USMILE): anti CMV antibody Most common infection transmitted by blood transfusion: CMY, 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 blood 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 positivi 1. 1:300 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 hematoerit- 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 XII, fibronectin 2. hepatitis risk Febrile transfusion reaction: patient has anti-HILA 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 develop antibodies ‘A. common in pregnancy- fetal matemal bleeds B. spontaneous abortions C. previous transfusionNote: 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> (2) g., anti-B IgM attaches to B positive donor cells—> (3) _ activates comy (4) _ intravascular hemolysis B. type Il hypersensitivity reaction patient has undetected antibodies that react ag A. extravascular hemolysis B. jaundice, drop in Hb, positive direct Coombs: reaction may be delay C. type IT hypersensitivity t donor RBC antigens— ed in some cases, 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 @) mother’s liver handles unconjugated bilirubin released by fetal macrophages (3) _ baby develops a mild anemia: weak antibody compared to anti-D antibodies B. may occur in first pregnancy C, no increase in severity with future pregnancies A. spherocytes in cord blood: not present in Rh HDN B. _ positive direct Coombs on cord blood RBCs C. 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 IgM, anti-B IgM, and anti-AB-Ig @) anti A or B IgM antibodies immediately destroy fetal RBCs in maternal circulation © Rh immune globulin: 1, anti-D from pooled human donors ‘A. passive immunization B. does not cross the placenta C. given to pregnant women who do not have anti-D at 28th week D. _ no hepatitis risk 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 test: (1) _ testis performed on maternal blood (2) 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 circulationNote: This material is copy ghted. All rights reserved. = Rh BDN: 1, mother Rh negative and baby Rh positive 2. first pregnancy with Rh + baby has no effect on baby % mother could be exposed to fetal RECs with D antigen during delivery and develop antibodies~ purpose of Rh immune globulin isto prevent this from occurring 4. if'subsequent pregnancies have Rh+ babies A. mal anti-D IgG antibodies cross placenta» B. attach to fetal RBCs—> C. RBCs extravascularly removed by fetal macrophages in the spleen-> D. _nconjugated bilirubin (UCB) is end-product of hemolysis (mother’s liver handles UCB)» E- fetus develops anemia (severe anemia, chance of heart failure and hydrops fetalis)-» F. bilirubin pigment can be detected in amniotic Quid (optical wavelength of 450) end mapped on a Liley graph to determine severity of hemolysis —> G px delivery, baby cannot handle UCB load and is often exchange transfused to prevent kernicterus 5. exchange transfusion: A. removes UCB B. removes antibodies C. corrects anemia Cross-section of brainstem with yellowish discoloration in a child: probably kerio Rh hemolytic disease of the newborn bh of! undenjegee Iya Question used during the board review: ‘FA blood group O, Rh-negative woman is pregnant with her fist child. She has a negative antibody Pere ane Brevious administration of Rh immune globulin, She delivers a blood group A, Rh. Rositive baby. The baby develops unconjugated hyperbilirubinemia 8 hours after bith, Which af the following statements correctly deseribes this case? A. 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 roowNote: This material is copyrighted. All rights reserved. pied): Cateactan of brpleegm, Te ppecsane IW PO Heryeie Cn lhich iw furl Cease BLving if the R een toale Thef Cardiovascular system ~ Summary of physical diagnostic signs in cardiovascular disease: Abbreviations usedl~ S,° fi heart sound, Sy: second heart sound, Ss: 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 auscultation 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 cardiac eycle relationships- ‘A. P wave: atrial depolarization B. PR interval: atrioventricular conduction time C. QRS: ventricular depolarization D. Se comes just before the QRS E, Si: comes at the same time as the QRS F. _ T wave: ventricular repolarization, or recovery G. Sy: comes just after the T wave 3. 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 aortic component (A2) precedes the pulmonic component (P2) Sy splits on inspiration owing to blood entering right heart: (1) negative intrathoracic pressure from diaphragm moving down @) delayed closure of PV @) becomes a single sound on expiration A; accentuated in essential hypertension P accentuated in pulmonary hypertension Inspiration A: <—> P, (separates) Expiration ‘AaP2 (single sound) 5. paradoxical split of S,~ P; comes before A2 and split occurs on expiration rather than inspiration B. duc 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. Syis 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 left atrium into the right atrium and PV closes even later than it normally does 7. physiologic S;~ ‘A. normal in children and young adults B. occurs in early diastole OpPemooe me 32Note: This material is copyrighted. All rights reserved. ue to rapid ventricular filling with vibration of vaive cusps and ventricular wall or {pact of ventricle against chest wall or sudden limitation of longitudinal expans Lv pathologie 8,~ A. abnormal after 40 y old B. due to blood entering a volume overloaded left or right ventricle (eg. volume overloaded left or right ventricle in left heart failur/tight heart failure @) eg, AV/MV regurgitation or PV/TV regurgitation C- rst cardiac sign of congestive heart failure: increased ventricular volume stretches the MV of TV ring-> volume overload from mitraltricuspid regurgitation D. left-sided S; increases in intensity on expiration F emit sided S; increases on inspiration (more blood in right heart on inspiration) S. heart sound~ A- coincides with atrial contraction in late diastolic filling and the @ wave in the jugular ‘venous pulse. B. duc to increased resistance to ventricular filling (decreased compliance) followi vigorous atrial contraction C. decreased compliance may be due to: (1) ventricular hypertrophy (left/right) or @) _ already volume overloaded ventricle (leigh) D. Suis absent in atrial fibrillation E. left-sided S, increases in intensity on expiration F afight-sided S« increases on inspitaion (more blood in right heart on inspiration) mid-systolie ejection clicks in MV/TV prolapse click is due to ballooning of excess valve tissue into the atrium during systole click is usually followed by a regurgitation murmur mafeuvers that cause click/murmur to come closer to $y are those that decrease volume in the lefv/right ventricle so systole occurs faster: (2) standing up (decreased venous return to the heart) (2) Valsalva maneuver G) anxiety (increased heart rate decreases filling of ventricle in diastole) Tuaneuvers that cause click/murmur to come closer to S are those that 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 have to contract against) opening snap in MV/TV stenosis A. occurs MV/TV (less common) stenosis B. due to nonpliable valve which has difficulty in opening in diastole until atrial contraction forces it open C- opening snap early in diastole indicates severe disease; correlates with intense atrial contraction P. opening snap that occurs later in diastole indicates less severe stenosis: correlates w ith less intense atrial contraction to open the valve heart murmur characte A. occur in systole and/or diastole B. mechanisms (1) structural valvular diseaseNote: This material is copy 1B. 14. 15. 16. ited. All rights reserved. 2) anemia 3) innocent (unrelated to structural or physiologic alterations, e.g., normal child) C. murmurs radiate (1) AV stenosis radiates into the neck 2) MV regurgitation radiates into axilla D. graded 1 to 6: (1) grade 3 easy to hear @) grade 4 to 6 often accompanied by palpable precordial thrill 3) _ grade 6 audible without stethoscope E. _ murmur/heart sound intensity with respirations: (1) right-sided murmurs and abnormal heart sounds increase on inspiration, (2) 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 murmur innocent murmur— A. occur in ~$0% of normal children B. due to turbulent pulmonary artery blood flow in systole C. tow grade (1 or 2) D. _ best heard with patient in supine position E. 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. _AV/PY stenosis (1) ejection type (2) crescendo/ decrescendo due to blood forcibly moving through constricted opening (3) _ produce concentric hypertrophy of left/right ventricle, respectively FE. MV/TV stenosis mid-diastolic murmur occurs after opening snap regurgitation (insufficiency) murmurs— A. problem with closing valves: incompetent B. _ valves closing in systole: MV/TV C. valves closing in diastole: AV/PV D. MV/TV regurgitation: (1) _ even intensity pansystolic (holosystolic) murmur due to blood refluxing into atria throughout systole 2) _ volume overload of atria and ventricles (hypertrophy/dilatation) AVIPV regurgitation— (1) 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 intrathoracic pressures B. _ physiologic effects: (1) decreases venous return of blood to right heart 2) decreases cardiac outputNote: This material is copy 18. 19, 20. 21. ghted. All rights reserved. ) 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 (2) moves systolic click/murmur closer to S; in mitral valve prolapse (3) decreases intensity of ¢j through the stenotic valve tion murmur of aortic stenosis: less blood ejected left parasternal heave A B. c sign of right ventricular hypertrophy right ventricle is located under the sternum hypertrophy due to: (1) _ pulmonary hypertension (called cor pulmonale) Q) PV stenosis @) TV regurgitation pericardial knock— AL B. C sign of constrictive pericarditis cardiac chambers hit thickened (often calcified) pericardium when filling in diastole causes: (1) TB worldwide 2) 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) (2) transmural acute myocardial infarction (3). Dressler’s autoimmuine pericarditis post infarction (4)_ systemic lupus erytheinatosus (MC manifestation of SLE) (©) acute rheumatic fever pulse pressure A. difference between systolic and diastolic pressure (normally 30 to 40 mm Hg) B. causes of a narrow pulse pressure— (2) 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 C. causes of a widened pulse pressure: (1) increased stroke volume: a AV/MV regurgitation b. hyperthyroidism (2) decreased TPR due to arteriolar vasodilatation: a. endotoxemia b. thiamine deficiency €. warm shock in metabolie acidosis 35Note: This material is copyrighted. All rights reserved. (3) increased venous return to the right heart from arteriovenous fistulas (arterial ‘enous 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 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 anacrotic limb (3) _ pulse amplitude of upstroke modified by a, elasticity of arterial wall b. amount of stroke volume €. total peripheral arteriolar resistance (TPR) d, blood pressure (4) down stroke is modified by: a. vessel compliance (elasticity) b. TPR (5) closure of aortic valve causes a momentary reversal in blood flow: produces a dicrotic notch in the down stroke (© smaller, secondary positive wave in the down stroke is due to: elastic recoil of the aorta and aortic valve elderly patients: (1) aorta loses elasticity a. rigid b. less compliant/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/MV regurgitation b. hyperthyroidism ¢. high output cardiac failure (2) decreased TPR: arteriolar vasodilatation (see 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: This material is copyrighted, All rights reserved. 8) causes: a. pericardial effusion (MCC) b. decreased lung complian * interstitial edema in severe asthma * severe pulmonary edema « interstitial fibrosis 23. Beck's triad signs of pericardial effusion A. neck vein distention on inspiration: Kussmaul's sign B. hypotension: decreased cardiac output C. muffled heart sounds: fluid in the pericardial cavity 24, jugular venous pulses (JVPs)~ A. normal JVPs (1) 3 positive waves: a, ¢, and v (2) 2 negative 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: due to restricted filling of right heart b. _eg., TV stenosis, pulmonary hypertension (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 @) 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 @) giant c-v wave: due to TV regurgitation as blood refluxes up into the right atrium during systole F. ywave (1) _ negative wave occupying most of diastole (2) due to opening of TV with rapid flow of blood into the right ventricle in diastole 37this material is copyrighted. All rights reserved, ‘Lipoprotein fractions in blood: Lipoprotein | Protein | TG | CH Comments fraction 2 3 Learries diet-derived TG- surfaced by apolipoprotein Bis, C. falsely elevates t TG level if not fasting, D. small amount of CH in chylomicrons does not alter serum CH levels: no need to fast 2.physiology— assembled in the small intestine and delivered to the peripheral circulation via the lymphatics, Teearries liver-derived TG- A. also. carries liver derived CH, B. surfaced by apolipoprotein Boo 2LDL is derived from VLDL in the peripheral blood- capillary lipoprotein lipase removes TG from VLDL and leaves CH behind in the LDL fraction L“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 mnthesis of CH, B, decreases LDL receptor synthesis, C. sreases esterification by acyl-CoA acyltransferase 3efunctions 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 =? actiwetes CAT 2. funetions— A. reservoir for apolipoproteins C and E that are subsequently attached to circulating chylomicrons and VLDL, B. HDL removes CH from atherosclerotic plaques (reverse CH transport), C. delivers CH to the liver for disposal 3. synthesis increased A. estrogen, B. exercise, C. red wine CH= cholesterol, HDL = high density lipoproteins, HMG CoA = S-hydroxy-3-methylglutaryl coenzyme A, LDL = low density lipoproteins, PH = phospholipid, TG = triglyceride, VLDL = very low density lipoproteins @ Fredrickson's phenotypic/genotypie classification: 1. type I- deficiency of APO C Il or capillary lipoprotein lipase 2. type I~ ‘A. _ polygenic hypercholesterolemia: 85% (MC type) familial combined hypercholesterolemia familial hypercholesterolemia pathogenesis: (1) absent or defective LDL receptors or (2) defective internalization of LDL complex clinical findings in familial hypercholesterolemia (1) _ premature coronary artery disease (CAD) and myocardial infarcts (2) Achilles tendon xanthomas are pathognomonic (75%) ~> vanthelismas axe 4/50 Sect) 38 aly bieSNote: This material is copyrighted. All rights reserved. F. laboratory findings (1) LDL>190 mg/éL 2) CH>260 mg/dl. 3) normal TG or increased TG (type IIb if increased) type I- A. familial dysbetalipoproteinemia: “remnant disease" B. _ pathogenesis: (1) absent or defective apo E (2) chylomicron and intermediate density lipoprotein (IDL) remnants are not cleared C. laboratory (1) CHand TG 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: (Q) _bypertriglyceridemia turbid infranate—> Q) 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 (I + IV = V) mechanisms, which combine to equal a type V phenotype C.clinical: (1) common in alcoholics and diabetic ketoacidosis Q)__ 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 Lipid deposits: 1, Achilles tendon xanthoma— familial hy 2. 4 xanthelasma- ‘A. yellow plaque on eyelid B. consider type Il hyperlipidemia 3. arcus senilis ‘A. rim of white around the outer part of the comea B. consider increased LDL if @ 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 IV or type V - jercholesterolemia 39Note: This material is copyrighted. All rights reserved. PS re No Vasq Vaseaen 7B, Seabdomtinal aortic aneurysms isthe MC type Most common vessels involved in atherosclerosis in descending order abdominal aorta no vasa vasorum below otifices of renal arteries coronary artery popliteal artery descending thoracic aorta internal carotid Atherosclerosis: 1. reaction to injury theory- factors damaging endothelial cells chemicals in cigarette smoke (¢.g., carbon monoxide) B. LDLoxidized LDL C. previous Chlamydia pneumoniae infection D. increased serum homocysteine: folate deficie 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 atherosclero: 1, aneurysm formation- ‘A. weakening of vessel wall with outpouching due to arterial pressure (1) Law of Laplace states that wall siress increases with increased radius Q)."-all aneurysms must enlarge as wall stress increases ire on USMLE) Mcc lofow Reval A@2 CC, abdominal aorta is the MC site for atherosclerosis le canbe demoed vyosel 2. coronary artery disease~ ischemic heart disease A. angina: MC manifestation B. acute myocardial infarction note €dsity moee eesiy YC. sudden cardiac death: eat ae (1) death within 1 hour awn bed supply (2) severe coronary artery atherosclerosis, (3) _ usually no‘thrombosis present D. chronic ischemic heart disease 3. peripheral vascular disease~ A. predominantly lower extremity disease: may hear a bruit over involved vesse B. clinical: (pain @) _ 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 , — diminished/absent femoral pulses 40Note: This material is copyrighted, All rights reserved. 4. circle of Willis disease A. cerebral infarction (usually pale infarct @)_ MC type of stroke B. cerebral atrophy (2) due to laminar necrosis of neurons in layers 3, 5 and 6 of the cerebral cortex (2) apoptosis of neurons- "red" neurons on H and E stains C. atherosclerotic aneurysms: e.g,, basilar artery vertebrobasilar artery disease A. transient ischemic attacks () dizziness Q) vertigo B. _ brain stem infarction “ 6. internal carotid artery disease- A. transient ischemic-attacks: due to embolization of plaque material with neurol deficits lasting <24 hours B. atherosclerotic stroke: (2) usually occur at bifurcation of the internal carotid artery (2) due to platelet thrombus overlying atherosclerotic plaque (3) _ 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: (embolism of atheromatous plaque material, or 2) emboli from left heart 7. renal artery disease A. renovascular hypertension MCC of secondary hypertension B. _ elderly men with severe atherosclerosis and uncontrollable hypertension C. high renin hypertension D. epigastric bruit 8. celine, superior and inferior mesenteric artery disease— A. small bowel infarction (1) _ usually thrombosis/embolism involving superior mesenteric artery (2) 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 (3) ischemic colitis: splenic flexure pain + bloody diarrhea (4) ischemic strictures: healing of infarction by fibrosis leads to large bowel obstruction from stricture formation 4 @ Aneurysms of the vascular system: 3K Ulta Sound is He gold stendaed for diy 1, abdominal aortic aneurysm— an aneukysra A. MC type of aneurysm: picturé'omUSMDE B. MC inmen over the age of $5 C. pathogenesis 41Note: 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 increases: further enlargement and ruptute is inevitable (3) often accompanied by a popliteal artery aneurysm: danger of thrombosis requiring leg amputation D. clinical (QZ) majority are asymptomatic (2) symptomatic a. pulsatile mass with mid-abdominal to lower back pain b. abdominal bruit (50%) ©. rupture MC complication (3) rupture triad: 9 8, abrupt onset of severe back pain (most rupture into the lef retroperitoneum) —> /e: Pink pain b/e aoe js RetePPRi Ue! ats b. hypotension diagnosis (1) abdominal ultrasound is gold standard test Q) size and risk for rupture color the Rix 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 (Q) most are congenital: not usually atherosclerotic in origin 2) _ vessels lack an internal elastic membrane and muscle wall at bifurcations of cerebral vessels D. associations: any cause of hypertension predisposes to berry aneurysms: (1) _ essential hypertension @2) adult polyeystic disease (10-15%) @) _ coarctation of the aorta (increased pressure in cerebral E. clinical Q) headache @) subarachnoid hemorrhage: a. severe, occipital headache b. “worst headache [ever had” followed by a loss of consciousness F. diagnosis Q) CT scan/MRI as a screen @) angiography confirms mycotic aneurysms- A. — weakening of the vessel wall secondary to an infectious processes: () eg, septic embolism Q) infective endocarditis 3) _ fungal vasculitis (Aspergillus, Mucor, Candida are vessel invaders) B. clinical (1) thrombosis 2) rupture els) 42Note: This material i copyrighted. Ait rights reserved 4. syphilitic aneurysm— A. males 40-35 ys of age B. cardiovascular manifestation of tertia Y syphilis ©. pathogene: () T. pallidum produces endarteritis obliterans ulitis_with infiltrate) of vasa vasorum of ascending and traneveess Portions of are leads to ischem ia of outer adventitial/medialtiss Weakening of aorta. oar ith retraction of the underlying endothelial tissue Producing “tree barking" of the endothelial surface» aneurysmal dilatation of aorta—> dilatation of aortic valve ring aortic regurgitation death from heart failure or rupture D. clinical (2) "aortic regurgitation with dilatation/hys ertrophy of left ventricle ) respiratory difficulties from airway encroashine 8) _ brassy cough from left recurrent (4) angina: due coronary a (5) _ bounding pulses (wate diagnosis () aortography (2) calcification inthe arch of aorta hight dissecting aortic aneurysm— mean age of 60-65 men > women MC catastrophic disorder of aorta MC aneurysm of ascending aorta pathogenesis: Q) pathology b teria ostia narrowing by fibrosis + hammer pulse) ly predictive of a syphilitic aneurysm Feop> lastie tissue fragmentation (95%) mucoid degeneration: cystic medial necrosis Marfan's syndrome (defect in fibillin) b> Ehlers-Danlos syndrome (defect in collagen) ©. > Pregnancy (increased plasma volume) & copper deficiency (cofactor in lysyl oxidase) coarctation of aorta (wall f trauma cause of dissection (1) hypertension applies a she stress) aring force to the intimal surface» intimal tear usually within 10 em ofthe aortic valve.» column of blood dissects under arterial pressure through the areas and progresses proximally and/or distally @) eventual sites of ruprure: 8. pericardial sac (MC COD) of weaknessNote: This material is copy Nittopeussile —» used +o ff, ated. All rights reserved, v N dlssethive toed Vi, IN Aissetling 102% atyoug’ inl mel Sptart-hyypartond b. mediastinum peritoneum . _ reentry through another tear to create a double barreled aorta G. types of dissections (1) type A aneurysm: a. MC and worst type b. _ involves ascending aorta @)__ type B aneurysm: begin below the subclavian artery and extend distally H. clinical (1) acute onset severe retrostemal chest pain with radiation into the back (2) AV regurgitation: due to dilatation of aortic valve ring by aneurysm (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% patiént profile! on USMLE- anterior chest pain, widening of the aortic root on echocardiogram, death in 3 days by tamponade ® Overview of venous system 1. 2. superficial veins (e.g., superficial saphenous veins) drain into the deep veins via communicating (penetrating) branches. 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: i 2 phlebothrombosis- thrombosis of a vein without inflammation, venous clots 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, inflammation, varicose veins) B. _ stasis of blood flow (e.g., bedrest) . _hypercoagulability (e.g., oral contraceptives), 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 C. 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: da ‘embolization clinical ‘A. swelling, pain, edema distal to the thrombosis B. development of varicosities and ulceration. 44Note: This material is copyri 10. e 1. Varicose v hted. All rights reserved, deep venous thrombosis (DVT) in the lower extremity— A. produces deep venous insufficiency: post-phlebitie syndrome B. 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 C. veins in the ankles rupture resulting (1) stasis dermatitis (swelling, hemorrhage, ulcers) @) _ secondary varicosities in the superficial saphenous system complications of venous thrombosis include A. — thromboembolism (2) 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 2) _phlebothrombosis (3) intravenous catheters (4) _ intravenous drug abuse clinical: (1) palpable cord @) pain, induration, heat, erythema migratory thrombophlebitis subtype of thrombophlebitis: A. venous thrombi disappear at one site and reappear at another B. may be a paraneoplastic sign of underlying pancreatic cancer (Trousseau's sign) definition— A. abnormally distended, lengthened and tortuous veins associated with (1) _ superficial saphenous veins: MC site 2) distal esophagus in portal hypertension (3) _ anorectal region (e.g., hemorrhoids) (4) left testicle (varicocele) B. 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 d, occupation of the individual: standing (2) 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- A. 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 ischemia) to supply blood to the arm Superior vena caval (SVC) syndrome: 1. secondary to extrinsic compression of the SVC from a primary lung cancer (90%) puffiness and blue to purple discoloration of the face, arms and shoulders CNS findings of dizziness, convulsions, and visual disturbances (congested retinal veins). 4. distended jugular veins Lymphatic disorders: 1. lymphatic vessels have an tumor invasion acute lymphangi ‘A. inflammation of lymphatics (“red streak”) B. Streptococcus pyogenes MCC: eg. cellulitis lymphedema interstitial collection of lymphatic fluid due to: A. congenital disease: (1) Milroy’s disease (2) Turmer’s syndrome B. _ blockage of the lymphatics: (1) _ radiation post-mastectomy (2) peau d'orange 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 lymphoma 2) trauma to thoracic duct ‘ 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 n B. _ CNS vascular abnormalities often located in the leptomeninges on the ipsilateral side: (1) _caleify (look like railroad tracks) Q) bleed 3) focus for seizure acti C. mental retardation hereditary hemorrhagic telangiectasia (Osler Weber Rendu disease) ‘A. AD disease: MC genetic vascular disorder B. small aneurysmal telangiectasias on the skin/mucous membranes q q complete basement membrane~ predisposes to infection and 46Note: This material c D. is copyrighted. All rights reserved. epistaxis GI bleeds: iron deficiency 3. spider telangiectasias— A. small arteriovenous communications B. associated with hyperestrinism: (1) _ pregnancy 2) cirhosis compression of the “body” of the spider causes the blood flow to the “legs” to disappear: petechia do not blanch (USMILB). 4. angiomyolipoma~ A. hamartoma composed of blood vessels, muscle and mature adipose tissue B. MC in kidneys 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 C. benign capillary proliferation on the skin and/or visceral organs D. silver stains identify them in tissue E. organism also causes cat seratch disease 6. 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 (USMLEY 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: () ADdisease @) cavernous hemarigiomas of the cerebellum (cerebellar hemangioblastoma), brain stem, eyes (8) _ increased incidence of renal adenocarcinoma and pheochromocytoma 8. angiosarcoma~ ‘A. sarcoma derived from vessel endothelium B. liver angiosarcomas: associated with exposure to: (1) vinyl chloride (MC) Q) arsenic @) thorotrast electron microscopy reveals Weibel-Palade bodies: (1) _ structural hallmark of endothelial cells (2) _ contain von Willebrand's factor D. _ histochemical stains positive for factor VIII 9, ‘Kaposi's sarcoma— A. — malignant tumor arising from endothelial cells (some debate on this origin) B, immunodeficiency variant develops in patient's taking immunosuppressive drugs (e.g. renal transplant patient) C. AIDS variant (1) MC cancer in AIDShis material is copyrighted. All rights reserved. > @) AIDS-defining lesion (3) due to Herpesvirus 8 (4) solitary to multiple red-purple lesions that progress from a flat lesion (macule) to a plaque to a nodule that ulcerates (8) _ microscopic: a. spindle cells (neoplastic element) with increased mitotic activity b. _hemosiderin deposition © _ locations: a. skin (MC location, picture on USMILE) b. mucocutaneous surfaces (oropharynx MC location) €. visceral locations (ung, GI tract, iymph nodes) M Rx A. chemotherapy B. _intralesional c-interferon (USMILE) 10, lymphangiosareoma- complicates chronic lymphedema due to modified radical mastectomy @ Large vessel vasculitis: 1, definition: aorta to large/medium sized muscular arteries 2. 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 artery E. clinical (2) 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 Fab: (1) _ elevated erythrocyte sedimentation rate (ESR): best screening test (2) definitive diagnosis: temporal artery biopsy G._ Rx: steroids 3. Takayasu arteritis (pulseless disease) A. Asian women white blue red @) ears and nose cyanotic @) often relieved by warmth infectious vasculitis A fungal vasculi () Candida vessel invading fungiNote: This material is copyrighted. All rights reserved, 2) Aspergittus @) Mucor species B. Rocky Mountain spotted fever: (1) rickettsial disease caused by Rickettsia rickettsiae (2) transmitted by the hard tick Dermace tor anderson (3) organisms invade vessel endothelium of arteriolesivenules. (4) inflammation and rupture of weakened vessel-> classic petechial lesions begin on the soles and palms of hand—> spread to trunk (centripetal spread (5) classic triad - arash b. fever ©. history of tick bite disseminated meningococcemia (Neisseria meningitidis) (@) small vessel vasculitis associated with capillary thrombosis and_petechial hemorrhages 2) sepsis precipitates DIC ) Waterhouse Friderichsens 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 viral vaseuli (1) hepatitis B @) rubella F. infective endocarditis: immunocomplex vasculitis: (J) Rotl’s spots in retina 2) Janeway’ 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 and pains, and anelevated ESR. A. temporal arteritis with polymyalgia B. Rx with corticosteroids 2 weight lifter with weakness inthe hand, numbness; and absent pulse= ] A. thoracic outlet syndrome B. sealenus anticus muscle spasm or cervical rib compresses the subclavian artery and brachial plexus id C: immunocomplex 3. picture of hemaigioma on face of a child leave it alone 4. calcification of digital vessels diabetes mellitus 5. MCC of anarteriovenous fistula trauma A. usually a knife injury B. may cause high output cardiac failure Classification of hypertension: 1. essential hypertension— 95% 2. secondary hypertension— A. renal disease:Note: This material is copyrighted. All rights reserved. BO (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 (2) 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: coaretation 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 @) alcohol @) cocaine ‘© Essential hypertension systolic blood pressure correlates with stroke volume 2, 3 iastolic blood pressure correlates with state of contraction of total peripheral resistance (TPR) arterioles— A oF 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 arteriole)" (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 increast TPR and increases diastolic blood pressure 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 increase in diastolic pressure (3) African-Americans have low renin hypertension: due to an increase in plasma volume pathology associated with hypertension (Q) concentric left ventricular hypertrophy:Note: This material is copyrighted. All rights reserved. a. MC complication b. potential for left heart failure 2) acute myocardial infarction: MC COD Q) hyaline arteriolosclerosis 4. insudation of protein into walls of arterioles by increased luminal press narrow vessel lumen b. produces small vessel ischemia (4) _ nephrosclerosis in the kidneys: a. 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 4. clinical accentuated As Renovascular hypertension 1. MC secondary cause of hypertension- A. pathogenesi (1) atherosclerosis of renal artery orifice in male 2) 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 (1) severe hypertension 2) epigastric bruit oy ©. laboratory J lanl Cloow does fem (1) high renin bypertension~ 71" "" gojety @) involved kidney has increased renal vein plasma renin activity ) _ uninvolved kidney has suppressed renal vein plasma renin activity (4) captopril markedly increases baseline plasm renin activity a. used asa 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 2. upright posture A. increased PRA B, decreases venous retum to heart» decreases cardiac output—> stimulation of renin release C. recumbent posture does the opposite: increases venous retum—> increases cardiac output-> decreases renin release 3. catecholamines A. increased PRA B. directly stimulate renin releaseNote: This material is copyrighted. All rights reserved. - C. _ Beblockers do the opposite 4. captopril (ACE inhibitor)~ A. increased PRA B. excellent screen for renovascular hypertension (1) _ see exaggerated levels post-stimulation owing to block of angiotensin II and loss 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 II levels and causes renal failure 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 7. renovascular hypertension— increased PRA 8. malignant hypertension— increased PRA 9. young hypertensives~ A. increased PRA B. sympathetic nervous system overactivity 10. African-American hypertensives- A. decreased PRA B. _ increased blood volume from sodium retention C. reason why diuretics are first choice in Rx 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 ventricles 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. _ aortitis 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 tissueNote: This material is copyrighted. All rights reserved. (3) myocarditis non-compliant (restricted filling): (2) amyloidosis 2) iron overload @) glycogen in Pompe's disease increased workload: (1) increased afterload 2) increased preload (volume overloaded) 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 oncotic pressure pulmonary edema ical findings~ symptoms outnumber signs decreased cardiac output: forward failure dyspnea: stimulation of J receptors in pulmonary interstitium pulmonary edema: due to increased pulmonary venous hydrostatic pressure left ventricular dilatation: () volume overload @) _Frank-Starling mechanisms at work left-sided S; heart sound: volume overloaded left ventricle left-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) Paroxysmal nocturnal dyspnea and/or pillow orthopnea at night: (1) "increased venous return at night due to lack of gravity effect when lying down cannot be handled by the left heart—» blood backs up into the lungs @) standing up or placing pillows under the head decreases venous return to the heart cough: (2) sputum rusty colored from alveolar macrophages phagocytosing RBCs Q) “heart faiture” 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 3) _ normal EF = 80/120 = 0.66 causes: ischemic injury MCC Rx (1) _use of inotropic agents (e-g., digitalis) @) decrease afterload with vasodilators (e.g., ACE inhibitors) 4. diastolic dysfunction type of LHF A, due to decreased compliance of left ventricle: (1) places increased load on the left atrium (2) pulmonary edema commonNote: This material is copyrighted, All rights reserved. Right heart failure (RHF): 1 c @) EF>0.40 causes: (1) _ left ventricular hypertrophy Q) restrictive cardiomyopathy 3) _ hypertrophic cardiomyopathy Rx: increase pre| by slowing heart rate (e.g., calcium channel blockers, B-b USMLE scenarios~ A mechanisms si A. B. chest x-ray appearance in heart failure: (2) prominent congestion of blood in the upper lobes (2) _ perihilar congestion: “bat-wing configuration (3) Kerley lines: represent fluid in the interlobular septa (4) _ patchy interstitial and alveolar infiltrates (5) pleural effusion microscopic appearance of lung in heart failure: (1) pulmonary edema: transudate @) alveolar macrophages with hemosiderin ("heart failure" cells) ilar to left heart failure (LHF)~ LHF is MCC right ventricular infarction blood builds up behind the failed right heart— AL B. c D. E. 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 + as clinical findings- ARSORP signs outnumber symptoms decreased cardiac output: backward failure volume overload of right ventricle right-sided S; heart sound: volume overload right-sided S, heart sound: decreased compliance tricuspid regurgitation: (2) stretching of tricuspid valve ring (2) _pansystolic murmur at left parasternal border (increases with inspiration) congestive hepatomegaly (2) nutmeg liver Q) increased LDH; isoenzyme (3) _ increased serum transaminases increased hydrostatic pressure in venous system: (1) ascites Q) dependent pitting edema (3) jugular neck vein distention decrease preload and afterload ACE inhibitor decreases preload (blocks aldosterone) and afterload (blocks angiotensin 11): spironolactone added owing to eventual increase in aldosterone diuretics decrease preloadNote: This material is copyrighted. All rights reserved. D. restrict salt and water (decreases preload) output failure: 1. mechanisms~ A. increase stroke volume: (1) hyperthyroidism 2) increase blood volume B. decrease blood viscosity: severe ariemia C. _vasodilate peripheral resistance arterioles (decrease total peripheral resistance): (1) increases venous return to the heart (2) causes of vasodilatation a, 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: a. surgically produced in radial artery for renal dialysis b. trauma: + knife wound usual eause * pressing afferent vessel causes slowing of heart rate (Branham’'s 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 © \USMLE question of fetal circulation (know this very wel 1, USMILE question on what is lower in umbilical artery blood of a normal fetus versus maternal arterial blood~ answer is PO; is lower in the umbilical artery ‘A. chorionic villus in the placenta is the primary site of O2/CO, exchange for the fetus B. normal values in pregnancy @Q) normal hematoerit (Het) is ~35% @) _O; saturation (Sa0,) is ~98% @)_ arterial PO, is ~105 mm Hg C, fetal Hb has a high affinity for Oz: ideal for gas exchange in chorionic villi of the placenta D, _ fetal laboratory parameters: () Het of ~ a, higher than mothers b. high Het also increases viscosity @) increased percentage of HOF (70% at birth @)__left-shifted ODC from HbF E, umbilical vein has an SaQ; ~80% and PO; 30-35 mm Hg: (1) thas the highest amount of oxygen in the circulationNote: This material is copyrighted. All rights reserved, @ 3 w 6) © ” it carries oxygenated blood from the chorionic villus to the fetal liver ~50% of the umbilical vein blood (SaO2 of ~80%) mixes with hepatic sinusoid blood (SaO; of 26%), which contains portal vein blood a, SaO; 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) remaining umbilical vein blood enters ductus venosus: drains directly into the Ivc IVC SaO; before entering the fetal right atrium is ~67%: most IVC-derived blood is directly shunted through a patent foramen ovale into the left atrium (SaO; ~60%) most SVC-derived blood enters right ventricle a. fetal pulmonary arteries are hy; 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 to left shunt): placenta-derived prostaglandin (PGE,) keeps patent ductus open . descending aorta SaO: is ~58% and the PO; is 20-23 mm Hg 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 maternal arterial blood, owing to the presence of more HOF in the fetal RBCs, which lefi-shifis the ODC greater O; capacity than maternal arterial blood (HBF has a higher affinity for O; than adult HbA) strophied from chronic vasoconstriction ‘7 Congenital heart disease (CHD) and what oxygen saturations would be in each type: see schematics of all the CHDs 1. step up of oxygen is compatible with a left to right shunt~ oxygenated blood (Sa0» 95%) from the left heart enters unoxygenated blood (SaO, 75%) with a step up of O; to 80" in the right heart 2. step down of oxygen is compatible with a right to left shunt~ unoxygenated blood (Sa0, 75%) from the right heart enters oxygenated blood (SaO; 95%) with a step down of O; to ~80% in the left heart 3. Eisenmenger’s syndrome— A. excess blood in the right heart from a left to right shunt causes volume overload, which produces: @ @ pulmonary hypertension right ventricular hypertrophy B. reversal of shunt occurs when right ventricular hypertrophy overrides left ventricle pressures: patient develops cyanosis (called cyanosis tardive) 4. ventricular septal defect (VSD)~ A. MC congenital heart disease: @ @) @) usually spontaneously corrects itself defect in the membranous septum associated with cri du chat (partial deletion of chromosome 5) and trisomy 18, B. initially a left to right shunt through a defect in the membranous septum o step up of O; to 80% in the right ventricle and pulmonary artery 60hypertension Lettto-right | fave A = Pa Ceteocane) [Rate [ewan] | et {ater ee) DT Systemepressure ) c fe aint. Mactinary (-sachinary ) je | to intracranial vessels |{ Posteuctal Ses WN Frese pew | Ww Ars : a =< exp it y ot Ao dates val aa |

180 bpm decreases the length of diastole, which decreases filling of the coronary arteries and left ventricle ventricular wall pressure A B. an increase in wall pressure increases Os consumption wall pressure increases when: (J) ventricles are hypertrophied or (2) when the radius of the ventricle is decreased owing to noncompliant muscle (most often the result of ischemia) ‘© Factors responsible for myocardial O; supply coronary artery blood flow— A B. « most important factor coronary arteries fil in diastole clinical correlations: (1) decreased cardiac output in aortic stenosis causes less filling of coronary arteries and the potential for angina (2) _aortitis 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 left anterior descending (LAD) coronary artery~ A supplies entire anterior portion of left ventricle: (1) danger of rupture in a transmural myocardial infarction 2) _ prone to mural thrombosis in anterior myocardial infarctions supplies anterior 2/3rds of interventricular septum: (Q) danger of permanent bundle branch blocks in anterior myocardial infarctions 2) _ permanent pacemaker is often required right coronary artery (RCA)- A. B, c supplies the entire posterior and inferior part of the left ventricle: responsible for epigastric pain in a myocardial infarction supplies the entire right ventricle: right ventricular infarction supplies posteromedial papillary muscle: danger of papillary muscle rupture and mitral regurgitation in myocardial infarctions supplies most of the blood to the arterioventricular node: danger of sinus bradycardia 6FO Note: This material is copyrighted. All rights reserved USMLE picture of coronary vessel: description 1. atherosclerosis: slit like spaces 2, dystrophic calcification: blue blotches 3. fibrofatty plaque: directly beneath endothelium 4. platelet thrombus: red mass blocking the lumen Types of ischemic heart disease: 1. 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: a ional (classical) angina MC variant severe fixed coronary artery atherosclerosis sudden onset of exercise-induced substernal chest pain lasting 1-15 min: relieved by resting and/or nitroglycerin Dx (1) exercise ECG (stress test) reveals ST depression: indicates subendocardial ischemia Q) confirmed with arteriography: intracoronary artery ultrasound recently used Printzmetal’s angina~ ‘A. secondary to coronary artery vasospasm: ? vasoconstrictive effects of thromboxane A7 released from small platelet thrombi overlying non-ocelusive atherosclerotic plaques B. chest pain at rest c. Dx: (1) stress ECG reveals ST elevation (2) represents transmural ischemia unstable (crescendo) angina— A. severe, fixed, nmultivessel atherosclerotic disease B. eccentric stenosis of vessels with disrupted plaques with thrombosis present (1) nonocclusive thrombus (2) _ release vasoconstrictive compounds like TXA C. frequent bouts of chest pain at rest D. Dx: (1) _ stress ECG is unsafe 2) ~20% progress to an acute myocardial infarction in 3 m 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 patency B. 90% patency rate after 10 years 2. saphenous veins— ‘A. 40-50% pateney rate after 10 years B. “arterialization” of the vessels, fibrosis, and occlusion 64+ This material is copyrighted. All rights reserved. Sudden eardiae death: 1. death within 1h 2. severe atherosclerotic CAD 3. usually mo occlusive vessel thrombus 4. die of ventricular arrhythmia 5. association with smoking and non-Q wave infarctions Chronic ischemic heart ase: 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 (AMI): 1, 0-4hs~no G/M change 2 4-412 hs A. noG change B. M shows coagulation necrosi 3. 12-24 hs- after 6 hs A. G shows early pallor B. _M shows more advanced coagulation necrosis 4 13d- A. G~ definite pallor B.__M~neutrophilic infiltrate + advanced coagulation necrosis 5. 3-74 ‘A. period of maximal sofiness B. time for ruptures C. macrophages move in to remove dead tissue 6 7-10d- A. Gisthe same as 3-7d B. —Mshows collagen deposition AMI complications: 1. arrhythn ‘A. MC complication B, ventricular arrhythmias c. Mc cop r 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 €. _posteromedial papillary muscle rupture: (1) _ right coronary artery (RCA) thrombosis (2) acute onset of mitral regurgitation and heart failure D. ventricular septum rupture: (1) LAD thrombosis (2) left to right shunt 4. mural thrombus— danger of embolization 5. pericarditis A. first week in transmural infarction () friction rub 2) fibrinous pericarditisNote: 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 7. prognosis depends on ejection fraction % USMLR picture of healed myocardial infarction: blotchy fibrosis unlike sheets of pale staining tissue as in a pale infarction Lab abnormalities in an acute myocardial infarction: 1. increase in CK-MB- A. begins in 4-8 hs B. CK-MB peaks in 24 hs C. disappears in 1.5-3 4 D. _ reappearance of CK-MB >3 dis a reinfarction 2. imerease in troponin-1— ‘A. begins in 2~6 hs B. peaks in 15-24 hs €. gone in7d } D. will likely replace LDH isoenzymes E. cannot identify reinfarction 3. LDH yp flip~ ‘A. begins to appear in 10 hs: (1) LDHsis 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 C. gone in7d D. mainly used to identify AMI after 3 d 4. increase in AST— A. begins 6-12 hs B. peaks 1-2.d C. gone ins-9d Sequence of microscopic findings and their correlation with changes on ECG in an acute myocardial infaretio 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 2) called reperfusion injury 3. symmetric T wave inversion correlates with area of ischemia 4. Qwave-area of necrosis 66Note: This material is copyrighted. All rights reserved. Rheumatic fever: t pathogenesis ss-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 streptococcal infection usually begins 2 pharyngitis Aschoff body is the pathognomonic lesion of rheumatic fever~ area of fibrinoid necrosis and reactive histiocytes in myocardial tissue jone’s crite ute rheumatic fever (RF) A. polyarthritis (MC initial presentation @) no permanent joint damage @) differential diagnosis: a. juvenile rheumatoid arthritis b. Henoch-Schonlein purpura B. carditis: (Q) pericarditis Q) myocarditis: MC COD in acute RF @) endocarditis a, mitral valve vegetations: develop along the line of closure of the valve b. mitral regurgitation (not stenosis) C. Sydenham's chorea (late manifestation Q) _ selflimited D. _ subeutaneous nodules (1) _ fibrinoid necrosis in nodules (2) occur on extensor surfaces 8) _ histologically the same as in rheumatoid arthritis rythema marginatum— (1) circular ring of erythema around normal skin @) vegetations on margin of the valve-> erythema marginatum F. minor eriteria— (1) clinical findings: a. arthralgias b. fever @) _ lab: elevated ESR or C-reactive protein @) ECG: prolonged PR interval (first degree block) G. supporting evidence of antecedent streptococcal infections 2) positive throat culture for group A streptococcus @) positive latex agglutination test 3) _ elevated or rising anti-streptolysin © (ASO) titer F Mitral stenosis: 1. 2. MCC is chronic rheumatic heart disease pathophysiology— A. volume overload in the left atrium and lungs B. decreased cardiac output physical Dx— A. accentuated S; due to closure ofa non-pliable valve 678 hypertencion —| PH hee — [ter avial hypertrophy + BZ ( ster”) ditaton PO~ uses on ssopreg.s | No LH regurgitation also resent Stenote MV opening es * Opening snap + Diastolic ru c \f/ oD ‘Hyperdynamic WA = WO ee \ ‘vorewoune | \SS, -7ph\_—_| poe ey DS Dy (ee ae] a IPprr_- | siatation sc PY y oa Concentie LH we Vv LA {Gresure overoacy * fata Ft * Blood hits anierorleatet { Poststenate } ditaton Stenotc AV vaive + Syatalc jection murmur =F Ampltuse of PMI Avicompetont | SHighihed dastate wing murmur FIGURE 10-3. Schematics of acquired valvular diseases of the heart. (A) represents mitral stenosis, (®) mitral regurgitation, (© sortie stenosis, and (D) aortic regurgitation. (See Figure 10-2 for 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 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 (Ortner's syndrome) = Mitral valve prolapse (MVP): 1. MC valvular disease in the young population 2. pathogenesis A. valve leaflets (anterior and/or posterior (MC) undergo myxomatous degeneration (USMLE): (2) _ increased glycosaminoglycans (dermatan sulfate) 2) causes redundant (voluminous) valve leaflets 3) __ 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 -sephysieal diagnosis (USMLE)= mid-systolic ejection, click occurs when valve prolapses into left atrium and is suddenly restrained by the chordae tendineae B. click followed by a mid o late systolic murmur: due to MV regurgitation C. click/murmur closer to S, when there is less left ventricular volume: e.g. (2) standing up (2) anxiety (USMIDE)? tachycardia leads to less diastolic filling 3) Valsalva maneuver: increased positive intrathoracic pressure decreases filling of right heart D. _ click/murmur move closer to S; when left ventricular volume is increased: (1) _ lying down/squatting: more venous blood retums to right heart 2) sustained hand grip exercise: positive intrathoracic pressure decreases cardiac output (3) passive leg lifting in the supine position 4. clinical A. usually asymptomatic, tall, thin women B. symptoms include (2) palpitations (MC) 2) chest pain @) fatigue C. rupture of the chordae produces acute mitral insufficiency say ae 68Note: This material is copyrighted. AUl rights reserved. a D. sudden cardiac death from ventricular tachycardia may occur: seen in Marfan’s syndrome (USMLE) 5. diagnosis— echocardiography 6. Rx of symptomatic cases— A. calcium channel blockers or B-blockers B, negative inotropic agents reduce the force of contraction * Mitral regurgitation: 1. causes A. MVP MC structural cause B. left heart failure: stretching of MV ring C. chronic rheumatic heart disease D. infective endocarditis, E, rupture of the papillary muscle: usually right coronary artery thrombosis 2. pathophysiology— A. reflux of blood into the left atrium during systole B. volume overload in the left ventricle and left atrium: leads to hypertrophy/dilatation of both chambers 3 ical Dx. pansystolic murmur with radiation into the axilla heard best at the apex increases on expiration Sy heart sound: volume overload Sy heart sound: decreased compliance I- volume overload handled well until late in the disease when pulmonary symptoms begin to surface, like dyspnea and cough r Aortic stenosis: L causes— A. MCC isa calcified congenital bicuspid valve B. chronic rheumatic heart disease C. degenerative changes associated with old age pathophysiology- A B. reduction in the valve orifice area offers increased resistance to the ejection of blood during systole: decreased stroke volume/eardiac ourput poststenotic dilatation of aorta owing to stream of blood hitting the wall under increased pressure overload in the left ventricle leads to concentric left ventricular hypertrophy delayed/diminished arterial pulse wave: (1) decreased pulse amplitude @) _ narrow pulse pressure ejection murmur during systole: (1) best heard in right sternal border with radiation into carotid (2) also heard along the sternal border/apex in the elderly (3) _ increases intensity on expiration clinieal- A. MC valvular lesion associated with angina: (1) decreased cardiac output leads to less filling of coronary arteries during diastole (2) _ hypertrophied heart receives less blood 69Note: This material is copy ighted. AU rights reserved. B. MC valvular lesion associated with syneope with exercise: due to reduced cardiae ‘output and less blood available to the brain C. MC cause of microangiopathic hemolytic anemia with schistocytes © Aortic regurgitation: 1. causes A. MCCis long-standing essential hypertension B, medial disease in the aortic root C. chronic rheumatic heart disease D. E. infective endocarditis: MC left-sided valve involved in TV drug abusers dilatation of aortic valve ring: (1) syphilitic aortic aneurysm @) dissecting aortic aneurysm (3) coarctation of the aorta F, ankylosing spondylitis: aortitis 2. pathophysiology— A. volume overload in the left ventricle from an incompetent valve that leaks blood back into the left ventricle during diastole: eft ventricular dilatation/hypertrophy B. increased stroke volume: due to Frank-Starling mechanisms . increased pulse pressure: hyperdynamic circulation (see below) 3. physical Dx- A. Corrigan’s pulse: water hammer pulse or bounding arterial pulse B. _ high-pitched blowing early diastolic murmur heard immediately after Sy (1) heard best along left sternal border (2) _ increases in intensity with expiration C. Austin Flint murmur: (1) regurgitant stream from AV valve hits anterior leaflet of mitral valve causing it to vibrate and produce a diastolic murmur (2) _ sign of significant aortic regurgitation 4: clinical volume overload tolerated well until late in the course of the disease when angina and heart failure occur J ‘© Tricuspid stenosis: 1. cause- usually associated with mitral stenosis post-chronic rheumatic heart disease 2. _pathophysiology- volume overload in right atrium and systemic venous congestion 3. physical Dx- ‘A. cannon @ wave in the jugular venous pulse: atrial contraction against a stenotic valve with reflux of blood back into the jugular vein diastolic murmur heard best along left sternal border (1) opening snap not commonly heard (2) _ murmur intensity increases on inspiration 4. clinical signs of systemic venous congestion A, neck vein distention B. congestive hepatomegaly C. dependent pitting edema Tricuspid regurgitation: 1. causes A. stretching of the tricuspid valve ring in right heart failure: MCC B. chronic rheumatic heart disease oNote: This material is copyrighted. All rights reserved. C. carcinoid heart disease D. _ infective endocarditis in TV drug abuse 2. pathophysiology~ A. _ blood regurgitates into the right atrium and the jugular venous system B. volume overloads right ventricle and atrium: hypertrophy/dilatation 3. physical Dx~ A. giant e-v jugular venous pulse wave: blood regurgitates into the atrium during systole B. _ pansystolic murmur along left sternal border: intensity increases with inspiration C. pulsating liver D. right sided S; and S,: increase in intensity on inspiration Pulmor stenosis 1. causes— ‘A. congenital B. association with carcinoid syndrome 2. pathophysiology pressure overload of right ventricle 3. physical Dx- A. systolic ejection murmur heard best in 2nd left intercostal space B. right ventricular hypertrophy C. cannon a wave @ Pulmonic regurgitation— 1. causes ‘A. usually a functional murmur induced from congestive heart failure an B. _ pulmonary hypertension 2. pathophysiology~ A. Volume overload of right ventricle B. right sided S; and S,: increase in intensity on inspiration 3. physical Dx: A. early diastolic murmur after S,: increases in intensity on inspiration B. called Graham Steell murmur if associated with pulmonary hyperten: eart dilatation Careinoid heart disease~ 1. carcinoid syndrome is a triad of- A. cutaneous flushing: serotonin effect B. diarrhea: serotonin effect 2. pathophysiology- metastatic carcinoid tumor in the liver from a primary cancer in the terminal ileum allows serotonin access to the venous system B, serotonin is fibrogenic causing tricuspid regurgitation and pulmonic stenosis Infective endocard 1. etiology~ A. Streptococcus viridans MCC followed by Staphylococcus aureus B. Staphylococcus aureus MCC in intravenous drug abuse C. Streptococcus bovis endocarditis/sepsis is associated with colon cancer pathogenesis A. septicemia seeds a normal or previously damaged valve B. common in cyanotic congenital heart diseaseNote: This material is copyrighted. All rights reserved pathology— ‘A. friable vegetations can embolize B. mitral valve MC valve involved followed by aortic valve C. tricuspid valve followed by aortic valve most often involved in intravenous drug abuse clinical A. immunocomplex vasculitis: (1) Roth’s spot in the retina, splinter hemorshages (2) Osler’s nodes (painful) on hands/feet (3) Janeway lesions hand and feet (painless) (4) _ glomerulonephritis with hematuria with RBC casts B. fever C. splenomegaly in more subacute cases laboratory blood cultures positive in majority of cases USMLE scenario described a murmur of tricuspid regurgitation in an intravenous drug abuser: infective endocarditis involving TV Libman Sacks endocarditis: associated with SLE involves mitral valve Sterile vegetations with fibrinoid necrosis Yegetations located all over the valve unlike rheumatic fever, whose vegetations are on the margin of the valve 5. usually not clinically significant Marantic vegetations: 1, paraneoplastic syndrome- 2. sterile vegetations in mucin producing tumors of colon/pancreas 3. mitral valve most often involved Myocarditis/pericarditis: 1. coxsackievirus is MC 2, USMLE showed a picture of lymphocytes in myocardial tissue on an endomyocardi Bx Congestive cardiomyopathy: 1. causes A. idiopathic in most cases B. _ previous myocarditis: coxsackie MCC C. drugs: doxorubicin, tricyclics postpartum: commonly used on USMLE alcohol: direct toxic effect or thiamine deficiency hypothyroidism large, heart with all chambers dilated left and right heart failure Hypertrophic cardiomyopathy Ht} conae of pudfin 1. pathogenesis . “ A. AD in some cases B. asymmetrically hypertrophied interventricular septum C- obstruction to blood flow is due to the anterior leaflet of mitral valve being drawn against the interventricular septum by Venturi effect,1 Anterior MY leatetcrawn Carsise output ‘Anterior MV leit obstructs oad How + Asymmetric septum | tic of ldlopathie hypertrophie subaortic stenoals. (See Figure 102 Tor list of abbreviations)Note: This material is copyrighted. AU rights reserved. e D. aberrant myofibers and conduction system in the septum: conduction disturbances responsible for sudden death 2 ical— MCC of sudden death in young people and athletes syncope with exercise and angina with exercise murmur intensity decreases and clinical improvement occurs with anything that increases left ventricular volume: (1) increased venous return to heart (squatting, lying down) (2) decrease cardiac contractility and heart rate to increase filling (B-blocker) D. murmur intensity increases and clinical condition worsens with less left ventricular blood volume or the use of inotropic drugs: (@) Valsalva © Pyglond AE | marr (2) cardiac inotropic agents like digitalis ae Epo Tug Ae, (3) _venodilators (amy! nitrite, nitrogtyceri ane 4 Restrictive cardiomyopath peak 2 becker 1, non-compliant heart— cannot fill properly “ pa 2. causes A. glycogen: Pompe's glycogenosis B. iron: iron overload disorders, C. amyloid: senile amyloidosis (amyloid derived from prealbumin) D. _ endocardial fibroelastosis in child: thick endocardial tissue ‘Cardiac myxoma: 1. MC primary adult heart tumor benign mesenchymal tumor 2. site A. usually left atrium B. ‘USMEB used right atrium on one exam 3. clinieal~ A. embolize B. fever C. syncope » Cardiac rhabdomyoma: 1 MC primary heart tumor.in children part of tuberous sclerosis complex Pericardial effusion: L causes— ‘A. viral pericarditis due to coxsackie virus MCC B. SLE: MC cardiac disease in SLE Cc. trauma pathophysiology— A. all pressures in all chambers are increased but the cardiac output is decreased B. chambers cannot fill up with blood during diastole C. _ blood refluxes back into the jugular vein on inspiration clinieal— Beck's triad: A. neck vein distention with inspiration (Kussmaul sign) B. ‘moffled heart sounds C. _ hypotension: associated with pulsus paradoxus (drop in blood preggure on inspiration) Dx- echocardiogram VBP. > font erimppiacion B‘Note: This material is copyrighted. All rights reserved. 5. R= pericardiocentesis Constrietive pericarditis: 1. causes A. TB MCC worldwide B. _ previous heart surgery is MCC in United States 2. _pathophysiology- A. heart cannot completely fill B. pericardial knock when ventricles hit thickened pericardium ® ECG questions on USMLE: 1, shortQTinterval- hypercalcemia 2. prolonged QT interval hypocalcemia 3. Uswaye- hypokalemia 4. peaked TPwave- hyperkalemia 5. SPdepression— subendocardial ischemia 6. SPelevation— transmural ischemia/infaretion 7. prolonged PR interval ‘AD first degree heart block B. common finding in patients on digitalis 8. atrial fibrillation 9. ventricular premature beats/tachyeardia 10, anterior myocardial infaretion= new Q waves in anterior leads I through IV } 11. _ inferior wall acute tiyoeardial infaretion— new Q waves in Il, Il, and aVF } 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 Questions used during the board review: | ‘FA 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 j 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 Sn-There is widening of the aortic knob on a chest x-ray. The mechanism for this patient’s condition is MOST CLOSELY related to. A. atherosclerosis, a defect in fibrillin adefect in collagen an infectious process ‘an acute myocardial infarction e poo 4Note: This material i copyrighted. All rights reserved. B (dissecting aortic aneurysm) = A 26-year-old woman Presents with @ history of chest palpitations Particularly when anxious, Physical exam reveals a mid-systolic ejection click followed bya murmur, The click and murmur more closer to Si when the patient is standing and closer vc Sz when the lying down, The {{eshanism for this patient's valvular disorder is MOST CLOSET y 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) A 28-year-old Patient has a family history of sudden cardiac death at a young age. The patient has a {yetolie lection murmur that decreases in intensity when the Patient is lying down and increases in vale, When standing up. An echocardiogram reveals abnormut movement of the anterior mitral valve leaflet against an asymmetrically thickened interventricular septum. The patient MOST LIKELY has, A. mitral vaive prolapse B. hypertrophic cardiomyopathy C.acongenital bicuspid aortic valve D. acardiac myxoma of the left atrium FE poriltetive endocarditis involving the mitral valve B (hypertrophic cardiomyopathy) ‘FA 65-year-old man on the Sth day of hospitalization for an acute anterior myocardial infarction has LIKED Y gget Shest Pain and an increase in both CK-MB and woponin-1.The patient MOST LIKELY has. A. papillary muscle dysfunction B. aright ventricular infarct C. ventricular aneurysm D. amyocardial rupture B. reinfarction he ‘Which ofthe following is present in BOTH len and right heart failure? A. Sy heart sound B. Pillow orthopnea C. Pulmonary edema D. Neck vein distention E. Dependent pitting edema A (Choice B in LHF, choice C in LHF, choice D in RHF, choice E in RHF) fs yyy)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 $20;% | A B c D Rightatrium [75 75 80 is | 7s] ght ventricle | 75 80 80, [as T Pulmonary 75 80 80 75 artery {Pulmonary vein | 95 5 95 93 | 95 3 Left ventricle | 95 95 95 95 | 80 80 Aorta [95 95 95 95 [80 80 SaO, = oxygen saturation B (A= SD, B= ASD, C= PDA, D = Tetralogy, E = transposition) ‘" A.30 year old man with a viral myocarditis who develops hypotension, neck vein dstent jon, a drop in blood pressure on inspiration, and muffled heart sounds most likely has A. _ hypertrophic cardiomyopathy B. constrictive pericarditis C. _hypovolemic shock D. a pericardial effusion E, _adissecting aortic aneurysm D (Beck's triad of pericardial effusion) Items 9-11 A. Aortic stenosis B, Aortic regurgitation C. Mitral stenosis D. Mitral regurgitation E. Tricuspid regurgitation o A 70 year old man with diminished pulses and a history of angina and syncope with exercise has an jection type murmut radiating into the carotid arteries A Year old man with left heart failure has an S3 and $4 heart sound and a pansystolie murmur located at the apex that increases with expiration D 4 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 E ‘2 Which of the following types of hepatitis is associated with a vasculitis characterized by p-ANCA antibodies? A. Hepatitis A B. Hepatitis B ©. Hepatitis C D. Hepatitis D E, Hepatitis E B (polyarteritis nodosa)Note: This material is copyrighted. All rights reserved. A 7 year old boy presents with a low-grade fever, arthralgias, colicky abdominal pain, and a palpable purpuric rash limited to the lower extremities. Laborato, studies reveal a guaiac-positive Stool, @ urinalysis with red blood cell (RBC) casts, hematuria, and mila proteinuria, and a CBC With @ normal Hb, Het, and platelet count. Which ofthe following is the mee likely diagnosis? A. Idiopathic thrombocytopenia purpura (ITP) B. Systemic lupus erythematosus (SLE) C. _ Poststreptococcal glomerulonephritis D. Rocky Mountain spotted fever E. Henoch-Schonlein vasculitisNote: This material is copyrighted All rights reserved. Respiratory system: ‘Arterial blood gas (ABG) interpretation: 1. review Fluids and Hemodynamics and Acid-Base 2. respiratory acidosis A. pH<7.35 B. PCO,>45 C. compensation is metabolic alkalo: (2) HCO; <30 mEq/L is acute respiratory acidosis @Q) HCO; >30 mEq/L is chronic respiratory acidosis 3. respiratory alkalosis: A. pH>7.45 B. PCO; C. metabolic acidosis is compensation: (1) HCO; 218 mEq/L is acute respiratory alkalosis (2) HCO; <12 mEq/L is chronic respiratory alkalosis metabolic acidosi A. pH<7.35 B. HCO; <22 C. respiratory alkalosi 5. metabolic alkalosis: A. pH>7.45 B. HCO; >28 C. respiratory acidosis is compensation: PCO; increased 6. mixed disorders: ‘A. 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 C. 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: (Q) normal pHt is is compensation: PCO; decreased @) PCOs< a. respiratory alkalosis b. salicylates overstimulate the CNS respiratory center, ! @) HCO; <22 a. — metabolic acido: b. salicylate is an acid and salicylates damage mitochondria leading to tissue hypoxia and lactic acidosis .ce schematic © Pulmonary function tests in restrictive and obstructive lung diseas 1. restrictive lung disease- A. problem in getting air into the lungs: decreased compliai B. elasticity is increased: once air is in the lungs, it comes out rapidly on expiration C. all volumes and capacities are equally decreased i D. _ forced expiratory volume in 1 second (FEV .) is decreased 8TLeve FIGURE 11-1. Schematic of the normal lung volumes and ca- pacities and the forced expiratory volume 1 second (FEV,..) and forced vital capacity (FV) in a normal person (A), a person with restrictive lung disease (B), and a person with obstructive lung disease (CQ). FRC (functional residual capacity) represents the volume of gas that remains in the lung at rest at the end of a normal respiration and is the most reproducible part of a pulmo- nary function test, since it does not require patient effort, Person A (Rormal individual) has an FEVin. of 4 L and an FVC of 5 L, with FEVie/FVC ratio = 0.80. Person B with restrictive lung disease has a “miniaturi¢ed” curve of person A. Note that the wee and FVC are the same (3 L) owing to the increase in lasticity in the lungs, hence FEVij«/FVC ratio = 1.0, Person C with the obstructive pattern is having difficulty in expelling from the lungs owing to decreased lung elasticity. FEVise = 1 L, FVC = 3 L, and FEVua/FVC ratio = 0.33. Both people B and C have reduced values for FEVise 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 faster. Person C has increased compliance (air easily enters the lungs): however, reduced elasticity causes the lungs to trap air on expira- tion, hence FEVisee and FVC are much lower than in person B and the FEVi../FVC ratio is reduced. TLC, total lung capacity; TV, tidal volume; VC, vital capacity.Note: This material is copyrighted, All rights reserved. (2) FEVice is how much air a person can expel from the lungs in 1 second after @ maximal inspiration (2) normal FEV is liters (3) usually <3 liters in restrictive disease E. _ forced vital capacity (FVC) is decreased: (@)_ FVC is how much air the patient can expel fro inspiration @) normal is $ Titers G) "offen the same value as FEVi,g. due to increased elasticity of the lungs F. ratio of FEVya/FVC is increased (2) normal is 4/5 = 0.80 (2) _ in restrictive disease, it is usually increased (3/3 = 100%) 2. obstructive lung disease A. problem with getting air out of the lungs rather than into the lungs: (1) compliance increased @) elasticity decreased B. residual volume is increased, since all the air cannot get out ofthe lungs: (2) this automatically increases the total lung capacity 2) other volumes and capacities are decreas C. forced expiratory volume in 1 second (FEV. is decreased: (1) normal FEV ec is 4 liters (2) usually <2 liters in obstructive disease D. forced vital capacity (FVC) is decreased: (1) normal is 5 liters @) usually <2 liters, due to decreased elas ratio of FEVisad/FVC is decreased: 1) normal is 4/5 = 0.80 2) _inobstructive disease, it is usually decreased (1/3 = 0.33) 3.__Summary of pulmonary function tests in obstructive and restrictive lung disease n the lungs after a maximal of the lungs Parameter Obstructive Restrictive [Total lung capacity (TLC) | Increased Decreased Residual volume (RV) Increased Decreased | Tidal volume (TV) Decreased Decreased Vital capacity (VC) Decreased Decreased [EVs Decreased Decreased) | Decreased Decreased | EVG Decreased Normal to increased Decreased Decreased forced expiratory volume | second, FVC = forced vital cap. with carbon monoxide » DL-co = diffusion capacity ‘© Causes of an increased alveolar-arterial gradient (A-a gradient): }; _ A-a> difference between the alveolar PAO; and arterial PaO; in the lungs 2. causes of increased gradient- A. ventilation without perfusion: Q) eg, atelectasis @) produces intrapulmonary shunting (3) giving 100% O; does not increase the PaO.this material is copyrighted, All rights reserved. B. perfusion without ventilation: (eg. pulmonary embolus (2) increased dead space (3) giving 100% O; does increase PO; since normally ventilated lung can make up the difference C. diffusion abnormalities: e.g., interstitial fibrosis D. right to left shunts in the heart: e.g., eyanotic 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 4. causes of hypoxemia with a normal A-a gradient A. depression of the respiratory center in the medulla 00 mm Hg @) eg,, barbiturates @) CNS injury B. obstruction of upper airway () eg,, café coronary 2) epiglotttis @) 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 C. _ non-immune mechanism: (1) _ aspirin blocks cyclooxygenase and leaves the lipoxygenase pathway open @) LTC-, D, Ez 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 jical— A. hoarseness 80Note: This material is copyrighted. All rights reserved. Atelectasis: L of fever 24 hs after surgery pathophysiology — A. collapse of alveoli due to mucus blocking terminal bronchioles B. distal resorption of air through the pores of Kohn clinical signs of consolidation A chect Yi A. increased tactile fremitus /viLRafion of chest when) hints) B. decreased percussion CC. clevated diaphragm (diaphragm moves up when alveoli collapse) D. chest lag on inspiration 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: () lecithin (phosphatidylcholine) @) synthesized by type IT pneumocytes, 3) _ stored in lamellar bodies ‘© Respiratory distress syndrome: 1, pathogenesis— A. decreased surfactant in fetus due to: (1) baby is premature @) poor glycemic control in mother with diabetes_ a. hyperglycemia in mother—> b. hyperglycemia in fetus—> ¢. increase in fetal release of insulin—> d. insulin inhibits surfactant synthesis) (3) cesarean section. a. no stress on baby—> b. no increase in cortisol pathophystology— A. widespread atelectasis—> B. _ massive intrapulmonary shunting—> hyaline membranes composed of protein from vessel leakage (diffusion defect) clinical— A. respiratory difficulty shortly after birth B, cyanosis complications— ‘A. superoxide free radical damage: (1) retrolental fibroplasia 2) bronchopulmonary dysplasia necrotizing enterocolitisNote: This material is copyrighted. All rights reserved. o C. intraventricular hemorthage D. patent ductus arteriosis with machinery murmur: due to persistent hypoxemia 5. Rx of RDS— A. positive end-expiratory pressure (PEEP) keeps airways from 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 C. trauma D. pneumonia , ha E, smoke inhalation tao —> Fangs collapte 2 pathophysiology wy ee i) d non-cardiogenic pulmonary edema B neutrophil-related injury with destruction of type II pneumocytes (loss of surfactant) and damage to pulmonary capillaries ("leaky capillary sy €. 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 mortality Spontaneous pneumothorax 1. causes A. idiopathic: (McC 2) tall, thin males @) rupture of subpleural bullae in apex of lung B. iatrogenic: e.g,, needle puncture of lung after perform Marfans syndrome 2. pathogenesis portion of the lung collapses: pleural cavity pressure is the same as the atmospheric pressure ical sudden onset of pleuritic type of chest pain tympanitic percussion note absent breath sounds diaphragm elevated trachea deviates to the side of the collapse 4. (USMLB/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 ga subclavian vein sti AL B, ie D. E. pneumothorax Tension pneumothorax: 1. cause- A. penetrating trauma to the lungsNote: This material is copyrighted, All rights reserved. B. _ tension pneumatocysts: (1) occur in patients with S. aureus pneumonia (e.g, cystic fibrosis) @) _intrapleural blebs occur that may rupture pathophysiology— ‘A. tear in the pleura allows air into the pleural cavity but prevents its exit B. increased intrapleural pressure shifts the mediastinal structures to the opposite side: compromises blood flow into the heart and out of the heart C. diaphragm is depressed on the affected side D. _ breath sounds absent on affected side E. __tympanitic percussion note 3. Rx- insert needle into the pleural cavity to relieve pressure ‘Typical vs atypical pneumonia: 1. typical— A. sudden onset of symptoms B. high fever €. productive cough: usually positive gram stain for bacteria D. signs of consolidation on physical exam and x-ray E. Streptococcus pneumoniae MCC F. chest x-ray is first step in management atypical A. insidious onset B. low grade fever C. non to mildly productive cough D. _ no signs of consolidation (interstitial pneumonia) E. Mycoplasma pneumoniae MCC followed by Chlamydia pneumoniae (TWAR agent) Community-acquired vs nosocomial pneumonia 1. community acquired~ MC due to Streptococcus pneumoniae 2. nosocor develops while in the hospital organisms in deScending order: (E.coli (2) P. aeruginosa (MC if a respirator is involved) @) S.aureus Differential for rusty colored sputum: 1. Streptococcus pneumoniae pneumonia 2. chronic congestive heart failure heart failure cells, 3. mitral stenosis 4. Goodpasture’s syndrome ‘Summary tables of infectious disease Microbial Epidemiology pathogen 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 material/respiratory | clinical practice droplet infection. ~100 serotypes (vaccine unlikely),Note: This material is copyrighted, AI rights reserved. syncytial (RSV) virus Influenzavirus MCC_of interstitial_pneumonia bronchiolitis with wheezing (50%) in infants ate falliwinter. Hand to hand transfer of infected material/respiratory droplet infection. Significant cause of among those over underlying renal, cardiac or hung problems. ‘Type A virus produces pandemics and epidemics (most severe form). Type B produces epidemics. Type C is involved in sporadic cases. Hemagelutinins 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 mortality especially (20%) and] 5 years of age who have | Dx with direct immunofluorescent techniques or ELISA test on nasopharyngeal swabs. Rx: ribavirin for very severe infections Mild cold to bronchitis to severe pneumonias (with exudate). Pneum- 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. Reye syndrome may occur in children. Rx: amantadine (inhibits viral uncoating or transcription of organisms, called antigenic drifts (point | viral RNA), mutations). Pandemics are due to antigenic shifts, which involve mutations in l | hemagglutinin (need new vaccine). | Rubeola Symptoms of rubeola begin to appear after the | Fever, cough, conjunctivitis, and (regular 4 d incubation period is finished. coryza (excessive nasal mucus measles) 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. Chlamydia Omithosis, or psittacosis, is a zoonosis (a| Primarily results in interstitial psittaci disease contracted from animals). Inhalation | pneumonitis. Rx: erythromycin. of C. psittaci from psittacine birds (parrots, L parakeets, pigeons, and turkeys). Chlamydia Droplet infection without an avian | Rx: tetracycline. pneumoniae | intermediate. 5% of community acquired TWAR) atypical pneumonias. —Seroepidemiologic relationship with coronary artery disease. Chlamydia Newbom pneumonia. ~10 to 20% of| Presents with staccato cough, con- trachomatis newborns that pass through an infected birth | junctivitis, tachypnea, bilateral inspir- canal develop pneumonia atory crackles, scattered expiratory wheezes, and hyperinflation (trap air), Afebrile. Eosinophilia, Rx: erythro- mycin, Coxiella Only rickettsia transmitted without a vector. | Sudden onset of high fever, headache, burnetii (Q Inhalation. Contracted by dairy farmers, | chest pain, myalgias. Interstitial fever) veterinarians associated with the birthing | pneumonia. Other problems: granulo- process of infected sheep, cattle and goats and handling of milk in these animals. USMLE: person shoveling sheep dung, matous hepatitis (50%), infec endocarditis. Rx: doxycycline.Note: This material is copyrighted, AN rights reserved. Mycoplasma pneumoniae of pneumonias in MCC of primary atypical pneumonia, | Nonproductive cough. Upper respira: 20% of pneumonias in adolescents. 50% | tory tract symptoms (pharyngitis, military recruits. | earache) precede pneumonic manifest- Incubation period 1-2 wks ations, Interstitial pneumonia. Low grade fever. Complications: bullous myringitis (hemorrhagic vesicles on the membranes), erythema multiforme (target-like 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: erythro- mycin or tetracycline | Microbiat Pathogen Gram Stain ‘Comments ‘Streptococcus pneumoniae ‘Staphylococcus Gram + lancet: diplococcus Gram + coceus shaped MCC_of community "acquired typical pneumonia (bronchopneumonia or lobar pneumonia), Rx: erythromycin. Pneumonia commonly follows influenza infections (MC aureus bacterial pathogen). Major pathogen in cystic fibrosis. Common cause of nosocomial pneumonia, Hemorrhagic pulmonary edema, abscess formation, and tension pheumatocysts (intrapleural blebs), which may rupture and produce pneumothorax. Yellow colored sputum, Hemophilus | Gram -vod ‘Common cause of pneumonia in cystic fibrosis and COPD. influenzae Pseudomonas aeruginosa Klebsiella pneumoniae Nocardia | asteroides Gram - thin rod Gram - fat rod with capsule Strict aerobe. Gram + filamentous bacteria. Partially acid fast Rx: TMP/SMX. Acute epiglottis in children. Decreased incidence due to immunization. Cause of inspiratory stridor, Thumbprint sign on lateral x-ray of neck. Rx: cefuroxime Water loving bacteria transmitted by respirators. Common cause of nosocomial pneumonia and MCC of pneumonia in cystic fibrosis. MC pneumonia in ICU/CCU (due to respirators). Blood vessel invader (hemorrhagic infarctions), Green colored sputum (pyocyanin). Rx: antipseudomonal f- | lactamase susceptible penicillins (¢.g., mezlocillin). neumonia commonly associated with alcoholics and MC pneumonia in nursing homes. Blood-tinged, mucoid sputum, Tends to involve the upper_lobes and cavitates Ii reactivation TB. Lobar consolidation and abscess formation are common. Rx: third generation cephalosporin Granulomatous —microabscesses inthe lungs in immunocompromised patients. Rx: TMP/SMX detinomyces ‘Anaerobe. Gram + Draining sinuses in the jaw, chest cavity, and abdomen Israeli filamentous bacteria, fur granules contain bacteria, Rx: ampicillin or penicillin G. Legionella Gram - rod (need IF | Water loving bacteria (water coolers), Pneumonia with dry pneumophila | stain or Dieterle silver | cough, malaise, flu-like symptoms, bloody sputum, and stain striking fever. Other findings: arthralgias, renal, and CNSNote: This material is copyrighted. All rights reserved. findings. Macrophage rather than a neutrophil response Th tissue, Can produce hyponatremia secondary to hypo- seninemic hypoaldosteronism from interstitial nephritis. Rx erythromycin o tetracycline + rifampin, Mycobacterium | Strict aerobe. Acid- ubercutosis | fast Droplet infection. Primary TB: upper part lower lobe, lower part of upper lobe, Ghon complex. Usually resolves Reactivation TB: upper lobe, cavitary lesion, Kidney MC extrapulmonary site Candida Not dimorphic, Bud- albicans ding yeasts and pseudo- hypha. Lung disease contracted from infect- ions of indwelling cath. Vessel invasion produces hemormhagie infardis. Rw amphotericin B or fluconazole eters | Goceidioides Dimorphi. Spherules | Flu-like sympioms and exihema nodosum (paul nodulce | immitis With endospores in tis- | on lower legs). Pneumonia may be localized (egg. shell sues. Inhaling arthro- spores while living or passing through the Southwest or San Joa- quin valley in Califor- nia ("valley fever"), Increased afier earth. quakes (USMLE) Cryptococcus | Not dimorphic, Bud- neoformans | ding yeast with narrow | based buds. Found in pigeon excreta (around buildings, outside of- fice windows, under bridges). MC fungal ‘opportunistic infection, 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 | Primary lung disease (40%). Produces @ 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 | | Histoplasma Dimorphic. MC syste- capsulatum | mic fangal infection MC in Midwest, Inhal- | ation of spores. Assoc- iation with bats, birds Starlings), cave exp- | lorers (spelunkers), abandoned warchous- es. Yeast forms in mac- rophages. Simulates TB lung disease. Dormant phase like TB (can reactivate). Produces coin lesions, consolidation, miliary spread, cavitation. Old infection sites characteristically contain salcified granulomas. MCC of _ sclerosing mediasini’s (bvous 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 Involves skin (skin has a verrucoid appearance resembling dermatitidis | have 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- ion, Aspergillus | Not dimorphic. Fruiting | Aspergilloma refers to a flngus ball (visible on xray) of fumigatus body and narrow-angl- | matted hyphae and fruiting bodies that develops in a | ed, branching septate | preexisting cavity in the lung (e.g., old TB site), Cause of hyphae. massive hemoptysis. Allergic bronchopulmonary di involves both type I and type III 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, Notdimorphic, Wide- | Clinical settings: 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 Pneumocystis | Reclassified as fungus. | Opportunistic infection. MC initial AIDS-defining infection. 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 organisms, 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/ui. stains. Foamy alveolar infiltrate. Occurs when CD, T helper count 200 cellsuk. Parasites with Ascaris, Strongyloides, hookworm. larval phase in lungs _ | ‘ USMLE scenarios with respiratory disease: 1. problems in eystie fibrosis patients associated with P. aeruginosa~ A. pneumonia B. _ bronchiectasis C. sepsis D. tension pneumothorax from ruptured pneumatocysts 2, MCC of pneumonia in eystie fibrosis P. aeruginosa 3. eaye™explorer” in Arizona» with respiratory infeetion~ coccidioidomycosis (not histoplasmosis, too dry a climate and mainly in Ohio and Midwest) 4, 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 5. respiratory problem associated with exposure to pigeons dung on window sill or under aibridge= cryptococcus 87Note: This material is copyrighted. AM rights reserved. diseases where Streptococcus pneumoniae is MCC- community acquired pneumonia meningitis in adults >18 otitis media spontaneous peritonitis in children with ascites sepsis in children with HbSS disease . sinusitis diseases where Pseudomonas aeruginosa is MCC- ‘A. ICU pneumonia (respirators) B. COD in bum patients, C. COD in cystic fibrosis D. _cellulitis/osteomyelitis in puncture wounds of foot in patient's with rubber footwear E, _ malignant external otitis in diabetes F. ecthyma gangrenosum G. hot tube folliculitis Aiseases where Hemophilus influenzae is MCC~ acute epiglottitis (decreased due to Hib immunization) MO/AIDS-defining infection Preumocystis carinii pneumonia elderly man, who lives at home with his wife, develops. pneumonia— Sireprococcus pneumonia ‘chest'x-ray-with right middle lobe pneumonia (obscures right margin of the heart)~ A. _ probably related to obstruction by a bronchogenic carcinoma B. could also be aspiration with the patient lying down on the right side afebrile infant with staccato cough, signs of hyperaeration, conjunctivitis~ Chic trachomatis pneumonia Lung abscesses 1. causes~ A. aspiration of oropharyngeal material is MCC: mixed aerobe/anaerobe infection B. lobar pneumonia C. _ hematogenous spread air/fluid level on x-ray ung locations with aspiration: standing/sitting— posterobasal segment right lower lobe lying down on back~ superior segment right lower lobe (MC site for abscess) lying om right side~ A. right middle lobe B. h I 1 3, posterior segment of right upper lobe ing on left side lingula Pulmonary embolus: 1. souree- femoral vein 2. 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-operativeNote: This material is copyrighted. All clinieal— sudden onset of dyspnea and tachypnea: MC symptom and sign, respectively fever pleuritie chest pain perfusion scan first step in work-up respiratory alkalosis mild hypoxemia increased A-a gradient pulmonary angiogram gold standard for Dx, TUSMLE Seenario~ gross photo of a large saddle embolus in a patient on prolonged bed rest usually die of acute right heart strain ‘Pulmonary hypertension: 1. causes- ‘A. chronic hypoxemia: (1) hypoxemia vasoconstricts pulmonary vessels and vasodilates peripheral vessels 2) high altitude residents (3) chronic lung disease loss of pulmonary vasculature: .¢., (Copp (2) restrictive lung diseases C._leftto right shunts with eventual volume overload of right heart D. _ mitral stenosis with backup of blood into pulmonary veins pathology~ A. atherosclerosis of pulmonary arteries B. smooth muscle hypertrophy of pulmonary vessels C. _angiomatoid lesions clinical— ‘A. accentuated P, B. cor pulmonale: Q) pulmonary hypertension (PH) leads to right ventricular hypertrophy (2) definition applies to primary PH of pulmonary artery or PH due to lung disease (3) _ does not apply to PH and RVH of cardiac origin of primary origin a eg, mitral stenosis b. left to right shunts C. primary PH occurs mainly in young women: progressive dyspnea, chest pain, syncopal episodes D. _ pruning of pulmonary arteries noted on x-ray Immotile cilia syndrome (Kartagener's syndrome): 1, absent dynein arm in cilia clinieal- A. situs inversus: (1) vessels and chamber in the heart are still normal (USMILE) 2) not a complete transposition infertility in males/females bronchiectasis sinus infectionsNote: This material is copyrighted. Al rights reserved Restrictive lung diseas 1. decreased compliance and increased elasticity due to interstitial fibrosis 2. causes~ A. pneumoconioses MCC: dust borne diseases B. sarcoidosis C. hypersensitivity lung diseases D. drugs: see Environmental pathology notes 3. coal worker's pneumoconiosis~ A. exposure to coal dust B. "black lung" disease C. increased incidence of TB but not cancer D. Caplan syndrome: rheumatoid nodules in lung 4. silicosis A. exposure to silica dust: ¢.g., sandblaster B. nodular, fibrotic masses in the lungs: filled with silica crystals C. increased risk for TB but not cancer D. association with Caplan’s syndrome 5. asbestosis A. exposure to asbestos: (1) pipe-fitter in shipyard (2) 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 (ferruginous body) looks like a dumbbell (fiber covered by iron) 6. hypersensitivity pneumonitis A. farmer’s lung: (1) _ inhalation of thermophilic actinomycetes, @) _see Immunopathélogy notes + coal worker's pneumoconiosis roe B. silo filler’s: inhalation of nitrogen dioxide fumes C._ byssinosis: (1) "Monday morning blues 2) _ patient works in a textile factory and has contact with cotton, linen, hemp 7. Hamman Rich lung— A. honeycomb lung B. end-stage of alveolitis syndromes: interstitial interstitial pneumonitis pneumonitis syndromes~ e.g., usual 8. sarcoidosis— ‘granulomatous disease of unknown etiology primarily targets the lungs: noncaseating granulomas in hilar nodes and parenchyma uveitis with blurry vision salivary gland enlargement ge er} MCC of non-infectiok’granulomatous hepatitis nodules in skin contain granulomas — lab: (1) increase in angiotensin convert 2) anergy to common antigens (3) low CD, T helper cell counts used up in producing granulomas guanhmes) OmmpomP enzymeNote: This material is copyrighted. All rights reserved. r (4) hypercalcemia Obstructive lung disease: 1. types- A. chronic bronchitis: (MC type @) clinical Dx~ productive cough >3 mths for 2 consecutive yrs B. emphysema C. bronchial asthma D. _ bronchiectasis 2.__summary chart comparing chronic bronchitis with emphysema— Parameter ‘Emphysema Chronic Bronchitis ‘Onset of dyspnea Progressive, constant, severe Intermittent and often exacerbates with infection Sputum production | Scant Increased and purulent Appearance “Pink puffer” (not cyanotic), thin, | “Blue bloater” (cyanotic due to weight loss respiratory acidosis), obese [AP diameter Increased (hyperinflation) Less hyperinflation than emphysema Breath sounds Diminished owing to hyperinflation | Wheezes and sibilant chonchi PaO; Mild hypoxemia at rest. Moderate to severe hypoxemia PaCO; Normal to low (respiratory | Increased to respiratory alkalosis, reason for “pink puffer”) owing acidosis~ trap CO: behind terminal bronchioles filled with mucous Total lung capacity ‘Markedly increased Normal to slightly increased Residual volume Cor pulmonale ‘Markedly increased Infrequent until late in the disease Mildly increased ‘Commonly present Ventilation/perfu- sion ‘Matched losses of ventilation (resp- iratory unit) and perfusion (loss of capillary bed) Major mismatch owing to primary involvement of the terminal bronch- iole (proximal to the respiratory unit, hence more units are affected) types of emphysema— A. emphysema involves portions of the respiratory unit: (1) respiratory bronchiol ? 2) alveolar duct @) aves § B. centrilobular emphysema: (1) primary type in smokers @) destruction of elastic tissue support in the respiratory bronchiole @) upper lobe involved . x panacinar emphysema: (1) +l antitrypsin (AAT) deficiency a. primary AR disease b. acquired in smokers: chemicals in smoke inactivate AAT 2) involves the entire respiratory unit (respiratory bronchiole, alveolar duct, and alveoli) (3)__ lower lobe disease D. \USMLE scenario: (1) identify x-ray of a patient with emphysema @) look for increased AP diameter and depressed diaphragms 1Note: This material is copyrighted. All rights reserved. 4. bronchiectasis A. cystic fibrosis is the MCC in the United States: TB is the MCC in third world countries B. pathogenesis (1) obstruction and infection (2) dilated bronchi extend to the lung periphery C. clinical: cough up cupfuls of fou! smelling sputum bronchial asthma— A. MC chronic 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 4 e. environmental pollutants smoke D. clinica ) episodic wheezing 2) nocturnal cough G) _ increased AP diameter dvetosir rapping 7) E. lab findings: { in’°sl'¥) Setondenily) (1) respiratory’ alkalosis~ may progress into respiratory acidosis if bronchospasm is not relieved @) hypoxemia faveg frgoehecl (3) decreased FEV sec values Ah, se opow ET (4) eosinophilia af thimalig , parle pt (8) positive skin tests for allergens Diet. dechodis oe Re: (1) albuterol medihaler for mild disease Titibife srmedidely , icosteroid medihaler for 2 4 a ® corticosteroid medihaler for moderate to severe disease, fo spittedy Spat ung cancer: 7 / 1. causes— 9 Nebssamy Phetonecoleyi A. seeneoplasia rite 4 J B. decreasing incidence in men/increasing incidence in women C. 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 (Inypercalcemia) C. small cell carcinoma: ectopically secrete ACTH (ectopic Cushings) and ADH (SiADH) 3. MC cancers of lung— metastasis: A. breast MCC B. renal adenocarcinomaNote: This material is copyrighted. All rights reserved. C.chorioe D. colorectal « hung site A. centrally located: (2) squamous cell @) small cell B. _ peripherally located: adenocarcinoma smoking relationships- A. squamous and small cell cancers: strongest relationship B. adenocarcinoma: (1) MC primary lung cancer in smokers and non-smokers 2) _bronchioloalveolar carcinoma has no smoking relationship clinical A. cough MC symptom B. weight loss C. hemoptysis: sometimes massive D. Pancoast tumor (superior sulcus tumor) (1) squamous cancer at lung apex involving brachial plexus and superior cervical ganglion (Horner's syndrome) (2) Homer's syndrome includes ipsilateral lid lag, miosis, anhydrosis E. superior vena caval syndrome ~ 4 F. clubbing A | sites for metastasis outside hilar lymph nodes | _// A adrenals MCC site Oppoiete Atecliamy C. brain > widlope D. _ bone: lytic metastases Pydeias: prognosis— eae A. best for squamous B. worst for smail cell: usually non-operable bronchial carein A. low grade malignant APUD tumor B. clinical Q) hemoptysis @) local metastasis @) carcinoid syndrome without need to metastasize “USMLE question about a roofer for 25 years and a smoker for 10 years: 1. greatest risk is for primary lung cancer 2 primary lung eaneer is more common than a mesothelioma, whether a smoker or not 3. 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 (Boerhaave's syndrome) 1, Hamman’s sign in the chest due to subcutaneous emphysema from air dissecting into the tissueNote: This material is copyrighted. All rights reserved. 2, 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: .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 CC. “popeorn type” of configuration on x-ray Mediastinum: 1, anterior mediastinum MC involved with disease— A. thymoma MC tumor followed by nodular sclerosing Hodgkin's disea 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 C. thymectomy is sometimes used in Rx of myasthenia gravis 3. middle mediastinum pericardial cyst MC disorder Pleural fui 1. lab findings that distinguish a transudate from exudate in pleural fluid— A. PF protein/serum protein ratio >0.5 is exudate B. PF LDHi/serumLDH 0.6 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 3. PF transudates~ congestive heart failure MCC 4. 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: r 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\sq/FVC ratio? 6 year old child with recurrent respiratory infections and steatorrhea 28 year old non-smoking male with bilateral lower lobe emphysema 56 year old smoker with productive cough, dyspnea, and cyanosis 10 year old girl with bronchial asthma requiring systemic steroids 39 year old dyspneic African American with bilateral hilar nodes ruop>Note: This material is copyrighted, All rights reserved. E (sarcoidosis, restrictive lung disease) ‘FA 45-year old woman 24 hours post-cholecystectomy develops fever and dyspnea. Physical exam reveals decreased percussion, increased tactile fremitus, and decreased breath sounds in the right 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 a pulmonary infarction a spontaneous pneumothorax An afebril rear-old man develops a 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. A. pleural effusion B. _bronchopneumonia C. tension pneumothorax D. pulmonary infarction E. spontaneous pneumothorax A newborn child develops dyspnea, tachypnea, intercostal muscle retractions, and cyanosis 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, aspiration of amniotic fluid group B streptococcus pneumonia decreased production of surfactant Chlamydia trachomatis pneumonia heart failure from congenital heart disease (RDS) ‘F Which of the following describes a pneumonia due to Mycoplasma pneumoniae rather than Streptococcus 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. a Pancoast tumor a thoracic outlet syndrome the superior vena caval syndrome obstructive lung disease without primary cancer obstructive lung disease with metastatic cancer from another primary site 95Note: This material is copyrighted, All rights reserved A (Homer's syndrome also present) A 65 year old man ith urinary retention secondary to prostatic hyperplasia, develops spiking fever, and tachypnea. Physical exam reveals intercostal muscle retractions and bilateral inspiratory crackles. A chest x-ray exhibits bilateral imtersttial and alveolar infiltrates. ABGs demonstra severe hypoxemia. You expect the blood culture reveals. A. gram positive diplocoeci 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) e Inspiratory stridor is commonly associated with. A. a respiratory syneytial virus infection B. aparainfluenza virus infection C. —aspirin-induced asthma D. rhinovirus infections E, — choanal atresia B (croup or laryngotracheobronchitis due to parainfluenza virus, ob: sign on lateral x-ray of neck) Chlamydia trachomatis and the respiratory A. an interstitial type of pneumonia B. _laryngotracheobronchitis (croup) C. the respiratory distress syndrome D. typical community-acquired pneumonia E. _ hospital-acquired (nosocomial) pneumonia A(RSV MCC of pneumonia and bronchiolitis in children) ‘% Which of the following is more often associated with Klebsiella pneumoniae than Pseudomonas aeruginosa? A. — Upper lobe cavitation B. Green-colored sputum C. Association with eystie fibrosis D. Association with respirators E. Productive cough A (choices B, C, D are features of P. aeruginosa, both have productive cous struction is in the trachea, "steeple" ‘syncytial virus are BOTH commonly associated with. choice E]) {In a 30 year old man who lives in Tennessee, you would expect a calcified solitary coin lesion in the lung to represent. A. a foreign body B. an old granuloma C. metastatic cancer D. primary lung cancer a bronchial hamartoma B (histoplasmosis)Note: This material is copyrighted. All rights reserved. fear non-smoking coal worker has arthritis and nodular lesions in the lungs. His PPD skin test is negative. You suspect the patient has. systemic lupus erythematosus Caplan's syndrome metastatic lung disease primary lung cancer miliary tuberculosis moop> In a 62 year old man who has been a roofer for 25 years and a smoker for 10 y following cancers would he be most likely prone to developing? A. Pleural mesothelioma B. Primary lung cancer C. Laryngeal carcinoma D. Oral cancer E, Pancreatic cancer B (asbestos exposure, same answer even if he was not a smoker) s, which of theNote: This material is copyrighted. All rights reserved, ‘Gastrointestinal =" Common infections in the oral cavity ‘Organism, Disease Clinical Comments Coxsackievirus A Herpangina Children between 310 yr. Fever, pharyngitis, cervical lymphadenopathy. Multiple vesicles and/or ulcers surrounded by erythema located on soft palate and pharyngeal tissue, Coxsackievirus A Hand-foot-mouth disease Young children, Fever and vesicles located in mouth and distal extremities. Herpes simplex typeI Gingivostomatitis Children <3 years old. Primary disease produces systemic signs of fever and cervical adenopathy. Painful vesicles usually develop on the lips, gingiva, oropharyngeal mucosa, Remains dormant in sensory ganglia. Recurrent herpes simplex (herpes labialis) is nonsystemic and involves the vermilion border of lips. Reactivated by stress, sunlight, menses. Epstein-Barr virus (EBV) Pharyngitis Hairy leukoplakia Infectious mononucleosis is commonly associated with an exudative pharyngitis/tonsillitis and painful cervical adenopathy. Palatal petechia are present. Bilateral white, hairy exerescences on lateral border of tongue. Pre-AIDS defining lesion. Virus induces squamous hyperplasia of the epithelium (not a _precursor to cancer). Rx: acyclovir Sweptococcus | Pharyngitis ~20-35% of cases of exudative pharyngitis/tonsilits, ‘Byogenes ‘tonsil Majority (~$0%) viral induced (adenovirus, EBV, coxsackievirus). Lab Dx: direct antigen detection or culture (gold standard). Rx: penicillin G. Candida albicans | Oral candidiasis Thrush (pseudomembranous candidiasis) may occur in neonates (while passing through the birth canal) or immunocompromised patients (common in AIDS). Pseudomembrane covers the oral mucosa, When wiped off, it leaves a bleeding mucosal surface. Gram stain reveals budding yeasts and pseudohypha. Pre-AIDS defining lesion. ‘® Leukoplakic lesions in mouth or genital area: Bx to R/O squamous dysplasia/eancer © Smokeless tobacco: verrucoid squamous cancer in the mouth ca ‘Squamous cancer in mouth: 1. causes— A. smoking MCC B. alcohol C. smoking/alcohol are synergistic. 2. sites A. lateral border of tongue MC site B. lower lip: note~ upper lip is a basal cell carcinoma C. under tongue 98.Note: This material is copyrighted, All rights reserved. o Oral pigmentation: 1. Peutz-Jeghers syndrome 2, Addison’s disease 3. Ph poisoning in adult Gum hyperplasia: 1, phenytoin 2. pregnane 3. scurvy 4. acute monocytic leukemia Deviation of uvula to the opposite side abscess Salivary glands: L mumps MC infection 2 mixed tumor MC neoplasm— parotid MC location Dysphagia for solids not liquids: sign of mechanical obstruction~ 1. strictures 2. Plummer-Vinson esophageal web associated 3. esophageal cancer 4. Barrett's esophagus with uleeration and stricture (USMLE) Dysphagia for solids and liquids: 1. peristalsis problem 2. causes- A. achalasia MCC B. _ progressive systemic sclerosis/CREST syndrome C. _ polymyositis: upper esophagus in striated muscle D. myasthenia gravis: upper esophagus in striated muscle ‘Odynophagia: 1. painful swallowing 2. MCC is esophagit TE fistula: 1. proximal esophagus ends blindly and distal esophagus arises from the trachea (ait in the stomach) z polyhydramnios in mother Polyhydramnios: 1. TE fistula 2. anencephaly 3 duodenal atresia (Downs Syéltomé) Patient with dysphagia and a fetid odor to his brea 1. Zenker’s diverticulum 2. MC diverticulum in the esophagus 3. pulsion diverticulum through an area of weakness in cricopharyngeus muscle 4 collects food (bad breath)/inflamed Motor disorders of esophagus: 1. achalasia is MC motor disorder of esophagus— a patient with exudative tonsillitis: _peritonsillar ron deficiency 99Note: This material is copyrighted, All rights reserved. A. failure of relaxation of LES sphincter due to absent myenteric ganglion cells: ganglion cells normally contain vasointestinal peptide, which relaxes the LES B. _aperistalsis and dilatation of proximal esophagus C. clinical: (1) regurgitation of undigested food at night (2) _ bird's beak appearance with barium study 2. comparison of achalasia with Hirschsprung’s disease— A. in Hirschsprung’s, both submucosal (Meissner’s) and myenteric plexus (Auerbach’s) are missing B. in Hirschsprung’s proximal bowel is dilated but does have peristalsis 3. comparison of achalasia with PSS/CREST syndrome— A. PSS/CREST have a relaxed LES B. both have absences of proximal esophageal motility C. both are best diagnosed with manometry 7 GERD: 1. relaxed LES 2. acid injury leads to ulceration of distal esophagus mucosa 3. Barrett's esophagus A. ulceration and stricture B._ distal adenocarcinoma MC eancer in esophagus 4. GERD MCC of nocturnal cough ‘© Esophagitis in AIDS: 1. Candida MCC 2. other eauses~ Herpes and CMV 3. odynophagia F Lye strictures: 1, alkalis produce liquefactive necrosis with stricture formation 2. acid produces coagulation necrosis ‘Vessels in esophageal varices: 1. left gastric (branch off the portal vein) and azygous vein 2. due to portal hypertension from cirrhosis of liver 3. rupture is MC complication and COD in cirrhosis 4. endoscopy is first step in management Mallory Weiss: 1. tear of distal esophagus 2. causes~ A. retching in alcoholics B. bulimia & Boerhaave's: 1. rupture of distal esophagus f 2. causes— A. — endoscopy MCC B. _ retching in alcoholic Cc. bulimia 3. Hamman's mediastinal crunch— A. complication of Boerhaave's B. _airdissecting subcutaneously (subcutaneous emphysema) 100Note: This material is copyrighted. All rights reserved. MC primary cancer of esophagus: 1, adenocarcinoma of distal esophagus: complication of Barrett's esophagus 2. squamous cancer MC in third world countries or if located in mid-esophagus ‘ USMLB: X-ray of baby with loops of bowel in left pleural cavity: 1. diaphragmatic hernia 2. posterolateral defect in diaphragm Hematemesis: 1. vomiting of blood 2, duodenal ulcer > gastric ulcer > esophageal varices Congenital pyloric stenosis: 1. vomiting 2-4 wks after birth of non-bile stained fluid 2. mass palpated in epigastrium 3. multifactorial inheritance 4, comparison with duodenal atresia ‘A. later disease has a Down syndrome relationship B, latter disease has vomiting of bile stained fluid at Vater C. latter disease has double bubble sign on x-ra D. latter disease has polyhydramnios in mother NSAID ulcers/erosions: 1, usually superficial erosive gastritis it PGE, which produces mucosal barrier— PGE; normally: ) increases blood flow to mucosa (2) _ increases secretion of mucous (3) _ increases secretion of bicarbonate into mucous misoprostol, a PGE; analog, is cytoprotective ith: atresia distal to ampulla of ir in stomach and proximal duodenum ‘Chronic atrophic gastritis: 1. type A~ > ‘A. body and fundus B. associated with autoimmune destruction of parietal cells in pernicious anemia C.achlorhydria: (Q) danger of adenocarcinoma Q) problems with digestion 3) 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 o H pylori: 1, gram negative rod 2. urease produeer~ urea converted to ammonia damages mucosal barrier 3. detected in Bx specimen 101Note: This material is copyrighted. All rights reserved. serology excellent but not useful in detecting recurrent disease complications— ‘A. gastric adenocarcinoma B. type B atrophic gastritis C. low-grade malignant lymphoma Re A. metronidazole B. _ bismuth subsalicylate C. tetracycline ‘© Comparison of gastric with duodenal ulcer: Characteristics Ulcer Duodenal Ulcer Percentage of 75% PUD Epidemiology | Male/Female ratio 1/1 Male/Female ratio 2/1. AD pattem in some Pathogenesis, Defective mucosal barrier due to- 1. H. pylori (>75% of cases), 2, mucosal ischemia (reduced PGE,), 3. bile reflux. 4. COPD, 5. renal failure. Blood group A relationship. No MEN I or If relationship, Smoking delays healing but not a cause of PUD. H. pylori association >90%: decrease bicarbonate in mucous barrier, 2, increased acid production. 3. blood group O relationship, 4. MEN I relationship associated with Zollinger Ellison syndrome component Pathogenesis— 1, 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 Gastrie ulcers do not predispose to [ No malignant potential. Not biopsied. potential cancer. Cancer can be. ulcerative |= and confused with gastric ulcer. Cannot tell malignancy by the size of an ulcer. Must Bx to R/O cancer. Complications Bleed and/or perforate (both less ‘common than duodenal ulcers). Bleed (MC complication), perforate (air under diaphragm radiates to left shoulder), gastric outlet obstruction, pancreatitis. Clinical Burning epigastric pain soon after eating. Pain increases with food (afraid to eat and lose weight), Relieved by antacids. Burning epigastric pain 1-3 hours after eating. frequently relieved by antacids or food (do not lose weight). Pain wakes patient at night. @ ZE syndrome: 1 2. 3. malignant islet cell tumor secreting gastrin uleers in usual place but can be multiple or in unusual places: association with MEN 1 laboratory— ‘A. increased basal and maximal acid output B. increased gastrin C. increase in gastrin with IV secretin test 102Note: e his material is copyrighted. All rights reserved, 4 Re A. proton blockers can decrease gastrin B. surgery 5. other causes of hypergastrinemin— ‘A. Hp or 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 node: 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 cancer in Japan- related to smoked foods 3. causes— H. pylori causally linked smoking nitrosamines adenomatous polyps achlorhydria is plastica. leather bottle stomach 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. HL. 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 2) _ bile obstruction @) cholestyramine (4) _ bacterial overgrowth (5) terminal ileal disease 103,‘Note: This material is copyrighted. All rights reserved. 2. tab 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 pancreatitis 3. lab alterations~ A. hypoalbuminemia B, fat soluble vitamin (A, D, E, K) deficiencies C. combined anemias: iron, folate, Bis 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 diarrhea in child- bodies develop against glia- | (iron deficiency) | ren. Adults have weight loss, din extract in gluten (best | and jejunum (fol-| diarthea, malnutrition. Risk of | screening test)- immune | ate deficiency). | small bowel T cell lymphoma, destruction of mucosal cells. Splenic atrophy. Gluten free diet Associations~ HLA B8, -Dr3 gold standard Rx. Lab: abnormal and -DQ2 and dermatitis D-xylose, anti-gliadin antibodies herpetiformis (vesicular skin (best test), anti-endomysial anti- disease). bodies. | Whipple's | Systemic disease of middle | Blunting of villi in | Present with fever, diarrhea, joint | disease aged males. Infection by | the jejunum and | pains, emaciation, peculiar gray- Trophermyma —_whippleii. | ileum, Heavy inf-| brown skin pigmentation, gen- Cannot culture. Only seen iltrate of foamy | eralized lymphadenopathy. Lab: with electron microscope. In | macrophages abnormal D-xylose. Rx with AIDS, MAI produces a lamina propria | TMP/SMX SSCS SSSSCSSCSCSCSSSSSSSSSsseseseseseseseeee eee ee eS eee Whipples-like syndrome: | (contain the ora- | anisms) which | blocks lymphatic uptake of fat, | Diarrhea: 1. causes— A. invasive () eg, Shigellosis 2) low volume diarrhea @)__ positive stool for fecal leukocytes secretory: (1) 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 diarthea due to enterotoxigenic E. coli (4) high volume diarrhea with osmolality similar to that of plasma (5) _ negative stool for fecal leukocytes 104‘Note: This material is copyrighted. All rights reserved. C. osmotic: (1) 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 H, best screen (2) certain laxatives (3) high volume diarrhea with osmolality lower than that of plasma (4) negative stool for fecal leukocytes © _ Microbial Pathogens Associated with Diarrhea Pathogen | Specific Pathogen Comments Virus Rotavirus (Reovirus) | MCC of childhood diarhea. Winter months, Fecal-oral route | Infects small intestine mucosa and damages brush border | enzymes and transport systems producing a watery, non- bloody diarrhea. Rotazyme test on stool establishes Dx. Norwalk (Picomavirus) | Common cause of both adult and childhood gastroenteritis (vomiting/diarrhea). Fecal-oral transmission Cytomegalovirus Common cause of diarrhea and biliary tract disease In AIDS. Bacteria [Food poisoning from |'S. aureus type (gram + coccus) occurs In 1-6 hs (sel preformed toxin Staphylococcus aureus, Bacillus cereus, Clostri- ium botulinum (adult) limited). Culture food. B. cereus (gram positive rods noted in stool) associated with fried rice/tacos (self-limited). Adult C. botulinum (gram positive rod) has heat labile exotoxin (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 colonization in bowel C. perfringens, C. botul- num (injand), Salmon ella enteritidis” ‘Clostridia: gram positive tod. C. botulinum in infants from eating spores in honey. Colonization first in bowel and then toxin production, Salmonella: gram negative rod and MCC of food poisoning in United States. C. perfringens accounts 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 diarthea. 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 105Note: This material is copyrighted. All rights reserved. Salmonella species Gram negative rods. Pathogenic Salmonella species Tnclade SOPH choleraesuis, “and typhimurium (MCC of enterocolitis, self-limited). Animal reservoirs (pouttry, | unles, lizards). Oral-feeal transmission. Typhoid. fevey (enteric fever) caused by S. gpphi (human reservoir) Einst week invades Peyer's patches (longitudinal ulcers) and Produces a septicemia (best culture medium for isolation. Second week diarthea (positive stool eulture) and classic | triad Of “bradycardia, absolute neutropenia, hepato. | splenomegaly. Complications: osteomyelitis (sickle disease), | Jaundice, renal failure, chronic carrier state (Persistence of Seeeeeee ees ; a| the organism 1 year post infection, MC in gallbladder), | Positive fecal smear (monon = of choice for typhoid and a 2 state. Cholecystectomy may : »| Mycobacterium Organisms swallowed from a primary Tous iw Ge Tung, | niberculosis Invade Peyer's patches in terminal ileum, Infections spreads | , via the circumferentially oriented lymphatics leading to | »| Stisture formation/obstruction, M. bovis MCC in third world | countries (unpasteu , Campylobacter jejuni — resembling ulcerative colitis, | Blood/mucus present in stool. Positive fecal leukocyte smear, | Usually self-limited. Rx: erythromycin or ciprofiosasin iy | severe cases Escherichia coli Gram negative rod. Produces toxin induced and lavage] diarrheas, Enteropathogenic strain: non-toxin type of mild diarea in | infants and young children, Mucosa not inflamed, Emerotoxigenie strains: some strains produce heat labile | CD toxin stimulating cyclic AMP (secretory: dione | fimilar to cholera, normal mucosa). Other strains prodice a heat stable (ST) toxin stimulates guanylate cyclase producing TMS, Ciarthea (MCC of traveler's diarrhea), Rx wite ‘TMP/SMX. Enteroinvasive strain: invade large intestine producing | mucosal necrosis/inflammation, | Rulerohemorrhagic strain: 0157:H17 serotype in raw famburgers. May produce hemolytic uremic syndrome cnt hemorrhagic or pseudomembranous colitis 106‘Note: This material is copyrighted. All rights reserved. cyclase in small bowel. Severe secretory diarrhea (“rice- | water stools”). Drinking contaminated water/eating contam- | inated seafood, especially crustacea (Gulf coast). Volume depletion, normal gap metabolic acidosis (lose bicarbonate), hypokalemia. Rx is. fluid replacement, Glucose enhances sodium uptake in oral supplements. Mortality ~ 40% if lett | Vibrio cholerae Curved gram negative rods. Enterotoxin stimulates adenylate | 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. Diarthea/abdominal pain. 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. Diarthea and | wasting syndrome, Rx with albendazole. | Giardia lamblia ‘MC protozoal cause of diarrhea in United States. Contracted | by ingesting cysts (mountain springs, etc.). Attach to small intestine mucosa (may involve biliary tract). Produces acute and chronic diarthea with malabsorption. Rx: metronidazole. F Amebiasi 1. flask shaped ulcers in the cecum 2. afebrile, bloody diarrhea 3. trophozoites phagocytose RBCs o ‘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 ‘@ AIDS patient diarrhea--?what organisms can be identified with the string test (Entero-Test): 1. Giardia 2, Strongyloides 3. Cryptosporidium 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- 94 107We a a a a D Note: This mat terial is copyrighted. All rights reserved. adhesions from previous surgery MCC: if no history of previous surgery, pick indirect inguinal hernia duodenal atresia: (1) _ association with Down syndrome 2) vomiting of bile stained fluid after birth (3) double bubble sign- air in stomach and proximal duodenum (4) polyhydramnios in mother Hirschsprung: (1) absent ganglion cells in rectum 2) empty rectal vault on rectal exam @) 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 G. intussusception: L li A B, & D, E (MC type (2) superficial epigastric artery medial to finger in canal (artery is lateral border of triangle of Hesselbach) 8) a, incarcerated small bowel in an indirect inguinal hernia sac b. sce picture on page 310 of review text direct inguinal hernia: (1) _ through posterior wall of triangle 2) artery lateral to finger umbilical herni: (1) common in children (2) common in pregnancy and ascites (1) terminal ileum intussuscepts into cecum (2) child with colicky abdominal pain and bloody diarrhea volvulus: (1) MC due to sigmoid colon twisting around mesentery 2) _ obstruction and infarction gallstone ileus: (2) elderly woman with chronic gallbladder disease (2) 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 cystie fibrosis in newborns qa leus (lack of peristal ofa small portion of bowel is called a sentinel loop (2) due to bowel close to an area of inflammation (3) acute pancreatitis~ sentinel loop near duodenum or transverse colon (4) _retrocecal appendicitis— sentinel loop of cecum inical— op thew pin —Feee jvteet Vx pains el colicky pain —* PA” toe BRS fiji i distended abdomen with no rebound tenderness. constipation obstipation: no gas sow! chap € dilated small bowel with air/fluid levels in step-ladder appearance (ot! dkay) 108‘Note: This material is copyrighted. All rights reserved. ‘© Sigmoid colon most common site for: 1, cancer in GI tract 2. — diverticular disease 3. polyps- exception: polyps of Peutz-Jeghers syndrome, which are MC in the small bowel @_ Hematochezia: / 1. 1039 of bright red blood per rectum 2. diverticulasis 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: (@) sudden onset of diffuse abdominal pain, bowel distention, and bloody diarrhea in elderly patient (2) no rebound tenderness unless peritonitis is present, (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, 2. ischemic colitis ‘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 3. angiodysplasia— ‘A. dilated vascularchannels in submucosa of cecum (2) _ increased wall stress related to increased diameter of cecum increases tension on blood vessels causing dilatation (2) second MCC of hematochezia (3) MC inelderty patients B. associated with: (1) von Willebrand's disease Q) aortic stenosis, @ Diverticular disease 1. small bowel diverticula A. uncommon B. site for bacterial overgrowth: (1) Biz deficiency (2) _ bile salt deficiency and malabsorption 2. Meckel’s diverticulum: ‘A. vitelline duct remnant; 2 feet from ileocecal valve B. true diverticulum C. MCC of iron deficiency in a newborn and young child (GI bleed) Dinero ao beset app wdlgeitio” 109‘Note: This material is copyrighted. alt rights reserved. 3. sigmoid diverticula Ar diverticula are juxtaposed to a blood vessel, which is the area of weakness: explains ‘why diverticula are the MCC of hematochezia B. diverticulitis MC complication (1) impacted fecalith serves as nidus for infection/inflammation @) clinically described asa "left sided” appendicii @) _ danger of perforation and peritonitis ©. diverticula are MCC of fistulas in G tacts colovesical fistula MC fisula , = _Comparison of ulcerative Colitis (UC) and Crohn's disease (cD): ( Kyyow/ Yh, Colf ) | Characteristic | Uleerative Coliti Crohn’s Disease ~~ = Pees > ) ) : extend up into left colon in cont- inuous fashion (no skip lesions) or involve entire colon, Does not involve other areas of GI tract, [Extent Mucosal and submucosal Transmural | disease J | Location Primarily targets the rectum, May | Terminal ileum alone (30%), jleum/colon] (0%), colon alone (20%). Anal involvemen | 75% fissures, fistulas, abscesses, Involves other areas of GI tract (mouth to anus), { Gross features Inflammatory polyps- pseudo- Polyps representing areas of inflamed residual mucosa, Friable, red mucosa bleeds easily when fouched. Ulceration/hemorthage, Colon shortened and mucosa flat in quiescent chronic disease, No skip areas. and narrow lumen. Skip areas (important fea. blestone patter, aphthoid ulcers (small muceeal ulcers, origin of linear ulcers, early sign), | Microscopic Active diseasey mucosal inflamma Very diasnostie features: noncaseating gran features, hile) omvPt abscesses (neutrop- | omas (60%), transmural inflammation hils). Dysplasia/cancer may be subserosal lymphocytic infiltration, i resent. Chronic disease: neutro- Phils replaced by lymphocytes? plasma cells, Dysplasia/cancer may be present, ‘Complications | Mor oF CD: 1. toxic | More common than UG. 1, Howie formation, 2.) megacolon _hypotonic/distended gbstrction, 3. disease in other ares of GI tract, | bowel, 2. sclerosing pericholan- | 4. calcium oxalate renal stones sits, 3. HLA B27 + ankylosing Spondylitis/uveitis, 4, pyoderma gangrenosum, 5. adenocarcinoma~ ~10%, greatest risks are pancolitis, | early onset of UC, and duration of disease >10 years Clinical Left sided “abdominal cramping | Right lover Quadrant colicky pain (obstruction ] ret obstruction), diarrhea with | in area’ of ‘emma ileum) with diarrhea, | blood/mucus, rectal bleeding, | Bleeding iteolon involvement. tenesmus (painful straining at stool), | Radiograph "Lead pipe appearance i chronle ; Siting” sign inthe terminal eum fom Inmiaal” disease, 10 narrowing by inflammation. Fistulas,‘Note: This material is copyrighted. All rights reserved. ® Young woman with intermittent bouts of diarrhea and constipation associated with cramping right and left lower quadrant pain: 1, irritable bowel syndrome~ intrinsic motility defect in bowel 2. flexible sigmoidoscopy is negative Melanosis coli: black colored colon due to laxative abuse 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 C. hamartomas 4. PS polyps— A. MC in small intestine B. hamartomas: very little risk for adenocarcinoma C. mucosal pigmentation 5. adenomatous poly] A. precursors for cancer: (1) villous adenoma worst type: sessile polyp 2) tubular adenoma MC type (looks like a strawberry on a stick) B. risk for cancer greatest: (1) polyp >2.em (2) _ has increased villous component Polyposis syndromes: 1. familial polyposis MC type- A. AD disease involving: (2) _ inactivation of APC suppressor gene on chromosome 5 (2) _ activation of ras oncogene (3) _ inactivation of p53 suppressor gene B. — 100% penetrance: () all will develop cancer by age 40 @) 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 2. Gardner's syndrome— ‘A. variant of familial polyposis B. AD inheritance C. benign osteomas in jaw D. — desmoid tumors in abdominal sheath 3. Turcot's syndrome- A. only AR polyposis B. brain tumors Carcinoid tumor/syndrome: 1. tip of appendix MC overall site~ A. APUD tumor with neurosecretory granules B. $100 antigen positive wo Ca WtNote: This mat is copyrighted, All rights reserved, C. yellow color 2. all carcinoid tumors are m: = = » ant . a A. size determines metastatic potential (>a Cm) » 2 = B. _appendiceal carcinoids rarely metastasize = 3. “terminal iteum MC site for tumor that metastasizes to liver to produce the carcinoid syndrome- = A. _ serotonin is fibrogenic and may cause bowel obstruction 2 B. portal vein drains serotonin to liver where itis metabolized and exereted in urine as 5- HIAA = inoi 4. carcinoid syndrome- 2 ‘A. metastasis to the liver from a primary in the small intestine 2 (1) metastatic nodules. drain serotonin into. hepatic vein tributaries: access to systemic circulation - @) flushing and diarrhea MC symptoms: due to serotonin 2 @) cardiac valvular lesions a. tricuspid regurgitation » b. pulmonic stenos > 5B. measure S-HIAA (metabolite of serotonin) in urine: tryptophan often depleted from i) 2 eased synthesis of serotonin > bronchial carcinoids do not have to metastasize to produce carcinoid syndrome * Colon cancer: : 1. risk factors~ A. age > tubular adenoma >2 em 4 familial polyposis (100% penetrance) Villous adenoma (villus component increases the cancet risk) > low fiber diet: increased exposure of mucosa to lithocholic acid >» smoking , Lynch syndrome (family cancer syndrome): (AD disease ] (2) type I limited to colon , Q) type Il is family cancer syndrome , a. colon cancer b. _breasvendometril/cervical cancers & gastric cancer 2. sereening— Ax Sool guaiae yearly afer $0 yenrs 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 rectosigmoid 60% B. _cecum/ascending colon 25% 4. clinical A. left side obstructs: change in bowel habits: annular configuration B. right side bleeds: @) polypoid (2) found later than left sided type PrEson 12Note: This material is copyrighted. All rights reserved. ____5:_Aster-Collin staging system for colorectal cancer— Stage Characteristies Prognosis ] A Tumor limited to the mucosa, Negative lymph 100% 5 year survival. | nodes. |B ‘Tumor involves the submucosa and invades into | ~ 60% 5 year survival. but not through the muscularis propria. No lymph node involvement. | BD ‘Tumor penetrates through the muscularis propria | 55% 5 year survivals | and extends into the serosa. No lymph node involvement. Cl and C2 | Same as BI and B2, respectively, except lymph | Cl, 30% 5 year survival C0001 nodes are involved. 5 year survival, D ‘Tumor with any level of invasion with or without | <5% year survival | lymph node involvement but distant metastasis is | present. 6. CEA~ used to follow-up for potential recurrences Acute appendicitis: 1, MC due to viral infection (adenovirus) in children lymphoid hyperplasia in appendix. ‘causes ischemic changes 2. MC due to an obstructing fecalith in adults 3. A. pain migrates from umbilicus to RLQ B. fever C. rebound tenderness at McBurney's point D. __Rovsing's sign: pain in RLQ when palpating LLQ E, psoas sign: pain when extending right thigh F. _ perforation MC complication ‘Abdominal Pain: 1. order for evaluating abdomen- A. inspection B. auscultation C. percussion D. palpation. 2. causes of pain— A. hollow viscera: (1) _ distention of the viscus with fluid or air @) forceful muscle contractions @) inflammation (4) ischemia B. solid viscera (1) stretching of capsule @) inflammation of capsule C. _ visceral peritoneum and greater omentum are not sensitive to pain D. mesentery, parietal peritoneum and peritoneum covering posterior abdomen are sensitive to pain 3. types of pain— A. visceral B. parietal 13 i i a a a a i a ee OO gsNote: This material is copyrighted. Al rights reserved. 4 1 8. C. referred visceral pais A. — mediated by small unmyelinated afferent C fibers (1) _ poorly localize pain to the midline of the abdomen Q) eat usually dull, slow in onset, and of long duration (3) mid-epigastric visceral pain a. duodenum b. hepatobiliary system © pancreas imbilical (mid-abdominal) pain: Jejununvileum b. — cecum/appendix ()_ mid-lower abdomen: 4) a. colon b. intemal reproductive organs parietal pain— ‘A. — mediated by both C and myelinated A & nerve fibers B. _pain more acute, sharp, and better localized C. “causes of parietal pain involve irritation of parietal peritoneal surface by: a) pus (2) bile (3) urine (4) cyst fluid (5) Glssecretions D. example of appendicitis: (J) pain begins in the periumbilical area when appendix becomes inflamed (2) _ shifts to RLQ (McBumey’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 entering the spinal cord from T6-T9 C.__ left shoulder pain with perforated duodenal ulcer and air under diaphragm irritating C4 pain onset~ A. explosive within seconds: e.g, perforated uloer B. rapidly progressive within 1~2 hours: e.g., strangulated bowel CC. gradual over several hour character of pain A. colicky pai (1) pain interspersed with pain free intervals of minutes to hours (2) _ sign of obstruction in a viscus that has peristalsis a. small bowel obstruction b. terminal ileal disease in Crohn’s disease B. steady pain (1) dull and aching Q) eg, ulcer pain C. stabbing pain (1) _ bowel infarction na‘Note: This material is copyrighted, All rights reserved. (2) acute pancreatitis obstipation- ‘A. absence of passage of both stool and flatus B. characteristic of mechanical bowel obstruction 10. rebound tenderness~ peritoneal inflammation 11, increased bowel sounds (hyperperistalsis)~ A. diarthea B. early obstruction 12. absent bowel sounds (ileus)~ ‘A. intestinal obstruction due to inhibition of bowel motility (1) adynamic or paralytic ileus (2) _ peritonitis B, _ mechanical obstruction (dynamic ileus): adhesions, Questions used during the board review: Yersinia enterocolitica Staphylococcus aureus Enterotoxigenie E. coli ‘An afebrile 22 year old man and several other members of his family developed severe vomiting ithout diarrhea ~1—6 hours after eating potato salad at a picnic. They all recovered uneventfully 12-24 hours later. Answer: G Items 1-5 A. Vibrio cholera B. Bacillus cereus C. Shigella sonnei D. Salmonelia typhi E. Campylobacter jejuni Fr. G. H ‘@ A 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 ‘F A 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 ‘F On a trip to India, a man develops a high fever associated with bradycardia, absolute neutropenia, and splenomegaly. A blood culture is positive for @ gram negative organism. Answer: D usNote: This material is copyrighted. AM rights reserved. Items 6-7 A. Yersinia enterocolitica B. Staphylococcus aureus C.— Enterotoxigenie £. coli D. Cryptosporidium parvum 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 m ® 4 25 year old medical student during Spring break in Tijuana, Mexico develops fever, vomiting, abdominal cramps, and watery diarthea ~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 buccal mucosa MOST LIKELY has an AIDS-defining lesion caused by... tongue and A. Epstein-Barr virus B. Candida albicans C. Kaposi's sarcoma D. cytomegalovirus EB. Herpes simplex qe An afebrile 25-year-old medical student presents with intermittent complaints of left and right lower quadrant abdominal pain and distention associated with alternating periods of mucoid diarshea 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) ‘F 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 E. rectum B néeNote: This material is copyrighted. All rights reserved. ‘F Which of the following characterizes ulcerative colitis rather than Crohn's disease? Discontinuous spread Toxic megacolon Fistula formation Perianal disease Obstruction moom> w ‘A38-year-old Asian woman has a long history of explosive diarrhea and abdominal distention after cating dairy products. The pathogenesis of this patient's diarrhea is MOST CLOSELY related to. A. antigliadin antibodies B. activation of cyclic AMP c raluminal osmotically active solutes D. mucosal injury with increased permeability E. _loss of the absorptive surface of the small bowel C (lactase deficiency) ‘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 extemal 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 patient’s condition is... ‘A. angiodysplasia B. ananal fissure C. diverticulitis D. hemorrhoids E. colon cancer E (also evidence of liver metastasis) 17 Bae A AAO AESBAA AAA AAAAAARADABADASAHRAKEAAEARAOAAAShAALA Aee a | Note: This material is copyrighted, All rights reserved. Hepatobiliary/Pancreas: F Liver function tests (LFTs): liver necrosis indicators ALT Se apeete 1. enzymes~ A. alanine transaminase: ALT B. Aspartate transaminase: AST C. Lactate dehydrogenase: LDH 2. AST (formerly SGOT)~ primarily a mitochondrial enzyme 3. ALT (formerly SGPT)— A. located in the cytosol B. more specific for liver disease than AST 4. transaminases increased in hepatocyte injury/negros A. alcoholic liver disease: o—4 fata eee, Ar () AST>ALT, since sil isa mitochondrial poison 2) _ enzyme levels rarely >200-300 U/L. B. viral hepatitis: () ALT>AST @) ALT last enzyme to return to normal (3) _ levels >1000 U/L in acute hepatitis 5. LDH- ‘A. increased in cell necrosis B. non-specific marker of p ‘© Liver function tests (LFTs): cholesta 1, enzymes- A. alkaline phosphatase (AP) B. y-glutamyl transferase: GGT €. 5'-Nucleotidase 2. 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 @) phenobarbital rane lary or metastatic tumor in the liver indicators Pylon C. AP is present (liver (2) bone @)_ placenta D. GGT primarily located in the liver in smooth endoplasmic reticulum 3. obstructive jaundice— A. AP and GGT are markedly increased (17) B. transaminases mildly increased (+) 4, alcoholic liver disease— A. AST>ALT B. * GGT disproportionately increased (T7) due to induced synthesis by alcohol 5. focal benign liver disease (granulomas)~ A. bilirubin, LDH, transaminases normal B, AP and GGT slightly increased (7) 18Note: This material is copyrighted. All rights reserved. 6. focal metastatic liver disease- as above except LDH also increased (7) 7. 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 if it is not liver in origin Liver function tests (LFTs): excretory indicators, see schematic 1. total bilirubin (TB) with fractionation into conjugated (CB) and unconjugated ilirubin (UCB), A. CBYTB x 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 CB >50%: primarily CB: obstructive jaundice ind urobilinogen relationship— Urine bilirubin Urine urobilinogen Interpretation Normal: absent trace CB <20%: absent tt extravascular hemolytic anemia CB 20-50%: tt tt viral hepatitis CB >50%: ttt absent obstructive jaundice Liver funetion tests (LFTs): index of severity of liver disease 1. severity index indicators— A. serum albumin B. prothrombin time (PT): best indicator 2. hypoalbuminemia and prolonged PT- ‘A. indicate severe functional impairment of the liver B, _ in cirrhosis, the prolonged PT does not correct with intramuscular vitamin K 3. 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 fy bridge C. in primary biliary cirshosis (PBC) IgM is elevated. autoantibodies— ‘A. increase in anti-mitochondrial antibody in PBC B. _ increase in anti-smooth muscle antibody in autoimmune hepatitis Liver funetion tests (LFTs): tumor markers 1. alpha fetoprotein (AFP)~ A. hepatoblastoma in children B. hepatocellular carcinoma in adults 2. a-1 antitrypsin (AAT) hepatocellular carcinoma Anatomy: 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 19 « « ‘ ‘ ‘ r r r r r r r é ‘ r r r « 5 ‘ « . éHeme (protoporphyrin + iron) heme oxygenase Protoporphyrin + iron Bi din + carbon monoxide (CO) v biliverdin reductase Peripheral Blood Unbound bilirubin (lipid soluble) Bilirubin + albumin (unconjugated bilirul Liver uptake of UCB by carrier proteins ‘UCB then binds to ligandins Macrophage Destruction RBC —Peglobin split off —p amino acid pool — UCB 1} UP-glucurony transferases (conjugating enzymes) Conjugated bilirubin (CB, no access to blood from here on im) canalicular transport system (rate limiting step) CB in common bile duct stored/concentrated in gallbladder (cholecystokin) Bowel CB in terminal ileum + colon bacterial reduction by B-glucuronidase ¥ (also present in breast milk) UCB 1 further reduction by bacteria Urobilinogen (colorless) oxidized to urobilin (color of stool) Enterohepatic circulation Liver (90%) Urine (10%, urobilin gives color to urine) CB= con} ‘iirhis ji Normal Biliru' Metabolismee ‘Note: This material is copyrighted. All rights reserved. 3. zone around the central vein is most susceptible to hypoxia and aleohol damage = Summary of acquired/genetic eauses of jaundice: 1. unconjugated (UCB) hyperbilirubinemia with CB <20%~ A. increased production (1) _ hereditary hemolytic anemias with extravascular hemolytic anemias a. congenital spherocytosis b. sickle cel disease @) acquired hemolytic anemias a. ABO hemolytic disease of newborn b. Rh hemolytic disease of newborn €. _ autoimmune hemolytic anemia @) _ ineffective erythropoiesis (RBC destruction in the bone marrow) a. severe P-thalassemia b. pernicious anemia/folate deficiency B. impaired uptake by hepatocytes: acute/chron C. impaired conjugation by hepatocytes | (1) Gilberts disease | a, 7 autosomal dominant b. second MCC of jaundice (hepatitis MCC) c. “increased production (mild hemolysis in 50%), decreased uptake, decreased conjugation 4. jaundice exacerbated by fasting liver disease e. liver histologically normal {fast the patient and note a doubling of bilirubin over the baseline g noRx (2) Crigler Najjar syndrome: genetic disease a. type I has total absence of UDPG transferase activity: incompatible with | life i b. type II has reduced UDPG transferase activity (activity increased with phenobarbital) ¢. liver histologically normal 4. 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 c. 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 >50%- A. Dubin-Johnson syndrome: @) AR (2) impaired canalicular transport system for CB i (3) _ black pigment in hepatocytes 120Note: This material is copyrighted. All rights reserved. (4) non-visualization of gallbladder with oral cholecystogram dye (5) abnormal clearance studies (6) benign disease B. _ Rotor's syndrome @ AR (2) _ pathogenesis same as Dubin-Johnson (3) normal liver (4) normal visualization of gallbladder (5) abnormal clearance studies C. intrahepatic cholestasis (1) drug induced: see table (2) primary biliary cirrhosis 3) _ intrahepatic biliary atresia in children D. extrahepatic cholestasis (1) extrahepatic biliary atresia in children @)__ stone in common bile duct: MCC in adults (3) carcinoma of head of pancreas (4) primary sclerosing pericholangitis: associated with ulcerative colitis ‘F _Viral hepatitis: see schematics and tables HAV ‘HBV HCV, EDV HEV Type of virus RNA‘ picoma- | DNA: hepadna-~ [RNA Mlavi- [Incomplete RNA | RNA? calei> virus: virus virus virus (requires | virus HBsAg). Prevalence | 40% 35% 20% 5% a% Transmission | Fecal-oral, Parenteral, close | Same as HBV. | Same as HBV. | Same as HAV food, water, | contact with an Coinfection (same anal intercour- | infected patient. needle has both se. 10% of infe- | Present in blood, viruses). Superin- ctions inday | semen, saliva, fection (exposed care centers % to HDV at later date) Incubation | 2-6 wks 2-6 mihs ST wks Same asHBV__|2-9 wks Clinical Traveler's hepa- | Serum sickness | MCC of post- | Cytolytie to hepa- | Poor prog- associations | titis (80%), drug | picture (5-10%): | transfusion he- | tocytes (rapid det- | nosis in pre= addicts (20%), | polyarthritis, urt- | patitis (1/3300 Jerioration with | gnant women homosexuals | icaria, nephritis, | chance). Com- | superinfections). | (20% morial- (35%), inmates | vasculitis (PAN). | mon in alcoh- | Drug addicts and_| ity). in jail Virus is not cyto- | olic liver dise- | homosexuals. lytic but CDs cy- | ase (25-60%). totoxic T cells Kill hepatocytes ‘Chronic car | None Yes: 10% in | Yes: 40-60% | Yes: 10-40% | None ier state/ehr- adults, 90% in ‘onic hepatitis ‘newborns left untreated Massive necr- | Rare MCC of fulmi- [Rare Common Common in osis nant hepatic nec- pregnant wo- rosis men. 121Hbe bs zit beset ptt Hav DNA , | a2 3 4S 2 24 +> Jaundice +——_# symptoms | $4 Seroiogic gap BST AEE Hee ig § ‘ ‘ ; ‘ ‘ ‘ ( ( ( ( ( ; ‘ ‘ ( ' ' ‘ ‘ ' ' Ant ~ HB. Te \ hints A Mewes plied? a“SS eS ee a a a ae a a Sa a ee ke ae Rae Ae Note: This material is copyrighted. All rights reserved. HAV HBV HCV EDV HEV Lab diagnosis | Anti-HAV-IgM: | See schematic | Anti-HCV: in- | Anti-HDV-lgM or | Anti-HEV> active disease. dicates infect- | IgG: indicates in- | IeM or IgG: Anti-HAV-IgG: ion, not protec- | fection, not prot | IgM indicates inactive disease, tive. ELISA | ective, current infec- protective, immunoassay tion. IgG in- tests positive dicates recov. in2-6 weeks. ery and prote- Recombinant, ction, immunoblot assay (RIBA) is confirmatory test along with polymerase chain reaction (PCR) testing. Active/Pas- Immune serum | Vaccine (active). |? Immune ser- | HBV vaccine pro | None sive immuniz-| globulin (pas- | Immune globulin | um globulin. | tects against HDV ation sive). Vaccine | (passive). and hepatocellular (active). carcinoma due to HBV 2 HBV 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 postnecrotic cirrhosis 5. recovery from HBV~ anti-HBs and anti-HBc-IgG vaccinated— only anti-HBs 7. chronic HBV- A. HBsAg>6 mths B. _ infective carrier if have HBV-DNA or HBeAg: correlates with chronic active hepatitis with piecemeal necrosis and fibrosis C. “healthy carrier" if lacking HBV-DNA/HBeAg: correlates with chronic Persistent hepatitis and portal triaditis 8. association of HBV with membranous glomerulonephritis and polyarteritis nodosa 9. summary of serologies HBsAg | HBeAg | Anti-HBc-IgM Anti-HBe-IgG | Anti-HBs | Interpretation negative | negative positive negative negative _| serologic gap | positive | positive | positive negative negative | acute infection or chronic IF >6 mths negative | negative | negative positive Positive | recovered from HBV | [negative | negative| negative negative Positive | immunized positive | negative | negative negative negative | earliest phase of acute HBV_ 122Note: This material is copyrighted. All rights reserved. Intravenous drug abuser in prison—type of hepatitis: HBV County jail with outbreak of hepatiti 1, HAV most likely 2. ravenous drug abusers, then HBV most likely Hepatitis most commonly chronic: HCV Hepatitis associated with urticaria, fever, arthralgias, and the nephrotic syndrome: 1. HBV 2. serum sickness type of disease type III immunocomplex mechanism 3. vasculitis associated with polyarteritis nodosa ‘Immunizations given at birth to a baby whose mother is positive for HBsAg: 1. Hep B vaceine (active immunization) 2. HBIG (passive immunization) ‘© Most common infeetion from accidental needle stick: ! 1. HBV 2. greatest viral burden in blood of all hepatitis viruses ‘S _ Summary of infectious diseases: [Disease ‘Comments Rickettsia Pathogenesis: Coxiella burnetii, Only rickettsia transmitted without a 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. Clinical/Pathology: interstitial pneumonia, granulomatous hepatitis (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 j 94 q4 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. Granulomaious | Pathogenesis: TB MC infectious cause (sarcoid MC non-infectious cause). Other hepatitis bacterial diseases include atypical Mycobacteria (M. avium-iniracellulare, MCC in AIDS), leprosy, brucellosis, syphilis (see below). Other non-infectious causes | include sarcoidosis (MC), drugs, primary biliary cirrhosis. | Syphitis Pathogenesis: Treponema pallidum. Clinical/Pathology: in congenital infection there is diffuse fibrosis without nodularity. In tertiary syphilis there is a sranulomatous 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), 123a ee ee Note: This material is copyrighted. All rights reserved. Parasitic Amebiasis Echinococcosis Gheep —herder's disease) Pe tales Schistosomiasis Bitharziasis) Clonorchiasis Pathogenesis: Entameba histolytica, Ingestion of food/water containing eysts. 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 enaymes (“histolytica”) to produce "flask shaped ulcers". Bowel inflammation produces diarthea containing blood and mucous, Afebrile (very characteristic). Trophozoites penetrate vessels | that 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 into the right lung eavity and lung, hematogenous dissemination throughout the body (e.g., brain). Lab: identify trophozoites (usually diarrheal 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: metronidazole, Pathogenesis: Echinococcus granulosis 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 actoss the peritoneum and penetrate the liver (75%) to | produce single or multiples cysts. Clinical/ Pathology: in the liver, larva develop into hydatid eysts 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 seolices that are referred to as "hydatid sand”. Rupture of oysts often produces fata 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 stem cirrhosis") 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 in a liver biopsy. Eosinophilia. Rx: 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. Eps are passed into the stool. Adults cause the bile duct epithelium to become hyperplastic and fibrotic leading to cholangiocarcinoma, Clinical/Pathol hepatomegaly, jaundice, diarthea. Lab: embryonated eggs are present in stool or duodenal aspirates. Eosinophilia. Rx: praziquantel. | 124Note: This material is copyrighted. All rights reserved. ‘@ USMLE scenarios: hydatid cysts in liver in sheepherder (Basque, Greek) F Congestive hepatomegaly: 1. MCC is right heart failure— nutmeg liver 2. transaminases elevated ‘= Prehepatic obstruction to blood flow: 1. portal vein thrombosis 2. aseitesivarices 3. no hepatomegaly ‘> Posthepatic obstruction to blood flow: 1. Budd-Chiari syndrome— -hepatic vein thrombosis 2. causes’ ‘A. polycythemia rubra vera MCC B. birth control pills 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 (fever @) neutrophil infiltration (3) neutrophilic leukocytosis. (4) ascites ©) Mallory bodies C. cirrhosis: irreversible 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 © Obstructive jaundice: 1, intrahepatic and extrahepa types~ stone in common bile duct MCC 2. bile contains cholesterol and bile salts/acids 3. clinical correlations— A, _ fat soluble vitamin deficiencies from reduction in bile salts leading to malabsorption B, _ hypercholesterolemia from backup of bile containing CHae _ = - BOX 16-2. Laboratory Aspects of Alcoholic Liver Disease, Alcohol metabolism: alcohol dehydrogenase (cytosol) aldchyide dehydrogenase (mitochondria) Aleohol acetaldehyde + NADH +H” ————® acetarer NADH+H™ —Pracety! CoA = = = oa) Ite increasais NADH, acetate (simply farry acid), and acetyl CoA are responsible for many of the metabolic and histological changes asvocined apa alcoholism. Increased NADH alters the redox @ Potential in favor of NADH over NAD", which reverses many biochemical reactions in the body. An Domne QADH over NAD" leads to an increase in the production of laeve acid, very low density lipoprotein (VLDL) and B-hydroxybutyric acid. B Lactic Acidosis > NADH » NAD Pyruvate ———__y Lactate > Metabolic acidosis d Lactate dehydrogenase , , ) ) F Glucose» Fasting hypoglycemia Rote how increased production of lactic acid produces metabolic acidosis (increased anion gap type) Since pyruvate is changed into lactate, there is less pyruvane available for gluconeogenesis, hence patients commonly have fasting hypoglycemia. Increased VLDL (Hypertriglyceridemia) NADH > NAD* 15 Bisphosphosiycerate —p glyceraldehyde 3-Po0, ps Dihydroxyacetone PO, NADH v NAD” acetate Glycerol 3-PO, TG (VLDL) Note how the increase in NADH reverses the reaction between 1,3-bisphosphoglycerate and siyeeraldehyde 3-phosphate in the glycolytic cycle in favor of glyceraldehyde 3-phosphate, which is carbomet into dikydroxyacetone phosphate (DHAP) and from HAP int glycerol 3-phosphate, the carbohydrate backbone of triglyceride (TG). Acetate, a simple fatty acid, may be used in the process of fnthesizing TG as well. An increase in VLDL in the liver result te fatty liver, while in the peripheral blood, the increase in VLDL leads to hypertriglyceridemia, (type IV hyperlipoproteinemia), Ketoacidosis (B-Hydroxybutyric Acid) Acetyl CoA —p Acetoacety! CoA HMG CoA —PAcetoacetic acid NADH wh: B-hydroxybutyrie acid (ketoacidosis) » may be converted by the liver into ketone bodies Acetyl CoA, the end-product of alcoho! metaboli (acetone, acetoacetate, hydroxybutyrate, hence cain tien site in the proximal tubules of the kidneys, the competition of uric acid with these ildtional acids often results in hyperuricemia and goutTh liver: bret cewtteol pills fou > gaboic skeoids (Se 8 ‘This material is copyrighted. AM rights reserved. C. generalized pruritus from bile salt deposition: Rx with cholestyramine D. CB>S0% E. clay colored stools: lack of urobilin pigment F. urine contains CB and no urobilinogen 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 ducts are destroyed D. increased anti-mitochondrial antibodies and IgM FE. _ association with Sjogren syndrome and renal tubular acidosis Secondary biliary cirrhosis: commonly noted in cystic fibrosis 44 A. jaundice B. danger of cholangiocarcinoma C. ERCP gold standard for diagnosis: see beading effect of bile duct ‘Chemical and drug-induced liver disease: | Morphologic ‘Chemical/Drag Pattern Acute hepatitis | 1. isoniazid 10-20% liver damage, toxic metabolite acetylhydrazine 2. salicylates 3. halothane~ symptoms after | week, fever precedes jaundice, metabolites formed from P450 system 4, methyldopa positive Coombs test 5. acetaminophen~ FR damage, Rx with N-acetylcysteine, MCC of drug-induced fulminant hepatitis Zonal necrosis | 1. zone I around triads yellow phosphorous poisoning, ferrous sulfate poisoning 2. zone Uff around central vein— carbon tetrachloride poisoning (CCl FR), ace- taminophen, Amanita mushroom poisoning. Tntrahepatic. 1, non-inflammatory type- oral contraceptives (estrogen responsible, interferes | cholestasis with intrahepatic bile excretion), anabolic steroids. 2. inflammatory type- erythromycin estolate, amoxicillin-clavulanie acid, chlorpromazine, thiazides | Fatty change 1. single droplet (nucleus peripherally displaced)— ethanol, corticosteroids, | j 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xe ‘Note: This material is copyrighted. All rights reserved. Morphologie Pattern | Vaseular lesions |, Budd-Chiani syndromes orl contraceptives 2. peliosis hepatis: oral contraceptives, anabolic steroid | 3. angiosarcoma~ vinyl chloride, arsenic, Thorotrast Tumors oF tumor- T1. benign tumors (hepatic or liver eal ‘adenoma)- oral contraceptives, anabolic | like conditions | steroids, tendency for rupture and inna itoneal hemorrhage (USMLE)-——_-_~» i 2. malignant tumors~ hepatocellular carcinoma and oral contraceptives/anabolic | ei ira steroids - » ; o BY cramiocianar 1. allopurinol “Ay B | hepatitis 2. hydralazine, hie » . . ' ) ) ) 3. sulfonamides | & r , f Ie 3 Bsstime they are taking anabolic steroids leading to liver eel adenoma Pele 2. spontaneous rupture of liver cell adenoma vi me chive o effect of estrogen on Producing liver cell adenoma with tendency to ruproe - ‘Birth control pills (estrogen component) and anabolic steroids effect on liver: 1. intrahepatic cholestasis 3 _ liver cell adenoma tendency to rupture during pregnancy 3. hepatocellular carcinoma oF : “Glevated and serum alkaline phosphatase is markedly elevated. we Patient is taking anabolic steroids (cholestatic jaundice) Hemochromatosis: 367.5 fost Common’ Genchia Disease jw US. We 1. AR disease * 2, unrestricted reabsorption of iron from small bowel 3. clinical By [ket target organ: cirthosis with 30% chance of hepatocellular carcinoma B. pancreas: (1) malabsorption @) diabetes mellitus C. _ skin hyperpigmented: "bronze diabetes" D. heart with restrictive cardiomyopathy E, iron overload findin, (1) increased serum iron @) decreased TIBC (3) increased percent saturation (4) _ increased serum ferritin F. Rx with phlebotomy 127‘Note: This material is copyrighted. Alll rights reserved. <& Wilson’s disease: 1 AR 4) 2 elt copper seeretion into bile if steiedas’s Gi peokin sy A. — chronic liver disease (1) low ceruloplasmin levels with subsequent increase in free copper in blood—> (2) Kayser-Fleischer ring in eye (3) _ lenticular nuclei degeneration (chorea, rigidity) low total copper due to low ceruloplasmin /A,, #4 fo oygne hues) high serumvurine copper Rx with penicillamine 2, decreased liver synthesis of AAT-+ panacinar emphysema 3. defective secretion of AAT by hepatocytes> chronic active hepatitisicirrhosis! 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 pregnaney— fatal unless baby delivered 4. pre-eclampsia— A. HELLP syndrome a jemolytic anemia (2) EL =clevated transaminases @) _LP=low platelets B. liver cell necrosis around triads ‘F Liver disease in children: 1. neonatal cholestasis ‘A. neonatal hepatitis MCC B. biliary atresia: (1) extrahepatic biliary atresia MC type (2) _ bile duct proliferation in triads (no proliferation in intrahepatic atresia) (3) _ radioactive dye cannot get into the small intestine (A) jaundice in first week of life C. metabolic diseases: () eg, galactosemia (2) tyrosinemia 2, Reye syndrome~ ‘A. infection associations are chickenpox and influenza B. rovesicular 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 1287 SEVCOUVLUGULELECELEULEELED eee eee eee 94 Note: This material is copyrighted. Al rights reserved. Cirrhosis 1. types~ A. micronodular/macronodular/mixed B. regenerative nodules lack normal liver architecture CC. _ intrasinusoidal hypertension due to regenerative nodules: leads to portal hypertension 2. portal hypertension A. esophageal varices B. caput medusae C. ascites D. hemorrhoids 3. hepatorenal syndrome~ acute renal failure without any gross or microscopic changes 4. hepatic encephalopathy- A. due to build up of ammonia and false neurotransmitters like octopamine and y- aminobenzoic 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 «y —~(2)__ female secondary sex characteristics ) (8) spider angiomas ( a#teiol’ yews Hatale (gee 4) palmar erythema 6. Dupuytren's contractures in fingers— fibromatosis involving tendon sheaths contracts fingers 7. ascites A. pathogenesis: (1) increased hydrostatic pressure in portal vein (2) decreased oncotic pressure @) secondary aldosteronism a decreased metabolism of aldosterone b. activation or renin-angiotensin-aldosterone system from decreased arterial blood volume B. danger of spontaneous peritonitis from E. coli C. use aldosterone blocker rather than loop diuretics: (1) produces a metabolic acidosis which increases the excretion of NH,’ in stool (2) use of loop diuretics produces a metabolic alkalosis causing greater bowel production of diffusible NHs: danger of precipitating hepatic encephalopathy Cavernous hemangiomas: MC benign tumor in liver Hepatic adenoma (liver cell adenoma) 1, associated with estrogens/anabolic steroids 2, tendency to rupture and produce intraperitoneal hemorrhage Hepatocellular earcinoma: (4/ays see i! « docks tou of cikehosis,) 1. causes— A. HBV MCC in United States: MC cancer in Far East due to chronic HBV liver disease + exposure to aflatoxins (molds in food) B. HCV 12944 ‘Note: This material is copyrighted. All rights reserved. C. hemochromatosis D. alcoholic cirrhosis 2. pathology- A. develops in a background of cirrhosis blood vessel invader C. neoplastic hepatocytes secrete bile A. weight loss B. abdominal pain due to rapid increase in bloody ascites C. _ increase in ALT is characteristic D. _ increase in AFP and AAT as tumor markers E, _ ectopic secretion of erythropoietin produces secondary polycythemia F. ectopic secretion of i ce factor produces hypoglycemia Metastasis is MC eancer of liver: lung cancer is MC primary site Gallbladder adenocarcinoma: 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 little bile salts/acids in bile (cirehosis) 2. types— A agar cholera tones B. calcium bilirubinate stones suggest extravascular hemolytic anemia C. most stones do not caleify 3. Dx- ultrasound is gold standard screening test 4. complications~ A. obstructive jatindice in common bile duct B. acute cholecystitis/pancreatitis C. gallbladder cancer Acute cholecystitis: 1. impacted stone in eystic duet 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 Cystie 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) 130Note: This material is copyrighted. All rights reserved. (2) _ increased Na’ reabsorption and decreased CI’ secretion into terminal bronchioles Ginfeetion) and pancreatic ducts (malabsorption: causes obstruction by thick mucus 2. complications~ A. respiratory infeotions/failure: (@ MCcop @) _P. aeruginosa MC pathogen @) MCC of bronchiectasis B. malabsorption: (1) pancreatic exocrine deficiency Q) diabetes mellitus C. secondary biliary cirrhosis D. total infertility in males(USMBE)= (Q) atresia of vas deferens (2) women have thick cervical mucus but can have children E. — meconium ileus in newborn 2. dosweat test 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 2. clinical A. fever B. _ pain in epigastrium with radiation into back 3. lab- e A. increased serum/urine 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 complicatioi (1) persistence of elevated amylase beyond one week @) mass in abdomen B. abscess: high mortality unless drained C. left-sided pleural effusion: contains amylase D. ARDS with hypoxemia E. hemorthagic pancreatitis: Q) Gray-Turmer sign in flank @) Cullen's sign around umbilicus F.__ hypocalcemia from enzymatic fat necrosis a bad sign S.CT best test for pancreatic disease 131‘Note: This material is copyrighted, All rights reserved. Chronic pancreatitis: 1. aleoholism MCC 2. lin ‘A. malabsorption B. severe pain C. diabetes mellitus D. _ predisposition to pancreatic cancer E, calcifications usually notes on x-rays Pancreatic cancer: 1. causes— A. smoking MCC B. chronic pancreatitis 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. Iab-CA19-9 © 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 cpts [AST [ALT | AP [GGT |LDH | Urine Urine % Bilirubin _| Urobilinogen | Viral hepatitis 20-50% | Tt | tttt | tt cas at tt ce | Aleoholie hepatitis 20-50% | Tt t t Mt | tt tt + (obstructive component) Cholestatie liver disease | >50% tt | tt | ttt | pitt] tt ttt Absent EHA <20% Mt | ON N N Tt | Absent tt RBC RBC (increased from bilirubin toad) Granulomas_|N N N tt | tt N Absent, N Metastasis N N N a tt Tt | Absent | ON Note: AST is present in RBCs 132bedded Note: ‘This material is copyrighted, All rights reserved, ‘Questions used during the board review: © A febrile 12 year old boy w c 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. viral hepatitis Reye's syndrome salicylate intoxication acetaminophen toxicity «>, antitrypsin deficiency Pooe> Which of the following serologic data best represents a patient who has recovered from hepatitis B? HBsAg | HBeAg | Anti-HBe-IgM | Anti-HBc-IgG | Anti-HBs A. | negative | negative positive negative negative | B._| positive positive negative negative C. | negative “negative positive positive | D. | negative | negative negative negative positive (A= serologic gap, B cute or chronic HBV, D = vaccinated) ‘F An afebrile 42 year old migrant worker from Mexico presents with bloody diarthea and right upper > qe ‘quadrant pain, The patient MOST LIKELY has... A. amebiasis B. echinococcosis C. avute cholecystitis D. ascending cholangitis E, metastatic colon cancer A 48-year-old alcoholic with cirrhosis and chronic pancreatitis has steatorrhea and a prolonged PT. ‘The PT does not correct to normal after giving an intramuscular injec of vitamin K. You conclude that the patient MOST LIKELY has. vitamin K deficiency a circulating anticoagulant an isolated factor deficiency inadequate synthesis of coagulation factors vitamin K deficiency secondary to malabsorption mpOB> 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 adefect in iron metabolism alphay-antitrypsin deficiency a defect in copper metabolism room> 133,o D (choice A <20%, choice B 20-50%, choice C <20%, choice E <: wr : This material is copyrighted. All rights reserved. Tn which of the following diseases would you expect a conjugated bilirubin >5 bilirubin? A. Gilbert's syndrome B. Chronic viral hepatitis C. Crigler-Najjar syndrome D. _ Stone in the common bile duct E, _ Extravascular hemolytic anemia % of the total 1%) 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 a palpable gallbladder and a light-colored stool. The patient MOST LIKELY has. A. hepatocellular carcinoma B. carcinoma of the gallbladder C. primary sclerosing cholangitis D. _ astone in the common bile duct E, carcinoma of the head of panereas 134Note: This material is copyrighted. All rights reserved. Kidney, lower urinary tract, male reproductive: ‘© _ Syndromes in renal disease: GN = glomerulonephritis Syndrome Characteristics ‘Examples Nephritie 1. glomerular — diseases are characterized by-_oliguria, hematuria, RBC casts, periorbital puffiness (retention of salt), and mild to moderate proteinuria, 1. type IV diffuse proliferative GN in SLE 2. post-strepiococeal GN 3. rapidly progressive crescentic GN- eg, Good- pasture's syndrome 4. IgA GN (Berger's disease)~ MC GN 5, Alport’s syndrome— hereditary nerve deafiness Nephrotie 1. glomerular diseases are characterized by- >3.5 gm/dL of protein/24 hours, oval fat bodies, fatty casts with Maltese crosses, generalized pitting edema, ascites 1. minimal change disease~ MCC in children 2. focal segmental glomerulosclerosis~ MC type in AIDS, IV drug abusers 3. membranous GN- MC type in adults, HBV association 4. membranoproliferative GN- type I associated with HCV $. diabetic glomerulosclerosis~ begins microalbuminuria 6. amyloidosis with 1. formation of _ crescents (parietal cells) in Bowman's space 2. rapid loss of renal function with hematuria and proteinuria. 3. worst prognosis of all types of GN. Rapidly progres- sive crescentic GN 1. end-stage disease for many diseases- Good- pasture’s disease, Wegener's granulomatosis, post- infectious GN ‘Acute renal | failure 1. abrupt reduction in GFR 2. oliguria (sometimes poly- uria) * 3. proportionate increase BUN‘creatinine (ratio <15/1) 4, tubular dysfunction— loss of concentration, FENa’ >1, renal tubular casts in 1. ischemie ATN= MCC is prerenal azotemia 2. nephrotoxic ATN- MCC is aminoglycoside followed by radiocontrast dye used in IVP ‘Chronic renal || failure (CRF) 1. reduction in GFR>3—6 mths 2. waxy and broad casts 3. proteinuria 4. metabolic acidosis 5. hypocalcemia vitamin D deficiency 6. hyperphosphatemia— cannot excrete 7. total loss of concentration/ 1. chronic GN 2. chronic pyelonephritis 3. end-stage diabetic nephropathy~ MCC of CRF dilution, 135CC ee Note: This material is copyrighted. All rights reserved. [Syndrome Characteristics Examples Renal tubular [1. type I~ defect in. proton/K* | 1. normal anion gap metabolic acidosis | acidosis (RTA) | pump in collecting tubule 2. urine pH usually >5.5 | 2. type II lower threshold for | 3. all have hypokalemia except for type IV | reclaiming bicarbonate in proximal tubule 3. type IV= destruction off jux- taglomerular apparatus, hypo- reninemic hypoaldosteronism, MC due to diabetes Urinary tract [1. ascending infection from an | 1. acute and chronic pyelonephriti infections incompetent vesicoureteral | valve | 2. fever, flank pain, lower urinary tract signs, WBC casts. Hypertension | 1. mean systolic pressure >140 | 1. essential hypertension— MC type mm Hg and diastolic pressure | 2. secondary hypertension- renovascular MC, >90 mm Hg on 3 separate | atherosclerosis in men, fibromuscular hyperplasia in ‘occasions women | 3. nephrosclerosis- type of renal disease seen in all types of hypertension Renal stones | 1. decreased water intake 1. ealeium stones~ MC type, radiodense, calcium . 2. reduced urine citrate~ norm. | oxalate MC type, calcium phosphate stones in ally binds excess calcium children 3. hypercaleiuria~ MC metab- | 2. magnesium ammonium phosphate~ struvite olic abnormality in urine, ex- | stones, due to urease producers | cess reabsorption of calcium in | 3, uric acid urate nephropathy from chemother- GI tract, apy, radiolucent stones 4. alterations in urine pH favor- ing stone precipitation- eg., alkaline pH with Proteus infections (urease producers) 136_ [Test pH ‘Note: This material is copyrighted. All rights reserved. SF" Chemical dipstick reactions in urinalysis: ‘Comments 1. pure vegans have an alkaline pH— citrate in fruits is converted into bicarbonate 2. meat eaters have an acid pH increased excretion of organie acids 3. urine pH is manipulated to prevent stone recurrence uric acid 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 5. 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 NaHl,PO, (titratable acidity) and NH,CI, exception is renal tubular acidosis where the pH is >5.5 9. alkalotie states generally have an alkaline urine pH exception of advanced metabolic alkalosis from vomiting, where excess reclamation of bicarbonate due 10 volume depletion causes a paradoxical aciduria Protein 1. proteinuria is the 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 dip: 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 nephropathy- microalbuminuria dipsticks are more sensitive (1.5-8 mg/dL) than standard dipsticks, ACE inhibitors prevent progression of the disease and SSA result will parallel each other e.g. Glucose 1. glucosuria is diabetes mellitus until proven otherwise 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, pentoses— does not detect sucrose (not a reducing sugar) 4. urine Clinitest is used as a screen for children <2 years of age to R/O one of the inborn errors of metabolism~ ¢.g., galactosemia, hereditary fructose intolerance , , , ’ ’ ’ ) ) L i Bilirubin 1. B-hydroxybutyrate ketoacidosis (alcoholics) will have a negative nitroprusside reaction ("masked ketosis") 2. ketones are normal in pregnancy 3. pathologic ketonuria— fasting/starvation, ketogenic diets, diabetic ketoacidosis, isopropyl alcohol poisoning, von Gierke's glycogenosis 1. only water-soluble conjugated bilirubin (CB) enters urine— pathologic finding. 2. bilirubinuria is present in hepatitis or obstructive jaundice irubinuia fs always a 3, bilirubinuria is not present in conditions with an excess in unconjugated bilirubin (UCB)~e.g., extravascular hemolytic anemia 137Note: This material is copyrighted. All rights reserved. Test Comments | Urobilinogen | 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 Blood 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 Aftican-Americans have unexplained microhematuria~ renal damage in both trait and disease Nitrite 1, detects nitrite produced by nitrate reducing bacteria— sensitivity 30%, specificity %) | 2. E.coli is a nitrate reducer and the MC urinary pathogen. Leukocyte | 1. leukocyte esterase reaction has a sensitivity/specificity of 80% for a UTI esterase 2. dipsticks for nitritefesterase are a good urine screen for infection and whether to culture urine or not ‘Classic urine casts: L 2 RBC casts— A. nephritic syndrome B. _eg,, post-streptococcal GN WBC casts— 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 casts~ chronic renal failure hyaline casts A. ghost-like castsynon-refractile, smooth borders B. sign of proteinuria C. no clinical significance in the absence of proteinuria fatty casts with Maltese crosses— nephrotic syndrome e crystals: calcium oxalate consider ‘A. calcium oxalate stone xX B. Crohn's disease C. ethylene glycol poisoning eystine- ‘A. hexagonal crystal C» B. indicates cystinuria Renal dysplasia: MC cystic disease in children no inheritance pattern abnormal development of one or both kidneys present as unilateral flank mass in most eases 138=i 3 = - =“ = = = = = > » > * * ] >» , , , } ) ; ; ‘Note: This material is copyrighted. All rights reserved. ‘Juvenile polycystic kidney 1 o AR disease bilateral disease oligohydramnios in mother: Potter's facies due to cramped quarters cysts in other organs incompatible with life Adult polyeystic kidney disease (APKD): 1. AD disease with hypertension 2. association with CNS berry aneurysms— © @ A. due to hypertension ( / B. subarachnoid hemorrhage due to ruptured aneurysm, [Miteu! Value piol@yse C. intracerebral bleed with hypertension also possible eysts not present at birth— A. develop in early teens B. screen with renal ultrasound Renal agenesis: oligohydramnios Potter facies: 1. child with cystic disease of kidneys 2. low set ears 3. parrot beak nose 4. hypoplasia of lungs due to oligohydramnios Retention eysts: 1. MC cyst in adults 2. acquired cysts derived from obstruction of tubules 3. cysts also acquired with hemodialysis Glomerulonephritis: 1. majority are immunocomplex (IC), 2. nomenelature~ if it ends in -itis, itis type IIL: exception is Goodpasture's syndrome, which is type TL diffuse if all glomeruli abnormal = focal if only a few glomeruli are abnormal proliferative if >100 nuclei membranous if membranes thick membranoproliferative if membranes thick and hypercellular munofluorescence (IF) A. always linear if anti-basement membrane antibodies are Present: ¢.g., Goodpasture's syndrome B. always lumpy bumpy (granular) if ICs are present: € £., post-streptococeal GN €. _cantell what is deposited in glomeruli: e.g., IgA deposits in IgA GN 4. electron microscopy (EM)- A. detects electron dense IC deposits B. detects fusion of podocytes (indicates nephrotic syndrome) and other structural abnormalities 5. GBM made by visceral epithelial cells (have podocytes and slit Pores)~ A; strong negative charge due to heparan sulfate: repels negatively charged proteins like albumin B. negative charge is lost in minimal change disease disorders— mp SORE 2 139Note: This material is copyrighted, All rights reserved. 2 Glomerular diseases commonly presenting as a nephritic syndrome: post-streptococcal GN— 3. A. B. systemic lupus erythematosus. A Alport’s syndrome— A microscopic: diffuse proliferative pattern with neutrophil infiltration pathogenesis: (1) post group A-streptococeal infection in a child (usually skin infection) with nephritic strains of streptococci Q) ICGN with planted bacterial antigens 3) activation of alternate complement pathway granular IF pattern EM with subepithelial deposits clinical: (1) smoky colored urine (hemoglobin converted into hematin with acid pH) 1-4 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, microscopic of type IV is diffuse proliferative GN (Q) “wire looping" of capillaries (subendothelial deposits) (2) neutrophilic infiltration with fibrinoid necrosis (3)__hematoxylin bodies (altered DNA) pathogenesis: () DNA-anti-DNA ICs @) activation of classical pathway granular IF EM with subendothelial deposits clinical: (1)* anti-dsDNA correlates with renal disease * (2) decreased C3 correlates with disease activity @) common COD in SLE microscopic: foam cells in glomeruli pathogenesis: (1) _ sex-linked dominant @) common in Mormons (3) abnormality of a5-chain type IV collagen (4) _ lack of a3-chain (Goodpasture antigen) (5) notan IC disease no IF pattern EM has no deposits 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 IA. (2) activates alternate pathway ) similar findings in Henoch-Schénlein purpura granular IF: only way to Dx is to document IgA 140pre 4 SsweuwnaseevvwvwvvvwevvvweeTreerere Eee.” ot pa oe has Asien am eee Ty pheotic 5. of rapidly progressive crescentic GN (RPGN)- A Note: This material is copyrighted. All rights reserved. EM with deposits in mesangium clinical (1) MC glomerulonephritis 2) MC in children/young adults (3) children present with gross hematuria a few days after an URI (4) adults present with asymptomatic microscopic hematuria and proteinuria () some cases become nephrotic (©) chronic in 30-50% (7) normal C3 TF you've Gof fils... Came OR microscopic: glomeruli compressed by crescents derived from parietal epithelium B. pathogenesis: (1) > Goodpasture’s disease (2) -*systemic diseases like SLE, polyarteritis, Wegener's granulomatosis G) drugs 4 (4) _ infectious disease: e.g., infectious endocarditis (5) _ antibody types: a. —_ anti-GBM (Goodpasture, type II reaction) 'b. _anti-neutrophil cytoplasmic antibodies (Wegener's) ce. ICs in some cases C. — Goodpasture’s disease: (1) anti-GBM: IgG antibody directed ageinst non-collagen domain of a3 type IV collagen in GBM and pulmonary capillaries (2) linear IF 3) 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 nephroticsyndrome: > 3-5) in) 2Y [ype 1. minimal change disease (lipoid nephrosis, nil disease)— * A. — microscopic normal except for positive fat stains in the glomerulus and tubules B. _ pathogenesis: (1) T cells produce lymphokine that destroys negative charge barrier (polyanion Joss) (2) selective proteinuria (albumin) C. negative IF D. EM shows fusion of the podocytes: no deposits E. clinical: (1) MCC of nephrotic syndrome in children 2) MC in boys between 6-8 ys old usually after URI 3) normal blood pressure (4) associations: a. atopic history b, nodular sclerosing Hodgkin’s disease (5) _ respond dramatically to corticosteroids 141Note: This material is copyrighted, All rights reserved. 2s membranous GN— A. microscopic with diffuse thickening of membranes but no cell proliferation B. epimembranous spikes with a "hair on end appearance" noted with special stains: correspond with subepithelial deposits of IgG and C3 C. 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 (3) malignancy Ave a. colon —» CéA b. malignant lymphoma granular IF EM with subepithelial deposits: fusion of podocytes clinical: (1) MCC of nephrotic syndrome in adults (2) ~40-$0% progress to end-stage disease (3) normal C3 focal segmental glomeruloselerosis (FSG)— ABS mal change disease spectrum in adults @) _NoIC deposits 3) associations a. HIV b. renal transplant patients ¢. intravenous heroin abuse EM with fusion of podocytes: no electron dense deposits clinical: (1) poor prognosis 2) recurrence after renal transplantation. @) normal C3. type I and IT membranoproliferative GN— A. microscopic has “tram tracks” in type I> type Il: ingrowth of mesangium between endothelial cell and GBM B. pathogenesis: (1) type Lis an IC disease: associations with hepatitis C, eryoglobulins, neoplasms. oF dewsedygSQ 7 2 Tas C2 nei factor ¢ autoantibody against alternate pathway C3 convertase (C3bBb) sa? y,causes sustained activation of C3 €. _ intramembranous deposits are C3. C. granular IF in type I and Tl D. EM: (1) type Ihas subendothelial deposits @) type If has intramembranous deposits: called dense deposit disease 142Note: This material is copyrighted, All rights reserved. E. clinical: (Q) type T mote common than type TL 2) always order HCV serologies in type MPGN @) poor prognosis (50% develop chronic renal failure in 10 years) (4) low C3 in both types (©) C3 nephritie factor in type II 1, Se Kimmelstiel Wilson disease (diabetic glomerulosclerosis)— pales)”. A. microscopic: J \yeor" (1) focal areas of glomerulosclerosis ("Christmas balls") due to protein wo) accumulation es) yo wl @) afferent and efferent hyaline arteriolosclerosis f eo (0 ac hyaline arteriolosclerosis of afferent/efferent arterioles B. pathogenesis: (1) non-enzymatic glycosylation of GBM and tubule basement membranes: increases vessel permeability to proteins @) glomerular hypertrophy from cytokine release from leukocytes ) osmotic damage due to toxic effect of sorbitol on endothelial cells and GBM (4) hyperfiltration damage to mesangium: increased GFR early in disease due to efferent arteriole hyaline arteriolosclerosis negative IF EM with fusion of podocytes clinical: (1) MC disease involving the glomerulus @) more common in type I than I DM (3) _tmicroalbuminuria is first sign of nephropathy (begins after ~10 years) six (4), captopril slows onset of nephropathy by decreasing angiotensin Ul; releases , pein 7 cressure on glomerulus | (8) _ hypertension occurs when proteinuria is present moo (6) retinopathy parallels nephropathy (7) MCC of end-stage renal disease in United States (8) _ other renal problems with DM a. renal papillary necrosis ! b. acute and chronic pyelonephritis 6. amyloidosis A. microscopic (1) thickening of GBM and mesangium (2) _ positive Congo red stain and apple green birefringence B. pathogenesis: deposition of amyloid derived from light chains in multiple myeloma or serum associated amyloid in reactive amyloidosis C. negative IF D. EM demonstrates amyloid fibrils E. clinical: ()__ kidneys are most commonly affected in systemic amyloidosis in 80% of cases (2) renal failure is MC COD in systemic amyloidosis, 143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 (2) molar pregnancy if the above occurs in first trimester ® BUN/Creatinine ratio in work-up of oliguria: 1. poxmal ratio is 10/1 2. prerenal azotemia~ A. due to decrease in cardiac, output: Renul : 10/1 (Q) heart failure Canythrs, C2) (2) hypovolemia B. ratio>15/1; (1) Clearance of creatinine. in urine decreases when glomerular, filtrgtion, rate decreases Ly Lie Weadt be Cleped feom bial, 43 guickly, due #6 CA 2) BUN increases disproportionately due to reabsorption in the proximal tubule 3) e.g. BUN 80 mg/dL, creatinine 2 mg/dL, 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 C. eg. 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 Nephrotoxic ATN: 1, aminoglycosides and IVP dyes MCC 2. damages the proximal tubule~ A. basement membrane intact B, _ better prognosis than ischemic ATN 144| © Laboratory differentiation of oliguria: Note: This material is copyrighted. All rights reserved. [Disorder FENa | UNa UOsm | Urinalysis mEq/L _| mOsm/kg Prerenal azotemia <1 [<0 J >500 Few hyaline casts. ‘Acute glomeruloneph- | 500 RBC casts, hematuria, ritis Acute tubularnecrosis [>I | >40__| 350 Renal tubular casts, renal tubular cells Postrenal azotemia =1__ [>a [350 Few WBCs, renal tubular cells. No casts. | 1, FENa = [Urine Na x Plasma creatinine] + [Plasma Na x Urine creatinine] x 100 2. tubular function intact: A. FENa B. UNa<40 C. UOsm >500 (kidney is concentrating) 3. tubular dysfunction: A. FENa>l B. UNa>40 : loss of tubular function leads to problems with sodium reabsorption C. UOsm <350 (kidney has lost its concentrating ability) indicate tubular dysfunction ‘© Chronic renal failure (CRF): 1, causes in descending order— ‘A. diabetic nephropathy B. hypertension C. — glomerulonephritis rapidly progressive crescentic GN focal nodular glomerulosclerosis a @) 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 C. BUN/creatipine ratio <15/1 D. Oveney. and Broad casts <7 (Hubule’'s dilated) E, _Flormocytic anemia due to loss of erythropoietin F. vitamin D deficiency: a) Q) @ G. renal osteodystrophy: @ @) 8) J. non-cardiogenie pulmonary edema ‘@ Acute pyelonephritis (upper urinary tract 1, mechanism— ‘A. ascending infection B, _vesicoureteral reflux 145 loss of 1a-hydroxylase enzyme and no second hydroxylation low calcium with normal to high phosphorous secondary hyperparathyroidism osteoporosis (bone is a buffer for acidosis) osteomalacia from vitamin D deficiency osteitis fibrosa cystica from hyperparathyroidism and increased osteoclastic activity increased bleeding ti I. hemorthagic pericard 1 (platelet dysfunction) fection) in females:‘Note: This material is copyrighted, All rights reserved. C. E.coli MC pathogen 2. clinical~ A. fever B. flank pain C. WBC casts D. lower urinary tract signs FE. danger of sepsis, Chronic pyelonephritis: 1. causes~ ‘A. MC secondary to vesicoureteral reflux B. obstruction 2. Ushaped cortical sears with underlying calyceal blunting Acute drug-induced interstitial nephritis: 1. drugs A. methicillin is prototype drag B. sulfonamides Cc. NSAIDs D. diuretics 2, mechanism—type IV cellular immunity 3. clinical A. abrupt onset of oliguria B. fever C.azotemia D. rash E. eosinophilia F. urinalys @ proteinuria (2) hematuria 3) WBC casts (4) eosinophiluria 4. Rx- withdraw drug and do not use again Analgesic nephropathy: 1. combination of aspirin + acetaminophen— A. aspirin inhibits synthesis of renal prostaglandins (vasodilator) leaving angiotensin IL 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, . sickle cell traivdisease 3. xray finding- IVP shows ring defect where papillae used to be 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 146EEE EE ED EE EEE IEEE OOP eee eTeeeerereee ‘Note: This material is copyrighted, All rights reserved. B. _ lead poisoning: (1) increases reabsorption of uric acid (2) _ 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 toxie to tubular epithelium Pb poisoning: 1, lead produces proximal tubule damage~ A, proximal renal tubular acidosis B. _ possible Fanconi syndrome (Q) proximal RTA. @)aminoaciduria @) uricosuria (4) hypoglycemia (8) _bypophosphatemia 2. produces interstitial nephritis ‘A. increase in uric acid reabsorption B. urate nephropathy C. hypertension D. gout ‘* Nephrosclerosis 1. Kidney of hypertension A. cortical surface cobblestoned: due to hyaline arteriolosclerosis leading to tubular atrophy and glomerular sclerosis B. kidneys small (1) proteinuria * Q) hematuria 2 I ‘A. renal failure B. potential for malignant hypertension ‘Malignant hypertension: 1, develops in background of essential hypertension and benign nephrosclerosis 2. gross/micro~ A. "flea bitten” kidney B, necrotizing arteriolitis with fibrinoid necrosis in glomerular capillaries causes flea bitten appearance CC. _ onion skinning of arterioles (hyperplastic arteriolosclerosis) 3. linical~ ‘A. extremely high blood pressure B. cerebral edema with papilledema C. progress to acute renal failure D. potential for intracerebral bleed 4. @Rxsnitroprusside(USMEE)” 147Note: This material is copyrighted. All rights reserved. ‘Most common site to evaluate in a child with hypertension: 1. kidneys~ A. Wilm’s tumor B. cystic kidney disease 2. 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 eo Diffuse cortical necrosis: 1. pale infarction 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 syndromes for pathogenesis at beginning of this section 2. calcium oxalate MC stone~ A. hyperealciuria MC metabolic abnormality B. _hypercalciuria due to excess reabsorption of calcium from gut clinical ‘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 A. increase water intake B. _hydrochlorothiazide increases calcium reabsorption © Angiomyolipoma: 1. hamartoma of kidneys 2, most commonly associated with tuberous sclerosis ‘Renal adenocarcinoma: 1. causes A. smoking MCC B. von Hippel-Lindau disease 2. gross/micro~ ‘A. hemorthagic mass >3 om: size determines malignant potential B. derives from proximal renal tubule: clear cells C. tendency for renal vein invasionNote: This material is copyrighted, All rights reserved. 3. clinical~ AL triad of 1) flank mass (2) hematuria; MC @) pain ‘ectopic secretion (1) erythropoietin: secondary poly (2) _parathormone like peptide: hypercalcemia with low PTH C. metastasis, (1) lungs: MC site a. “cannon ball" b. _hemorrhag (2) bone (lytic) @) skin Wilm’s tumor: 1, common childhood cancer 2. derives 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. linical~ 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 epispadias: 1, defect in genital tubercle 2. associated with exstrophy of bladder Urine drai ig 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. urinalysis A. positive dipstick for nitrites/leukocyte esterase 9494 B. pyuria C. bacteria D. hematuria 5 Re A. TMP/SMX. B. ampicillin 6. hemorrhagic cystitis often due to adenovirus 149 “USMEE:*fecesidraining fromumbilicusiin 4 day old: persistent umbilical (vitlline) sinusNote: This material is copyrighted. All rights reserved. Sterile pyuria (WBCs in the urine) and negative culture (standard culture) after 24 hours: 1. always think renal TB 2. could also be Chlamydia trachomatis~ non-specific urethritis = Complications of cyclophosphamide: 1. hemorrhagic cystitis 2. transitional carcinoma of the bladder Diseases where E, coli is MCC: 1. upper/lower UTT 2. sepsis in hospitalized patients 3. spontaneous peritonitis in adults with ascites 4. acute appendicitis in adults 5. acute cholecystitis in adults 6. traveler's diarrhea— enterotoxigenic strain 7. hemolytic uremic syndrome- enterohemorthagic strain with O157:H7 serotype ‘Transitional cell carcinoma of bladder: 1. causes- smoking MCC aniline dyes phenacetin cyclophosphamide benzidine 1 ‘A. painless hematuria B. usually papillary tumors C. tendency for recurrence and multifocality A. B. c D. zr. ‘© Bladder cancer associated with parasitic disease: 1. squamous cancer of bladder 2. Schistosoma hematobium- egg has a nipple at the end ‘@ Epididymitis: * 1. -<35 ys old A. GC B. Chlamydia trachomatis 2. >38ys old— A. Ecoli B. Pseudomonas aeruginosa ‘© Varicocele: 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 testicle: 1, testicle has a bluish black color, 2, absent cremasteric reflex 3. testicle drawn up into the inguinal canal 4. surgery imperative 1501. mumps— A. infertility uncommon B. — mostare unilateral C. older child or adult 2. syphilis 3. HIV Hydrocele: 1, scrotal mass that transilluminates 2. persistent tunica vaginalis Prostatic hyperplasia’ 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 is not increased after a rectal exam 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 2. dikydrotestosterone-mediated 3. clinical A. detected by rectal exam B. _perineural spread and extension into seminal vesicles is common C. screening test is rectal €xam + PSA D. _ confirmatory testis transrectal ultrasound with Bx E. osteoblastic metastasis with elevated alkaline phosphatase ‘& USMLE: elderly male with low back pain: 1. doa'reetal exam to R/O prostate-cancer hefore any other test 2. Note: This material is copyrighted. All rights reserved. FA 66 year old man with @ 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 di 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 A 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 C. _immunocomplex disease D. drug-induced interstitial nephritis . hematogenous spread of infection to the kidneys (acute pyelonephritis) ‘% 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 patient's lung and renal disease is most closely related to a A. type hypersensitivity reaction B. type Il hypersensitivity reaction C. type III hypersensitivity reaction D. type IV hypersensitivity reaction E. type Il and III hypersensitivity-reaction B Goodpasture) Items 6-7 A. IgA glomerulonephritis B. — Membranous glomerulonephritis C. Focal segmental glomerulosclerosis D. Rapidly progressive erescentic glomerulonephritis E. Type I membranoproliferative glomerulonephritis type I r A 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 left hilar mass, He also has generalized anasarca with 4* proteinuria, hypercholesterolemia, and fatty casts in the urine. Answer: B (association of lung cancer with membranous GN) A 34 year old male who is a known drug seeker and heroin addict comes to the emergency 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 casts on urine sediment Answer: C‘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 ient? A. Serum gonadotropins B. Chromosome analysis, C. Serum B-hCG - D. Surgical consult E, No treatment E (pubertal gynecomastia)Note: This material is copyrighted. All rights reserved. Female reproductive, breast: Sexually transmitted diseases: 1 Herpesvirus type 2 A B, go genital herpes MC due to herpesvirus, type 2 (HSV 2): sexually transmitted primary infection: (1) _ systemic signs and symptoms (2) painful vesicles that ulcerate 8) vesicles located on penis (4) _ lesions on labia, vulva, cervix: erosive cervicitis with discharge (8) proctitis: anal intercourse (6) vesicles heal within 3 wks and may recur every 46 wks (7) _ most infectious phase for congenital infections Fecurrent herpes without systemic signs or symptoms ‘Tzanck preparation (1) scrapings at base of vesicles 2) multinucleated squamous cells with intranuclear inclusions Rx: (1) acyclovir decreases the frequency of recurrences @) nocure pregnancy (1) viral shedding may occur without visible lesions 2) _ presence of viral shedding, babies must be delivered by Cesarean section human papillomavirus (HPV) A 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 (S)__koilocytic change-in squamous epithelium: wrinkled pyknotic nuclei surrounded bya halo (6) Rx: topical podophyllin HPV types 16 (most common), 18 and 31 other HPV squamous cancer associations Q) cervical Q) vulvar @) vaginal (4) anal squamous cell carcinoma (homosexual 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) 8. incubation period is 2~3 weeks post-sexual exposure dysuria thin watery exudate numerous neutrophils without bacteria on gram stain b, a. e. sterile pyuriaNote: This material is copyrighted. All rights reserved. f£ Rx: © single dose erythromycin * doxycycline (2) epididymitis in men < Chlamydial urethritis in women: 1 (1) acute urethral syndrome 2) mucopurulent cervicitis: a. source for conjunctivitis in newborns b. MCC of ophthalmia neonatorum © erythromycin eye drops have reduced this complication: usually occurs after 1 wk d. cervical Pap smear: Chlamydia produce red inclusions in endocervical cells (3) 30% of PID due to Chlamydia trachomatis 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 Q) fibrous stricture formation: a. localized lymphedema of scrotim/vulva b. women may have rectal strictures years of age C. Rx: doxyeyeline 5. Neisseria gonorrhoeae (GC)- | A. gram negative diplococcus ; B. women more likely to be asymptomatic carriers than men (1) men more likely to transmit to women after each sexual exposure (2) drug resistance: a. chromosomal mutations b. -BHlactamase production (plasmid mediated) C. clinical presentation in men: (1) GC urethritis MC presentation } @) creamy, purulent penile exudate within 2-5 d of exposure (3) stricture (4) epididymitis } ©) _ proctitis (homosexuals) (©) prostatitis (1) sterility D. Rx inmen: (1) 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) ! @)_cenvicts | a. MCsite | b. cervical discharge i = = «= o = = — « = — = «= = o = = « « = = @ = @ = @ @ = = = = = = = = = & = =Note: This material is copyrighted. All rights reserved. (4) Bartholin gland abscess (3) PID: a, during or shortly after menses b. lower abdominal pain €. adnexal tenderness on movement of the cervix (chandelier sign) a. fever €. elevated neutrophil count f. _perihepatitis results in Fitz-Hugh-Curtis syndrome: * adhesions + RUQpain & Rx with ceftriaxone (for GC) and doxyeyeline (Chlamydia) (6) complications of GC: a. sterility b. ectopic pregnancy from tubal scarring (MCC of ectopic) ©. disseminated gonocoecemia: © dermatitis * tenosynovitis © septic arthritis (1) birth contro! pills pro F, other GC infections: (1) pharyngitis (result of fellatio) (2) proctitis (anal intercourse): recurrent disease unless patient with GC proctitis is treated (USMILE) @)__ ophthalmia neonatorum: bilateral conjunctivitis in first week (USME) 6. Hemophilus ducreyi inst GC but not C) A. chancroid caused by the gram negative rod: gram stain shows a classic "schoo! of fish” orientation of the bacteria B. painful genital and perianal ulcers: suppurative inguinal nodes C. Rx: ceftriaxone or azithromycin or erythromycin 7. 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. E no lymphadenopathy Rx: doxycycline 8. Gardnerelta vaginalis A. bacterial vaginosis is caused by gram negative rod Gardnerella vaginalis B. often associated with other anaerobes like Mobiluncus and some Bacteroides species C. does not produce an inflammatory exudate (no neutrophils or erythema) D. commonly noted when vaginal pH between 5~5.5: reduction in Lactobac E. Gardnerelta adheres to surface of squamous cells: characteristic "clue cells F, potassium hydroxide added to discharge produces a fishy, amine-like smell G Rx J) Rx patient (not the partner) with metronidazole 2) avoid metronidazole in first trimesterNote: This material is copyrighted. All rights reserved. 9. syphilis A. caused by the spirochete Treponema pallidum: (1) primarily contracted by sexual contact (2) organism produces a vasculitis called endarteritis obl a. localized ischemic necrosis, b. heavy plasma cell infiltrate B. _ primary syphilis (1) solitary painless, indurated chancre @) 3-4 weeks after exposure (3) shaft of penis (4) labia | (5) _ chancre persists for 1-5 wks: spontaneously resolves secondary syphilis | (1) 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 ! (6) pericholang’ (©) meningitis (8) _ nephrotic syndrome (9) lesions heal in 4-12 wks (10) disease may enter latent phase D. latent syphilis: (1) usually asymptomatic @) positive serology @) 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 E. 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 : F. congenital syphilis: see genetics notes G. dark field microscopy: (1) considered gold standard for primary and secondary syphilis @) direct fluorescent tess just as accurate H. nonspecific serologic tests: (1) reagin antibodies react with eardiolipin 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 158Note: This material is copyrighted, All rights reserved b. false negatives in secondary syphilis due to antibody ¢ zone Phenomenon): must dilute serum until an agglutination reaction occurs (zone of equivalence) @) _RPR/VDRL become nonreactive after 1 yr in primary, 2 yrs in secondary, 2 yrs in latent syphilis (4) __VDRL test of choice on CSF in diagnosing neurosyphilis I. specific tests for syphilis: (Q) Fluorescent treponeme antibody-absorption test (FTA-ABS) —teponemal test with highest sensitivity/speeificity for Dx of syphilis in all 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 in sensitivity J Re (1) syphilis is only bacterial STD that has not chan, 2) exquisitely sensitive to penicillin (3) _ Jarisch-Herxheimer reaction (not a penicillin allergy) commonly occurs within a few hs of Rx of secondary syphilis: ed its antibiotic susceptibility a, fever b. headache ¢. intensification of rash 10, Candida albicans— A. Candida vaginitis: (1) causes: uncommonly transmitted sexually b. diabetes mellitus ¢. systemic antibiotics 4. pregnancy 2) _ intensely pruritic vaginitis with a "cottage cheese" discharge G) KOH preparation teveals budding yeasts with pseudohypha (4) Rx: fluconazole single dose 1. Trichomonas vaginalis A. flagellated protozoan (2) locates in the urethra (males and females), prostate, seminal vesicles, vagina (2) pear shaped B. vaginitis: (intense pruritus @) strawberry colored mucosa @) _leukorrhea (discharge) (4) urethritis © tumbli © Rx 8. patient/partner Rx with metronidazole b, metronidazole contraindicated in first trimester * Condom: best protection against syphilis and HIV (USMLE) notility of trophozoites in a hangi 1g drop prep of dischargeNote: This material is copyrighted. All rights reserved. @ Vulvar leukoplakia: 1. possible preeursor for squamous cancer or Paget's disease 2. doBx Lichen sclerosis 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, leukoplakie lesion ‘Squamous cancer of vulva: 1. MCeancer 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, cyst on lateral wall of vagina o Young girl with grape-tike masses protruding from the vagina: 1, embryonal rhabdomyosarcom: 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 Mallerian differentiation: (1) _ tubes, uterus, cervix, upper one-third of vagina are all affected (2) _ cervical stenosis and incompetence leads to repeated abortions 3. recent USMLE 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 * Cervical Pap smeat 1, must be endocervical cells (gold standard) indicates proper sampling of the endocervical canal where dysplasia occurs 2. superficial squamous cells indicate adequate estrogen 3. intermediate squamous cells~ indicate adequate progesterone 4. parabasal cells~ hormonally unstimulated squamous cells 5. normal non-pregnant adult woman— A. 70% superficial B. 30% intermediate 6. pregnancy/prepubertal~ 100% intermediates from progesterone effect % elderly woman not on estrogen— atrophic smear with predominantly parabasals 8 woman on unopposed estrogen~ 100% superficial 160Note: This material is copyrighted. All rights reserved © Cervical polyp 1. non-neoplastic 2. hangs out of cervical os 3. posteoital bleeding 7 Nabothian cysts: blocked endocervical glands with mucous retention (USMILE) F Koilocytosis: 1. HPV effect in squamous cells 2. _ pyknotic nucleus surrounded by a clear halo ® Cervical intraepithelial neoplasia (CIN): 1. related to HPV 2. CIN mild dysplasia that involves lower one/third 3. CIN T- moderate dysplasia that involves lower two thirds 4. CIN IIT severe dysplasia to carcinoma in situ that is full thickness dysplasia 5. requires 10 yrs to move from CIN I to CIN III 6. requires another 10 yrs to move from CIN III to invasive cancer ® Cervical squamous cancer: 1. causes A. HPV 16, 18: early onset of sexual activity with multiple partners increases exposure risk B. smoking C. birth control pills D. _ immunosuppression develops in transformation zone death due to renal failure from extension into the retroperitoneum and blockage of ureters 4. average age ~45 ys old * Gynecology cancers by decreasing incidence: endometrial > ovarian > cervical ‘® Gynecology cancers by decreasing mortality: ovarian > cervical > endometrial 'F Gynecology cancers by age: cervical 45, endometrial 55, ovarian 65 ® Sequence to menarche 1. breast budding 2. growth spurt 3. pubie hair 4, axillary hair—> 5. 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 FSH-> A. LH surge—> B. ovulation © Ovulation: 1, usually on day 14 2. indicators of ovulation~ ‘A. increase in temperature due to progesterone 161Note: This material is copyrighted. All rights reserved. ow e 4 B. subnuclear vacuoles in cells C. fering of cervical mucus D. _ presence of secretory endometrium on day 21 confirms ovulation has occurred E. _ mittelschmerz may occur: blood from ruptured follicle causes peritoneal irritation 3. birth control pills mixture of estrogen + progestins baseline levels of estrogen prevent midcycle estrogen surge preventing LH surge progestins arrest proliferative phase and lead to gland atrophy progestins inhibit LH cervical mucus is hostile to sperm alters fallopian tube motility progestins produce lipid abnormalities Secretory phase: 1, progesterone-mediated— ‘A. increase in gland tortuosity and secretion B. development of pseudodecidua Om RS OPP CC. most fixed stage of cycle 2. Arias-Stella (exaggerated secretory phase) indicates pregnancy Menses: 1. initiated by drop off in estrogen and progesterone 2. plasmin prevents menstrual blood from clotting excessive clots indicates menorthagia Implantation on day 21: 1. 3days in the tube 2. 2days in uterus Functions of FSH. 1. prepare follicle of month 2, increase aromatase synthesi 3. synthesis of LH receptors Functions of LH: 1. proliferative phase A. _ increase synthesis of 17-ketosteroids (DHEA and androstenedione) in theca interna B. DHEA converted into androstenedione C. androstenedione converted into testosterone D. testosterone enters granulosa cells and is aromatized into estradiol 2. LH surge induces ovulation 3. secretory phase- theca interna primarily synthesizes 17-hydroxyprogesterone Estrogens: 1. estradiol- ‘A. main estrogen in non-pregnant woman B. derived from aromatization of testosterone in granulosa cells of developing follicle in granulosa cells 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 162this material is copyrighted. All rights reserved. r Androgens in women: 1, androstenedione— A. 50% ovarian B, 50% adrenal cortex DHEA- A. 80% adrenal B. 20% ovary 3. DHEA-sulfate A. 95% adrenal cortex B. best test for adrenal origin of hirsutism/virilization 4. testosterone (0% from peripheral conversion of androstenedione into testosterone (oxidoreductase reaction B, 25% in ovaries C. 25% in adrenal cortex Sex hormone binding globulin (alias androgen binding globulin): binding protein for testosterone and estrogen higher affinity for testosterone high levels of SHBG decrease free testosterone levels synthesized in liver in women and liver and Sertoli cells in men estrogen and thyroid hormone increases synthesis of SHBG: reason for gynecoms men with hyperthyroidism androgens and insulin decrease synthesis of SHBG obesity and hypothyroidism have decreased SHBG: reason for hirsutism in these conditions Menopance: 1, mean age 52 yrs elevated gonadotropins~ 1 FSH best marker clinical— A. seccndary emexortion B. hot flushes decreased vagntlsectetions 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 bleeding 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 PGF2c: that increases uterine contractility (1) abortifacientNote: This material 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 cause~ 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 ovulatory types~ A. inadequate futeal 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. _ nomenses by 16 ys of age in an adolescent with good secondary sex characteristics 2. no bleeding post administration of progesterone— -—" PRages ROVE cly/enge te A. indicates thatthe uterus is not estrogen primed, or 1 bleedian aCe B. _ end-organ defect prohibiting exit of the menstrual blood PRepstetence. love 3. hypothalamie/pituitary defect Geom P&yestenove A. decreased FSH/LH: B. _ hypogonadotropic hypogonadism C. causes: (1) anorexia nervosa or weight loss syndrome Q) 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 C. probable Tumer’s syndrome (1) MC genetic cause of primary amenorrhea (2) poor secondary sex characteristics, 5. end-organ defect- ‘A. normal FSH/LH B. imperforate hymen C. _ Rokitansky-Kuster-Hauser: no vagina Secondary amenorrhea: definition— no menses for 3 mths pregnancy MCC hypogonadotropic hypogonadism— ‘A. prolactinoma B. anorexia nervosa/weight loss syndrome C. stress r: ) ohe °s Werna/ Her 164Note: 4 q This material is copyrighted. All rights reserved. D. _ bypopituitarism 4. hypergonadotropic hypogonadism— A. surgical removal 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 2. causes A. group B streptococcus (Streptococcus agalactiae) in pregnancy B. Neisseria gonorrhoeae C. IUD with Actinomyces israeli Endometrial polyp: 1, no malignant potential 2. menorrhagia Endometrial hyperplasia: 1. _ precursor for endometrial cancer simple and complex types due to unopposed estrogen— A. taking estrogen without progesterone B. obesity C. _ polycystic ovarian syndrome I, glands and stroma in myometrium- A. not endometriosis B. _ coarse, thickened myometrial tissue 2. clinical A. menorthagia B. pelvic pain C. dysmenorrhea Endometriosis: Dak 0 Patient © She Aes fen 1. glands and stroma gutside confines of the uterus~——jufyie. fe FecatiNg cf VAIN praeses ‘A. MC due to reverse menses metaplasia 1 yee C. _ hematogenous/lymphohematogenous spread y Heacyossi, only occurs in reproductive life ado mébeis x 2. clinical eS B. D, ‘A. MCC of secondary dysmenorhea B. _ ovaries most often involved (chocolate cysts) C. induration in pouch of Douglas D. dyspareunia E. intestinal obstruction 3. laparoscope best for Dx and Rx Endometrial carcinoma: 1. due to unopposed estrogen— ‘A. woman on unopposed estrogenNote: This material is copyrighted. All rights reserved. o B. early menarche/late menopause C.— nulliparity D. _ polycystic ovarian syndrome E. obesity F, Hx of breast cancer 2. bleeding in postmenopausal woman 3. MC gynecologic cancer with best prognosis: spreads down into endocervix and out into the wall of uterus Leiomyoma: MC benign tumor in women— A. sometimes called "fibroids" B. MC tumor of GI tract: MC in stomach clinical A. cause of menorhagia B. obstructive delivery Leiomyosarcoma: MC uterine sarcoma Ectopic pregnancy: 1, MCCis previous PID 2. rupture MC COD in early pregnaney 3. BehCG 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/eancer)—> estrogen inhibits FSH and enhances LH release—> continued cycle of LH stimulation—> lack of FSH causes atresia of follicles and large ovaries with subcortical cysts 2. clinical A. obesity B. hirsutism C. imegular menses D. infertility E. endometrial carcinoma 3. lab- A. _LHVFSH ratio >3/1 B, _ increased 17-Ketosteroids C. increased free testosterone D. _ increased weak estrogens 40 Re A. * birth control pills suppress LH B, + clomiphene if patient wants to become pregnant Follicular eyst: MC overall ovarian mass 166 eoNote: 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) 3. risk factors A. increased ovulation: birth control pills decrease incidence of ovarian cancer B. _ hereditary ovarian cancer syndromes: e.g., Lynch syndrome CC. Tumer’s syndrome: dysgerminoma 4. most malignant tumors spread by seeding- feel induration in pouch of Douglas ‘© Surface derived ovarian tumors: 1. benign— A, serous cystadenoma with cysts lined by cilia: Ospmoymcy Jy. fe (MC overall benign tumor . @) MC bilateral benign tumor B. mucinous cystadenoma: cysts lined by mucous secreting cells, C. Brenner's tumor: Walthard’s rests 2. malignant classification scheme also lists borderline types A. serous eystadenocareinoma: Q) MC primary cancer of ovary @) MC bilateral ovarian tumor (3) 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 ovary: 1, cystic teratoma MC (USMILE picture) A. undergoes torsion in adolescent B, xray shows calcifications CC. _ struma ovari is a teratoma with a component of functional thyroid tissue 2. dysgerminoma MC malignant tumor~ association with Tumer syndrome 3. yolk sac tumor — A. MC tumor in girl B. increased AFP r Sex cord stromal tumors: 1. fibroma MC type- A. benign tumor B. Meig syndrome (USMLE): (1)> fibroma Q)-Pascites 3) right sided pleural effusionNote: This material is copyrighted. All rights reserved. 2. granulosa cell tumor~ Corkins Ahonakse ) A. feminizing tumor B. low grade malignancy C. Call Exner bodies 3. thecomas— A. _ benign estrogen secreting tumors B. yellow color 4. Sertoli Leydig cell tumor— A. benign masculinizing tumor “ B. alias androblastoma or arrhenoblestoma Leydig cell tumor— Cmekes tSfosteeone) A. benign masculinizing tumor" B. alias hilar cell tumor C. contains crystals of Reinke 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 Chorionic villus/umbitical cord: 1. lined by trophoblastic tissue~ A. syncytiotrophoblast (1) 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 2. villus contains myxomatous appearing stroma with blood vessels : 3. two umbilical arteries and one vein (oxygenated blood)~ single artery has an increased incidence of congenital anomalies r Placenta abnormalities: 1, placenta previa— A. implants over cer B. painless bleeding abruptio placenta— A. retroplacental clot B. painful bleeding C, association with smoking/cocaine/hypertension 3. placenta accreta— direct implantation into muscle without intervening decidua 4. enlarged placentas— diabetes mellitus B. Rh hemolytic disease of newborn C. syphilis Los 168Note: This material is copyrighted, All rights reserved. 5. twin placenta— A. monochorionic are diamniotic (1) Siamese twins (USMLE) in monochorionic monoamniotic 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 6. bleeding 8-10 wk gestation— A. corresponds with drop in progesterone due to involution of corpus luteum of pr maintained by B-hCG B. not enough progesterone being synthesized by placenta sociated with identical twins whether monoanmiotic or gnaney Chor nionitis: usually Streptococcus agalactiae Preeclampsia/eclampsis 1, usually occurs in third trimester— think hydatidiform mole ifin first trimester 2. pathogenesis A. abnormal placentation causing mechanical or functional obstruction of spiral arteries leading to decreased perfusion in placenta: (1) F increase in angiotensin II, a vasoconstrictor (2) ¥ decrease in prostaglandin Ej, a vasodilator @) f increase in TXA2, a vasoconstrictor (4) y, decrease in nitric oxide, a vasodilator B. _ placenta exhibits premature aging A. preeclampsia: (0) hypertension (2) proteinuria (3) _ pitting edema B. eclampsia (1) seizures @) Rx with magnesium sulfete renal disease: swollen endothelial cells in glomerulus liver disease: see Hepatobiliary notes 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 H LP syndrome ‘© Gestational neoplasms: 1, hydatidiform mole (USMLE pieture)~ A. looks like a bunch of grapes B. complete mole: (1) 46 XX (90% a, both chromosomes of paternal origin (androgenesis) b. egg has no chromosomes or the chromosomes are inactive 169)Note: This material is copyrighted. All rights reserved « fertilized by one haploid X sperm that duplicates itself after fertilization 2) 10% of eggs 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 ehoriocarcinoma (4) preeclampsia in first trimester . uterus too large for gestational age b. increased BehCG partial mole: (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 + 1 Xxy @) embryo present (3) does not transform into choriocarcinoma invasive mole~ benign but does metastasize gestationally derived choriocarcinoma— 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 pH C. high salt content causes ferning when allowed to dry on a slide D. _ swallowed and recycled by the fetus E. _ polyhydramnios: GQ) too much fluid @) TE fistula @) duodenal atresia F. _ oligohydramnios: Q) too little fd @) fetal renal abnormalities AFP- high AFP: (1) open neural tube defects (2) 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 Il 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 thyroxine 170is material is copyrighted. All rights reserved. D. surfactant inhibited by insulin: see respiratory for RDS discussion F Urine estriol: | 1. derived from fetal adrenal, placenta, maternal liver 2. low levels indicate fetal, placental or maternal problem Breast | 7 Breast masses 1. fibrocystic change— y MC breast mass <30 years 4 cysts with apocrine metaplasia (red epithelial cells) Jvcing * duct hyperplasia (1) estrogen mediated (2) atypical ductal hyperplasia only risk factor for cancer D. fibrosis E. sclerosing adenosis in terminal duct lobules: small risk for cancer 2. bloody nipple discharge— A. <50 ys old: benign intraductal papilloma in lactiferous duct B, >50 ys old: consider ma 3. tumor <38 ys old A. fibroadenoma: (1) fircely movable mass , @) _ stroma is neoplastic component Jock Bou (3) stroma compresses ducts forming slit like spaces C sheet . @) estrogen-sensitive L fons 81 4. breast mass >50 ys old infiltrating ductal cancer Arius 7 yo * Breast lesions by location: de, mon 1. nipple/areola complex yeeny A. Paget's disease of breast: (1) rast-like lesion @) _ indicates underlying breast cancer infiltrating nipple epith B. _ breast abscess: | (1) usually associated with lactation Q) Staphylococcus aureus 2. Iactiferous 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 duct tubular carcinoma 5. terminal lobule~ A. sclerosing adenosis B. lobular carcinoma: (2) bilaterality: does not have to be the same type of cancer in other breast @) _ slow progression into invasion @) "Indian filing” of cancer cells throughout the stroma 171Note: This material is copyrighted. All rights reserved. () not palpable fibroadenoma cystosarcoma phyllodes: () malignant, bulky, fungating tumor @) rarely metastasizes ® Breast cancer risk: L 4. 5. 6. 1 = Mammograph; >50 ys old most important risk family histo} A. first generation relatives most important: (2) overrides age as most important risk fact (2) mother and/or sister B. young woman with a 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 @) _4g., mother had cancer at age 45, mammography in daughter should start at age 35 Hx of contralateral breast eancer— overrides age as major risk factor unopposed estrogen A. early menarche/late menopause B. _ nulliparity Hx of endometrial eancer radiation exposure Purpose is to detect non-palpable masses screening should begin at age 40 ys— A. every other year until 49 ys B. yearly from 50 ys on = Breast cancer types: L 2 intraductal carcinoma~ comedocarcinoma with central duct necrosis, infiltrating ductal carcinoma— A. simple type: MC overall type B. medullary carcinoma: (1) bulky (2) younger age bracket (3) _ pushing borders (4) large malignant cells with a lymphocytic infiltrate ()__ better prognosis than infiltrating ductal cancers C. colloid (mucinous) carcinoma: (1) elderly 2) tumor nests in lakes of mucus " . @) _g00d prognosis , 4 ON acejntane off He bRact, 4 D. Paget’sdisease: (ually 04M Y) i bee of app +aveklyity (1) nipple rash with underlying cancer invading epidermis causing the rash SKN! 2) poor prognosis E. inflammatory carcinoma: clinical tumor (1) worst breast cancer 172Note: This material is copyrighted. All rights reserved. (2) peau du orange appearance due to plugging of subepidermal lymphatics 3, lobular careinoma— A. MC terminal lobule cancer B, bilateral 4, stromal tumors- A. cystosarcoma phyllodes B. sarcomas: angiosarcoma MC type inical presentation of breast cancer: 1. presentation- A. MC presentation is a painless mass in upper outer quadrant B. _skin/nipple retraction C. peau du orange: inflammatory type 2. investigative tools- ' A. mammography > Use" + B. fine needle aspiration: most often used for sampling palpable mass 1" Shep iv meongeaet \olect pw -palpie masse Prognostic tools: 1. estrogen receptor assay (ERA) and progesterone receptor assay (PRA) A. ifpositive, indicates that ablative Rx is indicated: (1) tamoxifen is an anti-estrogen that blocks estrogen receptors 2)* protects against coronary artery disease and osteoporosis (B)* can produce endometrial cancer less likely to be positive in women in reproductive period of life: down-regulation of receptors from estrogen CC. more likely to be positive in postmenopausal women (1) up-regulation of estrogen receptors @)__ better remission rate S phase fraction— determines number of neoplastic cells in proliferating in the cell c) 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; omcogene- poor prognosis if present 5. grading of cancer le A. nuclear chromatin pattem B. necrosis @ Rx of breast cancer: 1, modified radical mastectomy A. all breast tissue including nipple B. axillary lymph nodes below axillary vein C. _pectoralis minor in most cases 2. lumpectomy with low axillary nodes (for staging) followed by radiation similar statistics as for modifiedNote: This material is copyrighted, All rights reserved. Questions used in the board review: tems 1-3 Infiltrating ductal careinoma Lobular carcinoma Fibrocystie change Intraductal papilloma Intraductal carcinoma 4 28-year-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-cm mass is palpated directly beneath the skin retraction. Non-tender, firm right axillary lymph nodes present in the lower axillary chain, Answer: A e A 26 year old woman without any family history of breast cancer complains of pain and 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 Iymph nodes are present Answer: C ‘FA 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 cervieal 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 an infiltrating ductal cancer an intraductal papilloma benign cyst fluid a fibroadenoma lobular cancerNote: This material is copyrighted, All rights reserved. ‘F The incidence of breast cancer has been increasing in the United States primarily due to. A. smoking B. poor diet C. mammography D. breast self-exam E. clinical breast exam o F old woman, gravida I, para 0, presents to the outpatient office for a routine prenatal visit at 34 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 120/15 mm HG, Her matemal grandfather has adult-onset diabetes, Her mother and maternal grandmother both have chronic hypertension. Which of the following is the most likely explanation for the findings in this patient? A. Preeclampsia B. Molar pregnancy C. Abruptio placenta D. — Gestational diabetes E. Primary renal disease | A 7 A 17 year old girl presents with a sudden of abdominal pain. Physical examination reveals « tender mass in the left adnexa. A pregnancy test is negative. An x-ray exhibits a mass lesion of the left ovary with focal areas of calcification. Which of the following best characterizes the ovarian ns mass? | A. Benign surface-derived tumor | B. Malignant surface-derived tumor C. Follicular eyst of the ovary D. Benign germ cell tumor | E. Malignant germ cell tumor D (cystic teratoma) | "A 66 year old nulliparous woman presents with abdominal distention despite a poor appetite. She underwent menopause 17 years ago, A rectal exam reveals induration in the rectal pouch of Douglas. She has a fluid wave in the abdomen and a left-sided pleural effusion. A thoracentesis shows clumps of malignant cells that stain positive for CA 128.Which of the following is the most likely diagnosis’ A. — Metastatic uterine leiomyosarcomas B. Metastatic endometrial cancer C. Metastatic ovarian cancer D. Metastatic cervical cancer E. Metastatic stomach caneNote: This material is copyrighted. All rights reserved. ‘@ A 28 year old woman, gravida 1, para 0, at 12 weeks’ gestation presents with painless vaginal bleeding. Her blood pressure is 160/95'mm Hg, there is 3+ proteinuria, and the uterus is larg gestational age. Which of the following is the most likely diagnosis? A. Gestational diabetes B, Placenta previa C.Abruptio placenta D. E Molar pregnaney Twin placenta D ‘7 Place the following neoplasms of the female genital tract in decreasing incidence (morbidity) and in decreasing mortality. 1 Cervix 2. Ovary 3, Endometrium “Morbidity Mortality | c aa 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 © A 22-year-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 increased, serum FSH low, LH/FSH ratio >3/1, serum total testosterone slightly increased, serum free testosterone increased, serum DHEA-sulféte normal, serum prolactin normal, and the serum TSH is normal. Based on these findings, you strongly suspect that the patient has. A. bilateral androgen-secreting tumors of the ovaries, B. deficiency of gonadotropin-releasing hormone C. _ polycystic ovarian syndrome D. adrenal Cushing's syndrome E. a gonadotropin-secreting pituitary tumor é 176Note: This material is copyrighted. All rights reserved. Endoerin 7 Examples of stimulation tests: 1, hypopituitarism: Gonadotropin releasing hormone (GnRH) stimulation test A. lack of an increase in gonadotropins over the baseline indicates an anterior pituitary disorder B. eventual rise in gonadotropins indicates a hypothalamic releasing factor disorder 2, hypopituitarism: growth hormone (GH) deficiency- A. stimulation with sleep: (1) best test @) GH and insulin-like growth factor 1 (somatomedin) are released around 5 AM 3) _IGF-1 is more sensitive test dopa and arginine: lack of an increase in GH or somatomedins indicates an anterior pituitary or hypothalamic disorder 3. 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 | 4. hypopituitarism: pituitary/adrenal axis A. metyrapone 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 1 L-deoxycortisol 117 ACTH in pituitary 11 11-deoxyeortiso! 11-OHase blocked by metyrapone —_-hydroxylase 144 cortisol @.— lack of an increase in ACTH and deoxycortisol indicates a hypothalamic, anterior pituitary problem increase in ACTH and dec of hypocortisolism B, _ insulin tolerance test: hypoglycemia stimulates the release of both GH and ACTH hypopituitarism: TRH stimulation test for prolactin— . A. TRH isa potent stimulator of prolactin B. good test for Sheehan's postpartum necrosis 6. posterior pituitary: diabetes insipidus A. differential for polyuria: (1) central/nephrogenic DI @) osmotic diuresis due to glucosuria in diabetes mellitus @) diuretics ise in deoxycortisol indicates an adrenal cause (4) hypercalcemia: metastatic calcification of kidney tubules (nephro disrupts normal dilution and concentration of urine (8) psychogenic polydipsia Icinosis)v Note: Thi material is copyrighted. All rights reserved. B. _ water deprivation test for central or nephrogenic DI (1) in anormal 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) = TBN: free water in the urine b. decrease the UOsm due to loss of free water in the urine 3) _ if intramuscular vasopressin (ADH) increases UOsm >50% from the baseline UOsm, the patient has central DI (4) _ if intramuscular vasopressin increases UOsm <45% from the baseline, the patient has nephrogenic DI (8) in psychogenic polyuria (compulsive water drinker), water deprivation resembles anormal person primary hypocortisolism (Addison’s disease) A. short ACTH stimulation test: @) does not distinguish hypopituitaris/hypothalamic cause of hypocortisolism from primary hypocortisolism (Addison’s disease) (2) cortisol remains decreased in both B. prolonged ACTH. (2) _ 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 AA TBW, due to loss of Suppression tests: 1. majority of hormone excess conditions are due to benign adenomas primary endocrine | gland hyperplasia or carcinoma are sometimes responsible for hormone access 2. in general, overaetive endocrine disorders cannot be suppressed exceptions include ‘A. prolactinomas are suppressed with bromocriptine (dopa analogue) B. pituitary Cushing's suppressed with high dose dexamethasone 3. oral glucose tolerance test for acromegaly— lack of suppression of GH or IGF-I indicates a functioning pituitary adenoma 4. Cushing’s syndrome— A. _ hypercortisolism: (1) _ patient taking corticosteroids 2) pituitary Cushing's @) adrenal Cushing's (4) ectopic Cushing B, dexamethasone suppression test: (1) dexamethasone is a cortisol analogue: should suppress ACTH in a normal person and reduce cortisol @) low dose dexamethasone suppression test: no suppression of a high baseline cortisol in pituitary/adrenal/ectopic Cushing’s syndrome () high dose dexamethasone suppression test: suppresses. cortisol in. pituitary Cushing's but not adrenal or ectopic Cushi metyrapone test (1) normally blocks 1 -hydroxylase in adrenal cortex 178Note: This material is copyrighted. All rights reserved (2) no change or increase in 11 -«leoxycortisol levels in pituitary Cushing’: indicates that pituitary tumor is responsive to a drop in cortisol induced by metyrapone 3) nochange in plasma ACTH or 11-deoxyconisol levels in adrenal or ectopic Cushing's 5. pheochromocytoma. A. catecholamine excess: usually a benign adenoma in adrenal medulla B. clonidine suppression test Q) suppression tesis are not usually performed (2) clonidine, an a agonist, normally decreases efferent sympathetic outflow: does not decrease catecholamines in pheochromocytoma 6. primary aldosteronism (Conn's syndrome)- mineralocorticoid excess from benign adenoma of zona B. isotonic saline infusion (1) _ isotonic saline should normally suppress aldosterone release by decre: release 2) _ in primary aldosteror lomerulosa ing renin n, there is a lack of aldosterone suppression Hypopituitarism: 1. adult A. non-functioning pituitary adenoma MCC of hypopituitarism (1) MENT(AD inheritance) association: a. pituitary tumor b. parathyroid adenoma ©. ZEsyndrome d. peptic ulcers (2) order of succession f trophic hormone deficiency a. gonadotropins—> b. GHS « TSH> 4. ACTH> e. prolactin B, Sheehan's postpartum necrosis: (1) sudden cessation of lactation (2) hemorthagic infarction of pituitary usually related to hypovolemic episode during delivery (3) normally, pituitary doubles in size during pregnancy , —_estrogen/progesterone inhibits prolactin release b. delivery of placenta removes inhibition and lactation begins 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: 1. main differences are in ACTH levels and electrolytes A. Addison's disease (primary hypocortisolism) (1) increased ACTH with hyperpigmentation (2) mineralocorticoid deficiency from destruction of adrenal cortex: a. severe hyponatremia 179Note: This material is copyrighted, All rights reserved. b. hyperkalemia © metabolic acidosis d. no response to prolonged ACTH stimulation (3) hypoglycemia due to lack of gluconeogenic effect of cortisol B, _ secondary hypocortisolism: (1) decreased ACTH (2) no mineralocorticoid deficiency @) 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. hypernatremia (increased POsm) with very low UOsm: lack of concentration of urine B. causes: (@) CNS trauma with severance of pituitary stalk (2) hypothalamic disease a, Hand-Schuller-Christian disease (histiocytosis X) b. sarcoidosis C. water deprivation: UOsm increases >50% with injection of ADH nephrogenic DI- A. same lab findings as central DI except UOsm is <40% increased after ADH administration B. causes: (1) drugs: a. lithium b. — demeclocyeline (2) severe hypokalemia: damages kidney tubules so they become refract (called vacuolar nephrops Clinical signs and symptoms and laboratory abnorm: 1. gonadotropin (FSH/LH) deficiene A. adult women: (secondary amenorrhea 2) decreased libido @)__ diminished secondary sex characteristics B. adult men (1) impotence (failure to sustain an erection) @) diminished secondary sex characteristics children: (1) growth and sexual maturation retardation (2) delayed fusion of epiphyses D. laboratory () low FSHand LH 2) lowestradioltestosterone 2. growth hormone (GH) deficiency~ A. adults: no effect on growth B. children: (1) dwarfism to ADH or ies of hypopituitarism: 180Note: This terial is copyrighted, All rights reserved. (2) delayed fusion of epiphyses C. laboratory: (1) low GH and IGF-1 4, insulin-like growth factor (IGF-1) is synthesized in the liver b. GH stimulates IGF 2) hypoglycemia: GH is a gluconeogenic hormone () _ no increase in GH or IGF with oral glucose tolerance test 3. thyroid stimulating hormone (TSH) defi A. adults: (1) dry, brittle hair (2) cold intolerance (3) weight gain (4) _ periorbital and facial puffiness (5) impaired memory (©) delayed Achill (7) muscle weaknes (8) _ yellowish skin: decreased conversion of B-carotene to retinoic acid in intestinal cells (9) constipation B. child (1) mental retardation: brain requires thyroxine for maturation by 2 ys of age @) _ increased weight but decreased heigh C. laboratory (low Ts (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, adrenocorticotropie hormone (ACTH) deficiency A. clinical (1) fatigue/weakness @) postural hypotension B. laboratory (2) low ACTH: di @) low cortisol @)__ fasting hypoglycemia: cortisol is gluconeog: reflex recovery (proximal muscle myopathy) iguishes it from Addison's disease (4) mild hyponatremia: mild inappropriate ADH owing to the inhibitory effect of cortisol on ADH (5) _ eventual increase in 17-OH with prolonged ACTH stimulation test (6) eosinophilia: due to the decrease in cortisol 5, _ prolactin deficiency— sudden cessation of lactation in a woman with Sh necrosis 6. antidiuretic hormone (ADH) deficiency see previous discussion an’s postpartum © Pituitary apoplexy: refers to hemorrhage/infarction of pituitary adenoma leading to hypopituitarism @ Nelson's syndrome: refers to enlargement of a preexisting pituitary adenoma secreting ACTH after both adrenal glands are removed 181Note: This material is copyrighted. All rights reserved. African pygmies: 1. GHlevels normal 2. low IGF-I Laron dwarfism: 1. end-organ unresponsiveness to GH effect 2. normal to increased GH 3. low IGF-1 GH excess: 1. GH functions~ ‘A. increase amino acid uptake in muscle B. gluconeogenesis C. stimulates synthesis and release of IGF-I in liver 2. IGF-I functions— A. linear and lateral bone growth B. chondrogenesis, C. growth of soft tissue D. best screening test for hyper- or hypofunction states 3. gigantism— 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-I (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: 1. MC pituitary tumor 2. elinieal- A. secondary amenorthea: prolactin inhibits GnRH B. _ galactorrhea C. impotence in males: no galactorrhea other causes of prolactine A. drugs: (X) birth control pills Q) hydralazine @) Hy blockers B. _ primary hypothyroidism: (1) low Ty increases TSH and TRH @) TRHisa stimulator of prolactin 4. Rx of prolactinoma~ ‘A. bromocriptine in most cases: dopamine analogue (inhibits prolactin) B. surgery if sella enlarged 182Note: This material is copyrighted. All rights reserved. r 1 2 Thyroid function studies: see schematics measured total serum T, (and T3)— A. B, reflects hormone that is (1) bound to thyroid binding globulin (TBG) 2) free, or metabolically active changes in either the free hormone level (hypo- or hyperthyroidism) or TBG concentration alter the total serum T, without affecting free Ts level (1) estrogen increases synthesis of TBG. a. increased total Ty b. normal TSH (2) androgens decrease synthesis of TBG a, decreased total Ts b. normal TSH resin T; uptake (RTU)~ A. B. reflects TBG concentration: reported as a percentage (2: preset amount of radioactive T; is added to a sample of patient serum: (1) radioactive T; binds to all available binding sites on TBG 2) _ left over is bound to a resin and measured (3) RTU is converted into a T; binding ratio (T', BR), by dividing measured RTU by reference serum mean RTU, which is 30 Patient RTU 30%, T, BR 303 (4) RTU and T, BR are low and high in hypo- and hyperthyroidism, respectively a. in hypothyroidism, more binding sites available on TBG, hence less is left over b. in hyperthyroidism, less binding sites available on TBG (saturated with T)), hence more is left over (S) TU 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 free T, index (FT) ‘A. calculated free T, hormone concentration B, calculated by multiplying the total serum T, by the T, BR C. FT Lis low and high in hypo- and hyperthyroidism, respectively D, FT ylis normal when the TBG concentration is high: increased total ; x decreased T, BR = normal FT,-1 E, _FTel is normal when the TBG concentration is low: decreased total T, x increased TBR = normal FT-1 serum TSH- A. ‘TSH has a negative feedback relationship with circulating T, and T; B. _TSHis single best test for Dx of primary hypothyroidism and hyperthyroidism (2) primary hypothyroidism: TSH increased 2) secondary hypothyroidism: TSH decreased (3) __ hyperthyroidism; TSH decreased C. TSH is always normal with alterations in TBG concentration since free T, levels are normalNormal ‘TSH = normal ‘TBG (Anabolic steroids) TRG TBC TBG (Estrogen Rx) =—— FreeTy=6 Thyroid gland Total T.=12 Free T,=6 TSH=normal Total T,=15 TSH = normal Hyperthyroidism TBG TBG TBG Total T, = 20 ‘TSH = suppressed” Note: This materia i copyrighted llrightsreserved, sam i Hillery trees => jfa pder l/c é Lf (herr > "f 6. radioactive Iis; uptake Tsp | arvc| gland > ry, apg A. Thay uptake is used to: | As of Frye I Vo 31 Phe (1) ‘detect nodules 2) _ provide an index of thyroid activity thyroid hormone is tyrosine with iodides attached to it (1) _ true hyperfunctioning of the gland (e.g., Graves" disease) increases I, uptake 2) _hypofunctioning gland has a decreased fy; uptake hot nodules: (1) functionally active ® 2) preferentially take upMn: remainder of the gland suppressed D. cold nodules: (1) inactive @) donot take up the Is: (clear space): normally functioning gland takes up the Is ot visualized, since ‘& ‘Thyroglossal duct eyst: midline cystic mass ‘2 Branchial cleft eyst: cyst in anterolateral neck * Thyroiditis: 1. acute thyroiditis A. infection caused by Staphylococcus aureus, Streptococcus pneumoniae or Streptococcus pyogenes B. _signs/lab of thyrotoxicosis but I, uptake is decreased 2. subacute granulomatous thyroiditis (de Quervain thyroiditis) 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. _ pathogenesis: (1) MCC hypothyroidism @) antibodies against“peroxidase (anti-microsomal antibodies) and thyroglobulin (anti-thyroglobulin antibodies) 8) cytotoxic T cell damage (4) _ inhibitory autoantibodies against TSH receptor that prevent hormone synthesis gross/micro: (1) _ enlarged gland with heavy lymphocytic infiltrate, germinal follicles 2) __ predisposes to primary malignant lymphoma of thyroid 4. Reidel’s thyroiditis intense fibrous tissue replacement of the gland eo Thyrold hormone excess: 1. hyperthyroidism A. excess synthesis of hormone: eg, Graves’ disease, toxie nodular 2. thyrotosicosi describes the end-organ effects excess thyroid hormone, regardless of the etiology e.g., thyroiditis, taking excess hormone } ited fe f sot hula ¢ if A To &Note: This material is copyrighted. All rights reserved. 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 Il hypersensitivity gross/micro~ A. symmetrical, nontender thyromegaly B. microscopic features of overactivity (1) scant colloid @) _ papillary infolding of the glands 3. clinical/ab features unique to Graves’ dis ‘A. infiltrative ophthalmopathy often associated with exophthalmos B. pretibial myxedema: excess glycosaminoglycan deposition C. _antimicrosomal and thyroglobulin antibodies present D. other features of thyrotoxicosis common to all types: (1) sinus tachycardia (2) _ atrial fibrillation: always order TSH when this arrhythm 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. _ B-blockers: block adrenergic effect of thyroid hormones on target organs B, drugs that decrease hormone synthesis: propylthiouracil only one that can be used in pregnancy C. if above does not correct in ~lyr, radiation ablation a is present used Toxie 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 thyroi B. _ pituitary/ hypothalamus dysfunction clinical A. muscle weakness: (DMC symptom (2) due to myopathy: inereased 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 Homo 185Note: This material is copyrighted. All rights reserved, L. diastolic hypertension J. yellow skin: increase in B-carotenes from decreased conversion into retinoic acid 3. lab- A. seetable B. _hypercholesterolemia 4 Rx A. levothyroxine B. follow patient with TSH levels until they become normal Goite 1, enlargement of thyroid gland 2, due to an absolute or relative deficien iodide deficiency 3. recurrent episodes of TSH stimulation (hyperplasia) and involution (colloid stage) A. causes gland to enlarge (1) initially diffuse enlargement @) 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. — 25% benign follicular adenoma C. 15% malignant 2. adult man/ehild~ usually cancer y of thyroid hormone~ most often associated with 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 foeal cervical lymph node involvement is the rule 3. excellent prognosis Follicular carcinoma: 1, gross/micro—- well circumscribed encapsulated tumor with capsular and/or blood vessel invasion invasive cancer without a capsule blood vessel invasion without lymph node metastasis is the rule pop more likely to have distant spread than papillary cancer: 1) lungs @) bone commonly takes up Is: Medullary carcinomas: 1. sporadic (80%) 2. familial (20%) ~ A. autosomal dominant MEN Ia and IIb synidromes: (1) MEN Ila syndrome: 186Note: Thi material is copyrighted. All rights reserved. a. medullary carcinoma b. primary hyperparathyroidism . pheochromocytoma 2) MEN Ib variant: a, medullary carcinoma b. mucosal neuromas involving the lips and tongue © pheochromocytoma 4. Marfanoid habitus 3. derive from parafollicular C ells: A. synthesize calcitonin B. calcitonin is a tumor marker for the cancer C. calcitonin is changed into amyloid in the tumor Summary of thyroid profile and Ij; uptake in thyroid disorde making the Dx olded areas are short cuts to Disorder Total Serum [RTU/TBR | FTI TSH Tn Ty Grave's Increased | Increased | Increased _| Suppressed _| Increased Factitious thyrotoxicosis Increased | Increased | Increased | Suppressed | Decreased Thyroiditis (acute, subacute) [Increased | Increased | Increased | Suppressed | Decreased | Primary hypothyroi Decreased | Decreased | Decreased [Increased | Decreased (Hashimoto) _ Secondary hypothyror Decreased | Decreased | Decreased | Decreased | Decreased (hypopituitarism | hypothalamic) Increased TBG Increased | Decreased [Normal | Normal | Non (increased estrogen) Decreased TBG Decreased | Increased Normal Normal (increased androgens) a RTU = resin T; uptake, FTs-l = free Ty index, TBR = 14 binding ratio, TSH hormone, | 131 = radioactive iodine I 131 uptake, TBG = thyroid binding globulin thyroid stimulating © Total serum caleium (see schematics): 1. measures calcium bound (40% albumin, 13% phosphate, citrates) + free (47%, i 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 calcium - serum albumin) +4 ized 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 calcium D. clinical evidence of tetany 4. clinical findings with hypocalcemia due to decreased ionized levels A. tetany B. clinical: (1) carpopedal spasm: Trousseau’s sign with blood pressure cuff, thumb flexes into palmNote: This material is copyrighted. All rights reserved. 2) Chvostek's sign: facial twitch after tapping the fac Primary hyperparathyroidism (HPTH): 1. MCC hypercalcemia in the ambulatory population 2, MC due to a benign parathyroid adenoma- composed of sheets of chief cells with nc intervening fat 3. PTH functions A. increase reabsorption of calciiim in kidneys: Na’/CI’ pump in e arly distal tubule in cortex B. decrease bicarbonate reclamation in proximal tubule: proximal renal tubular acidosis C. decreases phosphate reabsorption in proximal tubule D. increase synthesis of I-c-hydroxylase enzyme in proximal tubule for second hydroxylation of vitamin D: vitamin D reabsorbs calcium and phosphorots from the small bowel E, _ maintains ionized calcium levels: (1) receptor on the osteoblast (2) PTH causes release of IL-1 (osteoclast activating factor) 3) IL-1 activates the osteoclast to break bone down and maintain ionized calcium level (4) estrogen has inhibitory effect on IL-1 in women (S) _ testosterone has inhibitory effect on IL-1 in men 4. clinical A. most cases are asymptomatic and are discovered incidentally B. renal stones MC symptomatic presentation: (2) due to hypercalciuria (2) more calcium is released from bone tha kidneys C. peptic ulcer disease: hypercalcemia stimulates gastrs D. acute pancreatitis: hypercalcemia activates phospholipase in pancreas E, constipation F. polyuria: (1) metastatic calgification of kidney tubules Q) called nephrocalcinosis short QT interval diastolic hypertension bone disease: (1) osteitis fibrosa cystica (2) cystic lesion with hemorrhage (brown tumor) (3) usually involves the jaw reabsorbed back by PTH in the 5. lab- A. elevated serum PTH B. hypercalcemia CC. 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 F, _ hypercalciuria/hyperphosphaturia G. _chloride/phosphate ratio >33 188.Note: This material is copyrighted. All rights reserved. ‘7 Malignancy-induced hypercalcemia: pathogenesis includes 1. bone metastasis with activation of osteoclasts: A. MCC B. I/prostaglandins by cancer cells 2. ectopic secretion of a PTH-like peptide: A. primary squamous cell carcinoma of the lung B, renal adenocarcinoma C. breast cancer D. _PTH-like peptide increases calcium reabsorption in the kidneys (hypercalcemia) and decreases phosphorous reabsorption (hypophosphatemia) 3. hyperealcemia suppresses the patient's PTH as it does with all the other causes of hypercalcemia not related to primary HPTH * Other eauses of hypercalcemia: 1. sarcoidosis, 2. 3. vitamin D toxicity 4, — multiple myeloma ‘© Secondary HPTH 1. hyperplasia of all of the parathyroid glands as compensation for hypocalcemia 2. MCC is hypovitaminosis D from chronic renal failure Tertiary HPTH: 1, _ hypercalcemia that has developed from secondary HPTH 2. usually associated with chronic renal failure w Primary hypoparathyroidism: 1. __hypofunetion of the parathyroid glands leading to hypocalcemia 2. causes— previous thyroid surgery MCC B. autoimmune hypoparathyroidism: usually associated with polyendocrine deficiency syndromes (multiple endocrine gland deficiencies) C. DiGeorge syndrome linical— ‘A. reduction in total and ionized calcium level results in tetany (1) cireumoral paresthesias (numbness and tingling) @) positive Chvostek’s sign (3) _carpopedal spasm due to muscle spasms (Trousseau's sign) when taking a blood pressure B. calcification of basal ganglia 4. lab- A. low PTH B. hypocalcemia C. _hyperphosphatemia D. prolonged QT interval © Pseudohypoparathyroidism’ 1, _ SXD inherited disease characterized by end-organ resistance to PTH A. type I disease: (1) defect proximal to the generation of cAMP 2) receptor problemNote: This a terial is copyrighted, AN rights reserved. 3) _no cAMP response to infused PTH B, type Il disease: (1) defect distal to the genera 2) _post-receptor problem 3) cAMP response to infused PTH 2. elinical A. mild mental retardation B. short4th and Sth metacarpals (USMLE) 3. lab— A. hypocalcemia B. _ hyperphosphatemia C. normal to high PTH ion of cAMP. Other causes hypocalcemia: 1. hypomagnesemia. A. magnesium is a cofactor for adenylate cyclase, which generates cAMP (requ PTH activation), hence inhibiting PTH activity B, _ inhibits synthesis and release of PTH C. causes hypomagnes (1) alcoholic Q) diarrhea @) diuretics (4) aminoglycosides (5) cisplatin acute pancreatitis~ calcium used up in enzymatic fat necrosis, hypoalbuminemia~ MCC of hypocalcemia DiGeorge syndrome- see Immunopathology notes A. failure of 3rd and 4th pharyngeal pouches to develop B. _hypoparathyroidism C. absent thymus: T cell deficiency D. — truncus arteriosis: cyanotic CHD 5. hypovitaminosis D: A. chronic renal failure: MCC B. malabsorption C. cirrhosis D. lack of sunlight E. type I vitamin D-dependent rickets: (1) decreased 1a-hydroxylase 2) hypocalcemia and hypophosphatemia @) high PTH (4) normal 25(0H)D, (3) _low 1,25(0H):D; F, type Il vitamin D-dependent rickets: (1) absent vitamin D receptor (2) hypocalcemia and hypophosphatemia (3) high PTH 4) normal 25(OH)Ds (5) _ high 1,25(OH)2D, 190e OF = ,,89 pazuoy £= 89 pazqmoy €=,,8 pazuoy 9= PD Troy, O1=,,8D [OL ece6e eco ujungry urmngry VINIOTVOUGEAH WSIGIOWAHLVUVEOdAH ALVIS DLLOTVIIY uyunqiy VINANINAGTVOdAH NOLLIGNOD IVARONNote: ‘his material is copyrighted, All rights reserved. 6. hypoparathyroidism Summary of calcium, phosphorous and PTH related disorder Disorder Calcium [pTx Hypercalcemia Primary HPTH Tnoreased Decreased | Increased Malignancy (PTH-like peptide) | Increased Decreased | Decreased [Hypocaleemia Primary Hypoparathyroidism Decreased Tncreased | Decreased Pseuudohypoparathyroidism Decreased Increased Normal to Increased Secondary HPTH (Malabsorption) | Decreased Decreased _| Increased Secondary HPTH (Renal Failure) | Decreased : Increased Increased Hypoalbuminemia Decreased normal ionized — | Normal Normal caloium | Alkalosis| Normal— decreased ionized | Normal Increased calcium _ HPTH = hyperparathyroidism Graphic representation of PTH/calcium disorders: ‘Serum calcium 1, group A. A. low calcium and low PTH B. _ primary hypoparathyroidism C. DiGeorge syndrome D. hypomagnesemia ium and high PTH B. secondary hyperparathyroidism: (Q) chronic renal failure leading to hypovitaminosis D MCC (2) malabsorption leading to hypovitaminosis D 3. 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: (1) malignaney induced 2) sarcoidosis 191Note: = s material is copyrighted. All rights reserved. Adrenal gland: 1, zona glomerulosa produces aldosterone— A. activation of the renin-angiotensin-aldosterone system B. enzymes present (1) 21-hydroxylase @) (3) 18-hydroxylase a. activated by angiotensin IT b. —_deoxycorticosterone converted into aldosterone €. enzyme not present in other zones 2. zona fasciculata produces glucocorticoids— A. deoxycortisol B. cortisol C. enzymes present: (1) 17-hydroxylase: not present in zona glomerulosa Q) 21-hydroxylase 3) I -hydroxylase 3. zona reticularis produces sex hormones— A. estrogen: (1) aromatization of androstenedione (2) aromatization of testosterone B. androgens: (2) 17-Ketosteroids DHEA and androstenedione Q) testosterone C. enzymes present: same as fasciculata 4. urine for 17-hydroxycorticoids (17-OH)~ metabolites of 11-deoxycortisol (compound $) and cortisol 5. urine for 17-ketosteroids (17-KS)- A. dehydroandrosterone (DHEA) B. androstenedione 6. adrenal medulla~ A. neural crest origin B. _ synthesizes the catecholamines epinephrine (EPI) and norepinephrine (NOR) €. EPI and NOR: metabolized into biologically inactive metabolites by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT), respectively, and into the urinary metabolites metanephrine and vanillylmandelic acid (VMA), respectively D. _ metabolite of dopamine is homovanillic acid (HVA) Cushing's syndrome: 1. causes A. long-term glucocorticoid therapy MCC: zona fasciculata and reticularis atrophied B. pituitary Cushing's: sometimes called Cushing’s disease (1) tumor produces excess ACTH @) hyperplasia of zona fasciculata and reticularis . adrenal Cushing's Q) adenoma produces excess cortisol @) suppressed ACTH (3) adrenal tissue surrounding the adenoma is atrophic and contralateral zona fasciculata/reticularis is atrophied 192ed Hnayudsorg pussy jeusapy Jo anu (2) suazaysopry. 4 sev [sass] 2u049)8099)10) A asepfxoupay-fy | au019)s0)5>,04pcysqq ase|Axoapay-ty aseyonpas—n$ (g punodwos) josps024x09p-1 | ‘su1049)5099.1094x09p-} | a 4 I$ ("'p) audisays0ys04 oseyemore [ | secre phre wakes] astyanpasoprxo—> youvuiaad) joxd xoaph-L. ££ (5) au (i (D) suoypauaysoapuy <— suosay sattorg A aseysxoupay-zp srisyormgy asvsomosyaseuatospiyap plosaysixoupiy-de —p “ae 1 4 ouojousutasdssoupéy-z) <— — suojoususaag (619) auosa}so4pueydaoapsi asejousap p> auiKzus aBeavoyo uyeys 2 104 p>Note: This material is copyrighted. AUl rights reserved a D. ectopic Cushing's: (1) cancer ectopically secreting ACTH 2) zona fasciculata/reticularis exhibit hyperplasia pituitary Cushing's é A. MC type: also called Cushing's disease B, _ benign adenoma secreting ACTH adrenal Cushing's A. excess production of cortisol secondary to neoplasia (adenoma, carcinoma) ot hyperplasia) B. ACTH is suppressed 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 facies”) Q) upper back (“buffalo hump”) (3) _ trunk (truncal obesity) with sparing of the extremities (4) due to hyperinsulinism B. diastolic hypertension: due to increased synthesis of weak mineralocorticoids CC. ghicose 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 gluconeogenesis, sereening tests A. plasma ACTH B. _ low dose dexamethasone (cortisol analogue) test: cannot suppress cortisol C. 24hour urine for free cortisol (1) __ best screen (2) measures excess unbound cortisol confirmatory test- A. high dose dexamethasone test: suppresses cortisol in pituitary Cushing’s but not the other typesNote: This material is copyrighted. All rights reserved. Laboratory 1 Serum Cortisol tuitary Cushing's ‘Adrenal Cushing's Ectopic Cushing’ reased Increased Increased Urine for lp i cortisol | Increased Increased Increased Low dose dexamethasone Cortisol not suppressed Cortisol not suppressed Cortisol not suppressed High dose dexamethasone Cortisol suppressed Cortisol not suppressed Cortisol not suppressed Plasma ACTH [=Normal” to Increased_| Low Markedly Increased Metyrapone Deoxycortisol normal | Deoxycortisol not Deoxycortisol not to increased~ tumor is | increased increased not autonomous, hence it can increase ACTH synthesis in response to | hypocortisolism jormal” a plasma ACTH in the normal range is not normal in the presence of an increase in serw cortisol. ® Primary aldosteronism (Con's syndrome): see Fluids and Hemodynamics notes © Pheochromocytoma: 1. associations— A. neurofibromatosis, B. MEN Ila and IIb, 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 an: F. headache screening tests— A. 24 hour urine for soreen) C. hyperglycemia: (1) _glycogenolysis @2) gluconeogenesis Rx by surgery A. phenoxybenzamine hypertension c-adrenergic blocker used preoperatively to vanillylmandelic acid (VMA) and metanephrines (best overall neutrophilic leukocytosis: decreased adhesion molecule synthesis by catecholamines control B. _ -blockers to control tachycardia after hypertension controlled C phentolamine, an a-blocker used in hypertensive crisis, 194Note: This material is copyrighted. All rights reserved, Neuroblastoma: 1, malignant tumor of neural crest origin~ A. MC site of origin is adrenal medulla / B. posterior mediastinum deletion or rearrangement of the short arm of chromosome 1 leading to amplification of the N-mye oncogene 3. elinical— 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 is the single most important factor determining prognosis: B. cure rate is 85-90% under I year of age C. 15-40% cure rate in older children © Adrenal hypofunction: 1. causes~ | A. autoimmune destruction MCC chronic insuffi ey (Addison's disease) B, abrupt withdrawal of corticosteroids: MCC of acute adrenal insufficiency C. miliary TB: MCC worldwide D. disseminated meningococcemia. (1) Waterhouse-Friderichsen syndrome (2) DIC with bilateral adrenal hemorrhage E, congenital adrenal hyperplasia: alias adrenogenital syndrome (see Genetics notes) 2. clinical weakness hypotension: salt loss diffuse hyperpigmentation: increase in plasma ACTH 3. 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 in the urine D. hyperkalemia: no exchange of sodium for potassium 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 and its normal maintenance of the proton/K” ATPase pump in the collecting tubules G. eosinophilia: loss of the cortisol effect on eosinophils or hydrogen ions for potassium F Islet cell tumors: 1. insulinom: 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%) (Q) secrete excess insulin and C-peptides | 195Note: This material is copyrighted. All rights reserved. (2) fasting hypoglycemia: a. insulin inhibits gluconeogenesis, b. prolonged fast is the 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-peptide level 2) C-peptide is the best test for endogenous insulin release F. _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 leads to hyperacidity and peptic ulcer disease B. duodenum second MC location association with MEN I syndrome D. clinical: (1) single ulcers in the usual locations for peptic ulcers in most cases @) 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: 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 (« cells) with excess secretion of glucagon B. clinic (1) diabetes mellitus (glucagon is gluconeogenic) (2) characteristic rash called necrolytic migratory erythema somatostatinoma— A. malignant tumor of islet cells (8 cells) secreting excess somatostatin B. al achlorhydria: inhibits gastrin cholelithiasis: inhibits cholecystokinin diabetes mellitus: inhibits gastric inhibitory peptide, which normally stimulates insulin release 196Note: This material is copyrighted. All rights reserved. ! (4) steatorrhea: inhibits secretin and cholecystokinin ViPoma or pancreatic cholera or Verner Morrison syndrome ! A, malignant tumor of islets with excessive secretion of vasoactive intestinal peptide Bd (1) severe secretory diarrhea: VIP acts by stimulating cAMP similar to toxin in cholera and toxigenic £. coli @) hypokalemia and normal gap metabolic acidosis (3) achlorhydria Summary of type I and type II diabetes mellitus (DM 1. _ prevalence type 15-10% type 11 90-95% ical type [<20 years (80%) B. type Il >30 years of age 3. body habitus— | A. type [usually thin B. type II majority are obese Hx A. type | family Hx uncommon: ~50% concordance rate with identical twins B. type II family Hx is common Q) multifactorial inheritance @) ~90% concordance rate with identical twins. (3) _ increased in native Americans and African Americans 5. pathogenesis A. type I insulin lack: (1) presence of HLA-DR3 and -DR4 (90-95%): | a, B-islet cell destruction by viruses: coxsackie B virus, mumps, EBV rubella, rubeola b. _Beislet cell destruction by autoimmune disease: cytotoxic T cells prod “insulitis” ¢. _ Brislet 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) @) _ pancreas is devoid of B cells @) _islet ceil antibodies in 80% B. type Ihas no HLA relationship: (1) relative insulin deficiency: a. 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 receptors ©. postreceptor defects: © tyrosine kinase abnormalitiesNote: This material is copyrighted, All rights reserved. ‘* problems with translocation of GLUT-4 receptors to facilitate glucose absorption @) Bells are fibrosed and often contain amyloid initial symptoms— ‘A. type I rapid onset of polydipsia, polyuria, weight loss B. type Il insidious onset, symptomatic or asymptomatic 7. ketoacidosis A. type I may occur owing to insulin lack B. type Il has no ketoacidosis: (2) _ susceptible to hyperosmolar nonketotic coma @) enough insulin to prevent ketosis but not hyperglycemia @) _ 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 @) forms advanced glycosylation products (AGE) that alt 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 (8) _ microaneurysms in diabetic retinopathy: damage to pericytes weakens the vessel wall 2, 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 3. diabetic ketoacidosis (DKA)- see schematics ‘A. complication of type 1 DM ‘osylated Hb AIC) vessel permeability and 198,Note: This material is copyrighted. All rights reserved. pathogenesis of hyperglycemia: @ @ @ reduced uptake of glucose by adipose and muscle increase in glycogenolysis due to glucagon and counterregulatory hormones inerease in gluconeogenesis: a. primarily a glucagon effect b. most important factor pathogenesis of ketone bodies: @ increased lipolysis in adipose a, glucagon enhances hormone sensitive lipase—> increased release of fatty acids and glycerol increased amount of fatty acids for B-oxidation—> increased B-oxidation of fatty acids leading to an excess of acety] CoA—> converted into acetoacetate and BHB: Acc 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 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: w @) @) converted in the liver to glycerol 3 phosphate: liver is the only organ that can handle glycerol since it has glycerol kinase glycerol 3P converted into dihydroxyacetone phosphate DHAP is used as a substrate for gluconeogenesis hyperosmolar non-ketotic coma (HNKC)- primarily seen in type Il DM presence of enough insulin to prevent ketogenesis but not hyperglycemia accelerated atherosclerosis— ;chemic 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- DM is the MCC of blindness in United States microaneurysms rupture neovascularization peripheral neuropathy— DM is the MCC of distal symmetrical polyneuropathy in United States peripheral neuropathy is the MCC of pressure ulcers on bottom of feet autonomic neuropathy— cardiac arrhythmias gastroparesis impotence mucormycosis of the frontal sinuses leading to frontal lobe brain abscesses malignant external otitis from Pseudomonas aeruginosa A. B. A B. e@. D. A. B. ¢ A B. A B. &SUMMARY OF INSULIN ACTIVITY GL YCOGENESIS/FATTY ACID SYNTHESIS Glucose HMP shunt~ DNA Glucose 6-POy Glycogen synthesis (glycogen synthase) -PO, > VLDL (liver) v DHAP > Glycerol 3. Vv Pyruvate <——____ Malate malate dehydrogenase Pyruvate OAA Acetyl CoA citrdg 9 thase Citrate OAA Citrate lyase ‘Acetyl CoA > Malonyl CoA “Fatty acids Citrat inhibits B-oxidation Carnitine acyltransferase (mitochondria)SUMMARY OF INSULIN ACTIVITY = SENS ULIN ACTIVITY LIPIDS Chylomicrons VLDL ‘apillary lipoprotein lipase, (insulin enhances) - Glycerol + Fatty acids liver glycerol kinase Glycerol 3-PO, VLDL (stored in liver) ADIPOSE Glucose > Glucose 6-PO, =~ Glycerol 3-PO,—» TG (insulin +) aT Hormone sensitive lipase (insulin inhibits)DIABETIC KETOACIDOSIS HYPERGLYCEMIA Muscle Adipose TG Glycogenolysis Vv (+ gluca/cat) - Alanine hormone|sensitive lipase (+ glucagon/catecholamines) transaminase Glycerol + Fatty acids Pyruvate liver glycerol kinase Glycerol 3-PO, v DHAP GLUCONEOGENESIS HYPERGLYCEMIADIABETIC _KETOACIDOSIS ae A KETOACIDOSIS KETOGENESIS Adipose TG hormone sensitive lipase (+ glucagon/catecholamines) Liver¢— Glycerol + Fatty acids Carnitine acyltransferase Mitochondria B-Oxidation v Acetyl COA pe Ketogenesis (liver)Note: This material is copyrighted. All rights reserved. 13, M4 18, 1 Impaired glucose tolera have an increased risk for macrovs 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 home monitoring of blood glucose is mandatory Hb AIC evaluates long-term glycemic control A. represents mean glucose value for the last 3~4 mths, B. 6-7%is ideal sweeteners— have no deleterious effect in DM ce: patient who does not fit the established criteria for DM but who does cular disease and neuropathy separate occasions ational diabetes (GDM): refers to glucose intolerance that first develops during pregnanc: ‘A. increased placental size B. _anti-insulin effect of human placental lactogen A. all pregnant women between 24-28 wks gestation B. _ screened with a 50 gram glucose challenge followed by I hour glucose level €. _>140 mg/dl. isa positive screen confirmatory test- A. 3 hr 100 gram glucose tolerance test due to an; B. limits of the test set for highest sensitivity 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 Hypoglycemia: types- A. reactive type: adrenergic symptoms in fed state hyp (1) sweating 2) trembling @)_ anxiety B. fasting type: (1) neuroglycopenic (brain without glucose) in fasting a. dizziness b. confusion headache tate hypoglycemia: d, inability to concentrate stilin or oral sulfonylurea compounds is MCC of hypoglycemia patient on i aleohol- A. primarily produces a fasting hypoglycemia 200Note: This material is copyrighted. AM rights reserved B. ed NADH produced in its meta C. less pyruvate for gluconeogenesis ed glycogen stores in severe liver disease 4 carnitine deficieney— A. camitine is a cofactor i mitochondria B deficiency of camitine decreases the use of fatty acids for fuel C. all tissues are glucose dependent leading to hypoglycemia D. absence of ketone bodies, owing to rede! Bronidation of faty acids and lack of acetyl CoA as substrate 5. ketotic hypoglycemia in childhood gy MCC of hypoglycemia from 18 months to mi B. usually occurs in fasting state C. multiple etiotogies: (1) maple syrup urine disease 2) galactosemia (3) _ hereditary fructose intolerance 6. liver disease— A. decreased gly olism converts pyruvate into lactate in the transport of fatty acids (carnitine acy transferase) into the OL & aa 5 ig ogen stores - B. decreased gluconeogenesis 7% von Gierke’s glycogen storage disease~ see genetics notes (Questions used during the board review; Items a — ae {Pon [ RBUTBR] Frsindex [= | Tia ] Increased Increased Increased Decreased Increased j | B._| Increased “| Decreased | Norma Normal Not indicated C. | Increased | Increased Increased | Decreased | Decreased > D._| Decreased | Increased Normal | Normal [ Not indicated L Decreased | Decreased [Decreased [Incr RTUS resin T; uptake, T,BR=T, binding ratio A 45-year-old obese woman presents with a history of we Keep her awake at night. She states that she Ime lost seading a weight loss clinic. Physical exam reveal lid deep tendon reflexes, systolic hypertension, and ca itregul ce lukian medications other than the packet of pills giv Answer: C (taking excess hormone) Fan ed | Not indicated ight loss, weakness, and palpitations that over 30 pounds the last 8 months while fiare, a non-palpable thyroid gland, brisk Harly regular pulse. She is not taking any /en to her by the clinic, Shest. Physical exam reveals a {ate of 108 beats/minute, normal deep vear-old woman presents with complaints of chronie constipation and progressive weight sees ovet the last 6 months in spite of being on a pure vegan diet. She is currently on np Prescription or over-the-counter medications. Physical oxen exhibits a pale young woman withNote: This material is copyrighted. Alt rights reserved Periorbital puffiness, dry, yellow-colored. skin, Espiratory exam, delayed deep tendon reflexee, extremities Answer: E (primary hypothyroidism) A™~ Graves disease, D= Androgen effect Items 4-5 hormal sclera, a nor mal cardiovasctilar and and proximal muse le weakness in her lower PTH fear-old woman with diastolic hyperte With radiation of Pain into the right groin, negative dipstick for nitrite and leukocyte este, eG atals resembling the back ofan envelope, Answer: C (renal stone in primary HPTH) 7 _Annevbom presents with tetany Answer: A (DiGeorge syndrome, hyperparathyroidism, D a ain sitive dipstick for blood and a ‘am exhibits numerous RBCs and ediment ex: heart failure, and an ab could a = malignancy induced Which of the following eli anhypopituitarism? A. Low 11-deoxycortisol post-met B. Normal urine for 17 C. Hypernatremia D. Hyperkalemia E. Low TSH A (choices B and C occur in neither condition: 17 KS would be low in both of them and both would have hyponatremia; choice Dis only ,present in Addison's, choice E Panhypopituitarism) = Which of the ketoacidosis? A. Activation of ca sent thymic shadow Iso be primary hypoparathyroidism), and all other typ. 28 Of hypercalcemia nical and laborato "Y sbnormalites occur in BOTH Addison's disease and B = secondary tyrapone test -Ketosteroids is only present in following alterations in lipid metabolism is expected in a patient with diabetic pillary lipoprotein lipase B. Increased B-oxidation of fatty acids C. Decreased production of acetyl-CoA D. Increased fatty acid synthesis E. Inhibition of hormone sensitiv B (choice A occurs in the presence of Present; acetyl CoA should be when insulin is present; itis in DKA due to glucagon and cate re lipase insulin and is inhibited ir increased in DKA due to incre: hibited in DKA, choici -cholamines) in DKA, choice C occurs when insulin is ased B-oxidation of FAs: ch © E occurs when insulin is present:Note: This material is copyrighted, All rights reserved. A 22-year-old woman has been amenortheic for the last 6 months. She complains of a milky discharge from her nipples that has been 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 Ts 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 C. 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/L). 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. abenign tumor involving B-islet cells B. an early phase of type I diabetes mellitus C. abenign tumor involving a-islet cells D. ectopic secretion of an insulin-like factor | E. _ surreptitiously injected human insulin A (high C-peptide proves itis an insulinoma, would be suppressed if choice E was correct) o ‘A 39 year 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. _ pemicious anemia D. syringomyelia E. lumbar disk disease ‘A (osmotic damage of Schwann cells produces a sensorimotor peripheral neuropathy) SF” Water deprivation test for polyuria POsm post water | UOsm post UOsm post | deprivation _| water deprivation _| vasopressin _| normal 292 750 760 A. 312 98 B. 319 T10 | 288 760 ] wephrogenic diabetes mellitus, e.g. lithium, B = central diabetes insipidus, ©, head injury, C psychogenie polydipsia 203Note: This material is copyrighted. All rights reserved. Musculoskeletal, soft tissue: Synovial fluid (SF) analy 1, _ secreted by synovioeyte— A. joint lubricant that is rich in hyaluronic acid B, _ provides nourishment for articular cartilage 2. routine studies A. gross appearance: e.g., norm: B. WBC count and differential (2) normally <200 cells/uL 2) neutrophils <25% of the total count C. crystal analysis D. culture and gram stain if infection is suspected 3. crystal identification A. monosodium urate (MSU) crystals are needle shaped (monoclinic) (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 MSL crystal ly pale yellow yellow = negatively birefringent +> direction of slow ray of compensator B. _ calcium pyrophosphate erystals (CPPD): (1) _ can be needle shaped or chunky (2) blue crystal when parallel! to the slow ray indicates a positively birefring calcium pyrophosphate crystals (CPPD) ————— blue = positively birefringent +> direction of slow ray of compensator Osteoarthritis (OA): 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 ( interphalangeal) chondrocytes in articular cartilage require glucosamine in order to maintain the ‘macromolecular structure of cartilage: (1) glucosamine stimulates the synthesis of glycosaminoglycans (GAGS), which are the primary components of cartilage (2) most important factor predisposing weight bearing joint articular surface reveals erosions and cleft formation: clefts penetrate into the underlying subchondral bone (fibrillation) D. _ bone rubs on bone: dense sclerotic bone resembling ivory (eburnation) ips, knees) and hands (distal joint to OA is abnormal load placed on @ 204‘Note: This material is copyrighted. All rights reserved. E, subchondral bone cysts develop beneath the articular surface F, reactive bone formation occurs at the margins of the joints (1) produce osteophytes (bony spurs) 2) "“lipping” found in the vertebral bodies 3) 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 stiffness/enlargement D. narrow joint space E. no joint fusion 5. no specific Iab alterations Neuropathic arthropathy (Charcot's joint): 1, joint disease that develops secondary to a neurolo; 2. causes~ A. diabetes mellitus (MCC) B. syringomyelia CC. tabes dorsalis @ Rheumatoid Arthritis (RA): 1, description female-predominant chronic, systemic inflammatory disease occurring between 30-50 ys of age 2. pathogenesis— A. microbial infections: ? Epstein-Barr virus B. HLADR, + C. injury (Q) influx of CDs 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)-a > (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 ical~ see table disease 3. li 4. lab- see tableNote: This material is copyrighted. All rights reserved. ‘Juvenile Rheumatoid Arthritis (JRA): 1+ definition chronic synovial inflammatory condition that frequents patients under 16 years of age: 2. girls > boys 3. types of JRA~ Ar Stills disease (20%): systemic disease with fever, rash, lymphadenopathy, polyarthritis B. polyarticular (40%): disabling arthritis predominates C. — pauciarticular (40%): (1) arthritis in few joints 2) uveitis with the potential for blindness 4. Inb- RF negative (seronegative) in most cases ="_Comparison chart of osteoarthritis (OA) and rheumatoid Arthritis (RA A): Characteristic | Osteoarthritis Rheumatoid Arthritis Classification | Group I noninflammatory Group Il inflammatory [Sex/Age Female dominant. Middle to late | Female dominant All ages. decades of life | Possible HLA Al, BS HLA Dea | Pathogenesis | Degenerative Immunologie destruction ] Initial site oF | Articular cartilage Synovial tissue involvement Kay thnormal- [Cartilage ‘ibrilation, subchondral | Taflamed synovial Ussue Brows over arcu ities bone cYsts, osteophytes, secondary | carilage (pannus) and releases degradative avis ending to reduced joint | enzymes that degrade bone and sartilage, mobility without fusion Reactive fibrosis leads to fusion (ankylosis) of the joint and immobility Clinical Asymmetric involvement of weight | Symmetric joint involvement” Tavolves7 peering joints and small joints of | smaller joints and knee. Moming stiffness <1 hands (DIP and PIP). Mild morning | hr. Targets MCP and PIP joints in hones stiffness. ‘Heberden's nodes (DIP) | Ulnar deviation. Baker's eysis (synovial eyst and | Bouchard’s nodes (PIP), | in popliteal fossa (confused with popliteal | Compression neuropathies in | artery aneurysms). Extraarticular diseace, Ret vertebral column 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 or silicosis + RA lung disease), ffdrinous | 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 tunel | _| syndromeNote: This material is copyrighted, All rights reserved Characteristic _| Osteoarthritis Rheumatoid Arthritis Laboratory Slight elevation of alkaline phospha- | Positive rheumatoid factor (RF; IeM 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%) Sora Narrowing of joint space. | Narrowing of joint space from destruction of Osteophytes. Dense, sclerotic bone. | articular cartilage. Marginal bone erosions, | Subchondral bone cysts. Fusion (ankylosis) of joint. MCP = metacarpophalangeal joint PIP = proximal interphalangeal joint DIP interphalangeal joint F Gouty arthritis: 1. definition male dominant disease with hyperuricemia, recurrent attacks of acute arthritis, deposits of MSU (tophi) in soft tissue fypes— A. primary gout (Q) disorder in uric acid metabolism @) _underexeretion of urie acid MC @) overproduction less common secondary gout: (Q) diabetes mellitus @) polycythemia vera 3) leukemia (4) diuretic therapy (©) _ Rx disséminated carcinomas initial attack— A. usually involves metatarsophalangeal joint (big toe): called podagra B. inflammation due to an interaction of MSU erystals with mononuclear phagocytes-> (1) _ stimulates macrophage production of interleukin 1 (TL-1)-> 2) IL-1 initiates inflammatory reaction (e.g., fever) (3) MSU crystals lyse neutrophils—> (4) neutrophils release lysosomal enzymes and free radicals» (8) 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: (1) MC occur around affected joints @) granulomatous reaction with foreign body multinucleated giant cells surrounding a central core of amorphous MSU crystals complications~ A. deforming arthritis with erosion of cartilage and boneNote: This materi o is copyrighted, All rights reserved. renal disease (1) chronic interstitial nephritis Q) wrolithiasis 6. demonstration of MSU crystals in the SF is confirmatory, not hyperuricemia absolute neutrophilic leukocytosis acute attacks: reduce inflammation with (2) indomethacin (MC drug) @) colchicine: a. inhibits release of leukocyte-derived crystal induced chemotactic factor b. chemotactic factor initiates the inflammatory reaction in the joint when neutrophils phagocytose MSU erystals B. most are undetexcretors: determine this by a 24-hr urine collection (Q) Rx with uricosuric agents like probenecid or sulfinpyrazone (2) 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 chondrocaleinosis 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 2. associations Reiter syndrome psoriasis ulcerative colitis microbial pathogens: (1) Yersinia species Q) Shigella species 3. clinical- ‘A. targets the sacroiliac joint (1) _ sacroiliitis is first manifestation (2) _ stiffness upon wakening in AM @)__ subsides with activity B. _ vertebral column becomes immobile: (1) “bamboo spine” (2) _ fusion of the vertebra C. _aortitis: aortic regurgitation D. uveitis: blurry vision of cases) Sopp Reiter syndrome: 1, definition A. male dominant seronegative spondyloarthropathy: 208Note: This material is copyrighted. All rights reserved. § (1) urethritis (usually Chlamydia rachomatis) @)__non-infectious conjunctivitis 3) HLA B-27 positive arthritis B. inflammation at insertion of Achilles tendon is characteristic (USMLE) Psoriatic arthrit 1. definition HLA B27 positive seronegative spondyloarthropathy that occurs in <10% of patients with psoriasis: 2. pencil in eup deformity in fingers noted on x-ray Enteropathie arthritis: 1, definition HLA B27 positive arthritis associated with inflammatory bowel disease: 2. _associations~ post-gastroenteritis with Shigella, Campylobacter, Salmonella, or Yersinia species Bone/soft tissue infe 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 (1) neutrophils enzymatically destroy bone and leave behind devitalized portions of bone called sequestra @) chronic disease has extensive reactive bone formation in the periosteum called inyolucrum @) 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: (1) draining sinus tracts to the skin 2) ‘squamous cell carcinoma developing within the 3. tuberculous osteomyelitis A. 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. USMILE scenario: diabetic with wet gangrene of the foot followed by stiffening of the ‘jaw, neck stiffness, and increased irritability and increased hyperreflexia--? diagnosis A. patient hasitetamus B. Rx (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, (USMILE'scenario: patient steps om 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 arthritis/tendinitis Poo jus tract (USMLE) 209Note: This material is copyrighted, All rights reserved. eminated gonococcemia. decreased C5-C9: Q) final common pathway complement components required for phagocytosis of the organism (2) _GCis the MCC of septic arth knee MC large joint involved pustules on wrists/feet tenosynovitis wrists/feet yme disease— B. G, D. L A. pathogen Borrelia burgdorferi transmitted by Ixodes tick B. early disease— (1) erythema chronicum mi @) Rx with doxycycline 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 2) arthritis (3) myocarditis (4) Rx with ceftriaxone Osgood Schlatters: a 2. 3. inflammation of proximal propensity for active boys permanent knobby appearing knees apophysis at insertion of patellar tendon © Osteogenesis imperfecta: 2 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: 1 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 F Osteopetrosis: AD disease A. "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 eavity by bone: severe anemia 2is material is copyrighted. All rights reserved, B. _ pathologic fractures C. cranial nerve compression: vistal and he D. _ hydrocephalus 3. Ri bone marrow transplantation has been helpful owing to the introduction of normal osteoclasts ing loss * 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 pathologic fractures types: (1) _ primary (e.g., postmenopausal) @) secondary to an underlying disease (e.g heparin) 3. postmenopausal osteoporosis A. secondary to estrogen deficiency (2) “estrogen serves to dampen the release of interleukin-I (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 turnover: } 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: a. also a 50% reduction in incidence of ischemic heart disease >. unopposed estrogen increases the incidence of endometrial carcinoma: I Prevented by addition of progesterone (2) calcium (1500 mg) @) vitamin D 400-800 U (4) weight bearing exercise: walking, not swimming (USMLE) E. Rx of postmenopausal osteoporosis: (1) bisphosphonates: potent inhibitors of bone resorption ! (2) _calcitonin-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 nectosis ! (USMLE) / €. _ posterior dislocations are most dangerous 2. pelvie fractures— A. usually involve the symphysis, rami of the pubis, and ischium | B. bladder rupture and urethral tears are MC soft tissue injury 211his material is copyrighted, All rights reserved. €. associated with the greatest amount of blood loss of all fractures 3. scaphoid (navicular) 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 fragment is displaced upward and backward supracondylar fracture~ ‘A. distal fracture of humerus B. compromises brachial artery with dang forearm muscles'(USMEE) C. median nerve injury Avascular (aseptic) necrosis of bo1 1. pathogenesis~ occurs when the microcirculation within bone is disrupted leading to bone infaretion of Volkmann's ischemic contracture of 2, A. MC ina femoral head fracture in the elderly B. SLE patients on long-term corticosteroid therapy C. sickle cell disease 3. xeray- ‘A. bone has increased density on x-ray B. —MRUhas highest sensitivity Osteochondrosis: 1. aseptic necrosis involving the ossification centers of va 2. Legg-Perthe’s disease~ A. involves the femoral he: B. males > females C. 3-10 years of age D. pain in knee or limp E, _ secondary osteoarthritis Paget's disease of bone (osteitis deformans): 1, increased thickness of abnormal bone 2. pathogenesis ‘A. primarily occurs in elderly males: unknown etiology (2slow virus) B. _indecreasing order it targets: pelvis > skull > femur C. early phase of excessive osteoclastic resorption of bone D. late phase of excessive bone formation: (1) _ increased alkaline phosphatase (2) production of thick, weak bone (mosaic bone) without a normal lamellar structure ‘ommon 3. clinical— A. pathologic fractures B. head enlargement CC. increased risk for osteogenic sarcomas D. high output heart failure: arteriovenous connections in vascular bone 212Note: This material is copyrighted. All rights reserved. Ca q 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 pattem: subject to pathologic fractures single bone (monostotic) type polyostotic type associated with Albright's syndrome- ‘A. abnormal skin pigmentation (café au lait spots) B. _ precocious sexual development due to midline hamartoma in hypothalamus C. sites: ribs/femur/cranial bones Fibrous cortical defects/nonossifying fibromas: 1 2. essentially the same disease except for a difference in size— A. fibrous cortical defect 1-4 em B. _ nonossifying fibroma 5~10 cm 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: L 2 3. MC primary bone tumors in order of increasing age~ Ewing's sarcoma > osteogenic sarcoma > chondrosarcoma > multiple myeloma MC primary malignant tumors of bone in descending order of frequency- multiple myeloma > osteogenic sarcoma > chondrosarcoma > Ewing's sarcoma > giant cell tumor of bone ‘metastasis is the MC malignaney of bone~ breast cancer is MC primary site of origin Cartilaginous bone tumors: osteochondroma. A. children and adolescents B, metaphysis of long bones C.-MC benign bone tumor: (1) _ lobulated outgrowth of bone (exostoses) capped by benign proliferating cartilage 2) solitary (3) multiple called osteochondromatosis a. AD disease b. —chondrosarcoma risk greatest with multiple tumors enchondroma— A. children and adolescents B. tubular bones in hand C. benign tumor: ) solitary (2) multiple called enchondromatosis (Ollier’s disease): chondrosarcoma risk greatest with multiple tumors 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. (1) “popcorn” appearance on radiographs @) extends into metaphysis 4. chondrosareoma- 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 Bone forming tumors: 1. osteoma— ‘A. >40 years old B. sites: (1) sinuses (MC) @)_ facial bon: C. benign tumor: association with Gardner's syndrome 2. osteoid osteoma— A. 5-25 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 3. osteoblastoma— A. <30 years old B. vertebra > long bone C. benign tumor: oy t osteoid osteoma” @) pain not worse at pight and not relieved by aspirin 4. 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 (8) metastasize to lung e Ewing's sarcoma: 1. highly malignant primary bone tumor of marrow origin— ‘A. most frequently targets children in the first and second decades of life B. primitive neural phenotype and is associated with a ((11;22) translocationNote: This material is copyrighted. All rights reserved. q 4q C. sites: femur, flat bones of pelvis and tibia round cell” tumors: differential diagnosis includes (1) metastatic neuroblastoma (2) metastatic malignant lymphoma (3) acute lymphoblastic leukemia - fever with localized heat over the tumor anemia 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 tii 3. patholo, A. nonneoplastic component consisting of multinucleated giant cells, B, neoplastic mononuclear fibroblast-like cell that determines the biologic behavior of the tumor Masele disorders: 1. type I fibers~ 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) B. poor in mitochondria C. geared for anaerobic glycolysis D. react to training with hypertrophy: e.g., biceps muscle 3. 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 4. neurogenic atrophy- motor neuron or its axon degenerates leading to atrophy of both type | and II fibers 5. muscular dystrophy (MD)~ ‘A. inherited progressive primary muscle disease that MC presents in early childhood B. Duchenne’s: (2) SXR (70%) (2) MC and severe MD. = (3) deficiency of dystrophin: dystrophin normally anchors actin to the membrane glycoprotein (4) Becker's type is milder: defective dystrophin (USM) (S) progressive degeneration of type I and II fibers: progressive fibrosis and infiltration of muscle tissue by fatty tissue (pseudohypertrophy of calf muscle) (6) 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’s sign) d. death by twenty years of age fe. may affect cardiac muscle 218Note: This material is copyrighted, All rights reserved. (1) laboratory a, antenatal diagnosis (dystrophin defect) using recombinant DN/ technology b. serum CK/aldolase increased at birth © noclinical signs of disease + serum CK declines as muscle tissue is progressively replaced by fat and fibrous tissue ¢. female carriers have elevated serum CK activity C. myotonie: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 relax muscles (sustained grip) * cannot release grip on a golf club (USMIE) 4. frontal balding cataracts f testicular atrophy g- facial muscle wasting 1h. 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 myopathy 7. myasthenia gravis (MG) A. autoimmune disease: reduction in acetylcholine-receptors due to (1) _ presence of an autoantibody against the receptors @) type Il hypersensitivity reaction afflicts women in the second and third decades afflicts men in the sixth and seventh decades of life ~85% have thymic hyperplasia with germinal follicles representing B cell proliferation: site of antibody synthesis % may have thymomas clinical: (1) _ ptosis (first sign) Q) diplopia (3) muscle weakness improved with rest (4) dysphagia for solids and liquids G Dx: (1) Tensiton (edrophonium) test: a. inhibits acetylcholinesterase, which increases acetylcholine b, reverses muscle weakness 2) assays for anti-acetylcholine receptor antibody PoP sp 216Note: This material is copyrighted. All rights reserved. (3) anti-striated muscle antibodies BH Rx (1) _anticholinesterase drugs: pyridostigmine (2) surgical thymectomy (improvement in most cases) G)__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 2. Dupuytren's contracture~ A. MC fibromatosis B. involves palms of hands: contraction of fingers (usually the 4th and C. MC in alcoholics 3. desmoid tumor- A. fibromatosis of anterior abdominal wall in women B. associated with (2) previous trauma (2) multiple pregnancies (3) Gardner's syndrome ‘Soft tissue tumors: 1. lipomas- MC benign soft tissue tumor: } (arise in subcutaneous tissue 2) _ trunk, neck, proximal extremities | B. _noclinical significance 2. liposarcoma~ ‘A. thigh, retroperitoneum: second MC sarcoma B. MC occur in.men>50 years of age CC. lipoblasts identified with fat stains ! 3. fibrosareoma— ‘A. thigh, upper limb B. may arise after radiation 4, dermatofibroma— | A. lower extremities: elevated, red 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 CC. 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 embryonal rhabdomyosarcoma— A. MC sarcoma in children B. grape like masses protruding from the vagina or male urethra (2) thabdomyoblasts have eross-striationsNote: This material is copyrighted. All rights reserved. @) stain positive for desmin 8. leiomyoma— ‘A. MC benign tumor in women: myometrium of uterus B. MC benign GI tumor: MC in stomach C. uncommon outside the organs 9. Ieiomyosarcoma— A. MC sareoma in the GI tract and uterus B. uncommon outside organs 10. newrofibrosarcoma— A. major nerve trunks (sciatic) B, most arise in conjunction wit type I neurofibromatosis Autoimmune diseast 1. organ-specific A. Addison's disease B. pernicious anemia C. Hashimoto's thyroiditis 2. systemic~ A. SLE B. rheumatoid arthritis (RA) C. progressive systemic sclerosis (PSS) r 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) (2) _ histones: specific for drug-induced lupus @) acidic proteins: a. anti-Smith (Sm): 100% specificity and PV’ for SLE b. _anticribonucleoprotein (RNP): specific for mixed connective disease (4) nucleolar antigens B. 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 3. autoantibodies in autoimmune di | A. anti-acetyicholine receptor an | B. _anticentromere antibody | (1) CREST syndrome (60%) | 2) PSS (10%) ase body: myasthenia gravis (90%) C. anti-endomysial antibody: celiac disease D. _ anti-gliadin antibody: celiac disease (95%) E, _anti-glomerular basement membrane antibody 218Note: This material is copyrighted, All rights reserved. (1) Goodpasture’s syndrome (2) against an epitope from type IV coll omerulus and pulmonary capillaries gen in the basement membrane of the anti-insulin and anti-islet cell ant-bodies: (1) anti-insulin antibodies develop in pre-type I diabetes mellitus 2) _anti-islet cell antibodies in type I diabetes mellitus (60-90%) (3)__ antibodies not present in type Il DM anti-microsomal antibody: @) Hashimoto's autoimmune thyroiditis (97%) @) Graves disease H. _anti-mitochondrial antibody: primary biliary cirrhosis (90-100%) 1. _anti-neutrophil cytoplasmic antibdy (ANCA) (1) C (cytoplasmic) ANCA in Wegener’s granulomatosis (> 90%) . @) P (perinuclear) ANCA in polyarteritis nodosa (80%): antibody against myeloperoxidase J. anti-parietal cell and intrinsic factor antibodies: s (1) parietal cell antibodies present in 90% of pernicious anemia (PA) e (2) _ antibodies to intrinsic factor (IF) more specifie for PA . K. _anti-thyroglobulin antibody (2) Hashimoto's autoimmune thyroiditis (85%) é 2) Grave's disease (30%) é Systemic lupus erythematosus (SLE): definition. A. female dominant disorder: (1) _ polycional activation of B cells (2) hormonal: increased estrogen activity (3) _ environmental triggers: a. sunlight b. procainamide clinical . = A. skin: (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 joints: (1) arthritis or arthralgias involving small joints (e.g., hands) @) MC presenting symptom 3) morning stiffitess resembling RA avascular (aseptic) necrosis of the femoral head: complication of long-term corticosteroid therapy cardiovascular: (1) fibrinous pericarditis/eff n 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 patternNote: This material is copyrighted, All rights reserved. F, _hematologie: autoimmune hemolytic anemia/thrombocytopenia/Ieukopenia G. _anti-phospholipid antibodies: (lupus anticoagulant and anti-cardiolipin antibody @) _ mid-trimester fetal loss @) _ strokes H. renal disease: (1) diffuse proliferative GN MC type 2) correlates with presence of anti-dsDNA (3) common COD 1. _anti-SS-A (Ro) antibodies in pregnancy: newboms with complete heart block J. infeetion MC COD laboratory- 3 ‘A. positive serum ANA (9926) B. _ anti-dsDNA (70%) CC. 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 4 an A. : hydralazine also common offender B. differs from § (1) abrupt rather than slow onset @) very low incidence of renal/CNS involvement (8) absent anti-dsDNAJanti-Sm antibodies @ lement levels © tone (95%) antibodies © th discontinuance of the drug Progressive systemic selerosis (PSS): 1. definition— A. female dominant B. _ initially involves small vessels C. _ followed by excessive deposition of normal collagen in multiple organ systems 2. clinical A. skin: (1) __parchment-like appearance (2) swelling of fingers/hands @) tight facial features (4) multiple, punctate blood vessel dilatations (telangiectasias) (S) Raynaud's phenomenon: MC initial sign of PSS B. joints: polyarthritis c Gk (1) dysphagia for solids/liquids (lack of peristalsis) (2) malabsorption (3) _ wide-mouthed diverticula D. renal: @)__ glomerulonephritis Q) severe hypertension @) renal failureNote: This material is copyrighted. All rights reserved. E. pulmonary: (1) _ diffuse interstitial pneumonitis with fibrosis @) Mccop F. _ heart: left ventricular dysfunction 3. CREST syndrome- A. galcinosis (fingertips) and anti-centromere antibodies B. Raynaud's phenomenon C. esophageal motility dysfunction D. _ selerodactyly E. _ {elangiectasias 4. laboratory— A. positive ANA (70-90%) B. gantisScl-70 (70%): topoisomerase: |: (USMILE) CC. anti-centromere antibodies (30%) ‘F Dermatomyositis (DM) and polymyositis (PM): 1. definition both associated with an inflammatory myopathy with or without involvement of the sk clinical— ‘A. muscle pain and atrophy: shoulders commonly involved B. dysphagia for solids/liquids: involves striated muscle of upper esophagus C. _pufly eyelids with a purple-red discoloration (heliotrope eyelids) D. — Gottron’s patches over dorsum of PIP joints | E. _ increased risk for malignant neoplasms (15~20%): particularly lung cancer 3. Iaboratory— A. elevated serum creatine kinase B. positive anti-Jo-I antibodies C. Bx of muscle shows lymphocytic infiltrate ‘Mixed connective tissue disease (MCTD) 1. features of SLE, PSS, and polymyositis A. follows a more benign course than the autoimmune diseases B. rarely involves the kidney 2. anti-ribonucleoprotein (RNP) antibodies are present in most cases o Sjogren's syndrome: 1. definition A. female dominant disease B. associated with rheumatoid arthritis 2. clinical A. immune destruction of lacrimal/minor salivary glands (1) dry eyes (Keratoconjunctivitis) @) dry mouth (xerostomia) B. _ increased incidence of malignant lymphoma C. renal: tubulointersttial disease leads to distal renal tubular acidosis (type I) 3. laboratory- A. positive serum ANA (50-80%) B. _ anti-SS-A/Ro (70-80%) CC. anti-SS-B/La (50-70%: more specific than anti Ro antibodies D. _ positive theumatoid factor 221Note: This material is copyrighted. All rights reserved. E. confirmatory test: lip biopsy of a minor salivary gland demonstrating, lymphocytic destruction of the glands ‘Questions used during the board review: e A 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 mother has severe osteoarthritis. The right toe is swollen, hot and exquisitely sensitive to touch. Laboratory studie: reveil'abetroplliebuliooytons ad tft SSR. synovial tay a performed RaSedion We'ahave history, his problem is most likely related to. A. joint inflammation secondary to a positively birefringent crystal B, disseminated gonococcemia with septic arthritis C. underexeretion of uric acid in the urine D. _ osteomyelitis secondary to hematogenous spread of Staphylococcus aureus E, an HLA B27 positive spondyloarthropathy ut, MC due to underexeretion rather than overproduction) 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 BE, — Bouchard's nodes D all the other choices are findings in OA) a 28 year old man who works in a 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 diplococeus 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 returned 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 diplococcus ‘gram negative rod spirochete gram negative diplococcus intranuclear inclusion moom> D (disseminated gonococcemia due to Neisseria gonorrhoeae, a gram negative diplococcus)Note: This material is copyrighted. All rights reserved, Septic arthritis and tenosynovitis is most often associated with which one of the follo complement abnormalities? A. Clesterase inhibitor deficiency 2 B. C2 deficiency C. C 3 deficiency D, CSadeficiency E C5-C9 deficiencies E (associated with disseminated gonococcemia) ‘A veterinarian develops tenosynovitis within 24-hs of an animal bite. You suspect the offending organism is... A. Yersinia pestis Eikenella corrodens Fusobacterium Pasteurella multocida Staphylococcus aureus B. c D, ENote: This material is copyrighted. All rights reserved, Skin © Normal skin/dermatology terms: 1, epidermis— A. stratum basalis: actively dividing stem cells along the basement membrane B. stratum spinosum: prominent desmasome attachments C. stratum granulosum: granular layer with keratohyaline granules D. stratum comeum: anucleate cells with keratin: site for superficial dermatophytes 2. dermis~ papillary and reticular 3.__ dermatology terms _ - Term Definition Examples Hyperkeratosis Increased thickness of the stratum | Chronic dermatitis, lichen planus, comeum. Clinically, it is | psoriasis, ichthyosis, verruca vulgaris manifested as a scaly appearance | (wart) of the skin. Acanthosis Increased thickness of _ the | See above examples, epidermis that is most commonly due to hyperkeratosis. Parakeratosis Persistence of nuclei in the | Psoriasis stratum comeum layer. r Papillomatosis Spire-like projections from the | Verruca vulgaris. surface of the skin often associated with similar projections downward into the papillary dermis, Acantholysis Loss of cohesion between | Pemphigus vulgaris, squamous cells. Most commonly due to immunologic destruction 1. of the intercellular bridges. Macule Pigmented .or erythematous flat | Lentigo maligna, freckles (ephelides), L 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 lesion that extends into the | carcinoma, erythema nodosum. dermis. Plaque Flattened, elevated area on the | Psoriasis | epidermis >S mm that is often associated with erythema and scaling. Vesicle Fluid filled blister <5 mm in | Acute eczema, pemphigus diameter. Bulla Fluid filled blister >S mm in| Bullous pemphigoid, scalded skin diameter. syndrome Pustule Fluid filled “blister with | Impetigo, folliculitis inflammatory cé _| Umbilication Central crater or indentation in a Molluscum contagiosum, basal cell papule or nodule, | carcinoma 224Note: This material is copyrighted, Ail rights reserved. @ Bezema: 2. definition— skin lesions characterized by pruritus and distinctive gross and microscopic features acute eczema A. weeping, erythematous rash with vesicle formation B. _spongiosis (intercellular edema) in the epidermi ubacute eczem: A. crusts developing over ruptured vesicles, erythema and some scalin 1 of the epidermis B. hyperkeratosis with increased thickness of the stratum corneum chronic eczema— A. lichenification: thickening due to hyperkeratosis from constant scratching B. scaling C. _hyperpigmentation atopic dermatitis— A. type IgE 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 contact dermatitis— A. inflammatory disorder of skin assox irritating substances B. allergic contact dermatitis: (1) cell mediated type IV hypersensitivity reaction @) poison ivy-oak-sumac ated with exposure to various antigens and @) nickel (4) chemicals: a. household cleaners b. medications (S) CUSMEE'scenario® child develops a rash while running through bushes: poison ivy C. irritant contact dermatitis: (1) MC type @) nonimmunologic reaction due to a local toxic effect of a chemical on the skin (3) detergents present in soaps 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 ¢. _thiazides (2) USMLE scenarios: a. girl playing soccer is on tetracycline and distribution of rash is face, neck, forearms, and legs (shorts) b. _same\question asked with a'baseball player (lezs would not be involved) E. contact urticaria: (1) wheal and flare reaction: (2) IgE mediated 3) non-immunologic reactionNote: This material is copyrighted. All rights reserved. ca Seborrheic dermatitis: 1. definition scaly, often greasy type of derm: 2, locations— A. scalp: (2) dandruff @) le cap in infants B, face: (1) eyebrows (2) nasal creases 3. due to a Pityrosporum species (Malassezia furfur)~ disseminated in AIDS Superficial mycoses (dermatophytoses): 1, definition group of fungi confined to the stratum coreum or its appendages 2. tinea capitis— MC in children (1) circular, or ring-shaped patches (“ringworm”) of alopecia (hair loss) with erythema and scaling @) MCC is Trichophyton tonsurans: negative Wood's lamp, since the patho; infects the inner hair shaft pathogen @) Microsporum canis second MC pathogen: Wood's lamp positive, since the pathogen infects the outer hair shaft 3. other types of tine: 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: serapings 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) Macutopapular disorders: 1. definition combination of macules (flat, pigmented lesions) and papules (peaked lesions <1 cm) human papillomavirus (HPV)~ A. condyloma acuminata: venereal warts (HPV 6, 11) B. common warts: verruca vulgaris 3. molluscum contagiosum— A. poxvirus family B. _ bowl shaped lesion: (1) central area of umbilication filled with keratin @) viral particles in keratin debris €. MC in childrenNote: This material is copyrighted, All rights reserved. D. disseminate 4. measles (rubeola)- A. clinical: (fever @) conjunctivitis (8) _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 () not teratogenic (6) otitis media common (7) pneumonia: Warthin-Finkeldey giant cells (8) _ subacute sclerosing panencephalitis German measles (rubella) A. "three day measles" B. fever C. arthralgias (characteristic) D. painful postauricular lymphadenopathy (characteristic) | to 2 days prior to the onset of ‘ maculopapular rash: begins on the head and spreads downward E, _ teratogenic: see genetics notes 6. parvovirus B19- A. erythema infectiosum (fifth disease): Q) confluent maculopapular rash: (2) usually beginning on the cheeks (“slapped face" appearance) 3) _ extends centripetally to involve the trunk B. other parvovirus associations: Q) pure RBC aplasia (2) chronic arthritis (3) repeated abortions 7. roseola (exanthem subitum)— A. caused by herpesvirus 6 B, sudden onset of ¢ high fever that falls by crisis on the 3rd to 4th day C. _ followed by a maculopapular rash that begins on the trunk and spreads centrifugally 8. toxic 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: (Q) high fever (39°C) @) mental confusion @) diarrhea (4) hypotension (5) pharyngitis, (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 Rx with mafeillin (USMLE), HIVNote: This material is copyrighted. All rights reserved. 9. scarlet fever— A Strepiococeus pyogenes that generates an erythrogenic toxin ‘erythematous rash (sandpaper consistency): (1) _ begins on the trunk and limbs (2) resolves with desquamation circumoral pallor tongue initially has a “white strawberry” appearance: followed by a “red strawberry” appearance when desquamation occurs association with post-streptococcal glomerulonephritis 10. drug reactions— A B. * Papulosquamous MC skin lesion associated with drugs eg,, penicillin, sulfa drugs isorders: 1, actinic (solar) keratosis— A B. c pre-malignant skin lesion: (1) may progress to squamous cell carcinoma (2) _hyperkeratotic, pearly gray/white appearance induced by UVB light damage on sun exposed areas like the face, hand also associated with arsenic poisoning and forearms 2. lichen planus~ A. intensely prutitie, scaly, violaceous, flat-topped papules: (wrists Q) scalp B. oral mucosa (50%): (1) fine white net-like appearance called Wickham's striae (2) _ precursor for squamous cell carcinoma 3. psoriasis A. chronic disorder characterized by erythematous plaques secondary to an unregulated proliferation of keratinocytes: hyperplasia B. _ pathogenesis: f (Q) genetic factors (2) environmental factors: e.g., infection due to streptococcal pharyngitis (3) _ unregulated epidermal proliferation (4) microcirculatory changes in the superficial papillary dermis (5) associated with destructive arthritis if patient is HLA-B27 C. plaques: (1) located on scalp: MC location 2) pressure areas like the elbow (3) well-demarcated, flat, elevated salmon colored lesions (4) 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 (6) pitting of the nails D. _ microscopic (1) hyperkeratosis, 2) _ parakeratosis: persistent nuclei in the stratum comeum (3) 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 () 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) (©) collections of neutrophils in the stratum comeum: called Munro microabscesses EB Rx (1) topical steroids (2) methotrexate in resistant cases TUSMLE)scenario: picture of psoriatic plaques on elbow of Afican American iasis rosea— 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 lines of cleavage in a “Christmas tree” distribution ‘2 Yesiculobullous disorders: 1, herpesvirus type I and II 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 Tzanck prep of vesicles has multinucleated squamous cells with intranuclear inclusions like Herpes CC. cerebellitis is common: self-limited D. association with Reye's syndrome if patient takes aspirin 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 pust form honey colored, crusted lesions 2) sometimes superinfected with Staphylococcus aureus: adds a bullous component to the lesions C. associated with post-streptococcal glomerulonephritis 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 aureus the trunk: rash follows les that rupture to 229(s reserved. Note: This material is copyrighted. All rig 6 pemphigus vulgaris— A. autoimmune skin disease (1) [9G antibodies directed against the intercellular attachment sites (desmosomes) between keratinocytes 2) type II cytotoxic antibody hypersensitivity reaction B. _ produces vesicles (blisters <5 mm) and bulla: (1) _ lesions occur on skin and oa oral 2) _ vesicles are intraepidermal (3) suprabasal location: a. just above the basal cell layer b. 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 separat layer with minimal manual pressure C. Rx with systemic corticosteroids butlous pemphigoid~ A. autoimmune vesicular disease: IgG antibodies directed against the basement membrane B. vesicles are in a subepidermal location: (1) negative Nikolsky sign 2) _acantholysis is not present 8. dermatitis herpetiformis A. autoimmune vesicular disease (2) IgA immunocomplexes (type II immunocomplex reaction) located at the tips of the dermal papilla (2) subepidermal vesicles with neutrophils B. strong association with celine disease C. — anti-reticulin antibodies sasily from the basal 9. erythema multiforme— A. immunologic reaction: B. ski (vesicles 2) _ bullae with bull's eye lesions: "target cell” of the skin C. involves mucous membranes: (1) _ called Steven’s Johnson syndrome (2) response to an infection: e.., Mycoplasma pneumoniae (3) response to drugs: a. penicillin b. sulfa drugs (4) _ response to various autoimmune diseases (SLE) or pregnancy ‘© Pustular disorders: 1. Staphylococcus aureus~ A. gram positive coccus associated with (Q) — furuncles (boils) 2) carbuncles (furuncle with multiple sinuses) (3) bullous type of impetigo (4) _ scalded skin syndrome 230Note: This material is copyrighted, All rights reserved, (5) toxic shock syndrome (6) _hidradenitis suppurativa: a, abscess of apocrine glands b. usually in the axilla ‘ (1) paronychial infections (8) _ postoperative wound or stitch abscesses (9) postpartum breast abscesses 2. acne vulgaris— é ‘A. chronic inflammatory disorder involving the pilosebaceous unit in the skin B. obstructive type: (1) closed comedones (whiteheads) (2) open comedones (blackheads) ‘ C. inflammatory type: (1) __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: ] (1) 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 | F. aggravating factors: = (1) hormones (e.g, testosterone, progesterone, glucocorticoids) . 2) drugs (e.g, lithium) (3) occupational factors (e.g., grease) (4) dietary factors do not contribute to acne (¢.g., chocolate, nuts) “ 3. acne rosacen inflammatory disease of the pilosebaceous units on the face in middle aged individuals 7 © Urticaria: 1. definition urticaris (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: (1) foods (shellfish, peanuts) Q) drugs (eg. penicillin) (3) insect bites (e.g,, bee sting (4) _radiocontrast dyes B. _ may be immunocomplex (type II] induced: serum sickness like syndrome in HBV yedema— A. unlike urticaria, it is edema within the deeper subcutaneous tissue B. produces diffuse swelling of the involved tissue: (1) Cl esterase inhibitor deficiency @) bradykinin effect of ACE inhibitors or IV vancomycin ("red man' syndrome) 1. cellulitis with lymphangiitis ("red streaks” A. characteristic of Streptococcus pyogenes infections B. elaboration of hyaluronidase: allows exudate to spread through the subcutaneous tissue 231Note: This material is copyrighted. All rights reserved. F Atrophy of ski 1 ® Benign nodular and cystic 1 erysipelas A. due to Streptococcus pyogenes B. raised, erythematous ("brawny edema"): hot cellulitis C. usually on the face 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) (2) DNA-anti-DNA immunocomplexes that deposit in the basement membrane of the skin a. deposits noted in involved and uninvolved skin in SLE b. _ deposits only present in involved skin in chronie discoid lupus C. microscopic: (1) immune reaction leads to degeneration of the basal cells along the dermal- epidermal junction and hair shatts: 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 isorders: 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 PRESSRSTISILEDS) « caused by Sporothrix schencki: Q) acquired from traumatic implantation of the fungus growing in the soil @) commonly occurs in rose gardeners B. clinical: (J) lymphocutaneous disease: chain of suppurating subcutaneous nodules 2) Rx with oral potassium iodide Mycobacterium leprae ‘A. acid fast organism: (1) cause of leprosy 2) transmitted by direct contact or droplet infection B. _ tuberculoid type: (1) _ intact cellular immunity: granulomas can develop 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 lesions 232Note: This material is copyrighted, All rights reserved. G lepromatous type: (2) lacks cellular immunity (2) negative lepromin skin test (3) organisms easily identified in tissue within macropha; (4) associated with the classic leonine facies (8) skin biopsies: a. narrow zone berieath the epidermis that is free of org zone (USMLE) b. _ underlying Grenz zone contains foamy macrophages with organisms (6) neural involvement is a late feature of the disease s (lepra cells) anisms called Genz 5. keratoacanthoma~ A B, c. A. B. A B. c rapid growth of a crateriform lesion regresses and involutes with scarring histologically confused with a well-differentiated squamous cell carcinoma hema nodosum~ MCC of inflammation of subcutaneous fat (panniculitis) raised, erythematous, painful nodules usually on the ant associations: (1) _coccidioidomycosis/histoplasmosis\(USMILE) @) streptococcal infections (3) _ sarcoidosis (4) TBMeprosy (5) drugs (e.g., sulfonamides) portion of the shins Skin cancers associated with UV light damage (excluding malignant melanoma): 1, basal cell carcinoma (BCC). MC malignant tumor of the skin occurs on sun-exposed, hair-bearing surfaces locally aggressive, infiltrating cancer: (1) arises from the basal cell layer of the epidermis 2) multifocal (3) do not metastasize (4) locations a. inner aspect of the nose b. around the orbit upper lip appearance: (1) _ raised nodules containing a central crater @) _ external surface of nodule is pearly-colored and has prominent vascular channels visible beneath the surface 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 Jow but significant potential for metastasis: located on the face: ears, nose, lower lip predisposing causesNote: This material is copyrighted. All rights reserved. Epidermal inclusion cyst: L Pilar cyst (wen): scalp lesio 1. 2 Melanocytic disordes 1 (1) arsenic poisoning (2) chronic skin ulcers (3) ssinusitradts (particularly chronic osteomyelitis sUSMILR) (4) sites of previous radiation/burn scars (5) MC cancer associated with immunosuppressive therapy (USMLE!seenario: ulcer at orifice of chronically draining sinus that does not g with antibiotics, ete. derived from the epidermis of a hair follicle contains lipid-rich debris intermixed with laminated keratin material imilar to epidermal inclusion cyst except for the absence of a stratum granulosum layer in the cyst wall laminated keratin in the cyst vitiligo A. autoimmune destruction of melanocytes resulting in areas of depiamentation 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 seborrheic keratosis ‘A. benign epidermal tumor: B. presents on the skin of middle aged individuals raised, pigmented lesions with a verruca-like surface D, rapid increase in number called Leser-Trelat sign: possible gastric adenocarcinoma acanthosis nigricans— A. pigmented skin lesion commonly present in the axilla B, _ phenotypic marker for an underlying adenocarcinoma of the stomach freckles (ephelides)— x A. pigmented macular lesions that occur in sun-exposed areas of the sl B, not premalignant C. 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: !pregmaney:mask’” neyocellular nevus— A. _ benign tumor of neural crest-derived cells: contain modified melanocytes of various shapes (nevus cells) B. _ begin in early childhood as junctional nevi: (1) nests of pigmented nevus cells along basal cell layer Q) lat, pigmented lesions (3) _ junctional nevi develop into compound nevi compound nevus: (1) nevus cells extend into underlying superficial dermis (2) both a junctional and intradermal component (3) raised, pigmented, verruca-like lesions 234Note: This material is copyrighted. All rights reserved. (4) _ usually children/adolescents 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 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~ AL B, D, derive from melanocytes epidemiolog (1) affect both sexes equally @) more common in whites than African Americans 8) _ predilection for fair skinned, blue eyed persons with red or blond hair risk factors: (1) exposure to excessive sunlight at an early age single most important predisposing risk factor 2) Hx of severe sunburn @) dysplastic nevus syndrome (4) melanoma in first/second degree relative () _ xeroderma pigmentosum: AR disease with a lack of DNA repair enzymes (6) congenital nevus (7) lentigo maligna radial growth phase: (1) initial phase where melanocytes proliferate laterally within the epidermis, along the dermoepidermal junction, or within the papillary dermis (2) _ they do not metastasize while in this phase vertical growth phase: malignant cells penetrate into the underlying rei superficial spréading melanoma: (MC type (70%) @) _ primarily affects women >50 years of age (3) _ lower extremities/back MC sites (4) black, irregular, raised lesions (8) focal brown and/or red areas of discoloration (© _ foci of depigmentation and ulceration lentigo 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 nodular melanomas (15-30%): (1) lack radial growth phase (2) directly invade into dermis (3) _ poor prognosis, ‘acral lentiginous melanomas (2-89) (1) _ located on the palms/soles/subungual regions @) MC type in African Americans 3) WUSMLE tried to pass off a picture of a subungual hematoma for an a lentiginous melanoma sular dermis 235Note: This material is copyrighted. All rights reserved. J. 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 L. overall 5 year survival regardless of type is ~80% ‘© Acute intermittent porphyria (AIP): 1, porphyrin synthesis— A. drugs produce SER hyperplasia lead to a decrease in heme (part of cytochrome system): (2) barbiturates (2) alcoho! B. heme has a negative feedback on activity of 8-aminolevulinic acid synthase (rate limiting enzyme in porphyrin synthesis): see schematic C. drugs lowering heme, cause an increase in ALA synthase activity 2. enzyme deficiency 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 oc precipitates an acute porphyric attack clinieal- A, abdominal pain simulating acute abdomen: @) mistaken as a surgical abdomen 2) end up with a "bellyful of sears" B. _ intermittent exacerbations of neurologic dysfunction (psychosis (2) neuropathies (3) eventual dementia A. inorease 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 porphobilin B. increase in urine 5-aminolevulinic acid C. measure enzyme at any time A. _ periodic infusions of heme reduce the number of attacks B. avoid drugs that rev up the cytochrome system cutanea tarda (PCT): 1. acquired disease A. decreased activity of uroporphyrinogen decarboxylase: see schematic B. net result: (2) _ increased excretion of uroporphyrin I (urine is wine-red color on voiding) (2) slight increase in the formation of coproporphyrins (3) normal porphobilinogen levels 2. elinieal- A. _ photosensitive bullous skin lesions B. _hyperpigmentation 236Glycine + succinyl CoA | ALA synthase (rate limiting) 3-Aminolevulinie acid J ALA dehydrase Porphobilinogen > Porphobilin (color) raseey anton Uroporphyrinogen I | Uroporphyrinogen synthase (1 in AIP) ‘ Coproporphyrinogen I Uroporphyrinogen III Uroporphyrinogen decarboxylase ({ in PCT) Coproporphyrinogen IIT ‘ Protoporphyrinogen IX + Protoporphyrin IX + iron | Ferrochelatase Heme 4A Heme = ¥ ALA synthase activity Heme = 4 ALA synthase actiNote: This iaterial is copyrighted. All rights reserved. C. fragile skin D. increased amounts of vellus type hair (hypertcichosis) E. can be precipitated by alcohol Alopecia: 1, genetic predetermination MCC- MC in males 2. telogen effluyium- when all the hairs enter the resting phase at once ‘A. ~ postpartum B. birth control pills C. high fever D. crash diet ‘7 Irregular patches of hair loss in child: 1. trichotillomania 2. pulling out of one’s own hair 3. relationship to the dominant hand @ USMUB'SeHFIG? patient has hyperpigmented spots on the skin which when scratched become intensely pruritic and red 1, patient hasweticaria,pigmentosa. 2. masticelldisease— pressure causes the release of histamine setting up an urticarial reaction Questions used during the board review: A S2-year-old man with congestive heart failure develops cough and swelling in the deep subcutaneous tissue. He is most likely taking... a thiazide diuretic an ACE inhibitor a phenothiazine digitalis calcium channel blocker B (mechanism is the release of bradykini) '‘F 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 (IM. canis is Woods lamp positive, MCC of tinea capitis) room> FA 43-year-old woman presents with joint pains and a butterfly-like rash on the face. She is most likely taking, A. thiazides B. oral contraceptives C. hydralazine D. doxycycline E. barbiturates C (procainamide is another drug that is associated with drug-induced SLE)Note: This material is copyrighted, Ail rights reserved. 7 A 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 history of abdominal pain an increase in -aminolevulinie acid in his urine an increase in porphobitinogen in his urine colorless urine during these attacks a decrease in red blood cell uroporphyrinogen decarboxylase E (porphyria cutanea tarda) wo A3 roow> -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 increase in coproporphyrin C. be positive for blood D. _ have an excess amount of urobilinogen E, turn port wine color after exposure to light E (acute intermittent porphyria)Note: This material is copy ighted. All rights reserved. Central Nervous System/Special Senses vo Increased intracranial pressure: 1. causes~ A. noncommunicating hydrocephalus (see below) B. space occupying mass (e.g., metastatic tumor) C. cerebral edema: (1) _ intracellular (hyponatremia, ischemia) (2) extracellular: increased vessel permeability from tumor, inflammation, trauma, or lead poisoning 2, clinical A. uncal herniation: (1) medial portion of the temporal lobe herniates through tentorium cerebelli @) 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 occipital lobe B. cerebellar tonsils into the foramen magnum: cardiorespiratory arrest Hydrocephalus: 1. definition increase in CSF volume with distention of the ventricles 2. CSF flui ‘A. primarily produced by choroid plexus in lateral ventricles—> B. exits the fourth ventricle through the foramina of Luschka and Ma; C. enters the subarachnoid space —> D. reabsorbed by the arachnoid granulations into the dural venous sinuses 3. communicating hydrocephalus~ A. open communication, of CSF between ventricles and subarachnoid space B. causes: (2) increased production of CSF: e.g., choroid plexus papilloma @) block in the reabsorption of CSF by the arachnoid granulations: e.g., scarring post-meningitis, noncommunicating hydrocephalus— A. obstruction to CSF flow out of ventricles B. causes: (1) stricture of the aquedust of Sylvius? MCC in newborns (2) “tumors in the fourth ventricle: e.g., ependymoma (3) Amold-Chiari syndrome (4) Dandy Walker syndrome () blockage of CSF flow out of foramina of Luschka and Magendie: eg., inflammation, blood clot C. (USMLE scenario: (1) gross of a colloid cyst in the third ventricle (2) round object in third ventricle and cause of non-communicating hydrocephalus jeal— newborns: ventricles dilate and enlarge the h endie-> \d circumferenceNote: This material is copyrighted. All rights reserved, B. adults’ (1) progressive dementia Q) gait disturbances (3) 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 to rupture of a previously closed tube: increase in maternal a-fetoprotein in serum or amniotic fluid- folic acid taken before pregnancy protects the fetus from these defects anencephaly: A. complete absence of the brain B. absence of the fetal adrenal cortex CC. frog-like appearance D. polyhydramnios spina 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 Ls-S; meningocele: spina bifida and a cystic mass containing dura and arachnoid, meningomyelocele: cystic mass including the spinal cord Syringomyeli 1. definition fluid filled cavity (syrinx) within the cervical spinal cord clinical may be acquired later in life from ischemia, inflammation or trauma cervical cord enlargement associated with Amold-Chiari syndrome neurologic deficits: (1) oss of ‘pain and temperature sensation: disruption of the crossed lateral spinothalamic tracts @) atrophy of intrinsic muscles of the hands: 3. destruction of anterior hom cells b. confused with amyotrophic lateral sclerosis (no sensory changes ALS) 3) burmhands and do not know it (USMLE) Armold-Chiari malformation: malformation associated with— 1. clongation of the medulla and cerebellar tonsils through the foramen magnum 2. hydrocephalus 3. platybasia 4. meningomyelocele 5. syringomyelia Dandy-Walker syndrome: syndrome includes 1. hypoplasia of the cerebellar vermis 2. cystic dilatation of the fourth ventricle 3. hydrocephalusthis material is copyrighted. All rights reserved. © Phakomatoses 1. 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 selero: A. ADdisease B. clinical: Q) mental retardation @) skin lesions: a. adenoma sebaceum b. _ shagreen patches that are hypopigmented (USMLE) €. _periungual fibromas a, hamartomas: ‘* proliferations of astrocytes located in subependymal portions brain —> "candlestick drippings" within the ventricles angiomyolipomas in kidneys (3) thabdomyoma in the heart (USMLE) ‘Infections of the CNS: 1. general comments~ A. secondary to: (1) hematogenous spread (MCC) 2) traumatic implantation (3) _ local extension from nearby infections (4) _ ascent up the peripheral nerves: rabies (5) ascent up olfactory bulb: herpes types: GQ) leptomeningitis: a. MCtype b. hematogenous (2) encephalitis: inflammation of brain (3) cerebral abscess leptomeningitis: (Q) acute purulent (bacterial) 2) lymphocytic (viral) @) chronic granulomatous types: a. primary TB b. systemic fungi symptoms associated with leptomeningitis: (1) fever (2) headache (3) nuchal rigidity: positive Brudzinski and Kernig's test (4) altered sensoriumNote: This material is copyrighted, All rights reserved. E.__CSF findings in bacterial/viral meningitis: see CSF characteristics | Bacterial | Viral Total Cell Coum | 1,000-20,000 celisiul | <1,000 celisful. 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 protein Increased Increased Gram Stain Frequently positive (sen- | Negative sitivity 75 to 80%) a 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 1 infections: hemorrhagic necrosis of the temporal lobes b. Herpes zoster ©. _ progressive multifocal leukoencephalopathy (PML) cerebral abscess: (1) adjacent focus of infection: b. middle ear fc. usually solitary (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 (#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. | Eastem equine encephalitis has the greatest mortality. Wild birds are the natural host. | Herpes simplex type | 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‘Note: This material is copyrighted, All rights reserved. E.__ CSF findings in bacterial/viral meningitis: see Table_ CSF characteristics | Bacterial Viral Total Cell Count | 1,000-20,000 cellsful. | <1,000 celisfuL Differential Count | >90% polys First 24-48 hours, neutrophils, then switches - to lymphocytes/monocytes after 48 hs. CSF glucose Decreased Normal: exceptions mumps, herpes. protein Increased [Increased Gram Stain Frequently positive (sen- | Negative Lo __| sitivity 75 to 80%) — — S/S 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 (5) _ intranuclear inclusions: a. HSV infections: hemorrhagic necrosis of the temporal lobes ] b. Herpes zoster ©. _ progressive multifocal leukoencephalopathy (PML) G. cerebral abscess | (adjacent focus of infection: a, sinuses b. middle ear } usualy solitary (2) hematogenous spread: a, cyanotic heart disease b. —_bronchiecta c. usually multiple 2.__ summary of viruses associated with CNS infections— Pathogen | Specific Organism __| Disease/Comments Viruses Enieroviruses (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, Eastem 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 halitis in infants. * _ encephali 242 Oe eceeeaeeeereRekBRBPRRBRRRBPRRRBRBRARRRKRKKRASRRAARERLNote: This material is copyrighted. All rights reserved. Pathogen | Specific Organism Disease/Comments Varicella/zoster Cranial nerve inflammation/Meningoencephali Cerebellar inflammation: Herpes zoster (latent virus) may involve the trigeminal (V) nerve with painful vesicular lesions (shingles) or the VIIth 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 staze 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 (human 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. Cytomegalovirus Encephalitis: MC viral CNS infection in AIDS. Intracytoplasmic and intranuclear basophilic inclusions. MC congenital infection in children (encephalitis with periventricular calcification),Note: This material is copyrighted, All rights reserved [Pathogen | Specific Organism | Disease/Comments ] Poliovirus Myelitis/Encephalitis: Enterovirus that specifically attacks lower motor neurons, particularly the anterior horn 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 can occur 25-35 ys later. Sabin vac SALK, is a killed vaccine. Cannot use live vaccine in an immunocompromised host (AIDS), but SALK = vaccine can be used 3. summary of bacteria, fungal and parasitic infections of the CN! Pathogen | Specific Organism Disease/Comments - Bacteria Neonatal meningitis (<1 | Meningitis; All the infections are maternally mth): * MCC is group B | transmitted. Group B streptococcus is MCC of streptococcus (Streptococcus | neonatal meningitis (£. coli #2, Listeria agalactiae), gram positive | monocytogenes #3). Group B strep may produce coccus, * E coli: gram| infection in the first week or up to 4 months negative rod, 2nd MCC, « | later. Womenshould-avoid. goat's milk-eheese Listeria monocytogenes, 3rd | taavaidListeriosis ine is live. McC 1 mth to 18 years of age: © | Meningitis: Hemophilus influenza was once the Neisseria meningitidis-| #1 cause before immunization against | 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 diplocaccus, #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 close contacts must receive rifampin to eradicate the carrier state. ‘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 @ complication of primary TB in children. | Associated with post inflammatory scarring with noneommunicating hydrocephalus. CSF has <500 cells/ul. (Iymphocytes/mononuclear cells), high protein (forms a pellicle), normal to low glucose levels, and very low chloride levels. Treatment: Systemic corticosteroids are frequently used along with the anti-tuberculous drugs to combat the vasculitis and the potential for strokes and hydrocephalus. A tuberculoma is a granuloma that most commonly locates in the cerebellum as a mass lesion.Note: This material is copyrighted. All rights reserved. "Specific Organism Treponema pallidum (@piro- chete) Pathogen Disease/Comments Myelitis/Encephalitis/Meningoencephalitis: 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. Meningovaseular: 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, Paretic form: has generalized atrophy (neuronal loss) of the frontal cortex (organisms present), dementia, and an Argyll-Robertson pupil. Tabes dorsalis: spirochetes attack the posterior root ganglia or their afferent sensory axons between the posterior root ganglia and the cord producin, impaired joint position sense leading to a broad based ataxia and a positive Romberg’s test (lose balance with eyes closed, but restore balance with eyes open), loss of pain and vibration sensation, joint damage (Chercot Joints), sensory disturbances with "lightening pains", 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 245 MeningitisiAbscess; MC systemic fungal infection in immunocompromised hosts (¢.¢., 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 abscess in diabetic ketoacidosis)Note: This materi is copyrighted. All rights reserved. [Pathogen | Specific Organism Disease/Comments Parasites Toxoplasma gondii (sporo- | Encephalitis: MCC of a space occupying CNS zoan) lesion in AIDS. Congenital toxoplasmosis produces basal ganglia calcification _| Plasmodium falciparum (spo- | Encephalitis: P. falciparum parasitizes large / rozoen) numbers of RBCS that block capillaries and produce small necrotic and hemorrhagie foci ! | usually within the cortex and cerebellum. | ‘Naegleria fowleri (free living | (Mewingoencephalitis (USMIB):\ Protozoal ! amoebae) infection contracted by swimming in fresh water lakes. Infects the frontal lobes through the cribriform plate Trypanosoma brucei gamb-| Encephalitis: Transmitted by tsetse fly. Diffuse ense or rhodesiense (hemo- | neuronal degeneration. Produces sleepi flagellate) sickness (die of starvation). Trypanosomes in the blood. IgM elevated Taenia solium (tapeworm) | Cyst formation/Meningilis: _ (Gystieercosis (WSMEB)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 (subcutaneous tissue, brain, eye, muscle) with cyst formation. Calcified cysts are frequent sites for Jacksonian seizures. Hydrocephalus may occur. 4. slow virus diseases of the CNS— Type Disease [Comments Son Conventional | Subacute sclerosing pan- | SSPE is associated with the measles (rubeola) virus Agent encephalitis (SSPE) either 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 ye Progressive multifocal | PML, due to papovavirus (JC virus, SV40 virus), | leukoencephalopathy | infects and destroys oligodendrocytes (intranuclear | (PML) inclusions) leading to primary demyelination. It is | commonly observed in immunocompromised patients _ (Alps), | 246Note: This material is copyrighted, AM rights reserved. Type | Disease ‘Comments jeagptwent-/ CreutzfeldcJakob (CH) CI presents as « rapidly prograsive demon A ‘onal Agent | disease (subacute spong- | subviral transmissible agent known ae prion Horm encephalopathy) "| (extracellular protein with no nucleic acid) bas rao identified. Transmitted by corneal transplantation, improperly sterilized cortical electrodes (neuron surgery), contaminated pituitary growth hormone (no longer used), or eating human brains (called kuru | confined to New Guinea head hunters). It is nor transmitted person to person and is a health hazard to 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 occurs within 1 yr 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 of the brain: (2) most commonly secondary to an acceleration-deceleration injury @) eg,, car accident B. contusions occurring at the site of impact are coup injuries - 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 of the frontal and temporal lobes 3+ diffuse axonal injury sheariig of axons located in the white matter tree in the brain and/or brain stem ‘meningeal tears— A. occur with basilar and orbital skull fractures B. frequently results in loss of CSF fluid through the nose (thinorrhea) and/or ears (ctorrhea) C. CSF has a lower protein and glucose and higher chloride than serum 5. acute epidural hematoma— A. definition: (1) fracture of the temporoparietal bone with severance of the middle meningeal artery (2) _ artery lies between the dura and inner table of bone B. initially unconscious but then becomes lucid G- _atterial bleeding creates a blood filled space between the calvarium and dura DP. intracranial pressure increases leading to herniation and death unless ane -* removed 6. subdural hematoma— A. definition: (2) collection of venous blood between the dura and the arachnoid m 247Note: 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 veins between venous sinus located over the convexities of the cerebral hemispheres (5) _ organized blood clot over convexity of brain B. fluctuating levels of consciousness €. CT scans best examination for demonstrating intracranial hemorthages in the first 48 hs: MRI is best after 48 hs Vascular injuries in the CNS: 1, neurons and neuroglial cells susceptible to oxygen deprivation (hypoxia) or hypoglycemia— A. neurons most sensitive in descending order: (1) hippocampus (2) cerebellum (Purkinje cells) @)_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) @) astrocytes a. blood-brain-barrier b. repair cell ©. analogous to fibroblast, except collagen is not produced (8) 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 (2) _ infarction due to liquefactive necrosis, C. intracerebral bleed (10%) (1) _ intracerebral hemorrhage most often due to hypertension (2) 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)Note: This material is copyrighted. All rights reserved. G. (1) _ usually in distribution of the middle cerebral artery (MCA) 2) _ pale infarct because there is usually no reperfusion 3) hemorrhagic if they do reperfuse (20%) microscopic: (1) _ reactive astrocytes (gemistocytes) proliferate at the margins of infarct @) _ microglial cells (macrophages of CNS) remove lipid debris 3) _ response to injury is called gliosis (4) cystic area after 10 days to 3 weeks majority preceded by transient ischemic attacks (TIAs) (1) due to embolization of platelet or cholesterol plaque material into the peripheral vessels — on — (2) _ results in transient neurologic deficits lasting <24 hours “> //ei.gs > @) deficits not resolving within 24 hours are called strokes fe//3,.4.., clinical manifestations of MCA occlusion: RY hts t ng (1) contralateral hemiparesis and sensory loss Peneliny Stroke @) 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 (A) visual field defects: a. contralateral inferior quadrantanopsia or b. homonymous hemianopsia (S) deviation of the head and eyes toward the side of the lesion vertebrobasilar arterial system strokes: (1) vertigo 2) ataxia 3) _ ipsilateral sensory loss in fave and contralateral hemiparesis and sensory loss in the trunk and limbs majority of patients survive and recover some function 3. embolic stroke~ A B. thromboemboli originating in left heart or plaque material from internal carotid MC associated with a hemorrhagic infarction in the distribution of MCA. (2) area of infarction usually limited to the gray matter at the periphery of the brain (2) hemorrhagic because of reperfusion of the occluded vessel (3) mortality ~30% 4. intracerebral hemorrhage- A B. G D. MC secondary to vascular changes related to hypertension: (1) vascular changes occur in penetrating branches of lenticulostriate vessels (2) formation of Charcot-Bouchard macroaneurysms—> @) rupture of aneurysms—> (4) _ intracerebral hemorrhage (clot, not infarct) locations: (1) _ basal ganglia (35-50% in the putamen) (2) thalamus (10%) (3) pons (10%) (4) cerebellar hemispheres (10%) 30-40% mortality effective Rx of hypertension has its greatest benefit in preventing strokes 249Note: This material is copyrighted. All rights reserved. 5. subarachnoid hemorrhages AL B. c majority secondary to rupture of a congenital berry aneurysm (80%): arteriovenous malformations less common cause patients (usually women) between the ages of 40~65 ys old congenital aneurysms: (2) absence of intemal elastic lamina and smooth muscle in the media of cerebral 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 hemod) b. presence of hypertension: ynamic stress or * essential hypertension * due to adult polycystic kidney disease * 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 clinical (1) sudden onset of severe occipital headache ("worst headache I have ever had") followed by a loss of consciousn (2) _ blood in subarachnoid space covers entire surface of brain (@) ~25% die from first bleed (4) _ additional 25-35% die by end of first year owing to rebleeds 6. — lacunar infarets— A small (<1 em) eystic spaces: represent areas of microinfarction secondary to: (1) _ hyaline arteriolosclerosis due to hypertension (MCC) (2) hyaline arteriolosclerosis due to diabetes mellitus pure motor strokes with or without dysarthria: posterior limb of internal capsule pure sensory strokes involve the thalamus ‘© Demyelinating disorders of the CNS: B. 2. multiple sclerosis (MS)- 1g disorders of the white mater refer only to those disorders that: directly attack myelin synthesizing cells: a. oligodendrocytes in the CNS: e.g, viruses b. Schwann cells in the PNS: e.g., osmotic damage in diabetes mellitus myelin sheet without destruction of the axon: e.g., multiple sclerosis, Guillain-Barré MC demyelinating disease: autoimmune destruction of the myelin sheath epidemiology (1) - slightly female predominant disease 2) _ targets patients between the ages of 20 and 40 ys @) disease may be triggered at an early age by exposure to a virus: ? herpesvirus 6 (4) HLA-DR, haplotype gross/micro: (2) demyelinating plaques located in the white mater of brain/spinal cord: white mater looks like gray mater 2) favored locations: a. surface of the optic nerves and optic chiasm b. cerebellar pedunclesNote: This material is copyrighted. All rights reserved. . brain stem d. angles of the ventricles (3) _ microglial cells with phagocytosed lipid (4) reactive gliosis (5) _ mild perivenular lymphoid (T cell)/plasma cell infiltrate D. clinical (1) episodic course punctuated by acute relapses and remissions 2) _ sensory and motor dysfunction: a. paresthesias b. weakness (3) optic neuritis a, blurry vision or sudden loss of vision b. MS is MCC of optic neuritis (4) cerebellar incoordination (ataxia) (©) nystagmus (6) _ intention tremor (bilateral internuclear ophthalmople; fasciculus (8) _ scanning speech: sound drunk CSF fluid findings: (1) lymphocytes (T lymphocytes) 2) elevated y-globulins @) normal glucose (4) oligoctonal bands: a. small bands in the y-globulin region noted on high resolution electrophoresis, b. indicative of demyelinating disease : demyelination of medial longitudinal ‘% Dysmyelination disorders (leukodystrop! 1. definition— A. genetic inborn errors of metabolism B. enzyme deficiencies that result in the synthesis of abnormal myelin (dysmyelination) in the white mater 2. adrenoleukodystrophy. A. SXR disease B. _ enzyme deficiency (2) accumulation of long chain fatty acids (2) brain (dysmyelination) (3) _ adrenal cortex (adrenal insufficiency) 3, metachromatic leukodystrophy- A. MC leukodystrophy B. AR disease C. deficiency of aryl 4. Krabbe's disease— A. AR leukodystrophy B. deficiency of galactocerebroside f-galactocerebrosidase accumulation of galactocerebroside in large multinucleated, histiocytic cells (globoid cells) in the CNS fatase A, 251Note: This material is copyrighted. All rights reserved. ‘© Alzheimer's disease (AD): ai 4. MCC dementia (~80%)~ A. multisinfaret dementia #2 B. Alzheimer's either presenile (<65 years) or senile (65 years) pathogenesis/associations— A. reduced acetylcholine levels: acetylcholine plays a role in learning B. aluminum toxicity €. chromosome 21 coding for an Alzheimer precursor protein (APP), part of which is amyloid- (A-B) protein: (1) toxic to neurons (2) association with Down syndrome (USMLE) D. apolipoprotein gene F, allele e4 located on chromosome 19 (1) produces a product that increases the neurotoxicity of the A-P protein (2) cause of familia! late-onset type abnormalities with chromosome 14: synthesizes a Tau microtubule protein located in neurofibrillary tangles gross/micro— ‘A. cerebral atrophy: (1) neuronal loss in temporal, frontal, parietal lobes (2) neuronal loss in: a, nucleus basalis of Meynert b. amygdala @ ¢. substantia nigra brain stem ©. hippocampus (3) _ neurofibrillary tangles: pairs of filaments coiled like a DNA helix (4) _ senile plaques: a, most important lesion b. contains a core of A-B amyloid surrounded by neurites (S) _granulovacuolar degeneration clinical— A. general impairment of higher intellectual function without any focal neurologic deficits B. MC COD in patients with Down syndrome that reach age 40 clinical diagnosis: confirmation at autopsy ‘2 Wdiopathic parkinsonism: definition— A. movement disorder B. degeneration and depigmentation of neurons in the substantia nigra and locus ceruleus C. deficiency of dopamine D. generally occurs in patients over 45 ys of age substantia nigra— ‘A. part of the striatal system involved in voluntary muscle movement: (Q) caudate @) putamen (3) _ globus pallidus (4) subthalamus (©) thalamusNote: This material is copyrighted. All rights reserved. dopamine is principal neurotransmitter of afferents in the nigrostriatal tract that connects the substantia nigra with the caudate and putamen neuronal loss with depigmentation and intracytoplasmic, eosinophilic bodies called Lewy bodies (example of ubiquination) 3. clinical~ A. extrapyramidal signs and symptoms (1) cog-wheel rigidity @) resting tremor (“pill rolling”) (3) bradykinesia: slowness of voluntary movement that is misinterpreted as weakness B. _ expressionless face C. stooped posture D. _ festinating gait: progressively shortened accelerated steps E. _ blepharospasm 4. Rx- replacement and prevention of reuptake and metabolism of dopamine 5. acquired causes of Parkinson’s disease A. postencephalitic Parkinsonism B. diseases that damage the basal ganglia (1) ischemia @) chronic carbon monoxide poisoning (3) Wilson’s disease (4) drugs: a. phenothiazines b. reserpine © MPTP, a meperidine analog that damages dopaminergic neurons ‘* Huntington's disease (HD): 1. AD trait with a delayed appearance of symptoms until » mean age of 35-45 years of age— A. atrophy and loss of striatal neurons: (1) *eaudate nucleus (i/ of caudate) @) putamen (8) _ frontal cortex B. triplet repeats of CAG on the short arm of chromosome 4 C. decrease in: (2) _y-aminobutyric acid (a false neurotransmitter) @) acetylcholine (3) substance P 2 ical chorea extrapyramidal signs dementia anticipation: (1) progressively worse disease in future generations (2) due to addition of triplet repeats @ Friedreich’s ataxia: 1. AR disease 2. degeneration of- A. spinocerebellar tractsNote: This material is copyrighted. All rights reserved. 4 B, posterior columns C. pyramidal tracts D. peripheral nerves 3. association with triplet repeats: anticipation 4. retinitis pigmentosum A. tunnel vision B. _ blindness Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease): 1. loss of upper motor neurons (spasticity) and lower motor neurons (muscle atrophy, muscle fasciculations)— A. some cases associated with a defect in the zinc/eopper binding superoxide dismutase (SOD;) on chromosome 21 B. oxygen free radical destruction of motor neurons 2. clinical A. atrophy of the intrinsic muscles of the hand and forearms with hand weakness: first sign B. spastic changes in the lower legs €. no sensory signs or bladder problems D. average survival 2-3 ys: respiratory failure MC COD 3. Werdnig Hoffmann’s disease~ childhood version of ALS Wilson's disease: 1, AR disease with a defect in copper excretion in bile 2. chronic liver disease at early age 3. decreased ceruloplasmin: 4. free copper deposits in— ‘A. lentiform nucleus (putamen and globus pallidus) B__Descemet’s membrane in the eye to produce Kayser Fleischer ring min Biz deficiency: 1, subacute combined degeneration of the spinal cord 2. posterior column and lateral corticospinal tract demyelination Alcohol abuse: 1. complications in CNS— A. cortical atrophy B. — Wernicke-Korsakoff's syndrome complex C. cerebellar atrophy: particularly Purkinje cells D. _ central pontine myelinolysis: demyelination discase associated with rapid correction of hyponatremia 2. Wernicke's encephalopathy~ A. thiamine deficiency acute onset of- () confusion Q) ataxia 3) nystagmus (4) ophthalmoplegia C. _ hemorthages with associated hemosiderin pigmentation: Q) ‘mamillary bodies (USMLE) @) third ventricleNote: This material is copyrighted, All rights reserved. (3) floor of the fourth ventricle (4) _ neuronal loss and gliosis involving these same areas 3. Korsakoff's psychosis— A. more advanced stage of Wernicke's encephalopathy B. targets the limbic system €. inability to form new memories (antegrade amnesia) or recall old ones (retrograde amnesia) © Tumors of the CNS and PNS: 1. risk factors— A. Turcot syndrome: only AR hereditary polyposis syndrome B. _ neurofibromatosis: (1) optic gliomas 2) meningiomas 8) acoustic neuromas (unilateral or bilateral) adult primary brain tumors~ A. 70% supratentorial B. _ order of decreasing frequency: (1) glioblastoma multiforme (high grade, malignant astrocytoma) (2) meningioma (benign) . @) acoustic neuroma (schwannoma, benign) (4) ependymoma in cauda equina 3. childhood primary brain tumors— A. 70% are infratentorial B. in descending order of frequeney they are: (2) cerebellar astrocytoma (benign cystic tumor) (2) medulloblastoma in cerebellum (malignant) (3) brain stem gliomas (4) ependymomas (fourth ventricle) 4. astrocytomas— A. ~70% ofall the neuroglial tumors B. _astrocytomas: grade I and IL are benign C. anaplastic astrocytoma: grade ITI and malignant D. _ glioblastoma multiforme: () grade IV and malignant (2) 40-70 yr old (3) # frontal lobes (4) commonly cross corpus callosum () _ arise de novo, or by malignant transformation of a lower grade astrocytoma (6) hemorrhagic tumors with multifocal areas of necrosis and cystic degeneration (7) hemorrhagic necrosis with pseudopalasading of neoplastic cells around areas of necrosis and vascular channels (8) seed the neuraxis (9) rarely metastasize outside the CNS E. Rx of astrocytoma: radiation oligodendrogliomas- A. benign tumor of oligodendrocyte B. frontal lobes of adults C. calcifications visible on x-ray (USMLE)Note: This material is copyrighted, All rights reserved 6. ependymomas~ ‘A. benign tumors: fourth ventricle in children B. MC intraspinal tumor in adults: (1) myxopapillary pattern (2) lumbosacral portion of the spinal cord (3) orientation of ependymal cells around vascular channels (perivascular pseudorosettes) (4) _ ependymal cells contain blepharoplasts 7. medulloblastomas~ A. MC primary malignaney of brain in children: second MC primary brain tumor in children B. malignant primitive neuroectodermal tumors: 2) arise in the midline of the cerebellar vermis from the fetal external granular layer (2) seed neuraxis @) _ invade fourth ventricle 8. meningiomas— A. MC benign tumor of brain in adults (1) arise from arachnoidal eells @) second MC primary brain tumor in adults 3) women > men B. associations (1)-> neurofibromatosis (2) deletions on the long arm of chromosome 22 3) _previous Hx of radiation C. locations (1) convexities of brain: parasagittal MC site 2) olfactory groove @) _ lesser wing of the sphenoid (4) _ spinal cord (thoracie segment) D. _ gross/micro: Q) 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 “psammoma bodies (calcified bodies): only benign tumor with psammoma bodies 9. CNS lymphomas- os A: MCC are metastatic high grade non-Hodgkin's lymphomas of B lymphocyte origin meningeal spread and spare parenchyma B. primary CNS lymphomas: (1) multifocal in their distribution 2) _ 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Note: This material is copyrighted. All rights reserved. 10. schwannomas (neurilemomas)— A. _ benign tumors derived from (1) cranial nerves @) spinal nerve roots )__peripheral nerves B, MC intracranial site is the cerebellopontine angle’ (1) _ involvement of the VIIIth eranial nerve: called C. acoustic neuroma: (1) tinnitus (MC symptom) (2) sensorineural deafness (3) _ sensory changes in trigeminal nerve distribution D. microscopic: (Q) "zebra tumor" @) compact Antoni type A areas interspersed with loosely structured myxomatous appearing areas designated Antoni type B areas E, (USMUE scenarios’ CT with enlarged intemal acoustic meatus in a patient with tinnitus, nerve deafness 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 Schwann cells: wustic neuroma microglial cells are the reservoir for HIV in the CNS 2. 2 primary CNS lymphoma~see previous discussion 3. aseptic meningi 4. encephaliti 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 vacuolar myelopathy ‘A. subacute combined degeneration of spinal cord B. similar to Biz deficiency but not due to By, deficiency 6. peripheral neuropathy ‘opportunistic infections— A. CMV: MC CNS virus B. _ toxoplasmosis: (1) MC parasite 2) 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” syndromeNote: This material is copyrighted, All rights reserved, B. _ axonal degeneration: muscle atrophy and fasciculations C. combinations of the two ‘A. diabetes mellitus: @Mec (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 = 2) _ pyridoxine 3. Guillain-Barré syndrome. A. MCC acute peripheral neuropathy: autoimmune demyelination syndrome B. _ presents with an ascending or descending paralysis C. high CSF protein levels + few lymphocytes D. _ Rx: plasmapheresis (USMLE) 4. Chareot-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- acute onset of unilateral facial nerve (VIIth nerve) paralysis HSV I may be implicated Lyme's disease if bilateral: Vilth nerve MC cranial nerve involved clinical: (1) drooping of the comer of the mouth 2) difficulty with speaking (3) _ inability to close the eye (4) drooling 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 F Menetrier disease: increased endolymph in inner ear dizziness vertigo sensory hearing lossNote: 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. allergic seasonal 2 Glaucoma: 1, increase in intraocular pressure fluid cannot exit canal of Schlemm 2. linical~ 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 oeclusion— polycythemia MCC 7 Uveitis! 1, inflammation of uveal tract (choroid, ciliary body, iris)— A. clinical: (pain @) blurry vision (3) _ severe photophobia (4) congestion of ciliary vessels around cornea (8) miotic pupils (© _ poor light reflex (7) _ normal pressures 2. veauses (USMLE)- ‘A. ankylosing spondylitis B. rheumatoid arthritis CC. sarevidosis D. juvenile rheumatoid arthritis © Optic neuritis: 1, inflammation of optic nerve 2. causes- 289Note: This material is copyrighted. All rights reserved. A. multiple sclerosis MCC B. methyl alcohol poisoning 3. clinical~ A. pain B. blurry vision CC. flame hemorrhages around nerve D. danger of optic atrophy: (2) cupping of disk margin 2) pale disk due to absence of disk vessels ‘® Macular degeneration: MCC of blindness in elderly ‘© 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 lateratization 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 Presbycusis: MCC of sensorineural hearing loss in elderly Otosclerosis: 1, MCC of conduction deafness in elderly 2. middle ear ossicles fuse © Otitis media: 1. MC conduction deafness in children pathogens in descending order: A. Streptococcus pneumoniae B. Hemophilus influenzae C. Moraxella catarrhalis 2, Rxwith amoxicillin Absence seizures: 1, abrupt onset of impaired consciousness (stare into space) 2. 34H 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 « - « « - « = é « - « = - é = - - - - « « = « « « = = = =Note: 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 Bi> deficiency B (Wilson's disease) roa year-old neuropathologist developed a rapidly progressive dementia and died. The pathogenesis of his disorder is related to. A. adecrease in acetylcholine levels, B. deficiency of dopamine C. neuronal damage by amyloid D. alow virus disease involving prions E. subacute sclerosing panencephalitis D (IK 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) ‘Which of the following represents a primary brain tumor that would more likely develop in a child rather than an adult? A. Glioblastoma multiforme B. Medulloblastoma C. Malignant lymphoma » D. Acoustic neuroma E, Meningioma B or An afebrile 52 year old smoker with weight loss, cough, and hemoptysis, develops a seve headache associated with unilateral lid lag, ophthalmoplegia, and mydriasis. An MRI reve: 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 hemiation E. _ cerebellar herniation into the foramen magnum D (patient has metastatic lung cancer to the brain)Note: This material is copyrighted. All rights reserved. F 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. B-amyloid protein B. lacunar infarcts C. decreased dopamine levels D. _aslow virus disease E. _ atriplet repeat disorder ‘A (classic Down syndrome-Alzheimer's disease question) ‘7 Recurrent episodes of blurry vision, scanning speech, and paresthesias is most closely associated with A. multiple sclerosis B. — Wemicke's encephalopathy C. 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/an. ependymoma medulloblastoma demyelinating disease meningioma acoustic neuroma E (sensory changes are due to VilIth nerve tumor in cerebellopontine angle impinging on the Vth CN) r roop> ‘A 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 a/an. ‘A. atherosclerotic stroke B. intracerebral hematoma C. embolic stroke D. glioblastoma multiforme E, AV malformation C (atrial fibrillation is the MC arrhythmia) © A 62-year-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 patient's clinical findings most closely relate to. A. amyotrophic lateral sclerosis B. atherosclerotic stroke C. pure motor stroke D. Parkinson's disease E, _ post-poliomyelitis syndrome D 262Note: This material is copyrighted. All rights reserved. © 4 30-year-old 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, CC. amyotrophic lateral sclerosis D. spinal cord tumor E, Bp deficiency ‘A (classic question between syringomyelia and ALS) © A 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 ° ® Which of the following is more often associated with Escherichia coli than Pseudomonas aeruginosa? Osteomyelitis from puncture wounds through rubber footwear Malignant otitis externa in a diabetic patient Pneumonia in an intensive care unit Death in a patient in a burn unit Meningitis in a newborn roopp 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. _ aneutrophil dominant cell count C.apositive VDRL D. spirochetes E, _ xanthochromia C (tabes dorsalis)Note: This materi is copyrighted, All rights reserved. Anatomy Questions: 1 Gap junction: 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 pla everted (calcaneovalgus-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 : where does sperm penetrate (zona pellucida) Where is metaphase IT 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 directet 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 Eye closed cannot open and eye deviated down and out: oculomotor nerve palsy; eye down and. in: trochlear nerve pals 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 mild lid 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) ar flexion, foot dorsiflexed and 264Note: This material is copyrighted, All rights reserved 28. Patient with bilateral lateral rectus muscle weakness: increase in intracranial pressure (classic sign; papilledema usually present) 29. Paralysis of upward gaze in an infant: hydrocephalus secondary to stenosis of the aqueduct of Sylvius (this is called Parinaud’s syndrome) 30, Multiple ocular motor nerve disorders: diabetes mellitus (common cranial nerve palsies from ‘osmotic damage to nerves) 31. Weakness of the quadriceps muscle and an absent knee jerk reflex: herniated Ls-L, disk 32, Pain in the hip and lateral quadriceps, numbness of the anterolateral leg and the webbed space between the great toe, 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 34. 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 Cs-Cs (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) 35. Patient has paralysis of the oculomotor nerve after a head injury: uncal herniation with compression of the Ilrd nerve (ptosis of eye, mydriasis) 36. Numbness of the thenar aspect of the hand: median nerve (carpal tunnel) 37. Wrist bone with greatest incidence of aseptic necrosis: navicular bone (scaphoid) 38. Supracondylar fracture: injury to brachial artery and median nerve; danger of ischemic contractures in forearm muscle (Volkmann's ischemic contracture) 39. Know the fetal circulation: ductus venosus and umbilical vein have the highest oxygen content 40. EM of alveolus with macrophage, type II pneumocytes (lamellar bodies [surfactant]) 41, EM of small bowel with microvilli on the surface 42. Histologic section of seminiferous tubule: identify cell that makes sex hormone binding globulin (Sertoli cell); Sertoli cell also synthesizes inhibin (negative feedback with FSH) 43. Know the bands in skeletal muscle: A band has myosin ATPase 44. Respiratory bronchiole: last airway structure with cilia 45. Terminal bronchioles: cilia but n6 goblet cells; site of obstruction in asthma, bronchitis 46. EM: know normal organelles in a cell~see picture in First AID for Boards 47. Know normal structures CT exams of the chest, abdomen, leg, arm, CNS 48. Voice hoarseness post thyroid surgery: injury to laryngeal nerve 49. MRI of orbit: find superior oblique muscle 50. MRI of abdomen: identify splenic artery above the pancreas 51. Chest x-ray: fluid in the costophrenic sulcus in CHF 52. Barium study of small intestine: need to know how to separate from large bowel; superior mesenteric artery supplies small bowel 53, 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 54. Neuroanatomy: emphasis on blood supply and lesions of the brainstem and cortex, all of the cranial nerves and their functions 55. MRI of the carotids with occlusion of the anterior cerebral artery: would effect the contralateral leg 56. Schwannoma in jugular foramen: weakness of palate/loss gag reflew/laryngeal paralysis (X), trapezius/sternocleidomastoid (XI), loss taste sensation posterior third of tongue (IX) 57. Weber syndrome: lesion of oculomotor nerve and UMN signs with a midline, midbrain lesion chronic 265Note: This materi 62. 63 64 65 66. 68. 69, 70. 71 72 is copyrighted, All rights reserved. Horner’s syndrome lion light reflexes with eye diagrams of pupils: one set is an oculomotor nerve lesion nd area of oculomotor nerve Frontal lobe lesion: affects personality Bitemporal hemianopsia: lesion at the optic chiasm; commonly a 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 knowing it: syringomyelia in cervical cord and involvement of crossed spinothalamies: syringomyelia C2 transection of fasciculus gracilis: effects vibration and fine touch of lower extremity only CN III 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 MRI of liver: had to identify the hepatic vein vessel emptying into the inferior vena cava 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 diagram of vertebra and sympathetic trunk; pick cervical sympathetic Urine draining from umbilicus in 4 day old: persistent urachal sinus Femoral neck fracture: bleeds into the capsule, may compromise medial femoral circumilex , posterior dislocations are most dangerous artery leading to avascular necrosNote: his material is copyrighted. 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Microbiology Questions: Mechanism of action of Streptococcus agalactiae (group B streptococcus): inhibits phagocytosis Cause of an immunodeficiency with a high IgM: defect in isotype switching Cyclosporine necessary in identical twin transplant—2why: there is still some dil MHC sites from crossover of chromosomes durisig 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 cells (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 deficiencies; must irradiate the donor blood to 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 (POR test) Staphylococcus aureus: protein A attaches to Fe receptor of macrophages, hence blocking opsonization of bacteria Proteus mirabilis: moves with flagella; urease producer C. diphtheria: toxin inhibits elongation factor 2 by ADP-ribosylation, hence blocking protein synthesis Mycoplasma pneumoniae: requires sterols Pneumonitis (larval transmigration) + ova in stools: Ascaris or hookworm; not Strongyloides (thabditiform larvae in the stool not eggs) Latex agglutination reactions: antibody to capsular antigens is attached to the beads Locations of eells 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 Tumbling motility, Gram positive rod: Listeria monocytogenes; invades mononuclear cell, 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 : transmitted by mosquito (Aedes aegypti; same mosquito as in yellow fever); “breakbone 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 River blindness: Onchocerca, bite of blackfly, do skin biopsy, ivermectin Rhinovirus: 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 in vagina: responsible for the acid pH Influenza vaccine: killed; ege-based Pruritic skin lesion in Gulf War veteran: cutaneous leishmaniasis due to bite of sandfly ce in 267Note: This material is copyrighted. All rights reserved. 34 37 58 59. 60. 61 62 63 64 Hib vaccine: antibody against capsular polysaccharide In addition to the normal childhood. immunizations, what additional immuni recommended in sickle cell disease and cystic fibrosis: Pneumococcus (Pneumovax is given after 2 years of age) Which live vaccine can be given to a patient with AIDS: MMR (MMR is given only because the natural infection for measles is worse than the one that potentially could happen with the attenuated virus) List the live vaccines: MMR, varicella, OPV, BCG, smallpox, and yellow fever List the polysaccharide vaccines: Pneumococcus and Hib (meningococ example) List the killed virus vaccines: influenza, rabies, SALK vaccine List the immunizations that are contraindicated in patients with anaphylactic reactions against eges: MMR, influenza, yellow fever List immunizations that are contraindicated in patients with anaphylactic reactions against neomycin: MMR, varicella (neomycin is used as a preservative) ‘errucoid lesion in lower extremity in a patient returning from South America: South American blastomycosis, yeast with a ships wheel appearance; North American blastomycosis bas wide based buds AIDS patient with 2 peaks in the natural history of his disease: p2: 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 Braton’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 inoidence of leukemia/lymphoma Part of a vaccine that is antigenic: polysaccharide capsule Person working with animal hides develops lung disease: Bacillus cmthrax (woolsorter's disease) Cryptococcus: evades host destruction via its polysaccharide capsule Child with anemia and diarrhea—? parasite: hookworm produces iron deficiency Lymphocutancous nodules in a rose gardener: sporotrichosis; treat with potassium iodide Elderly male smoker with non-productive cough, bacteria fails to grow on ordinary media (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 Hyperacute rejection of a transplant: ABO incompatibility or patient had anti-HILA antibodies against an HLA antigen in the graft, type Il hypersensitivity reaction HLA-A, B, C code for class I antigens: CDs cytotoxic T cells recognize HLA-D loci code for class I antigens: CD, helper T cells, macrophages recognize tions are influenza | vaccine is another 268Note: Tt 67. 68. 69. 70. ‘material is copyrighted. 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Graft ys host reaction: NK cell mediated; common in bone marrow and liver transplants; rash, Jaundice (necrosis of bile ducts), diarrhea, danger in T cell deficient patients Receptor for EBV: CD2, on B cells; polyclonal stimulator causing increased synthesis of immunoglobulins“ reason for hypergammaglobulinemia in AIDS; increased divisions increase risk for 8:14 and Burkitt'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, hemorthage, renal failure; viral RNA in lun tissue (PCR test) Blastomycosis: spores associated with beaver dams and inland water ways; broad-based-bud shipwheel appearing yeast is South American blastomycosis Impetigo: most commonly caused by group A streptococcus CDs: 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 26921, Note: This material is copyrighted, All rights reserved. Biochemistry Questions: Rate limiting reaction in cholesterol synthesis: HMG Co reductase Findings in PKU: mousy odor; tyrosine missing, hence it must be supplied in the diet, can diagnose by amniocentesis and finding the abnormal gene; eliminate phenylalanine from diet (Nutrasweet is aspartate and phenylalanine, so cannot use it) 1 cell disease: inability 10 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 fat in adipose Uncoupling agents (c.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, etc. 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 AA) 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: camitine (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 (.g. 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 acetylcholinestorase, 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 hepatocyte 270Note: This material is copyrighted. All rights reserved. 36. 37, 38, 39 40. 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: avetoacetate CoA transferase (a thiotransferase enzyme) in order to convert AcAc into acetoacetyl CoA. McArdles disease: absent muscle phosphorylase; increased glycogen in muscle; no increase in lactic acid after exercise Pregnant woman is a beer drinker-~what supplements does she necd: 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 alcohol syndrome and ‘would need folate; iron is not affected by beer drinking Insulin: key hormone of the fed state; glucagon: key hormone of the fasting state Mannose 6-phosphate: involved in transfer of dolichol (lipid) in the RER in the synthesis of O- linked glycosides Know all the lysosomal storage diseases: see Genetics notes; two SXR diseases are Fabry’s and Hunter’s syndrome Know alll the reactions involving NAD/NADH and NADP/NADPH: see Nutrition notes Major source of NADPH: HMP shunt; malate dehydrogenase reaction to a lesser extent; NADPH supplies reducing equivalents 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 Mechanism of ketoacidosis in DKA: increased [)-oxidation of fatty acids and production of acetyl CoA, which is used by the liver to synthesize ketone bodies Promoter location: linear gene drawing with labels: pick upstream location Energy source for protein synth P Isoenzyme with 2 genes, 4 subunits:,LDE HHHH Second messengers: atrial natriuretic peptide: cGMP, insulin: tyrosine kinase, nicotinic: ion channels; see Katzung/Trevor pharmacology for more second messenger relationships Best method of detecting relatedness of a new bacteria: restriction fragment length polymorphism Enzyme used for PCR: DNA polymerase Source of glucose in a brain in starvation: alanine (transaminated into pyruvate) Glutamine: most abundant amino acid, carries ammonia in nontoxic form ‘Tyrosine: thyroid hormone, synthesis of melanin, synthesis of neurotransmitters (dopamine, Nor, Epi), decreased in PKU (must supply tyrosine in diet) Glycine: inhibitory neurotransmitter blocked by tetanus toxin, synthesis of 6 aminolevulinie a in heme synthesis, synthesis of bile acids/salts 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 jcenzymes; 5 isotypes: LLLL, LLLH, LLHH, LHHH, id false neurotransmitters— reason why they are given for Rx 2Note: This material is copyrighted. All rights reserved, Pharmacology Questions: 1 10, IL 12 B 14. 2. 24 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 dilution 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) Mechanism of loop diuretic: blocks Na-K-2CI cotransport pump in the thick the renal medulla; also blocks calcium reabsorption Cyanide poisoning treatment: review in environmental pathology chapter; amyl nitrite and thiosulfate ‘Thrush: may be a complication of a corticosteroid inhaler 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 'P430 system in the liver: makes drugs water soluble Angioedema and renal failure: ACE inhibitor relationship 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 Allopurinol action in purine synthesis: blocks xanthine oxidase (schematic of purine metabolism 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) Yellow coloration of the skin that can be mistaken for jaundice chlorpromazine and arsenic produce a blue-gray color to the skin Diffuse erythema followed by separation of the skin (scalded skin syndrome or toxic epidermal necrolysis) -?drug: barbiturates, sulfonamides, phenytoin, NSAIDs Hair loss in a woman~drug: oral contraceptives (predictable side effect; estrogen causes hair to be at same stage of development; may also occur after delivery) 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) 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) Elderly woman on thiazides is most at risk for developing: gout ‘Tardive dyskinesia, malignant syndrome (sweating, hyperpyrexia, autonomic instability): neuroleptics 2 drug: quinacrine:Note: This material is copyrighted. All rights reserved. 46 47 48, 49. 50. 1 Antipsychotic drug requi defects) Nephrogenic diabetes insipidus—? drug: lithium for bipolar disturbances Drug contraindicated with MAO inhibitors: epinephrine Use of phentolamine: non-selective a-blocker that lowers blood pressure during surgery for a pheochromocytoma Mechanism of AZT: inhibits reverse transcriptase; produces a macrocytic anemia unrelated to folate/B 12 Treatment of Pb poisoning: BAL and EDTA Drugs involved in folate metabolism: phenytoin blocks intestinal conjugase (polyglutamate to monoglutamate, BCP blocks uptake of monoglutamate, methotrexate/TMP-SMX block dihydrofolate reductase Cromolyn sodium: stabilizes mast cell membrane preventing release of preformed mediators and release of prostaglandins/leukotrienes after the release reaction Methotrexate: blocks dihydrofolate reductase and the conversion of dihydrofolate to tetrahydrofolate Glucuronyl transferase in liver renders compounds water soluble Cyclooxygenase: aspirin inhibits irreversible, NSAIDs reversible Thromboxane A;: synthesized in platelet; vasoconstrictor and increases platelet aggregation, also a bronchoconstrictor Effect of proton blockers: blocks H'-K"-ATPase proton pump in parietal cell; not a receptor mediated event; Hz blockers: blocks Hz 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: blocks the prostaglandin receptor, which normally inhibits adenylate cyclase and cAMP production ‘Treatment of schistosomiasis and clonorchiasis: praziquantel 7-fold membrane spanning protein-? drug: propranolol a blocker Phase 3 clinical trials: double blind Ticlopidine: substitute for aspirin in preventing strokes, CAD if the patient is allergic to aspirin; causes neutropenia Drug induced SLE: procainamide and hydralazine Overdose of suecinylcholine: use acetylcholine blockers Finasteride: blocks 5-ct reductase, which converts testosterone into dihydrotestosterone, hence testosterone would increase proximal to the block and dihydrotestosterone would decrease; increases hair growth Flutamide, cyproterone, spironolactone: block androgen receptor, hence testosterone! dihydrotestosterone increase but have not physiologic effect, Ketoconazole: inhibits testosterone synthesis (suppresses adrenal steroid synthesis) Leuprolide: GnRH analogue, which when given in sustained fashion, inhibits FSH and LH, hence lowering testosterone and estrogen levels ACE inhibitors: increase in renin and ATI, but a decrease in ATI and aldosterone; aldosterone eventually increases, hence the addition of spironolactone to keep aldosterone suppressed increases longevity in CHF Arsenic poisoning: dimercaprol Chloroquine in treatment of malaria-malaria recurred-why?: exoerythrocytic/hepatic stage (eg, P. vivax, P. ovale); drug kills active disease but does not eradicate hepatic stage Primaquine in treatment of malaria: not good in the active stage but does kill the hepatic stage of P. vivax and ovale visual exal tion: thioridazine (also produces heart conductionNote: Th jaterial is copyrighted. All rights reserved. Dantrolene: reduces the release of calcium from the sarcoplasmic reticulum of skeletal muscle; antispasmodic drug; also used in treating malignant hyperthermia 53, 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 54. 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 (f-selective agonist; bronchodilator); albuterol may cause hypokalemia~ drives K" into cells 57. Acetylcholine breakdown: occurs in the synapse into choline and acetate by acetylcholinesterase in the cleft; products are recycled and not excreted 58. Know the graph of NOR/EPVisoproterenol and effects on blood pressure and heart rate, plus the effect of c;-blockers: see graph in Katzung/Trevor book 59. Amphotericin: disrupts cell membrane permeability; binds to ergosterol in the membrane 0. Ketoconazole: inhibits the metabolism of nonsedating antihistamines like Seldane leading to cardiac arrhythmias 61. Be very familiar with second messengers: see Harvey/Champe biochem book page 80 62. Opioid toxicity: naloxone (opioid receptor antagonist) 63. Opioids: no tolerance to miosis and constipation 64, Codeine: metabolized into morphine in small amounts owing to significant first pass metabolism ‘of morphine in the liver 65, Delirium tremens: use benzodiazepines 66. Lovastatin: inhibits HMG CoA reductase 67. Patent ductus arteriosus: keep open with PGE 68. Penicillin: (i-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 autolytic enzymes in the cell wall 69. Cephalosporins + aminoglycosides: synergistic effect of enhancing nephrotoxicity 70. Erythromycin: interacts with the SOS 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 71. Chloramphenicol: gray baby syndrome (dose related aplastic anemia) 72. Sulfonamides, dapsone: may precipitate hemolysis in G6PD deficiency 73. ‘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 74. Metronidazole: produces a disulfiram-like reaction 75. Fluconazole: treatment of esophageal candidiasis in AIDS 76. Ganciclovir: first drug used in treating CMV retinitis, the most common cause of blindness in AIDS; foscarmet is used if ganciclovir does not work 77. Cholinomimetic used in treating open angle glaucoma: pilocarpine, physostigmine 78. Dobutamine: inotropic (increase contractility) vasodilator (decreases afterload) that activates cul and B1>B2activity without much chronotropic effect: used in the treatment of shock (cardiogenic) associated with hypotension, hypotension associated with renal failure or CHF 274Note: This material is copyrighted. All rights reserved. 80. 81 Answer: D (children, unlike adults, do not commonly develop @ mixed metabolic a alkalosis. Rx is to perform gastric lavage and add activated charcoal and to produce an Dopamine: stimulates cardiac BI receptors, peripheral a-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 1 receptors 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 chloride ion channels (flumazenil blocks this effect by blocking the receptor for benzodiazepines and is the treatment of choice for benzodiazepam overdose) An elderly woman on thiazides is most at risk for developing A. diabetes mellitus B. gout C.arenal stone D. metabolic acidosis E. hyperkalemia 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 idosis and respiratory Ikaline 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, 85, 86. 88, 89. 90. Trazodone: second generation anti-depressant; inhibition of serotonin reuptake; sedation; may cause priapism retinitis pigmentosum may be a complication 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 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 (acetylcysteine treatment replaces GSH) Digitalis toxicity: treat with digoxin antibodies (FAB fragments) Cephalosporins: first generation: drug of choice for surgical prophylaxis in many cases; second generation: sinusitis (cefuroxime), mixed anaerobic infections; third generation: meningitis, GC (ceftriaxone) Cromolyn sodium in asthma: only for prophylaxis; blocks early and late asthmatic responses to allergensNote: This material is copyrighted. All rights reserved, 91. 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 D2 receptors Fever in a patient on a loop diuretic: 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 Antihypertensive and antiarrhymic drug that lowers blood pressure and inereases heart rate: calcium channel blocker, e.g., nifedipineNote: 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 2. Most effective nephron site for acid excretion: proximal tubule of the kidney 3. Nephron site for ADH effect: collecting tubule Nephron site for greatest generation of free water/most susceptible to ischemia: thick ascending limb in the medulla Compression of the thorax under water: produces a restrictive pattern on PFT Constriction of the efferent arteriole: increases the GFR and decreases renal plasma flow 7. Know Starling equation for GFR ml/min: GFR = Kf [(Poc - Pas) - Roc], where Kf = hydraulic conductance in ml/min. mm Hg or filtration coefficient in ml/min . mm Hg, Poc = hydrostatic pressure in the glomerular capillary in mm Hg (pushes fluid out of the capillary; e-g., +45 mm Hg; it is increased if the efferent arteriole is constricted and decreased if the afferent arteriole is, constricted), Pgs = hydrostatic pressure in Bowman's space in mm Hg (pushes fluid into the capillary; e.g., -10 mm Hg), and toc = the oncotie pressure in the glomerular capillary in mm Hig (brings fluid back into the capillary; e.g., -19 mm Hg); the net filtration is the 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: Toc, Which becomes increased [pulls fluid back into the glomerular capillary; using the above example-~ 10 + 45 - 38 = 0 net pressure]; it is the only factor that does not remain constant along the length of the capillary owing to differences in protein concentration; the high gc 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 (L GFR/4 RPF), constrict efferent arteriole increases FF (1? GFR/L RPF), increase plasma protein concentration, hence increasing gc, decreases the FF ( GFR/no change RPF); decreasing. plasma protein concentration, hence decreasing mec, increases the FF (7 GFR/no change RPF): constricting the ureter, decreases PBS, hence decreasing GFR and the FF without affecting RPF ( GERJno change RPF) > 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 uuspid 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, venodilation, 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 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 a chart form; increase in body temperature, vasodilatation of vessels in skin an