Liver

Question 1

Alcohol Liver Disease (Fatty Liver)

Answer 1

• Increased FA in blood w/increased synthesis of TAGs in liver
• Mico/Macro Steatosis _{^{(++ of TAGS in cytoplasm)}}
  
  • _{^{Fatty liver (reversible)-<u>Step 1</u>}}
  • _{^{<strong>Injury to Hepatocyte-<u>Step 2</u></strong>}}
• Alcohol abuse
• _{^{Excessive NADH by <u><strong>Alcohol dehydrogenase (P-450)</strong></u>}}
• _{^{Acetaldehyde>lipid peroxidation><u>Membrane injury</u>}}
• _{^{Shunting lipids towards lipid biosynthesis}}
• _{^{Increases Fat <u><strong>(Steatosis) </strong></u><strong>w/impaired Lipoproteins</strong>}}
• _{^{Increased peripheral catabolism of fats}}
• _Other Causes: _
• Diabetes mellitus _{<u>^{(fatty changes=Idiopathic Cirrhosis)}</u>}
  
  • _{^{Nonalcoholic Fatty Liver (macrovesicular steatosis)}}
• Hypoxia
• Steroid use
• CCl4 poisoning

Question 2

Alcohol Liver Disease (Hepatitis)

Answer 2

• Presents ater a drinking binge
• Neutrophilic rxn-Chronic inflammatory cell seen _{^{(Neutropilic leukocytosis)}}
• Mallory body _{^{(Intermidiate filaments)}}=Irreversible injury
  
  • _{^{Red, globular, Rope like}}
  • _{^{PMN found around <u>Mallory bodies (intracellular)</u>}}
  • _^AST>ALT
• Presentation:
• Hepatomegaly w/Fever
• Elevated Alkaline phosphatase, aminotransferase, Gamma-Glutamyl transferase
• Late stage (Cirrhosis):
• Micro & Macro nodular on surface of liver

Question 3

Alcohol Liver Disease (Cirrhosis)

Answer 3

• Chronic disease:
• Loss of vascular architecture
• Formation of “regenerative nodule”
  
  • _{^{<u>Micro=</u>Alcohol & Iron}}
  • _{^{<u>Macro=</u>Hepatitis & Wilson}}
  • _{^{<u>Mixed</u>=late stage alcohoics}}
  • _{^{Liver appears small/atrophy}}
• Fibrosis bands separating the regenerative nodule=”Bridging”
  
  • _{^{<strong>Dissaperance of Central vein</strong>}}
  • _{^{Use Trichrome staining ID excess collagen}}
  • _{^{Blood vomit due to esophageal varices}}
• Activation of Stellate cells & fibroblasts=_{^{Excess production of collagen (1&3)}}
  
  • _{<strong>^{<u>Space of Disse</u> = Loss of fenestration of sinusoids}</strong>}
• Other Causes=Hep C
  
  • _{^{<strong>MORE ALT than AST</strong>}}

Question 4

Cirrhosis-Hemochromatosis

Answer 4

• “Bronze Diabetes”
  
  • _{^{damage to beta cells}}
  • _{^{Hyperpigmentation}}
• Micronodular w/Kupffer & Hepatocytes Full of Granular brown deposits _{^{(Hemoseiderin)}}
• Can progress to Heptocellular Carcinoma
• Associated w/Cardiac failure
• Primary cause:
• _{^{Recessive disorder-<u>Mutation in C282Y gene on chromosome 6</u>}}
  
  • _{^{HFE Overexpression}}
  • ^{_{Prevents sensing of iron lvls in GI}}
• _{^{Loss of reg of intestinal absorption of Iron (OVERLOAD)}}
• _{^{Ferritin lvl >50g}}
• Secondary cause:
• _{^{Ineffective erythropoiesis <u>(B-thalassemia or megablastic anemia)</u>}}
• _{^{Long term transfusion}}
• _{^{Sideroblastic anemia}}
• _{^{Sickle cell}}

Question 5

Cirrhosis-Wilson Disease

Answer 5

• Excess Cu+ in tissue/organs
• Autosomal recessive-WD gene assoc w/Canlicular_{^{<strong><u> (liver transport)</u></strong>}}
• Areas affected:
• Liver-Necrosis, hepatitis, cirrhosis
• Brain-Putamen ^{_{(psychosis, chorea)}}
• Eye-Kayser-Fleisher ring
• Diagnosis:
• Ceruliplasmin Decrease
• Hepatic copper INCREASE
• Urine copper INCREASE
• Slit Lap test=Copper deposit on Descemet membrane _^(cornea)

Question 6

Cirrhosis-Alpha-1-Anti/trypsin

Answer 6

• Macro-Nodular
• Pan-lobular emphysema Lungs _^(inferior)
• Defective secretion of Alpha-1 from hepatocytes due to Misfolding (builds up hepato-toxic)
• AAT gene PiMM=Normal
• Homozygous PiZZ (Complete Def)
• PAS + stain of periportal area on liver
  
  • _{^{Shows large white areas w/<strong>Blue spots</strong>}}
  • _{^{<u><strong>Diastase</strong></u> removes glycogen=<strong>RED</strong>}}
• Liver tansplant = Host Vs Graft HEPATITIS _^(CMV)

Question 7

Cirrhosis-Portal HTN (Ascities)

Answer 7

• Ascities=500+ml of transudate in peritoneal cavity
  
  • _{^{Fluid thrill/Wave present}}
• Fibrosis=HTN high venous pressure w/increase in cap hydrostatic pressure
• Low production of albumin _{^{(liver damage)}}=low plasma oncotic pressure
• Leakage of hepatic lymph into peritoneal cavity _{^(transudate)}
• Renal retention of Na+/Water due to secondary hyperalsosteronism _^(HTN)

Question 8

Cirrhosis-Portal HTN (Portosystemic Shunts)

Answer 8

• Esophagus varices _{^{(bloody vomit)}}
  
  • Several prominent-_{^{dilated, dark blue, sub-mucosal BV}}
• Budd-Chiari syndrome=_{^{Veno-occulsive disease}}
  
  • _{^{Thrombosis of major hepatic veins due to <u>blood retention in liver</u>}}
  • _{^{<strong>Associated with smoking & OTC</strong>}}
• Veno-occlussive disease: _{^{Assoc w/chemotherapy followed by bone marrow transplant (weight gain w/hepatomegaly)}}
• Blood in GIT=accumulation of Ammonia
• Rupture=GI bleeding
  
  • _{^{Caput medusa}}
  • _^Hemorrhoids
• Hypersplenism:
  
  • _{^{Sequestration of WBC, RBC, platelets}}
  • _{^{Hyperplasia w/<em><strong>NORMAL</strong></em> cell morpholog}}y

Question 9

Viral Hepatitis

Answer 9

• Hep B-Enveloped dsDNA _{^{(carrier state)}}
• _{^{Transmitted parenteral or close contact (<u>sex or needles)</u>}}
• Increase in Heptocell Carcinoma_{^{<u><em> (Alpha-feto marker)</em></u>}}
• _{^{Hep E + = Super infection <u>(LARGE increase in ALT/AST)</u>}}
• _{^{Tumor cells arranged in nests w/central lumen (bile)}}
• _{^{dense bundles of collagen <strong><u>(PAN assoc)</u></strong>}}
• _{^{10% turns chronic w/HEP E}}
• HEP E- Indian/hispanic pt oral-fecal route Fulimant liver failure (mortality in pregers)
• HEP A- Assoc w/food or water contamination _{^{<u>(NOT chronic)</u>}}
• Clinical:
• Diffuse granular cytoplasm _{^{“Ground glass hepatocytes”}}
• Bridging fibrosis _{^{(chronic)= more common<u> HEP c</u>}}
• Ballooning degeneration w/apoptosis _^(Acute)
  
  • _{^{Massive necrosis}}
  • _{^{Fever w/ALT increase}}
  • Councilman bodies _{^{(extracellular)-Apoptosis}}
• Broad scar w/Macro nodular

Question 10

Hepatic Failure

Answer 10

• Loss of fnx due to massive necrosis or chronic liver cell degradation
• _{^{Massive hepatic necrosis <u>(Wilson, Hepatitis, Drugs)</u>}}
• _{^{Acute fatty liver due to pregnancy <u>(necrosis)</u>}}
• _{^{Palmer erythema & Gyenecomastic <u>(Decreased detox/removal</u>)}}
• _{^{<em><strong>Hypoalbuminemia</strong></em> <u>(decreased production of albumin)</u>}}
• Appearance:
• _{^{Spider telangiectasia <u><strong>(several locations)</strong></u>}}
• _{^{Fetor hepaticus<strong> (musty smell of body) </strong>due formation of mercaptans <u><strong>(Thiols)</strong></u> from methionin in <u><em><strong>GIT</strong></em></u>}}
• _{^{Encephalopathy due to}} Hyperammonenmia
  
  • _{^{Massive GI bleed same presentation}}
• _{^{Impairs neural function (asterixis/Tremor)}}
• _{^{Cerebral edema><strong><em><u>Sudden death</u></em></strong>}}
• _{^{Decreased Coagulopathy DUE to decreased production of 2, 7, 9, 10}}
  
  • _{^{<strong>Cause sudden death</strong>}}
  • _{^{<strong>Prolonged PT, PTT</strong>}}

Question 11

Hepatorenal Syndrome

Answer 11

• Impairment of kidneys in chronic liver disease ^_(cirrhosis)
• Lowered renal perfusion due to _systemic vasodialation _
• Clinical:
• Drop in unrine output
• Accumulation of BUN & Creatinine
• Kidney fnx improves w/Liver improvement

Question 12

Neonatal Jaundice

Answer 12

• “extra hepatic Biliary Atresia”
• Complete absence of extra hep tree _{^{first 3 months of life}}
• Linked to neonatal hep=Giant cell of hepatocytes
• Assoc w/cong heart disease & Volvulus
• Clinical:
• Liver appears “stony” due to fibrosis
• Dark green color due to cholestasis
• HIGH elevation of Alkaline phosphatase
• Increased DIRECT bilirubin (6-12mg/dl)
• Neonatal Hepatitis: 2 week presentation w/failure to thrive, portal tract infiltrates (giant cells)

Question 13

Primary Sclerosing Cholangitis

Answer 13

• Inflammation & fibrosis around bile ducts
  
  • _{^{Onion skin thickening}}
• Segmetal dilation of intrahepatic & extrahepatic bile ducts _{^{(Beaded column)}}
• Associated w/Ulcerative colitis linked to colon cancer
• Increased risk of cholangiocarcinoma
• _{^{Inflammation assoc w/<strong>underlying Autoimmune</strong> (ulcerative colitis)}}
• Lab values:
• Increase of alkaline phosphatase
• P-ANCA _{^{(ulcerative colitis)}}
• Increase in IgM
  
  • _{^{Hypergamaglobulinemia}}

Question 14

Primary Biliary Cirrhosis

Answer 14

• Primary-Autoimmune(Anti-mitochon-Ab)
• Granulomatous-Non suppurative
• _{^{Cond where immune system CAN not form reactive O2 species}}
• _{^{Pruritis, fatigue, xanthomas}}
• Appears green nodular/Atrophy of liver
  
  • _{^{Destruction of intrahepatic bile ducts}}
  • _{^{Epi cells, <u><strong>lymphocyte</strong></u>, plasma cells, eosinophilic infiltrate}}
• Lab Increase in-
• _{^{Conj hyperbilirubinemia}}
• _{^{Alkaline phosphatase <u>(cholestatic pattern of liver disease)</u>}<strong> VERY HIGH</strong>}
• _{^{Antimitochondrial Ab}}
• Associated w/-
• Sicca syndrome _{^{(Sjogrens)=ANA w/SSA&B}}
• Scleroderma _{^{(Thickening of epi-HTN)-ANA wSCL70}}
• Rheumoatoid arthritis _{^{(high RF & secondary amyloidosis)}}
• _^SLE

Question 15

Secondary Biliary Cirrhosis

Answer 15

• Causes:
• Bile duct obstruction (chronic)
• Stone in common bile duct
• Tumors of biliary tree OR head of pancreas
• Children=Biliary atresia or CF
  
  • _{^{Failure to form Gallbladder}}
• Appearance:
• Scarring
• very dark green liver
• All features of cholestasis

Question 16

Bilirubin Metab

Answer 16

• Product of RBC lysis=Heme + Globin
• Heme=Unconj bilirubin + Iron
  
  • _{^{Iron in center of Heterocyclic ring}}
  • _{^{Hemo oxygenase (HMOX)><strong>Biliverdrin 4</strong>}}
  • _{^{Biliverdin reductase><strong>Bilirubin 4</strong>}}
• Too much RBC lysis = ++ Unconj bilirubin
  
  • _{^{Extravascular hemolysis}}
• Acute inter prophyria: Involved w/biosynthesis of HEME
  
  • _{^{Def in porphobilinogen deaminase}}
  • _{^{CNS symp (sympathetic)}}
  • _{^Hepatomegaly}

Question 17

Jaundice (Extravasular Lysis)

Answer 17

• Yellow discoloration of skin & scelra _^(icterus)
• Bilirubin lvls rise above 2-2.5 mg/dL
  
  • _{^{Lvls high as 30-40 in severe cond}}
• Cause:
• Excessive production of bilirubin _{^{(RBC lysis)}}
  
  • _{^{Unonj bilirubin=Urobilinogen}}
• Megaloblastic anemia:
  
  • _{^{higher indirect than direct}}
  • _{^{Pigmented bile stone <u>(gallbladder)</u>}}
• Erythroblastosis fetalis (Rh/Anti-Rh):
  
  • ^{_{Mother Rh(-) & Baby Rh(+)}}
  • ^{_{Ab IgG cross placenta}}
  • ^{_{Splenic sequestration (RBC lysis)}}
• Jaundice
  
  • _{^{Decreased UGT1A1 activity}}
  • _{^{Kernicterus @ basal ganglia}}
  • _{^{Treat w/phototherapy}}

Question 18

Issues w/UGT1A1

Answer 18

• Crigler-Najjer syndrome:
• Complete lack of bilirubin UGT1A1
• FATAL-death w/in 18 months
• Autosomal recessive
• Type 2:
• Partial defect of UGT1A1
• Deep yellow skin
• Total bilirubin (3-6 mg/dl)
• Treat: Phenobarbital _{^{(improves glucoronidation)}}
• Gilbert syndrome:
• Decreased expression of UGT1A1
• Common/Benign condition
• Jaundice occurs during STRESS w/unconj hyperbilirubinemia

Question 19

Jaundice (Conj. Hyperbilirubinemia)

Answer 19

• Overall Decreased hepatocellular excretion
  
  • _{^{Bilirubin glucoronides (conjugates)}}
• *Dubin-Johnson=Dark Red liver*
  
  • Dark urine
• *Rotor=NO discoloration*
  
  • _{^{Def of canalicular membrane transporter}}
• Durg induced = _{^{Oral contraceptive pill or Cyclosporin}}
• Hepatitis-systemic infection:
• ALT > AST
• Elevation in BOTH indirect/direct _{^{<u><strong>(more Direct)</strong></u>}}
• Obstruction:
• Impaired bile flow (intra/extra hepatic)

Question 20

Jaundice (Obstruction)

Answer 20

• Post/Extra Hepatic causes:
• _^Gallstone
• _{^{Carcinoma head of pancreas <strong><u>(palpable GB)</u></strong>}}
• _{^{Extra-hepatic biliary atresia}}
• _{^{Primary sclerosing cholengitis}}
• _{^{Liver fluke <strong><u>(Clonorchis Sinenesis)</u></strong>}}
• _{^{Bile duct tumor}}
  
  • _{^{++Conj bilirubin in blood}}
  • _{^{++in urine (dark)}}
  • _{^{Pale stool (mal-absorb of Vit A,D,E,K)}}
  • _{^{Green liver}}
• Intra Hepatic:
  
  • _{^{Drug induced (<u><strong>chlorpromazine</strong></u>)}}
• Destruction of intrahepatic bile duct:
  
  • _{^{Primary scleorosing cholengitis}}
  • _{^{Primary biliary cirrhosis (auto-immune)}}
  • _{^{Graft Vs Host 5-15 days after}}

Question 21

Cholestasis

Answer 21

• Bile cannot flow from liver to duodenum
• Intracellular bile pigment ++ in hepatocytes & bile ducts=Obstruction
  
  • _{^{Major feature of OBSTUCTIVE jaundice}}
  • _{^{Linked to CF pts<u> (panacinar atrophy iselts of lang)</u>}}
• Presents:
• Skin pruritis
• Skin Xanthomas
• Increase in alkaline phosphatase
• Apoptotic cells seen
• Kupffer cells contain regurg bile pigments

Question 22

Choleithiasis (Gallstones)

Answer 22

• Cholesterol stone-_{^{Most common}}
• Made of ^{crystalline cholesterol monohydrate}
• Stones are radiolucent _{^{(not seen in X-ray)}}
• Bile SUPERsaturated w/cholesterol
• Hypo-motility of GB=Stone formation
• Pigment stone:
• Made of-Bilirubin, Ca+2, salts, mucin
• Black = strerile bile _{^{(Conj bile)}}
• Brown = Gram - bacterial infection
  
  • _{^{E. coli}}
• _{^{Pt=white obese women over 50 can present w/no underlying symptoms finding stone}} “Incidental finding”
• High risk:
• _{^{Hyperlipidemia}}
• _{^{Estrogen (<strong><u>Oral contraceptive)</u></strong>}}
• _{^{Obesity or RAPID weight loss}}
• _{^{Extravascular Hemolysis <u><strong>(Sickle cell)</strong></u>}}

Question 23

Choleithiasis (Gallstones)-Clinical

Answer 23

• Acute calculus cholecystitis w/stones
• Obstruction in Cystic duct _{^{(Inflammation of GB)}}
• _{^{Pain RUQ, fever, nausea}}
• _{^{Layered w/fibrinous exudate (<u><strong>thickening of wall</strong></u>)}}
• _{^{Subsides in 7-10 days}}
• Choledocolithiasis _{^{(Stones in GB migrate)}}
• _{^{Obstructive Jaundice}}
  
  • ^{_{Stone in CBD=Non-palpable GB}}
  • _{^{Carcinoma head of Pan-Quick onset w/Palpable GB}}
• _{^{Acute cholengitis (E.coli)}}
  
  • _{^{Same presentation BUT with <strong><u>Jaundice</u></strong>}}
• _{^{Def of Vit A, D, E, K}}
• Choleithiasis (stones IN GB)
• _{^{Acute pancreatitis (stone in pancreatic duct)}}
• _{^{Increases risk of carcinoma of GB}}
• _{^{Gallstone ileus-GI obstruction}}
• _{^{Stones can be <u><em>silent for years</em></u>}}
• _{^{<em><u>Colicky pain-</u></em>Spasmodic RUQ pain}}

Question 24

Choleithiasis & Crohn’s

Answer 24

• When terminal ileum involved
• Loss of bile = Stratorrhea
• Increased Blie acid wasting:
• Free cholesterol Increase=Crystals
• Bowel fat + Intraluminal Ca+2
• No Ca+2 to combine w/Oxalate
• Oxalate absorbed=Kidney stone
• Development of mixed stones