Block 2 (Part 1-Liver)

Question 1

Liver anatomy

Answer 1

spans 5th intercostal to costal margin
right lobe is 70%, separated by falciform ligament (and round ligament=umbilical vein)
Portal triad= portal vein, proper hepatic artery, common bile duct
Caudate lobe superior to quadrate lobe
Common bile and pancreatic ducts enter 2nd duodenum with sphincter of Oddi

Question 2

Liver lobules

Answer 2

Classic lobule= endocrine= central vein in the middle, with portal vein, hepatic artery, and bile duct around it with sinusoids(fenestrated)/space of disse in between
Portal lobule= exocrine= triad in the middle
Hepatic acinus= four sided with two triads and two central veins
Kupffer cells= phagocytic, line sinusoids
Stellate cells= in space of disse, causes damage

Question 3

Gall bladder effect on bile

Answer 3

gall absorbs water, Na, Cl, HCO3

concentrates everything else

Question 4

Cholecystokinin (CCK)

Answer 4

fatty foods in duodenum cause release
stimulates gall bladder contraction and relaxation of sphincter of Oddi
acts on acini in pancreas to produce enzymes

Question 5

Secretin

Answer 5

acts on duct epithelium to produce bicarbonate rich solution to neutralize acids

Question 6

Pancreatic proteins (protein)

Answer 6

Trypsin, chymotrypsin, carboxypolypeptidase
all secreted in inactive form, activated by enterokinase or trypsin
Also trypsin inhibitor prevents activation until intestine

Question 7

Pancreatic proteins (carbs and fats)

Answer 7

carbs: amylase
fats: pancreatic lipase (micelles)

Question 8

Heme catabolism

Answer 8

Macrophage: heme ring opened- biliverdin- bilirubin
Blood: albumin carries to liver
Liver hepatocytes: bilirubin conjugated (UGT1A1) (also can bind with Ligandin in the cells) with glucuronic acid- excreted (MOAT)
GI tract: converted by bacteria to urobilinogen
Kidney: conversion to urobilin, excreted

Question 9

Lab test for serum bilirubin

Answer 9

van den Bergh assay
conjugated is water soluable, methanol is added to get total, unconjugated is calculated
direct=conjugated,, indirect=unconjugated

Question 10

Neonatal jaundice

Answer 10

low activity of UGT1A1 at birth (somewhat normal, but can be worse)
unconjugated
if bad, can cause Kernicterus (brain damage)
Tx: phototherapy

Question 11

Inherited unconjugated hyperbilirubinemia

Answer 11

all due to UGT1A1 mis-expression, all autosomal recessive
Crigler-Najjar I: absent (bad)
“” “” II: markedly reduced (can be benign or bad)
Gilbert Syndrome: reduced (benign)

Question 12

Inherited conjugated hyperbilirubinemia

Answer 12

both rare, defects in bilirubin secretion
Dubin-Johnson: MOAT defect
Rotor syndrome: unknown

Question 13

Other causes of jaundice

Answer 13

hemolytic: increased unconjugated
Obstructive: increased conjugated
Hepatocellular: increased unconjugated

Question 14

Bile acids

Answer 14

synthesized by cholesterol in liver
secreted into bile canaliculi
emulsifying agents, facilitate fat-soluble vitamin absorption
Primary bile acids are converted to secondary by bacteria in the gut
Bile acid+ glycine or taurine conjugation= bile salts (more soluble)
Most recycled by enterohepatic circulation

Question 15

Normal liver lab values

Answer 15

AST: 10-45
ALT: 8-40
Alk Phos: 40-129
Total Bili: 0.2-1
Direct bili: 0-0.2
INR: 0.9-1.3
Albumin: 3.5-5
GGT: 0-50

Question 16

ALT (SGPT) and AST (SGOT)

Answer 16

located in hepatocytes (AST in cytoplasm and mitochondria, ALT is cyto only)
elevated in hepatocellular damage
both use PLP as cofactor (ALT more sensitive)
ALT is more specific for liver
AST can be elevated in MI
AST:ALT more than 2:1 is alcoholic liver
ALT more than AST = viral hepatitis

Question 17

Alkaline Phosphatase

Answer 17

located on surface of liver cells adjacent to bile canaliculi
elevated in biliary obstruction or cholestasis
check GGT to verify liver origin
is also elevated in increased osteoblastic activity in bone

Question 18

Bilirubin

Answer 18

product of blood cell breakdown
Conjugated increased in: liver injury, bile duct probs, rare metabolic probs
Unconjugated increased in: hemolysis, Gilbert’s

Question 19

Albumin and INR

Answer 19

Indicators of liver synthetic function

INR is better unless other clotting issues

Question 20

Hepatocellular damage DDX

Answer 20

alcohol
viral hepatitis
autoimmune hepatitis
hemochromatosis
Wilson's dx
fatty liver (steatosis)
a1-antitrypsin def
drugs

Question 21

Cholestasis/Obstructive DDX

Answer 21

stones
strictures
pancreatitis
primary biliary cirrhosis (PBC)
primary sclerosing cholangitis (PSC)
drugs
tumors
(viral hep, alcoholic liver)

Question 22

Inflammation grade and Fibrosis stage

Answer 22

Inflam grade: 0-4

Fibrosis stage: 0-4,, none, portal, periportal, septal/bridging, cirrhosis(nodules)

Question 23

Hepatic necrosis

Answer 23

acute cell death
can lead to acute liver failure
causes: acetaminophen, viral Hep (NOT HepC)
Fulminent liver failure= acute liver failure + coagulopathy +encephalopathy

Question 24

Alcoholic Liver Disease

Answer 24

normal- fatty liver- alcoholic hepatitis (IL8, inflammation)- cirrhosis(fibrosis)
AST/ALT more than 2-3, ALT<300
usually not increased alk phos
macrocytic anemia, in end stage has increased INR, thrombocytopenia
Tx: abstinence, nutritional support,, glucocorticoids, pentoxifylline (anti-TNFa)
Treat IF: 4.6(PT-PTc)+TBili is more than 32

Question 25

Ethanol metabolism (and consequences)

Answer 25

Ethanol - alcohol dehydrogenase - acetaldehyde - aldehyde dehydrogenase - acetic acid or: Alcohol - CYP2E1 (MEOS) - acetaldehyde Increased NADH: inhibits TCA cycle, reduced fatty acid oxidation Increased acetaldehyde: activated stellate cells in space of disse to form collagen, Kuppfer cells produce TNFa, microfilaments sheared (bubble cells)

Question 26

Non-alcoholic Fatty Liver Disease (NAFL)

Answer 26

most common cause of elevated transaminases histo looks like alcoholic Steatosis without inflammation or cell injury risks: metabolic syndrome: obesity, high fasting glucose, hypertriglyceridemia,, age, males, hispanics Tx: weight loss, vitE, pioglitazone

Question 27

Non-alcoholic Steatohepatitis (NASH)

Answer 27

Worse version of NAFL | Steatosis WITH inflammation and hepatocellular injury (ballon heatocytes)

Question 28

Hereditary hemochromatosis

Answer 28

mutant HFE gene - C282Y, autosomal recessive HFE regulates absorption of iron from small intestine,, if defective, fails to down-regulate transferrin- Fe is over-absorbed iron deposits- free radicals risks: european present: liver fxn abnormalities, skin hyperpigmentation, diabetes, weakness, etc All occurs later in females bc menstruation Tx: phlebotomy

Question 29

Wilson Disease

Answer 29

autosomal recessive Copper underexcretion acute liver failure + neurological/psychiatric probs Low ceruloplasmin, high urine copper get Cu deposits (Kayser-Fleischer rings in eye) Tx: Trientine, Zinc, Penicillamine (chelators)

Question 30

a1-antitrypsin deficiency

Answer 30

A1AT inhibits elastase, is made in the liver most common genetic liver dx in kids in adults, can cause hepatitis, cirrhosis, and emphysema autosomal co-dominant (M is normal, S and Z are not),, PiZZ causes lung and liver dx Lungs: loss of fxn, proteolytic damage to connective tissue- emphysema Liver: gain of fxn, A1AT Z not secreted, triggers hepatotoxic events

Question 31

Autoimmune hepatitis

Answer 31

``` hepatocyte inflammation autoantibodies more females, assoc with other autoimmune ALT,AST more than 1000 elevated gamma-globulin and IgG interface hepatitis, plasma cell infiltrates Type 1: adults, nucleus (ANA and ASMA) Type 2: kids, microsome (anti-LKM) Tx: prednisone +/- azathioprine ```

Question 32

Primary Biliary Cirrhosis (PBC)

Answer 32

chronic, progressive, cholestatic liver dx destruction on intrahepatic bile ducts autoimmune (caucasian women) anti-mitochondrial antibodies (AMA) - target PDC-E2, loc on membrane of biliary epithelial cells elevated IgM, AMA+, increased alk phos Sx: fatigue, severe pruritis (bile salts in skin), hypercholesterolemia, steatorrhea fat-soluble vitamin def (vit A,D,E,K) assoc with Sjogren's syndrome Tx: ursodeoxycholic acid (UDCA)

Question 33

Hepatitis A

Answer 33

RNA virus, fecal-oral, has vaccine and immune globulin bc vaccine takes 2 weeks NO chronic poor hygene areas, day care, etc usually kids ALT spikes early, then IgM lasts for a few months, then IgG lasts forever

Question 34

Hepatitis E

Answer 34

fecal-oral, NO chronic travel to endemic area ALT spikes, then IgM for a few months, then IgG for life

Question 35

Hepatitis B

Answer 35

DNA virus, has vaccine and IG, but vaccine works quick, give both to positive mothers leading cause of hepatocellular carcinoma chronic more likely if infected young, symptoms more likely if infected old sexual or IVDU transmission Acute: HBsAg and IgM-HBc up early then down, IgG-HBc stays forever, IgG-HBs comes up a few months later (confers immunity) Chronic: HBsAg stays around, IgG-HBs never shows up. Seroconversion: IgG-HBe shows up years later Chronic infxn can cause cirrhosis and liver cancer Diagnosis: surface Ag+: current infxn surface ab+: immune core antibody (natural exposure): IgM=recent, IgG=old Tx: interferon, Entecavir, Tenofovir

Question 36

Hepatitis D

Answer 36

Only with HBV Coinfection (simul): usually results in eradication of both viruses, and life immunity (anti-HBs sticks around, IgG-HDV goes away) Superinfection: IgG-HDV sticks around, but is not immune, HDV RNA sticks around too

Question 37

Hepatitis C

Answer 37

``` RNA virus, several genotypes Usually goes chronic mostly IVDU, also sexual or transfusion Causes cirrhosis then cancer HepC antibody always remains present viral RNA only in viremic Tx: interferon, but changing rapidly ```

Question 38

Benign liver lesions

Answer 38

Hemangioma Focal Nodular Hyperplasia (FNH) Adenoma

Question 39

Malignant liver lesions

Answer 39

``` Hepatocellular Carcinoma (HCC)-common Cholangiocarcinoma (CCA) ```

Question 40

Liver lesion associations

Answer 40

Contraceptives= adenoma liver disease= hepatocellular carcinoma Hx of PSC= cholangiocarcinoma Hx of other cancer= metastatic

Question 41

Hemangioma of liver

Answer 41

``` most common benign NON-cirrhotic congenital vascular malformations can get giant NO malignant potential ```

Question 42

Focal Nodular Hyperplasia (FNH)

Answer 42

``` second most common benign liver lesion NON-cirrhotic reaction to intrahepatic anomalous artery- hyperperfusion women, usually small lesions Central stellate scar NO malignant potential ```

Question 43

Hepatic adenoma

Answer 43

``` benign liver lesion NON-cirrhotic prolif of hepatocytes women, childbearing age assoc with contraceptives asyptomatic Multiple can be seen with glycogen storage dx, DM RISK of hemorrhage and Malignant transformation (esp in pregnancy) Tx: resection ```

Question 44

Hepatocellular Carcinoma (HCC)

Answer 44

Most common, incidence increasing visualized with "washout" bc more arterial flow and less venous flow in tumor alpha-fetoprotein is often elevated (non-specific) often caused by viral hepititis

Question 45

Cirrhosis diagnostic features

Answer 45

cachexia, jaundice, ascites, spider angioma, edema, gynecomastia, palmar erythema, hair loss, encephalopathy, caput medusa, splenomegaly (many caused by increased estrogen or increased NO vasodilation) elevated bili, AST, ALT, alk phos, INR thrombocytopenia, leukopenia, renal insuff, hyponatremia

Question 46

Budd-Chari Syndrome

Answer 46

hepatic vein thrombosis

Question 47

Complications of cirrhosis

Answer 47

variceal bleeding (esophagus, Tx: b-blockers, octreotide, banding) ascites (from loss of albumin and vasodilation leading to Na/H2O retention in kidneys, also causes hyponatremia,, Tx: diuretics) spontaneous bacterial peritonitis (SBP) (infected ascites fluid, gram-) hepatorenal syndrome (complication of ascites, vasodilated) hepatopulmonary syndrome (bc vasodilated hepatic encephalopathy (asterixis hand flop, worsened by volume depletion, Tx: lactulose, rifaximin

Question 48

Fulminant Liver failure

Answer 48

acute liver failure + coagulopathy + encephalopathy | also cerebral edema (from ammonia)