GI Pathology 3

Question 1

liver anatomy

Answer 1

*lobule architecture
*dual blood supply (hepatic artery, portal vein; single blood drainage
*functions of hepatocytes:
-secretion of bile
-metabolism of sugar, fatty acids, amino acids
-detoxification of blood
-storage
-synthesis/secretion

Question 2

liver injury

Answer 2

*recall the tremendous regenerative capacity and functional reserve of the liver

1. reversible changes: mild ischemic/toxic injuries (steatosis, cholestasis)
2. irreversible changes: severe injuries (necrosis, apoptosis)
3. fibrosis: end result of chronic inflammation (cirrhosis)

Question 3

laboratory evaluation of the liver - tests for hepatocyte integrity

Answer 3

cytosolic hepatocellular enzymes:
1. AST (serum aspartate aminotransferase)
2. ALT (serum alanine aminotransferase)
3. LDH (serum lactate dehydrogenase)

Question 4

laboratory evaluation of the liver - tests for biliary excretion function

Answer 4

*substances normally secreted in bile:
1. serum bilirubin (total and direct)
2. urine bilirubin
3. serum bile acids

*plasma membrane enzymes (from damage to bile canaliculus):
1. serum alkaline phosphatase
2. serum gamma-glutamyl transpeptidase (GGT)

Question 5

laboratory evaluation of the liver - tests for hepatocyte synthetic function

Answer 5

*proteins secreted into the blood:
1. serum albumin
2. coagulation factors (prothrombin [PT] and partial thromboplastin [PTT] times (fibrinogen, prothrombin, factors V, VII, IX, and X))

*hepatocyte metabolism:
1. serum ammonia
2. aminopyrine breath test (hepatic demethylation)

Question 6

ascites - pathophysiology

Answer 6

1. increased portal venous pressure:
   -increased capillary hydrostatic pressure and leakage of fluid from the vascular space
2. increased liver sinusoidal hypertension:
   -increased fluid in hepatic lymphocytes
3. albumin
   -decreased plasma oncotic pressure and leakage of fluid from the vascular space

*CIRRHOSIS = leading cause

Question 7

serum alpha-fetoprotein

Answer 7

*a tumor marker for HCC (hepatocellular carcinoma)
*not specific but a useful adjunct

Question 8

alcohol liver disease

Answer 8

*hepatic parenchymal damage due to alcohol consumption
*most common cause of liver disease in the West

Question 9

alcohol liver disease - pathology

Answer 9

1. steatosis (fatty liver - lipid accumulation)
   -heavy, greasy liver
   -resolves with abstinence
2. hepatitis
   -clinically: painful hepatomegaly; elevated enzymes (AST:ALT > 2)
   -chemical injury to hepatocytes (Mallory bodies in hepatocytes)
3. cirrhosis (long-term complication)

Question 10

cirrhosis

Answer 10

*end-stage liver damage
-disruption of parenchyma by fibrous bands and regenerative nodules
-mediated by TGF-beta stellate cells
*common causes include alcoholic liver disease & chronic viral hepatitis

Question 11

acute (<6mo) hepatitis - pathology

Answer 11

*depends on cause
*LOBULAR inflammation
*hepatocellular apoptosis/necrosis (viral or drug/toxin)
*steatosis/Mallory bodies (alcohol)

Question 12

chronic (>6mo) hepatitis - pathology

Answer 12

*PORTAL inflammation
*portal-lobular “interface” inflammation
*periportal FIBROSIS

Question 13

primary biliary cirrhosis (PBC)

Answer 13

*autoimmune chronic granulomatous inflammatory destruction of small/medium-sized intrahepatic bile ducts
*associated with other autoimmune diseases (Sjogren syndrome); more common in WOMEN
*ANTIMITOCHONDRIAL ANTIBODY > 90% of cases
*pathology = FLORID DUCT LESION

Question 14

primary sclerosing cholangitis (PSC)

Answer 14

*inflammation and obliterative fibrosis of intrahepatic and extrahepatic bile ducts with dilation of preserved segments
*associated with ULCERATIVE COLITIS; more common in men
*p-ANCA positive
*pathology: PERIDUCTAL “ONION-SKINNING” FIBROSIS/STRICTURES

Question 15

primary biliary cirrhosis (PBC) - pathology

Answer 15

florid duct lesions (chronic granulomatous destruction of intrahepatic bile ducts)

Question 16

primary sclerosing cholangitis (PSC) - pathology

Answer 16

*periductal “onion-skinning” fibrosis/strictures
*dilated uninvolved ducts “string of pearls” sign

Question 17

non-alcoholic fatty liver disease

Answer 17

*hepatic steatosis in individuals who do not consume excessive alcohol
*metabolic syndrome, obesity, DM2, HTN, hyperlipidemia
*diagnosis of exclusion: ALT > AST
*increased risk of hepatocellular carcinoma

Question 18

hepatocellular carcinoma (HCC) - pathology

Answer 18

*solitary, multiple, or diffuse w/or defined borders
*background of cirrhosis
*intrahepatic metastases = satellite nodules
*ABSENT FEATURES OF NORMAL LIVER:
-no bile ducts or hepatic triads
-green appearance with “constipated” bile
*variable morphology

Question 19

cholangiocarcinoma

Answer 19

*malignant tumor of the intrahepatic or extrahepatic bile ducts
*arise in setting of chronic inflammation
*RUQ pain and signs of biliary obstruction

Question 20

cholangiocarcinoma - pathology

Answer 20

*extrahepatic or intrahepatic
*MUCIN-PRODUCING ADENOCARCINOMAS
*LYMPHOVASCULAR and PERINEURAL invasion

Question 21

hemochromatosis - histology stain

Answer 21

*Prussian blue iron stain (dyes the excess iron blue)