pathology of viral and non viral liver disease

Question 1

acute hepatitis

Answer 1

Clinical:

• Breakdown of any of the following functions: lipid/carb/protein metabolism, coagulation factor production, detox, storage of vitamins and glycogen, albumin production, bile processing and secretion.
• Liver failure leads to jaundice and scleral icterus, ascites and peripheral edema due to hypoalbuminemia, spider angiomata and palmar erythema, gynocomastia in men, coagulopathy, encephalopathy (due to accumulation of ammonia), and renal failure.
• Portal hypertension leads to esophageal varices and hemorrhoids and caput medusa.
• Acute hepatitis: lobular disarray, inflammation, widespread hepatocyte injury, but no fibrosis

Question 2

chronic hepatitis

Answer 2

Chronic hepatits: less prominent inflammation and injury, portal-tract inflammation, fibrosis. More spotty/less severe looking. Regenerative nodules.

Question 3

Understand the various histologic patterns of liver injury and how they are used to generate a differential diagnosis or diagnosis

Answer 3

• ballooning degeneration or shrunken necrosis (interface, then bridging)
• inflammatory cells are characteristic but not definitive
• Lymphocytes – many hepatitides; common in viral
• Neutrophils – common in steatohepatitis
• Eosinophils – common in drug injury
• Plasma cells – common in autoimmune hepatitis
• Cytoplasmic accumulations include fat, bile, iron, copper, viral particles
• Process of fibrosis: chronic cycles of injury and regeneration, activated stellate cells deposit collagen, architectural and vascular reorganization, and cirrhosis.
• Tri-chrome stain strains Type I collagen in blue.
• Portal–>then periportal (extended arms)–>then bridging–>then cirrhosis.

Question 4

Understand the difference between the grade of disease and stage of disease in chronic hepatitis

Answer 4

• Grade = amount of inflammation or injury

- Stage = amount of fibrous tissue deposition

Question 5

Understand the importance of hepatocellular carcinoma in chronic liver disease and how the prognosis is determined

Answer 5

90% of patients are cirrhotic. Most common primary malignant liver tumor. Poor long-term survival. Occurs mostly in patients with chronic liver disease (Hep C or B, alcohol).

Question 6

what is the viral hep that isnt rna

Answer 6

Hep B which is dna

Question 7

what are the two fecal oral Heps

Answer 7

A and E

Question 8

what is the most prominent hep virus in US

Answer 8

C

Question 9

what is most prominent world wide

Answer 9

B

Question 10

what hep is carcinogenic

Answer 10

B

Question 11

what does hep B look like microscopically

Answer 11

ground glass cytoplasmic inclusions

Question 12

what virus is dependent on Hep B machinery

Answer 12

Hep D, IV drug abuse setting in the us

Question 13

What Hep virus has a high mortality in pregnant women?

Answer 13

Hep E,

Question 14

Autoimmune hep often associated with what serologic thing

Answer 14

anti-smooth muscle antibodies, elevated overall IgG

Question 15

Primary biliary cirrhosis-

Answer 15

• autoimmune, middle aged women, small caliber bile ducts
• elevated igm, Anti-mitochondrial antibody (AMA) is positive in 90% of PBC cases.
• pronounced lymphocytic and granulomatous inflammation
• intrahepatic
• associated with RA, SLE, Sjogrens

Question 16

Primary sclerosing cholangitis-

Answer 16

• autoimmune, men>women, large caliber bile ducts, and -Hypergammaglobinemia,
• periductal onion skin fibrosis
• intra and extrahepatic, segmental
• 70% associated with ulcerative colitis,

Question 17

major cause of acute liver failure in the us, intrinsic hepatotoxin

Answer 17

Tylenol

Question 18

Wilson disease-

Answer 18

accumulation of copper due to inability to excrete it into the bile

Question 19

Autoimmune hepatitis

Answer 19

• Includes autoimmune hepatitis, PBC, and PSC.
• typically affects women in association with other autoimmune disease. Autoantibodies (ANA, ASMA) plays major role in diagnosis. Elevated IgG.
• PBC (misnomer- not necessarily cirrhosis) is an immune-mediated attack of intrahepatic small caliber bile ducts. Anti-mitochondrial Ab is elevated in 90% Elevated IgM.
• PSC is an immune-mediated obliterative fibrosis (“onion-skin”) of larger caliber bile ducts – both intra- and extrahepatic. Diagnosis via alternating biliary strictures and dilation on cholangiography. No specific serologic findings.

Question 20

7. Describe the features of drug induced liver injury including acetaminophen toxicity.

Answer 20

• Patterns of injury can mimic other disease: necrosis, cholestasis, steatosis, steatohepatitis, acute/chronic/autoimmune hepatitis
• Can be instrinsic (dose-related) or idiosyncratic (unpredictable)
• Acetaminophen:
• Centrilobular necrosis (Zone 3)
• Major cause of acute liver failure requiring transplant in US

Question 21

Steatosis/steatohepatitis

Answer 21

• Accumulation of fat in hepatocytes.
• Steatosis caused by metabolic syndrome, alcohol, drug effect, Wilson Disease,viral infection.
• Steatohepatitis caused by alcohol, metabolic syndrome, drug effect. Often chronic.
• Why alcohol? Large carb load short circuits the feedback control of lipogenesis. Increased lipolysis peripherally.Beta-oxidation pathway is impeded, as is packaging of VLDL.
• Mallory bodies
• Lipid influx (chylomicrons, lipolysis, carbs) > lipid clearance (beta oxidation, VLDL)
• NASH is associated with obesity, Type II Diabetes, hypertriglyceridemia. Increasing prevalence in US.
• Same effects as alcohol but large delivered lipid load.

Question 22

Hereditary Hemochromatosis

Answer 22

• AR inheritance of HFE gene mutations leading to abnormally increased iron absorption in duodenum.
• Liver disease, diabetes, HF

Question 23

Wilson Disease

Answer 23

• AR inheritance of mutated ATP7B gene (transporter involved in bile excretion of copper) leading to copper overload throughout the body.
• Liver disease and neuopsychiatric problems

Question 24

Alpha-1 antitrypsin deficiency

Answer 24

• AR.
• A protease inhibitor. With PiZZ disease genotype, most develop pulmonary emphysema and about 10% develop liver disease.

Question 25

Hepatocellular carcinoma (HCC)

Answer 25

90% of patients are cirrhotic. Most common primary malignant liver tumor. Poor long-term survival. Occurs mostly in patients with chronic liver disease (Hep C or B, alcohol).

Question 26

Cholangiocarcinoma

Answer 26

Neoplasm of the bile ducts. May be intra- or extrahepatic. PSC is a major risk factor. Usually presents at an advance stage. 1 and 2 year survival 25% and 13% respectively

Question 27

Hemangioma

Answer 27

Benign neoplasm of dilated vascular spaces. Most common primary hepatic tumor. Incidence of 2%. More common in females (1:4) . Most common presentation is vague RUQ pain, early satiety, nausea, vomiting. But usually small and asymptomatic.

Question 28

Focal nodular hyperplasia (FNH)

Answer 28

Second most common primary hepatic mass. Presumed hyperplastic parenchyma due to a vascular anomaly. Commonly found in association with hemangiomas. More common in women than men (4:1). Diagnosed in the 3rd - 4th decade of life. Usually asymptomatic

Question 29

Hepatocellular adenoma

Answer 29

women-child-bearing age.
Associated with oral contraceptive use.
Presents with RUQ pain (most are asymptomatic).
Risk-rupture into abdomen with hemorrhage.
Low risk of malignant transformation (5%)