Liver and GB remainder of part I and part II

Question 1

pathogenesis of alcoholic steatosis

Answer 1

• increased lipogenesis
• increase release of FA from fat cells
  increased storage of FA in the liver
• increased lipolysis
• decreased/lack of lipophagy
• decreased adipokines
• decreased release of VLDL from the liver

Question 2

pathogenesis of alcoholic steatohepatitis

Answer 2

• cytokines by kupffer cells
• ROS
• toxic alcohol metabolites
• fibrosis by stellate cells

Question 3

etiology of cirrhosis

Answer 3

• HBV
• HCV
• Alcoholic liver disease
• Hemochromatosis
• Nonalcoholic fatty liver disease

Question 4

compensated cirrhosis

Answer 4

w or w/o gastroesophageal varices

No sign of hepatic damage

Question 5

decomp cirrhosis

Answer 5

Jaundice
Hepatic encephalopathy
Ascites
Variceal hemorrhage

Question 6

portal hypertension

Answer 6

structural changes: fibrosis
dynamic changes: increased vasoconstrictors
decreased vasodilators

Question 7

ascites

Answer 7

• Main clinical consequences of portal hypertension
• portal hypertension -> Splanchnic Arterial Vasodilation -> Decrease in Effective Arterial Volume -> Decrease in Renal Blood Flow -> renin-angiotensin activation

Question 8

Clinical consequences of iron overload

Answer 8

• increased non-transferrin-bound iron (NTBI)

- excess oxygen radicals

Question 9

Hereditary Hemochromatosis

Answer 9

• HFE gene mutation -> reduced hepcidin
• Lipid peroxidation
• Interaction of ROS and iron with DNA
• Stimulation of collagen formation
• Clinical consequence: Fibrosis and cirrhosis

Question 10

HAV

Answer 10

• no chronic infection
• oral-fecal route
• vaccination
• lifelong immunity
• Hepatocellular damage and destruction by HAV-specific CD8+ T lymphocytes and NK cells

Interferon-gamma

symptomes: Sudden onset of nausea, vomiting, anorexia, fever, malaise and abdominal pain
Within a few days to a week, dark urine, pale stools followed by jaundice and pruritus

Question 11

HBV

Answer 11

• cccDNA -> chronic infection
• blood, birth, bonking
• Immune-mediated liver injury
  Cytotoxic T cell-mediated lysis
  Direct cytotoxic liver injury
  Role of viral variants

Question 12

phases of HBV infection

Answer 12

Immune-tolerance phase
- HBeAg-positive
- high levels of HBV replication with normal ALT levels
- limited liver inflammation
Immune-clearance/reactive phase
- ALT levels are typically elevated or fluctuating,
- higher risk of liver fibrosis
Immune-control phase
- very low or undetectable HBV DNA levels
- normal ALT and minimal fibrosis progression
- anti-HBe positive
Immune-escape phase
- in some people
- rising HBV DNA levels despite HBeAg negativity
- caused by virions that do not express HBeAg because of genetic mutations
- anti-HBe positive

Question 13

HCV

Answer 13

• mutation - > viral persistence -> chronic HCV hepatitis
  pathogenesis:
• Chronic hepatitis C
• Liver cirrhosis
• Hepatocellular carcinoma
• uses many cancer hallmarks

Question 14

NAFLD types

Answer 14

• NAFL: nonalcoholic fatty liver: hepatic steatosis is present without evidence of inflammation
• NASH: nonalcoholic steatohepatitis may progress to cirrhosis

Question 15

pathogenesis of NASH

Answer 15

• Kupffer cells:
  pro-inflammatory mediators and pro-fibrotic factors
• Stellate cells:
  fibrogenesis
• Hepatocytes
  FC accumulation in the mitochondria -> ROS and lipid peroxidation

Question 16

Clinical Features of NASH/NAFLD

Answer 16

Triad: insulin resistance, T2DM, obesity

Question 17

Insulin Resistance and NAFLD

Answer 17

• hyperinsulinemia
• hyperlipidemia
• hyperglycemia

Question 18

HCC’s risk factors

Answer 18

• cirrhosis
• HBV
• HCV
• HH
• alcohol
• chronic liver disease/injury
• aflatoxin

Question 19

HCC pathogenesis

Answer 19

repeated hepatocyte damage -> Stepwise accumulation

Question 20

Pathogenesis of Cholelithiasis

Answer 20

supersaturation of bile with cholesterol

hypomotility of the gallbladder

defective conversion of cholesterol to bile acids

hypersecretion of mucus in the gallbladder

Question 21

Cholelithiasis Clinical Features

Answer 21

biliary colic that may be excruciating

Cholecystitis, in association with stones, also causes pain

Pain is localized to right upper quadrant or epigastrium that may radiate to the right shoulder or the back

Question 22

Cholecystitis Pathogenesis

Answer 22

Acute calculous cholecystitis

• chemical irritation and inflammation of a gallbladder obstructed by stones
• prostaglandins released

Acute acalculous cholecystitis
- ischemia and trauma

Chronic Cholecystitis
- fibrosis and thickening of the gallbladder

Question 23

Cholestatic Liver Disease

Answer 23

hepatocellular: an impairment of bile formation
obstructive: abnormal bile flow occurs after it is formed

Question 24

Pathogenesis of Pruritus in Cholestatic Disease

Answer 24

Endogenous opioids

Lysophosphatidic acid and autotoxin

Question 25

Pathogenesis of Gallbladder Carcinoma

Answer 25

• APBJ: reflux of pancreatic secretions into the biliary tree (liver, gallbl. and biliary ducts) -> KRAS mutation (is involved in cell growth/proliferation)
• chronic gallstones -> inflam -> p53 mutation