Liver and GB remainder of part I and part II Flashcards
pathogenesis of alcoholic steatosis
- 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
pathogenesis of alcoholic steatohepatitis
- cytokines by kupffer cells
- ROS
- toxic alcohol metabolites
- fibrosis by stellate cells
etiology of cirrhosis
- HBV
- HCV
- Alcoholic liver disease
- Hemochromatosis
- Nonalcoholic fatty liver disease
compensated cirrhosis
w or w/o gastroesophageal varices
No sign of hepatic damage
decomp cirrhosis
Jaundice
Hepatic encephalopathy
Ascites
Variceal hemorrhage
portal hypertension
structural changes: fibrosis
dynamic changes: increased vasoconstrictors
decreased vasodilators
ascites
- Main clinical consequences of portal hypertension
- portal hypertension -> Splanchnic Arterial Vasodilation -> Decrease in Effective Arterial Volume -> Decrease in Renal Blood Flow -> renin-angiotensin activation
Clinical consequences of iron overload
- increased non-transferrin-bound iron (NTBI)
- excess oxygen radicals
Hereditary Hemochromatosis
- HFE gene mutation -> reduced hepcidin
- Lipid peroxidation
- Interaction of ROS and iron with DNA
- Stimulation of collagen formation
- Clinical consequence: Fibrosis and cirrhosis
HAV
- 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
HBV
- cccDNA -> chronic infection
- blood, birth, bonking
- Immune-mediated liver injury
Cytotoxic T cell-mediated lysis
Direct cytotoxic liver injury
Role of viral variants
phases of HBV infection
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
HCV
- mutation - > viral persistence -> chronic HCV hepatitis
pathogenesis: - Chronic hepatitis C
- Liver cirrhosis
- Hepatocellular carcinoma
- uses many cancer hallmarks
NAFLD types
- NAFL: nonalcoholic fatty liver: hepatic steatosis is present without evidence of inflammation
- NASH: nonalcoholic steatohepatitis may progress to cirrhosis
pathogenesis of NASH
- Kupffer cells:
pro-inflammatory mediators and pro-fibrotic factors - Stellate cells:
fibrogenesis - Hepatocytes
FC accumulation in the mitochondria -> ROS and lipid peroxidation
Clinical Features of NASH/NAFLD
Triad: insulin resistance, T2DM, obesity
Insulin Resistance and NAFLD
- hyperinsulinemia
- hyperlipidemia
- hyperglycemia
HCC’s risk factors
- cirrhosis
- HBV
- HCV
- HH
- alcohol
- chronic liver disease/injury
- aflatoxin
HCC pathogenesis
repeated hepatocyte damage -> Stepwise accumulation
Pathogenesis of Cholelithiasis
supersaturation of bile with cholesterol
hypomotility of the gallbladder
defective conversion of cholesterol to bile acids
hypersecretion of mucus in the gallbladder
Cholelithiasis Clinical Features
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
Cholecystitis Pathogenesis
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
Cholestatic Liver Disease
hepatocellular: an impairment of bile formation
obstructive: abnormal bile flow occurs after it is formed
Pathogenesis of Pruritus in Cholestatic Disease
Endogenous opioids
Lysophosphatidic acid and autotoxin
Pathogenesis of Gallbladder Carcinoma
- 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
