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Patho of Alcoholic & Metabolic Liver Disease

Terms in this set (26)

Cirrhosis
- end stage chronic liver disease
- fibrous septa surrounding regenerative nodules of hepatocytes
- result from persistent necrosis
Causes of cirrhosis
ETOH, nonalcohlic fatty liver disease, chronic hepatitis, biliary disease, metabolic disease
MICRONODULAR cirrhosis
- AKA laennec cirrhosis
- nodules less than 3mm
- in most countries the cause is alcohol abuse*
MACRONODULAR cirrhosis
- associated w/ chronic hepatitis
- can progress from micronodular
- may result from confluent submassive necrosis
Pathogensis of cirrhosis
- collagen I and III deposited in lobule
- new vascular channels shunt blood
- loss of fenestrations in sinusoids
- results in impared secretions of protesin, albumin, clotting factors and lipoproteins
- Stellate cells : major source of collagen
- biliary channel injury, resulting in jaundice
Activated Kupffer Cells
- secrete cytokines that stimulate stellate cells
Clinical features of cirrhosis
- anorexia, weight loss, debilitation
- jaundice
- impaired pulmonary oxygenation
- complications of portal hypertension
- development of hepatocellular carcinoma
Alcoholic Liver Disease
- 5th leading cause of death
- 30% of pts abuse Etoh
- can lead to hepatic steatosis, alcoholic hepatitis, cirrhosis (irreversible)
Hepatic Steatosis
- shunting of normal substrates away from catabolism and towards lipid biosynthesis
- impaired assembly & secretion of lipoproteins
- increased peripheral fat catebolism
- can being as microvesicular but lead to macrovesicular which displaces nucleus to the periphery of the cell
- REVERSIBLE
- fatty, greasy gross appearance
- mild elevation of serum bilirubin and alkaline phosphatase
Alcoholic Hepatitis
- hepatocyte swelling & necrosis, accumulation of fat, water and proteins
- may have cholestasis
- Mallory bodies: hepatocytes accumulate cytokeratin filaments & proteins
- neutrophilic reaction
- lymphocyte and macrophage infiltration into hepatic parenchyma
- typically will have sinusoidal and perivenular fibrosis that separate the parenchyma
- grossly liver is mottled red w/ bile stained areas
- fatty change, hepatocellular necrosis, fibrosis, nedule regeneration
Alcoholic Cirrhosis
- initially the liver is yellow tan fatty and may be enlarged
- over years progresses to shrunken brown relatively non fatty organ weighing less than one kg
- fibrotic septae progress from portal to portal, from sinusoids to central until nodules form
- fat is progressively lost
- bile stasis
- a paucity of Mallory Bodies at this statey
Complications of alcoholic cirrhosis
- esophageal verices
- hepatic encephalopathy
- splenomegaly
- caput medusae
- hemorrhoids
Pathogenesis of alcoholic liver disease
- short term alcoholic use is reversible in changes
- daily intake can lead to irreversible damange
- women are more susceptible to damage
Alcohol and its metabolies
- impaired methioinine leading to oxidative injury
- induction of cytochrome P450
- alcohol effects microtubule and mito function
- metabolite acetaldehyde induces lipid peroxidation injuring hepatocytes
- alcohol is inflamm
- can cause malnutrition
- induces release of bacterial endotoxin int he gut
- alcohol releases endothelins which are potent vasoconstrictors
clinical features of alcoholic liver disease
- initially asymptomatic
- malaise, anorexia, wt loss, tender hepatomegaly
- hyperbilirubinemia
- increased serum aminotransferase
- increased alkaline phosphatase
- hypoproteinuria
- distended and, muscle wasting, jaundice
Causes of death in alcoholic liver disease
hepatic coma, massive GI hemorrhage, infection, aspiration pneumonia, hepatorenal syndrome, alcoholic overdose, hepatocellular carcinoma, trauma
Hemochromatosis
- excessive accumulation of body iron
- Primary = genetic defect in intestinal iron absorption; defect in gene HFE on chromosome 6
- Secondary = transfusions, anemia
- usually males 50-60
Morphology of hemochromatosis
- deposition of hemosiderin in liver, pancreas, heart
- cirrhosis
- pancreatic fibrosis
- skin pigmentation
- joint synovial lining: hemosiderin
Clinical features of hemochromatosis
- cirrhosis, skin pigmentation, DM
- increased risk of hepatocellular ca
Wilsons Disease
- copper deposited in the liver, brain, eye
- inability to excrete copper into bile
- can lead to acute hepatitis, chronic hepatitis, cirrhosis
- Kayser-Fleisher rings on cornea
- requires chelation therapy
Alpha 1 Antitrypsin Deficiency (plasma glycoprotein made by hepatocytes)
- low levels of protease inhibitor, permits tissue destructive enzymes to go unchecked
- may present in liver and lung disease
- may lead to chronic hepatitis or cirrhosis
- increased risk of HCC
- most common genotype is PiMM; most common mutation is a derease in circulatin levels PiZ >> accumulation in A1AT-Z in endoplasmic reticulum of hepatocytes
Neonatal Hepatitis
- onset of jaundice b/t 1 wk and 2 months
- usually idiopathic
- focal necrosis, giant cell transformation
- long term prognosis is not good
Reyes Síndrome
- fatty liver & encephalopathy
- elevated serum ammonia
- may be linked to aspirin + viral infections
- may have fatty change in skeletal muscle kidneys and heart
- most recover
Secondary Biliary Cirrhosis
- extrahepatic bile duct obstruction
- jaundice, pruritis, dark urine
- conjugate hyperbilirubineamia
- firbrosis and cirrhosis
Primary Biliary Cirrhosis
- destruction of intrahepatic bile ducts
- middle ages women
- possibly autoimmune, anti mitochonridal antibodies
- increased serum alkaline phosphatase and cholesterol
- progressive liver failure
Primary sclerosing cholangitis
- inflammation, fibrosis, dilation of obstructed bile ducts
- associated w/ inflammatory bowel disease
- pruritis, fatigue, jaundice
- increased risk of cholangiocarcinoma
- liver transplant is definitive tx
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