Week 4: pathology of alcoholic and non alcoholic fatty liver disease

Question 1

Pathophysiology of alcohol fatty liver disease

Answer 1

1. production of acetaldehyde during metabolism
   - increase in NADH/NAD+ ratio. Alteration in redox potential -> increased FA synthesis and decreased FA metabolism
2. Decrease in mitochondrial beta-oxidation
3. oxidative stress
   - formation of ROS
4. Immune system
   - Kupffer cells: produce superoxides
   - PMNs: Il8 elevated, attracts neutrophils
   - lymphocytes: stimulated by endotoxins, cause increase in inflammation
5. Stellate activation
   - activated by alcohol. transforms into myofibroblast like cells: synthesis and secretion of collagen matrix

Question 2

Two less common variants of acute alcoholic liver disease

Answer 2

These two have better prognosis

1. acute alcoholic fatty liver with or without cholestasis
2. Alcoholic foamy degeneration: microvesicular foamy hepatocytes

Question 3

Pathology of acute alcoholic fatty liver

Answer 3

• gross: smooth, enlarged liver, often 3000g+. greasy and yellow surface
• histo: macrovesicular fatty change, initially perivenular.
• cholestasis seen in some cases
• enlarged mitochondria may be seen within heptatocytes

Question 4

Pathology of alcoholic hepatitis

Answer 4

• gross: normal sized, smooth liver, cut surface is firm but smooth.
• micro: sclerosis of terminal hepatic venules, with sinusoidal collagen present in adjacent perivenular sinusoids
• perivenular hepatocytes are often swollen and may contain mallory bodies
• neutrophils present in lobules and portal tracts
• satellitosis: PMNs circle hepatocyte containing mallory bodies

Question 5

Pathology of chronic alcoholic liver disease

Answer 5

1. portal and perivenular fibrosis
   - eventual bridging of portal and perivenular (pericentral) fibrosis
2. cirrhosis-early
   - gross: large liver, smooth to slightly granular
   - micro: distorted architecture from fibrosis. poorly formed small regenerative nodules. Varied degrees of fatty change
3. moderate/advanced cirrhosis
   - gross: normal to small in size, nodules
   - micro: distortion of architecture, dense fibrous septa
   - mild to moderate bile duct proliferation and lymphocytic infiltration
   - cord-sinusoid pattern

Question 6

non alcoholic fatty liver disease

Answer 6

• associated with metabolic syndrome: central obesity, elevated TGs, decreased HDL, HTN, abnormal glucose tolerance
• mostly asymptomatic
• AST and ALT elevated, but less than 100

Question 7

Pathophysiology of non alcoholic fatty liver disease

Answer 7

• Hepatic TGs increase susceptibility of liver to injury
• FFAs undergo b-oxidation or esterification forming TGs, leading to hepatic fat accumulation, mito dysf. , and activation of inflammatory pathways
• insulin normally suppresses adipose tissue lipolysis, but insulin resistance results in increase efflux of FFA from adipose
• oxidative stress leads to active fibrogenesis and steatohepatitis

Question 8

Pathology of non alcoholic steatohepatitis

Answer 8

• looks similar to alcoholic hepatitis
• portal and perivenular fibrosis
• portal lymphocytic infiltrates
• macrovesicular fatty change
• mallory bodies
• severe fibrosis and cirrhosis may develop