Metabolic Liver Diseases Flashcards
What is nonalcoholic fatty liver disease? (NAFLD)
- the most common cause of chronic liver dz in the world
What are risk factors for NAFLD? Risks caused by NAFLD?
- obesity/metabolic syndrome
- contributes to progression of other liver diseases
- increased risk of HCC
- hispanic > african american > caucasian
What is the pathogenesis of NAFLD?
two hit model:
- insulin resistance leads to hepatic steatosis
- hepatocellular oxidative injury leads to liver cell necrosis and inflammatory reactions
- metabolic syndrome leads to dysfunctional adipose tissue, decreased production of adiponectin, increased TNFa, IL-6 = hepatocyte apoptosis
- apoptosis also due to oxid. damage to mitochondria and plasma membranes
- mitochondria further damaged by decreased autophagy and formation of Mallory-Denk bodies
- scar tissue deposition activates stellate cells
- stellate cells also activated through hedgehog signaling path (level of path coordinates w/stage of fibrosis in NAFLD)
What are the morphological changes in NAFLD?
- Similar to alcoholic hepatitis, but:
- Mononuclear cells more prominent
- Portal fibrosis more prominent
- Mallory-Denk less common
What are the clinical symptoms/ labs in NAFLD?
- nonspecific symptoms w/RUQ pain or asymptomatic
- increased AST, ALT
What is the treatment for NAFLD?
Address the underlying metabolic syndrome (wt loss, treat hyperlipidemia, insulin resistance)
What is the WHO criteria diagnosis of metabolic syndorme?
One of:
- diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, or insulin resistance
Two of:
- BP >140/90
- TGs >1.695 and HDL .9 (M), >.85 (F), or BMI >30
- Microalbuminuria: urinary albumin exr >20 or albumin : Cr >30
What is hemochromatosis?
Excessive iron absorption deposited in parenchymal organs such as the liver and pancreas followed by heart, joints, and
endocrine organs
- primary - hereditary
- secondary - excessive intake
How do the different forms of hemochromatosis appear?
Primary - slow progression w/sxs appearing in 4th-5th decades for males, later (if ever) for females cuz of menstruation
Secondary - usually associated w/ineffective erythropoiesis or excessive iron from transfusions + increased absorption
What are the symptoms of fully developed severe hemochromatosis?
- Micronodular cirrhosis in all patients
- diabetes mellitus in 75-80%
- Abnormal skin pigmentation in 75-80%
What is hereditary hemochromatosis caused by?
a mutation in the HFE gene, whose product is involved in intestinal iron uptake by its effects on hepcidin levels (intestinal absorpt. of dietary iron is abnormal)
How does iron cause toxicity?
- lipid peroxidation via iron-catalyzed ROS
- stimulates collagen formation by activation of hepatic stellate cells
- interaction of ROS and FE w/DNA leads to lethal cell injury, predisposition to HCC
REVERSIBLE if cells not fatally injured (and removing excess iron helps)
What is the morphology of hemochromatosis?
- deposition of hemosiderin in liver, pancreas, other organs
- seen with prussian blue stain
How does the liver look in hemochromatosis:
Initially: golden-yellow hemosiderin granules form, fibrous septa develop
- leads to small shrunken liver w/ micronodular cirrhosis
- iron directly hepatotoxic, NO INFLAMMATIOn
Late stages: liver dark brown-black due to Fe accumulation
How does the pancreas look in hemochromatosis?
Intensely pigmented
• Diffuse interstitial fibrosis
• Parenchymal atrophy
• Hemosiderin in islet and acinar cells
