Fatty Liver Disease Flashcards
How does alcohol lead to fatty liver?
- Increase in NADH leads to inc in FA synthesis and a dec in fatty acid oxidation
- This leads to FA accumulation in hepatic cytoplasm
- Then esterification
- Stored as TGs
How does alcohol cause liver damage?
- ETOH metabolism creates ROS that attack lipids (lipid peroxidation)
- Kupffer cells are activated leading to cytokine/oxidant production
How does alcohol cause fibrosis
Compounds produced from ETOH metabolism activate stellate cells to lay down collagen in the liver
(necroinflammatory and fibrotic changes which can lead to alcoholic hepatitis or cirrhosis)
What compounds can activate stellate cells?
- acetaldehyde
- ROS
- products of lipid peroxidation
- TGF-beta (kupffer cells)
Symptoms of fatty liver
- Non/mild (fatigue, anorexia, abd discomfort etc)
- Tender hepatomegaly on exam
Fatty liver labs
Inc liver enzymes
Best treatment for fatty liver?
Decrease alcohol or wt dep on cause
What is alcoholic hepatitis
After years of heavy drinking get constitutional symptoms. If severe get ascites, HE and vacices
How long does it take for fatty liver to happen?
days-wks of drinking chronically
What liver lab is more elevated with alcohol abuse?
AST (mitochondria due to ROS)
What is a mallory body?
Seen in alcoholic hepatitis, intermediate keratin filament proteins
What cures cirrhosis
transplant only
List 3 alcoholic liver diseases
- Fatty Liver 2. Alcoholic Hepatitis 3. Alcoholic Cirrhosis
What is NAFLD?
Non alcoholic fatty liver disease
What are the 3 entities of NAFLD?
- NASH
- Steatosis
- Cirrhosis
What are the risk factors for NAFLD?
- obesity
- hyperglycemia
- T2D
- HyperTG
- associated with metabolic syndrome and insulin resistance
What 2 things contribute to pathogenesis of NAFLD?
Insulin resistance and oxidative stress on hepatocytes leads to NAFLD
How does insulin resistance lead to accumulation of fat in hepatocytes?
- Increased lipolysis (FA floating around)–>ROS–>lipid peroxidation
- Hyperinsulinemia (inc glycolysis and synthesis of FFAs, dec hepatic production of Apo B which allows export of TGs in VLDL)
Ratio of AST/ALT in NASH
AST 3x ALT
metabolic damage
Who gets NASH more? M or F
F
Potential drug to treat NASH
Pioglitazone (TZD)
NAFLD is associated with…
insulin resistance and metabolic syndrome
What is the number 1 cause of crytogenic cirrhosis?
NASH
