Flashcards in Fatty Liver Disease Deck (25)
What are the 2 main causes of liver failure and death in the US?
(1) alcoholic liver disease
(2) hepatitis C
How much alcohol consumption poses a risk factor for liver disease?
Male: 6-8 drinks
Female: 3-4 drinks
Describe normal alcohol metabolism.
(1) ADH converts alcohol to acetaldehyde.
(2) ALDH converts acetaldehyde to acetate.
Each step also converts NAD+ to NADH.
J: Deficiency of this enzyme causes flushing syndrome after the consumption of alcohol.
What is ALDH?
Describe alcohol metabolism when blood alcohol is high.
(1) MEOS converts alcohol to acetaldehyde.
(2) aldehyde or xanthine oxidase converts acetaldehyde to acetate.
Each step consumes NADPH and produces an oxyradical.
How does alcohol lead to a fatty liver?
(1) Increased NADH.
(2) Increased fatty acid synthesis and decreased mitochondrial beta-oxidation of fatty acids.
(3) Fatty acids accumulate in hepatocytes and are esterified and stored as triglycerides.
How does alcohol cause liver damage?
(1) Alcohol metabolism leads to oxidative stress and lipid peroxidation.
(2) Kupffer cell are activated, leading to cytokine and superoxide production.
How does alcohol cause fibrosis?
Stellate cells, the primary collagen-producing cells in the liver, are activated by:
(3) products of lipid peroxidation
What are the primary collagen-producing cells in the liver?
What is the clinical presentation of a fatty liver?
(1) no to mild symptoms: fatigue, malaise, anorexia, abdominal discomfort
(2) tender hepatomegaly
(3) mild AST/ALT increase
Is fatty liver reversible?
Yes, just stop drinking.
What is the clinical presentation of alcoholic hepatitis?
(1) constitutional symptoms
(2) esophageal varices
(4) hepatic encephalopathy
(7) palmar erythema
What is the LFT profile of alcoholic hepatitis?
AST:ALT is 2:1.
What are the histological features of alcoholic hepatitis?
(1) macrovesicular steatosis
(2) acute inflammation
(3) centrilobular hepatocyte swelling
(4) ballooning degeneration
(5) Mallory bodies
J: This is used to determine the risk of death in a patient with acute hepatitis.
What is the Maddrey discriminant function?
How is alcoholic hepatitis treated?
(1) no alcohol
(2) adequate nutrition
What is NAFLD?
Non-alcoholic fatty liver disease. It appears histologically like alcohol-induced disease but in a non-drinker or little-drinker.
What is an unwanted progression of NAFLD?
What are risk factors for NAFLD?
What is another name for metabolic syndrome?
Insulin resistance syndrome.
What are the 2 main mechanisms by which insulin resistance leads to fat accumulation I the liver?
(1) increased lipolysis
How does increased lipolysis lead to NAFLD?
(1) Increased FFAs leads to increased uptake by hepatocytes, mitochondrial beta-oxidation overload, and accumulation of FFAs within hepatocytes.
(2) FFAs induce cytochrome P450 enzymes, leading to production of oxyradicals and lipid peroxidation.
How does hyperinsulinemia lead to NAFLD?
(1) Increases glycolysis leading to increased synthesis of FFAs.
(2) Decreases hepatic production of ApoB-100, leading to decreased assembly and secretion of VLDL.
How is NAFLD treated?
(1) weight reduction
(2) insulin-sensitizing agents (pioglitazone, metformin)