Flashcards in Love your Liver Deck (32)
What is the striking difference between normal liver and cirrhotic liver?
amount and type of ECM
fibrotic - more interstitial collagen replacing low density basement membrane
What activates stellate cells?
paracrine stimuli from Kupffer cells, endothelial cells, tumor cells and inflammatory cells (also stimulate proliferation)
What determines whether cells undergo apoptosis vs. necrosis?
mitochondrial energy production decreased, damage by anoxia, bile acids, etc. --> necrosis
mitochondrial energy production sufficient --> caspase activiation and apoptosis
When are inflammatory infiltrates of PMNs seen in liver and when with lymphocytes?
PMN - alcohol and fat
lympho - virus, autoimmune, immunoallergic
Why does portal HTN develop with cirrhosis?
resistance to portal blood flow through liver to central veins due to fibrosis
What is the threshold for alcoholic liver disease in men and women?
women - 20 grams ethanol/day
men - 2-3x greater (40-60 gms/day)
What are examples of the alcoholic threshold in beer, wine, and 80 proof liquor for women and men?
women - 1.5 ounces 80 proof liquor/day, 1 12 oz beer/day, ~1.5 5 oz glasses wine/day
men - 3.5-5 ounces 80 proof liquor/day, 3-4 12 oz beers/day, 3-5 5 oz glasses wine/day
What combination is suggested to result in significant alcoholic liver disease?
combo of malnutrition and alcohol in genetically susceptible individual
How does alcohol lead to fatty liver?
byproducts of alcohol metabolism are substrates for triglyceride synthesis
alcohol increases release of dietary FA from adipocytes
What associations are present with NAFLD?
usually obesity (often accompanied by diabetes and hyperlipidemia)
What is considered secondary fatty liver disease?
steatosis in a patient with a recognizable co-factor like drug or virus
What is NASH?
non-alcoholic steatohepatitis - when inflammation on top of fatty liver - potential to progress to fibrosis and cirrhosis
What are the two causes of microvesicular fat in liver?
fatty liver of pregnancy
What is steatonecrosis?
steatosis plus inflammation, PMN infiltration, Mallory bodies
necrosis and apoptosis
What is the clinical presentation of steatosis?
often asymptomatic, possible hepatomegaly
What is the clinical presentation of steatohepatitis?
variable, fever, jaundice, ascites, confusion possible in alcoholic hepatitis
similar, but less common, in NAFLD
What conditions does pruritis suggest?
PBC and PSC
What conditions does arthritis suggest?
What conditions does impotence suggest?
What are extra-abdominal manifestations of patients with alcoholic liver disease?
spider nevi, palmar erythema, Dupuytren's contractures, secondary hypoalbuminemia, parotid enlargement, gynecomastia, testicular atrophy
What hepatic enzymes are seen in steatosis and cirrhosis?
AST almost always elevated, ALT may be normal
AST and ALT almost always 2 in alcoholic and <1 in viral hepatitis
What explains the relative suppression of ALT in steatosis and cirrhosis?
non hepatic sources of AST (red cells, skeletal or cardiac muscle)
decreased co-enzymes (pyridoxal phosphate)
cytosolic and mitochondrial localization of AST, ALT only cytosolic
What is the general picture of most NAFLD?
hepatic enzyme levels less striking
actual liver function (measured w bilirubin) normal
What protein levels are seen with steatosis and cirrhosis?
albumin levels fall with sig. liver dz
total protein normal since gamma globulins increase
vitamin K dependent clotting factors decrease - long PTT
What cell reactions are seen in alcoholic hepatitis?
possible leukemoid reaction with WBC up to 50,000
hemoglobin normal or slight decrease unless GI bleeding
What are non-invasive findings suggestive of cirrhosis?
thrombocytopenia or leukopenia
varices on esophageal studies
collaterals seen on ultrasonography
serum markers of fibrosis
What are the principles of management for steatosis and cirrhosis?
abstinence (alcohol if alcoholic, food if NAFLD)
pharm therapy (corticosteroids with severe, acute decompensation, maybe colchicine (anti-fibrotic) and propylthiouracil (anti-thyroid)
What are the five most common etiologies of chronic liver disease?
viruses, drugs, toxins, immune rxns, ischemia and obstruction
What are the sequelae of acute vs. chronic liver disease?
acute - usually none, complete recovery
chronic - extensive fibrosis and eventual cirrhosis