Love your Liver

Question 1

What is the striking difference between normal liver and cirrhotic liver?

Answer 1

amount and type of ECM

fibrotic - more interstitial collagen replacing low density basement membrane

Question 2

What activates stellate cells?

Answer 2

paracrine stimuli from Kupffer cells, endothelial cells, tumor cells and inflammatory cells (also stimulate proliferation)

Question 3

What determines whether cells undergo apoptosis vs. necrosis?

Answer 3

mitochondrial energy production decreased, damage by anoxia, bile acids, etc. –> necrosis
mitochondrial energy production sufficient –> caspase activiation and apoptosis

Question 4

When are inflammatory infiltrates of PMNs seen in liver and when with lymphocytes?

Answer 4

PMN - alcohol and fat

lympho - virus, autoimmune, immunoallergic

Question 5

Why does portal HTN develop with cirrhosis?

Answer 5

resistance to portal blood flow through liver to central veins due to fibrosis

Question 6

What is the threshold for alcoholic liver disease in men and women?

Answer 6

women - 20 grams ethanol/day

men - 2-3x greater (40-60 gms/day)

Question 7

What are examples of the alcoholic threshold in beer, wine, and 80 proof liquor for women and men?

Answer 7

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

Question 8

What combination is suggested to result in significant alcoholic liver disease?

Answer 8

combo of malnutrition and alcohol in genetically susceptible individual

Question 9

How does alcohol lead to fatty liver?

Answer 9

byproducts of alcohol metabolism are substrates for triglyceride synthesis
alcohol increases release of dietary FA from adipocytes

Question 10

What associations are present with NAFLD?

Answer 10

usually obesity (often accompanied by diabetes and hyperlipidemia)

Question 11

What is considered secondary fatty liver disease?

Answer 11

steatosis in a patient with a recognizable co-factor like drug or virus

Question 12

What is NASH?

Answer 12

non-alcoholic steatohepatitis - when inflammation on top of fatty liver - potential to progress to fibrosis and cirrhosis

Question 13

What are the two causes of microvesicular fat in liver?

Answer 13

fatty liver of pregnancy

Reye’s syndrome

Question 14

What is steatonecrosis?

Answer 14

steatosis plus inflammation, PMN infiltration, Mallory bodies
necrosis and apoptosis

Question 15

What is the clinical presentation of steatosis?

Answer 15

often asymptomatic, possible hepatomegaly

Question 16

What is the clinical presentation of steatohepatitis?

Answer 16

variable, fever, jaundice, ascites, confusion possible in alcoholic hepatitis
similar, but less common, in NAFLD

Question 17

What conditions does pruritis suggest?

Answer 17

PBC and PSC

Question 18

What conditions does arthritis suggest?

Answer 18

hemochromatosis

Question 19

What conditions does impotence suggest?

Answer 19

hemochromatosis

Question 20

What are extra-abdominal manifestations of patients with alcoholic liver disease?

Answer 20

spider nevi, palmar erythema, Dupuytren’s contractures, secondary hypoalbuminemia, parotid enlargement, gynecomastia, testicular atrophy

Question 21

What hepatic enzymes are seen in steatosis and cirrhosis?

Answer 21

AST almost always elevated, ALT may be normal

AST and ALT almost always 2 in alcoholic and <1 in viral hepatitis

Question 22

What explains the relative suppression of ALT in steatosis and cirrhosis?

Answer 22

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

Question 23

What is the general picture of most NAFLD?

Answer 23

hepatic enzyme levels less striking

actual liver function (measured w bilirubin) normal

Question 24

What protein levels are seen with steatosis and cirrhosis?

Answer 24

albumin levels fall with sig. liver dz
total protein normal since gamma globulins increase
vitamin K dependent clotting factors decrease - long PTT

Question 25

What cell reactions are seen in alcoholic hepatitis?

Answer 25

PMN leukocytosis possible leukemoid reaction with WBC up to 50,000 hemoglobin normal or slight decrease unless GI bleeding possible thrombocytopenia

Question 26

What are non-invasive findings suggestive of cirrhosis?

Answer 26

``` splenomegaly thrombocytopenia or leukopenia varices on esophageal studies collaterals seen on ultrasonography serum markers of fibrosis ```

Question 27

What are the principles of management for steatosis and cirrhosis?

Answer 27

abstinence (alcohol if alcoholic, food if NAFLD) nutritional support pharm therapy (corticosteroids with severe, acute decompensation, maybe colchicine (anti-fibrotic) and propylthiouracil (anti-thyroid)

Question 28

What are the five most common etiologies of chronic liver disease?

Answer 28

viruses, drugs, toxins, immune rxns, ischemia and obstruction

Question 29

What are the sequelae of acute vs. chronic liver disease?

Answer 29

acute - usually none, complete recovery | chronic - extensive fibrosis and eventual cirrhosis

Question 30

When should certain diagnostic tests be ordered with liver disease?

Answer 30

if acute hepatitis based on enzymes - look for virus, drug or toxin if obstructive pattern, ultrasound obstructive pattern but absence of duct obstruction - look for autoimmune PBC and PSC chronic hepatitis - viral serologies, iron studies for hemochromatosis, ceruloplasmin for Wilson, alpha 1 antitrypsin

Question 31

If iron studies are abnormal, what is the next step?

Answer 31

testing for HFE gene mutation

Question 32

When is biopsy necessary for patients with hemochromatosis?

Answer 32

if abnormal hepatic enzymes - risk for HCC | not necessary if diagnosis made before enzymes abnormal