NAFLD and liver cirrhosis Flashcards
List 3 categories of liver function tests, and an example test of each.
1) Tests to measure synthesis and metabolic function: Decrease means abnormal function. Tests include serum albumin, coagulation tests (PT and aPTT), direct bilirubin (bilirubin conjugated by glucoronic acid)
2) Tests to measure tissue damage: Increase means damage. Tests include transaminases (aspartate-AST and alanine-ALT) and alkaline phosphatase (bile duct damage)
3) Tests to measure excretion: Increase means obstruction. Total bilirubin. If he doesn’t specify total in exam, assume total.
What is the difference between NAFL and NASH?
NAFL: Reversible and due to accumulation of fat in hepatocytes (steatosis).
NASH: Not easily reversible, has inflammation, hepatocyte injury (ballooning) and fibrosis.
What are the 3 cell type that play damaging roles in fatty liver?
1) Hepatocytes: Driven by excess fatty acids. Mitochondrial strain (ROS, apoptotic pathway), Endoplasmic reticulum (ER) stress and activated death receptors.
2) Macrophages: Increase inflammation upon liver damage.
3) Stellate cells: Increase fibrosis upon liver damage.
What is autophagy, and how does it protect from fatty liver diseases?
Cell forms a membrane around damaged part of the cell to “eat itself.” In the liver, it helps to get rid of mitochondria and excess/damaged protein.
Autophagy is good and has a protective role by getting rid of lipotoxins and damaged cellular components.
What is portal circulation, and list 3 collaterals that develop in portal hypertension.
Intestine absorbs water and nutrients. Waste goes through liver via blood entering into the liver from two places (portal vein* and hepatic artery).
Upon complications, blood can go back through circulation via following routes:
1) Stomach
2) Anal
3) Umbilical vein
What is TIPS, and list one side effect of TIPS.
Transjugular Intrahepatic Portosystemic Shunt (TIPS): Bypass the portal vein to hepatic vein.
May worsen metabolic symptoms of cirrhosis and lead to hepatic encephalitis (altered level of consciousness due to liver failure).
List 1 signaling pathway that leads to liver fibrosis, and 1 that protects from fibrosis.
TGFβ leads to liver fibrosis.
PPARγ protects the liver.
List 3 therapeutic strategies to treat liver fibrosis.
1) Removal of causative agent: Hepatitis, alcohol, lipids.
2) Increase collagen lysis: Increase MMPs, inhibit MMP inhibitors
3) Deactivate hepatic stellate cells (HSCs): Use anti-inflammatory agents, antioxidants (inhibit HSC activation), and/or HSC modulators
T/F: Increase in both direct and total bilirubin indicates bile duct obstruction.
True, total bilirubin is the key here. Direct bilirubin can increase too.
T/F: Fatty acids can induce mitochondrial stress and apoptosis in hepatocytes.
True
T/F: Carbamazepine, an anti-epileptic drug, can enhance autophagy to protect liver.
True, carbamazepine is an anti-epileptic drug that can enhance autophagy to protect the liver.
T/F: Risk of hepatic encephalitis increases in patients who received TIPS to relieve portal hypertension.
True
What liver enzymes are released when there’s liver damage?
Aspartate (AST) and Alanine (ALT).
Anything over 40 is bad.
Liver cirrhosis
Tissue gets stiff.
Liver dysfunction leads to jaundice (bilirubin accumulation), ammonia toxicity from gut microbiota, ascites fluid accumulation in abdomen, and estrogen metabolism (spider angioma, gynecomastia).
What are the 3 therapeutic strategies in NASH?
1) Prevent fatty acid oversupply: Diet, exercise, inhibit lipogenesis, PPARγ activator (thiazolidinediones - TZD).
2) Reduce damage: Antioxidants and anti-inflammatory agents.
3) Inhibit fibrosis: Prevent progression into cirrhosis.
