9: Liver Biochem Flashcards
Why is the liver an impressive organ?
Largest solid organ in the body
Two sources of blood supply to liver, what, and how much they contribute
- Portal vein: nutrient rich blood from GI; 75%
2. Hepatic artery: O2 rich blood; 25%
One way out of the liver for blood
Into the IVC
Does liver have G6P? What is the point?
Yes, it permits release of free glucose into blood
Name some blood proteins that are formed in the liver
albumin, Igs, apoproteins, fibrinogen, prothrombin, blood coagulation factors, APPs, CRP, bilirubin
Why is it good that the liver gets first access to enteric blood?
Can utilize ingested material and turn it into useful forms + harmful products can be converted safely and excreted
Two major functions of bile acids and salts
- Emulsification/digestion/absorption of fats + fat-soluble vitamins
- Elimination of cholesterol, prevention of cholesterol precipitation
How are bile salts considered detergents?
Theyre amphipathic
Purpose of bile acids being detergents
Help form micelles to increase surface area of lipids for digestion by lipases
PKa of taurocholic and glycocolic acids and why this matters
Taurocholic acid: pKA 2
Glycocolic acid: pKa 4
Duodenum has a pKa of 6, so these two acids are good for emulsification
Bile acid binding resins
Drugs that lower cholesterol
How do bile acid binding resins work? Four steps
- Bile acid binding resins cause large increase in bile acid excretion
- Increase bile acid synthesis
- Depletion of liver cholesterol pool
- Increased hepatic uptake of LDL from circulation
How much bile acid is reabsorbed vs excreted daily
95% reabsorbed, 5% excreted
Gallstone composition
Bile supersaturated with cholesterol
Two ways gallstones can form
- Insufficient secretion of bile salts/phospholipids
2. Excess cholesterol secretion into bile
Side effects of chronic disturbance in bile salt metabolism
Steatorrhea, deficiency in fat soluble vitamins
Xenobiotics
Compounds ingested from outside with no nutritional value (pharmacological agents, recreational drugs, food additives, etc.)
Metabolites
Compounds made in the body
Goal of hepatic metabolism of metabolites and xenobiotics
Increase hydrophilicity for easier excretion
How do agents that inhibit CYP work?
Drug forms a stable complex with CYP -> inhibits metabolism of other drugs that are substrates of that CYP
Four examples of agents that inhibit CYPs
Itraconozole, clarithromycin, cyclosporine, grapefruit juice
Three examples of agents that stimulate CYPs
St. John’s Wort, rifampicin, carbamezepine
Personal medicine and CYPs
Allelic variation of CYPs exist - genotyping CYPs can allow for understanding of an individual’s response to a particular drug
Liver cirrhosis
Result of chronic hepatitis characterized by fibrosis of liver lobes
Mechanism in liver cirrhosis
Stellate cells increase ECM synthesis -> infiltrates liver -> interferes with hepatocyte function
Major mechanism for liver diseases
Normally leaky basement membrane between endothelial cells and hepatocytes replaced by high density membrane containing fibrillar collagen + spaces between endothelial cells and fenestrations in plasma membrane are lost, causing impairment of free exchange of material between hepatocytes and blood
Liver function panel: values to look for
- Transaminases: ALT, AST
- Albumin, alkaline phosphatase, PT, bilirubin, urea (BUN), glucose, triacyglycerol
- Cholesterol: total, VLDL, LDL, HDL
