Biochemistry of Liver Flashcards
Describe hepatic circulation
- Blood flows out of the liver through three hepatic viens into the IVC
- Oxygen rich blood flows into the liver through hepatic artery and nutrient rich blood from bowel comes in via portal vein
- Bile flows out through bile duct
Describe hepatocytes
- 60% of cells in the liver
- Carry out metabolic fxns of liver
- respond to hormones and have receptors and transporters to carry out signal paths can regenerate
Describe endothelial cells
Present in the lining of sinusoids, don’t form tight basesment membrane with hepatocytes
Loose and have pores and fenestrations in plasma membrane to allow excchange of material from liver to blood and vise versa
Kupffer cells
- Lining of sinusoids
- Macrophages protecting liver from gut microbes
- remove damaged dead RBCs
- Secrete cytokines
- Well dev endocytic and phagocytic fxns
- Lots of lysosomes
Hepatic stellate cells
- Lipid filled cells for storage of vitamin A
- Control turnover of hepatic CT and ECM and regulate contractility of sinusoids
Hepatic stellate cells during cirrhosis?
- stimulated by various signals to increase synthesis of ECM material. This will infiltrate the liver interferring with fxn of hepatocytes
Pit cells?
NK cells for defense against toxic agens or viruses
Cholangiocytes
line bile duct and control bile flow rate and bile pH
Functions of the liver
- Carb Metabolism
- Lipid metabolism
- Nucleotide biosynthesis
- Protein and AA metabolism
- Urea cycle
- Synthesis of blood proteins
- Bilirubin metabolism
- Waste management, inactivation, detoxification and biotransformation of metabolites and xenobiotics
What is the major role of the liver?
Monitoring, synthesizing, recycling, distributing, and modifying metabolites
Describe the livers unique circulation
- It has low portal pressure
- The two sources of blood from the enteric circulation and periphery mix in the sinusoids
What are the structural features of the liver and what do they allow for?
- Lacks basement menbrane and absence of tight jxn btw hepatocytes and endothielial cells
- Gaps btw endothelial cells
- Fenestrations in endothelial membrane
- Allows for Greater access and iincreased contact btw liver and blood
What is bile made of
- Bile acids, bile salts, cholesterol, phospholipids, fatty aids, proteins, bile pigments and inorganic salts
What do bile acids and salts help with?
- Emulsification of fats
- Absorption of fat soluble vitamins
- digestion and absorption of fats
- prevention of cholesterol precipitation
- elimination of cholesterol
Where are bile acids and salts synthesized from?
From Hepatic cholesterol, made in hepatocytes, releawsed into bile canaliculi and stored and concentrated in gall bladder
What is the RLS of bile acid/salt synthesis? Where does it occur in the cell?
- 7a-hydryoxylase acting on cholesterol to create 7a-hydroxycholesterol
- ER of hepatocytes
Why does bile acid need to be conjugated? Which conjugated version is favored?
- The pH of duodenum is 6 and cholyl CoA is also 6 so it wont be a good detergent, it isn’t ionized. If we add glycine and make Glycocholic acid with a pKa of 4 it will be ionized. If you add Taurine and make Taurocholic acid it will have a pKa of 2 and be even more ionized.
- 3:1 in favor of adding glycine to get glycocholic acid (pKa 4)
What are the secondary bile acids and what are they derived from?
Deoxycholic acid from cholic acid and Lithocholic acid from chenodeoxycholic acid
How are secondary acids formed?
Bacteria deconjugate and dehydroxylate to form secondary bile acids which are absorbed by ileum and excreted in feces but mostly recycled to liver via enterohepatic circulation
How do cholesterol lowering drugs work?
They bind are bile acid binding resins. Non absorbable bile acid binding resins like cholestryamine cause an increase in excretion of bile acids and the rate of bile acid synthesis is increased by induction of 7a hydroxylase and this depletes the liver cholesterol pool. Increases hepatic uptake of LDL cholesterol from circulation lowering plasma levels.
What are gallstones and what causes them?
- Crystals made of bile supersaturated with cholesterol
- Cholelithiasis: insufficient secretion of bile salts or phospholipids into gall bladder or excess cholesterol secetion into bile
- Chronic disturbances in bile salt metab leads to malabrorption syndroms such as steatorrhea and deficiency in fat soluble vitamins
What are Xenobiotics?
- Compounds ingetsted from the outside with no nutritional value and potentially toxic, includes:
- Pharmacological agents
- Recreational drugs
- Components of food such as preservatives, additives and coloring
What are the phases for inactivation and detoxification of xenobiotics?
- Phase 1: increase polarity
- Phase II: functional gorups are conjugated to make molecules more amendable for safe excretion
What catalyzes phase 1 of liver detox and inactivation of xenobiotics?
CytochromeP450
