W2 P+P of Liver Flashcards
what are the metabolic functions of the liver
regulation of metabolism of carbohydrates, amino acids and lipid
Describe the metabolism of carbohydrates by the liver and in what way it is regulated
This is hormonally regulated
- Gluconeogenesis: glucose produced from AA
- Glycolysis: to form pyruvate then acetyl coA (aerobic) or lactate (anaerobic)
- Glycogenesis: glucose to glycogen
- Glycogenolysis: to release glucose
Describe fat metabolism by the liver
chylomicrons are processed, synthesis of cholesterol and lipoproteins, ketogenesis in starvation (for neural function)
Describe protein metabolism by the liver
plasma proteins are synthesised
transamination and deamination of AA
Conversion of ammonia to urea
Which hormones are deactivated by the liver
insulin, glucagon, ADH, steroid hormones
Which hormones are activated by the liver
- vitamin D –> 25-hydroxyvitamin D2 (further activated to 1,25- dihydroxyvitamin D3 in kidneys)
- conversion of thyroid hormone
State the 4 Major functions of the liver
- Storage
- Synthesis of proteins
- Detoxification
- Protection
What does the liver store
- Fat soluble vitamins ADEK in hepatocytes
- Water soluble vitamin B12 (hydroxycoblamin)
- iron, copper
- glycogen
what proteins does the liver process
- Coagulation factors II, VII, IX, X and Proteins C,S,Z
- Albumin
- complement proteins
- apolipoproteins
- carrier proteins
how does the liver provide protection
- Kupffer cells (liver macrophages) digest old RBC and bacteria
- immune factors eg acute phase proteins
detoxification by liver
- Endogenous substances eg bilirubin for Hb breakdown
- Exogenous substances like xenobiotics (drugs, ethanol)
What secretes bile
liver and bile duct cells (cholangiocytes)
where is bile before a meal
Stored and concentrated in the gall bladder (sphincter of oddi closed)
Describe release of bile
- smooth muscle in gall bladder contracts due to presence of chyme in duodenum via CCK and vagal impulses causing the sphincter of Oddi to open
- bile enters duodenum via cystic duct and common bile duct
what does the bile being slightly alkaline help?
neutralisation of chyme
pH adjustment for enzymes
protection of mucosa
micelle formation
Contents of hepatocyte juices
- primary bile acids
- water and electrolytes (Na+, K+, HCO3-, Ca2+, Cl-)
- lipids and phospholipids
- cholesterol
- IgA
- Bilirubin
- Metabolic wastes and conjugated drug metabolites
what is bilirubin
Breakdown product of porphyrin of Hb, makes urine yellow and faeces brown
what is cholelithiasis
what is it caused by
Gall Stones
Concentration of bile in GB due to reabsorption of water, excess cholesterol relative to bile acids and lecithin
Best treatment for cholelithiasis
Laparoscopic cholecystectomy if causing symptoms
Treatment for cholelithiasis with impaired renal function and small/medium bile stones and side effects of treatment
Ursodeoxycholic acid
Diarrhoea
What is biliary colic
Symptoms
symptomatic cholelithiasis
colic (sudden pain) occurs due to a gallstone temporarily blocking the cystic duct.
Pain in right upper part of the abdomen, lasts from 15 minutes to a few hours.
Treatment of Biliary colic and what can make it worse
Analgesia
Morphine can make it worse (SOO constricts)
Buprenorphine, pethidine
Treatment for biliary spasm
Atropine, GTN
how are bile salts reabsorbed
By active transport in the terminal ileum
how do bile salts return to the liver from the SI
hepatic portal circulation
via active and passive transport
how does body compensate for loss of small amount of bile acid via colon
resynthesis using hepatic cholesterol
Name primary and secondary bile salts and how 1 is converted to 2
Cholic and chenodeoxycholic are dehydroxylated by bacteria to deoxycholic and lithocholic
what happens to secondary bile acids
Return to liver, turned into bile salts
Name the three Bile acid sequestrants
Colveselam
Colestipol
Colestyramine
Action of bile acid sequestrants
Bind to bile acids, preventing their reabsorption
How do bile acid sequestrants lower LDL
- conversion of cholesterol to bile salts in liver
- increased LDL receptors on hepatocytes
- increase LDL cholesterol clearance from plasma
Clinical uses of bile acid sequestrants
hyperlipidaemia
cholestatic jaundice (itch)
bile acid diarrhoea
Limitations and adverse effects of bile acid sequestrants
large doses, diarrhoea, reduced absorption of fat soluble vitamin and some drugs (thiazide diuretics)
Main organ of drug metabolism
Liver
Phase I of drug metabolism
Oxidation, Reduction, Hydrolysis
makes drug more polar by adding a reactive group, allowing for conjugation
Phase II of drug metabolism
Conjugation of chemically reactive groups
Where do phase I oxidation reactions occur
haem groups in ER of hepatocytes
where do phase II reactions occurs and do they result in
Liver
Inactive products
Glucouronidation
Part of phase II
transfer of glucouronic acid to electron rich atoms of substrate
What is hepatic encephalopathy
Symptoms
In hepatic failure, detoxification of ammonia to urea fails so blood NH3 levels rise, having a toxic effect on CNS
Drowsiness, incoordination, coma, death due to cerebral oedema
Treatment of hepatic encephalopathy
- Lactulose (acidifies stoo, converts NH3 to NH4 which isnt absorbed)
- antibiotics :neomycin, rifamixin (suppress colonic flora therefore ammonia production)
