W2 P+P of Liver

Question 1

what are the metabolic functions of the liver

Answer 1

regulation of metabolism of carbohydrates, amino acids and lipid

Question 2

Describe the metabolism of carbohydrates by the liver and in what way it is regulated

Answer 2

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

Question 3

Describe fat metabolism by the liver

Answer 3

chylomicrons are processed, synthesis of cholesterol and lipoproteins, ketogenesis in starvation (for neural function)

Question 4

Describe protein metabolism by the liver

Answer 4

plasma proteins are synthesised
transamination and deamination of AA
Conversion of ammonia to urea

Question 5

Which hormones are deactivated by the liver

Answer 5

insulin, glucagon, ADH, steroid hormones

Question 6

Which hormones are activated by the liver

Answer 6

• vitamin D –> 25-hydroxyvitamin D2 (further activated to 1,25- dihydroxyvitamin D3 in kidneys)
• conversion of thyroid hormone

Question 7

State the 4 Major functions of the liver

Answer 7

• Storage
• Synthesis of proteins
• Detoxification
• Protection

Question 8

What does the liver store

Answer 8

• Fat soluble vitamins ADEK in hepatocytes
• Water soluble vitamin B12 (hydroxycoblamin)
• iron, copper
• glycogen

Question 9

what proteins does the liver process

Answer 9

• Coagulation factors II, VII, IX, X and Proteins C,S,Z
• Albumin
• complement proteins
• apolipoproteins
• carrier proteins

Question 10

how does the liver provide protection

Answer 10

• Kupffer cells (liver macrophages) digest old RBC and bacteria
• immune factors eg acute phase proteins

Question 11

detoxification by liver

Answer 11

• Endogenous substances eg bilirubin for Hb breakdown

- Exogenous substances like xenobiotics (drugs, ethanol)

Question 12

What secretes bile

Answer 12

liver and bile duct cells (cholangiocytes)

Question 13

where is bile before a meal

Answer 13

Stored and concentrated in the gall bladder (sphincter of oddi closed)

Question 14

Describe release of bile

Answer 14

• 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

Question 15

what does the bile being slightly alkaline help?

Answer 15

neutralisation of chyme
pH adjustment for enzymes
protection of mucosa
micelle formation

Question 16

Contents of hepatocyte juices

Answer 16

• primary bile acids
• water and electrolytes (Na+, K+, HCO3-, Ca2+, Cl-)
• lipids and phospholipids
• cholesterol
• IgA
• Bilirubin
• Metabolic wastes and conjugated drug metabolites

Question 17

what is bilirubin

Answer 17

Breakdown product of porphyrin of Hb, makes urine yellow and faeces brown

Question 18

what is cholelithiasis

what is it caused by

Answer 18

Gall Stones

Concentration of bile in GB due to reabsorption of water, excess cholesterol relative to bile acids and lecithin

Question 19

Best treatment for cholelithiasis

Answer 19

Laparoscopic cholecystectomy if causing symptoms

Question 20

Treatment for cholelithiasis with impaired renal function and small/medium bile stones and side effects of treatment

Answer 20

Ursodeoxycholic acid

Diarrhoea

Question 21

What is biliary colic

Symptoms

Answer 21

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.

Question 22

Treatment of Biliary colic and what can make it worse

Answer 22

Analgesia
Morphine can make it worse (SOO constricts)
Buprenorphine, pethidine

Question 23

Treatment for biliary spasm

Answer 23

Atropine, GTN

Question 24

how are bile salts reabsorbed

Answer 24

By active transport in the terminal ileum

Question 25

how do bile salts return to the liver from the SI

Answer 25

hepatic portal circulation | via active and passive transport

Question 26

how does body compensate for loss of small amount of bile acid via colon

Answer 26

resynthesis using hepatic cholesterol

Question 27

Name primary and secondary bile salts and how 1 is converted to 2

Answer 27

Cholic and chenodeoxycholic are dehydroxylated by bacteria to deoxycholic and lithocholic

Question 28

what happens to secondary bile acids

Answer 28

Return to liver, turned into bile salts

Question 29

Name the three Bile acid sequestrants

Answer 29

Colveselam Colestipol Colestyramine

Question 30

Action of bile acid sequestrants

Answer 30

Bind to bile acids, preventing their reabsorption

Question 31

How do bile acid sequestrants lower LDL

Answer 31

- conversion of cholesterol to bile salts in liver - increased LDL receptors on hepatocytes - increase LDL cholesterol clearance from plasma

Question 32

Clinical uses of bile acid sequestrants

Answer 32

hyperlipidaemia cholestatic jaundice (itch) bile acid diarrhoea

Question 33

Limitations and adverse effects of bile acid sequestrants

Answer 33

large doses, diarrhoea, reduced absorption of fat soluble vitamin and some drugs (thiazide diuretics)

Question 34

Main organ of drug metabolism

Answer 34

Liver

Question 35

Phase I of drug metabolism

Answer 35

Oxidation, Reduction, Hydrolysis makes drug more polar by adding a reactive group, allowing for conjugation

Question 36

Phase II of drug metabolism

Answer 36

Conjugation of chemically reactive groups

Question 37

Where do phase I oxidation reactions occur

Answer 37

haem groups in ER of hepatocytes

Question 38

where do phase II reactions occurs and do they result in

Answer 38

Liver | Inactive products

Question 39

Glucouronidation

Answer 39

Part of phase II | transfer of glucouronic acid to electron rich atoms of substrate

Question 40

What is hepatic encephalopathy | Symptoms

Answer 40

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

Question 41

Treatment of hepatic encephalopathy

Answer 41

- Lactulose (acidifies stoo, converts NH3 to NH4 which isnt absorbed) - antibiotics :neomycin, rifamixin (suppress colonic flora therefore ammonia production)