Liver

Question 1

What are the main functions of the liver?

Answer 1

Metabolic: Carbs, fats, proteins, steroid hormones, insulin, aldosterone, bilirubin, drugs; Synthetic: Albumin, clotting factors (II, VII, IX, X), fibrinogen, cholesterol, 25-OH vitamin D; Immunological: Kupffer cells; Storage: Glycogen, vitamins A & D, iron; Homeostasis: Glucose regulation; Bile production for fat digestion; Clearance of toxins, drugs, bilirubin

Question 2

What is the functional unit of the liver and how is it structured?

Answer 2

Liver is made of hexagonal lobules; Blood enters via portal vein (nutrients) and hepatic artery (oxygen); Flows through sinusoids between hepatocytes; Drains into central vein; Hepatocytes line sinusoids, processing blood; Bile flows in opposite direction toward bile duct

Question 3

What are the roles of hepatocytes?

Answer 3

Filter/process nutrients, toxins, and drugs; Produce albumin; Aid metabolism; Secrete bile into bile canaliculi for fat digestion

Question 4

What is the function of albumin produced by the liver?

Answer 4

Maintains oncotic pressure; Transports drugs like warfarin, aspirin, ibuprofen; Can be outcompeted by bilirubin; Low albumin → fluid leaks into tissues → oedema, ascites in liver disease

Question 5

What clotting functions does the liver perform?

Answer 5

Synthesizes vitamin K–dependent factors (II, VII, IX, X); Supports clotting cascade → produces fibrinogen; Vitamin K is fat-soluble → absorption depends on bile; Liver disease → increased bleeding risk

Question 6

How is bilirubin processed in the liver?

Answer 6

RBCs → broken to haem + globin; Haem → iron + biliverdin → bilirubin; Bilirubin binds albumin → liver; Liver conjugates bilirubin (water-soluble) for excretion in bile; Excess → jaundice (yellow skin/eyes), pale stool

Question 7

How does the liver metabolize carbohydrates?

Answer 7

Glycogen storage; Converts galactose/fructose to glucose; Gluconeogenesis; Uses glucose sensor mechanisms; Glycogen phosphorylase and PP1 regulate glycogen synthase

Question 8

What roles does the liver play in fat metabolism?

Answer 8

Stores and processes lipids; Produces cholesterol; Handles fat-soluble vitamin metabolism (A, D); Helps in bile production for fat digestion

Question 9

What are the two phases of drug metabolism in the liver?

Answer 9

Phase I: Oxidation, reduction, hydrolysis via CYP450 → polar metabolites; Phase II: Conjugation (glucuronidation, acetylation, sulfation) → inactive, water-soluble drugs

Question 10

What are CYP450 enzymes and why are they important?

Answer 10

Membrane-bound enzymes with iron moiety; Metabolize lipophilic substances; Handle endogenous molecules (e.g. steroids); Vital for Phase I metabolism; Polymorphisms affect individual drug responses

Question 11

What is CYP450 polymorphism and its significance?

Answer 11

Genetic variation in CYP enzymes; Alters metabolism and efficacy of drugs; E.g. 10% can’t convert codeine → morphine; Inducers ↑ enzyme levels (e.g. rifampin); Inhibitors ↓ enzyme activity (e.g. grapefruit juice)

Question 12

What are Phase II reactions in drug metabolism?

Answer 12

Conjugation with groups like glucuronide, sulfate, acetyl; Converts drugs to inactive, water-soluble forms; Enhances renal excretion; Slow acetylators = prolonged drug effects

Question 13

What is the extraction ratio in hepatic drug metabolism?

Answer 13

High-extraction drugs: Rapidly metabolized, limited by blood flow; Low-extraction drugs: Metabolized slower, limited by liver cell function; Affects dosing and first-pass metabolism