GIT

Question 1

What factors influence glucose homeostasis? What happens to glucose homeostasis in the absence of insulin? By what mechanism does glucose cause the release of insulin?

Answer 1

1. Factors influencing glucose homeostasis
   - Glucose ingestion and absorption in the small intestine
   - Glucose reabsorption from kidney
   - Glucose uptake into the peripheral cells, muscles and fat
   - Gluconeogenesis by liver
2. Absence of insulin causes
   - Reduce peripheral uptake of glucose into muscles and fats
   - Reduce glucose uptake into liver
   - Increase gluconeogenesis
   - Reduce glycogen synthesis
3. Glucose cause release of insulin by
   - Binding to GLUT2 receptors on B-cells of pancreas
   - Converted into pyruvate -> Enters citric acid cycle -> Produces ATP + Triggers K+ efflux and Ca influx
   - Stimulates release of pre-formed insulin granules

Question 2

How is iron absorbed from the gastrointestinal tract? What factors reduce iron absorption from the gastrointestinal tract? How is iron transported in the plasma? What are the mechanisms that regulate iron absorption? Physiologically, how is iron lost from the body?

Answer 2

1. Iron absorption
   - Ingested mainly as Fe 3+ (ferric)
   - Absorbed mainly in duodenum and some in stomach
   - Fe3+ oxidised to Fe2+ (Ferrous) by ferrous reductase or gastric acid
   - Fe2+ enters enterocytes via iron transporter
   - Dietary heme is absorbed directly by enterocytes via heme transporter
   - Heme oxidised by heme reductase into Fe2+
   - Fe2+ then converted into Fe3+
   - Bound to ferritin to be stored
2. Factors influencing iron absorption
   - Surgical: Gut resection, partial gastrectomy
   - Physiological: High iron stores, recent high iron dietary intake
   - Drugs: Antacids, acid-lowering drugs, antibiotics that alter acid in the stomach
3. Iron is transported by
   - In the form of Fe3+ bound to transferrin
   - To liver and bone marrow
4. Mechanisms regulating iron absorption is unclear but can be influenced by
   - Recent iron dietary intake
   - Iron stores in body
   - Erythropoeisis state in bone marrow
5. Iron can be lost in
   - Gut
   - Menstruation/bleeding
   - Saturation of transferrin

Question 3

List the principal functions of the liver. Describe the metabolism of bilirubin.

Answer 3

1. Functions of liver
   - Bile formation (500mls/day)
   - Synthesizes albumin, protein, clotting factors
   - Inactivates and detoxifies drugs
   - Absorbs and metabolises nutrients and vitamins absorbed from the enteric circulation
   - Role in immunity -> Producing immunoglobulins, Kupffer cells
   - Glucose homeostasis -> Gluconeogenesis, glycogen synthesis and lysis
   - Repackages lipids
2. Metabolism of bilirubin
   - Formed from breakdown of haem in RBC
   - Unconjugated bilirubin is insoluble in plasma
   - Bound to albumin to be transported to liver
   - Glucuronidation to become conjugated bilirubin
   - Excreted into bile which enters gut
   - In the gut, bilirubin oxidised to urobilinogen by gut bacteria
   - 20% reabsorbed into enterohepatic circulation
   - Bilirubin is excreted as stercobilin in gut and urobilin in urine