Physiology - Gastrointestinal

Question 1

List the enzymes secreted from the exocrine pancreas and what they do

Answer 1

-trypsin: digests proteins, polypeptides
-chymotrypsin: digests proteins, polypeptides
-elastase: digests elastin and some proteins
-carboxypeptidase: digests proteins (cleaves terminal bonds)
-lipase: digests triglycerides
-alpha-amylase: digests starch
-ribonuclease: digests RNA

Question 2

Describe the regulation of pancreatic juice secretion

Answer 2

-exocrine secretion from alveolar gland acinar cells under hormone control, stimulated by secretin and CCK
-secretin stimulates secretion of alkaline pancreatic juice poor in enzyme content
-CCK and ACh act on acinar cells to stimulate release of zymogen granules and pancreatic juice rich in eyzymes

Question 3

Describe the composition of pancreatic juice

Answer 3

alkaline
high HCO3- content
cations, anions
digestive enzymes (proenzymes)
1500ml secreted per day

Question 4

What factors regulate gastric secretion

Answer 4

-cephalic phase: food in mouth triggers vagal stimulation that stimulates gastrin secretion (stimulates HCL)
-gastric phase: meal constituents tiggers gastrin secretion and stretch stimulates vagal flow
-intestinal phase: fats/carbohydrates/acids in duodenum inhibits gastric acid secretion

Question 5

Describe how carbohydrates are digested (enzymes and location) and absorbed

Answer 5

digestion:
-mouth: salivary alpha amylase begins digestion of starch (polysaccharides to disaccharides)
-duodenum: pancreatic alpha amylase acts on polysaccharides to disaccharides
-brush border cells: sucrase, lactase and maltase convert disaccharides to monosaccharides
-colon: bacteria break down oligosaccharides

absorption:
-hexoses (glucose) are rapidly absorbed across the small intestine wall, all removed before the terminal ileum
-glucose crosses the membrane via SGLUT-1 co-transported with Na+ (secondary active transport)
-glucose is then transported into the interstitium via GLUT-2 (facilitated diffusion)

Question 6

Describe the enzymes required for the digestion of lipids and their location

Answer 6

-mouth: lingual lipase secreted by von Ebner gland on dorsal surface of tongue and can digest TAG
-stomach: gastric lipase is of little importance
-duodenum: pancreatic lipase responsible for most fat digestion

Question 7

What processes are involved in the digestion of lipids

Answer 7

-lingual, gastric & pancreatic lipase
-emulsification of fats in SI by bile acids to form micelles (contain fa + monoglycerides + cholesterol in core)
-lipids diffuse out of micelles along the brush border and enter enterocytes by carriers
-inside enterocyte, fatty acids and monoglycerides are re-esterified to form TAG and then chylomicrons are formed
-chylomicrons are released by exocytosis and enter lymphatics via lacteals, then enter the thoracic duct

Question 8

Describe how proteins are digested and absorbed in the gastrointestinal tract

Answer 8

Digestion:
-stomach: chief cells secrete pepsinogen, activated to pepsin by gastric acid and initiates digestion by catalysing the hydrolysis of peptide bonds
-small intestine: pancreatic endopeptidases (trypsin, chymotrypsin and elastase) cleave non-terminal polypeptide bonds
-small intestine brush border: exopeptidases (such as amino/carboxy/dipeptidases) cleave terminal peptide bonds and release individual amino acids
-colon: small amount of protein digestion by bacteria

Absorption:
-two phases: first into intestinal mucosal cells, then out into interstitial fluid, capillaries and portal blood
-seven transport systems move amino acids into enterocytes (both sodium dependent and independent, mostly co-transported with Na+ and Cl-)
- five transport systems move amino acids out of enterocytes
-absorption is rapid in the duodenum and jejunum and minimal in the ileum

Question 9

How does protein absorption and digestion differ in infants and young children compared to an adult

Answer 9

infants absorb more undigested protein, resulting in more food allergy but passive immunity

Question 10

Explain the mechanisms of absorption of water and electrolytes in the gastrointestinal tract

Answer 10

water:
moves passively driven by electrochemical gradients, mostly reabsorbed in the jejunum

sodium:
absorption = SI and colon: NaCl crosses apical membrane via Na+/H+ exchanger and Cl-/HCO3 exchanger
distal colon: Na+ crosses apical membrane via Na+ channels
secretion = SI and colon: via Na+/K+/2Cl- co-transporter

Question 11

How is bilirubin produced and metabolised in the body

Answer 11

1. bilirubin comes from breakdown of RBC
2. Hb breaks down into globin and heme
3. heme further broken down into Fe3+ and biliverdin
4. biliverdin converted to unconjugated (indirect, water insoluble) bilirubin by biliverdin reductase in circulation
5. unconjugated bilirubin binds to albumin in circulation and is then taken up by the liver
6. in the liver, unconjugated bilirubin is conjugated (direct, water soluble) via glucuronidation and secreted into the intestine
7. in intestine, conjugated bilirubin is converted back to unconjugated form by intestinal bacteria to urobilinogen
8. urobilinogen either excreted in faeces or enters portal vein, re-enters circulation and excreted in urine

Question 12

What is the composition of bile

Answer 12

-water (97%)
-bile salts (0.7%): cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid
-bile pigments (0.2%): conjugated bilirubin and biliverdin
-cholesterol (0.06%), lecithin (0.01%), inorganic salts

Question 13

What are the causes of jaundice

Answer 13

1) Unconjugated hyperbilirubinaemia
-excess production of bile = haemolytic aneamia
-reduced hepatic intake = hepatitis, cirrhosis
-impaired bilirubin conjugation = physiological jaundice of the newborn

2) Conjugated hyperbilirubinaemia
-decreased hepatocellular excretion = medications (OCP)
-impaired intra/extra-hepatic bile flow = primary biliary cirrhosis, biliary atresia
-hereditary syndrome = dublin johnson

Question 14

What are the principle functions of the liver

Answer 14

Nutrition:
- bile formation: up to 500ml per day
- absorption, metabolism, regulation and storage of nutrients such as vitamins, iron, AAs, lipids and glycogen

Synthesis: synthesis of protein, coagulation factors, albumin

Detoxification/inactivation of drugs and toxins: P450 enzymes, removal of ammonia

Immunity: filtering/phagocytosis via Kupffer cells, synthesis of acute phase proteins, complement proteins, cytokines

Question 15

How is iron absorbed from the gastrointestinal tract

Answer 15

-ingested iron is in the ferric (Fe+3) form, but the ferrous (Fe+2) form is absorbed
-minimal absorption in stomach but gastric secretions dissolve iron and aid conversion to ferrous form
-most absorption occurs in the duodenum
-Fe+3 is converted to Fe+2 by duodenal cytochrome B
-Fe+2 is then absorbed into enterocytes by the DMT1 transporter on the apical membrane
-Fe+2 exits cell into the interstitium via ferroportin 1 on basolateral membrane
-Fe+2 is then converted to Fe+3 by hephaestin

Question 16

What mechanisms regulate iron absorption?

Answer 16

Dietary Fe intake
Status of iron stores
EPO

Question 17

What factors reduce iron absorption from the gastro-intestinal tract

Answer 17

-dietary: phytic acids (cereals), oxalates and phosphates bind iron to produce insoluble compounds
-surgical: duodenal surgery
-physiological: high iron stores
-drugs: antacids, some antibiotics

Question 18

How is iron transported in plasma

Answer 18

Fe+2 is converted to Fe+3, which binds to transferrin

Question 19

What are the main factors that influence plasma glucose level

Answer 19

-overall balance between glucose entering and leaving the bloodstream

1) dietary intake
2) cellular uptake
3) hepatic production versus storage
4) renal filtration (freely filtered but reabsorbed up to Tmax)
5) hormonal effects

Question 20

What hormones effect plasma glucose levels

Answer 20

increase BSL: noradrenaline, glucagon, growth hormone, cortisol
decrease BSL: insulin, insulin like growth factor

Question 21

What are the potential pathways for glucose metabolism in the body

Answer 21

glucose is normally phosphorylated to glucose-6-phosphate, which may follow several pathways:
1) converted back to glucose
2) stored in glycogen
3) converted to pyruvate, then acetyl-CoA and enters the citric acid cycle: aerobic or anaerobic metabolism

Question 22

Name the principle ketone bodies and how are they formed and when do they accumulate

Answer 22

KBs: acetoacetate (AcAc), beta-hydroxybutyrate (BHB), acetone

Produced by the liver from fatty acids:
- acetyl-CoA is converted to acetoacetyl-CoA
- acetoacetyl-CoA is converted to AcAc
- AcAc is converted to BHB and acetone (not metabolised in liver, enters circulation)

Excess ketones: diabetes, fasting/starvation, high fat low carb diet

Question 23

What happens to glucose homeostasis in the absence of insulin (physiological effects of insulin deficiency)

Answer 23

-plasma hyperglycaemia due to:
decreased peripheral uptake of glucose into muscle and fat
reduced uptake of glucose by the liver
increased glucose output by the liver and lack of glycogen synthesis

-intracellular glucose deficiency
-protein/fat catabolism
-secondary osmotic diuresis, dehydration, ketosis

Question 24

By what mechanism does glucose cause the release of insulin?

Answer 24

• glucose enters pancreas beta cells via GLUT-2, glycolysis to generate ATP and pyruvate
• this blocks ATP-sensitive K channels (KATP), leads to depolarisation
• opening of voltage-dependent Ca channels allows Ca to enter the cell
• exocytosis of insulin vesicles

Question 25

Describe the process of vitamin metabolism

Answer 25

• Most vitamins are absorbed in the upper small intestine, except for B12 which is absorbed in the ileum
• Water soluble vitamins such as Vit B12 and folate absorption are Na+ independent, whereas the
  remaining seven water soluble vitamins (e.g. riboflavin, niacin, thiamine, ascorbic acid) are cotransported with Na+ and therefore Na+ dependent
• Fat soluble vitamins such as A,D,E and K are initially ingested by cholesterol esterase into micelles
• Highly INSOLUBLE in the gut unless first broken down

Question 26

Describe the metabolism and formation of Vitamin D

Answer 26

• Vitamin D3 (cholecalciferol) is produced in the skin from 7-dehydrocholesterol (7-DHC) by the action of sunlight
• Vitamin D3 is metabolised by enzymes of the cytochrome P450 superfamily
• 25-hydroxylation occurs in the liver, which converts Vitamin D3 into 25-hydroxycholecalciferol
• 25-hydroxycholecalciferol is converted to 1,25 dihydroxycholecalciferol in the kidneys