Physiology

Question 1

Describe the enzymes required for the digestion of carbohydrates & their location.

Answer 1

• Mouth - salivary amylase
• Duodenum - pancreatic amylase
• Intestinal brush border - oligosaccharidases
  
  • isomaltase, lactase, curase, maltase
• Final oligosaccharides
  
  • alpha-dextrins, maltose, lactose, sucrose are metabolised to one of the hexoses (monosaccharides - galactose/fructose/glucose)

Question 2

Please describe how carbohydrates are absorbed from the gastrointestinal tract.

Answer 2

• Two phases
  
  • first into intestinal mucosal cell
  • second into interstitial fluid (ECF) & thus into capillaries & portal blood
• Glucose/galactose
  
  • secondary active transport with sodium - low conc of Na inhibits transport (ie Na dependent) - co-transporters SGLT-1 & SGLT-2
  • facilitated diffusion into ECF by GLUT-2
• Fructose
  
  • facilitated diffusion by GLUT-5 into cell, then GLUT-2 into ECF
• Ribose/Deoxyribose - diffusion

Question 3

Describe the enzymes required for the digestion of proteins & their location.

Answer 3

• Stomach - pepsinogens activated by gastric HCL (pH 1.6-3.2) to pepsins result in polypeptides
• Small intestine lumen (pH 6.5) - proteolytic enzymes of the pancreas & intestinal mucosa, polypeptides -> amino acids
  
  • endopeptidases (trypsin, chymotrypsin, & elastase) exopeptidases
• Brush border - polypeptides -> amino acids
  
  • amino/carboxy/endo/di peptidases
• Cytoplasm of mucosal cells (after absorption by active transport)

Question 4

Describe how proteins are absorbed from the gastrointestinal tract.

Answer 4

Two phases

• First into intestinal mucosal cell
  
  • seven different transport systems for amino acids (Na dependent and independent)
• Second into interstital fluid (ECF), capillaries/portal blood
  
  • 5 different transport systems

Question 5

Describe the enzymes required for the digestion of lipids & their location.

Answer 5

• Stomach
  
  • lingual lipase (works on TGs)
• Small intestine
  
  • pancreatic lipase - requires colipase for maximal activity (TGs)
  • pancreatic bile-salt activated lipase (TGs, cholesterol esters, vitamins, phospholipids)
  • cholesteryl ester hydrolase (cholesterol)

Question 6

What other process is involved in the digestion of lipids?

Answer 6

• Emulsification
• Micelles
  
  • formed from bile salts, lecithin, & monoglycerides surrounding fatty acids, monoglycerides, & cholesterol
• Transport lipids through ‘unstirred layer’ to brush border of mucosal cells.

Question 7

Describe how lipids are absorbed from the gastrointestinal tract.

Answer 7

Two phases

• First into intestinal mucosal cell
  
  • passive diffusion & carriers
• Second into ECF, thus into capillaries/portal blood (FFAs), or lymphatics (chylomicrons)
  
  • Dependent on size
  • < 10-12 carbons - directly into portal blood (FFAs)
  • > 10-12 carbons - reesterified to TGs or cholesteryl esters & packaged in chylomicrons (coating of protein, chol, & phospholipids)

Question 8

Describe the characteristics of nerve fibres responsible for transmission of ‘fast pain’?

Answer 8

• Myelinated A delta fibres
• 2-5um diameter
• conduction rates 12-30m/s
• end in dorsal horn (lamina 1 & 5)
• neurotransmitter is glutamate

Question 9

What are the differences between A delta nerve fibres & those responsible for transmission of ‘slow’ or second pain?

Answer 9

• myelinated A delta fibres vs unmyelinated C fibres
• A delta fibres 2-5um diameter vs C fibres are smaller 0.4-1.2um diameter
• A delta end in dorsal horn lamina 1 & 5, C fibres also dorsal horn but lamina 1 & 2
• A delta neurotransmitter is glutamate, C fibres is substance P
• different sensation - C fibres dull/intense/diffuse
• different locations as less A delta fibres in deeper structures

Question 10

What do you understand by the term referred pain?

Answer 10

• Same embryonic segment or dermatome
• Eg diaphragm to shoulder tip

Question 11

What are the major factors determining the plasma glucose level?

Answer 11

1. Concept: Balance between glucose entering the bloodstream & glucose leaving the bloodstream
2. Dietary intake
3. Cellular uptake (particularly muscle/fat/hepatic)
4. Hepatic glucostat/glycogenisis, glycogenolysis, gluconeogenesis
5. Renal freely filtered but PT reabsorbed to Tmax
6. Hormonal effects on these (esp 1,3,4)

Question 12

List the hormones which effect plasma glucose levels.

Answer 12

Decreased BSL

• Insulin, Insulin-like GF 1 & 2
• Insulin via glucose uptake (all tissues), glyconeogenesis. Liver: gluc -> fat. IGF: similar but less

Increased BSL

• Catecholamines (Nor/Adr partic) > Glucagon > GH > Cortisol > Thyroid
• Catechol - B receptor -> inc cAMP -> glycogenolysis/gluconeogenesis
• Glucagon - inc cAMP direct
• TFTs - absorption + inc glycogenolysis (liver) + insulin breakdown inc
• Cortisol - permissive to glucagon/catecholamines + some glucogenesis, prot -> gluc, dec uptake
• GH - gluc liver, insulin block, dec tissue uptake

Question 13

What are the principal functions of the liver?

Answer 13

• Bile formation (500mls/day) - excretion, elimination, digestion
• Synthesis - protein, coag, binding prot, albumin
• Inactivation/detox - drugs, toxins, active circ substances
• Nutrient vitamin absorption, metabolism/control (eg glucostat) AAs, lipids, fat soluble vitamins
• Immunity (partic gut organisms) - Kupffer/macrophages in sinusoid endothelium

Question 14

Describe bilirubin’s path from production to excretion.

Answer 14

1. Most formed by breakdown of Heme/Hb
2. Bilirubin bound to albumin
3. In liver active transported (OATP) -> dissociates & crosses cell membrane -> binds to cytoplasmic proteins
4. Conjugated by gluc-transferase in ER with glucoronic acid to H2O soluble bil-digluc
5. Bil-digluc active transport against gradient to bile canaliculi to gut (< 5% bil/bil-digluc reflux to blood)
6. Intestinal mucosa relatively impermeable
7. Gut bacteria act/convert most to urobilinogens
8. Some bile pigments/urobilinogens/unconj bil reabsorbed in portal circ, most resecreted (enterohepatic circulation)
9. Small amounts of urobilinogen in blood, excreted in urine as urobil, and excreted in faeces as stercobil

Question 15

What factors control blood glucose levels?

Answer 15

• Dietary intake
• Rate of entry into cells
• Glucostatic activity of the liver
  
  • Storage of glycogen
  • Breakdown of glycogen
  • Gluconeogenesis

Question 16

What are the potential pathways for glucose metabolism in the body?

Answer 16

• Aerobic
• Anaerobic
• Glycogen
• Pentoses

Question 17

1. Physiologically what are the acute consequences of insulin deficiency?
2. Describe the biosynthesis of insulin.

Answer 17

1. Intracellular glucose deficiency -> extracellular excess -> protein & fat catabolism.
2. B cells as a precursor hormone -> insulin released from the cell with C peptide

Question 18

Describe the structure of the insulin receptor.

Answer 18

• 2 alpha & 2 beta glycoprotein subunits

Question 19

Name the principal pancreatic enzymes & the substances upon which they act.

Answer 19

• Trypsin, Chymotrypsin - proteins, polypeptides
• Elastase - elastin & other proteins
• Carboxypeptidase A & B - proteins, polypeptides
• Colipase - fat droplets
• Pancreatic lipase - triglycerides
• Bile salt-acid lipase - cholesterol esters
• Pancreatic amylase - starch
• Deoxyribonuclease & Ribonuclease - DNA/RNA
• Phospholipase A2 - phospholipids

Question 20

Describe the regulation of pancreatic juice secretion.

Answer 20

• Primarily under hormonal control
• Secretin acts on the duct to cause production of copious amounts of very alkaline pancreatic juice poor in enzymes
• As flow of pancreatic juice increases it becomes more alkaline (because exchange of HCO3 for Cl in the distal duct is inversely proportional to flow)
• CCK acts on acinar cells to cause release of zymogen granules -> pancreatic juice rich in enzymes
• Acetylcholine also stimulates release of zymogen granules (minor effect, vagally-mediated pancreatic juice secretion in response to sight/smell of food)

Question 21

Describe the metabolism and excretion of bilirubin.

Answer 21

• Breakdown of haemoglobin leads to bilirubin which is bound to albumin in the circulation
• In the liver it dissociates & free bilirubin enters the hepatic cell where it is conjugated by glucuronyl transferase with 2 molecules of uridine diphosphoglucuronic acid (UDPGA) to form bilirubin diglucuronide & EDP. Diglucuronide is more soluble than free bilirubin
• Mostly passed into the bile ducts & excreted via the intestines
• Small amount enters the blood & is measurable as conjugated bilirubin in the blood

Question 22

What factors regulate gastric secretion?

Answer 22

• Neural & hormonal
• Cephalic/Gastric/Intestinal
• Cephalic
  
  • food in mouth -> vagus n
  • phsyiologic states -> hypersecretion
• Gastric
  
  • food in stomach, local receptors (eg to AA/protein digestions) -> post ganglionic neurons -> parietal cells -> acid secretion
• Intestinal
  
  • fats, carbs, & acid in duodenum inhibit gastric acid secretion, pepsin secretion, & motility by neural & hormonal mech eg peptide YY
• Neural
  
  • Vagal increases gastrin secretion in G cells by GRP -> stimulates gastric acid & pepsin secretion & motility
  • Hypoglycaemia via vagus n to stimulate acid & pepsin secretion
• Alcohol & caffeine stimulate gastric secretion

Question 23

Describe the composition of pancreatic juice

Answer 23

• Cations, anions, HCO3, digestive enzymes
• Proenzyme trypsinogen converted to trypsin by enteropeptidase from brush border
• Trypsin converts chymotrypsinogens, proelastase, procarboxypeptidases to active enzymes
• Digestive enzymes in zymogen granules from acinar cells, are discharged by exocytosis into pancreatic ducts