VIVA: Physiology - Gastrointestinal system and metabolism Flashcards
(28 cards)
How is bilirubin produced in the body?
By breakdown of haemoglobin
Haem is initially converted to biliverdin and then to bilirubin
How is bilirubin metabolised?
- Bound to albumin in the circulation
- Dissociates in the liver and free bilirubin enters hepatocytes via organic anion transport polypeptide (OATP)
- Conjugated in liver cells*:
- UDP glucuronyl transferase located in smooth ER acts on bilirubin to form bilirubin-diglucuronide (BiliG) which is H2O soluble - BiliG is actively transported against concentration gradient by MDRP-2 to bile canaliculi, bile ducts and then to intestine:
- Small amounts of BiliG and free bilirubin leak into circulation, and are excreted in the urine - Intestinal phase*:
- Intestinal bacteria acts on BiliG to form unconjugated bilirubin, urobilinogen and stercobilinogen which are excreted via the gut - Enterohepatic circulation*:
- Unconjugated bilirubin and urobilinogen can re-enter the portal circulation and be re-secreted - Urobilinogen may enter the general circulation to be excreted by the kidneys
Describe the composition of bile
3 to pass:
- 97% water
- Bile pigments (conjugated bilirubin + biliverdin)
- Bile salts (cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid)
- Inorganic salts
- Others: cholesterol, fatty acids, lecithin, fat
What are the causes of jaundice?
Unconjugated hyperbilirubinaemia
- Excess production of bilirubin* (e.g. haemolytic anaemia)
- Decreased uptake of bilirubin into hepatic cells
- Disturbed intracellular protein binding or conjugation
Conjugated hyperbilirubinaemia:
- Disturbed secretion of conjugated bilirubin into the bile canniculi
- Intra- or extra-hepatic bile duct obstruction*
*needed to pass
How does the body regulate plasma calcium?
1,2-dihydroxycolecalciferol*:
- Increases Ca2+ absorption from GIT and kidneys
PTH*:
- Mobilises Ca2+ from bone
- Increases Ca2+ reabsorption in kidneys
- Increases 1,25-dihydroxycolecalciferol formation in kidneys
Calcitonin*:
- Inhibits bone resorption
- Increases Ca2+ excretion in urine
*mention PTH and vitamin D with correct direction of effect on calcium to pass
How is the synthesis of 1,25-dihydroxycolecalciferol regulated?
1,25-DHCC formed in kidneys by 1a-hydroxylase
Low Ca2+ increases PTH secretion* which stimulates 1a-hydroxylase and increases 1,25-DHCC formation*
Low PO4^3- directly stimulates 1a-hydroxylase
High Ca2+ and PO4^3- inhibits 1,25-DHCC* (increases inactive 24,25-DHCC instead)
*needed to pass
By what mechanism does glucose cause the release of insulin?
- Glucose taken up via specific GLUT-2 transporters in beta cells of the pancreas
- Converted to pyruvate and metabolised to glutamate via citric acid cycle, which primes insulin granules for release
- Production of ATP also triggers (via K+ efflux) Ca2+ influx which causes exocytosis of granules
How is iron absorbed from the gastrointestinal tract?
- Most ingested iron is ferric (Fe3+) but the ferrous (Fe2+) form is absorbed
- Minimal absorption in stomach but gastric acid dissolves iron and aids reduction of ferric (Fe3+) to ferrous (Fe2+) form, with formation of soluble complexes*
- Fe3+ converted to Fe2+ by ferric reductase*
- Duodenum is the major site of absorption
- Iron is transported into enterocytes via DMT1
- Some intracellular ferrous iron converted to ferric form and bound to ferritin
- Remainder binds to basolateral transporter ferroportin (FP) and transported to interstitial fluid aided by hephaestin (Hp), where it is then converted to ferric form and bound to transferrin
- Dietary haem is absorbed by an apical haem transporter (HT1)* and iron is removed from the porphyrin in cytoplasm by haem oxidase
*needed to pass + one other
What factors reduce iron absorption from the gastrointestinal tract?
Dietary*:
- Phytic acid (cereals), oxalates and phosphates bind Fe to produce insoluble compounds
Surgical*:
- Partial gastrectomy (decreased stomach acid)
- Duodenal surgery
- Illness (e.g. ulcers, sprue)
Physiological*:
- High iron stores
- High recent Fe diet
- Amount of erythropoiesis
Drugs*:
- Antacids
- Acid-lowering drugs
- Some antibiotics
*1 needed to pass
How is iron transported in the plasma?
Fe2+ converted to Fe3+ and bound to transferrin
List the principal functions of the liver
3/5 with an example to pass:
1. Bile formation (500ml/day)
2. Synthesis:
- Proteins (including albumin)
- Coagulation factors
3. Inactivation / detoxification:
- Drugs
- Toxins
- Active circulating substances
4. Nutrient vitamin absorption, metabolism and control:
- Glucostasis
- Amino acids
- Lipids
- Fat-soluble vitamins
5. Immunity (especially gut organisms):
- Kupffer cells (macrophages) in sinusoid endothelium
Explain the mechanisms of absorption of water and electrolytes in the gastrointestinal tract
Absorption *:
- After meals: fluid reuptake due to coupled transport of nutrients * (e.g. glucose and Na+), ~8800ml reabsorbed
- Between meals: NaCl enters across apical membrane via coupled activity of Na+/H+ exchanger and a Cl-/HCO3- exchanger (electroneutral mechanism in small intestine and colon)
- In distal colon, Na+ enters the epithelial cell via ENaC (electrogenic mechanism)
*needed to pass + one mechanism of sodium absorption
Explain the mechanisms of water and electrolyte secretion in the gastrointestinal tract
Secretion:
- Cl- secretion occurs continuously in the small intestine and colon*
- Cl- uptake occurs via Na+/K+/2Cl- co-transporter and is secreted into the lumen via Cl- channels (CFTR = cystic fibrosis transmembrane conductance regulator)
- Water endogenous secretions* ~7000ml
*needed to pass + one mechanism of Cl- secretion somewhere
Describe the balance of water absorption and secretion in the gastrointestinal tract
Input:
- Ingested 2000ml
- Endogenous secretions 7000ml
Output:
- Reabsorbed 8800ml
Balance in stools 200ml
Describe the enzymes required for digestion of carbohydrates, and their location
- Saliva: salivary amylase
- Duodenum: pancreatic amylase
- Brush border: oligosaccharidases (e.g. alpha-dextrinase or isomaltase, lactase, sucrase, maltase, trehalase)
- Final metabolism of oligosaccharides: alpha-dextrins, maltotriose, trehalose, lactose, sucrose are metabolised to one of the hexoses (monosaccharides: glucose, fructose, galactose)
Describe how carbohydrates are absorbed from the gastrointestinal tract
Two phases:
1. Into intestinal mucosal cell:
- Glucose/galactose undergoes secondary active transport with Na+ via co-transporters SGLT1 and SGLT2 (low concentration of Na+ inhibits transport)
- Fructose undergoes facilitated diffusion from intestinal lumen via GLUT5
2. Into interstitial fluid, capillaries and portal blood:
- Glucose/galactose/fructose enters interstitium by facilitated diffusion via GLUT2
- Ribose/deoxyribose undergo diffusion
Describe the enzymes required for digestion of lipids and their location
2/4 to pass:
Mouth:
- Lingual lipase (from Ebner’s gland) is activated in the stomach and acts on triglycerides
Small intestine:
- Pancreatic lipase acts on triglycerides (requires co-lipase for maximal activity)
- Pancreatic bile-salt-activated lipase acts on triglycerides as well as cholesterol esters, some vitamins and phospholipids
- Cholesteryl ester hydrolase acts on cholesterol
What processes other than enzymatic degradation are involved in digestion of lipids?
2/3 to pass:
- Emulsification
- Micelle formation: formed from bile salts, lecithin and monoglycerides surrounding fatty acids, monoglycerides and cholesterol
- Transport of lipids through “unstirred layer” to brush border of mucosal cells
Describe how lipids are absorbed from the gastrointestinal tract
- Into enterocytes:
- Via passive diffusion and specific carriers - Out of enterocytes:
- If FFAs with <10-12 carbons, directly enters portal blood
- If FFAs with >10-12 carbons, re-esterified to triglycerides or cholesteryl esters and packaged in chylomicrons with coating of protein, cholesterol and phospholipids, then enter lymphatic circulation
Describe how proteins are digested in the gastrointestinal tract
- Stomach:
- Pepsinogen is activated by gastric acid producing pepsin which cleaves bonds between amino acids * to produce polypeptides - Small intestine:
- Powerful proteolytic enzymes from pancreas and intestinal mucosa hydrolyse amino acids
- Pancreatic enzymes include endopeptidases (e.g. trypsin, chymotrypsin, elastase) and exopeptidases
- Brush border enzymes include amino-, carboxy-, endo- and di-peptidases
*needed to pass
How are proteins absorbed from the gastrointestinal tract?
- Into enterocytes:
- Seven transport systems, five of which require Na+ (similar to glucose co-transport) and two of which are Na+-independent *
- Absorption is rapid in duodenum and jejunum, slow in ileum - Out of enterocytes:
- Five different transport systems *
*needed to pass
How does protein absorption and digestion differ in infants and young children compared with adults?
1/2 to pass:
- Infants absorb more undigested protein
- Results in increased incidence of food allergy but important for passive immunity
List the enzymes secreted from the exocrine pancreas, and give at least 3 examples of substrates that these enzymes work on
- Proteins and polypeptides digested by:
- Trypsin
- Chymotrypsins
- Elastase (acts specifically on elastin and some other proteins)
- Carboxypeptidase A and B - Lipid digested by:
- Pancreatic lipase (triglycerides)
- Co-lipase (fat droplets)
- Bile salt acid lipase (cholesterol esters)
- Cholesterol ester hydrolase (cholesterol esters)
- Phospholipase A2 (phospholipids) - Carbohydrates digested by:
- Pancreatic alpha amylase (starch)
- Ribonuclease (RNA)
- Deoxyribonuclease (DNA)
*needed to pass + 2 examples with matched substrates
Describe the regulation of pancreatic juice secretion
Primarily under hormonal control:
- Secretin acts on the duct to cause production of copious amounts (1500ml/day) 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 proportional to flow
- Secretin also promotes bile secretion
- CCK acts on acinar cells to induce release of zymogen granules and pancreatic juice rich in enzymes *
- ACh also stimulates release of zymogen granules (? basis of vagally-mediated pancreatic juice secretion in response to sight/smell of food)
*needed to pass
