VIVA: Physiology - Gastrointestinal system and metabolism Flashcards
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
Describe the composition of pancreatic juice
- Cations
- Anions (especially HCO3-)
- Digestive enzymes:
- Found in zymogen granules in acinar cells in alveolar glands, and discharged by exocytosis into pancreatic ducts
- Proenzyme trypsinogen converted to trypsin by endopeptidase from brush border
- Trypsin converts chymotrypsinogens, proelastase, procarboxypeptidases to their active forms
What factors regulate gastric secretion?
- Cephalic:
- Food in mouth stimulates vagal response to increase secretion
- Psychologic states (e.g. anger, hostility) also induce hypersecretion - Gastric:
- Food in stomach acts on local receptors which stimulate postganglionic neurons acting on parietal cells to increase acid secretion - Intestinal:
- Fats, carbohydrates and acid in duodenum inhibit gastric acid and pepsin secretion as well as motility, by neural and hormonal mechanisms (e.g. peptide YY) - Neural:
- Vagal stimulation increases gastrin secretion in G cells via gastrin-releasing peptide: gastrin stimulates gastric acid and pepsin secretion as well as motility
- Hypoglycaemia stimulates vagal response
- Alcohol and caffeine also increase gastric secretion
What are the mechanisms that regulate iron absorption?
Precise mechanisms are uncertain but probably related to:
- Recent dietary intake of iron
- State of body iron stores
- State of erythropoiesis in bone marrow
Physiologically, how is iron lost from the body?
- Shedding of enterocytes
- Menstruation
