GASTROINTESTINAL VIVAS
2006-2, 2003-2
Describe how proteins are digested in the gastrointestinal tract
- Stomach: Proenzyme pepsinogens (secreted by chief cells) are activated by the gastric
acid (HCl-, secreted by parietal cells) to produce pepsins and these cleave bonds between
amino acids
- Small bowel: Proenzymes are secreted by the pancreas and activated in the small intestine
- Proteolytic proenzymes from pancreas:
 Endopeptidases (act at interior peptide bonds, activated at site of action by brush border
hydrolase - enterokinase): trypsin(ogen), chymotrypsin(ogen), and (pro)elastase, and note
trypsin itself activates these other proenzymes
 Exopeptidases (cleave side chains at carboxyl ends of polypeptides):
(pro)carboxypeptidase A (aliphatic side chains) and B (basic side chains)
- Intestinal mucosa has the activating enterokinase (aka enteropeptidase)
How are proteins absorbed from the gastrointestinal tract?
- Via di- and tri-peptides, very little larger peptides
- Rapid in duodenum and jejunum, slow in ileum
- 50% from digested food, 25% from proteins in the digestive juices, 25% from desquamated
mucosal cells
- Only 2-5% escapes digestion in small bowel -> bacteria in large. Protein in stool from bacteria and
cellular debris
- Two phases:
1. Mucosal cell via 7 transport systems: 5 require Na+, 2 require Na+ and Cl-, and 2 are Na+
independent
2. Interstitial fluid (via 5 transport systems) => capillaries and portal blood
- Na+ similar to glucose transport
How does protein absorption and digestion differ in infants and young children compared to
adult?
- Infants absorb more undigested protein (endocytosis => exocytosis)
- Results in more food allergy (as high as 8%) but passive immunity (IgAs in maternal colustrum, M
cells and Peyer’s patches => IgA and secretory immunity)
2006-1
What factors regulate gastric secretion
3 stimuli of gastric secretion (hormonal x2 and neural)
1. Gastrin
- Hormone released by G cells in antrum
- In response to neurotransmitter (GRP) and amino acids in gastric lumen
- Via bloodstream => fundus: directly on parietal cells w/ release of HCl- (note negative feedback)
2. Histamine: Gastrin also acts on ECL => histamine => H2 receptors on parietal cells => HCl3. ACh – neural stimulation of parietal and chief cells by enteric nerve endings
3 phases of secretion
1. Cephalic: Vagal input from dorsal vagal complex => gastrin releasing peptide (GRP)
2. Gastric: constituents in stomach (e.g. via receptors for amino acids), vaso-vagal stretch, buffering
acid w/ loss of negative feedback
3. Intestinal: fats and carbohydrates in duodenum inhibit HCl- and pepsin (by secretin and CCK)
Negative feedback: H+ => somatostatin => inhibits G cells (gastrin), ECL cells (histamine), parietal
cells (HCl-), H+ also has a direct effect on G cells to decrease gastrin secretion
- Peptide YY: inhibits gastric acid secretion and motility (? is the gastric inhibitory peptide)
2010-1, 2005-2 (composition of)
Name the principal pancreatic enzymes and the substances upon which they act
-
The pancreas secretes proenzymes that are activated at required site (95% of proteins in juice)
Also contains a trypsin inhibitor to prevent autodigestion
In pancreatitis phospholipase A2 is activated (by trypsin) in the ducts
Pancreatic juice is alkaline (pH ~8.0) with a high HCO3- content
Contains cations (Na+, K+, Ca2+, Mg2+) and anions (HCO3-, SO42-, HPO42-)
About 1500ml is secreted per day
Enzyme
Trypsin(ogen)
Chymotrypsin(ogen)
(Pro)elastase
(Pro)carboxypeptidase A
(Pro)carboxypeptidase B
(Pro)phospholipase A2
(Pro)colipase
Pancreatic lipase
Bile salt-acid lipase
Pancreatic -amylase
Ribonuclease
Deoxyribonuclease
Substrate
Proteins and Polypetides
Endopeptidases
Activated by
Enterokinase in brush border
Exopeptidase: Aliphatic side chains
Exopeptidase: Basic side chains
Phospholipids
Fat droplets
Triglycerides
Cholesterol esters
Starch
RNA
DNA
Trypsin
Cl-
Desribe the regulation of pancreatic juice secretion
- Primarily under hormonal control (secretin and CCK, also ACh)
Secretin
- From S cells in upper small intestine
- Acts on the ducts (via cAMP) => copious alkaline juice ( HCO3-) w/  enzymes
- As flow of pancreatic juice  it becomes more alkaline because exchange of HCO3- for CI- in the
distal duct (inversely proportional to flow)
- Also stimulates bile secretion, decreases HCl-, and may cause contraction of the pyloric sphincter
CCK (cholecystokinin)
- From musosal cells in upper intestine
- Acts on acinar cells (via phospholipase C) to cause of release of zymogen granules and
pancreatic juice rich in enzymes but low in volume
- Also stimulates gall bladder contraction (hence the name), inhibits gastric emptying, has a trophic
effect on pancreas, and enhances motility in the bowel
Acetylcholine also stimulates release of zymogen granules (minor effect ?basis of vagally-mediated
pancreatic juice secretion in response to sight/smell of food)
2003-2
Describe the enzymes required for the digestion of carbohydrates and their location
Ingested
Saliva/pancreas
=>
Brush border
Absorbed
Polysaccharides
Oligosaccharides
Oligosaccharidases
-amylases
(starch)
- Maltose (di)
- Isomaltase
Hexoses
- Maltriose (tri)
- Maltase
(Monosaccharides)
- Galactose
- -dextrin (poly) - Sucrase
- Fructose
Disaccharides
Disaccharidases
- Glucose
- Lactose
- Lactase
- Sucrose
- Trehalase
Sucrose => Fructose + Glucose, Lactase => Galactose + Glucose, Trehalose and Maltose => Glucose x2
Please describe how carbohydrates are absorbed from the gastrointestinal tract
- Hexoses are rapidly absorbed across the wall of the small intestine
- Almost all before reaching the terminal ileum
- Two phases: first into intestinal mucosal cell and second into interstitial fluid (ECF) and thus into
capillaries and portal blood
Glucose/Galactose
- Undergoes co-transport from the intestinal lumen with Na+ via SLGT-1&2 (a low concentration
of lumenal Na inhibits b/c driven by concentration gradient)
- The Na+ is actively transported into the lateral intercellular spaces
- The glucose moves by facilitated diffusion into the ICF via GLUT-2
- Thus glucose transport is by secondary active transport
Fructose
- By facilitated diffusion from intestinal lumen by GLUT-5 and then GLUT-2 into ICF
2003-2
Describe the enzymes required for the digestion of lipids and their location
- Lingual lipase (Ebner’s Gland): active in the stomach on triglycerides, minimal significant activity
- Pancreatic lipase: requires colipase for maximal activity (triglycerides)
- Pancreatic bile-salt activated lipase (not only triglycerides but also cholesterol esters, some
vitamins & phospholipids)
- Cholesteryl ester hydrolase (cholesterol)
What other process is involved in the digestion of lipids?
- Emulsification: due to the detergent action of bile salts, lecithin and monoglycerides
- Micelles: If the concentration is high micelles form with formed from bile salts surrounding fatty
acids, monoglycerides and cholesterol – a hydrophilic outer layer and hydrophobic centre
- Transport lipids thru “unstirred layer” to brush border of mucosal cells
Please describe how lipids are absorbed from the gastrointestinal tract
- Two phases: first into intestinal mucosal cell and second into interstitial fluid (ECF) and thus into
capillaries and portal blood (FFA – free fatty acids) or into lymphatics (chylomicrons)
1. Into enterocytes: passive diffusion & carriers
2. Out of enterocytes: depending on size (< 10-12 carbons => directly into portal blood (FFA’s)
OR > 10-12 carbons => reesterified to triglycerides or cholesteryl esters and packaged in
chylomicrons (coating of protein, cholesterol and phospholipids)
2008-1, 2004-2
Please describe how ingested iron is absorbed
- Most ingested iron is ferric (Fe3+) but the ferrous (Fe2+) form is absorbed
- Minimal absorption in stomach but gastric secretions dissolves iron and aid conversion to the
ferrous form
- Fe3+ reductase activity is associated with the Fe transporter in the brush border
- Almost all absorption in duodenum
- Iron is transported into enterocytes via DMT1
- Some stored as ferritin
- Remainder transported out via ferroportin 1 (basolateral transporter) in the presence of
hephaestin
- Then converted to ferric form in plasma and bound to transferrin
- Dietary heme is absorbed by an apical transporter and iron is removed from the porphyrin in
cytoplasm
- Note: 70% of Fe in body is in Hb, 3% in myoglobin, remainder in ferritin (present in eneterocytes
and other cells)
What are the mechanisms that regulate iron absorption?
- Precise mechanisms uncertain, probably related to:
- Recent dietary intake of iron
- State of body iron stores
- State of erythropoiesis in bone marrow
- The regulatory mechanisms are unclear
Physiologically, how is iron lost from the body? 2004-2
- Gut cells
- Menstruation
2009-2, 2006-1
What are the principal functions of the Liver?
1. Bile formation (500 mls a day): Excretion, elimination, digestion
2. Nutrient and vitamin metabolism/control
- Glucose and other sugars (glucose buffer function)
- Amino acids
- Lipids (fatty acids, chlesterol, lipoproteins
- Vitamins, both fat and water soluble
3. Inactivation and detoxification
- Ammonia metabolism/excretion via the urea cycle
- Toxins, steroids, hormones, drugs
4. Synthesis
- Acute phase proteins
- Albumin
- Clotting factors
- Binding proteins (steroid and hormone binding)
5. Immunity (particulary gut organisms): Kupffer/Macrophages in sinusoid endothelium
Describe bilirubins path from production to excretion
- Most formed by breakdown of Heme/Hb by marcphages => biliverdin
- Biliverdin rapidly reduces to bilirubin
- Bilirubin bound to albumin
- In liver actively transported (OATP) as dissociates => binds to cytoplasmic proteins
- Conjugated by glucuronyl transferase (in ER) with glucoronic acid to H2O soluble bilirubin
diglucuronide
- Active transport into bile canaliculi (small amount escape into the blood => urinary excretion)
- Thus plasma contains mostly free bilirubin (w/ albumin) and conjugated bilirubin
- The bilirubin is delivered in bile to intestines (via bile ducts)
- Intestinal mucosa relatively impermeable to conjugated bilirubin
- Gut bacteria convert most => urobilinogens (colourless)
- Some bile pigments, urobilinogens and unconjugated bilirubin are reabsorbed in portal circulation
- Most resecreted => enterohepatic circulation
- Small amounts urobilinogens enter the general circulation and are excreted in urine
- Small amount are excreted in the stool => stercobilinogen which is oxidized to stercobilin