Gastrointestinal Physiology Flashcards
Structure of the intestinal barrier
- mucus layer secreted by goblet cells impermeable to bacteria, which are sloughed off my peristalsis
- have villi then microvilli which greatly increase the surface area
- high reserve capacity i.e much bigger than we actually need to allow for a considerable safety margin when it comes to absorption, also adapts to size of the animal
- sites of absorption: CHO (duodenum/jejunum), PRO (duodenum/jejunum, ileum), FAT (ileum), water and salts (duodenum/jejunum), SCFA (colon)
Intestinal absorption and how we can measure
- uses saturable facilitated transporters, and either by paracellular diffusion (through tight junctions), or through the transcellular route (via the apical membrane)
- can measure via balance studies (what goes in must come out) or tolerance tests (looking at bloods to determine absorption)- these are cheap and noninvasive, but give no information on the site of absorption
- can use perfusion studies- where participants are given a test sample tube to swallow and rate of perfusion=rate of absorption. This is more expensive and invasive though
Possible routes for water absorption
- simple cellular diffusion doesnt make sense as intracellular water would have to be replaced every few seconds
- water is taken up in the early small intestine for dilution of the luminal contents then reabsorbed later in the small intestine and colon
- aquaporins form a barrel structure with alpha helices which have hydrophobic and hydrophilic domains (so water moves through into cell). Cannot be the only mechanism though as knockout mice didnt die of thirst
- from rehydration studies we know that water uptake is enhanced by glucose and Na (now recommended to give those with short bowel syndrome 90 mmol/L Na to enhance water uptake), therefore some absorption may be via SGLT-1 (gated mechanism)
Glucose and fructose absorption
- occurs via GLUT2 (non active facilitative transporter) in high glucose concentrations (has high Km). There is one on the basolateral side and one on the serosal side. ‘Taste receptors’ on the epithelium allow for this absorption
- in low glucose concentrations this occurs via SGLT1 (ion coupled transporter) which has a low km for glucose
- fructose is absorbed by GLUT5 on basolateral side and GLUT2 on serosal side
Adaptations for glucose absorption for diabetic patients
- increased microvilli length
- enhanced potential difference to optimise SGLT1 transport
- increased synthesis of SGLT1, GLUT2 and GLUT5
- signals for these adaptations could come from hypoinsulinemia, hyperglycaemia, altered levels of other hormones such as glucagon
Adaptations for glucose absorption during fasting and stress
- fasting: mucosal hypoplasia, but enhancing potential difference means efficient SGLT1 transport
- stress: lower SLGT1 levels and higher GLUT2 levels
Adaptation of glucose absorption in critical illness and in short bowel syndrome
- critical illness: in ICU have lower rates of GLUT2, SGLT1, and taste receptors
- in SBS glucose absorption is better if give maltose or partially hydrogenated starch rather than pure glucose. Monomers clipped off creating high local concentration of glucose which are absorbed by transporters
Process of lipid assimilation
1) in stomach emulsified by gastric lipase. The antrum grinds up so it can move into the pylorus
2) small intestine (jejunum and ileum) then form micelles using pancreatic lipase and bile salts which can be absorbed on the brush border
3) at high concentrations on the mucosal surface, diffusion via the ‘flip flop’ mechanism predominates. At lower concentrations, absorption via a translocase predominates
4) absorbed into the lymphatic system and so hit the liver last
Lipid movements (chylomicrons, VLDL etc)
- chylomicrons formed in the gut and move to the periphery and liver (large source of energy for the heart)
- VLDLs formed in the liver and go to the periphery
- LDLs formed in the periphery from IDLs and VLDLs
- HDLs carry cholesterol from the periphery back to the liver for disposal
Process of protein assimilation
1) luminal digestion (safety measure as brush border enterocytes are very efficient), with gastric and pancreatic enzymes for polymeric substrates (such as endo and exopeptidases)
2) brush border digestion. This can be via PEPT1 (promiscuous transporter for di and tri peptides, accounts for 2/3. Peptides broken down further in intracellular peptidases). Also brush border peptidases which act further to break down short peptides to free amino acids which can diffuse down concentration gradient via the paracellular route (~1/3)
Protein sources for enteral diets
- conditions often lead to delays in gastric emptying, therefore want something which is rapidly emptied and reduces risk of bezoar formation
- partially hydrolysed di and tri peptides offer a good solution, such as tripeptid
The relationship between prebiotics and probiotics
- prebiotics provide subtrates for fermentation on colonic microbbiome and cause fecal bulking (increased bacterial content) and immunomodulation due to promotion of good bacteria
- fermentation causes production of SCFA which promote differentiation and maturation of the gut, an energy source for colonocytes, and reduces the pH which re-promotes growth of good bacteria and enhances absorption of Ca
Major features of the enteric nervous system
- myenteric plexus: lies between the outer longitudinal and circular muscle layers
- submucosal plexus: lies between the muscularis mucosae and circular muscle layer
Intestinal motility: braking and accelerating effects
- fatty acids (FA) in duodenum provides a brake to the system to increase absorption, and allows for pancreatic secretin release (neutralises stomach acid), and CDK to activate gall bladder bile salt release
- FA also apply brake when hit ileum (even stronger) as dont want spill over into the colon (can give oleic acid to relieve symptoms of dumping syndrome)
- plasma glucose slows intestinal motility
- SCFA in the colon increase intestinal motility as want to prevent reflux of agents back into the ileum
