Digestion and absorption in GI tract Flashcards
Digestive functions
Localised to different areas of the gut where:
-optimal pH of enzymes differ
-some enzymes may be secreted as inactive precursors, and need enzymatic activation
-some enzymes exist as membrane bound forms
-Objective is to break macromolecules down into monomer or dimer units for absorption
Absorption functions
-Mainly in small intestine, but also water in colon
-Requiring a variety of transport mechanisms specific for particular molecules
-If transport is against a gradient, energy must be used (primary or secondary active transport)
Small intestine villi structure
Membrane pumps, enzymes and transporters in small intestine enterocytes
Enzymes - required for digestion of macromolecules
Transporters - required for absorption of many solutes (products of digestion)
Na pump:
-Maintains Na gradient (low Na inside cell) which is required by many transporters
-Creates osmotic gradient in intracellular space, which drives water absorption from lumen
Protein digestion step 1 (pepsin and HCL)
-Starts with pepsin and HCl in the stomach
Protein digestion step 2 (chyme)
Chyme has a LOW pH and contains:
-Solubilised, slightly digested carbohydrates
-Solubilised, partly digested proteins
-Slightly digested fats
-Intrinsic factor which enables Vit B12 to be absorbed in the small intestine
For further digestion to take place:
-other enzymes are supplied (from pancreas and made by enterocytes)
-pH has to be neutralised
-bile salts needed for fat digestion
Protein digestion step 3 (duodenum)
In duodenum:
-Enterokinase on brush border of duodenal enterocytes activates pancreatic trypsinogen
-This activates proteolytic enzymes of the pancreas
Protein digestion step 4 (duodenum)
-Pancreatic trypsin, elastase & chymotrypsin (endo-peptidases) cleave peptide bonds in protein interior, producing short peptides
-Pancreatic carboxypeptidases (exopeptidase) remove amino acids from the carboxyl ends
-Aminopeptidases (exo-peptidase) on brush border of enterocytes remove amino acids from the amino terminal of peptides
Amino acid and peptide absorption
-Amino acids absorbed via Na+-linked lumenal transporters, then exit on basolateral side
-Di- and tri-peptides absorbed via H+-linked lumenal transporters, then hydrolysed to amino acids before exiting on basolateral side
Why is infant small intestine wall permeable to peptides?
-Allows for absorption of growth factors and antibodies from colostrum (first milk)
Types of carbohydrate in food
Carbohydrate digestion summary
1) Salivary amylase
-optimum pH is 6.8, so some hydrolysis in the mouth
-swallowed bolus then enters acidic stomach
2) Pancreatic amylase
-optimum pH is 7.1
3) Small intestine membrane-bound disaccharidases:
-optimum pH values between 6 and 7
Carbohydrate digestion (molecular level)
Pancreatic amylase:
-Cleaves straight chains but cannot cleave bonds at branch points
-Produces short oligosaccharides, maltose (disaccharide) and maltriose (trisaccharide)
-Further digestion of these and other disaccharides (lactose, sucrose) to monosaccharides by brush border enzymes
Carbohydrate absorption
Apical/lumenal side:
-SGLT (Na-linked transporter) for glucose & galactose, secondary active transport
-Fructose via GLUT5, facilitated diffusion
Basolateral side:
-GLUT2 transport for all three hexoses, facilitated diffusion
-Na pump maintains Na gradient
Fat digestion summary
Enzymes: mainly pancreatic lipase but some gastric lipase
Other requirements:
-Colipase
-Bile salts
-Right pH
=>for digestion in duodenal lumen
-Beta lipoprotein
=>Inside enterocyte, to ‘package’ lipid for export as chylomicrons
4 steps in fat digestion
-Emulsification of fat in lumen (requires bile salts)
-Action of lipase to convert TGs to MGs and FAs
-Formation of micelles (made of MGs, FAs, bile salts, etc)
-Diffusion of micelles to epithelial cell brush border
What is the action of lipase?
-Breaks down triglycerides into 2 fatty acids + monoglyceride
4 steps in fat absorption
-Trans-membrane transport of the free FAs and MGs (by diffusion through the lipid core)
-Intracellular resynthesis of triglyceride (in the SER)
-Incorporation of the TG into chylomicrons, together with beta-lipoprotein, cholesterol, etc
-Efflux of the chylomicrons on the basolateral side of the cell, into nearby lacteals
Enterohepatic recirculation of bile salts
-95% bile salts reabsorbed, mainly in terminal ileum
-Transported back to liver via portal vein, and re-extracted by hepatocytes to be re-exported in bile juice
-Can be turned over 3-4 times during digestion of a single large meal
-Overall loss of 5-10% per day in faeces compensated by de novo synthesis in liver
Water absorption in colon
-Net water absorption (following Na+ down osmotic gradient)
-Water and Na reabsorption stimulated by aldosterone
-Resident microflora are prevented from crossing epithelial barrier, but they help to produce vit. K and folic acid which are absorbed here
Other absorptive functions of GI tract
Minerals
-Specific mechanisms for absorption of mineral ions such as Ca2+, Fe2+ etc
Vitamins
-Specific mechanisms for B & C vitamins
-Fat-soluble vitamins generally absorbed with lipids, in SI
Drugs
-Absorbed best when non-ionised, both in the SI (right pH) and colon
-Limited absorption of a few drugs (e.g. aspirin) across gastric mucosa
Absorption of Vitamin B12
-Haptocorrin protects B12 from acidic stomach
-IF produced in stomach and takes over from Haptocorrin, protecting it and allowing it to be absorbed in intestines
-Vit B12/IF complex binds to cubam receptor, taken up in distal ileum
Absorption of calcium
Calcium is an active signalling molecule so need to stop it acting in the enterocyte - calbindin
-Paracellular route (Claudin 2 +12)
-Enters through TRPV6/Cav1.3, binds to calbindin, exits via Ca ATPase pump and Na/Ca exchanger
Absorption of iron
-Cannot absorb Fe3+ only Fe2+
-Dyctb converts 3+ to 2+, 2+ can be transported
-Fe2+ enters through DMT1
-Heme is converted to Fe2+ by Hemeoxygenase (HO-1)
-Fe2+ can be stored in cell as ferritin or transported into blood via ferroportin transporter
Causes of malabsorption (failure to digest)
Failure to digest macromolecules in chyme due to:
-interruption of the enterohepatic circulation of bile salts
-failure to deliver pancreatic enzymes
-poor co-ordination of gastric emptying with delivery of pancreatic & biliary secretions
Causes of malabsorption (failure to absorb)
Failure to absorb:
-lactose, because brush border lactase is absent, and lactose remains in lumen (alactasaemia)
-lipids because of lack of beta-lipoprotein required to make chylomicrons
-lipids because of failure of lipid digestion
-sufficient water because it is retained in lumen accompanying increased solute load
-sufficient water because of increased salt & water secretion caused by bacterial infection
Malabsorption leading to anaemia (Vit B12)
Failure to absorb vit B12
-Absorption in ileum (specific transporter recognises the vit B12 only when complexed with intrinsic factor)
-Insufficient intrinsic factor results from:
-gastric atrophy
-an autoimmune condition - patient mounts immune response against their own intrinsic factor or parietal cell
-Result: Disturbance in erythropoiesis, resulting in much fewer, but macrocytic rbc
Malabsorption leading to anaemia (Iron)
-Absorption in SI, requiring specific transport mechanisms
-Assisted by previous acid pH in stomach, which helps maintain the Fe3+ ions in a soluble state for later absorption
-Result:failure to make sufficient haemoglobin, resulting in microcytic rbc
Osmotic diarrhoea
Osmotic diarrhoea as a result of malabsorption:
-incomplete absorption leaves an increased solute load in the SI lumen
-water stays with it (osmotic effect)
Outcome:
-Much increased volume of lumenal contents, stimulating peristalsis
-Undigested fats may also have a laxative effect
-Many of the partially digested food stuffs are fermented in the colon (by local microflora), resulting in formation of gases (e.g. H2), distension (pain)
Secretory diarrhoea
Secretory diarrhoea in response to bacterial infection:
e.g. Vibrio cholerae and E coli toxins increase the secretory activity of intestinal crypt cells
Diarrhoea secondary to intestinal mucosa damage
e.g. coeliac disease (autoimmune condition mainly of SI caused by an adverse reaction to gluten)
e.g. Crohn’s disease (inflammatory condition, mainly affecting ileum & colon)
