Overview
This lecture covers absorption in the gastrointestinal tract: what absorption is, the five factors that determine how much of a substance crosses the epithelium, the cellular transport mechanisms that carry it, and then a site by site and nutrient by nutrient account of what is absorbed where. Sodium and water dominate by volume and set the pattern for everything else, since most solute uptake is sodium coupled and water follows the osmotic gradient. The closing theme is recycling: most of what the gut absorbs was secreted by the body in the first place, so absorption has to match secretion or large losses follow.
What absorption is
- The gastrointestinal tract moves, secretes, digests and absorbs.
- Absorption is the net passage of a substance from the lumen of the gut across the epithelium to the interstitial fluid.
Factors affecting absorption
The lecture builds a five item list:
- Surface area
- Motility
- Adequate digestion
- Penetration, comprising solubility, size, transporters and pathways
- Removal of substances from the interstitial space
Surface area. The mucosa is amplified at three successive scales, shown as villi, then epithelial cells, then microvilli. Relative surface increase, taking the intestine as a plain cylinder as 1:
| Structure | Relative surface increase (cylinder = 1) |
|---|---|
| Intestine as a cylinder | 1 |
| Circular folds | 3 |
| Villi | 30 |
| Microvilli | 600 |
Motility. Illustrated by segmentation: successive points along the tube narrow and widen over time, producing back and forth mixing of the contents rather than net forward propulsion.
Adequate digestion. Illustrated with the carbohydrate digestion scheme (see Carbohydrates below).
Removal from the interstitial space. Illustrated by an unlabelled schematic of a substance “X” moving from outside into and across a compartment, with flow continuing away from it.
Warning
Several slides in this lecture carry no text and the transcript flags them as uninterpretable: Slide 3 (a radiograph of a bird’s head and neck, no caption, relation to absorption not stated), Slide 16 (the “X” schematic above, its compartment and arrows unlabelled) and Slide 41 (a photograph of a lamb, no caption, placed in the Proteins section). Their intended teaching point is not recoverable from the slides.
Absorption mechanisms
- Absorption uses diffusion, carriers, and passive or active transport.
- Substances use a variety of methods, and a single substance may use more than one.
- Sodium permeability and transport is the key mechanism.
- Water follows the osmotic gradient.
- Lipids cross by diffusion.
Epithelial transport models
Three cell diagrams are given and then recapped together, all drawn as lumen / cell / interstitial fluid.
Secretory epithelia.
- Basolateral: an Na+/K+/2Cl- cotransporter brings Na+, K+ and 2Cl- into the cell; the Na+/K+-ATPase (ATP to ADP) exports Na+ and imports K+; a K+ channel returns K+ to the interstitial fluid.
- Apical: a Cl- channel lets Cl- leave into the lumen.
- H2O and Na+ then follow into the lumen by the paracellular route, so NaCl and water are secreted together and osmotically coupled.
Transport in the small intestine (absorptive cell).
- Apical: Na+/glucose cotransporter (glucose in with Na+); Na+/amino acid cotransporter (amino acids in with Na+); Na+/H+ exchanger (Na+ in, H+ out to lumen); Cl-/HCO3- exchanger (HCO3- out to lumen, Cl- in).
- Basolateral: facilitated glucose transporter and facilitated amino acid transporter carrying both out to the interstitial fluid; K+ channel; Cl- channel; Na+/K+-ATPase (Na+ out, K+ in).
- Water moves paracellularly from lumen through to interstitial fluid.
Colon.
- Apical: Na+ channel entry; K+ efflux into the lumen; Na+/H+ exchanger (Na+ in, H+ out); Cl-/HCO3- exchanger (Cl- in, HCO3- out).
- Basolateral: Na+/K+-ATPase (Na+ out, K+ in); Na+/K+/2Cl- cotransporter bringing Na+, K+ and 2Cl- in; a Cl- exit route marked on the diagram itself with a question mark, so that pathway is left unconfirmed by the slide.
Jejunal villus and crypt. The villus carries goblet cells and APUD cells; the crypt below it carries Paneth cells.
Absorption: what and where
- Mouth and oesophagus: minimal.
- Stomach: ethanol, aspirin.
- Small intestine: everything, 90%.
- Colon: water and sodium, with K+ secretion. Under neural and hormonal control (aldosterone). Also absorbs bacterial products (short chain fatty acids, vitamins) and drugs.
The site schematic (Slides 28, 35 and 43) runs from stomach through jejunum and ileum to colon, and shows both what is absorbed and what enters the lumen:
- Entering the lumen: bile from the stomach level of the diagram, and pancreatic secretions.
- Absorbed at the jejunum: Ca2+, Mg2+, Fe2+; monosaccharides; disaccharides; most water-soluble vitamins; NaCl and water (circled in red on the slide).
- Secreted into the jejunum: amino acids, fat and fat-soluble vitamins.
- Absorbed at the ileum: vitamin B12 and bile salts, with bile salts also secreted into the ileum.
Warning
On Slide 28 the transcript places amino acids and fat/fat-soluble vitamins on the secretion side of this crowded schematic. That sits awkwardly with the rest of the lecture, where amino acids are absorbed with Na+ in the small intestine (Slide 40) and fat-soluble vitamins are absorbed in micelles with bile salts (Slide 44). The direction of transport for those two labels on Slide 28 should be checked against the original figure; it is recorded here as the slide reads.
Sodium and water
Sodium and water absorption are co-ordinated, and absorption must match secretion or there is large net loss.
Sodium
- About 1000 mmol/day reaches the gut, mostly from secretions rather than diet.
- 90% is absorbed in the small intestine by solute co-transport.
- 10% is absorbed in the colon, by K+ exchange, SCFA and ENaC.
- 5 to 10 mmol/day is lost to faeces.
Water
- About 10 L/day, again mostly from secretions.
- 90% absorbed in the small intestine by solute co-transport.
- 1 L handled in the colon.
- 0.1 L lost to faeces.
- Water moves down the osmotic gradient created by Na+ absorption.
Daily balance figures from the combined diagram, as H2O (L per 24 h) / Na+ (mmol per 24 h):
| Stage | H2O (L/24 h) | Na+ (mmol/24 h) |
|---|---|---|
| Intake | 1.5 | 150 |
| Saliva (upper GI tract) | 1.5 | 60 |
| Gastric juice (stomach) | 3.0 | 150 |
| Bile | 1.0 | 150 |
| Pancreatic juice | 1.0 | 150 |
| Intestinal secretion | 2.0 | 300 |
| Absorbed, small intestine | 9.0 | 800 |
| Absorbed, colon | 0.9 | 150 |
| Excreted | 0.1 | 10 |
Carbohydrates
- Absorbed in the duodenum and jejunum.
- Amylase digests to disaccharides; brush border enzymes complete digestion to monosaccharides; absorption is by Na+ co-transport.
Luminal phase, from the digestion figure:
- α-amylase cleaves part of a glycogen molecule to maltose, maltotriose and α-limit dextrins.
- Of starch and glycogen, α-amylase yields roughly 30% as α-limit dextrins (G5 to G9) and 70% as malto-oligosaccharides (shown as 5%, 40% and 25% fractions, G4 to G8).
Brush border phase, enzyme then product then carrier:
- Lactose, by lactase, to galactose and glucose, taken up on the galactose and glucose carriers.
- Sucrose, by sucrase, to fructose and glucose.
- α-limit dextrins, by α-dextrinase, to glucose.
- Malto-oligosaccharides, by glucoamylase, to glucose.
- Glucose enters on SGLT1 together with Na+; fructose enters on GLUT5.
Proteins
- Protein reaching the gut comes from diet, sloughed cells and secretions.
- Digested by pepsin and pancreatic proteases, then brush-border peptidases.
- Amino acids are absorbed with Na+.
- Di- and tripeptides are also absorbed.
Minerals and vitamins
- Calcium: duodenum, vitamin D dependent.
- Iron: proximal duodenum; absorption and storage depend on iron status.
- Fat-soluble vitamins D, E, K and A: absorbed in micelles with bile salts.
- Water-soluble vitamins: absorbed on carriers.
- Vitamin B12: requires intrinsic factor and is absorbed in the distal ileum.
Vitamin B12 pathway, in order:
- Parietal cells in the stomach secrete intrinsic factor into the GI tract lumen.
- In the duodenum and jejunum, intrinsic factor binds dietary vitamin B12.
- In the terminal ileum, the complex is taken up into enterocytes by receptor-mediated endocytosis.
- B12 is released into the bloodstream, where it is bound to the serum carrier protein transcobalamin.
Lipids
- The main dietary lipid is triglyceride, with others alongside.
- Bile salts emulsify the lipid.
- Pancreatic lipase hydrolyses it.
- Products are carried in micelles.
- Absorbed lipid leaves the enterocyte as chylomicrons, which enter the lymph.
- One slide in this section shows only the product name Xenical (orlistat), struck through with a large X, with no accompanying text [slide does not elaborate].
Enterohepatic circulation and recycling
- Many substances secreted from the liver in bile are reabsorbed in the GI tract and recycled, so that they are not lost.
- Circuit, in order: the liver secretes bile salts into the common bile duct; they pass through the gallbladder, where bile is stored, into the duodenum; they travel along the small intestine to the ileum; most are reabsorbed there and returned to the liver in the hepatic portal vein.
- The diagram gives two separate figures: the liver synthesises bile salts (5%), and 5% is lost in faeces. The slide does not state a link between them.
- Closing point: most of what we absorb came from us, so reabsorption and recycling are very important, and failure of them means loss.
Self-test
- Define absorption as the lecture defines it.
- List the five factors affecting absorption, and give the sub-components of the penetration factor.
- State the relative surface increase for circular folds, villi and microvilli, taking the intestine as a cylinder as 1.
- Describe what segmentation does to intestinal contents, and why this is listed as a factor affecting absorption rather than as propulsion.
- Describe the transporters on the apical and basolateral membranes of a secretory epithelial cell, and explain how NaCl and water end up in the lumen.
- Describe the apical and basolateral transporters of the small-intestinal absorptive cell.
- Distinguish the colonic epithelial cell from the small-intestinal absorptive cell in terms of how Na+ enters the cell.
- Name the cell types shown in the jejunal villus and in the crypt.
- List what is absorbed in the mouth and oesophagus, the stomach, the small intestine and the colon.
- According to the small-intestine absorption schematic, what is absorbed at the jejunum and what is absorbed at the ileum?
- State the daily sodium load reaching the gut, where it mostly comes from, the proportions absorbed in small intestine and colon, and the faecal loss.
- State the daily water load, the proportions handled by small intestine and colon, the faecal loss, and the driving force for water absorption.
- Predict what happens if absorption fails to match secretion in the small intestine, and explain why the secreted volumes make this consequential.
- Describe the steps of carbohydrate digestion from starch or glycogen to absorbed monosaccharide, naming the enzymes and the carriers.
- What proportion of amylase products are α-limit dextrins and what proportion are malto-oligosaccharides?
- List the sources of protein presented to the gut, the enzymes acting on it, and the forms in which it is absorbed.
- Distinguish how fat-soluble and water-soluble vitamins are absorbed.
- Describe the steps of vitamin B12 absorption from stomach to bloodstream, and predict the consequence of terminal ileal disease for this pathway.
- Describe the steps of lipid handling from dietary triglyceride to entry into the lymph.
- Describe the enterohepatic circulation of bile salts, and state the two percentage figures the slide gives.
- Sodium transport is described as the key absorption mechanism. Draw together the carbohydrate, protein and water sections to explain why.
Answers
Reveal answers
- The net passage of a substance from the lumen of the gut across the epithelium to the interstitial fluid.
- Surface area; motility; adequate digestion; penetration; removal of substances from the interstitial space. Penetration comprises solubility, size, transporters and pathways.
- Circular folds 3, villi 30, microvilli 600, against the plain cylinder as 1.
- Segmentation narrows and widens successive points along the tube over time, moving contents back and forth to mix them rather than propelling them forwards; it is listed as a factor affecting absorption because it mixes contents against the absorptive surface rather than advancing them along it.
- Basolateral: Na+/K+/2Cl- cotransporter brings Na+, K+ and 2Cl- in; Na+/K+-ATPase pumps Na+ out and K+ in; a K+ channel returns K+ to the interstitial fluid. Apical: a Cl- channel releases Cl- into the lumen. Na+ and H2O then follow paracellularly, so NaCl and water are secreted together and osmotically coupled.
- Apical: Na+/glucose cotransporter, Na+/amino acid cotransporter, Na+/H+ exchanger (Na+ in, H+ out), Cl-/HCO3- exchanger (HCO3- out, Cl- in). Basolateral: facilitated glucose and facilitated amino acid transporters exiting to the interstitial fluid, K+ channel, Cl- channel, Na+/K+-ATPase. Water crosses paracellularly.
- In the small intestine Na+ enters apically coupled to solutes (glucose, amino acids) and on the Na+/H+ exchanger; in the colon Na+ enters through an apical Na+ channel as well as on an Na+/H+ exchanger, and the colonic cell also secretes K+ into the lumen. The colon diagram leaves the basolateral Cl- exit route marked with a question mark.
- Villus: goblet cell and APUD cell. Crypt: Paneth cell.
- Mouth and oesophagus, minimal. Stomach, ethanol and aspirin. Small intestine, everything, about 90%. Colon, water and sodium with K+ secretion, under neural and hormonal control (aldosterone), plus bacterial products (SCFA, vitamins) and drugs.
- Jejunum: Ca2+, Mg2+, Fe2+, monosaccharides, disaccharides, most water-soluble vitamins, and NaCl and water. Ileum: vitamin B12 and bile salts. The same schematic puts amino acids and fat/fat-soluble vitamins on the secretion side at the jejunum, and bile salts as also secreted into the ileum.
- About 1000 mmol/day, mostly from secretions rather than diet; 90% absorbed in the small intestine by solute co-transport, 10% in the colon by K+ exchange, SCFA and ENaC; 5 to 10 mmol/day lost in faeces.
- About 10 L/day, mostly from secretions; 90% absorbed in the small intestine, 1 L handled in the colon, 0.1 L lost in faeces; water moves down the osmotic gradient created by Na+ absorption.
- There is large net loss of water and sodium. Secretions are the dominant input, about 10 L and 1000 mmol/day against an intake of only 1.5 L and 150 mmol, so a small shortfall in absorption loses body fluid, not just ingested fluid.
- α-amylase cleaves starch or glycogen to maltose, maltotriose, α-limit dextrins and malto-oligosaccharides. At the brush border, lactase splits lactose to galactose and glucose, sucrase splits sucrose to fructose and glucose, α-dextrinase splits α-limit dextrins to glucose, and glucoamylase splits malto-oligosaccharides to glucose. Glucose is taken up on SGLT1 with Na+, fructose on GLUT5, galactose and glucose on their brush-border carriers.
- About 30% α-limit dextrins (G5 to G9) and about 70% malto-oligosaccharides (given as 5%, 40% and 25% fractions, G4 to G8).
- Sources: diet, sloughed cells and secretions. Enzymes: pepsin, pancreatic proteases, then brush-border peptidases. Absorbed as amino acids with Na+, and also as di- and tripeptides.
- Fat-soluble vitamins D, E, K and A are absorbed in micelles with bile salts; water-soluble vitamins are absorbed on carriers, mostly at the jejunum, with B12 the exception requiring intrinsic factor and the distal ileum.
- Parietal cells in the stomach secrete intrinsic factor; in the duodenum and jejunum it binds vitamin B12; in the terminal ileum the complex is taken into enterocytes by receptor-mediated endocytosis; B12 is released into the blood bound to transcobalamin. Terminal ileal disease removes the uptake step, so B12 is not absorbed even though intrinsic factor binding is intact.
- Bile salts emulsify dietary triglyceride and other lipids; pancreatic lipase hydrolyses them; products are carried in micelles; absorbed lipid leaves as chylomicrons, which enter the lymph.
- Bile salts are secreted by the liver into the common bile duct, pass through the gallbladder into the duodenum, travel along the small intestine to the ileum, and are mostly reabsorbed there and returned to the liver in the hepatic portal vein. The slide gives two figures: the liver synthesises bile salts (5%), and 5% is lost in faeces.
- Na+ permeability and transport is named as the key mechanism. Glucose and amino acids enter the enterocyte on Na+-coupled apical cotransporters, so their absorption depends on the Na+ gradient maintained by the basolateral Na+/K+-ATPase; water has no active transporter and simply follows the osmotic gradient created by Na+ absorption; and the colon absorbs the residual Na+ by channel, exchange and SCFA-linked routes. Failure of Na+ absorption therefore costs carbohydrate, protein and fluid uptake at once.