Lecture 5 Digestion and absorption
We have considered how food is moved in the gut and how various secretions of the gut and associated organs are controlled by the passage of food through the gut. All these processes are a co-ordinated process which culminates in the digestion and absorption of the nutrients in food. In this lecture we consider the process of digestion of the various food groups, and how they are absorbed for use in the body.
This lecture covers: Blood and lymph supply to and drainage from the villus. Digestion and absorption of carbohydrates. Digestion and absorption of proteins. Digestion and absorption of fats. Special cases of absorption - vitamins, calcium, iron. Absorption of water and electrolytes.
The blood supply to the villus is adapted for the absorption of nutrients in the blood stream and the lymphatics. Each villus is supplied with artery and vein and lymphatic lacteal which serve as routes for absorption and distribution of the nutrients from food around the body.
In cases when the blood supply to the gut is reduced oxygen exchange between the artery and vein at the base of the villus may result in necrosis of the tip of the villus. This results in a reduced surface area for absorption and the problems associated with this (diarrhoea, steatorrhoea, malnutrition, vitamin and mineral deficiencies).
Digestion of carbohydrates
Digestion of carbohydrates is through catalytic hydrolysis of a 1,4 bonds between monosaccharides. This reaction is catalysed by salivary amylase in saliva, which is inactivated in the stomach by low pH, and by pancreatic amylase in the small intestine. These enzymes break down starches to maltose (disaccharide) and to polymers of glucose molecules of between 3 and 9 molecules in length. These enzymes are not capable of hydrolysing a 1,6 bonds, so branched carbohydrates are not broken down.
Enzymes immobilised on the brush border of the enterocyte break down the disaccharides and glucose polymers to monosaccharides - mostly glucose but also some fructose. Branched polysaccharides are hydrolysed by the action of a -dextrinase, also on the brush border. The action of these enzymes results in a high concentration of monosaccharides at the brush border which means there are large quantities of sugars available for transport into the cell.
Absorption of monosaccharides
Glucose is transported into the cell by a sodium dependent mechanism which transports glucose and sodium ions. This uses the energy generated by the sodium ion gradient to transport the sugars into the enterocytes. The transporter will not move sodium ions unless glucose is also bound to it. Fructose is transported via facilitated diffusion, and is converted to glucose in the cell. Glucose is transported out of the enterocytes into the extracellular space by facilitated diffusion.
If carbohydrate absorption is disrupted, the high concentration of sugar in the chyme results in osmotic pressures which interrupts the absorption of water. This results in diarrhoea. It is not commonly found as in high sugar concentration glucose can be dragged with the bulk flow of water through the gap junctions between the cells. If there is a deficiency of carbohydrases then the complex sugars are not broken down and therefore exert an osmotic effect. Additionally if there is gut pathology which results in villus atrophy then there is a decreased surface area for absorption and diarrhoea results.
Importantly with respect to dentistry, when artificial sugars were first used it was found that although the rate of dental caries is reduced if carbohydrates are replaced by e.g. saccharin, the lack of absorption of the artificial sugar resulted in diarrhoea due to the osmotic effect.
Protein digestion begins in the stomach with the action of pepsin. This is an important enzyme as it is the only protease capable of digesting collagen. Other proteases are released by the pancreas by the action of cholecystokinin, as inactive precursors. Trypsinogen is activated in the duodenum by enterokinase (or enteropeptidase) to trypsin. Trypsin activates the other protease precursors secreted from the pancreas. Interestingly the proteolytic action of trypsin also inactivates the proteases in the gut.
Protease action converts proteins to amino acids and di-, or tri-peptides. The amino acids and di- and tri-peptides are absorbed by specific transporter proteins. Di- and tri-peptides are then broken down to amino acids by cytoplasmic peptidases.
Amino acids are transported into and out of the enterocyte by sodium dependent transport in a manner similar to glucose.
Fat digestion and absorption is dependent upon bile. Bile secreted from the liver and released into the gut by the action of CCK on the gall bladder acts as an emulsifier to break up fat globules to facilitate digestion. Pancreatic lipase is a water soluble enzyme and can therefore only act on the surface of fat globules. The detergent action of bile salts, particularly lecithin is required to disperse the fat into small globules for efficient lipase digestion.
Fats are also digested by catalytic hydrolysis. Pancreatic lipase hydrolyses neutral fats to give free fatty acids and 2-monoglycerides.
Free fatty acids and monoglycerides are also not water soluble. A further action of bile is the formation of micelles. These are small (3-6nm) and formed of molecules of bile acids. These are compounds which have a sterol or fat soluble portion, and a polar group. The micelle consists of aggregations of free fatty acids, mono-glycerides in the middle with the polar ends of the bile salts enabling solution in water.
The micelles serve the function of 'shuttling' products of fat digestion from the site of digestion to the brush border where they can be absorbed into the enterocyte. This serves two purposes. Firstly it removes the products of fat digestion so that they do not inhibit the action of the lipase (product inhibition) and secondly it transports the insoluble digestion products to the cell membrane where they can diffuse directly into the cell.
Excess fat in the stools is termed steatorrhoea. The stools are pale in colour, bulky and highly smelly. They also float. Steatorrhoea is associated with poor fat absorption, due, for example to coeliac disease or gluten enteropathy, when villi are lost and absorption greatly decreased. Fat absorption can also be affected by acid hypersecretion as pancreatic lipase is acid-labile and fats are therefore not digested or lack of bile salts.
There is some recent thought that bile acid recirculation in the adult is a detrimental process, as this serves to increase plasma cholesterol levels due to low excretion of cholesterol. An interesting reference on this can be found in News in Physiological Sciences February 99. Copies available from me as not in the library.
Water and electrolyte absorption
As we have seen sodium can be absorbed in a variety of ways from the gut. It diffuses into enterocytes down it's concentration gradient, but is also actively taken up in co-transport with both glucose and amino acids. It is also co-transported with other ions such as chloride, or exchanged such as with hydrogen ions.
Sodium ion absorption drags other ions such as chloride with it, electrical effect. Water also passes through the tight junctions by bulk flow, following the movement of ions.
Sodium resorption from the gut is stimulated by aldosterone in dehydration - revise the renin-angiotensin- aldosterone system if you don't remember this.
Absorption of special cases - nutrients which require specific transport mechanisms
Disorders of electrolyte/fluid absorption.
We have already mentioned the consequences of disorders in fluid absorption i.e. diarrhoea on several occasions. Hyper-osmotic chyme for whatever reason will result in water remaining in the gut and thereby resulting in diarrhoea.
In cholera the toxin produced by the causative organism activates the chloride channel in enterocytes through which chloride ions are normally secreted. This channel is opened by the action of the second messenger cyclic AMP, which is activated by cholera toxin. Thus the diarrhoea associated with cholera is a secretory diarrhoea caused by massive efflux of chloride ions from the enterocyte and retention of water in the gut rather than it being absorbed.
There are a great many members of the family of vitamins, and we will cover the effects of their lack in the last lecture in this series. The vitamins can be separated into the fat soluble and water soluble classes. All the vitamins are absorbed by passive diffusion, either in the water soluble or fat soluble compartments except for three special cases.
Vitamin B1 (thiamine). This water soluble vitamin is absorbed by a sodium dependent transport mechanism similar to glucose and the amino acids.
Vitamin C Humans require vitamin C for collagen formation. It is absorbed by both passive diffusion and sodium dependent active transport in humans.
Vitamin B12. We have discussed the role of intrinsic factor, secreted by the parietal cells in lecture 3. To recap, vitamin B12 requires intrinsic factor for two reasons. Firstly the complex of vitamin B12 and intrinsic factor is resistant to digestion. Secondly, the complex is absorbed by receptor mediated uptake in the distal ileum. Without intrinsic factor, pernicious anaemia develops.
The absorption of calcium from the gut is dependent upon parathyroid hormone. Low circulating calcium levels are detrimental to health as disruption of calcium balance has particularly profound effects on excitable cells. Loss of the parathyroid glands (for example through thyroidectomy) results in tetany of muscles if left untreated. Low calcium concentrations release the inhibition of the release of PTH, which is effected by normal serum calcium levels (>9-10mg/dl). Lowering of calcium levels below this concentration causes PTH release due to a relief of inhibition. PTH stimulates the conversion of 25, hydroxy- vitamin D3 to 1,25 dihydroxy-vitamin D3 in the kidney. This acts on enterocytes in the gut to directly stimulate the transcription of the gene encoding the calcium binding protein. This action results in more calcium binding protein being expressed in the membrane of the cell, which promotes calcium absorption thereby returning calcium plasma levels to normal. The relationship between PTH and Ca is tightly controlled - once calcium levels in plasma are restored, PTH secretion is rapidly turned off.
Iron is also an essential mineral, which is of course particularly important in oxygen transport in haemoglobin. Iron uptake in the gut is mediated by an binding protein, transferrin. This protein binds two molecules of iron and is then taken up into the cell by receptor mediated pinocytosis. Once in the cell the iron is either stored by binding to an intracellular protein ferritin, if plasma iron levels are high, or is transported out of the cell and bound to plasma transferrin for transport around the body. Plasma transferrin is similar to the molecule found in the lumen of the gut, but is not the same protein.