Digestion and absorption

3.4.1 General concepts

Digestion refers to the chemical and physical modifications which render ingested food constituents absorbable by the small intestine. Absorption is the process by which the products of digestion move from the lumen of the small intestine into the enterocytes and thence into the bloodstream or lymphatic system. A complex meal may be fully digested and absorbed in 3 hours.

After the digested food has passed through the wall of the small intestine, nutrients other than fats or fat-soluble substances enter the venules within the lamina propria. The venules eventually lead to the portal vein, which conveys nonlipid products of digestion from the intestine to the liver. Most of the absorbed non-lipid material passes through the liver, whose cells extract nutrients for storage or metabolic processing. The only exception to this portal route are the internal iliac veins which drain directly back into the systemic circulation (Granger et al., 1987). The nutrient-enriched blood that has passed through the liver is then sent to the heart and thence to the lungs. The oxygenated blood returns to the heart for redistribution to all parts of the body. The nutrients pass from the blood capillaries into the extracellular fluid from which the cells take up the nutrients they need.

Bile produced by the liver is secreted continuously into the gall bladder, which discharges it intermittently into the duodenum. Bile is necessary for the emul-sification of ingested fats. Many vital micronutrients, including vitamin D, folate and vitamin B, are conserved through their excretion in bile and subsequent reabsorption by the small intestine (enterohepatic circulation). The liver also produces copious amounts of lymph to sustain the lymphatic system. Absorbed lipids and lipid-soluble substances in the form of chy-lomicrons are transported via the lymphatic system and thoracic ducts to the subclavian veins and into the systemic circulation, bypassing the liver.

Digestion commences as soon as the food enters the mouth. Chewing helps to break up large particles of food, whilst also mixing food with saliva, which acts as a lubricant and contains the enzymes salivary amylase and lingual lipase. Lingual lipase has only a minor role in digestion of dietary triglycerides; however, salivary amylase plays a major role in digestion of dietary starch. Most of the enzymatic activity of salivary amylase occurs in the stomach, where there is a much longer time for it to interact with the starch.

In the stomach, the churning action and the presence of hydrochloric acid and pepsin convert the food bolus into a liquid chyme. The stomach has three regions with regard to its glandular secretions: the fundus (in the proximal stomach), the body and the antrum (in the distal stomach). The folds of the stomach lining contain microscopic gastric pits into each of which drain four or five gastric glands. The mucosa of the body and fundus contains oxyntic glands whereas the mucosa of the antrum contains pyloric glands. Oxyntic glands are lined by parietal cells that secrete hydrochloric acid and intrinsic factor and by chief cells that secrete pepsinogen (the precursor of pepsin) and gastric lipase. The pyloric glands contain almost no parietal cells or chief cells but, rather, contain mucus-secreting cells and G cells, which produce the hormone gastrin.

Most absorption takes place and is completed in the small intestine. On arrival at the duodenum, the acidic chyme is buffered by the bicarbonate in pancreatic juice and bile. Brunner's glands in the duodenum produce an alkaline secretion containing mucus. The proteases, amylase, lipase and other enzymes of pancreatic origin are also secreted into the duodenum. The final stages of digestion take place on the luminal surface or within the epithelial cells lining the small intestine. When absorption has been accomplished, the jejunum and ileum are actively involved in the regulation of electrolyte and fluid balance. The various stages of digestion are co-ordinated by the action of the nervous system, endocrine system and circulatory system.

The principal functions of the colon are (1) absorption of water and inorganic salts (mainly sodium) from the chyme to form solid faeces and (2) storage of faecal matter until it can be expelled.

3.4.2 The luminal environment within the small intestine

The bulk luminal phase of the upper gastrointestinal tract is characterized by a wide range of pH values. Postprandial pH values in humans are within the following ranges: 1.8-3.4 in the stomach, 6.8-7.8 in the lower small intestine, and 3.5-7 in the duodenum and proximal jejunum.

Bulk contents of the intestinal lumen are mixed by segmentation and peristalsis, and water and solutes are brought to the surface of the mucosa by convection. However, the luminal environment immediately adjacent to the brush-border membrane is stationary and unaffected by gut motility. The lack of convective mixing in this region creates a series of thin layers, each progressively more stirred, extending from the surface of the enterocyte to the bulk phase of the lumen. Together, these are the so-called 'unstirred layer', whose effective thickness in the human jejunum has been calculated to be 35 |m based on the rate of disaccharide hydrolysis at the brush border, rather than the 600-|m value derived from osmotic transient measurements (Levitt et al., 1992).

Solute movement within an unstirred layer takes place by diffusion, which is slow compared to the convective movement in the bulk luminal phase. The pH at the luminal surface is approximately two units lower than that of the bulk phase and varies less than ±0.5 units despite large pH variations in the intestinal chyme. It has been suggested that the formation of the low-pH microclimate is due to the presence of mucin which covers the entire surface of the epithelium (Nimmerfall & Rosenthaler, 1980; Shiau et al., 1985). Mucopolysaccharides possess a wide range of ioniz-able groups and hence mucin is an ampholyte. If the luminal chyme is of low pH, the ampholyte is positively charged and so it repels additional hydrogen ions entering the microclimate. If, on the other hand, the chyme is alkaline, the ampholyte becomes negatively charged and retains hydrogen ions within the microclimate. In this manner, the mucin layer functions as a restrictive barrier for hydrogen ions diffusing in and out of the microclimate.

3.4.3 Adaptive regulation of intestinal nutrient transport

Many patterns of adaptation fall into one or the other of two categories: (1) a non-specifically increased absorption of all nutrients, arising ultimately from an increase in the animal's overall nutrient requirements, and with an increase in absorptive surface area as the primary mechanism, and (2) phenomena involving the induction or repression of a specific transport mechanism, depending on the dietary availability or body store of the transported substrate.

Non-specific anatomical adaptation to changing metabolic requirements and food deprivation

Increases in metabolic requirements such as arise during pregnancy, lactation, growth, exercise and cold stress are met by an increased absorption of all available nutrients, mediated at least in part by an induced increase in food intake (hyperphagia). The increased absorption is due to an increase in mucosal mass per unit length of intestine and a consequent increase in absorptive surface area. Not only is there an increase in the total number of cells (hyperplasia) but the villi become taller.

The mammalian intestine adapts to prolonged food deprivation by dramatically slowing the rate of epithelial cell production in the crypts in order to conserve proteins and biosynthetic energy. This effect on mitosis and enterocyte renewal leads to markedly shortened villi. Because cell migration along the crypt/villus axis is also slowed, more cells lining the villi are functionally mature. Therefore, food deprivation, by reducing mucosal mass and increasing the ratio of transporting to nontransporting cells, effectively increases solute transport per unit mass of intestine.

Dietary regulation of intestinal nutrient carriers

It is well established that certain intestinal nutrient carriers, including those transporting a number of sugars and amino acids, are adaptively regulated by their substrates. This type of regulation is transient and reversible. For example, the rate (V ) of active glucose uptake doubles within 12 hours when mice fed a carbohydrate-free diet are switched to a high-carbohydrate diet (Diamond & Karasov, 1984). If the same mice were switched back to the carbohydrate-free diet, it would take up to 3 days for the glucose uptake to revert to the original rate. The sole mechanism responsible for these changes is a corresponding increase or decrease in the number of carriers at both the apical and basolateral membranes of the ente-rocytes. There is no effect on numerous variables of intestinal structure, such as length, circumference, weight, villus dimensions and density, and area at the villus level. The signal for regulation of brush-border glucose transport is the luminal concentration of sugars - not only glucose itself, but also nontransporting sugars. The signal for the basolateral glucose transport is yet to be established, but it involves signals from the plasma. The signals are perceived in the intestinal crypts, where the carrier proteins are synthesized within the developing enterocytes. The observed lag in response is attributed to the time taken for the cells to migrate from crypt to villus.

According to the adaptive regulation/modulation hypothesis (Karasov, 1992), a carrier should be repressed when its biosynthetic and maintenance costs exceed the benefits it provides. The benefits can be provision of either metabolizable calories or an 'essential' nutrient, i.e. a nutrient such as an essential amino acid which cannot be synthesized in the body and must be obtained from the diet. Glucose carriers are up-regulated when the dietary supply of glucose is adequate or high because glucose provides valuable calories. The down-regulation of glucose carriers during a deficiency of glucose can be explained by the biosynthesis and maintenance costs outweighing the benefits of transporting this 'nonessential' nutrient.

One might expect carriers for water-soluble vitamins to be down-regulated by their substrates and up-regulated in deficiency of the vitamins. The rationale in this case is that carriers for these essential nutrients are most needed at low dietary substrate levels; at high levels the required amount of the vitamin could be extracted from the lumen by fewer carriers or even cross the enterocyte by simple diffusion. As vitamins do not provide metabolizable energy, there is nothing to gain from the cost of synthesizing and maintaining carriers when the vitamin supply is adequate or in excess.

The prediction of suppressed transport of vitamins at high dietary intakes has proved to be true for ascorbic acid, biotin and thiamin, but not for pantothenic acid, for which carrier activity is independent of dietary levels (Ferraris & Diamond, 1989). It appears that intestinal carriers are regulated only if they make the dominant contribution to uptake, as is the case for the three regulated vitamins. It can also be reasoned that carriers for ascorbic acid, biotin and thiamin would need to be regulated, because nutritional deficiencies of these vitamins can and do occur. In contrast, there is no need to regulate pantothenic acid carriers, because this vitamin is found naturally in almost all foods and cases of deficiency are extremely rare.

3.4.4 Alcoholism and its effect on intestinal transport

Chronic alcoholism is a complex disorder often characterized by malnutrition, vitamin deficiencies (particularly thiamin, vitamin B6 and folate) and diarrhoea. Among the possible mechanisms for these disturbances are alterations in intestinal digestion, absorption and secretion. The following is based on a review by Wilson & Hoyumpa (1979) of the possible mechanisms by which ethanol directly affects intestinal transport.

Chronic ingestion of ethanol (1.09 M) results in shortening of the villi in the jejunum and degenerative changes in cellular ultrastructure of both jejunal and ileal villi. However, disturbances in intestinal function have been observed in the absence of such changes and so the changes cannot fully account for the impaired transport of nutrients.

The ethanol molecules (CH3CH2-OH) insert into the lipid bilayer of the plasma membrane with their hydrocarbon portions positioned between hydropho-bic regions of membrane lipids and proteins. Ethanol causes a molecular rearrangement of membranes, which loosens the membrane and makes it more fluid. This effect of ethanol may increase the permeability of the gut wall and allow passive movement of large antigenic molecules, toxins and pathogenic organisms through the gut wall and into the bloodstream. It may also interfere with the conformational changes that carrier proteins need to make to effect solute transport. After chronic treatment with ethanol, cells adapt to this change in membrane fluidity by incorporating more rigid fatty acids into membrane phospholipids.

Ethanol inhibits the cell's sodium pump thereby interfering with sodium-coupled active transport of glucose, amino acids and certain water-soluble vitamins.

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