Nutrient Absorption

M. Ellert



The major function of the small intestine is absorption--of nutrients, water, electrolytes, etc. This is an essential function of the gastrointestinal system, and it plays a significant role in regulating the water and electrolyte balance of the body. As described below, the total daily amount of GI secretions is about 8 liters, virtually all of which is reabsorbed; in addition, about 2 liters of ingested fluid must also be absorbed. Obviously, malabsorption, or derangements of the normal absorptive function, can have extremely serious consequences. The daily loss of 8-10 liters of fluid during cholera has just as severe an effect as an equivalent loss from the renal system in uncontrolled diabetes. The surface area of the intestine is well suited to its function: the structural adaptations of mucosal folds, villi and microvilli give a total absorptive area for the small intestine of 200-500 m2, or a 600-fold increase over the projected surface area of a smooth-surfaced tube of equivalent length. The small intestine normally absorbs far in excess of body needs--the major portion of this organ can be removed without deleterious effect. Yet disturbance of the normal absorptive function--by inadequate digestion, accelerated motility, etc.--can rapidly result in serious malnutrition, dehydration or electrolyte imbalance; in young children, diarrhea can quickly become life-threatening.

Absorption of a substance by the intestine signifies its passage through the intestinal epithelium and into the blood or lymph, whereas secretion implies movement in the opposite direction. With regard to absorption, at least two components are involved: (1) movement from the intestinal lumen into the apical (mucosal) end of the absorbing cell and (2) movement from the basilar (serosal) end of the absorbing cell into the subcellular space (and subsequently, into the circulatory or lymphatic systems). Substances entering at the apical surface may be metabolized within the cell, or may appear at the basilar surface in a changed form. For most substrates, movement across the epithelial cell is bidirectional. Therefore, net movement or net flux of a substrate is the difference between movement into and movement out of the cell (absorption vs. secretion, or influx vs. efflux).

Transport across the intestine may be active or passive: active transport requires energy, whereas passive transport does not. Also, active transport may involve movement of a substance against a concentration gradient (that is, from a region of lower to higher concentration), while substances that are passively transported always move with the concentration gradient. Facilitated diffusion is a type of passive transport which, unlike simple diffusion, uses a carrier; it is therefore more rapid than simple diffusion.

Active transport mechanisms have been identified for intestinal absorption of many substances including glucose, galactose, amino acids, calcium, iron, folic acid, ascorbic acid, thiamin and bile acids. Fructose, riboflavin and vitamin B12 (in combination with intrinsic factor) are among the substances absorbed by facilitated diffusion.

Figure 1 illustrates the possible types of movement across the small intestine, for any given substance.


An important function of both small intestine and colon is the absorption of water and electrolytes. Approximately 2000 ml of food and drink is ingested daily, and the volume of gastrointestinal secretions (salivary, gastric, biliary, pancreatic and intestinal) is about 8,000 ml daily; therefore, approximately 10 liters of fluid enters the intestine each day. Of the 8 liters secreted, about 1-1.5 liters enter as saliva, 2-3 liters are secreted by the stomach, about 2 liters enter as bile and pancreatic secretion (about 1 liter each), and about 2 liters are secreted by the small intestine. (Please note that these figures are approximate, not absolute. Volumes may vary, depending on experimental method and conditions.) Of the 10 liters which enters the gut each day, only about 1 liter passes into the colon, about 90% having been absorbed across the small intestinal epithelium. Only about 150 ml is lost in the feces daily, with the remainder being absorbed by the colon. It should be obvious that any derangement in intestinal fluid absorption would profoundly influence the balance of fluid and electrolytes in the body, and that the normal functioning of the intestines plays a significant role in regulating water and electrolyte balance.

The net absorption or net secretion of water in the intestine is the result of bidirectional movements of water from mucosa to serosa (m-->s flux or absorption) and from serosa to mucosa (s-->m flux or secretion). In the human intestine, these unidirectional fluxes exceed net movement 2-3 fold. The rate and direction of net fluid movement depend on tonicity of the meal, and move toward the achievement of isotonicity.

The intestinal mucosal surface consists of a bimolecular lipid membrane, which (presumably) contains small pores or channels. Water and water-soluble substances can hypothetically enter the cell through these pores only, while lipid-soluble substrates can directly cross the lipid cell membrane. Specialized protein pores, referred to as aquaporins (AQP) have been identified in many tissues, including colon epithelium; water channel isoforms in small intestinal epithelium remain to be discovered.

Intestinal absorption of water is a passive process and requires movement of solutes. Water accompanies solute and moves across the intestinal mucosa in response to osmotic gradients. The rate of water uptake in any region of the intestine is a function of solute absorption in this region. All areas of the intestines (including small bowel and colon) absorb water, the relative amounts absorbed depending on the presence of solutes, and the types of solutes present. In the jejunum, the active transport of sugars and amino acids causes passive movement of salt and water, which accounts for most of the water uptake in this area. In the ileum, most water movement is accounted for by active sodium transport. As described in Johnson (Gastrointestinal Physiology), coupled water and sodium transport involves a specialized mechanism that pumps sodium into the lateral spaces, resulting in relatively high osmotic pressure in that region. Water then enters the lateral space from the cell (transcellular flux) and--perhaps--the lumen (paracellular flux), reducing the osmotic pressure but increasing the hydrostatic pressure. Fluid is then forced out of the lateral space into the interstitial space. The net effect is that isotonic fluid is transported from the lumen into the extracellular fluid. This hypothesis of fluid absorption is illustrated in Figure 12-5, on page 137 of the Johnson resource.


In contrast to water transport, intestinal transport of sodium is quite a complex process, actually a number of different processes. Apparently a number of different mechanisms exist, there is considerable variation between species, and much of the available information is largely theoretical.

Mechanism(s): both passive and active mechanisms exist, for Na+ transport by the small intestine. Active transport can be independent or linked to the transport of other solutes (e.g., sugars). The latter is referred to as coupled transport or cotransport. It has been postulated that independent pumping of Na+ by a pump in the basolateral membrane accounts for about 20% of the total Na+ absorbed by active transport mechanisms; the remaining 80% is absorbed via cotransport. Cotransport with sugars is illustrated in Figure 11-6, on page 114 of the Johnson reference. Cotransport with amino acids or (primarily in the ileum) bile acids proceeds by a similar, if not identical, mechanism. Cotransport with Cl- probably accounts for most of the sodium absorption in the mammalian small intestine. This “carrier coupling” of Na+ and Cl-, whereby both ions enter via a common carrier, should be distinguished from “electrical coupling” of Na+ and Cl-, wherein Cl- passively follows the movement of Na+ across the epithelial membrane. In all instances of coupled transport, the addition of one cotransported species greatly enhances the absorption of the other. The driving force for all types of active Na+ transport is the hydrolysis of ATP, catalyzed by the N+/K+ ATPase located at the basolateral membrane. This “pump” exchanges Na+ (out) for K+ (in), thus maintaining a steep electrochemical gradient for the entry of Na+ from the lumen. Passive transport of Na+ occurs largely through the lateral spaces and tight junctions. That is, it is largely paracellular, as opposed to active transport which appears to be largely transcellular. Once Na+ has entered the cell (by whatever mechanism), it is pumped out by the Na+ pump at the basolateral border. The proposed mechanism(s) for Na+ (and Cl-) transport in the small intestine is shown in Figure 12-2 on page 133 of the Johnson resource.

Site: Sodium absorption occurs by different mechanisms in different parts of the intestine: in the jejunum, sodium is mostly absorbed via cotransport, as a result of active uptake of sugars and amino acids (both of these processes require the presence of Na+); in the ileum Na+ itself is absorbed actively, against a significant electrochemical gradient. In the jejunum, sodium transport is greatly influenced by fluid movement and is stimulated by the presence of sugars; in the ileum, none of these factors affect sodium movement. Sodium is also actively absorbed in the colon.


In the presence of bicarbonate, sodium can be absorbed from the jejunum against electrochemical gradients (i.e., actively). Bicarbonate absorption in the jejunum appears to be mediated by active secretion of hydrogen ions; in this case, the link between sodium and bicarbonate transport may be explained by sodium-hydrogen exchange. If bicarbonate concentration in the luminal contents falls below 40-45 mM, bicarbonate will be secreted by the ileum or colon; it will be absorbed by the ileal mucosa if its concentration is greater than 40-45 mM. Secretion of bicarbonate is to some extent coupled with chloride absorption in an ion exchange process (countertransport), but each ion is secreted or absorbed by other mechanisms as well. Colonic secretion of bicarbonate appears to be an active process (see Colonic Absorption below).


A major part of chloride absorption may be due to sodium absorption, for there is a close parallel between the absorption of these two electrolytes (see above). Chloride is largely not transported against electrochemical gradients, but is rather absorbed and secreted down an electrochemical gradient. However, there is some evidence for the existence of an active transport mechanism, as well.

Congenital chloridorrhea is apparently the only specific disturbance of ion transport in human ileum. This rare condition is characterized by excessive loss of Cl- and water in stools, resulting in persistent hypochloremic, hypokalemic alkalosis, and episodes of severe Na+ and K+ dehydration.


As with other substrates, the net movement of K+ across the intestinal mucosa is determined by the difference between two opposing unidirectional fluxes; compared to sodium fluxes, potassium fluxes are small. Net movement of K+ in jejunum and ileum occurs only down the electrochemical gradient (i.e., it is largely passive). Potassium diffuses primarily through the lateral spaces and tight junctions. In the colon potassium is usually secreted, and the luminal concentration must be above 25 mEq/L for net absorption to take place. This explains why potassium deficiency tends to develop in diarrhea. Potassium secretion by the colon appears to be a passive process.

Calcium and Iron

In contrast to the complete and largely unregulated absorption of the common monovalent electrolytes, the divalent cations calcium and iron are incompletely absorbed, and this absorption is regulated, depending on body stores of these ions. If there is a positive balance of calcium or iron, intestinal absorption is reduced; increased absorption results in the case of a negative balance.


Iron balance differs from that of other trace elements in that it is regulated primarily by absorption, not excretion. Because the body's ability to excrete iron is very limited, intestinal iron uptake is closely restricted to about 1 mg, which is the amount usually excreted daily in the urine and feces. This is a small fraction (0.03%) of the total body iron content. Relatively large amounts are lost, of course, during menstruation. The exact amount absorbed is determined by many factors, which may be classified as luminal, epithelial and corporeal. These will be discussed in more detail later.

Site. Dietary iron is taken up largely in the duodenum and upper jejunum, but any segment of small bowel is capable of absorbing reduced iron. There is much evidence that iron uptake in the proximal small intestine is at least partly energy-dependent (active), particularly at low iron concentrations. At higher luminal concentrations of iron, a non-energy-dependent mechanism seems to prevail.

Mechanism. The transfer of iron from the intestinal lumen to the portal circulation involves two separate phases: the passage of iron across the brush border into the epithelial cell and the subsequent transfer of some of this iron across the basal (serosal) surface of the cell into the blood. Iron deficiency seems to facilitate the passage of dietary iron across the serosal barrier into the blood, so that less iron accumulates in the mucosa. The serosal surface of the cell is apparently the major site of control of iron entry into the body. However, there is evidence that uptake of iron at the mucosal surface may also be affected by the body's iron status.

It should be noted that there are two kinds of iron in the diet with respect to the mechanism of absorption: heme iron (derived from hemoglobin and myoglobin) and non-heme iron (derived mainly from cereals, vegetables, fruits, etc.). Heme iron forms a relatively minor part of dietary iron intake; even in diets with a high meat content it accounts for only 10-15% of the total iron intake. However, the bioavailability (portion absorbed) of heme iron is higher than that of non-heme iron (22% vs. 2%). One probable reason is that heme iron is absorbed as an iron-porphyrin complex directly into the mucosal cells, and is not as affected by dietary factors which inhibit iron uptake. Iron bioavailability will be further discussed below.

The iron absorption process may be divided into the following steps:

  1. The adsorption of ionic iron to receptors located in the brush border of the mucosal cells (enterocytes). For this uptake iron must be in a soluble form. The amount of non-heme iron transferred from the gut lumen to the epithelial cell depends on the abundance of receptors on the brush border. The receptor population increases in iron deficiency.
  2. Iron uptake by enterocytes. Heme iron is not taken up by brush-border receptors but directly enters the mucosal cell, where the complex is broken down by xanthine oxidase and the iron released.
  3. Iron transport within enterocytes. After passing into the cell (probably by an energy-dependent process) much of the iron is apparently transported to the serosal surface as a small molecular weight compound which is in equilibrium with ferritin. Ferritin (an iron-protein complex [20% Fe], which contains aggregates of ferric hydroxide and a protein, apoferritin), occurs in other parenchymal cells and is believed to be the chief storage form of iron. The ferritin found in mucosal cells appears to be relatively iron-poor and is apparently in continuous equilibrium with the absorbed iron as it travels across the cell. If excess iron is absorbed across the brush border, the mucosal ferritin may become saturated and thus cease to equilibrate with absorbed iron. This implies that in the mucosa, as in other tissues, ferritin is a mechanism for dealing with excess intracellular iron. Most ferritin-bound iron is lost when the epithelium exfoliates.
  4. Transfer of part of the iron from enterocytes directly to the blood. Iron is transported through the cytoplasm to the basolateral membrane by a transport protein (similar but not identical to transferrin--see below), which conveys it to the intercellular space. Iron is transported in plasma bound to transferrin, a single polypeptide chain with a molecular weight of 75,000-80,000. Transferrin readily circulates in the interstitial spaces and exchanges iron with all cells of the body.
  5. Return of the remaining iron to the lumen. Mucosal iron not transferred to the portal blood is returned to the intestinal lumen when the mucosal cell is sloughed off at the tip of the villus (human mucosal cells apparently migrate to the villus tip in 2-8 days). Since iron can also enter mucosal cells from the blood, this mechanism affords a means of ridding the body of a certain amount of excess iron. In cases of iron overload such as hemosiderosis, this mechanism is assisted by the migration and exocytosis of iron carried by iron-loaded macrophages.

Factors controlling absorption. These may be classified as intraluminal, mucosal, and corporeal as shown in Figure 2.

Intraluminal factors are present in the lumen of the gut (largely the form of iron which is present, and the presence of other ingested or secreted compounds). Mucosal factors include structural and functional characteristics of the intestinal epithelial cell, primarily its iron content. “Corporeal” factors include body iron stores. The most important regulator and stimulant of iron absorption is a negative iron balance. This will be reflected in decreased body iron stores and consequently in reduced iron content in intestinal epithelial cells. Each of the three classes of factors affecting iron absorption will be discussed below.

Table 1: Intraluminal Factors Affecting Iron Absorption
Absorption proportional to amount
Ferrous is better absorbed than ferric
Ascorbic, succinic and other organic acids
Reducing compounds
Amino acids
Sugars (Fructose, Sorbitol)
Dietary fiber (bran, lignin)
Inorganic elements;
Ca, Mn, Cu, Cd, Co
Egg yolk
Intrinsic factor
Stabilizing factor
Secretions other than bicarbonate Bicarbonate

  1. Intraluminal factors are summarized in Table 1. Although, as stated above, body iron balance is the major regulatory factor in intestinal iron absorption, specific luminal factors which affect the bioavailability of iron are also important. Iron lack is the most common deficiency state found in humans; it is widely prevalent in both developing countries and highly industrialized nations. It has been estimated that more than 5 million adult women in the United States have iron deficiency anemia, and at least 10 million have iron reserves insufficient to meet the demands of menstruation and pregnancy. This situation exists in spite of the fact that the average United States diet contains more than five times the amount of iron hypothetically needed to maintain iron balance. The problem is apparently the poor availability of dietary iron (of 10 mg dietary iron, only 1 mg will be absorbed). Thus the luminal factors affecting iron bioavailability can be quite crucial, and it may be that the most useful and readily found therapy for iron deficiency might be the addition of such factors as ascorbic acid to the diet.

    Some of the factors affecting iron availability are summarized in Table 1. Many components of the complex modern diet may either stimulate or inhibit iron absorption: for example, a “meat factor” present in animal protein (excluding dairy products) enhances the absorption of non-heme iron; chelates may either facilitate absorption (ascorbic acid) by forming a complex with iron that remains soluble at the high duodenal pH, or they may impair iron absorption (EDTA, a common antioxidant added to foods) by effectively competing for iron with the intestinal mucosa; phosphate and calcium seem to reduce iron absorption; bran, presumably due to its phytate content, decreases iron absorption from bread. Apparently, chelated iron compounds are absorbed by mechanisms other than those for unchelated iron salts. The heme chelate of iron, present for example in ingested meat, is not affected by many of the factors which alter the rate of uptake of iron salts.

    Recently a model has been proposed whereby the availability of iron in a given meal may be calculated. This method takes into account five factors--total iron, heme iron, non-heme iron, ascorbic acid, and meat/poultry/fish--the iron content of the meal can then be classified as having high, medium or low availability. It should be noted that although meat has a marked stimulatory effect on iron absorption, the absorption of iron from a vegetarian diet can be very high (equivalent to meat-containing diet) if the ascorbic acid content is also high.

    Infants absorb 50-70% of the iron in human milk, as contrasted with 10% of the iron in cow's milk, and 3-5% of the iron in iron-fortified proprietary formulas. This difference is apparently due to the composition of these substances--i.e., the presence in human milk of substances which promote or inhibit iron absorption. Recent studies suggest that the addition of supplemental food to the diet of the breast-fed infant impairs the bioavailability of the iron from human milk.

    Although iron absorption is promoted by a more acidic environment (which promotes solubility of iron salts), taking antacids concomitantly does not necessarily render supplemental iron ineffective. Much depends on the choice of an appropriate antacid.

    The decreased iron absorption seen in elderly individuals may be due at least in part to achlorhydria, which is much more common in the elderly.

  2. Mucosal factors. As should be evident at this point, the amount of iron stored in intestinal epithelial cells is a key factor in regulating iron absorption: iron-loaded cells generally absorb far less iron than iron-deficient cells (An exception to this is in idiopathic hemochromatosis, when iron absorption is actually increased despite iron overload).

    In addition, there is a phenomenon known as mucosal block, whereby the intestine is temporarily refractory to iron absorption following the ingestion of a large dose of iron. Because of this refractory period, the replacement of storage iron in an iron-deficient subject is a necessarily slow process. Iron absorption is also affected by “epithelial” factors which are far less specific: for example, decreased absorptive surface area, defective epithelial cells, or decreased mucosal blood flow will decrease the absorption of iron (and all other absorbable substances).

  3. Corporeal factors. Two major “corporeal” factors related to the regulation of iron absorption are the status of body iron stores and the rate of erythropoiesis. Decreased body iron stores are associated with increased intestinal absorption of iron, and vice versa. This means that iron absorption will be increased in some pathological conditions like anemia and hemorrhage, and in the physiological conditions of menstruation, pregnancy and lactation. Increased erythropoiesis (stimulated, for example, by high altitude hypoxia, hemolysis or following hemorrhage) is also accompanied by increased absorption of iron, and vice versa. Absorption from a typical Western diet rises to a maximum of 3-4 mg daily when the body is depleted of iron and falls to less than 0.5 mg daily when iron overload is present. The mechanism whereby mucosal cells alter their iron-absorbing capacity in response to changes in iron stores or erythropoiesis remains unclear.


    Calcium is absorbed as the divalent cation. Most dietary calcium is not ionic, and is insoluble at a neutral pH. Gastric acid solubilizes Ca++ salts and allows their absorption from the intestine.

    Site: Calcium is absorbed from the duodenum and upper jejunum primarily by an active vitamin D-dependent transcellular process; in the ileum, the predominant process is passive vitamin D-independent, paracellular diffusion. Absorption of Ca++ in the ileum is about one-third as rapid in the upper small intestine. Although the duodenum is the region of most efficient calcium absorption, the greatest proportion of calcium is probably absorbed in the ileum, especially under conditions when transcellular transport is decreased, as in old age.

    Mechanism: Not much is known about the mechanism of, or factors influencing, the paracellular transport of calcium. The active (transcellular) transport of calcium is a three-step process: first Ca++ is absorbed from the lumen (probably via facilitated diffusion), then moved through the cytosol from the apical to basolateral surface, and finally extruded across the basolateral membrane into the interstitial fluid. Vitamin D apparently influences each of the three steps. Since the first step is more rapid than the latter steps, intracellular Ca++ concentration rises during absorption. Because of the potential toxicity of calcium to the cell, little calcium entering from the lumen is permitted to diffuse freely across the cell to the basolateral membrane. Mitochondria, with an impressive capacity to accumulate calcium, may facilitate the movement of calcium across the cell. Other organelles (such as lysosomes and smooth endoplasmic reticulum) may also be involved. Such cellular structures, as well as other mechanisms which keep intracellular Ca++ concentration in the micromolar range, are usually referred to as calcium buffers. Calcium buffers in the intestinal epithelial cell include a specific calcium-binding protein (CaBP or calbindin). The active transport mechanism is probably located on or near the basal and/or lateral surfaces of the mucosal cell. Mg++ and Co++ appear to compete with calcium by consistently causing a decrease in the mucosal-to-serosal flux of Ca++.

    Controlling factors: It has been postulated that the active metabolite of Vitamin D--1,25-dihydroxycholecalciferol--acting on intestinal cells like a steroid hormone, causes increased Ca++ absorption by stimulating the synthesis of calbindin. However, recent studies indicate that Ca++ transport can occur in some species when calbindin is absent, and such transport may decline to very low levels in the presence of abundant calbindin. Although calbindin is certainly involved in the complex process of intestinal calcium transport, it is probably not the only protein induced by Vitamin D. Brush border alkaline phosphatase and a Ca-dependent ATPase have also been found to be stimulated by the vitamin. Other proteins induced by Vitamin D seem to correlate with increased Ca++ absorption, and are currently under investigation.

    As with iron, the net amount of Ca++ absorbed is regulated to meet the body's needs. Factors affecting the rate of intestinal absorption of Ca++ include: plasma Ca++ concentration (i.v. infusion of calcium immediately suppresses duodenal and jejunal Ca++ absorption in normal subjects), parathyroid hormone (promotes absorption, probably indirectly by stimulating production of 1,25-dihydroxycholecalciferol), reproductive status (absorption more rapid in pregnancy), dietary calcium or phosphorus (low levels of either will stimulate the rate of intestinal Ca++ absorption probably by stimulating parathyroid hormone production), bioavailability, the presence of other dietary factors, age (younger animals absorb more rapidly) and degree of physical activity (calcium is lost from the body, regardless of “adequate” intake, during periods of prolonged immobilization). There is evidence that impaired calcium absorption in the elderly may be due, at least in part, to inadequate production of 1,25-dihydroxycholecalciferol; other factors may include age-associated structural changes in intestinal mucosa, estrogen withdrawal in postmenopausal women, achlorhydria (more common in elderly), low intake of Vitamin D, and the development of a relative resistance to vitamin D in the aging small intestine.

    Calcium transport is affected by a number of hormones: it appears to be stimulated by growth hormone, insulin and gastrin, as well as parathyroid hormone, while it is apparently inhibited by cortisol, thyroxine, glucagon and (possibly) somatostatin. Only about 30% of dietary calcium is absorbed; the remaining 70% is excreted in the feces.

    The regulation/secretion of Ca++ transport, and its role in overall calcium balance, is illustrated in Figure 3 and in Figure 12-6, on page 139 of the Johnson resource.


    The absorption of fat-soluble and water-soluble vitamins is adequately discussed on pages 128-130 of the Johnson resource.

    Colonic Absorption

    As indicated in the preceding discussion, the colonic mucosa absorbs water, sodium and chloride and secretes potassium and bicarbonate. Sodium can be absorbed against a large concentration gradient, primarily (or solely) via independent (uncoupled) active transport. This active, electrogenic process is apparently located at the basolateral membrane. The colon seems to conserve Na+ more efficiently than the small intestine: it absorbs about 95% of luminal sodium, as compared to 75% absorbed by the small bowel. Bicarbonate is secreted against an electrochemical gradient. Chloride absorption is linked to bicarbonate secretion and sodium transport. Potassium may be absorbed or secreted, depending on the luminal concentration: it is absorbed if the concentration exceeds 15 mEq/L, and is secreted if it falls below this value. Since luminal [K+] is usually less than 15 mEq/L, net secretion normally occurs. Passive diffusion across tight junctions is the primary mechanism of potassium transport in the colon. The passive uptake of water (which largely follows sodium absorption) serves to convert the liquid ileal contents to semisolid feces. Most water and sodium are absorbed in the ascending and transverse colon. The colon has some reserve capacity for absorption; it normally absorbs about 1000 ml daily, but it can apparently absorb as much as 4500 ml if the need arises. This may be very useful in compensating for the decreased absorptive ability of the small bowel in some disease states. When the colonic absorptive capacity is exceeded, diarrhea results, with mainly small bowel contents being lost from the body. However, potassium is also added to this fluid while it traverses the colon (because luminal [K+] is well below 15 mEq/L), and K+ loss may be substantial. Water and electrolyte absorption from the intact human colon may be increased by salt depletion, mineralocorticoids, angiotensin and decreased colonic motility; colonic absorption is decreased by ADH (antidiuretic hormone), bile salts, fatty acids, certain diuretics, and inflammation of the colonic mucosa.

    Small Intestinal Secretion (Succus Entericus)

    The succus entericus is the exocrine secretion of the small intestine; it does not include any of the hormones secreted by the intestinal mucosa.

    Composition. The composition of the fluid secreted by the small intestinal mucosa varies somewhat in different parts of the intestine. As an example, duodenal secretion contains more mucus, due to the presence of Brunner's glands in this area. In general, small intestinal secretion is a thin, colorless or faintly straw-colored fluid. It contains water, mucus, cellular debris (including some intact cells), inorganic salts, and some enzymes.

    The concentration of sodium, potassium, calcium and total anions is relatively constant; in both the jejunum and ileum, these concentrations are similar to those of the serum. [Cl-] and [HCO3-] have a reciprocal relation; [HCO3-] is low in jejunal secretion and high in ileal secretion.

    The organic matter of the intestinal secretion consists of mucus, enzymes and cellular debris. The enzymes include: a pepsin-like protease, an amylase, a lipase, at least two peptidases, sucrase, maltase, lactase, enterokinase, alkaline phosphatase, nucleophosphatases and nucleosidases. When intestinal secretion is collected without cellular debris, it contains only the enzymes enterokinase (which activates trypsin) and amylase, in small amounts. The presence of other enzymes in the succus entericus is probably accounted for by the exfoliation of epithelial cells into the intestinal lumen. The intracellular enzymes appear in the intestinal juice as a result of such cellular shedding and subsequent disintegration. Except for the amylase, the digestive enzymes described above (peptidases, disaccharidases, etc.) act primarily in the intestinal brush border, prior to the absorption of the end products of such digestion.

    Functions. The function of the mucus secreted by Brunner's glands is to protect the duodenal mucosa from digestion by the gastric juice; secretion rates rapidly increase in response to irritating stimuli. Mucus is also secreted by goblet cells throughout the intestine in response to vagal stimulation, or to irritation or distention. This secretion lubricates the epithelial surface and protects it from mechanical damage by solid food material. The enzymes present in the succus entericus may have some digestive function but, as mentioned above, they act intracellularly for the most part, with the exception of enterokinase and amylase. Several really important functions of the succus entericus are related to its large water content: (1) water is a reactant in hydrolysis, which is the chemical process involved in digestion; (2) water is also necessary as a solvent and as a medium of suspension for the solids which are dissolved or suspended in the chyme; (3) in fat digestion, the succus entericus serves as a source of water for suspension and emulsification of fat particles; (4) water serves as a vehicle for absorption.

    Factors controlling secretion. Brunner's glands secrete mucus in response to direct tactile or irritating stimuli of the mucosa, vagal stimulation, and intestinal hormones, especially secretin. These glands are inhibited by sympathetic stimulation; such stimulation may, therefore, leave the duodenal bulb area unprotected and may have some connection with the high incidence of peptic ulcers in this area. Distention of the small intestine causes copious secretion from the crypts of Lieberkühn. Tactile or irritating stimuli can also cause intense secretion. For the most part then, small intestinal secretion is regulated by the presence of chyme in the intestine--the greater the amount of chyme, the greater the secretion. A number of regulatory peptides (including VIP, CCK, GRP, and gastrin) have been shown to enhance intestinal secretion, while others (including vasopressin, somatostatin, aldosterone and angiotensin) may enhance net absorption. Except in the duodenum, the quantity of fluid secreted by the small intestine is never very great (usually a few milliliters per hour). It is difficult to accurately determine the amount actually secreted because of the intestine's enormous absorptive capacity. It is evident that the mucosa is capable, under certain circumstances, of moving tremendous amounts of fluid into the intestinal lumen, as shown by the great loss of water that occurs through the gut in such pathological states as cholera, diarrhea or intestinal obstruction. Toxins such as Vibrio cholerae and diarrheagenic strains of E. coli apparently increase secretion by acting through the same mechanisms as those employed in normal secretion. There is therefore considerable clinical relevance to the understanding of these mechanisms.


    Definition. The dictionary definition of diarrhea is “an abnormally frequent discharge of semisolid or fluid fecal matter from the bowel.” While this definition implies an increase in BOTH frequency and fluidity of stools, diarrhea may exist with only one of these factors present. Because there may be considerable variation in normal bowel habits, both in the population at large, and from day to day in the same individual, it is difficult to precisely define diarrhea. However, when the stool weight is in excess of 250 grams, and/or the stool contains over 70% water, it is usually perceived by the patient as diarrhea.

    Classification. Diarrhea of less than 14-day duration is arbitrarily described as acute, while that of longer duration is referred to as chronic. Acute diarrhea of less than 7-day duration is generally toxic or infectious and is almost always self-limited. Chronic diarrhea presents a more complicated diagnostic picture, with a range of possible etiologies. Diarrhea can also be classified by the underlying causative mechanism, as secretory or osmotic. Although one cause or the other usually predominates, diarrhea may also be of mixed (secretory AND osmotic) cause, for example motility disorders, such as irritable bowel syndrome.

    Secretory diarrhea implies increased secretory activity of the alimentary tract and/or inhibition of electrolyte and water absorption. The 24-hour stool volume is usually greater than 1 liter, stool volume does not decrease with fasting, and the stool pH is about neutral. Secretory diarrhea may be due to: 1) any of a variety of secretory agents: bacteria (E. coli, Vibrio cholerae, Shigella, etc.), drugs (methylxanthines such as caffeine and theophylline, some laxatives), hormones (VIP, CCK, GIP, glucagon, secretin, etc.); 2) neoplasms, with or without hormone production (e.g., gastrinoma); or 3) mucosal injury (celiac sprue, inflammatory bowel disease). As described above, physiological mechanisms exist for both secretion and absorption of fluid and electrolytes. Stimulation of the normal secretory processes, whether or not there is a defect in absorption, can result in diarrhea. Because sodium is the major cation, it is lost in excess of potassium in secretory diarrhea.

    Osmotic diarrhea is caused by the presence of unabsorbable or poorly absorbable solute in the alimentary canal. In contrast to secretory diarrhea, it is characterized by 24-hour stool volume less than 1 liter, decreased stool volume with fasting, and decreased stool pH. This condition may be due to impaired carbohydrate absorption (e.g., lactose intolerance), or laxative abuse; it may also be seen postsurgically (e.g., after partial gastrectomy). Osmotic diarrhea may occur with a normal dietary intake, if digestion and absorption are impaired, or it may occur from ingestion of solutes for which there is no absorptive mechanism. Since the unabsorbed or unabsorbable solute holds water, the intraluminal water content may exceed the reabsorptive capacity of the bowel, and diarrhea results. While electrolyte depletion (particularly of sodium) is the net result of secretory diarrhea, in osmotic diarrhea much of the solute present is material other than electrolytes. Also, the colon will conserve sodium but not potassium (see above). Therefore, the net effect of osmotic diarrhea is water and potassium depletion.

    Mixed diarrhea. In diarrhea due to motility disorders (hypermotility), ingested solute may have an osmotic effect, if only because there is insufficient time for normal digestive and absorptive processes to occur. On the other hand, there may also not be time for reabsorption of normal amounts of secretion, so there may be the appearance of a secretory diarrhea.


    Osmotic laxatives are poorly absorbed compounds (such as various magnesium salts, some salts of sodium or potassium, lactulose, glycerin and sorbitol) which prevent absorption of water by the intestine, thereby increasing the fluidity of the stool. In other words, they cause an osmotic diarrhea.

    Bulk laxative agents are non-absorbable, hydrophilic vegetable fibers, which stimulate bowel action mostly by their bulk. Because they retain water, the stool remains soft.

    Stimulant laxatives are drugs (such as castor oil and phenolphthalein) which stimulate accumulation of water and electrolytes in the intestinal lumen, and also enhance intestinal motility, in some cases by direct toxic effect on the mucosa.