Ganong’s Review of Medical Physiology, 24th Edition

CHAPTER 26 Digestion, Absorption, & Nutritional Principles


After studying this chapter, you should be able to:

image Understand how nutrients are delivered to the body and the chemical processes needed to convert them to a form suitable for absorption.

image List the major dietary carbohydrates and define the luminal and brush border processes that produce absorbable monosaccharides as well as the transport mechanisms that provide for the uptake of these hydrophilic molecules.

image Understand the process of protein assimilation, and the ways in which it is comparable to, or converges from, that used for carbohydrates.

image Define the stepwise processes of lipid digestion and absorption, the role of bile acids in solubilizing the products of lipolysis, and the consequences of fat malabsorption.

image Identify the source and functions of short-chain fatty acids in the colon.

image Delineate the mechanisms of uptake for vitamins and minerals.

image Understand basic principles of energy metabolism and nutrition.


The gastrointestinal system is the portal through which nutritive substances, vitamins, minerals, and fluids enter the body. Proteins, fats, and complex carbohydrates are broken down into absorbable units (digested), principally, although not exclusively, in the small intestine. The products of digestion and the vitamins, minerals, and water cross the mucosa and enter the lymph or the blood (absorption). The digestive and absorptive processes are the subject of this chapter.

Digestion of the major foodstuffs is an orderly process involving the action of a large number of digestive enzymes discussed in the previous chapter. Enzymes from the salivary glands attack carbohydrates (and fats in some species); enzymes from the stomach attack proteins and fats; and enzymes from the exocrine portion of the pancreas attack carbohydrates, proteins, lipids, DNA, and RNA. Other enzymes that complete the digestive process are found in the luminal membranes and the cytoplasm of the cells that line the small intestine. The action of the enzymes is aided by the hydrochloric acid secreted by the stomach and the bile secreted by the liver.

Most substances pass from the intestinal lumen into the enterocytes and then out of the enterocytes to the interstitial fluid. The processes responsible for movement across the luminal cell membrane are often quite different from those responsible for movement across the basal and lateral cell membranes to the interstitial fluid.



The principal dietary carbohydrates are polysaccharides, disaccharides, and monosaccharides. Starches (glucose polymers) and their derivatives are the only polysaccharides that are digested to any degree in the human gastrointestinal tract. Amylopectin, which typically constitutes around 75% of dietary starch, is a branched molecule, whereas amylose is a straight chain with only 1:4α linkages (Figure 26–1). The disaccharides lactose (milk sugar) and sucrose (table sugar) are also ingested, along with the monosaccharides fructose and glucose.


FIGURE 26–1 Left: Structure of amylose and amylopectin, which are polymers of glucose (indicated by circles). These molecules are partially digested by the enzyme amylase, yielding the products shown at the bottom of the figure. Right: Brush border hydrolases responsible for the sequential digestion of the products of luminal starch digestion (1, linear oligomers; 2, alpha-limit dextrins).

In the mouth, starch is attacked by salivary α-amylase. The optimal pH for this enzyme is 6.7. However, it remains partially active even once it moves into the stomach, despite the acidic gastric juice, because the active site is protected in the presence of substrate to some degree. In the small intestine, both the salivary and the pancreatic α-amylase also act on the ingested polysaccharides. Both the salivary and the pancreatic α-amylases hydrolyze 1:4α linkages but spare 1:6α linkages and terminal 1:4α linkages. Consequently, the end products of α-amylase digestion are oligosaccharides: the disaccharide maltose; the trisaccharide maltotriose; and α-limit dextrins, polymers of glucose containing an average of about eight glucose molecules with 1:6α linkages (Figure 26–1).

The oligosaccharidases responsible for the further digestion of the starch derivatives are located in the brush border of small intestinal epithelial cells (Figure 26–1). Some of these enzymes have more than one substrate. Isomaltase is mainly responsible for hydrolysis of 1:6α linkages. Along with maltase and sucrase, it also breaks down maltotriose and maltose. Sucrase and isomaltase are initially synthesized as a single glycoprotein chain that is inserted into the brush border membrane. It is then hydrolyzed by pancreatic proteases into sucrase and isomaltase subunits.

Sucrase hydrolyzes sucrose into a molecule of glucose and a molecule of fructose. In addition, lactase hydrolyzes lactose to glucose and galactose.

Deficiency of one or more of the brush border oligosaccharidases may cause diarrhea, bloating, and flatulence after ingestion of sugar (Clinical Box 26–1). The diarrhea is due to the increased number of osmotically active oligosaccharide molecules that remain in the intestinal lumen, causing the volume of the intestinal contents to increase. In the colon, bacteria break down some of the oligosaccharides, further increasing the number of osmotically active particles. The bloating and flatulence are due to the production of gas (CO2 and H2) from disaccharide residues in the lower small intestine and colon.


Lactose Intolerance

In most mammals and in many races of humans, intestinal lactase activity is high at birth, then declines to low levels during childhood and adulthood. The low lactase levels are associated with intolerance to milk (lactose intolerance). Most Europeans and their American descendants retain sufficient intestinal lactase activity in adulthood; the incidence of lactase deficiency in northern and western Europeans is only about 15%. However, the incidence in blacks, American Indians, Asians, and Mediterranean populations is 70–100%. When such individuals ingest dairy products, they are unable to digest lactose sufficiently, and so symptoms such as bloating, pain, gas, and diarrhea are produced by the unabsorbed osmoles that are subsequently digested by colonic bacteria.


The simplest treatment for lactose intolerance is to avoid dairy products in the diet, but this can sometimes be challenging (or undesirable for the individual who loves ice cream). Symptoms can be ameliorated by administration of commercial lactase preparations, but this is expensive. Yogurt is better tolerated than milk in intolerant individuals because it contains its own bacterial lactase.


Hexoses are rapidly absorbed across the wall of the small intestine (Table 26–1). Essentially all the hexoses are removed before the remains of a meal reach the terminal part of the ileum. The sugar molecules pass from the mucosal cells to the blood in the capillaries draining into the portal vein.


TABLE 26–1 Normal transport of substances by the intestine and location of maximum absorption or secretion.a

The transport of glucose and galactose is dependent on Na+ in the intestinal lumen; a high concentration of Na+ on the mucosal surface of the cells facilitates and a low concentration inhibits sugar influx into the epithelial cells. This is because these sugars and Na+ share the same cotransporter, or symport, the sodium-dependent glucose transporter (SGLT, Na+ glucose cotransporter) (Figure 26–2). The members of this family of transporters, SGLT 1 and SGLT 2, resemble the glucose transporters (GLUTs) responsible for facilitated diffusion (see Chapter 24) in that they cross the cell membrane 12 times and have their –COOH and –NH2 terminals on the cytoplasmic side of the membrane. However, there is no homology to the GLUT series of transporters. SGLT-1 is responsible for uptake of dietary glucose from the gut. The related transporter, SGLT-2, is responsible for glucose transport out of the renal tubules (see Chapter 37).


FIGURE 26–2 Brush border digestion and assimilation of the disaccharides sucrose (panel 1) and lactose (panel 2). Uptake of glucose and galactose is driven secondarily by the low intracellular sodium concentration established by the basolateral Na, K ATPase (not shown). SGLT-1, sodium-glucose cotransporter-1.

Because the intracellular Na+ concentration is low in intestinal cells (as it is in other cells), Na+ moves into the cell along its concentration gradient. Glucose moves with the Na+ and is released in the cell (Figure 26–2). The Na+ is transported into the lateral intercellular spaces, and the glucose is transported by GLUT 2 into the interstitium and thence to the capillaries. Thus, glucose transport is an example of secondary active transport (see Chapter 2); the energy for glucose transport is provided indirectly, by the active transport of Na+ out of the cell. This maintains the concentration gradient across the luminal border of the cell, so that more Na+ and consequently more glucose enter. When the Na+/glucose cotransporter is congenitally defective, the resulting glucose/galactose malabsorption causes severe diarrhea that is often fatal if glucose and galactose are not promptly removed from the diet. Glucose and its polymers can also be used to retain Na+ in diarrheal disease, as was discussed in Chapter 25.

As indicated, SGLT-1 also transports galactose, but fructose utilizes a different mechanism. Its absorption is independent of Na+ or the transport of glucose and galactose; it is transported instead by facilitated diffusion from the intestinal lumen into the enterocytes by GLUT 5 and out of the enterocytes into the interstitium by GLUT 2. Some fructose is converted to glucose in the mucosal cells.

Insulin has little effect on intestinal transport of sugars. In this respect, intestinal absorption resembles glucose reabsorption in the proximal convoluted tubules of the kidneys (see Chapter 37); neither process requires phosphorylation, and both are essentially normal in diabetes but are depressed by the drug phlorizin. The maximal rate of glucose absorption from the intestine is about 120 g/h.



Protein digestion begins in the stomach, where pepsins cleave some of the peptide linkages. Like many of the other enzymes concerned with protein digestion, pepsins are secreted in the form of inactive precursors (proenzymes) and activated in the gastrointestinal tract. The pepsin precursors are called pepsinogens and are activated by gastric acid. Human gastric mucosa contains a number of related pepsinogens, which can be divided into two immunohistochemically distinct groups, pepsinogen I and pepsinogen II. Pepsinogen I is found only in acid-secreting regions, whereas pepsinogen II is also found in the pyloric region. Maximal acid secretion correlates with pepsinogen I levels.

Pepsins hydrolyze the bonds between aromatic amino acids such as phenylalanine or tyrosine and a second amino acid, so the products of peptic digestion are polypeptides of very diverse sizes. Because pepsins have a pH optimum of 1.6–3.2, their action is terminated when the gastric contents are mixed with the alkaline pancreatic juice in the duodenum and jejunum. The pH of the intestinal contents in the duodenal bulb is 3.0–4.0, but rapidly rises; in the rest of the duodenum it is about 6.5.

In the small intestine, the polypeptides formed by digestion in the stomach are further digested by the powerful proteolytic enzymes of the pancreas and intestinal mucosa. Trypsin, the chymotrypsins, and elastase act at interior peptide bonds in the peptide molecules and are called endopeptidases. The formation of the active endopeptidases from their inactive precursors occurs only when they have reached their site of action, secondary to the action of the brush border hydrolase, enterokinase (Figure 26–3). The powerful protein-splitting enzymes of the pancreatic juice are secreted as inactive proenzymes. Trypsinogen is converted to the active enzyme trypsin by enterokinase when the pancreatic juice enters the duodenum. Enterokinase contains 41% polysaccharide, and this high polysaccharide content apparently prevents it from being digested itself before it can exert its effect. Trypsin converts chymotrypsinogens into chymotrypsins and other proenzymes into active enzymes (Figure 26–3). Trypsin can also activate trypsinogen; therefore, once some trypsin is formed, there is an auto-catalytic chain reaction. Enterokinase deficiency occurs as a congenital abnormality and leads to protein malnutrition.


FIGURE 26–3 Mechanism to avoid activation of pancreatic proteases until they are in the duodenal lumen. Pancreatic juice contains proteolytic enzymes in their inactive, precursor forms. When the juice enters the duodenal lumen, trypsinogen contacts enterokinase expressed on the apical surface of enterocytes, Trypsinogen is thereby cleaved to trypsin, which in turn can activate additional trypsin molecules as well as the remaining proteolytic enzymes.

The carboxypeptidases of the pancreas are exopeptidases that hydrolyze the amino acids at the carboxyl ends of the polypeptides (Figure 26–4). Some free amino acids are liberated in the intestinal lumen, but others are liberated at the cell surface by the aminopeptidases, carboxypeptidases, endopeptidases, and dipeptidases in the brush border of the mucosal cells. Some di- and tripeptides are actively transported into the intestinal cells and hydrolyzed by intracellular peptidases, with the amino acids entering the bloodstream. Thus, the final digestion to amino acids occurs in three locations: the intestinal lumen, the brush border, and the cytoplasm of the mucosal cells.


FIGURE 26–4 Luminal digestion of peptides by pancreatic endopeptidases and exopeptidases. Individual amino acids are shown as squares.


At least seven different transport systems transport amino acids into enterocytes. Five of these require Na+ and cotransport amino acids and Na+ in a fashion similar to the cotransport of Na+ and glucose (Figure 26–3). Two of these five also require Cl. In two systems, transport is independent of Na+.

The di- and tripeptides are transported into enterocytes by a system known as PepT1 (or peptide transporter 1) that requires H+ instead of Na+ (Figure 26–5). There is very little absorption of larger peptides. In the enterocytes, amino acids released from the peptides by intracellular hydrolysis plus the amino acids absorbed from the intestinal lumen and brush border are transported out of the enterocytes along their basolateral borders by at least five transport systems. From there, they enter the hepatic portal blood.


FIGURE 26–5 Disposition of short peptides in intestinal epithelial cells. Peptides are absorbed together with a proton supplied by an apical sodium/hydrogen exchanger (NHE) by the peptide transporter 1 (PepT1). Absorbed peptides are digested by cytosolic proteases, and any amino acids that are surplus to the needs of the epithelial cell are transported into the bloodstream by a series of basolateral transport proteins.

Absorption of amino acids is rapid in the duodenum and jejunum. There is little absorption in the ileum in health, because the majority of the free amino acids have already been assimilated at that point. Approximately 50% of the digested protein comes from ingested food, 25% from proteins in digestive juices, and 25% from desquamated mucosal cells. Only 2–5% of the protein in the small intestine escapes digestion and absorption. Some of this is eventually digested by bacterial action in the colon. Almost all of the protein in the stools is not of dietary origin but comes from bacteria and cellular debris. Evidence suggests that the peptidase activities of the brush border and the mucosal cell cytoplasm are increased by resection of part of the ileum and that they are independently altered in starvation. Thus, these enzymes appear to be subject to homeostatic regulation. In humans, a congenital defect in the mechanism that transports neutral amino acids in the intestine and renal tubules causes Hartnup disease. A congenital defect in the transport of basic amino acids causes cystinuria. However, most patients do not experience nutritional deficiencies of these amino acids because peptide transport compensates.

In infants, moderate amounts of undigested proteins are also absorbed. The protein antibodies in maternal colostrum are largely secretory immunoglobulins (IgAs), the production of which is increased in the breast in late pregnancy. They cross the mammary epithelium by transcytosis and enter the circulation of the infant from the intestine, providing passive immunity against infections. Absorption is by endocytosis and subsequent exocytosis.

Absorption of intact proteins declines sharply after weaning, but adults still absorb small quantities. Foreign proteins that enter the circulation provoke the formation of antibodies, and the antigen–antibody reaction occurring on subsequent entry of more of the same protein may cause allergic symptoms. Thus, absorption of proteins from the intestine may explain the occurrence of allergic symptoms after eating certain foods. The incidence of food allergy in children is said to be as high as 8%. Certain foods are more allergenic than others. Crustaceans, mollusks, and fish are common offenders, and allergic responses to legumes, cows’ milk, and egg white are also relatively frequent. However, in most individuals food allergies do not occur, and there is evidence for a genetic component in susceptibility.

Absorption of protein antigens, particularly bacterial and viral proteins, takes place in large microfold cells or M cells, specialized intestinal epithelial cells that overlie aggregates of lymphoid tissue (Peyer’s patches). These cells pass the antigens to the lymphoid cells, and lymphocytes are activated. The activated lymphoblasts enter the circulation, but they later return to the intestinal mucosa and other epithelia, where they secrete IgA in response to subsequent exposures to the same antigen. This secretory immunity is an important defense mechanism (see Chapter 3).


Nucleic acids are split into nucleotides in the intestine by the pancreatic nucleases, and the nucleotides are split into the nucleosides and phosphoric acid by enzymes that appear to be located on the luminal surfaces of the mucosal cells. The nucleosides are then split into their constituent sugars and purine and pyrimidine bases. The bases are absorbed by active transport. Families of equilibrative (ie, passive) and concentrative (ie, secondary active) nucleoside transporters have recently been identified and are expressed on the apical membrane of enterocytes.



A lingual lipase is secreted by Ebner’s glands on the dorsal surface of the tongue in some species, and the stomach also secretes a lipase (Table 26–1). They are of little quantitative significance for lipid digestion other than in the setting of pancreatic insufficiency, but they may generate free fatty acids that signal to most distal parts of the GI tract (eg, causing the release of CCK; see Chapter 25).

Most fat digestion therefore begins in the duodenum, pancreatic lipase being one of the most important enzymes involved. This enzyme hydrolyzes the 1- and 3-bonds of the triglycerides (triacylglycerols) with relative ease but acts on the 2-bonds at a very low rate, so the principal products of its action are free fatty acids and 2-monoglycerides (2-monoacylglycerols). It acts on fats that have been emulsified (see below). Its activity is facilitated when an amphipathic helix that covers the active site like a lid is bent back. Colipase, a protein with a molecular weight of about 11,000, is also secreted in the pancreatic juice, and when this molecule binds to the –COOH-terminal domain of the pancreatic lipase, opening of the lid is facilitated. Colipase is secreted in an inactive proform (Table 26–1) and is activated in the intestinal lumen by trypsin. Colipase is also critical for the action of lipase because it allows lipase to remain associated with droplets of dietary lipid even in the presence of bile acids.

Another pancreatic lipase that is activated by bile acids has been characterized. This 100,000-kDa cholesterol esterase represents about 4% of the total protein in pancreatic juice. In adults, pancreatic lipase is 10–60 times more active, but unlike pancreatic lipase, cholesterol esterase catalyzes the hydrolysis of cholesterol esters, esters of fat-soluble vitamins, and phospholipids, as well as triglycerides. A very similar enzyme is found in human milk.

Fats are relatively insoluble, which limits their ability to cross the unstirred layer and reach the surface of the mucosal cells. However, they are finely emulsified in the small intestine by the detergent action of bile acids, phosphatidylcholine, and monoglycerides. When the concentration of bile acids in the intestine is high, as it is after contraction of the gallbladder, lipids and bile salts interact spontaneously to form micelles (Figure 26–6). These cylindrical aggregates take up lipids, and although their lipid concentration varies, they generally contain fatty acids, monoglycerides, and cholesterol in their hydrophobic centers. Micellar formation further solubilizes the lipids and provides a mechanism for their transport to the enterocytes. Thus, the micelles move down their concentration gradient through the unstirred layer to the brush border of the mucosal cells. The lipids diffuse out of the micelles, and a saturated aqueous solution of the lipids is maintained in contact with the brush border of the mucosal cells (Figure 26–6).


FIGURE 26–6 Lipid digestion and passage to intestinal mucosa. Fatty acids (FA) are liberated by the action of pancreatic lipase on dietary triglycerides and, in the presence of bile acids (BS), form micelles (the circular structures), which diffuse through the unstirred layer to the mucosal surface. Not shown, colipase binds to bile acids on the surface of the triglyceride droplet to anchor lipase to the surface and allow for its lipolytic activity. (Modified from Westergaard H, Dietschy JM: Normal mechanisms of fat absorption and derangements induced by various gastrointestinal diseases. Med Clin North Am 1974 Nov;58(6):1413–1427.)

Lipids collect in the micelles, with cholesterol in the hydrophobic center and amphipathic phospholipids and monoglycerides lined up with their hydrophilic heads on the outside and their hydrophobic tails in the center. The micelles play an important role in keeping lipids in solution and transporting them to the brush border of the intestinal epithelial cells, where they are absorbed.


Pancreatectomized animals and patients with diseases that destroy the exocrine portion of the pancreas have fatty, bulky, clay-colored stools (steatorrhea) because of the impaired digestion and absorption of fat. The steatorrhea is mostly due to lipase deficiency. However, acid inhibits the lipase, and the lack of alkaline secretion from the pancreas also contributes by lowering the pH of the intestine contents. In some cases, hypersecretion of gastric acid can cause steatorrhea. Another cause of steatorrhea is defective reabsorption of bile salts in the distal ileum (see Chapter 29).

When bile is excluded from the intestine, up to 50% of ingested fat appears in the feces. A severe malabsorption of fat-soluble vitamins also results. When bile salt reabsorption is prevented by resection of the terminal ileum or by disease in this portion of the small intestine, the amount of fat in the stools is also increased because when the enterohepatic circulation is interrupted, the liver cannot increase the rate of bile salt production to a sufficient degree to compensate for the loss.


Traditionally, lipids were thought to enter the enterocytes by passive diffusion, but some evidence now suggests that carriers are involved. Inside the cells, the lipids are rapidly esterified, maintaining a favorable concentration gradient from the lumen into the cells (Figure 26–7). There are also carriers that export certain lipids back into the lumen, thereby limiting their oral availability. This is the case for plant sterols as well as cholesterol.


FIGURE 26–7 Intracellular handling of the products of lipid digestion. Absorbed fatty acids (FA) and monoglycerides (MG) are reesterified to form triglyceride (TG) in the smooth endoplasmic reticulum. Apoproteins synthesized in the rough endoplasmic reticulum are coated around lipid cores, and the resulting chylomicrons are secreted from the basolateral pole of epithelial cells by exocytosis.

The fate of the fatty acids in enterocytes depends on their size. Fatty acids containing less than 10–12 carbon atoms are water-soluble enough that they pass through the enterocyte unmodified and are actively transported into the portal blood. They circulate as free (unesterified) fatty acids. The fatty acids containing more than 10–12 carbon atoms are too insoluble for this. They are reesterified to triglycerides in the enterocytes. In addition, some of the absorbed cholesterol is esterified. The triglycerides and cholesterol esters are then coated with a layer of protein, cholesterol, and phospholipid to form chylomicrons. These leave the cell and enter the lymphatics, because they are too large to pass through the junctions between capillary endothelial cells (Figure 26–7).

In mucosal cells, most of the triglyceride is formed by the acylation of the absorbed 2-monoglycerides, primarily in the smooth endoplasmic reticulum. However, some of the triglyceride is formed from glycerophosphate, which in turn is a product of glucose catabolism. Glycerophosphate is also converted into glycerophospholipids that participate in chylomicron formation. The acylation of glycerophosphate and the formation of lipoproteins occur in the rough endoplasmic reticulum. Carbohydrate moieties are added to the proteins in the Golgi apparatus, and the finished chylomicrons are extruded by exocytosis from the basolateral aspect of the cell.

Absorption of long-chain fatty acids is greatest in the upper parts of the small intestine, but appreciable amounts are also absorbed in the ileum. On a moderate fat intake, 95% or more of the ingested fat is absorbed. The processes involved in fat absorption are not fully mature at birth, and infants fail to absorb 10–15% of ingested fat. Thus, they are more susceptible to the ill effects of disease processes that reduce fat absorption.


Increasing attention is being focused on short-chain fatty acids (SCFAs) that are produced in the colon and absorbed from it. SCFAs are 2–5-carbon weak acids that have an average normal concentration of about 80 mmol/L in the lumen. About 60% of this total is acetate, 25% propionate, and 15% butyrate. They are formed by the action of colonic bacteria on complex carbohydrates, resistant starches, and other components of the dietary fiber, that is, the material that escapes digestion in the upper gastrointestinal tract and enters the colon.

Absorbed SCFAs are metabolized and make a significant contribution to the total caloric intake. In addition, they exert a trophic effect on the colonic epithelial cells, combat inflammation, and are absorbed in part by exchange for H+, helping to maintain acid–base equilibrium. SCFAs are absorbed by specific transporters present in colonic epithelial cells. SCFAs also promote the absorption of Na+, although the exact mechanism for coupled Na+–SCFA absorption is unsettled.



Vitamins are defined as small molecules that play vital roles in bodily biochemical reactions, and which must be obtained from the diet because they cannot be synthesized endogenously. A discussion of the vitamins that are critical for human nutrition is provided towards the end of this chapter, but here we are concerned with general principles of their digestion and absorption. The fat-soluble vitamins A, D, E, and K are ingested as esters and must be digested by cholesterol esterase prior to absorption. These vitamins are also highly insoluble in the gut, and their absorption is therefore entirely dependent on their incorporation into micelles. Their absorption is deficient if fat absorption is depressed because of lack of pancreatic enzymes or if bile is excluded from the intestine by obstruction of the bile duct.

Most vitamins are absorbed in the upper small intestine, but vitamin B12 is absorbed in the ileum. This vitamin binds to intrinsic factor, a protein secreted by the parietal cells of the stomach, and the complex is absorbed across the ileal mucosa.

Vitamin B12 absorption and folate absorption are Na+-independent, but all seven of the remaining water-soluble vitamins—thiamin, riboflavin, niacin, pyridoxine, pantothenate, biotin, and ascorbic acid—are absorbed by carriers that are Na+ cotransporters.


A total of 30–80% of ingested calcium is absorbed. The absorptive process and its relation to 1,25-dihydroxycholecalciferol are discussed in Chapter 21. Through this vitamin D derivative, Ca2+ absorption is adjusted to body needs; absorption is increased in the presence of Ca2+ deficiency and decreased in the presence of Ca2+ excess. Ca2+ absorption is also facilitated by protein. It is inhibited by phosphates and oxalates because these anions form insoluble salts with Ca2+ in the intestine. Magnesium absorption is also facilitated by protein.


In adults, the amount of iron lost from the body is relatively small. The losses are generally unregulated, and total body stores of iron are regulated by changes in the rate at which it is absorbed from the intestine. Men lose about 0.6 mg/d, largely in the stools. Premenopausal women have a variable, larger loss averaging about twice this value because of the additional iron lost during menstruation. The average daily iron intake in the United States and Europe is about 20 mg, but the amount absorbed is equal only to the losses. Thus, the amount of iron absorbed is normally about 3–6% of the amount ingested. Various dietary factors affect the availability of iron for absorption; for example, the phytic acid found in cereals reacts with iron to form insoluble compounds in the intestine, as do phosphates and oxalates.

Most of the iron in the diet is in the ferric (Fe3+) form, whereas it is the ferrous (Fe2+) form that is absorbed. Fe3+ reductase activity is associated with the iron transporter in the brush borders of the enterocytes (Figure 26–8). Gastric secretions dissolve the iron and permit it to form soluble complexes with ascorbic acid and other substances that aid its reduction to the Fe2+ form. The importance of this function in humans is indicated by the fact that iron deficiency anemia is a troublesome and relatively frequent complication of partial gastrectomy.


FIGURE 26–8 Absorption of iron. Fe3+ is converted to Fe2+ by ferric reductase, and Fe2+ is transported into the enterocyte by the apical membrane iron transporter DMT1. Heme is transported into the enterocyte by a separate heme transporter (HT), and HO2 releases Fe2+ from the heme. Some of the intracellular Fe2+ is converted to Fe3+ and bound to ferritin. The rest binds to the basolateral Fe2+ transporter ferroportin (FP) and is transported to the interstitial fluid. The transport is aided by hephaestin (Hp). In plasma, Fe2+ is converted to Fe3+ and bound to the iron transport protein transferrin (TF).

Almost all iron absorption occurs in the duodenum. Transport of Fe2+ into the enterocytes occurs via divalent metal transporter 1 (DMT1) (Figure 26–8). Some is stored in ferritin, and the remainder is transported out of the enterocytes by a basolateral transporter named ferroportin 1. A protein called hephaestin (Hp) is associated with ferroportin 1. It is not a transporter itself, but it facilitates basolateral transport. In the plasma, Fe2+ is converted to Fe3+ and bound to the iron transport protein transferrin. This protein has two iron-binding sites. Normally, transferrin is about 35% saturated with iron, and the normal plasma iron level is about 130 μg/dL (23 μmol/L) in men and 110 μg/dL (19 μmol/L) in women.

Heme (see Chapter 31) binds to an apical transport protein in enterocytes and is carried into the cytoplasm. In the cytoplasm, HO2, a subtype of heme oxygenase, removes Fe2+ from the porphyrin and adds it to the intracellular Fe2+ pool.

Seventy per cent of the iron in the body is in hemoglobin, 3% in myoglobin, and the rest in ferritin, which is present not only in enterocytes, but also in many other cells. Apoferritin is a globular protein made up of 24 subunits. Ferritin is readily visible under the electron microscope and has been used as a tracer in studies of phagocytosis and related phenomena. Ferritin molecules in lysosomal membranes may aggregate in deposits that contain as much as 50% iron. These deposits are called hemosiderin.

Intestinal absorption of iron is regulated by three factors: recent dietary intake of iron, the state of the iron stores in the body, and the state of erythropoiesis in the bone marrow. The normal operation of the factors that maintain iron balance is essential for health (Clinical Box 26–2).


Disorders of Iron Uptake

Iron deficiency causes anemia. Conversely, iron overload causes hemosiderin to accumulate in the tissues, producing hemosiderosis. Large amounts of hemosiderin can damage tissues, such as is seen in the common genetic disorder of hemochromatosis. This syndrome is characterized by pigmentation of the skin, pancreatic damage with diabetes (“bronze diabetes”), cirrhosis of the liver, a high incidence of hepatic carcinoma, and gonadal atrophy. Hemochromatosis may be hereditary or acquired. The most common cause of the hereditary forms is a mutated HFE gene that is common in the Caucasian population. It is located on the short arm of chromosome 6 and is closely linked to the human leukocyte antigen-A (HLA-A) locus. It is still unknown precisely how mutations in HFE cause hemochromatosis, but individuals who are homogenous for HFE mutations absorb excess amounts of iron because HFE normally inhibits expression of the duodenal transporters that participate in iron uptake. Acquired hemochromatosis occurs when the iron-regulating system is overwhelmed by excess iron loads due to chronic destruction of red blood cells, liver disease, or repeated transfusions in diseases such as intractable anemia.


If hereditary hemochromatosis is diagnosed before excessive amounts of iron accumulate in the tissues, life expectancy can be prolonged substantially by repeated withdrawal of blood.


The intake of nutrients is under complex control involving signals from both the periphery and the central nervous system. Complicating the picture, higher functions also modulate the response to both central and peripheral cues that either trigger or inhibit food intake. Thus, food preferences, emotions, environment, lifestyle, and circadian rhythms may all have profound effects on whether food is or is not sought, and the type of food that is ingested.

Many of the hormones and other factors that are released coincident with a meal, and may play other important roles in digestion and absorption (see Chapter 25) are also involved in the regulation of feeding behavior (Figure 26–9). For example, CCK either produced by I cells in the intestine, or released by nerve endings in the brain, inhibits further food intake and thus is defined as a satiety factor or anorexin. CCK and other similar factors have attracted great interest from the pharmaceutical industry in the hopes that derivatives might be useful as aids to dieting, an objective that is lent greater urgency given the current epidemic of obesity in Western countries (Clinical Box 26–3).


FIGURE 26–9 Summary of mechanisms controlling food intake. Peripheral stimuli and inhibitors, release in anticipation of or in response to food intake, cross the blood-brain barrier (indicated by the broken red line) and activate the release and/or synthesis of central factors in the hypothalamus that either increase or decrease subsequent food intake. Food intake can also be modulated by signals from higher centers, as shown. Not shown, peripheral orexins can reduce production of central inhibitors, and vice versa. (Based on a figure kindly provided by Dr Samuel Klein, Washington University.)

Leptin and ghrelin are peripheral factors that act reciprocally on food intake, and have emerged as critical regulators in this regard. Both activate their receptors in the hypothalamus that initate signaling cascades leading to changes in food intake. Leptin is produced by adipose tissue, and signals the status of the fat stores therein. As adipocytes increase in size, they release greater quantities of leptin and this tends to decrease food intake, in part by increasing the expression of other anorexigenic factors in the hypothalamus such as pro-opiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), neurotensin, and corticotropin-releasing hormone (CRH). Leptin also stimulates the metabolic rate (see Chapter 18). Animal studies have shown that it is possible to become resistant to the effects of leptin, however, and in this setting, food intake persists despite adequate (or even growing) adipose stores—obesity therefore results.

Ghrelin, on the other hand, is a predominantly fast-acting orexin that stimulates food intake. It is produced mainly by the stomach, as well as other tissues such as the pancreas and adrenal glands in responses to changes in nutritional status—circulating ghrelin levels increase preprandially, then decrease after a meal. It is believed to be involved primarily in meal initiation, unlike the longer-term effects of leptin. Like leptin, however, the effects of ghrelin are produced mostly via actions in the hypothalamus. It increases synthesis and/or release of central orexins, including neuropeptide Y and cannabinoids, and suppresses the ability of leptin to stimulate the anorexigenic factors discussed above. Loss of the activity of ghrelin may account in part for the effectiveness of gastric bypass procedures for obesity. Its secretion may also be inhibited by leptin, underscoring the reciprocity of these hormones. There is some evidence to suggest, however, that the ability of leptin to reduce ghrelin secretion is lost in the setting of obesity.


Humans oxidize carbohydrates, proteins, and fats, producing principally CO2, H2O, and the energy necessary for life processes (Clinical Box 26–3). CO2, H2O, and energy are also produced when food is burned outside the body. However, in the body, oxidation is not a one-step, semiexplosive reaction but a complex, slow, stepwise process called catabolism, which liberates energy in small, usable amounts. Energy can be stored in the body in the form of special energy-rich phosphate compounds and in the form of proteins, fats, and complex carbohydrates synthesized from simpler molecules. Formation of these substances by processes that take up rather than liberate energy is called anabolism. This chapter consolidates consideration of endocrine function by providing a brief summary of the production and utilization of energy and the metabolism of carbohydrates, proteins, and fats.



Obesity is the most common and most expensive nutritional problem in the United States. A convenient and reliable indicator of body fat is the body mass index (BMI), which is body weight (in kilograms) divided by the square of height (in meters). Values above 25 are abnormal. Individuals with values of 25–30 are considered overweight, and those with values >30 are obese. In the United States, 34% of the population is overweight and 34% is obese. The incidence of obesity is also increasing in other countries. Indeed, the Worldwatch Institute has estimated that although starvation continues to be a problem in many parts of the world, the number of over-weight people in the world is now as great as the number of underfed. Obesity is a problem because of its complications. It is associated with accelerated atherosclerosis and an increased incidence of gallbladder and other diseases. Its association with type 2 diabetes is especially striking. As weight increases, insulin resistance increases and frank diabetes appears. At least in some cases, glucose tolerance is restored when weight is lost. In addition, the mortality rates from many kinds of cancer are increased in obese individuals. The causes of the high incidence of obesity in the general population are probably multiple. Studies of twins raised apart show a definite genetic component. It has been pointed out that through much of human evolution, famines were common, and mechanisms that permitted increased energy storage as fat had survival value. Now, however, food is plentiful in many countries, and the ability to gain and retain fat has become a liability. As noted above, the fundamental cause of obesity is still an excess of energy intake in food over energy expenditure. If human volunteers are fed a fixed high-calorie diet, some gain weight more rapidly than others, but the slower weight gain is due to increased energy expenditure in the form of small, fidgety movements (nonexercise activity thermogenesis; NEAT). Body weight generally increases at a slow but steady rate throughout adult life. Decreased physical activity is undoubtedly a factor in this increase, but decreased sensitivity to leptin may also play a role.


Obesity is such a vexing medical and public health problem because its effective treatment depends so dramatically on lifestyle changes. Long-term weight loss can only be achieved with decreased food intake, increased energy expenditure, or, ideally, some combination of both. Exercise alone is rarely sufficient because it typically induces the patient to ingest more calories. For those who are seriously obese and who have developed serious health complications as a result, a variety of surgical approaches have been developed that reduce the size of the stomach reservoir and/or bypass it altogether. These surgical maneuvers are intended to reduce the size of meals that can be tolerated, but also have dramatic metabolic effects even before significant weight loss occurs, perhaps as a result of reduced production of peripheral orexins by the gut. Pharmaceutical companies are also actively exploring the science of orexins and anorexins to develop drugs that might act centrally to modify food intake (Figure 26–9).


The amount of energy liberated by the catabolism of food in the body is the same as the amount liberated when food is burned outside the body. The energy liberated by catabolic processes in the body is used for maintaining body functions, digesting and metabolizing food, thermoregulation, and physical activity. It appears as external work, heat, and energy storage:


The amount of energy liberated per unit of time is the metabolic rate. Isotonic muscle contractions perform work at a peak efficiency approximating 50%:


Essentially all of the energy of isometric contractions appears as heat, because little or no external work (force multiplied by the distance that the force moves a mass) is done (see Chapter 5). Energy is stored by forming energy-rich compounds. The amount of energy storage varies, but in fasting individuals it is zero or negative. Therefore, in an adult individual who has not eaten recently and who is not moving (or growing, reproducing, or lactating), all of the energy output appears as heat.


The standard unit of heat energy is the calorie (cal), defined as the amount of heat energy necessary to raise the temperature of 1 g of water 1°, from 15 to 16°C. This unit is also called the gram calorie, small calorie, or standard calorie. The unit commonly used in physiology and medicine is the Calorie (kilocalorie; kcal), which equals 1000 cal.

The caloric values of the common foodstuffs, as measured in a bomb calorimeter, are found to be 4.1 kcal/g of carbohydrate, 9.3 kcal/g of fat, and 5.3 kcal/g of protein. In the body, similar values are obtained for carbohydrate and fat, but the oxidation of protein is incomplete, the end products of protein catabolism being urea and related nitrogenous compounds in addition to CO2 and H2O (see below). Therefore, the caloric value of protein in the body is only 4.1 kcal/g.


The respiratory quotient (RQ) is the ratio in the steady state of the volume of CO2 produced to the volume of O2 consumed per unit of time. It should be distinguished from the respiratory exchange ratio (R), which is the ratio of CO2 to O2 at any given time whether or not equilibrium has been reached. R is affected by factors other than metabolism. RQ and R can be calculated for reactions outside the body, for individual organs and tissues, and for the whole body. The RQ of carbohydrate is 1.00, and that of fat is about 0.70. This is because H and O are present in carbohydrate in the same proportions as in water, whereas in the various fats, extra O2 is necessary for the formation of H2O.





Determining the RQ of protein in the body is a complex process, but an average value of 0.82 has been calculated. The approximate amounts of carbohydrate, protein, and fat being oxidized in the body at any given time can be calculated from the RQ and the urinary nitrogen excretion. RQ and R for the whole body differ in various conditions. For example, during hyperventilation, R rises because CO2 is being blown off. During strenuous exercise, R may reach 2.00 because CO2 is being blown off and lactic acid from anaerobic glycolysis is being converted to CO2 (see below). After exercise, R may fall for a while to 0.50 or less. In metabolic acidosis, R rises because respiratory compensation for the acidosis causes the amount of CO2 expired to rise (see Chapter 35). In severe acidosis, R may be greater than 1.00. In metabolic alkalosis, R falls.

The O2 consumption and CO2 production of an organ can be calculated at equilibrium by multiplying its blood flow per unit of time by the arteriovenous differences for O2 and CO2 across the organ, and the RQ can then be calculated. Data on the RQ of individual organs are of considerable interest in drawing inferences about the metabolic processes occurring in them. For example, the RQ of the brain is regularly 0.97–0.99, indicating that its principal but not its only fuel is carbohydrate. During secretion of gastric juice, the stomach has a negative R because it takes up more CO2 from the arterial blood than it puts into the venous blood (see Chapter 26).


The metabolic rate is affected by many factors (Table 26–2). The most important is muscular exertion. O2 consumption is elevated not only during exertion but also for as long afterward as is necessary to repay the O2 debt (see Chapter 5). Recently ingested foods also increase the metabolic rate because of their specific dynamic action (SDA). The SDA of a food is the obligatory energy expenditure that occurs during its assimilation into the body. It takes 30 kcal to assimilate the amount of protein sufficient to raise the metabolic rate 100 kcal; 6 kcal to assimilate a similar amount of carbohydrate; and 5 kcal to assimilate a similar amount of fat. The cause of the SDA, which may last up to 6 h, is uncertain.


TABLE 26–2 Factors affecting the metabolic rate.

Another factor that stimulates metabolism is the environmental temperature. The curve relating the metabolic rate to the environmental temperature is U-shaped. When the environmental temperature is lower than body temperature, heat-producing mechanisms such as shivering are activated and the metabolic rate rises. When the temperature is high enough to raise the body temperature, metabolic processes generally accelerate, and the metabolic rate rises about 14% for each degree Celsius of elevation.

The metabolic rate determined at rest in a room at a comfortable temperature in the thermoneutral zone 12–14 h after the last meal is called the basal metabolic rate (BMR). This value falls about 10% during sleep and up to 40% during prolonged starvation. The rate during normal daytime activities is, of course, higher than the BMR because of muscular activity and food intake. The maximum metabolic rate reached during exercise is often said to be 10 times the BMR, but trained athletes can increase their metabolic rate as much as 20-fold.

The BMR of a man of average size is about 2000 kcal/d. Large animals have higher absolute BMRs, but the ratio of BMR to body weight in small animals is much greater. One variable that correlates well with the metabolic rate in different species is the body surface area. This would be expected, since heat exchange occurs at the body surface. The actual relation to body weight (W) would be


However, repeated measurements by numerous investigators have come up with a higher exponent, averaging 0.75:


Thus, the slope of the line relating metabolic rate to body weight is steeper than it would be if the relation were due solely to body area (Figure 26–10). The cause of the greater slope has been much debated but remains unsettled.


FIGURE 26–10 Correlation between metabolic rate and body weight, plotted on logarithmic scales. The slope of the colored line is 0.75. The black line represents the way surface area increases with weight for geometrically similar shapes and has a slope of 0.67. (Modified from Kleiber M and reproduced with permission from McMahon TA: Size and shape in biology. Science 1973;179:1201. Copyright © 1973 by the American Association for the Advancement of Science.)

For clinical use, the BMR is usually expressed as a percentage increase or decrease above or below a set of generally used standard normal values. Thus, a value of +65 means that the individual’s BMR is 65% above the standard for that age and sex.

The decrease in metabolic rate related to a decrease in body weight is part of the explanation of why, when an individual is trying to lose weight, weight loss is initially rapid and then slows down.


The first law of thermodynamics, the principle that states that energy is neither created nor destroyed when it is converted from one form to another, applies to living organisms as well as inanimate systems. One may therefore speak of an energy balance between caloric intake and energy output. If the caloric content of the food ingested is less than the energy output, that is, if the balance is negative, endogenous stores are utilized. Glycogen, body protein, and fat are catabolized, and the individual loses weight. If the caloric value of the food intake exceeds energy loss due to heat and work and the food is properly digested and absorbed, that is, if the balance is positive, energy is stored, and the individual gains weight.

To balance basal output so that the energy-consuming tasks essential for life can be performed, the average adult must take in about 2000 kcal/d. Caloric requirements above the basal level depend on the individual’s activity. The average sedentary student (or professor) needs another 500 kcal, whereas a lumber-jack needs up to 3000 additional kcal per day.


The aim of the science of nutrition is the determination of the kinds and amounts of foods that promote health and well-being. This includes not only the problems of under-nutrition but those of overnutrition, taste, and availability (Clinical Box 26–4). However, certain substances are essential constituents of any human diet. Many of these compounds have been mentioned in previous sections of this chapter, and a brief summary of the essential and desirable dietary components is presented below.


An optimal diet includes, in addition to sufficient water (see Chapter 37), adequate calories, protein, fat, minerals, and vitamins.


As noted above, the caloric value of the dietary intake must be approximately equal to the energy expended if body weight is to be maintained. In addition to the 2000 kcal/d necessary to meet basal needs, 500–2500 kcal/d (or more) are required to meet the energy demands of daily activities.


The Malabsorption Syndrome

The digestive and absorptive functions of the small intestine are essential for life. However, the digestive and absorptive capacity of the intestine is larger than needed for normal function (the anatomic reserve). Removal of short segments of the jejunum or ileum generally does not cause severe symptoms, and compensatory hypertrophy and hyperplasia of the remaining mucosa occur. However, when more than 50% of the small intestine is resected or bypassed (short gut syndrome), the absorption of nutrients and vitamins is so compromised that it is very difficult to prevent malnutrition and wasting (malabsorption). Resection of the terminal ileum also prevents the absorption of bile acids, and this leads in turn to deficient fat absorption. It also causes diarrhea because the unabsorbed bile salts enter the colon, where they activate chloride secretion (see Chapter 25). Other complications of intestinal resection or bypass include hypocalcemia, arthritis, and possibly fatty infiltration of the liver, followed by cirrhosis. Various disease processes can also impair absorption without a loss of intestinal length. The pattern of deficiencies that results is sometimes called the malabsorption syndrome. This pattern varies somewhat with the cause, but it can include deficient absorption of amino acids, with marked body wasting and, eventually, hypoproteinemia and edema. Carbohydrate and fat absorption are also depressed. Because of defective fat absorption, the fat-soluble vitamins (vitamins A, D, E, and K) are not absorbed in adequate amounts. One of the most interesting conditions causing the malabsorption syndrome is the autoimmune disease celiac disease. This disease occurs in genetically predisposed individuals who have the major histocompatibility complex (MHC) class II antigen HLA-DQ2 or DQ8 (see Chapter 3). In these individuals gluten and closely related proteins cause intestinal T cells to mount an inappropriate immune response that damages the intestinal epithelial cells and results in a loss of villi and a flattening of the mucosa. The proteins are found in wheat, rye, barley, and to a lesser extent in oats—but not in rice or corn. When grains containing gluten are omitted from the diet, bowel function is generally restored to normal.


Treatment of malabsorption depends on the underlying cause. In celiac disease, the mucosa returns to normal if foods containing gluten are strictly excluded from the diet, although this may be difficult to achieve. The diarrhea that accompanies bile acid malabsorption can be treated with a resin (cholestyramine) that binds the bile acids in the lumen and prevents their secretory action on colonocytes. Patients who become deficient in fat soluble-vitamins may be given these compounds as water soluble derivatives. For serious cases of short bowel syndrome, it may be necessary to supply nutrients parenterally. There is hope that small bowel transplantation may eventually become routine, but of course transplantation carries its own long-term disadvantages and also requires a reliable supply of donor tissues.

The distribution of the calories among carbohydrate, protein, and fat is determined partly by physiologic factors and partly by taste and economic considerations. A daily protein intake of 1 g/kg body weight to supply the eight nutritionally essential amino acids and other amino acids is desirable. The source of the protein is also important. Grade I proteins, the animal proteins of meat, fish, dairy products, and eggs, contain amino acids in approximately the proportions required for protein synthesis and other uses. Some of the plant proteins are also grade I, but most are grade II because they supply different proportions of amino acid and some lack one or more of the essential amino acids. Protein needs can be met with a mixture of grade II proteins, but the intake must be large because of the amino acid wastage.

Fat is the most compact form of food, since it supplies 9.3 kcal/g. However, often it is also the most expensive. Indeed, internationally there is a reasonably good positive correlation between fat intake and standard of living. In the past, Western diets have contained large amounts (100 g/d or more). The evidence indicating that a high unsaturated/saturated fat ratio in the diet is of value in the prevention of atherosclerosis and the current interest in preventing obesity may change this. In Central and South American Indian communities where corn (carbohydrate) is the dietary staple, adults live without ill effects for years on a very low fat intake. Therefore, provided that the needs for essential fatty acids are met, a low-fat intake does not seem to be harmful, and a diet low in saturated fats is desirable.

Carbohydrate is the cheapest source of calories and provides 50% or more of the calories in most diets. In the average middle-class American diet, approximately 50% of the calories come from carbohydrate, 15% from protein, and 35% from fat. When calculating dietary needs, it is usual to meet the protein requirement first and then split the remaining calories between fat and carbohydrate, depending on taste, income, and other factors. For example, a 65-kg man who is moderately active needs about 2800 kcal/d. He should eat at least 65 g of protein daily, supplying 267 (65 × 4.1) kcal. Some of this should be grade I protein. A reasonable figure for fat intake is 50–60 g. The rest of the caloric requirement can be met by supplying carbohydrate.


A number of minerals must be ingested daily for the maintenance of health. Besides those for which recommended daily dietary allowances have been set, a variety of different trace elements should be included. Trace elements are defined as elements found in tissues in minute amounts. Those believed to be essential for life, at least in experimental animals, are listed in Table 26–3. In humans, iron deficiency causes anemia. Cobalt is part of the vitamin B12molecule, and vitamin B12 deficiency leads to megaloblastic anemia (see Chapter 31). Iodine deficiency causes thyroid disorders (see Chapter 19). Zinc deficiency causes skin ulcers, depressed immune responses, and hypogonadal dwarfism. Copper deficiency causes anemia and changes in ossification. Chromium deficiency causes insulin resistance. Fluorine deficiency increases the incidence of dental caries.


TABLE 26–3 Trace elements believed essential for life.

Conversely, some minerals can be toxic when present in the body in excess. For example, severe iron overload with toxic effects is seen hemochromatosis, a disease where the normal homeostatic mechanisms that regulate uptake of iron from the diet (Figure 26–8) are genetically deranged. Similarly, copper excess causes brain damage (Wilson disease), and aluminum poisoning in patients with renal failure who are receiving dialysis treatment causes a rapidly progressive dementia that resembles Alzheimer disease (see Chapter 15).

Sodium and potassium are also essential minerals, but listing them is academic, because it is very difficult to prepare a sodium-free or potassium-free diet. A low-salt diet is, however, well tolerated for prolonged periods because of the compensatory mechanisms that conserve Na+.


Vitamins were discovered when it was observed that certain diets otherwise adequate in calories, essential amino acids, fats, and minerals failed to maintain health (for example, in sailors engaged in long voyages without access to fresh fruits and vegetables). The term vitamin has now come to refer to any organic dietary constituent necessary for life, health, and growth that does not function by supplying energy.

Because there are minor differences in metabolism between mammalian species, some substances are vitamins in one species and not in another. The sources and functions of the major vitamins in humans are listed in Table 26–4. Most vitamins have important functions in intermediary metabolism or the special metabolism of the various organ systems. Those that are water-soluble (vitamin B complex, vitamin C) are easily absorbed, but the fat-soluble vitamins (vitamins A, D, E, and K) are poorly absorbed in the absence of bile and/or pancreatic enzymes. Some dietary fat intake is necessary for their absorption, and in obstructive jaundice or disease of the exocrine pancreas, deficiencies of the fat-soluble vitamins can develop even if their intake is adequate. Vitamin A and vitamin D are bound to transfer proteins in the circulation. The α-tocopherol form of vitamin E is normally bound to chylomicrons. In the liver, it is transferred to very low density lipoprotein (VLDL) and distributed to tissues by an α-tocopherol transfer protein. When this protein is abnormal due to mutation of its gene in humans, there is cellular deficiency of vitamin E and the development of a condition resembling Friedreich ataxia. Two Na+-dependent L-ascorbic acid transporters have recently been isolated. One is found in the kidneys, intestines, and liver, and the other in the brain and eyes.





TABLE 26.4 Vitamins essential or probably essential to human nutrition.a

The diseases caused by deficiency of each of the vitamins are also listed in Table 26–4. It is worth remembering, however, particularly in view of the advertising campaigns for vitamin pills and supplements, that very large doses of the fat-soluble vitamins are definitely toxic. Hypervitaminosis A is characterized by anorexia, headache, hepatosplenomegaly, irritability, scaly dermatitis, patchy loss of hair, bone pain, and hyperostosis. Acute vitamin A intoxication was first described by Arctic explorers, who developed headache, diarrhea, and dizziness after eating polar bear liver. The liver of this animal is particularly rich in vitamin A. Hypervitaminosis D is associated with weight loss, calcification of many soft tissues, and eventual renal failure. Hypervitaminosis K is characterized by gastrointestinal disturbances and anemia. Large doses of water-soluble vitamins have been thought to be less likely to cause problems because they can be rapidly cleared from the body. However, it has been demonstrated that ingestion of mega-doses of pyridoxine (vitamin B6) can produce peripheral neuropathy.


image A typical mixed meal consists of carbohydrates, proteins, and lipids (the latter largely in the form of triglycerides). Each must be digested to allow its uptake into the body. Specific transporters carry the products of digestion into the body.

image In the process of carbohydrate assimilation, the epithelium can only transport monomers, whereas for proteins, short peptides can be absorbed in addition to amino acids.

image The protein assimilation machinery, which rests heavily on the proteases in pancreatic juice, is arranged such that these enzymes are not activated until they reach their substrates in the small intestinal lumen. This is accomplished by the restricted localization of an activating enzyme, enterokinase.

image Lipids face special challenges to assimilation given their hydrophobicity. Bile acids solubilize the products of lipolysis in micelles and accelerate their ability to diffuse to the epithelial surface. The assimilation of triglycerides is enhanced by this mechanism, whereas that of cholesterol and fat-soluble vitamins absolutely requires it.

image The catabolism of nutrients provides energy to the body in a controlled fashion, via stepwise oxidations and other reactions.

image A balanced diet is important for health, and certain substances obtained from the diet are essential to life. The caloric value of dietary intake must be approximately equal to energy expenditure for homeostasis.


For all questions, select the single best answer unless otherwise directed.

1. Maximum absorption of short-chain fatty acids produced by bacteria occurs in the

A. stomach.

B. duodenum.

C. jejunum.

D. ileum.

E. colon.

2. A premenopausal woman who is physically active seeks advice from her primary care physician regarding measures she can take to ensure adequate availability of dietary calcium to ensure bone health later in life. Which of the following dietary components should enhance calcium uptake?

A. Protein

B. Oxalates

C. Iron

D. Vitamin D

E. Sodium

3. A decrease in which of the following would be expected in a child exhibiting a congenital absence of enterokinase?

A. Incidence of pancreatitis

B. Glucose absorption

C. Bile acid reabsorption

D. Gastric pH

E. Protein assimilation

4. In Hartnup disease (a defect in the transport of neutral amino acids), patients do not become deficient in these amino acids due to the activity of

A. PepT1.

B. brush border peptidases.

C. Na+, K ATPase.

D. cystic fibrosis transmembrane conductance regulator (CFTR).

E. trypsin.

5. A newborn baby is brought to the pediatrician suffering from severe diarrhea that worsens with meals. The symptoms diminish when nutrients are delivered intravenously. The child most likely has a mutation in which of the following intestinal transporters?

A. Na, K ATPase



D. H+,K+ ATPase



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