117 CHAPTER 11 Digestion and Absorption of Nutrients
deficit of the bile acids in a condition known as the bacterial overgrowth syndrome (in which stasis in the upper intestine leads to bacterial overgrowth, with deconjugation of bile acids by the bacteria). Free bile acids are absorbed passively in the jejunum because they are largely unionized at the duodenal pH. Bile acids need to be ionized to form micelles.
Therefore the unionized state leads to impairment of fat absorption as well as impaired absorption of cho- lesterol and fat-soluble vitamins. Bile acid deficiency does not interfere with digestion, so in this case free fatty acids and monoglycerides appear in the stool.
• Mucosal cell transport is, of course, necessary for all nutrients, but it is of particular importance in fat absorption because the absorbed fatty acids or mono- glycerides must be reconstituted to triglycerides and then formed into chylomicrons. No disease has been associated with triglyceride synthesis; however, there is a disease of inadequate chylomicron formation called abetalipoproteinemia. This condition is caused by a failure to synthesize MTP, which is necessary for the initial steps that bring apolipoprotein B together with triglyceride in the process of chylomicron formation. The synthesis of apolipoprotein B is in fact normal in affected persons, so the condition is misnamed.
• Lymphatic transport is necessary for the absorption of fat that has been reconstituted to chylomicrons.
This step is defective in two rare diseases, congenital lymphangiectasia and Whipple’s disease.
Thus by considering the steps in fat absorption, it is possible to predict the diseases that can lead to malabsorp- tion. Steatorrhea, which attends malabsorption, can be alleviated to a large degree by diets containing triglycerides of medium- rather than long-chain fatty acids. The expla- nation for the benefit of this dietary maneuver is that glyc- erol esters of medium-chain fatty acids are hydrolyzed faster than are ester linkages involving long-chain fatty acids. Medium-chain fatty acids are water soluble and can be absorbed from aqueous solution. In addition, they are transported directly into portal blood without involvement of chylomicrons.
118 CHAPTER 11 Digestion and Absorption of Nutrients may be predicted from two facts: folic acid is a strongly
electronegative compound (with a molecular weight of 441), and uncouplers of respiration (hence energy produc- tion) interfere with its absorption.
Vitamin B12 (cobalamin) absorption requires intrin- sic factor, a glycoprotein secreted by the parietal cell of the gastric mucosa. Binding of intrinsic factor to dietary vitamin B12 is necessary for attachment to specific recep- tors located in the brush border of the ileum. Initially cobalamin is released from foods by food preparation and exposure to light. It is then recognized by the cobal- amin binding protein, haptocorrin (a glycoprotein), which in humans is secreted in saliva and is resistant to digestion by acid and pepsin. Thus haptocorrin protects intrinsic factor during its transit through the stomach.
In the duodenum, the haptocorrin is digested by pan- creatic enzymes, and the vitamin then forms a complex with intrinsic factor that is resistant to digestion. The presence of calcium (Ca2+) or magnesium (Mg2+) and an alkaline pH are necessary for optimal attachment of the intrinsic factor–B12 complex to the receptor, a process that does not require energy. The actual uptake of B12 is presumed to be by pinocytosis; however, this point is not clear. Any disease condition that interferes with the production or secretion of intrinsic factor or with the attachment of the intrinsic factor–B12 complex to its receptor in the ileum leads to malabsorption of vitamin B12.
The fat-soluble vitamins (A, D, E, and K) depend on solubilization within bile salt micelles for intestinal absorption. Vitamin A, or retinol, is ingested as β-car- otene and absorbed as such. Once in the enterocyte, β-carotene is cleaved intracellularly into two retinol molecules. Esters of dietary vitamins D and E, as noted
earlier in this chapter, are digested by cholesterol ester hydrolase before their solubilization in micelles. Dietary vitamin K (K1) is absorbed in the intestine by an active transport system, whereas bacterially derived K2 is taken up passively from the lumen. Except for retinol, which is reesterified, the fat-soluble vitamins appear in exocy- tosed chylomicrons biochemically unaltered by meta- bolic processes within the enterocyte. The chylomicrons are then extruded into the lymphatics and transported via the thoracic duct into the blood. Thus the absorp- tion of fat-soluble vitamins depends on the absorption of dietary lipids. In fact, a fatty meal is necessary for absorption of reasonable amounts of vitamin E. Defects leading to fat malabsorption result in deficiencies of fat-soluble vitamins.
Abnormality in Vitamin Absorption
Pernicious anemia occurs when the body does not make enough red blood cells because of malabsorption of vita- min B12. The most common cause is the failure to secrete sufficient intrinsic factor, which is usually the result of atrophic gastritis and the absence of parietal cells.
This is an autoimmune condition, and the body pro- duces parietal cell antibodies that destroy the intrinsic factor–secreting parietal cells. In rare instances perni- cious anemia can be caused by the absence of pancreatic proteases and the failure of intrinsic factor to be released from haptocorrin so that it cannot bind vitamin B12. Surgical removal of the ileum also results in pernicious anemia because that is the only site of vitamin B12 absorp- tion. The liver stores a 3- to 5-year supply of vitamin B12, so patients do not show symptoms of the condition until several years after it develops. The condition is treated by vitamin B12 injections.
S U M M A R Y
• Digestion is the chemical breakdown of food by enzymes secreted into the lumen of the gut and those associated with the brush border of enterocytes.
• All physiologically significant absorption of nutrients occurs in the small intestine, the mucosal surface of which is greatly increased, thus providing a large area for uptake.
• The major luminal breakdown of carbohydrates is cat- alyzed by amylase. Breakdown of remaining glucose polymers and other disaccharides is carried out by spe- cific enzymes in the brush border membrane. Glucose and galactose share an Na+-dependent, secondary active transport mechanism for absorption.
• The major enzymes involved in the luminal digestion of protein are secreted in inactive forms by the pancreas and are then activated by trypsin after its own activation by enterokinase.
• Dipeptides, tripeptides, and amino acids are absorbed across the brush border membrane by a variety of trans- port processes. Larger peptides are broken down into these absorbable forms by peptidases associated with the brush border. Absorbed small peptides are hydro- lyzed to amino acids within the cytoplasm, and almost all absorbed protein leaves the enterocyte in the form of amino acids.
119 CHAPTER 11 Digestion and Absorption of Nutrients
K E Y W O R D S A N D C O N C E P T S
Brush border Enterocytes Goblet cells Paneth cells Digestion
Luminal/cavital digestion Contact/membrane digestion Unstirred layer of fluid Glycocalyx
Passive diffusion Facilitated diffusion Active transport Starch
Steatorrhea Sucrose Lactose Maltose Amylopectin Lactase deficiency Endopeptidases Exopeptidases Trypsinogen
Enterokinase Chymotrypsinogen Proelastase
Procarboxypeptidases A and B Triglycerides
Phospholipids Sterols Emulsification Carboxyl ester lipase Gastric lipase Pancreatic lipase Colipase Phospholipase A2 Cholesterol esterase Nonspecific esterase Micelles
Critical micellar concentration Enterohepatic circulation Fatty acid–binding proteins Chylomicrons
Apolipoprotein
S E L F - S T U D Y P R O B L E M S
1. What is the evidence that a separate carrier sys- tem for small peptides is involved in amino acid absorption?
2. What is the evidence that micelles are involved in the absorption of fat breakdown products, and why are they important?
• Fat droplets are suspended in an emulsification by the action of lecithin, bile salts, peptides, and other such agents.
Colipase displaces a bile salt molecule from the fat-water interface, thereby allowing pancreatic lipase to digest the triglycerides. Pancreatic lipase is essential for fat digestion and produces 2-monoglycerides and free fatty acids.
• The breakdown products of fat digestion are solubilized in micelles by bile salts and other amphipathic mole- cules. Micelles diffuse through the unstirred layer, and
fat digestion products are absorbed from the micelles at the enterocyte brush border membrane.
• Within the enterocyte, triglycerides and phospholipids are resynthesized and packaged into chylomicrons that contain apoprotein on their surface. Chylomicrons are exocytosed into the intercellular space. Too large to enter capillaries, the chylomicrons enter lacteals and eventually reach the blood via the thoracic lymph duct.
SUGGESTED READINGS
Ahnen DJ. Nutrient assimilation. In: Kelly WN, ed. Textbook of Internal Medicine. Philadelphia: Lippincott; 1989.
Ganapathy V. Protein digestion and absorption. In: Johnson LR, ed. Physiology of the Gastrointestinal Tract. 5th ed. Vol. 2. San Diego: Elsevier; 2012.
Hamilton RL, Wong JS, Cham CM, et al. Chylomicron-sized lipid particles are formed in the setting of apolipoprotein B deficiency. J Lipid Res. 1998;39:1543–1557.
Mansbach II CM, Abumrad NA. Enterocyte fatty acid handling proteins and chylomicron formation. In: Johnson LR, ed.
Physiology of the Gastrointestinal Tract. 5th ed. Vol. 2. San Diego: Elsevier; 2012.
120 CHAPTER 11 Digestion and Absorption of Nutrients
Milne MD. Hereditary disorders of intestinal transport. In: Smythe DH, ed. Intestinal Absorption. New York: Plenum Press; 1974.
Said HM, Nexo E. Mechanism and regulation of intestinal absorption of water-soluble vitamins: cellular and molecular aspects. In: Johnson LR, ed. Physiology of the Gastrointestinal Tract. 5th ed. Vol. 2. San Diego: Elsevier; 2012.
Tso P. Intestinal lipid absorption. In: Johnson LR, ed. Physiology of the Gastrointestinal Tract. 3rd ed. New York: Raven Press;
1994.
Wellner D, Meister A. A survey of inborn errors of amino acid metabolism and transport in man. Annu Rev Biochem.
1980;50:911–968.
Whitcomb DC. Hereditary pancreatitis: new insights into acute and chronic pancreatitis. Gut. 1999;45:317–322.
Wright EM, Sal-Rabanal M, Loo DDF, Hirayama BA.
Sugar absorption. In: Johnson LR, ed. Physiology of the Gastrointestinal Tract. 5th ed. Vol. 2. San Diego: Elsevier;
2012.
O B J E C T I V E S
• Indicate the sources of fluid and electrolytes in the gastrointestinal (GI) tract and their sites of absorption.
• Describe the mechanisms involved in and the location of the sites for the absorption of sodium, potassium, chloride, bicarbonate, and water.
• Understand the mechanism and significance of the intestinal secretion of fluid and electrolytes.
• Explain the difference between osmotic and secretory diarrheas and discuss the disorders that may lead to each.
• Discuss the basic steps involved in the absorption of calcium and iron and how each is regulated.
Fluid and Electrolyte Absorption
12
Minerals and water enter the body through the intestine and provide the solutes and solvent water for body fluids.
The electrolytes of primary importance include sodium (Na+), potassium (K+), hydrogen ion (H+), bicarbonate (HCO3−), chloride (Cl−), calcium (Ca2+), and iron (Fe2+).
Each of these ions has one or more mechanisms by which it is transported across the intestinal epithelium. This chap- ter considers these mechanisms and their relationship with water absorption and secretion.