Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
❖ CASE 31 A 23-year-old male college student presents to his primary care physician with abdominal pain, bloating, flatulence, and diarrhea after eating ice cream. He denies fever, sick contacts, or recent travel. His father has a history of similar symptoms. The patient is diagnosed with lactose intolerance and is given medications to help him digest dairy products. ◆ ◆ ◆ What products of carbohydrate digestion are absorbed in the small intestine? What products of protein digestion are absorbed in the small intestine? What products of lipid digestion are absorbed in the small intestine? 258 CASE FILES: PHYSIOLOGY ANSWERS TO CASE 31: GASTROINTESTINAL DIGESTION AND ABSORPTION Summary: A 23-year-old man has a history of abdominal pain, bloating, flatulence, and diarrhea shortly after eating ice cream. ◆ Carbohydrate digestion products absorbed: Glucose, galactose, and fructose. ◆ Protein digestion products absorbed: Amino acids, dipeptides, and tripeptides. ◆ Lipid digestion products absorbed: Fatty acids, monoglycerides, cholesterol, and lysophospholipids. CLINICAL CORRELATION Lactose intolerance is a problem that results from an absence of lactase in the brush border of the small intestine. Lactase is responsible for breaking down lactose into glucose and galactose, which are absorbed. The undigested and unabsorbed lactose increases the osmotic gradient of the luminal contents, preventing the absorption of water. The increased retention of fluid results in the symptoms of diarrhea with its abdominal distention and cramping. The bacteria in the colon ferment the lactose into a variety of gases, leading to increased flatulence. This condition may be inherited (adult lactase deficiency) or secondary (temporary) after acute infectious gastroenteritis or mucosal damage from nonsteroidal anti-inflammatory drugs (NSAIDs) or other medications. Chronic small intestinal disorders also may cause lactase deficiency because of brush border mucosal damage. Patients with this condition are encouraged to study ingredient labels on foods and avoid products that contain milk, lactose, or dry milk solids. Lactase supplements may be taken 30 minutes before consumption of the lactose-containing products to prevent symptoms. APPROACH TO GASTROINTESTINAL DIGESTION AND ABSORPTION Objectives 1. 2. 3. 4. Describe the digestion and absorption of carbohydrates. Describe the digestion and absorption of proteins. Describe the digestion and absorption of lipids. Discuss the absorption of vitamins. CLINICAL CASES 259 Definitions a-dextrinase: An enzyme located on enterocyte brush border membranes that is involved in the digestion of starch. Maltase-glucoamylase: An enzyme located on enterocyte brush border membranes that is involved in the digestion of starch and maltose. Sucrase-isomaltase: An enzyme located on enterocyte brush border membranes that is involved in the digestion of starch and sucrose. Lactase: An enzyme located on enterocyte brush border membranes that is involved in the digestion of lactose. DISCUSSION The complex nutrients ingested in a meal for the most part cannot be absorbed intact from the gastrointestinal tract. They first must be broken down, mostly by enzymatic processes, to simpler molecules. These molecules then are absorbed by a variety of passive and active mechanisms. The major nutrients involved are carbohydrates, proteins, lipids, and vitamins. Carbohydrates The major carbohydrates in the diet are complex starches (amylopectin and amylose) and the disaccharides sucrose, maltose, lactose, and trehalose, none of which can be absorbed as such. The digestion of starch begins in the mouth through the action of salivary amylase. This enzyme is active not only in the mouth as the food is chewed and swallowed but also in the orad stomach until it mixes with and becomes inactivated by gastric acid. No further carbohydrate digestion takes place after that until gastric contents are emptied into the duodenum. There, contents are mixed with pancreatic amylase, which continues the breakdown. The products of salivary and pancreatic amylase digestion are maltose, maltotriose, and a-dextrins. Ingested disaccharides undergo no breakdown until they reach the small intestine. In the intestine, the digestion of the oligo- and disaccharides continues through the actions of enzymes located on enterocyte brush borders. The enzymes a-dextrinase, maltase-glucoamylase, and sucrase-isomaltase hydrolyze the products of starch digestion by amylase to yield glucose. Sucraseisomaltase also hydrolyzes sucrose to glucose and fructose. Lactose is hydrolyzed entirely by lactase to yield glucose and galactose, and trehalose is hydrolyzed entirely by trehalase to yield glucose. The glucose and galactose liberated during digestion are absorbed across the enterocyte apical membrane by a shared secondary active transport system (termed SGLT-1) that is driven by the coabsorption of sodium. Fructose, in contrast, is absorbed via facilitated diffusion through the actions of the carrier GLUT-5. After entering the enterocyte, all three monosaccharides 260 CASE FILES: PHYSIOLOGY exit from the basolateral membrane by facilitated diffusion, using the carrier GLUT-2. Most of the enzymes involved in carbohydrate digestion are present in relatively high amounts throughout life. Lactase, however, is high at birth and then in most people decreases in later life. In many people, the enzyme decreases to such low levels by the third and fourth decades that lactose intolerance develops, as described in this case. Proteins Dietary protein and the protein contained in gastrointestinal secretions and from cells shed into the lumen of the gastrointestinal tract are acted on by several enzymes to yield amino acids and oligopeptides. The process of protein digestion begins in the stomach through the action of pepsin, which itself is an enzyme protein derived from the precursor pepsinogen, which is secreted by chief cells of the stomach. Once activated by acid, pepsin acts as an endopeptidase to cleave interior peptide bonds. The major digestion of protein, however, takes place in the small intestine. There, contents are mixed with the many proteases secreted by the pancreas as proenzymes. A key enzyme is trypsin, which is secreted as trypsinogen. The initial secreted trypsinogen is converted to trypsin through the action of the brush border enzyme enterokinase. This trypsin then not only attacks peptide bonds in the ingested proteins but also converts additional trypsinogen and the precursors chymotrypsinogen, proelastase, and the procarboxypeptidases to their active forms. Together, these endo- and exopeptidases liberate amino acids and peptides of varying length. In addition to this luminal digestion, there are peptidases on the brush border that assist in the breakdown of larger peptides to di- and tripeptides and amino acids. Unlike the situation in carbohydrate absorption, where only monosaccharides are absorbed, di- and tripeptides are absorbed readily across enterocyte apical membranes along with amino acids. Several carrier-mediated transport systems are involved in peptide and amino acid absorption, including some that are secondary active systems that require sodium. Once in the cell, most dipeptides and tripeptides are hydrolyzed to amino acids, which then exit with the other amino acids through transporters on enterocyte basolateral membranes. Lipids Triglycerides, phospholipids, and cholesterol esters are the major lipids contained in the diet. Their digestion and absorption are rather complicated because of their insolubility in water. The breakdown of triglycerides begins in the mouth through the actions of lingual lipase. However, this activity, along with the activity of gastric lipase, accounts for only about 10% of triglyceride breakdown. Perhaps more important is the mechanical dispersal CLINICAL CASES 261 and emulsification of lipids that take place in the stomach as a result of gastric contractions. This prepares the lipids for further emulsification and breakdown by chemical (bile) and enzymatic processes in the small intestine. Once in the small intestine, the lipid is acted on by pancreatic lipase, which is anchored to emulsified lipid droplets by colipase, which also is secreted by the pancreas. Colipase serves to anchor lipase to the fat droplet and to facilitate the passage of fat digestion (fatty acids and monoglycerides) to adjacent bile salt micelles. Phospholipids present in the diet and in biliary secretions and sloughed cells are broken down by pancreatic phospholipases, mainly phospholipase A2, to fatty acids and lysophospholipids. Cholesterol esters are broken down by pancreatic cholesterol ester hydrolase (nonspecific hydrolase). The products of lipid digestion, except for some of the medium-chain and short-chain fatty acids, are taken up into micelles, which deliver them to enterocyte apical membranes. There they diffuse from the micelles and are absorbed, along with the medium- and short-chain fatty acids, mostly by simple diffusion. Once inside the enterocyte, triglycerides, containing mostly long-chain fatty acids and phospholipids are resynthesized and combined with cholesterol to form, along with apoproteins, chylomicrons. These relatively large lipoproteins fuse with the enterocyte basolateral membrane and are secreted by exocytosis to be taken up in the lymph. The medium- and short-chain fatty acids pass through the enterocytes unchanged and are taken up into the bloodstream. Vitamins Vitamins are contained in the complex foods that humans ingest and are liberated and absorbed through some of the same processes discussed above. Many of the vitamins, such as thiamine (B1), riboflavin (B2), C, biotin, folic acid, niacin, and pantothenic acid, are water soluble and enter across enterocyte apical membranes by secondary active transport coupled to sodium. Pyridoxine (B6) is water soluble and appears to be absorbed by restricted diffusion. The cobalamin (B12) that is released during digestion in the stomach is bound to and protected by glycoproteins (R proteins) secreted by salivary glands and gastric cells. The B12 released from this complex and from food during digestion in the upper small intestine is bound to intrinsic factor, another glycoprotein secreted by gastric parietal cells. This complex, which is protected from further digestion, is propelled to the ileum, where it is taken up by a carrier-mediated transport mechanism. Other vitamins, such as A, D, E, and K, are fat soluble. Once released from foods during digestion, mainly in the small intestine, they are taken up into micelles and delivered to enterocyte apical membranes, where they are absorbed mainly by simple diffusion. 262 CASE FILES: PHYSIOLOGY COMPREHENSION QUESTIONS [31.1] Tests show that glucose is absorbed as expected by a patient if sucrose, lactose, or glucose is ingested, but not if complex starches are ingested. These data indicate a defect in which of the following? A. B. C. D. E. [31.2] A patient is experiencing steatorrhea. Tests show that the enterohepatic circulation of bile salts is normal and that absorption of orally administered glucose is normal. A disorder in which of the following is most likely to be present? A. B. C. D. E. [31.3] Bile acid secretion Brush border enzyme levels Epithelial sodium-coupled glucose transport Pancreatic enzyme secretion Villus surface area Brush border enzyme levels Gastric motility Ileal motility Pancreatic enzyme secretion Villus surface area A patient presents with signs of cystinuria. Tests indicate that when a solution of free amino acids is infused intraduodenally, absorption of arginine is impaired; however, if a solution of dipeptides is infused intraduodenally, arginine absorption is almost normal. These data indicate that the patient has a deficiency in which of the following? A. All sodium-coupled secondary active transport pathways in intestinal epithelia B. Basic amino acid transporters in intestinal epithelia C. Bile acid synthesis D. Epithelial cell peptidase activity E. Pancreatic enzyme secretion Answers [31.1] D. The fact that free glucose is absorbed readily indicates that villus surface area and sodium-coupled transport are normal. The fact that glucose is absorbed when disaccharides are ingested indicates that brush border enzymes are intact. Because complex starches must be broken down first by enzymes secreted by salivary glands (minor) and the pancreas, the impaired glucose absorption seen when starches are ingested, points toward a problem with pancreatic enzyme secretion.