CHAPTER 23: THE DIGESTIVE SYSTEM: PHYSIOLOGY OF DIGESTION AND ABSORPTION

How is each type of nutrient processed? PROTEINS

- Proteins digested in the GI tract include: 1. Dietary proteins (typically about 125 g per day) 2. Enzyme proteins secreted into the GI tract by its various glands (15-25 g) 3. Protein derived from sloughed and disintegrating mucosal cells - Healthy individuals digest much of this protein all the way to its amino acid monomers. - Protein digestion begins in the stomach when pepsinogen secreted by the chief cells is activated to pepsin - Pepsin functions optimally in the acidic pH range found in the stomach: 1.5-2.5 - Pepsin, which hydrolyzes 10-15% of ingested protein, is inactivated by the high pH in the duodenum

Nucleic Acids

- The nuclei of the cells of ingested foods contain DNA and RNA. - Pancreatic nucleases in pancreatic juice hydrolyze the nucleic acids to their nucleotide monomers. - Intestinal brush border enzymes (nucleosidases and phosphatases) then break the nucleotides apart to release their nitrogenous bases, pentose sugars, and phosphate ions - Special carriers in the epithelium of the villi actively transport the breakdown products of nucleic acid digestion across the epithelium. These then enter the blood

Vitamin Absorption

- The small intestine absorbs dietary vitamins, and the large intestine absorbs some of the K and B vitamins made by its gut bacterial "guests." - As we already noted, fat-soluble vitamins (A, D, E, and K) dissolve in dietary fats, become incorporated into the micelles, and move across the villus epithelium passively (by diffusion) - Most water-soluble vitamins (B vitamins and vitamin C) are absorbed via specific active or passive transporters. - The exception is vitamin B12, which is a very large, charged molecule. - Intrinsic factor, produced by the stomach, binds to vitamin B12. - The vitamin B12-intrinsic factor complex then binds to specific mucosal receptor sites in the terminal ileum, which trigger its active uptake by endocytosis

Mechanisms for Absorption (2)

- There is much more flowing through the alimentary tube than food monomers. - Indeed, up to 10 L of food, drink, and GI secretions enter the alimentary canal daily, but only 1 L or less reaches the large intestine. - Virtually all of the foodstuffs, 80% of the electrolytes, and most of the water (remember water follows salt) are absorbed in the small intestine. - Although absorption occurs all along the length of the small intestine, most of it is completed by the time chyme reaches the ileum. - The major absorptive role of the ileum is to reclaim bile salts to be recycled back to the liver for resecretion. - The absorptive capacity of the small intestine is truly remarkable and it is virtually impossible to exceed

How is each type of nutrient processed? LIPIDS

- Triglycerides are the most abundant fats in the diet. - The small intestine is the primary site of lipid digestion because the pancreas is the major source of fat-digesting enzymes, or lipases

Lipoprotein Lipase

- While in the bloodstream, the triglycerides of the chylomicrons are hydrolyzed to free fatty acids and glycerol by lipoprotein lipase, an enzyme associated with capillary endothelium. - The fatty acids and glycerol can then pass through the capillary walls to be used by tissue cells for energy or stored as fats in adipose tissue. - Liver cells then endocytose and process the residual chylomicron material

Water Absorption

- pproximately 9 L of water, mostly derived from GI tract secretions, enter the small intestine daily. - Water is the most abundant substance in chyme, and 95% of it is absorbed in the small intestine by osmosis. - Most of the rest is absorbed in the large intestine, leaving only about 0.1 L to soften the feces - The normal rate of water absorption is 300 to 400 ml per hour. - Water moves freely in both directions across the intestinal mucosa, but net osmosis occurs whenever a concentration gradient is established by the active transport of solutes (particularly Na+) into the mucosal cells. - In this way, water uptake is effectively coupled to solute uptake and, in turn, affects the absorption of substances that normally pass by diffusion. - As water moves into mucosal cells, these substances follow along their concentration gradients

The steps of lipid digestion and absorption in the small intestine are? (1)

STEP 1: Emulsification. - Because triglycerides and their breakdown products are insoluble in water, fats need special "pretreatment" with bile salts to be digested in the watery environment of the small intestine. - In aqueous solutions, triglycerides aggregate to form large fat globules, and only the triglyceride molecules at the surfaces of such fatty masses are accessible to the water-soluble lipase enzymes. - However, bile salts vastly increase the surface area exposed to pancreatic lipases by breaking large fat globules into many smaller droplets. - Without bile, lipids could not be completely digested during the time food spends in the small intestine - Bile salts have both nonpolar and polar regions. - Their nonpolar (hydrophobic) parts cling to the fat molecules, and their polar (ionized hydrophilic) parts allow them to repel each other and interact with water. - As a result, fatty droplets are pulled off the large fat globules, forming a stable emulsion—an aqueous suspension of fatty droplets - Emulsification does not break chemical bonds. It just reduces the attraction between fat molecules so they can be more widely dispersed

The process of digesting and absorbing carbohydrates in the small intestine (steps)

STEP 1: Pancreatic amylase breaks down starch and glycogen into oligosaccharides and disaccharides - Starchy foods and other digestible carbohydrates that escape being broken down by salivary amylase are acted on by pancreatic amylase in the small intestine. - About 10 minutes after entering the small intestine, starch is entirely converted to various oligosaccharides, mostly maltose STEP 2: Brush border enzymes break oligo- and disaccharides into monosaccharides - Intestinal brush border enzymes further digest these products to monosaccharides. - The most important brush border enzymes are dextrinase and glucoamylase, which act on oligosaccharides composed of more than three simple sugars, and maltase, sucrase, and lactase, which hydrolyze maltose, sucrose, and lactose respectively into their constituent monosaccharides. - Because the intestine can absorb only monosaccharides, all dietary carbohydrates must be digested to monosaccharides to be absorbed STEP 3: Monosaccharides are cotransported across the apical membrane of the enterocyte - Glucose and galactose, liberated by the breakdown of starch and disaccharides, are shuttled by secondary active transport with Na+ into the enterocytes STEP 4: Monosaccharides exit across the basolateral membrane by facilitated diffusion. - All types of monosaccharides move out of the enterocytes by facilitated diffusion and pass into the capillaries via intercellular clefts

The process of digesting and absorbing proteins in the small intestine (steps)

STEP 1: Pancreatic proteases break down proteins and protein fragments into smaller pieces and some individual amino acids - Protein fragments entering the small intestine are greeted by a host of proteolytic enzymes. - Trypsin and chymotrypsincleave the proteins into smaller peptides. - Carboxypeptidases split off one amino acid at a time from the end of the polypeptide chain that bears the carboxyl group STEP 2: Brush border enzymes break oligo- and dipeptides into amino acids - A variety of brush border peptidases liberate individual amino acids from either end of a peptide chain (carboxypeptidasesand aminopeptidases), while dipeptidases break pairs of amino acids apart. - Carboxypeptidases and aminopeptidases can independently dismantle a protein, but the teamwork between these enzymes and between trypsin and chymotrypsin, which attack the more internal parts of the protein, speeds up the process tremendously STEP 3: Amino acids are cotransported across the apical membrane of the enterocyte - Several types of carriers transport the different amino acids resulting from protein digestion. - Most of these carriers, like those for glucose and galactose, are coupled to the active transport of sodium. - Short chains of two or three amino acids (dipeptides and tripeptides, respectively) are also actively absorbed using H+-dependent cotransport. - They are digested to their amino acids within the enterocytes. STEP 4 Amino acids exit across the basolateral membrane via facilitated diffusion - They then enter capillaries via intercellular clefts

Electrolyte Absorption

- Absorbed electrolytes come from both ingested foods and gastrointestinal secretions. - Most ions are actively absorbed along the entire length of the small intestine. - But absorption of iron and calcium is largely limited to the duodenum

Potassium

- Potassium ions move across the intestinal mucosa passively by facilitated diffusion (or leaky tight junctions). - As water is absorbed from the lumen, rising potassium levels in chyme create a concentration gradient for its absorption. - Anything that interferes with water absorption (resulting in diarrhea) not only reduces potassium absorption but also "pulls" K+ from the interstitial space into the intestinal lumen

Mechanisms for Absorption (1)

- Absorption is the process of moving substances from the lumen of the gut into the body - Absorption is the process of moving substances from the lumen of the gut into the body. - Recall from Chapter 4 that epithelia are polarized and have an apical and basal side. - Because tight junctions join the epithelial cells (enterocytes) of the intestinal mucosa at their apical surfaces, substances usually cannot move between cells. - Instead, materials must pass through the enterocytes. - Materials enter an enterocyte through its apical membrane from the lumen of the gut, and exit through the basolateral membrane into the interstitial fluid on the other side of the cell (as shown at right). - Once in the interstitial fluid, substances diffuse into the blood capillaries. - From the capillary blood in the villus they are transported in the hepatic portal vein to the liver. - The exception is some lipid digestion products, which enter the lacteal in the villus to be carried via lymphatic fluid to the blood. - Remember that the structure of the plasma membrane means that nonpolar substances, which can dissolve in the lipid core of the membrane, can be absorbed passively. - All other substances need a carrier mechanism. - Most nutrients are absorbed by active transport processes driven directly or indirectly (secondarily) by metabolic energy (ATP)

Sodium, Chloride, and Bicarbonate

- Absorption of sodium ions in the small intestine is coupled to active absorption of glucose and amino acids - In other words, Na+ is actively pumped out of the enterocytes by a Na+-K+ pump after entering those cells. - Usually, chloride ions passively follow Na+. In the terminus of the small intestine, HCO3− is actively secreted into the lumen in exchange for Cl−

Calcium

- Calcium absorption is closely related to blood levels of ionic calcium. - The active form of vitamin D promotes active calcium absorption. - Decreased blood levels of ionic calcium prompt parathyroid hormone (PTH) release from the parathyroid glands. - Besides facilitating the release of calcium ions from bone matrix and enhancing the reabsorption of calcium by the kidneys, PTH stimulates activation of vitamin D to calcitriol by the kidneys, which in turn accelerates calcium ion absorption in the small intestine

Mechanism of Digestion: Enzymatic Hydrolysis

- Digestion is a catabolic process that breaks down large food molecules to monomers (chemical building blocks). - Digestion is accomplished by enzymes secreted into the lumen of the alimentary canal by intrinsic and accessory glands - Enzymatic breakdown of any food molecule is hydrolysis because it involves adding a water molecule to each molecular bond to be broken (lysed). - Most digestion is done in the small intestine. - Pancreatic enzymes break large chemicals (usually polymers) into smaller pieces that are, in turn, broken down into individual components by the intestinal (brush border) enzymes - Alkaline pancreatic juice neutralizes the acidic chyme that enters the small intestine from the stomach. - This provides the proper environment for operation of the enzymes. - Both pancreatic juice (the main source of lipases) and bile are necessary for fat breakdown

Digestion ____ food into ____ that are absorbed across the ___ ____

- Hydrolyzes; nutrients; gut epithelium

How is each type of nutrient processed? CARBOHYDRATES

- In the average diet, most (up to 60%) digestible carbohydrates are in the form of starch - Only three monosaccharides are common in our diet: glucose, fructose, and galactose - The more complex carbohydrates that our digestive system is able to break down to monosaccharides are the disaccharides sucrose (table sugar), lactose (milk sugar), and maltose (grain sugar), and the polysaccharides glycogen and starch - Digestion of starch (and perhaps glycogen) begins in the mouth - Salivary amylase, present in saliva, splits starch into oligosaccharides, smaller fragments of two to eight linked glucose molecules. - Starch digestion continues until salivary amylase is inactivated by stomach acid and broken apart by the stomach's protein-digesting enzymes

Iron

- Ionic iron, essential for hemoglobin production, is actively transported into the mucosal cells, where it binds to the protein ferritin - The intracellular iron-ferritin complexes then serve as local storehouses for iron. - When body reserves of iron are adequate, only 10-20% is allowed to pass into the portal blood, and most of the stored iron is lost as the enterocytes later slough off. - However, when iron reserves are depleted (as during acute or chronic hemorrhage), iron uptake from the intestine and its release to the blood accelerate. - In the blood, iron binds to transferrin, a plasma protein that transports it in the circulation

The steps of lipid digestion and absorption in the small intestine are? (2)

STEP 2: Digestion - Pancreatic lipases catalyze the breakdown of triglycerides by splitting off two of the fatty acid chains, yielding free fatty acids and monoglycerides (glycerol with one fatty acid chain attached) STEP 3: Micelle formation - Just as bile salts accelerate lipid digestion, they are also essential for the absorption of its end products. - As the water-insoluble products of fat digestion—the monoglycerides and free fatty acids—are liberated by lipase activity, they quickly become associated with bile salts and lecithin (a phospholipid found in bile) to form micelles - Micelles are collections of fatty elements clustered together with bile salts in such a way that the polar (hydrophilic) ends of the molecules face the water and the nonpolar portions form the core - 500 times smaller and easily diffuse between microvilli to come into close contact with the apical cell surface. - Without micelles, the lipids would simply float on the surface of the chyme (like oil on water), inaccessible to the absorptive surfaces of the enterocytes

The steps of lipid digestion and absorption in the small intestine are? (3)

STEP 4: Diffusion - Upon reaching the enterocytes, the various lipid substances leave the micelles and move through the apical plasma membrane by simple diffusion STEP 5: Chylomicron formation - Once the free fatty acids and monoglycerides enter the enterocytes, the smooth ER converts them back into triglycerides. - The triglycerides are then combined with lecithin and other phospholipids and cholesterol, and coated with a "skin" of proteins to form water-soluble lipoprotein droplets called chylomicrons STEP 6: Chylomicron transport - The milky-white chylomicrons are too large to pass through either the plasma membrane of the enterocyte or the basement membrane of a blood capillary. - Instead, the chylomicron-containing vesicles migrate to the basolateral membrane and are extruded by exocytosis. - They then enter the more permeable lacteals. - Thus, most fat enters the lymphatic stream for distribution in the lymph. - Eventually the chylomicrons are emptied into the venous blood via the thoracic duct, which drains the lymphatics of the digestive viscera