Chapter 20 - The Digestive System 

Digestion and Absorption of Nutrients and Water
Carbohydrates
     Most digestible carbohydrates are in the form of polysaccharides including starch in plant products and glycogen in animal products. Some polysaccharides cannot be digested. These include cellulose, or plant fiber, which forms dietary fiber. Disaccharides in the diet include sucrose and lactose. Monosaccharides such as glucose and fructose form a smaller component but are the most absorbable form of carbohydrate. Other carbohydrates are broken down into monosaccharides to be absorbed. 
  Digestion of Carbohydrates
     Salivary amylase, secreted in the oral cavity, and pancreatic amylase begin digestion but are incapable of completely reducing starch and glycogen to glucose monomers. They reduce starch and glycogen to maltose (glucose-glucose, a disaccharide) or short branched polysaccharides called limit dextrins
     Enzymes present on the apical membrane of absorptive cells lining the small intestines known as brush border enzymes complete digestion. These brush border enzymes include limit dextrinase, glucoamylase, sucrase, lactase and maltase. Transport proteins located near these digestive enzymes facilitate absorption of glucose monomers. 
  Absorption of Carbohydrates
     Glucose and galactose enter epithelial cells via sodium-linked secondary active transport across the apical membrane. Fructose enters by facilitated diffusion. The sugars exit the cells across the basolateral membrane by facilitated diffusion. 
Proteins
     Proteins are not absorbed until enzymes break them down into amino acids in the lumen of the gastrointestinal tract. However, some short peptides (dipeptides and tripeptides) can by absorbed by enterocytes. 
  Digestion
    Protein digestion requires two types of enzymes:
1. Endopeptidases which split polypeptides at interior bonds;
2. Exopeptidases which cleave off  amino acids at either end of the polypeptide. 
     Digestion begins in the stomach with the action of pepsin. Pepsin is converted from pepsinogen by other pepsin molecules that are activated by HCl acid secreted by parietal cells. 
     Pepsin digests proteins into smaller peptides but cannot break them down completely into amino acids. Pepsin also requires the acidity of the stomach environment to remain active. Protein digestion is completed in the small intestines by enzymes secreted by the pancreas and by enzymes bound to the intestinal brush border
     Trypsinogen and chymotrypsinogen are converted into trypsin and chymotrypsin, respectively. These enzymes can only break some of the peptide bonds. Complete breakdown of the peptides into amino acids require the action of carboxypeptidase and aminopeptidase which consecutively split off amino acids at opposite ends of the peptide chain.  
     Trypsinogen is converted into trypsin by enterokinase, a brush border enzyme. Trypsin can then activate chymotrypsinogen, converting it into chymotrypsin, and procarboxypeptidase, converting it into carboxypeptidase.  
  Absorption
     Amino acids enter the absorptive epithelial cells via sodium-linked secondary active transport across the apical membrane. Amino acids are then transported across the basolateral membrane by facilitated diffusion
Lipids
  Digestion
     Lipid digestion begins in the mouth with lingual lipases and continues in the stomach where gastric lipase is added to the mixture. Most digestion of lipids occurs in the small intestines where chyme is mixed with lipases in pancreatic juice. Lipids being hydrophobic form globules. Lipases are hydrophilic and can only act upon the lipid on the globule's surface
   Action of Bile Salts
     Bile salts enhance the digestive action of lipases by breaking down fat globules into smaller droplets in a process called emulsification. This increases the surface area where lipases can act. 
     Bile salts are synthesized by hepatocytes and are secreted in bile which mixes with chyme. Bile salts are derived from cholesterol. Cholesterol is hydrophobic but when converted to bile salts possess a number of oxygen containing polar groups that are hydrophilic. Because all the polar groups are located on one side of the molecule, the molecule is amphipathic. The bile salts break up the fat globules into smaller hydrophilic coated droplets that more readily mix with water. 
  Action of Pancreatic Lipase
     Pancreatic lipases work on the lipids on the surface of the lipid droplets by breaking the bonds of fatty acids on either end of the glycerol backbone. The fatty acids  and monoglycerides are released into solution. Of these end-products of digestion some are absorbed by the epithelial cells while others remain in aggregations called micelles
     The fat droplets gradually disappear as they move down the small intestines toward the colon. In the ileum the bulk of the bile salts are absorbed and recycled by the liver by a pathway referred to as the enterohepatic circulation.
  Absorption of Lipids
     Fatty acids and monoglycerides enter the enterocytes by simple diffusion. Inside the enterocytes the molecules are reassembled into triglycerides and are packaged into large particles called chylomicrons. The chylomicrons are secreted across the basolateral membrane by exocytosis.
     The chylomicrons enter the lymphatic capillaries. The flow of lymphatic fluid carries the chylomicrons to the bloodstream.
     
Absorption of Vitamins
     The fat soluble vitamins A, D, E and K are absorbed with lipids as they readily dissolve in lipid droplets, micelles and chylomicrons. Water soluble vitamins are absorbed by the action of special transport proteins.
     Vitamin B12 requires intrinsic factor secreted by the stomach for absorption. Intrinsic factor forms a complex with vitamin B12 and is absorbed in the ileum. Vitamin B12 is necessary for synthesis of hemoglobin. Vitamin B12 deficiency causes pernicious anemia.
Absorption of Minerals
  Absorption of Sodium and Chloride
    In the duodenum and jejunum, sodium and chloride are absorbed along with water by paracellular transport. Absorption of sodium occurs in the jejunum, ileum and colon by active transport that depends upon the action of the Na+/K+ pump on the basolateral membrane. Absorption of sodium is generally coupled to chloride absorption to maintain electrical neutrality.
  Absorption of Potassium
    Potassium is passively absorbed in the small intestines but may be absorbed or secreted in the colon depending on electrochemical gradients. A decrease in the concentration of potassium in chyme occurs with severe diarrhea and this can cause hypokalemia. 
  Absorption and Secretion of Bicarbonate
    Bicarbonate is passively absorbed in the jejunum. Some of the bicarbonate is reabsorbed by a mechanism which involves the reaction of H+ with bicarbonate to form carbonic acid. The carbonic acid breaks down into water and CO2 which diffuses into the enterocyte. CO2 then converts back to bicarbonate once in the enterocyte. Bicarbonate then crosses the basolateral membrane by facilitated diffusion.
    In the ileum and colon bicarbonate is secreted in exchange for chloride ions. 
  Regulated Absorption of Calcium
    The absorption of calcium is tied to the body's needs. In the duodenum and jejunum absorption occurs in two steps:
1. Calcium binds to calcium-binding protein on the brush border and is then taken into the cell. 
2. Calcium is transported out of the cell by a Ca2+ pump on the basolateral membrane. 
  Absorption of Iron
     The absorption of iron requires a protein called transferrin. Transferrin binds to iron in the lumen of the small intestines and is taken into the enterocyte by receptor-mediated endocytosis. Iron may then be stored in the form of ferritin or transported across the basolateral membrane. In the blood it is transported by another kind of transferrin
Absorption of Water
     About 95% of the water present in the duodenum is absorbed by the time chyme reaches the colon. Absorption of water is a passive process driven by the osmotic gradient created by the transport of solutes, especially sodium. 
General Principles of Gastrointestinal Regulation
     Most ingested nutrients are completely absorbed. In other words, the digestive system absorbs all the nutrients it can no matter the quantity ingested. The neural and hormonal regulatory mechanisms work to control conditions in the lumen of the GI tract. 
  Neural and Endocrine Pathways of Gastrointestinal Control
     Most functions are controlled by the enteric nervous system. The enteric nervous system is influenced by the autonomic nervous system and hormones secreted by the endocrine cells of the stomach and small intestines
     Conditions within the lumen of the GI tract are monitored by three kinds of receptors:
1. Mechanoreceptors - which detect the stretch of the wall.
2. Chemoreceptors - monitor the concentration of various substances, including H+ and fats.
3. Osmoreceptors - monitor the osmolarity of the lumenal contents. 
     The effector organs of the GI tract are the smooth muscle and the secretory cells. Four endocrine hormones are known to exert an effect on the GI tract. The hormones include:
Gastrin - secreted in the stomach.
Cholecystokinin, Secretin, Glucose-dependent Insulinotropic Peptide  (GIP) - secreted in the duodenum and jejunum.
 
  Short and Long Reflex Pathway
     Short Reflex Pathways - Signals travel from receptors, to the intrinsic nerve plexuses and then directly to the effectors.
     Long Reflex Pathways - Signals travel from  receptors, to the CNS, to intrinsic nerve plexuses and then to the effectors. These pathways usually involves the sympathetic and parasympathetic nervous systems. The parasympathetic nervous system promotes activity by increasing muscle activity and fluid secretion. The sympathetic nervous system promotes a reduction in gastrointestinal activity. 
  Phases of Gastrointestinal Control
     Cephalic-Phase Control - Control of gastrointestinal function by stimuli arising in the head (smell, taste, thought of food). 
     Gastric-Phase Control - Control by stimuli arising in the stomach.
     Intestinal-Phase Control - Control by stimuli arising in the small intestines.  
  Regulation of Food Intake
     Food intake is strongly affected by various psychosocial influences. 
     Physiological regulation can be short or long term. 
     Short term controls follow absorption of nutrients from a typical meal. For example, pancreatic islet cells secrete insulin, and cholecystokinin (CCK) is secreted by endocrine cells in the duodenum. Both hormones act upon the hypothalamus to reduce the sensation of hunger. Signals that come from mechanoreceptors and chemoreceptors from the lumen in response to the presence of food also suppress hunger.
     Leptin is a hormone secreted by adipose cells that plays a role in long term regulation. When caloric intake exceeds the body's demand leptin is secreted. Leptin acts on appetite-control centers in the hypothalamus to reduce the sensation of hunger. Leptin also increases the body's metabolic rate
Gastrointestinal Secretion and Its Regulation
  Saliva Secretion
     Mechanoreceptors and chemoreceptors convey information about food texture and taste to the salivary center of the medulla which controls autonomic output to the salivary glands. Information about the sight and smell of food is conveyed to the salivary center by input from the cerebral cortex.
  Acid and Pepsinogen Secretion in the Stomach
     Parietal cells of the stomach secrete acid by the reaction of water and carbon dioxide catalyzed by carbonic anhydrase. The hydrogen ion is actively transported into the lumen of the stomach by a pump that exchanges the hydrogen ion for the potassium ion. Bicarbonate exits the cell through the basolateral membrane in exchange for the chloride ion. The chloride ion then leaves the cell through the apical membrane. Hydrochloric acid is thus secreted into the lumen. 
     Cephalic-phase stimuli increase activity of the parasympathetic nerves to the stomach which stimulates secretion of acid by the parietal cells and pepsinogen by the chief cells. G cells are also stimulated to produce gastrin which also stimulates secretion by both the parietal and chief cells. Histamine, secreted by cells in the stomach lining, also stimulates acid secretion by the parietal cells. 
     Once in the stomach the presence of proteins and the distention of the stomach wall relay signals that trigger the release of acid and pepsinogen. G cells are also stimulated to release gastrin. The exit of food from the stomach withdraws the stimuli that stimulated gastric secretion. A rise in gastric acidity also suppresses gastrin secretion by the G cells. 
     The entry of food into the duodenum stimulates mechanoreceptors, chemoreceptors and osmoreceptors. Signals relayed via long and short reflex pathways decrease acid and pepsinogen secretion in the stomach. Signals are relayed to endocrine cells in the small intestines that secrete CCK, secretin and GIP and these also suppress secretory activity by the parietal and chief cells. 
  Secretion of Pancreatic Juice and Bile
     Pancreatic secretion is influenced mainly by stimuli during the intestinal phase although cephalic-phase and gastric-phase stimuli also play a role. The strongest influence is the secretion of CCK and secretin in response to the presence of food in the duodenum. 
     CCK acts primarily on the acinar cells which produce a relatively small volume of fluid containing water, electrolytes and digestive enzymes. Secretin acts primarily on the ducts to produce a larger volume of bicarbonate-rich secretion. When both hormones are present they each amplify the other's effects in a phenomenon called potentiation. 
     The primary stimulus for the secretion of secretin is the acidity of the chyme entering the duodenum. Since secretin stimulates secretion of bicarbonate rich fluid this results in a decrease in the acidity of the chyme. This reduction in the acidity of the chyme is necessary for the proper functioning of the enzymes in the duodenum. 
     The secretion of CCK is caused by the presence of fat and protein digestive products in the duodenum. CCK increases the secretion of enzymes by the acinar cells
     CCK and secretin also effect secretion of bile and its entry into the duodenum. Secretin acts upon the liver by stimulating bile secretion and CCK promotes gall bladder contraction and relaxation of the sphincter of Oddi allowing bile to enter the duodenum. 
  Rates of Fluid Movement in the Digestive System 
     The fluid that enters the GI tract each day comes from the liver and pancreatic secretions (~ 2 liters), salivary gland secretions (~ 1.5 liters), secretions by glands of the stomach and small intestines (~ 3.5 liters) and ingested water (~ 2 liters). Most of this total (approximately 8.5 liters) is absorbed by the small intestines and the colon also absorbs some. Only a small amount (~ 100 ml) is eliminated in the feces
Gastrointestinal Motility and Its Regulation
  Electrical Activity in the GI Smooth Muscles
     Pacemaker cells clustered in the muscle layers of the GI tract produce slow, spontaneous, graded potentials known as slow waves. When these slow waves bring the membrane potential to threshold, action potentials are triggered. Electrical activity, including both slow waves and action potentials, spread rapidly throughout the smooth muscle because of gap junctions between neighboring cells. 
     Different regions of the GI tract have pacemaker cells that have their own frequencies. The patterns of electrical activity created in this way in each region is called the basic electrical rhythm (BER). 
     BER is relatively constant but can be influenced by hormones and nervous activity. Parasympathetic activity promotes increased contractile force while sympathetic activity decreases contractile force. The increase in contractile force is due to an increase in the height of the slow waves rather than in their frequency. In other words, there is a greater change in membrane potentials that leads to an increase in the number of action potentials. 
     The relationship between electrical activity and contractile activity in the GI tract may vary. In the stomach the force of the contraction of the smooth muscle varies with the membrane depolarization. Action potentials further increase the force of contraction. In the small intestines, only action potentials lead to contractions and the force of contraction varies with the frequency of action potentials. 
  Peristalsis and Segmentation
    The BER sets up waves of contractions that travel longitudinally down the intestinal tract. These waves are called peristalsis
    Alternating contractions of the muscle layers of different segments of the small intestines are responsible for churning or back-and-forth movements called segmentation. 
  Chewing and Swallowing
     The upper part of the GI tract, mouth, pharynx and upper esophagus is controlled by skeletal muscle and control comes directly from the CNS.
     Chewing is under both conscious and unconscious control. Unconscious chewing is controlled by the chewing reflex. The presence of food in the mouth stimulates pressure receptors that reflexively inhibit jaw-closing muscles allowing the jaw to drop. When the jaw drops the pressure on the pressure receptors is relieved and the jaw-closing muscles become dis-inhibited. The alternate opening and closing of the jaw is thus maintained by this reflex. 
     Chewing mechanically breaks down the food and mixes it with saliva forming a semisolid mass called a bolus. When the bolus is ready to be swallowed it is pushed by the tongue to the back of the mouth and into pharynx where it stimulates mechanoreceptors. The signals go to the swallowing center in the medulla where muscle contractions are coordinated as part of the swallowing reflex. 
     The swallowing reflex involves:
1. The bolus presses down on the epiglottis. At the same time muscles raise the larynx. Both actions insure that the glottis is covered. Inspiratory muscles are inhibited at the same time. 
2. The upper esophageal sphincter relaxes
3. Stretch receptors trigger peristalsis (wave of contraction) and the peristaltic wave propels the bolus to the stomach. 
4. The lower esophageal sphincter relaxes
5. Secondary peristaltic waves follow if the bolus fails to enter the stomach. 
     As part of the swallowing reflex the swallowing center causes relaxation of the smooth muscles in the upper part of the stomach. 
  Gastric Motility
     Stomach motility accomplishes two tasks:
1. Mixing of food and gastric juice to form a semisolid paste called chyme.
2. Regulated emptying of the chyme into the small intestines.
  Gastric Motility Patterns
     About three times a minute a peristaltic wave travels from the upper body of the stomach toward the pylorus which mixes the stomach contents. Peristaltic waves also propel some chyme forward into the duodenum
     The rate of gastric emptying depends on:
1. Composition of chyme
2. Volume of chyme
3. Force of gastric contractions
  Regulation of Gastric Motility
     The force of gastric contraction increases in response to gastrin and decreases in response to CCK, secretin and GIP
     Gastric motility is controlled by:
Cephalic-phase stimuli
   Pain, fear, depression inhibit gastric motility and anger and aggression stimulate it. 
Gastric-phase stimuli
    Stomach distention
Intestinal-phase stimuli
    Conditions in the duodenum (distension, acidity, osmolarity, fat content) regulate gastric emptying. 
  Vomiting
     Vomiting is the forceful expulsion of the stomach contents, and sometimes intestinal contents, through the mouth. Stimuli that trigger vomiting include illness, strong emotional states, severe pain, severe distension of the stomach or small intestines, motion sickness, or ingestion of substances that stimulate vomiting known as emetics. 
     The vomiting center of the medulla coordinates the vomiting reflex. This reflex involves increasing the abdominal pressure by deep inspirations followed by closure of the glottis and strong contractions of the abdominal muscles. When the abdominal pressure is high enough the lower esophageal sphincter relaxes and this allows the stomach contents to enter the esophagus. 
  Motility of the Small Intestines
   Motility Patterns in the Small Intestines
     The presence of chyme in the small intestines causes brief periods of peristaltic contraction that propels the chyme forward and longer periods of segmentation during which neighboring regions of the small intestines alternately relax and contract. Segmentation facilitates the mixing of the chyme with bicarbonate, digestive enzymes and bile. The stirring also aids absorption by bringing the chyme into contact with the mucosa.  
     During fasting peristalsis and segmentation are replaced by migrating motility complexes which are a series of intense contractions that periodically move through the intestines and clean it of its contents. 
  Regulation of Motility of the Small Intestines
     Moderate distension of the small intestines trigger short and long reflexes that propel chyme forward. Gastrin stimulates motility in the ileum and promotes relaxation of the ileocecal sphincter
     Special Reflexes:
Intestino-intestinal Reflex
   Severe distension or injury to any portion of the small intestines inhibits motility in the rest of the small intestines. 
Ileogastric Reflex
   Distension of the ileum inhibits gastric motility.
Gastroileal Reflex
   Chyme in the stomach triggers increased motility in the ileum. 
  Motility of the Colon
     Motility of the colon facilitates absorption of water and minerals and propels the contents toward the rectum for storage and elimination. 
   Motility Patterns in the Colon
     The basic pattern of activity is haustration which is similar to segmentation. The segments (called haustra) are permanent folds in the wall. Haustration occurs at the rate of two per hour. 
     About three to four times a day a different pattern called mass movement occurs. A mass movement is like a peristaltic wave except that the contraction is held longer. Mass movement propels the feces forward and sweeps the colon clean
   Regulation of Motility of the Colon
     Special reflexes include:
Colon-colonic reflex
   Distention of one part of the colon causes relaxation of the remaining parts.
Gastrocolic reflex
   Distention of stomach increases colonic motility and increases the frequency of mass movements.
  Defecation
     Control of defecation is both conscious and unconscious through the defecation reflex. The presence of feces in the rectum stimulates stretch receptors that trigger several events:
1. Contraction of smooth muscle in the rectal wall raises the pressure within.
2. Peristaltic contractions in the sigmoid colon propel more fecal material toward the rectum further increasing the pressure.
3. The internal anal sphincter relaxes while the external anal sphincter contracts.
When the pressure rises to a critical level the external anal sphincter also relaxes allowing defecation to proceed. Defecation can be controlled voluntarily by contracting the external anal sphincter.