The Digestive System

• The digestive system performs 5 basic functions:

• Motility - Movement of food through the digestive tract.
• Secretion - Release of substances to the outside of a cell via an exocrine or endocrine route.  Examples include enzymes, HCl, bile salts, mucus, hormones
• Digestion - Breakdown of complex food molecules to smaller subunits, which can be absorbed.

• Carbohydrates Simple sugars
• Proteins Amino acids, small peptides
• Fats Glycerol + fatty acids

• Absorption - Movement of molecules from lumen of digestive tract into the blood or lymph.
• Storage and elimination of indigestible food molecules.

Layers of GI Tract - Mucosa, submucosa, muscularis, serosa

• Regulation of the GI tract

• Autonomous Cells (Cells of Cajal)

• Some cells are capable of generating spontaneous graded slow wave potentials that, if brought to threshold, will initiate A.P.'s and smooth muscle contraction.

• Intrinsic sensory neurons

• Myenteric + submucosal plexuses = enteric nervous system
• Located in walls of digestive tract
• Coordinate local activity in tract by, for example, regulating peristalsis and intestinal reflexes.

• Extrinsic nerves - Nerves from the ANS that regulate the activity of the GI tract.
• Gastrointestinal hormones (Gastrin, Ghrelin, Secretin, CCK, GIP)

• Mouth

• Responsible for taste (gustation)
• Chewing (mastication) - Process that grinds, breaks up, and mixes food with saliva. Saliva has many functions.
• Saliva is secreted by 3 pairs of salivary glands.
• Salivary enzymes (amylases) begin process of carbohydrate digestion. Digestion in mouth is minimal and involves no absorption.
• Salivary secretion can be either unconditioned (occurs when food is in the mouth) or conditioned (occurs without oral stimulation).
• Swallowing (deglutition) - Involves sequentially programmed events under the control of a swallowing center in the medulla..

• Pharynx and Esophagus

• Propels mass of food (bolus) forward by peristalsis (contractions of the circular smooth muscle that push the bolus ahead of the contraction.)
• Gastroesophageal sphincter regulates passage of food into stomach and prevents reflux out of the stomach.
• Sphincters prevent large volumes of air from entering and regurgitation. Excessive gas can lead to burping (eructation).
• No digestion in esophagus.

• Stomach

• Capable of filling, storing, mixing, and emptying.
• Mixing and emptying occur by peristalsis.
• Main factor affecting gastric emptying is the amount of chyme (mixture of food and digestive juices) in the stomach.
• Factors in the duodenum can also affect gastric emptying. These include presence of fat and acid, and distension of duodenum.
• Emotion and pain can influence gastric function.
• Secretes mucus, HCl, pepsinogen, intrinsic factor (IF). IF facilitates the absorption of vitamin B₁₂ which is necessary for normal RBC maturation). Deficiency of IF leads to pernicious anemia.
• H⁺ ions are pumped into the gastric juice by a H⁺/K⁺ ATPase pump.
• Pepsinogen, in the presence of HCL, is converted to pepsin which digests protein.
• Secretes the hormones ghrelin and gastrin

• Gastrin stimulates gastric secretions, motility, and growth of mucosa.
• Ghrelin is a newly discovered hormone that may play a role in regulating hunger.

• Control of gastric secretion involves 3 phases:

• Cephalic, gastric, intestinal phases  (See pages 610-612)

• Does not absorb food, but can absorb alcohol and aspirin.

• Small intestine (SI)

• 3 segments - Duodenum, jejunum, ileum
• Most digestion and absorption occur in the duodenum and jejunum.
• Most contractile activity of the SI occurs by segmentation = simultaneous contractions and relaxations of smooth muscle that propel chyme along the length of the SI.
• Weak peristaltic waves also occur in the SI.
• Digestion in the SI lumen is accomplished by pancreatic enzymes.
• SI is remarkably well adapted for its role in absorption. Has modifications which dramatically increase the surface area for absorption.

• Plicae circularis (large folds) - 3-fold increase
• Villi (finger-like projections) - 10-fold increase
• Microvilli or brush border (Projections arising from cells that make up the villi and contain some enzymes) - 20-fold increase

• Ileum - Some absorption (bile salts, Vitamin B₁₂, water) occurs here.
• Secretes hormones

• Secretin:

• + by HCL in duodenum
• Inhibits gastric function
• + bicarbonate secretion from pancreas

• Cholecystokinin (CCK):

• + by nutrients in the duodenum
• Inhibits gastric function
• + pancreatic enzyme secretion
• + gallbladder contraction

• Gastric inhibitory peptide (GIP):

• + by fat, acid, and distension of duodenum
• Inhibits gastric function
• + insulin secretion

• Large intestine (colon)

• Extends from cecum to anus.
• Some absorption occurs here (salts, water, and some vitamins).
• Primary function is to dry, by extracting water, and store fecal material.
• Elimination of feces (defecation) is under reflex control by the defecation reflex.
• When defecation is delayed too long, more water than usual is reabsorbed and constipation results.
• Diarrhea is the opposite of constipation.
• Large intestine does not secrete digestive enzymes because digestion is complete before chyme ever reaches the colon.
• Colon is a rich source of bacteria that synthesize Vitamin K (essential for normal blood clotting) and vitamin B.
• Flatulence - Passage of intestinal gas derived either from swallowed air or generated from the actions of bacteria.

• Liver

• Largest internal organ in the body.
• Produces and secretes bile and bile salts (derived from cholesterol) which aid in the emulsification and absorption of fats by the formation of water-soluble micelles that can carry the products of fat digestion to their absorptive site.
• Bile also contains bilirubin (derived from the breakdown of heme). Gives bile its yellow color. In the intestine, bilirubin is acted upon by bacteria to produce urobilinogen that gives rise to the brown color of feces. When excreted into the urine it contributes to urine's yellowish color.
• Most bile salts are reabsorbed in the small intestine and returned to the liver via the enterohepatic circulation.
• Processes nutrients after absorption from the digestive tract via the hepatic portal system.
• Stores glycogen and fats; releases glucose and fatty acids into blood.

• Gallbladder

• Located under the liver.
• Stores and concentrates bile.
• Target organ of the hormone CCK.

• Pancreas (exocrine portion)

• Secretes enzymes (e.g., amylase, trypsin, lipase).
• Many enzymes are produced in inactive form = zymogens.
• Trypsinogen (inactive form) is activated to trypsin by the brush border enzyme enterokinase.
• Secretes bicarbonate which neutralizes stomach acid in the small intestine and facilitates enzyme function.
• Secretion is hormonally regulated by secretin and CCK.

Digestion and Absorption

• Carbohydrates

• Polysaccharides (starch) are digested by amylases (salivary and pancreatic).
• Dietary carbohydrates are presented to the small intestine in the form of disaccharides (lactose, maltose, sucrose).
• Enzymes located in the microvilli break down the disaccharides into monosaccharides.

• Lactose galactose + glucose
• Maltose glucose + glucose
• Sucrose fructose + glucose

• Glucose and galactose are absorbed across the membrane of the microvilli by secondary active transport (cotransport).
• Glucose and galactose leave the epithelial cells by moving down their concentration gradients and enter capillaries within the villi.
• Fructose is moved to the blood by facilitated diffusion (passive carrier mediated transport of a substance down its concentration gradient).

• Proteins

• Proteins are broken down by pepsin and pancreatic enzymes into free amino acids and small peptides.
• Amino acids are cotransported into the epithelial cells by secondary active transport.
• Amino acids enter the capillaries within the villi.
• Small peptides are absorbed by a membrane carrier and are further broken down into amino acids by peptidases.

• Lipids (not water soluble; must be transformed prior to absorption).

• Dietary fat is emulsified to smaller fat droplets by bile salts.
• Lipase cleaves fat monoglycerides and fatty acids (FA).
• Monoglycerides and FA's are carried in micelles, formed from bile components.
• Monoglycerides and FA's leave micelles and diffuse through cell membrane.
• Monoglycerides and FA's are resynthesized into fats.
• Fats aggregate and are coated with protein to form chylomicrons.
• Chylomicrons are released from the cell by exocytosis into the central lacteal (lymph vessel) of the villi.
• Chylomicrons enter venous blood via thoracic duct.
• Once in the blood the fat component of the chylomicrons is cleaved by the enzyme lipoprotein lipase which provides FA's and glycerol to the tissues.