1. in stomach and duodenum, ulcers -- areas with destroyed mucosa, exposing underlying tissue to acid and protease -- may occur, sometimes due to excessive acid secretion, sometimes due to excessive intakes of alcohol or aspirin-like drugs. Also, acid may rise past a weak lower esophageal sphincter, causing "heartburn" and, in the long run, damage to esophageal tissue (gastroesophageal reflux disease -- GERD).

2. 30 years ago, treatments used to involve "antacids" (base to neutralize acid), surgical cutting of vagus nerve to stomach, sometimes even total gastrectomy.

3. "H2 blockers" available since early 1970's (e.g., Tagamet, Zantac, Pepcid) transformed treatment, blocking the main pathway of parietal cell activation (histamine binding to basolateral histamine receptors -- "H2" type -- activating adenylyl cyclase, elevating cAMP). They inhibit acid secretion by ~75% (much more effective than cutting vagus nerve). and were the best selling prescription drugs from ~1975-1995

4. Most recently, "acid pump inhibitors" (Prilosec) have taken over best-seller spot; inhibit acid secretion by up to 99% if taken daily; commonly prescribed for severe GERD.

5. In 1990's, infection of stomach lining by H. pylori bacteria was found to play an important, though not fully understood, role in gastric ulcers, with a large percentage of ulcer patients having H. pylori infection. Eradication of the infection with antibiotics, in addition to use of acid inhibitors, leads to very high rate of "permanent" ulcer cure (no recurrence after 5 years), while treatment with only acid inhibitors leads to very high rate of recurrence within 5 years.

1. smell and taste of food, anticipation, initiate secretion of gastric juice via autonomic (vagus) innervation -- minor effect.

2. G cells, in pyloric mucosa, sense peptides in gastric contents and increase secretion of gastrin, which triggers histamine-containing cells in mucosa to release histamine. Histamine binds to H2 receptors on parietal cells, activating them via a cAMP pathway to fuse H,K-ATPase-containing vesicles with the luminal membrane, initiating acid secretion. (Major pathway stimulating acid secretion.)

3. Gastric mucosa senses pH of gastric contents and modulates gastrin release to maintain contents at pH ~2. Thus, antacids (i.e., acid neutralizers, rather than acid inhibitors) ultimately lead to increased acid secretion and increased levels of base (alkali) in the body. (Acid inhibitors also result in higher gastrin levels, but block its ultimate activation of parietal cells.)

4. Intestinal feedback: secretin and gastric inhibitory peptide, released by duodenum in response to entry of chyme from stomach, inhibit gastric secretion as well as gastric motility.

1. Water can cross gastric mucosa

    a. When plain water is ingested, net flow of water across gastric mucosa may be from lumen into body.

    b. But, when food is in stomach, net flow of water is from body into lumen of stomach.

        i. Much of this flow is in the form of gastric juice,

        ii. but some is drawn osmotically across mucosa by the increasing osmolarity of chyme as large food molecules are broken down into numerous smaller, osmotically active molecules.

2. Most nutrient molecules are not absorbed by stomach.

3. Alcohol and aspirin are absorbed from stomach, because they are water soluble enough to diffuse toward mucosal surface, but hydrophobic enough to cross cell membranes without any specific membrane transporters.

1. food must be eaten in very small amounts, very frequently,

2. vitamin B₁₂ supplements must be taken, and

3. care should be taken to eat properly cleaned food.

1. seemingly random contractions of circular muscles pinch small intestine into segments,

2. cause local mixing of contents to increase access of enzymes to substrates and increase likelihood of digestive products encountering mucosal surface for absorption.

3. more frequent contractions in duodenum than farther along small intestine cause net movement of chyme slowly toward large intestine.

1. begins toward end of digestive period

2. mainly to sweep last bit of chyme from small intestine

1. circular folds -- large enough to be visible

2. microscopic finger-like projections of mucosa called villi

    a. villus lined by simple columnar epithelium consisting of mostly digestive/absorptive cells, interspersed with some mucous cells

    b. interior of villus contains blood capillaries and small terminal lymphatics.

3. digestive/absorptive cells have microvilli on luminal membrane, containing membrane-bound digestive enzymes and nutrient transporters.

1. amino acids, dipeptides, and tripeptides can be taken up across luminal membrane by transporters, often coupled to Na+ or H+ uptake.

2. intracellular enzymes complete breakdown to single amino acids for facilitated diffusion across basolateral membrane toward blood.

1. membrane-bound enzymes complete process begun by soluble amylase.

2. monosaccharides taken up via transporters, usually coupled to Na+ uptake

3. this process allows low-cost treatment of cholera victims

    a. cholera toxin turns on excessive secretion of NaCl and water by intestinal cells; victims can die quickly of dehydration.

    b. if victims are given a solution of water, glucose, and NaCl, the Na+/glucose transport mechanism can be maximally activated; uptake of solutes and water by this mechanism can substantially offset losses of solutes and water caused by cholera toxin, so water loss is greatly reduced and victims can survive until infected cells die and slough off in 2-3 days.

1. pass from bile salt micelles hydrophobically through luminal membranes of absorptive cells,

2. are resynthesized into triglycerides inside cells,

3. then combined with proteins into multi-molecular packets called chylomicrons, which leave basolateral membrane by exocytosis.

4. Chylomicrons, too big to pass through capillary walls, are taken up by the more porous lymphatic vessels (called "lacteals" in the intestines, because the fat particles give the lymph a milky appearance).

1. In lower right abdomen, small intestine empties into large intestine through ileocecal valve, which prevents back-flow into small intestine.

2. Lower right end of large intestine is the cecum, a short pouch with attached appendix.

    a. Appendix (a short, narrow vestige of much longer functional cecum in many herbivores for bacterial digestion of cellulose) contains many lymphatic nodules in its wall,

    b. but can be overwhelmed by trapped bacteria and become infected, inflamed and swollen, with life-threatening consequences if it ruptures into abdominal cavity.

3. ascending, transverse, descending, and sigmoid colon:

    a. much larger diameter than small intestine

    b. Ascending and descending colon are attached to back of abdomen, holding large intestine in a fixed position; transverse colon "hangs" between fixed portions, just beneath stomach. Colon continues through sigmoid (S-shaped) region to short, vertical rectum terminating at anus.

    c. no villi on colonic mucosa, so much less surface area than in small intestine

    d. Epithelium is simple columnar, with many more mucus-secreting cells than in small intestine, to lubricate passage of increasingly solid contents.

4. anus

    a. In anal canal, epithelium changes from simple cuboidal to stratified squamous for additional protection against abrasion.

    b. surrounded by two sets of sphincter muscles

        i. inner -- smooth ("involuntary") muscle

        ii. outer -- skeletal ("voluntary") muscle

1. absorbs of most of remaining water in chyme, secondary to active reabsorption of NaCl -- about 1 liter/day, to make waste more compact and semi-solid. (Most water taken into, or secreted into, GI tract has already been reabsorbed by small intestine.)

2. houses many bacteria, mostly benign

    a. Bacteria consume some unabsorbed nutrients (often fats, but other nutrients when a specific malabsorption syndrome exists, e.g., for lactose), some indigestible matter (cellulose), and dead cells released from intestinal lining.

    b. Some bacteria synthesize the fat-soluble vitamin K, which is then absorbed, along with some lipids, across colonic mucosa.

3. motility

    a. Circular muscles contract in a manner similar to segmentation in small intestine, but much more slowly (sustained for minutes rather than seconds); slow mixing allows adequate water absorption from all contents.

    b. Stronger contractions of larger segments of colon (mass action) move contents along.

    c. Occasionally, mass action pushes contents (now called feces) into rectum, which usually remains empty.

        i. Rectum contracts, putting pressure on anal sphincters and inner sphincter involuntarily relaxes (defecation reflex).

        ii. After early childhood, external sphincter becomes trained to remain contracted until voluntarily relaxed for defecation (passage of feces through anus) -- example of "habituated" subconscious control of skeletal muscle.

        iii. If defecation does not occur, contraction of rectum pushes feces back into sigmoid colon, and rectum remains empty until next mass action.