1. in a sense, "outside" the body, like the hole through a donut;

2. however, multiple barriers along tube allow maintenance of specialized environments (combining secretions and ingested substances) within various segments.

1. mucosa, facing lumen (cavity of tract)

  a. epithelium

    i. single cell layer ("simple" epithelium) along most of tract

    ii. multiple cell layers ("stratified") at either end

  b. loose connective tissue: contains capillaries and smallest lymphatics serving the epithelium

  c. very thin muscle layer -- muscularis mucosae ("muscle of the mucosa")

2. submucosa: loose connective tissue, containing blood vessels, lymphatics, and nerves

3. muscularis (main muscles of tract): mostly involuntary "smooth" muscle

  a. circular layer

  b. longitudinal layer

  c. oblique layer (in stomach only)

  d. nerves run between muscle layers

4. serosa -- connective tissue, continuous with connective tissue "mesenteries" (which connect to body wall and carry blood vessels and nerves to GI tract)

1. components of secretion:

  a. water to soften and moisten food in preparation for swallowing

  b. mucus -- lubricates food to facilitate swallowing, and slows drying of moist surfaces in mouth and pharynx

  c. enzyme, amylase, that starts breakdown of starch (a branched polymer of glucose subunits) into disaccharides (maltose), trisaccharides, and some branched oligosaccharides

  d. lysozyme, an enzyme that kills many bacteria

  e. bicarbonate to neutralize acid -- some from food, some from bacteria -- that could damage teeth and gums

  f. lipase, mentioned in text, is not a very important constituent of saliva (most lipase is secreted farther along GI tract, by pancreas)

2. control of secretion, by autonomic nervous system

  a. primary stimuli: taste (especially sour) and smell of food, chewing motions (but not the thought of food)

  b. low rate of secretion during sleep; can increase ~20-fold during eating

1. swallowing is voluntarily initiated, but continued by series of involuntary reflexes

  a. Tongue moves food backward and up against soft palate; reflexes take over.

  b. Soft palate moves up to block nasopharynx.

  c. Epiglottis moves down to close off top of air passage (glottis/larynx).

  d. Muscles of pharynx constrict in a wave, from nasopharynx down toward esophagus.

  e. Upper esophageal sphincter relaxes, providing the only outlet for food compressed by pharyngeal constriction, allowing clump of food, called a bolus, to enter esophagus.

2. Reflex sequence may occasionally fail to close epiglottis fully, allowing some food or water to enter larynx, causing coughing or choking.

3. A sharp inhalation when food is in the mouth, but swallowing has not been initiated (e.g., a hiccup, gasp, or quick breath to cool hot food), can suck food into larynx, sometimes completely blocking breathing.

  a. Local muscles cannot move the food.

  b. "Heimlich maneuver" -- sharp external compression of abdomen up into diaphragm, and inward compression of lower rib cage -- may apply enough air pressure below the food to dislodge it back into pharynx, to be coughed out or properly swallowed.

1. striated, skeletal ("voluntary") muscle in upper 1/3

2. smooth muscle in lower 2/3

1. storage -- allows rapid consumption of large meal, then releases contents gradually for slower digestion by small intestine

2. liquefaction -- food becomes liquid called chyme

3. initiation of protein digestion, by acid and proteolytic enzyme

4. destruction of bacteria and viruses by strong acid and proteolysis

5. mixing and controlled propulsion toward small intestine (peristalsis)

1. regions -- fundus, body, pylorus

2. three muscle layers -- circular, longitudinal, oblique -- for mixing and peristalsis; thinnest at fundus, thickest at pylorus

3. Lining of stomach lumen is thrown into numerous folds called rugae to increase surface area.

4. mucosal lining with simple columnar epithelium that dips into numerous gastric glands

  a. deep, narrow glands in fundus and body contain acid-secreting parietal cells, enzyme-secreting chief cells, and mucous cells.

  b. shallow, wider glands in pylorus contain mucous cells and some gastrin-secreting (endocrine) G-cells.

1. Muscle layers are partly contracted when stomach is empty.

2. Muscles relax to allow expansion when food enters.

3. Expansion initiates periodic contractions that mix stomach contents, further reduce size of food particles, and push contents toward pyloric sphincter.

4. control of motility:

  a. cephalic phase -- smell and taste (even thought) of food start gastric motility through autonomic innervation.

  b. gastric phase -- initiated within stomach

    i. Stretching stimulates motility, especially peristalsis.

    ii. motility also stimulated by hormone, gastrin (more later)

  c. intestinal phase -- feedback from intestines inhibits gastric motility:

    i. neural pathway -- initiated by stretching of duodenum

    ii. release of hormones from duodenum -- secretin, cholecystokinin (CCK), and gastric inhibitory peptide -- due to sensing of acid, protein, and fat in duodenal lumen

1. acid secreted by parietal cells

  a. Membrane-spanning H,K-ATPase enzymes pump H⁺ out across luminal membrane, in exchange for K⁺ (uses one ATP, pumps one H⁺, one K⁺ per cycle).

  b. H⁺ comes from ionized water (H⁺ and OH^-) at cytoplasmic pH of 7.0.

  c. Excess OH^- left in cell is reacted with CO₂ to form bicarbonate (HCO₃^-), which exits basolateral membrane via the Cl^-/HCO₃^- exchanger.

  d. Exit of HCO₃^- down its concentration gradient drives Cl^- into cytoplasm, to ~30 mM -- higher than its electrochemical equilibrium.

  e. Cl^- exits luminal membrane through channels, down an electrochemical gradient, to act as negative counter-ion for H⁺.

  f. Both ions draw water isosmotically from cells, so total secretion is isotonic HCl, ~150 mM.

    i. pH < 0.9 in gland lumen

    ii. diluted and buffered by ingested food and water, in main cavity of stomach, to pH ~2

2. pepsinogen secreted by chief cells

  a. converted to pepsin, in acid, by removal a peptide fragment

  b. Fragment inhibits pepsin, by non-covalent interaction, until both reach cavity of stomach and are diluted by mixing with food.

  c. Acid denatures ("uncoils") most proteins, facilitating attack by pepsin.

  d. Pepsin, most active at pH ~2, breaks only a few specific peptide bonds in proteins so protein digestion is only begun in stomach.

1. Parietal cells also secrete intrinsic factor, a glycoprotein that binds vitamin B₁₂  and facilitates its uptake by small intestine.

2. protective secretions by surface cells

  a. mucus, which spreads over luminal surface of stomach, slowing diffusion of H⁺ toward cells

  b. bicarbonate, which diffuses outward through mucus layer, establishing pH gradient -- pH 2 in stomach contents, closer to neutral at cell surfaces

  c. Mucus/bicarbonate layer also limits cellular exposure to active pepsin.

  d. Nevertheless, surface cells live only a few days, while parietal and chief cells live several weeks.