The Digestive System

1. The Digestive System Gastrointestinal tract Physiology Dr. Suaad M. Ghazi MBChB, MSc, PhD

2. Objectives of Lecture 8 1. Explain absorption of amino acids, Na+, Cl-, K+ ions and water.

3. Digestion of proteins ♦ Meats and vegetables. ♦ Proteins are formed of long chain of amino acids bound together by peptide linkages. Digestion of proteins in the stomach ♦ For pepsin to cause any digestive action on protein, the stomach juices must be acidic (pH 2 – 3). ♦ When pH 5 completely block the activity of pepsin. ♦ Pepsin digestion represents 10 - 30% of the total protein digestion. ♦ This splitting of proteins is a process of hydrolysis occurring at the peptide linkages between the amino acids.

4. ♦ Pepsin, the active form of pepsinogen, is a proteolytic enzyme that begins the process of protein digestion. ♦ Pepsinogen is released from the chief cells during all three phases of digestion. ♦ During the cephalic phase of secretion, vagally stimulated cholinergic neurons within the enteric nervous system directly stimulate chief cells to release pepsinogen.

5. ♦ During the gastric phase of secretion, low pH activates local reflexes (mediated by the release of acetylcholine) that enhance pepsinogen secretion. The low pH of the stomach is also responsible for converting pepsinogen into pepsin. ♦ During the intestinal phase of secretion, secretin enhances pepsinogen release. Thus, the presence of H+ within the duodenum during the intestinal phase of secretion may contribute to pepsinogen secretion.

6. Digestion of proteins by pancreatic secretions ♦ Most protein digestion occurs in the small intestine under the influence of the proteolytic enzymes of the pancreatic secretion. ♦ Trypsin and chymotrypsin can split protein molecules into small polypeptides. ♦ Carboxypolypeptidase leaves individual amino acids from the carboxyl ends of the polypeptides.

7. Digestion of peptides by epithelial peptidases of small intestine ♦ The brush border of the small intestine contains several different enzymes for hydrolyzing the final peptides linkages of the remaining dipeptides and other small polypeptides as they come in contact with the epithelium of the villi. The enzymes responsible are aminopolypeptidase and several dipeptidase.

8. ♦ When the food has been properly masticated and is not eaten in too large a quantity at any one time, about 98% of all the proteins finally become either amino acids or dipeptides that can be absorbed into the blood.

9. Absorption of amino acids (1) Most proteins are absorbed in the form of amino acids (dipeptides and tripeptides) by Na+-dependent cotransport system in the brush border of the epithelial cell. Once inside the enterocytes, intracellular peptidases digest some of the polypeptides to amino acid. The amino acids are then transported from cell to blood by facilitated diffusion.

10. (2) Larger molecules, especially in newborn infant, are engulfed by the plasma membrane of the epithelial cell (endocytosis), move through the cytoplasm, and are released on the opposite side of the cell by the reverse process (exocytosis).

11. ♦ The capacity to absorb intact proteins is greater in a newborn infant and antibodies secreted in the mother’s milk may be absorbed by the infant in this manner, providing a short term passive immunity until the child begins to produce its own’ antibodies. ♦ Inadequate absorption of proteins due to lack of trypsin is a common in pancreatic diseases.

14. Absorption of Proteins and Carbohydrates Figure 14.13

15. Absorption of Na+, Cl- and K+ ions  Electrolytes and H2O may cross intestinal epithelial cells by either cellular or paracellular.  The major ions that are absorbed in the small intestine and proximal colon are Na+, K+, and Cl-. ♦ Primarily achieved by the Na+-K+-ATPase pumps located at the basolateral membrane of the enterocytes.

16. Absorption of NaCl, K, HCO3-, and water from small intestine and proximal colon.

17. This pump creates low intracellular concentration of Na+. This will leads to: • [1] Na+ enters the enterocyte • By passive diffusion down its electrochemical gradient. • By Na+- Cl- co-transport system (major mechanism). • By a Na+-glucose, Na+-amino acid, Na+-(di- or tri-) peptide or Na+- water-soluble vitamins (except B12 and folic acid) co-transport system (Na+ enhances glucose absorption in the Glucose-saline solutions). • By Na+-H+ counter-transport

18. [2] Cl- enters the enterocyte through • Passive diffusion down its electrochemical gradient established by the active transport of Na+. • Na+-Cl- co-transport (major mechanism). • Cl--HCO3- counter-transport.

19.  In the small intestine  Na+–glucose cotransport, Na+–amino acid cotransport, and Na+–H+ exchange mechanisms are most important.  In the colon  passive diffusion via Na+ channels is most important.

20.  The Na+ channels and Na+-K+- ATPase of the colon are similar to those in the renal distal tubule and are stimulated by aldosterone.  Dehydration  aldosterone secreted by the cortices of the adrenal glands  within 1-3 hr   sodium absorption by the intestinal epithelium   absorption of chloride ions, water, and some other substances.

21.  This effect of aldosterone is especially important in the colon because it allows virtually no loss of sodium chloride in the feces and also little water loss.  However, in doing so, it causes significant amounts of K+ to be lost from the body.

22. Colonic reabsorption of Na and secretion of K ions.

23. [3] Absorption and secretion of K+ ions  The daily dietary K+ intake 100 mmol is excreted by the distal tubules of the kidney.  10% of the ingested K+ is excreted via the intestine.  85 % of ingested K is reabsorbed across the intestinal mucosa through simple diffusion mainly via paracellular route .  As water is absorbed from the lumen, rising potassium levels in chyme create a concentration gradient for its absorption.

24.  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.  In large intestine, K+ is actively secreted in the colon by a mechanism similar to that for K+ secretion in the renal distal tubule which is stimulated by aldosterone.

25.  In diarrhea, K+ secretion by the colon is increased because of a flow rate–dependent mechanism similar to that in the renal distal tubule.  There is less for [K+] in colon to rise up to significant level to act as chemical gradient force against the active and passive secretion of K.  Therefore, excessive loss of K+ in diarrheal fluid causes hypokalemia.

26. Absorption of water  Water is transported across the small intestinal membrane entirely by the process of osmotic diffusion or through paracellular route between the enterocytes.  Most of the water in the GIT is absorbed in the jejunum. Duodenum serving as the site of osmotic equilibration of chyme.

27.  Most of the remaining water and electrolytes are absorbed in the proximal half of the colon absorbing colon.  The distal colon functions for storage  the storage colon.  In contrast to the small intestine, the colon has a limited capacity to absorb water (3 to 6 L per day). This is because the highly impermeable nature of the tight junctions connecting the colonic epithelial cells.

28. Absorption and secretion of bicarbonate ions in the intestine  Absorption of bicarbonate from the small intestine occurs in the jejunum.  Bicarbonate ions reabsorbed from the upper small intestine in form of CO2 which is readily absorbed into the blood and expired through the lungs.  This is important because large amounts of bicarbonate ions have been secreted into the duodenum in both pancreatic secretion and bile.

29.  The mucosa of the large intestine actively secretes bicarbonate ions.  It actively absorbs equal amounts of chloride ions in an exchange transport process (Cl--HCO3- counter-transport).  The bicarbonate helps neutralizing the acidic end products of bacterial action in the colon.

30. Intestinal Ca2+ absorption  Ca2+ is reabsorbed in the duodenum and upper jejunum.  About 30–80% of dietary Ca2+ typically is absorbed and is exactly controlled in relation to the need of the body for Ca2+. [A] 1/3 of the net Ca2+ uptake occurs passively via the paracellular route across the tight junctions. [B] 2/3 of the net Ca2+ uptake occurs actively through regulated Ca2+ transport pathways in the enterocytes and is stimulated by vitamin D as follows:

31. ■ Ca2+ enters the enterocytes due to electrochemical gradient via the Ca2+ channels. ■ to prevent  in intracellular free Ca2+ concentration, Ca2+ binds to the protein calbindin within the cytoplasm, the synthesis of which is totally dependent on vitamin D. ■ Extrusion of Ca2+ from the cells occurs by primary active transport (Ca2+-ATPase) and secondary active transport (3Na+/Ca2+ exchange), against a large electrochemical gradient.

32. Vitamin D increases synthesis of calbindin and both apical and basolateral transporters. It is inhibited by phosphates and oxalates because these anions form insoluble salts with Ca2+ in the intestine. Fe++ ions are actively absorbed from the small intestine which is regulated according to the body need. K, Mg, phosphate, and other ions can also actively absorb through the mucosa.

33. The vitamin B12-intrinsic factor complex is propelled along the small intestine to the terminal ileum.  Specific transporters located on the enterocyte microvilli bind it.  Binding requires calcium and is optimal at pH 6.6.  Absorption is an active transport process.

34. Regulation of intestinal Ca2+ absorption.