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14- Secretion and non occlusive ischemic gut.docx

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PHGY 313
Russell Jones

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Lecture 14 - Neural Control of GI function & salivary glands Presented by: Nour Malek Today's lecture will be in two parts: 1. Understanding the small intestine and its functions 2. Secretory glands since they're important Brief overview of digestion: Chyme goes to small intestine and leads to the secretion of secretin and CCK.  Secretin causes the release of alkaline pancreatic juice and alkaline bile  CCK causes more pancreatic juice secretion, contraction of gall bladder, and relaxation of sphincter of Oddi. o Important because we don't want the lumen of the small intestine to be too acidic or lipid absorption won't occur without a neutral/alkaline environment  95% of water we take in is absorbed in SI Cholera: What is it?  Massive loss of fluids  Note: tetracycline inhibits bacterial growth by inhibiting protein synthesis Case Study 1. What causes the symptoms? a. At the tips of villi there are cells that absorb water and ions. b. Rate of water transport differs and how it diffuses depends on osmotic gradient, which depends on the potential difference across the membrane. Anions can passively diffuse in the membrane. Active transport of Na+ across the basolateral border (passive across apical membrane) c. The Na+ gradient provides the driving force for the inward movement of 2 Cl anions into the cell with 1 Na and 1 K+. The K+ immediately exits into the lumen to balance the gradient. Cl- then goes to the lumen through CFTR. Na+ also enters the lumen by going between cells down its gradient. This makes the lumen more hypertonic and lets water flow into lumen. d. Cholera virus binds to Gm1 receptors in brush borders, increases cAMP levels, which prolongs the opening of CFTR channels. This causes more Cl- and Na+ to move into lumen, and water follows. This will lead to diarrhea.4 types of diarrhea: i. Secretory- secretions are too high for colon to reabsorb efficiently ii. Poor Na+ transport- water follows ionic movements so inhibiting Na+ flow inhibits water flow iii. Osmotic diarrhea- lumen filled with hypertonic fluid (same as lactose intolerant patients) iv. Hypermotility (Water not absorbed fast enough). Cholera patients suffer from secretory diarrhea. e. Hypokalemia: In addition to diarrhea, there's hypokalemia. The more Na and Cl moving into lumen means more K+ taken out of cell to balance the gradient. If it's less than 25mM, it's dangerous because K+ allows the excitability of cells. Messing with its concentration can cause defects in neurons, skeletal muscle, and arrhythmias. f. Acidosis: Increased secretions of HCO3 into the lumen so more H+ flows into the blood and acidosis occurs. 2. What is the rationale behind the treatment? a. Keep in mind Na permeability changes across the intestine, so it's HIGH in duodenum and lower in ileum. Change in permeability is due to brush border surface areas go down and tight junctions less leaky. Na+ is reabsorbed via different transporters: i. Na/K ATPase pump (apical border)- maintains electrochemical gradient ii. Na/H+ HCO3- neutralizer- Na+ is transported out against a high gradient for H+ to come in and neutralize HCO3- iii. Na+ dependant glucose transporter SGLT 1-Symport of Na and glucose/galactose back into the cell from the lumen but inhibited by K+. b. IV replaces fluid because it's isotonic. Less water will be secreted. 3. Are changes in the intestinal motility involved in this condition? a. Motility is important because it 1) mixes digestive fluids with chyme and 2) keeps things moving along the intestine. i. Spontaneous motility- ONLY depends on movement of stomach (oscillating membrane potentials) ii. Migrating myoelectric complex- Depends on nerve stimulation b. In cholera, the large secretion of water into the lumen causes distention in the lumen, where stretch activated receptors cause hypermotility. 4. What are the main cell types in the intestinal epithelium? a. Absorptive columnar Cell- Absorbs things from tip of the villi. Makes up 90% of epithelium. Rich in mitochondria, low in ribosomes, and have microvilli to increase sndface area. b. Goblet- 2 most common cells in epithelium covering villi. They move up from the base to the tip of the villi as they mature. They produce a glycoprotein, and are replaced every 6 days. c. Paneth cells- aka granular cells. Protect from bacteria and located in the crypts of Lieberkuhn. High levels of rER and golgi in order to produce and secrete enzymes d. A
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