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The stomach
Lecture 3
31
Pharmacology
Professional
10/20/2012

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Term
What is the purpose of the mesenteric membranes?
Definition
Keep the stomach in place -- lesser and greater omentums
Term
What is the anatomy of the stomach?
Definition
- Cardial stomach - portion right after the stomach. Produces ONLY mucus
- Fundus - raises up. Mucus, gastric acid, enzymes, and intrinsic factor
- Body/corpus - main part - MOST amount of gastric acid, mucus, and intrinsic factor.
- Antrum - just before pyloric. Mucus, enzymes, and the HORMONE gastrin
- Pyloric canal- empties into duodenum, ending at the pyloric sphincter. ONLY mucus.
** folds called rugae, allow for expansion
Term
What parts of the stomach secrete intrinsic factor? What is it?
Definition
The fundus and the body/corpus. Required for absorption of b12
Term
What is the anatomy of gastric glands?
Definition
- Chief cells - produce enzymes
- Parietal cells - produce acid and intrinsic factor
Term
How large can the stomach expand to?
Definition
Up to 4 L, expanded by chyme and gastric juice
Term
What provides blood flow to the stomach?
Definition
Right and left gastric arteries
Right and left gastropiploid arteries
Not much nutrient absorption, what is absorbed goes to the hepatic portal vein.
Term
What are the major functions of the stomach?
Definition
- Temporary storage of food - receptive relaxation through VIP, NO, CCK. MAIN FUNCTION
- Mechanical breakdown of PROTEINs by HCl and pepsin
- Mixing - formation of chyme
- Propulsion towards intestines
- Production of intrinsic factor
Term
How is gastric emptying controlled?
Definition
- By BOTH stomach distention and duodenum
- Vagal PSNS stimulation increases motility
- Gastrin - slows emptying, signalled by proteins
- Enterogastrones are inhibitory - CCK, Secretin, GIP
- Duodenum has reflexes to the presence of acid, irritation, foods, and distention --> inhibition
** goal is to slow emptying, allow stomach to work longer.
Term
Where is acid secreted in the stomach?
Definition
In the gastric lumen. Beneath that is (should be) a mucous/bicarbonate layer to protect the COLUMNAR/goblet cells of the stomach.
Goblet cells produce mucus, columnar cells produce bicarb.
Term
How are parietal cells activated?
Definition
Activated during meals - TV turn into microvilli and intracellular canaliculus is developed. Hydrogen/potassium ATPase pump is active.
**An active parietal cell secretes acid and intrinsic factor!
Term
What secretagogues are responsible for acid release?
Definition
- Ach -- on M3 receptors - act directly and indirectly by releasing histamine
- GASTRIN - from G cells in antrum - directly and indirectly by histamine release
- Histamine - from EC-like cells
Term
What are mechanisms for direct acid release from parietal cells?
Definition
- Ach acts on M3 --> IP3/Calcium --> ATPase pump
- Histamine acts on H2 --> cAMP/PKA --> ATPase pump
- Gastrin acts on CCKb --> IP3/calcium --> ATPase pump
Term
What are mechanisms for indirect release of acid from parietal cells?
Definition
- Ach or gastrin stimulate EC-like cells to release histamine --> histamine acts of H2 receptor of parietal cell --> cAMP/PKA and activation of ATPase pump
Term
What are the steps to the parietal cell forming HCl?
Definition
- Gastrin, histamine, or Ach directly or indirectly stimulate the cell, activating the ATPase pump
- carbonic acid breaks down bicarb into hydrogen ions.
- ATPase exchanges H/K, while and exchanger brings Cl inside the cell in exchange for HCO3-
- Chlorine and K channels exist, allowing the Cl- and K+ to leave. H+ + Cl- = ACID!
Term
What are functions of high acidity in the stomach?
Definition
- KILL microorganisms present in food
- Denature proteins
- Break down plant cell walls
- Activation of pepsinogen released from chief cells.
Term
What can inhibit secretion of acid endogenously?
Definition
- Prostaglandins - from stomach. reduce cAMP
- Stomatostatin - from D cells
- Enterogastrones: Secretin (S cells), CCK (I cells), GIP (K cells), VIP (enteric nerves)
Term
How do infant chief cells differ from adult physiology?
Definition
Pepsinogen is not produced - rennin is produced that breaks down only milk.
Term
What is the only function of the stomach necessary for life?
Definition
Manufacture of intrinsic factor
Term
How is cobalmin handled by the stomach/small intestine?
Definition
- Bound to proteins in food, released in the stomach by acid.
- Parietal cells secrete intrinsic factor
- Haptocorrin binds to B12 in the stomach, prevents degradation. Removed in the small intestine
- In the small intestine, IF-B12 complex forms. B12 can now be absorbed.
Term
What are the 4 phases of digestion?
Definition
- Cephalic phase - prepares the stomach for the arrival of food. 20% of acid secreted. Under Vagal control
- Gastric phase - 60-70% of acid. Stimulation of receptors by food. PEPSIN breaks down protein. ENS and vagovagal reflexes inhibit D cell release of somatostatin
- Intestinal phase - control rate of gastric emptying, last phase of acid release
- Interdigestive phase
**Acid is it's own negative feedback
Term
What are the function of Ach in the stomach?
Definition
- Direct binding to parietal cell --> acid release
- Binds to M3 on chief cells - pepsinogen release
- M3 on EC-like cells - histamine release --> parietal cells
- Bind to G cells to release gastrin --> parietal cells
** Ach moderates acid cleavage of pepsinogen to pepsin!
Term
What happens if acid or fat gets into the small intestine?
Definition
Neural response - increase in SNS, constriction of pyloric sphincter. Decrease in PNS
Release of CCK, Secretin, and GIP to slow gastric emptying.
Enhanced digestion in the STOMACH.
Term
What do enterogastrones stimulate?
Definition
- CCK (I cells) - stimulates pancreas acinar cells and gallbladder
- Secretin (S cells) - stimulates pancreas duct and liver - bicarbonate and bile
- All 3 - Inhibits stomach release of gastrin, acid, and pepsinogen.
Term
How are ghrelin levels effected by consumption of meals?
Definition
- Low during consumption of meals
- High during fasting
** stimulates GH secretion
** stimulates appetite
Term
How does leptin control body weight?
Definition
Leptin is released from adipose, turns off appetite.
**More adipose, less of an appetite.
Term
What is gastritis?
Definition
Inflammation of the rugae, can be caused by H. pylori
Term
What is peptic ulcer disease?
Definition
An ulcer in the GI tract that is usually acidic.
- Gastric ulcer - in the stomach. Usually decreased protection in MUCOSA rather than oversecretion of acid
- Duodenal ulcer - in duodenum. Increased parietal cells = increased acid/pepsin, increased SENSITIVITY to gastrin
- Esophageal ulcer - in esophagus, usually caused by GERD
Term
What are the major causes of PUD?
Definition
- H.Pylori - more duodenal ulcers. MOST COMMON CAUSE
- Impaired mucosa - NSAIDS!, steroids, stress
- Hypersecretion - Zollinger-ellison --> elevated gastrin release
Term
What is H. Pylori?
Definition
A lifelong infection of a bacteria that burrows into the stomach and intestinal lining. Burrows into the antrum or duodenum to protect itself from acid.
** Production of ammonia to neutralize acid
** Initiation of inflammatory response --> injection of CagA --> NFkB --> release of IL-8 attracts PMNs and release of TNF and IL-1.
** Humoral and Cellular immune rxn leads to chronic inflammation
Term
How do NSAIDs cause PUD?
Definition
- Loss of epithelial cell fxn - mitochondria uncoupling
- Inhibition of prostaglandin synthesis through COX inhibition --> decreased mucus, bicarb, and increased acid
- increased free radicals
- direct toxicity
**Attraction of NEUTROPHILS promotes inflammation
Term
What is zollinger-ellison syndrome?
Definition
The least common source of PUD, tumors produce excessive gastrin --> increased acid release. NO negative feedback!
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