L11- Gastroduodenal Secretions & Control Flashcards
Gastric Secretions
- HCl
- Intrinsic factor
- Pepsinogen
- Mucus
- Bicarbonate
- Gastrin
- Histamine
Secretions of Gastric Cell Types
A. Surface Epithelial Cells
- Secretes mucus and an alkaline fluid (bicarbonate)
- Protects epithelium from mechanical injury & gastric juice
B. Neck Mucous Cells
- secretes mainly mucus, some pepsinogen
C. Chief (Peptic) Cells
- secretes pepsinogen
D. Parietal (Oxyntic) Cells
- Secretes HCl & Intrinsic Factor
E. Enterochromaffin-Like Cells
- secretes histamine
F. D-cells
- secretes somatostatin
G. G-cells
- mainly pyloric glands
- secretes gastrin
Functional Anatomy of the Stomach
A) Cardiac glandular region
- secretes mucus
B) Proximal/body (80%)
- oxyntic gland mucosa
- parietal, chief and mucous neck cells
- Secretes HCl, Intrinsic factors, pepsinogen
C) Pylorus Distal (Antral, 20%)
- Pyloric gland mucosa
- Mainly Gastrin & Mucous cells, few chief cells, almost no parietal cells
- Secretes gastrin, small amount of pepsinogen, mucus
Rate of secretion of gastric juice
Rate of secretion controlled by endocrine, neural and paracrine signals.
Property and ionic composition of gastric juice
- Gastric juice is isotonic to plasma
- pH ranges about 2-3
- Ionic composition various with the rate of gastric secretion
- Basal rate: primarily NaCl
- Increase [H+] [Cl-] with incease in secretion rate
- Basal rate greater at night, lowest in early morning
Gastric Acid Functions
- Converts inactive pepsinogen to active pepsin
- Provides optimal pH for pepsin activity
- Denatures ingested protein
- Breaks up cells & connective tissue
- Bacteriostatic
Intracellular mechanism of HCl secretion
The followings occur in parietal cells:
1) Intracellularly, CO2 and H2O react to form carbonic acid, catalyzed by Carbonic anhydrase (high concentration in parietal cells)
2) Carbonic acid then dissociates into H+ ion and HCO3-
3) The bicarbonate ions move out of the parietal cells on the capillary side, in exchange for chloride ions through an exchange pump
4) Cl- released on lumneal side
5) Intracellular H2O, on the other hand, breakdown into Hydrogen ion and hydroxide ion
6) Hydrogen ion produced by breakdown of water then secreted into the lumen by primary active transport and exchange pump
7) Hydroxide ions formed from water are neutralized by combination with hydrogen ions generated from CO2 and H2O
Control of Gastric acid secretion
STIMULANTS
Paracrine - Histamine
- Histamine released from ECL cells
- Act on H2 receptors on parietal cells
- Strongest stimulant of HCl secretion
Neurocrine - vagal stimulation
- Depends on neural input from vagal nerve
- ACh acts on muscarinic receptors (M1 in ECL cells, M3 in parietal cells)
- Stimulates release of HCl by parietal cells; histamine by ECL cells; (gastrin by G-cells?)
Endorcine - Gastrin
- Secreted by G cells
- Stimulates histamine release and synthesis by ECL cells
- Trophic effects on ECL cells
- Stimulates acid secretion by parietal cells via CCKB receptors
INHIBITOR
Somatostatin
- inhibits gastric secretion
Secondary messengers in gastric acid secretion control
Histamine (Paracrine)
- Histamine binding with H2 receptor will activate adenylyl cyclase, leading to increase in cAMP
Vagal Nerve (Neurocrine)
- Acetylcholine binding with muscarinic receptors will lead to IP3, increasing intracellular calcium ion concentration [Ca2+] i
Gastrin (Endocrine)
- After gastrin binding with CKKB receptor, intracellular calcium concentration will increase
Increased Calcium ion & cAMP concentration will activate protein kinase.
Ultimately these intracellular secondary messagers will control the transfer of H+/K+-ATPase (aka Proton Pumps) from cytoplasmic vesicles to plasma membrane, where it can allow the secretion of H+
Drugs targeted to reduce gastric acid secretion
1) H-2 receptor blockers
**- **Tagamet (cimetidine)
- Zantac (ranitidine)
- Pepcid (famotidine)
2) Proton pump inhibitors (PPI)
- Prilosec (omeprazole)
- Nexium
Antrectomy
Antrectomy (distal gastrectomy) is a procedure in which the portion of the stomach distal to the antrum is excised.
Before availability of effective antacid drugs, this is used to treat hypersecretion of HCl as it will remove majority of the G cells in antrum. Leading to decreased gastrin release and reduced HCl secretion
Gastrinoma
A tumor in the pancreas or duodenum that secretes excess of gastrin. There is hypersecretion of the HCl acid into the duodenum leading to ulceration. Excessive HCl acid production also causes hyperperistalsis, and inhibits the activity of lipase, causing severe diarrhea.
Functional Phases of Gastric Secretion
1) Cephalic Phase
2) Gastric Phase
3) Intestinal Phase
Cephalic Phase of HCl Secretion stimulation
Stimuli: Chewing, swallowing, taste and smell of food
-> Vagal impulse excite enteric secretomotor neurons to parietal, G and ECL celss
Gastric Phase of HCl Secretion stimulation
Stimuli:
1) Gastric distension (-> Local and vagovagal reflexes stimulate parietal cells and release of histamine and gastrin)