What are 3 main functions of Gastric Juices?
- Intrinsic factor (IF)
- B12 uptake in terminal ileum
- Absence of IF by destruction of parietal cell leads to B12 deficiency
- Results in Pernicious anemia
- Mucus-bicarbonate barrier
- Protect from gastric mucosa from HCl
- Prevents digestive action of pepsin on the walls of the stomach
- Hydrochloric acid
- Activates Pepsinogen into Pepsin
- Kills some bacteria entering stomach
3. Protein Digestion
- Regulated by Vagal stimulation
- Only secreted with low gastric pH
How is acid secreted from Parietal Cell?
1. CO2 and H20 passively enters parietal cell
- Converted to H+ and HCO3- by Carbonic Anhydrase
2. H+ moves out of the cell into the gastric lumen by H+-K+ Pump (ATP needed)
- In exchange for K+
- HCl depends on H+-K+ Pump
3. Cl- passively moves into the gland lumen from cell
- H+ and Cl- bind together in the lumen creating HCl
4. HCO3- exits basolateral membrane
- By Cl-HCO3 exchanger
*Na+-H+ exchanger regulates intracellular pH
What does the Vagus Nerves stimulate Directly?
1. Parietal Cells
- NT: ACh
2. G cells
- NT: GRP
How does Gastrin indirectly stimulate Parietal Cells?
1. Vagus Nerve stimulates G cells
- Releasing Gastrin
2. Gastrin enters systemic circulation
- Delivered back to stomach
3. Gastrin simulates H+ from the Parietal Cells
*Gastrin binds to CCKb receptors
- Stimulates the release of Histamine from ECL cells
What are Antimuscarinic agents?
- Blocks M3 receptors of Parietal Cells
- Blocks only Direct simulation of Parietal cell from the Vagus Nerve
- However, does not block HCl secretion completely
*Vagus stimulates ACh affecting M3 receptor on Parietal cells
- Goes through Gq (PIP2, IP3, DAG, Ca release fro ER, Protein Kinase C, Phospholipase C)
What is Gastrin-receptor antagonist?
- Blocks CCKb receptors
- Prevents release of Histamine
*G cells release Gastrin
- Binds to CCKb receptors going through Gq
- IP3 and Ca release
What is H2R Antagonist?
- Blocks histamine action on parietal cells
*H2 Receptor goes through Gs
- Increase cAMP (Adenyl Cyclase, phosphokinase A)
What are Inhibitors of the proton pump?
- Inhibits H+ and K+ ATPase
- Inhibit H+ transport to gastric lumen
- Preventing H+ to bind to Cl-
What is Prostaglandins E2?
- Inhibits HCl secretion
- Simulates secretion of mucus and bicarbonate
*NSAIDs inhibit prostaglandin
- Increase HCl
- Results in Erosive gastritis or peptic ulcers
What are Mucosal protective agents?
1. Sucralfate (subcitrate)
- Binds to ulcers and coats it
- Protects from acid and pepsin
- Stimulates prostaglandin release
- Mucus and bicarbonate output
What is Somatostatin?
1. Inhibits H+ secretion through both direct and indirect pathway
2. Inhibits histamine release from ECL cells
3. Inhibits gastrin release from G cells
What are 4 Inhibitors of Gastric Secretion?
- Inhibits G cells (gastrin inhibited)
- Inhibit parietal cell secretion
- Inhibit G cells and Histamine from ECL cells
- Inhibit parietal cell secretion
What is H.pylori?
1. Contains Urease
- Converts urea to Ammonia
- Alkalize environment
- Allows H. pylori to survive in gastric lumen
2. Urea breath test
- Patient swallows 14C-urea
- Urease converts urea to ammonia and 14CO2
- Detects CO2 output
3. Inhibits Somatostatin secretion
- Stimulates H+ secretion
4. Inhibits HCO3 secretion
What occurs during vomiting?
1. Stomach becomes Metabolic Alkalosis
2. Loss of HCl from gastric lumen
3. No HCl can arrive to small intestines to stimulate pancreatic HCO3-
- Arterial blood becomes alkaline
What is Pepsinogen?
1. Secreted from Chief cells
2. Initiates protein digestion
3. Activated by Vagal stimulation of chief cells
- Low pH needed
What is Zollinger-Ellison syndrome? (Gastrinoma)?
1. Gastrin-secreting tumor of the pancreas
- Acid-secreting cells at maximal activity
- Results in Gastrointestinal mucosal ulceration
2. Increase numbers of parietal cells
3. Hypertrophy of gastric mucosa
4. Increase Basal Acid Output
- Used for diagnosing ulcers and Zollingers
5. Leads to Diarrhea and malabsorption
- Increase acidity inactivates pancreatic enzymes
6. Increase in Insulin, Glucagon, and Gastrin
What are Brunner's glands?
- Above Sphincter of Oddi
- First part of Duodenum
- Produce alkaline mucus and Urogastrone
- Inhibits parietal and chief cells
- Protect duodenum from acidic chyme
- Lubricates intestinal walls
What are 2 types of Cl- Channels in the Intestines?
1. cAMP- activated CFTR Cl- ion Channel
- NT: VIP
2. Ca2+ -activated Cl- channel
- ACh and Serotonin are both secretagogues (promotes secretion)
What is Cystic Fibrosis?
1. Mutation of CFTR gene
- On long arm of Chromosome 7
2. Abnormal thick mucus secretion
- Cl- unable to pass through cell surface due to thick mucus
*CFTR protein allows for Cl- to pass through
- Sweat will have elevated Cl-
- Indication of Cystic fibrosis
What are the properties of the Large Intestines?
1. Secretes Bicarbonate
- Pt with diarrhea loses bicarbonate
- Cause metabolic acidosis
2. Secretes Potassium
- Diarrhea can lead to Hypokalemia
*Aldosterone and Glucocorticoids
- Increase Sodium absorption and Potassium Secretion
What is VIPoma?
1. Pancreatic endocrine tumor
- From Islet cells
- Produce VIP (Vasoactive intestinal peptide)
2. Signs and Symptoms
- Watery diarrhea
- Fluid and electrolyte replacement
- Mimics Somatostatin