2 - Stomach II: Gastric Secretion

Question 1

Objectives: Descrive how gastric acid secretion is regulated

Equation Summary

Stimulants:

ACh

Histamine

Gastrin

Calcium (Ca²⁺) and cAMP

Answer 1

• Summary: CO2+H2O->H+HCO3
• Stimulants of Acid Secretion:
  
  • Acetylcholine (ACh)
    
    • Binds to Muscarinic receptors on parietal cell membrane
    • (+) Phospholipase C-> IP3 -> release of Ca²⁺
  • Histamine (+Gastrin = STRONG ACTIVATOR)
    
    • Binds to H2 receptors on parietal cell membrane
    • Activates adenylate cyclase to form cAMP
  • Gastrin
    
    • Binds to gastrin/CCK receptors on parietal cell membrane
    • (+) Phospholipase C-> IP3 -> release of Ca²⁺
  • Ca²⁺ and cAMP increase concentration of (H,K) ATPase and Cl- channels in apical membrane

Question 2

Objectives: Descrive how gastric acid secretion is regulated

Potentiation

Histamine

ACh

ECL

Answer 2

• Potentiation
  
  • Occurs with simultaneous administration of TWO stimulants = greater than sum of response from either alone
• Benefit
  
  • Small amounts of substances can lead to large results
• Histamine
  
  • Potentiates actions of gastrin and ACh
  • H2 Receptor Blockers effective in inhibiting acid secretion because they block histamin and potentiation efefct on ACh and gastrin
• ACh
  
  • Potentiates histamine and gastrin
• ECL (Enterochromaffin-like) - Gastrin and ACh receptos
  
  • ​Gastrin stimulates release and synthesis of histamine and proliferation of cells
  • ACh stimulates release and synthesis of histamine (not as much as gastrin) ​

Question 3

Objectives: Descrive how gastric acid secretion is regulated

Inhibitors

Answer 3

• Inhibitors of Acid Secretion
  
  • (-) Low pH inhibits Acid Secretion
    
    • ​After meal, pH rises, leading to acid secretion
    • As stomach empties, pH drops
    • Gastrin release inhibited - negative feedback mechanism
  • (-) Somatostatin Release inhibits:
    
    • Acid Secretion by parietal cells
    • Gastrin Secretion by G cells
  • (-) Chyme in Duodenum
    
    • Neural and Humoral mechanisms
    • Inhibit Gastrin release by G-cell and/or acid secretion by parietal cell

Question 4

Objectives: Describe phases of gastric acid secretion

Basal Secretion

Cephalic Phase

Gastric Phase

Intestinal Phase

Answer 4

• Basal Secretion
  
  • Initiation: Absence of all stimulation
  • Lowest in evening, highest in morning
• Cephalic Phase - Central processing to vagal nucleus
  
  • Initiation: Chewing, Swallowing
  • Stimulus at Parietal Cell: Acetylcholine released from Vagus n.
• Gastric Phase - Entry of food into stomach
  
  • Initiation:
    
    • a. Distension
    • b. Digested Protein
  • Stimulus at Parietal Cell
    
    • a. Vagovagal and local reflex lead to ACh release
    • b. Gastrin release from G-cells
• Intestinal Phase - Protein digestion in duodenum
  
  • Initiation
    
    • a. Distension
    • b. Digestion Protein
  • Stimulus at Parietal Cell
    
    • a. Hormonal/nervous mechanism
    • b. Gastrin release

Question 5

Objectives: Describe the causes of ulcers

Gastric Ulcer

Duodenal Ulcer

Answer 5

• Gastric Ulcer
  
  • Protective barrier of stomach breaks down; injury by acid and pepsin
  • Usually distal stomach
  • H+ secretion into stomach reduced because some acid leaks into gastric mucosa
• Duodenal Ulcer - Acid entering duodenum
  
  • More common
  • Defect in acid defense mechanism, high acid levels
  • Pepsin potentiates ulcer formation initiated by acid
  • Lower levels of bicarbonate secretion

Question 6

Objectives: Describe the causes of ulcers

Causes of Damage

Answer 6

• Helicobacter Pylori infection
  
  • Almost all ulcer patients infected; breaks down gastric epithelial barrier
  • NH₄⁺ produced by bacteria damage gastric mucosal cells
  • (-) Somatostatin -> (+) Gastrin & (+) Acid Production
• NASAIDs (aspirin)
• Alcohol

Question 7

Objectives: Describe the causes of ulcers

Tratment

Answer 7

• Antiobiotics - H. Pylori
• Proton-Pump Inhibitors - Block H,K ATPase
• Usually combine these + Pepto Bismol

Question 8

Objectives: Explain how vomiting is regulated, and describe the effects of protracted vomiting

Mechanism

Control

Chemoreceptor Trigger Zone (CTZ)

Answer 8

• Mechanism
  
  • Nause and vomiting can occur together or independently
  • Waves of contraction bein in distal small intestin, move GI contents toward stomach
  • Retching = dry heaving
  • Autonomics Firing = salivation, sweating, increased RR, irregular HR
• Control - Medulla
  
  • Stimulation:
    
    • Tickling throat (NTS)
    • Distension of stomach/duodenum
    • Motion sickness
    • Pain
    • Sights / Smells
  • Direct activation causes vomiting w/out nausea or retching
• Chemoreceptor Trigger Zone (CTZ)
  
  • Area Prorema
  • (+) Emetics, Drugs, Radiation Sickness
  • Receptors in Stomach / Duodenum
  • ECL Cells -> Serotonin -> (+)Vomit
    
    • ​Can block with antagonists

Question 9

Objectives: Explain how vomiting is regulated, and describe the effects of protracted vomiting

Morning Sickness

Longterm Effects of Vomiting

Answer 9

• Morning Sickness
  
  • Protect fetus from toxins
  • 5/1000 suffer from hyperemesis
• Effects of Protracted Vomiting
  
  • Metabolic Alkalosis (loss of acid)
  • Hypokalemia due to loss of K+ in vomitus, decreased K+ uptake
  • Hyponatremia due to loss of Na+ in vomitus
  • Dehydration