02-14 Gastric Acid Secretion

Question 1

OBJECTIVE: Describe the anatomy of the stomach by region

• function of region (3 major fxns BOLDED)
• secretion in region

Answer 1

Three regions:

1. cardia/(LES technically esophagus)
   
   • fxn: let food in, ctrl belch/reflux
   • secretion: mucus & HCO3-
2. fundus and corpus
   
   • fxn: RESEVOIR, tonic force for EMPTYING, gastric acid prod
   • secretion: mucus & HCO3- plus:
     
     • H+ & IF (parietal cells)
     • pepsinogens (chief cells)
     • lipases
3. antrum and pylorus
   
   • fxn: crush/mix food, sieving, ctrl emptying
   • secretion: mucus & HCO3- PLUS
     
     • somatostatin
     • gastrin

Question 2

OBJECTIVE: Name the different gastric gland + their location, cells they contain and products

Answer 2

Foveolar cells (Stomach verion of goblet cells seen in bowel) are everywhere

• Located: throughout stomach
• Fxn: secrete mucus
• Come from mucous neck cell → precursor cell

Oxyntic Glands (Fundus & Body)

• Parietal Cells: HCl & IF
• ECL Cells: histamine
• Chief cells (at bottom of gland): pepsinogen, gastric lipase
• D Cells: somatostatin paracrine

Pyloric Glands (Pylorus & Antrum)

• G-cells: gastrin
• D-cells: somatostatin

Question 3

Histo layers of stomach

Answer 3

1. mucosa
2. deep mucosa or lamina propria
3. submucosa
4. muscularis propria
5. serosa

Question 4

OBJECTIVE: parietal cell in resting vs. stimulated state

Answer 4

RESTING STATE

• PPs are inside tubulovesicles and inactive
• canaliculus is collapsed
• low flow of acid (one yellow pump on the canaliculus)

STIMULATED STATE

• tubulovesicles fuse w/ canaliculus which expands
• the now-active PPs exchange H for K, and create HCL → lumen

Question 5

The proton pump is actually what type of enzyme?

Answer 5

H+/K+-ATPase anti-porter

Question 6

alkaline tide

Answer 6

efflux of HCO3- into bloodstream as byproduct of gastric acid production

Question 7

Describe the 3 types of signal transmission in stomach.

Answer 7

1. neurocrine
2. endocrine
3. paracrine

Specifics on next slide.

Question 8

OBJECTIVE: Name the neurocrine, endocrine, and paracrine mechanisms that regulate acid secretion by the parietal cell

Answer 8

1. ENDOCRINE apical side of endocrine cells have microvilli facing lumen
   
   • respond to a specific aspect of the intraluminal milieu such as pH/somolality ∆ or specific nutrients.
   • Hormonal acid mediators: CCK, gastrin, glucose insulinotropic peptide (GIP), secretin
2. NEUROCRINE

• Nerves (secretomotor neurons) sense stimuli (nutrients, pH, osm) in lumen + mov’t of contents/distension
• msg can go to ENS or CNS or both. In both cases, activation → ∆s GIT secretory or motor activity
• Neurotrans acid mediators: Ach, gastrin releasing peptide (GRP)

1. PARACRINE
   
   • Hay solamente few paracrine responses
   • help reg acid secretion.
   • Paracrine acid mediators: 5-HT, and somatostatin.

Question 9

OBJECTIVE: Name and describe the different phases of gastric acid secretion

Answer 9

Interdigestive: basal secretion; 15% of acid for meal

Cephalic: smell, sight, thought, taste, swallowing of food triggers; 30% of acid for meal

• vagus → ENS (nerv trans) →
  
  • ACh→ direct parietal stim
  • ACh→ ECL (para) → histamine → parietal
  • ACh & GRP (nerv) → G-cell → gastrin (endocrine) → ECL → histamine → parietal

Gastric, 50% of acid secreted for a meal:

1. incr in pH from food entering stomach shuts of inhibitory somatostatin production by pH sensing D-cell → allows vagal msg to “be heard” by the G cell
2. distention increases vagal firing ramping up cephalic processes listed above
3. AAs and protein stimulate G-cells to release gastrin directly

**Intestinal Phase **only 5% of acid for meal

1. Poorly understood: complex interplay of stim and inhib
2. Stimulatory factors:
   
   • Amino acids in small intestine (and plasma) stimulate gastrin release
3. Inhibitory factors:
   
   • Chyme in upper intestine inhibits gastric acid secretion, possibly via secretin/GIP

Question 10

Why do ulcer pts get pain ~2hrs after meal?

Answer 10

see image

Question 11

OBJECTIVE: Explain the acid-electrolyte composition of gastric secretion and how it becomes modified at different levels of acid secretory activity.

Answer 11

• at low rates of secretion (resting), it’s mostly NaCl sol’n w/ HCO3- pH = 4
  
  • little H+
• at higher rates of secretion (w/ stim), K+ and Cl- increase slightly and H+ goes through the roof (pH < 1.5)

You can think of these as two separate secretions (Two compartment model: parietal and non-parietal):

1. the low rate secretion is a constant, basal secretion of a more alkaline sol’n w/ ~same [Na+] as plasma
2. high rate secretions are a separate acidic secretion

At rest non-parietal dominates

w/ stim parietal secretion dominates

Question 12

OBJECTIVE: What are the metabolic consequences of prolonged vomiting?

Answer 12

• dehydration
• Alkalosis
  
  • hypochloremic
  • contraction
• hypokalemia
• hypochloremia

Question 13

OBJECTIVE: What are the changing patterns of intragastric fluid volumes and electrolyte and acid contents during the course of a meal?

Answer 13

see image

Question 14

OBJECTIVE: Describe the mucosal barrier in the stomach.

Answer 14

Gastric mucosa prevents H+ back leakage allowing million fold [H+] gradient.

• *Visible mucus**: gel, that entraps the alkaline component of surface cell secretion + dead/shed mucus-containing surface cells
• *Insoluble mucus**: protects mucosa from both physical and chemical damage during meal
• neutralizes some acid (by precipitates into clumps and passes into duodenum w/ chyme)
• prevents pepsin from coming in contact w/ mucosa.

Question 15

OBJECTIVE: What are the anti-secretory meds we covered? Mech/site of action?

Answer 15

• PPIs - irreverisbly inhibit H/K-ATPase proton pump
  
  • omeprazole, pantoprazole, esomeprazole, rabeprazole, lansoprazole
• H2 blockers - block basal secretion of acid mediated by histamine from ECL cells
  
  • famotidine (Pepcid AC) is strongest, others include cimitidine, ranitidine, & nizatidine
• cholinergics - none are specific to the M3 muscarinic ACh receptor, not really clinically helpful just mechanistic point
  
  • metoclopramide
  • theoretically could use atropine but too many side effects