gastric acid secretion ulcers and GORD

What is the role of Gastric acid

Aids food digestion

optimises pepsin activity

affects drug absorption

defence mechanism against pathogens-bactericidal

Which cells are found in the small intestine

Describe the stomach anatomy

Where is gastric acid produced

parietal cells

forms HCL

stomach pH 2-3

How is HCl produced

CO2 + H20 → H2CO3

H2CO3 dissociates into bicarbonate and H+

H+ is secreted into the lumen in exchange for K+

Using H+/K+ ATPASE

Bicarbonate is secreted into the plasma in exchange for Cl-

Cl- into lumen through ion channels

H+ and Cl- → HCl

Na+/K+ balance restored

What pathways control GA secretion

Neuronal and hormonal pathways

Muscarinic pathway and parasympathetic system

Which hormone controls gastric acid secretion

Histamine

Where is histamine released

Enterochromaffin-like cells

Which cells activate gastric acid secretion

Parietal cell H2 receptors

Control of Gastric Acid Secretion in Parietal Cells step 1

ACh from nerves acting on M₃ receptors

stimulated in response to sight, smell, taste of food

Step 2

Histamine from ECL cells acting on H₂ receptors

 increases H+/K+ ATPase activity

Step 3

Gastrin from G cells 

 acts on cholecystokinin receptors in ECL 

 acts directly on parietal cell

Step 4

PGE₂

inhibits HCl release from parietal cells

stimulates bicarbonate secretion 

Simulation of Gastric Acid Secretion

Initiated by food in stomach

Reflex stimulation of enteric nerves

G cells directly responsive to foodstuffs

Inhibition of Gastric Acid Secretion 

Inhibited by neural and hormonal reflexes

Somatostatin from D cells

Inhibit histamine release from ECL

Directly inhibit parietal cells

Inhibit gastrin release

stage 1 of gastric acid secretion, cephalic phase

• Stimulus: Sight, thought, and smell of food.

• Pathway:

  • Cerebral cortex → Conditioned reflex.

  • Stimulation of taste and smell receptors → Hypothalamus and medulla oblongata → Vagus nerve.

• Effect: Prepares stomach for digestion.

Stage 2 Gastric acid secretion, gastric phase

• Stimulus:

  1. Stomach distension: Activates stretch receptors via vagovagal and local reflexes.

  2. Food chemicals and pH: G cells respond to peptides, caffeine, and rising pH.

• Effect: Gastrin release → Stimulates stomach secretions and activity.

Stage 3 intestinal phase

• Stimulus: Low pH, partially digested food, fats, or hypertonic solutions in the duodenum when the stomach empties.

• Effect:

  • Enteric gastrin briefly released to blood.

  • Slows stomach activity to coordinate digestion in the small intestine.

How does the mucus barrier protect the stomach

Gel polymer of hydrated mucin glycoproteins

Secreted by surface mucous epithelial cells

Generates a continuous alkaline mucus barrier

Protects stomach lining from acid and pepsin

Mucus production under hormonal control

Mucosal damage

If damage occurs

this can have pathological effects

Mucous damaging products are produced more than mucosal protecting products

Peptic Ulcer

Ulceration of stomach and duodenum

Symptoms: heartburn, abdominal pain, bloating

Cause: H.pylori, chronic NSAID use, smoking, stress

Complications: death, gi bleeding,perionitis,cancer

H.pylori

H.pylori damages protective mucus layer

the bacteria colonise the stomach mucosa

Acid passes through weakened mucus layer causing an ulcer

GORD

Symptoms: heartburn, acid reflux, bloating, belchng, pain swallowing

Complications: ulceration, scarring, cancer

doesn’t generate mucus or bicarbonate, contents damage the stomach

H.pylori

thrives in acidic environment

common in population

asymptomatic

How can we treat

Antibiotic therapy

Amoxicillin, metronidazole, clarithromycin

but some resistance

Treatment: Bismuth chelate

Toxic effect on bacteria

Inhibits bacterial adhesion

Inhibits bacterial proteases

Treatment: Antacids

Simple neutralisation of stomach acid 

Sodium bicarbonate (Alka Seltzer)

HCO₃^-  buffers H⁺

Calcium carbonate (Tums, Rolaids)

CO₃^2-  buffers H⁺

Aluminium hydroxide (Gaviscon)

OH-  binds H+

Magnesium hydroxide (Milk of Magnesia)

OH-  binds H+

SCAM acronym

not very effective

can affect the absorption of other medications

can be contraindicated

Treatment: inhibit acid secretion

Targets:

Muscarinic antagonists – obsolete

H₂ antagonists

Cholecystokinin receptor antagonists

Proton pump inhibitors

Muscarinic Antagonists 

M₁ selective antagonist eg. pirenzipine

 Inhibits vagus-induced histamine release

 Non-selective muscarinic antagonist eg. atropine

 Also has direct effects on parietal cells

H₂ Receptor Antagonists

blocks histamine receptor

eg. cimetidine, famotidine

Histamine released from ECL

H₂ receptors on parietal cells

H₂ Receptor Antagonists

disadvanatges

Cimetidine numerous drug interactions

CytP₄₅₀  inhibitor

Decreased phase I metabolism 

Reduced renal clearance

Decreases hepatic blood flow

Reduced liver excretion

Effect on gastric pH increases absorption of acid-labile drugs

Famotidine fewer interactions

PPI profile

• Irreversibly block H+/K+ ATPASE in parietal cell

• Prevent H+ secretion, inhibits HCl

• example: omeprazole, esomeprazole, pantoprazole

PPI MOA

• Passes through stomach→ enteric capsule

• Absorbed in SI into blood

• Accumulate in acid environment of parietal cell canaliculi

• Activated as pro-drug

• Prolonged effect

• Irreversibly blocks proton pump

Potassium competitive acid blockers

Don’t need to be activated, much faster than PPI, stable in acid conditions don’t need capsule

Example of PPI

Binds to K+

Inhibit H⁺/K⁺ ATPase

eg. vonoprazan

Combination Therapy

PPI plus antibacterial therapy 

Decrease acid secretion

Eliminate helicobacter

Combination therapy very effective

Most ulcers heal after 1-2 months

Treatment: Cytoprotective drugs

Enhances mucosal barrier

Alginates: e.g. gavison, forms a barrier between acid and stomach

Sucralfate: Protective barrier at site, stimulate mucus + prostaglandins which act on parietal cells which inhibits HCL secretion

Affects absorption of other meds

Treatment: Prostaglandin agonists

Prostaglandin inhibits HCl

so we use analogues e.g. misoprostol

Effect of Prostaglandin agonists

reduces gastric acid and pepsin secretion via inhibition of ECL cell

stimulates mucus and bicarbonate secretion by epithelium

increases mucosal blood flow by dilator action on arterioles

BUT CAN INDUCE LABOUR

Treatment: NSAID

Block COX, reduces prostaglandins

LEADS to GI irritation

How do NSAIDS affect GI, mechanisms

Direct irritation of stomach lining

Inhibit prostaglandin production via action on COX

Removes cytoprotective effects

Decreases platelet aggregation – increased bleeding

Stomach PG production is mainly by the COX-1 isoform

Celecoxib selective COX-2 inhibitors spare stomach

Achlorhdria

Lack of HCl in stomach

side effect of PPI, surgery, H.P, cancer

PPI

Can affect Vitamin D absrotion

Provide a named example of the drugs

Antibiotics - amoxicillin, metronidazole, clarithromycin

Antacids - sodium bicarbonate (Alka Seltzer), calcium carbonate (Tums, Rolaids), aluminium hydroxide (Gaviscon), magnesium hydroxide (Milk of Magnesia)

Muscarinic antagonists – pirenzepine, atropine

H₂ receptor antagonists - cimetidine, famotidine, 

Proton pump inhibitors - omeprazole (Prilosec), esomeprazole (Nexium), pantoprazole, vonoprazan

Cytoprotective drugs – alginates (Gaviscon), sucralfates, prostaglandin analogues (eg. misoprostol)