Stomach Anatomy and Secretions

Stomach Anatomy

• The cardiac region is a few centimeters around the esophageal opening into the stomach
• The fundus is the part of the stomach above a horizontal line drawn from the cardiac opening
• The corpus (body) is the main part of the stomach between the fundus and pyloric antrum
• The antrum (pyloric antrum) is the dilated part of the stomach before the pyloric region
• The pyloric region includes the pyloric canal and pylorus, which is the opening of the stomach into the duodenum

Stomach Glandular Secretions

• Gastric glands in the pylorus and cardiac regions secrete mucus
• Deep glands in the body and fundus contain specialized cells
• Parietal (oxyntic) cells secrete hydrochloric acid (HCl) and intrinsic factor
• Chief (zymogen/peptic) cells secrete pepsinogen
• Neck cells secrete soluble mucus via vagal stimulation
• Surface epithelial cells in the fundus, body, pylorus, and esophagus secrete insoluble mucus, protecting against mechanical friction and HCl

Characteristics of Gastric Secretion

• Volume: typically 2-2.5 Liters per day
• pH: highly acidic, around pH 1
• Consists of 99% water
• Solids account for 1% of the secretion

Organic and Inorganic Components

• Organic components (0.4%): include enzymes like pepsinogen, gastric lipase, gelatinase, rennin, mucus and intrinsic factor
• Inorganic components (0.6%): hydrochloric acid (HCl), sodium (Na) and potassium (K)

Phases of Gastric Secretion

• Cephalic Phase: Accounts for 1/3 of gastric secretion, triggered by conditioned and unconditioned stimuli involving the vagal nucleus and acetylcholine release
• Gastric Phase: Contributes 2/3 of gastric secretion. It is stimulated by long vagal-vagal reflexes, short submucosal reflexes, and gastrin release
• Intestinal Phase: Inhibitory, triggered by enterogastric reflexes and hormones like enterogastrone

Acid (HCl) Secretion process

• Oxyntic cells possess numerous mitochondria and intracellular canaliculi
• Hydrogen ion concentration in gastric juice is one million times higher than in plasma
• Parietal cells secrete an isotonic solution of HCl
• Parietal cells have a pH of 7-7.2, similar to other cells

Functions of Hydrochloric Acid (HCl)

• Sterilization: Achieved via the high acidity of gastric content (acid chyme)
• Protein Digestion: Facilitates by activating pepsinogens and providing an optimum pH for pepsin
• Hydrolysis: Induces some protein hydrolysis
• Bile and Pancreatic Secretion: Stimulates the flow by promoting secretin release

Additional Functions of HCl

• Gastric Emptying: Plays a role in regulating, as acidic chyme in the duodenum triggers reflex inhibition
• Milk Curdling: Aids milk digestion by prolonging its stay in the stomach
• Iron Absorption: Converts ferric salts to ferrous form, which is more easily absorbed
• Calcium Absorption: Provides an acidic medium that helps ionize calcium and prevents its precipitation

Achlorhydria and Pernicious Anemia

• Destruction of oxyntic cells leads to achlorhydria and pernicious anemia

Inhibitory Factors of HCl Secretion

• Certain gastrointestinal hormones
• Enterogastric reflex
• Prostaglandins (especially E), which antagonize histamine effects, resulting in decreased cAMP levels

Stimulatory Factors of HCl Secretion

• Acetylcholine (ACh) stimulates M3 muscarinic receptors, increasing intracellular calcium
• Histamine stimulates H2 receptors, which increases cAMP levels
• Gastrin H directly stimulates gastrin receptors, which increases intracellular calcium. It also indirectly increases histamine release from EC1 enterochromaffin-like cells

Mucosal Barrier Composition

• Insoluble mucosa gel-like layer
• Integrity of mucosal membrane
  • Impermeable to H+ ions
  • Actively pumps H+ into the lumen and Na+ into the intestinal fluid
• Prostaglandins stimulate mucus secretion and HCO3- production, reduce acid secretion, and increase mucosal blood flow

Additional Mucosal Barrier Info

• Hydrochloric acid (HCl) secreted crosses this barrier in finger-like channels, leaving the gel layer intact
• Bicarbonate (HCO3) is trapped in the mucus gel, creating a pH gradient

pH Gradient

• pH is 1-2 at the luminal side and 6-7 at the surface epithelium

Causes of Peptic Ulcers: Breakage of Mucosal Barrier by:

• Alcohol
• Aspirin & non-steroidal anti-inflammatory drugs (NSAIDs)
• Helicobacter pylori bacteria
• Prostaglandin (PG) reduction which affects mucus and HCO3 secretion

Cellular Changes Due to Barrier Damage

• Hydrogen (H+) diffuses from the lumen into cells
• Sodium (Na+) diffuses from plasma into cells
• Increased H+ and Na+ result in high intracellular concentrations
• Damages cellular metabolic functions, leads to ulcer formation

Causes of Peptic Ulcers: Excess HCl Secretion

• Zollinger-Ellison Syndrome: Overgrowth of APUD cells in the pancreas, leading to increased gastrin in the blood and, subsequently, increased HCl and duodenal ulcers

Peptic Ulcer Treatments:

• Block H2 receptors (histamine): e.g., cimetidine
• Inhibition of H+ - K+ ATPase in apical membrane: e.g., omeprazole

Peptic Ulcer treatments

• Eradication of Helicobacter pylori: Use of antibiotics
• Avoidance of non-steroidal anti-inflammatory drugs, NSAIDs
• Surgical removal of gastrin-secreting tumors

Intrinsic Factor

• Parietal (oxyntic) cells in the body and fundus of the stomach secrete
• It is essential for vitamin B12 absorption in the lower ileum
• Deficiency leads to decreased B12 absorption, leading to pernicious anemia

Pepsin Secretion

• Chief or peptic cells of the gastric glands secrete pepsinogen, which is converted to active pepsin by HCl
• Start protein digestion as a proteolytic enzyme
• Works as an endopeptidase, breaking down proteins into peptones, proteoses & polypeptides at an optimum pH 1.5 – 3.2

Gastric Motility: Distal Motor Unit

• Antrum, Pylorus, and Sphincter contribute to the processing and emptying of gastric contents
• The thick wall facilitates mixing and emptying
• Peristalsis is stronger and faster in the pylorus

Contractions

• The contractions start in the antrum, move through the pylorus, and end in the duodenum
• Pylorus contracts for longer than the duodenum does
• Partial contraction of the antrum prevents the passage of solid food

Neural Control

• Controlled by vagal cholinergic fibers using acetylcholine (Ach)

Gastric Motility: Proximal Motor Unit

• The fundus and body of the stomach
• Thin wall aids in storage of food and receptive relaxation

Response to Stimuli

• Gastric distension
• Swallowing initiates pharyngeal and esophageal movements that relax the stomach
• Vago-vagal reflex regulates this

Reflex Mechanism

• As little as 50ml can trigger stomach relaxation increasing to 1-1.5 per Liter.

Regulation of Gastric Evacuation (Emptying)

• Gastric Distension: Stimulates myenteric and vagal-vagal reflexes
• Intestinal Factors: Acidity, irritation, lipids, fats, distension, and hypertonicity decrease emptying. Influenced by entero-gastric reflexes and hormones like enterogastrone, GIP, secretin and CCK

Additional influences

• Consistency of food: Fluids empty faster than solids
• Reflexes from outside the GI tract: Pain and emotions alter emptying

Factors Affecting Gastric Emptying

• Volume of food: A large volume of food increases the rate of stomach emptying
• Type of food: Protein rich stimulate gastrin hormone and increase emptying, fats and fatty acids slow emptying
• Consistency of food: Fluids pass easily, while solids take longer to be processed thus digested
• Nervous tension: Anxiety, anger stimulates motility leading to enhancement of emptying while fear and depression inhibit motility, slowing emptying