Digestive System Part 2: The Stomach, Liver, Gallbladder, Pancreas, and Small Intestine

The Stomach

Structure and Function

The stomach acts as a temporary storage tank and is responsible for the initial stages of protein digestion. It produces up to 3 liters of acidic gastric juice per day, which contains hydrochloric acid (HCl), pepsin, and, in infants, rennin. The stomach also secretes intrinsic factor, which is essential for vitamin B12 absorption and thus for life, as its absence leads to pernicious anemia. Gastric lipase contributes minimally to lipid digestion. The muscular action of the stomach mixes food with gastric juice, converting it into chyme. Absorption in the stomach is limited, with alcohol and aspirin being notable exceptions due to their lipid solubility.

Regulation of Gastric Secretion

Gastric secretion is regulated by neural and hormonal mechanisms. Long reflexes are mediated by the vagus nerve (parasympathetic nervous system), while short reflexes are local. Hormones such as gastrin and histamine play key roles. Parietal cells have receptors for three stimulatory chemicals: acetylcholine (ACh), gastrin, and histamine. Histamine is the most potent stimulator, acting on the proton pump (H+-K+ ATPase) on the apical surface of parietal cells. Gastric secretion occurs in three phases: cephalic (preparatory), gastric (most active), and intestinal (winding down).

Phases of Gastric Secretion

• Cephalic Phase: Triggered by the sight, smell, taste, or thought of food before it enters the stomach.

• Gastric Phase: Lasts 3–4 hours, providing two-thirds of gastric juice. Both ACh and gastrin stimulate histamine secretion. Very low gastric pH (<2) or increased sympathetic activity inhibits secretion.

• Intestinal Phase: Begins with a brief stimulatory effect (intestinal gastrin release) but is quickly overridden by inhibitory signals as the intestine fills. Inhibition is mediated by the enterogastric reflex and enterogastrones (secretin and CCK), triggered by duodenal distension and the presence of acidic, fatty, or hypertonic chyme.

Mechanism of HCl Secretion by Parietal Cells

Parietal cells secrete HCl into the stomach lumen via the H+-K+ ATPase pump. The process involves the generation of H+ and HCO3- from CO2 and H2O by carbonic anhydrase. H+ is pumped into the lumen in exchange for K+, while HCO3- is exchanged for Cl- (alkaline tide). Cl- diffuses into the lumen, combining with H+ to form HCl.

Secretion of Pepsin by Chief Cells

Chief cells secrete pepsinogen, an inactive precursor stored in zymogen granules. Once released into the stomach lumen, pepsinogen is activated to pepsin by HCl. Pepsin hydrolyzes proteins into peptides, with an optimal pH of 2–3. Acetylcholine is the primary stimulus for pepsin secretion.

Regulation of Gastric Motility and Emptying

The stomach stretches to accommodate food, with pressure remaining constant until about 1.5 L is ingested. This is due to receptive relaxation (reflex-mediated, extrinsic) and gastric accommodation (intrinsic smooth muscle property). Peristaltic waves, set by the Basic Electrical Rhythm (BER) from enteric pacemaker cells, move toward the pylorus at a rate of 3 per minute. Distension and gastrin increase contraction force, which is strongest near the pylorus. Only small amounts of chyme pass through the pyloric valve at a time; the rest is retropulsed back into the stomach.

Regulation of Gastric Emptying

The duodenum regulates gastric emptying by responding to stretch and chemical signals. The enterogastric reflex and enterogastrones (secretin, CCK) inhibit gastric secretion and slow emptying to prevent overfilling. Carbohydrate-rich chyme empties quickly, while fatty chyme delays emptying (up to 6 hours or more).

Liver, Gallbladder, and Pancreas

Overview and Functions

The liver, gallbladder, and pancreas are accessory organs associated with the small intestine. The liver produces bile, a fat emulsifier. The gallbladder stores and concentrates bile, while the pancreas supplies digestive enzymes and bicarbonate to neutralize stomach acid.

Liver Anatomy

The liver is the largest gland in the body (~1.4 kg), located in the right hypochondriac and epigastric regions. It has four lobes: right, left, caudate, and quadrate. The falciform ligament separates the right and left lobes and suspends the liver from the diaphragm and anterior body wall. The liver produces about 900 ml of bile daily.

Liver Lobule Structure

The liver is organized into lobules, each containing a central vein, portal triads (branch of hepatic artery, portal vein, and bile duct), liver sinusoids, stellate macrophages, and bile canaliculi. Blood flows from the portal triads through sinusoids to the central vein, while bile flows in the opposite direction toward the bile duct.

Composition and Function of Bile

Bile is a yellow-green, alkaline solution containing bile salts, bile pigments (mainly bilirubin), cholesterol, neutral fats, phospholipids, and electrolytes. Only bile salts and phospholipids aid in lipid digestion. The main bile salts are cholic acid and chenodeoxycholic acid, which are cholesterol derivatives that emulsify fats. Bile salts are amphipathic molecules, meaning they have both hydrophilic and hydrophobic regions, allowing them to surround fat droplets and aid in emulsification.

Bile salts are conserved and recycled via the enterohepatic circulation. The main bile pigment, bilirubin, is converted to urobilinogen or stercobilin by intestinal bacteria. Bile production increases after a fatty meal, with the key stimulus being the return of recycled bile salts to the liver.

The Gallbladder

The gallbladder is a thin-walled muscular sac that stores and concentrates bile by absorbing water and ions. Muscular contractions expel bile into the cystic duct, which joins the common hepatic duct to form the bile duct, delivering bile to the duodenum. Supersaturation of bile with cholesterol and stasis can lead to gallstone formation (biliary calculi).

The Pancreas

The pancreas is mostly retroperitoneal, with its head encircled by the duodenum and its tail abutting the spleen. It produces 1200–1500 ml of pancreatic juice daily. The exocrine pancreas consists of acinar cells that produce digestive enzymes and duct cells that secrete bicarbonate. Bicarbonate neutralizes acidic chyme entering the duodenum, protecting the intestinal mucosa and providing an optimal pH for enzyme activity.

Composition of Pancreatic Juice

• Electrolytes (mainly bicarbonate)

• Proteases (secreted in inactive form)

• Amylase

• Lipases

• Nucleases

Enteropeptidase, a brush border enzyme, activates trypsinogen to trypsin, which then activates other proteases (chymotrypsinogen and procarboxypeptidase).

Regulation of Bile and Pancreatic Secretion

During fasting, the hepatopancreatic sphincter is closed, causing bile to back up into the gallbladder. Cholecystokinin (CCK), released in response to fatty chyme in the duodenum, stimulates gallbladder contraction, pancreatic enzyme secretion, and relaxation of the hepatopancreatic sphincter. Secretin stimulates secretion of a bicarbonate-rich fluid from the bile ducts and pancreatic ducts. Recirculating bile salts are the major stimulus for bile production and secretion by the liver.

The Small Intestine

Structure and Regions

The small intestine is 6–7 meters long (2–4 meters in situ due to muscle tone) and extends from the pyloric sphincter to the ileocecal valve. It consists of three regions:

• Duodenum: ~25 cm, mostly retroperitoneal

• Jejunum: ~2.5 m

• Ileum: ~3.6 m, joins the large intestine at the ileocecal valve

The superior mesenteric artery supplies blood, and veins drain into the hepatic portal vein.

Modifications for Absorption

The small intestine has several structural adaptations to increase surface area for absorption:

• Circular folds: Permanent folds of mucosa and submucosa that slow chyme movement and increase absorption.

• Villi: Finger-like projections, longest in the duodenum, that increase surface area.

• Microvilli: Cytoplasmic extensions of enterocytes forming the brush border, which contains digestive enzymes.

Histology of the Small Intestine Wall

The mucosal epithelium contains five main cell types:

• Enterocytes: Absorptive cells with microvilli; absorb nutrients on villi and secrete intestinal juice in crypts.

• Goblet cells: Produce mucus for lubrication and protection.

• Enteroendocrine cells: Secrete hormones such as secretin and CCK.

• Paneth cells: Secrete antimicrobial agents (defensins and lysozyme).

• Stem cells: Continuously divide to replace all cell types; villus epithelium is renewed every 2–4 days.

Mucosa-associated lymphoid tissue (MALT), including Peyer's patches, protects against microorganisms. The submucosa contains areolar connective tissue and duodenal glands that secrete alkaline mucus. The muscularis externa has two layers. The small intestine produces 1–2 liters of slightly alkaline (pH 7.4–7.8) intestinal juice daily, mainly in response to hyperosmotic or acidic chyme.