GI

Factors affecting GIT motility

Major organs and their functions

Gut Wall

The gut wall has four major layers, from the lumen outward.

Enteric nerve plexuses

MCQ tip: Auerbach = motility; Meissner = mucosal secretion and local regulation.

Smooth muscle physiology

• GI smooth muscle exhibits electrical activity that influences contraction.
• Slow waves are rhythmic fluctuations in membrane potential; they are not, by themselves, action potentials.
• Spike potentials occur when the membrane reaches threshold and permit increased Ca²⁺ entry, triggering contraction.
• Interstitial cells of Cajal act as pacemaker cells and help coordinate electrical activity.
• Stretch, acetylcholine and excitatory enteric signals can increase contraction; inhibitory transmitters such as nitric oxide promote relaxation.

Enteric, Autonomic and Hormonal Regulation

Enteric Nervous System (ENS)

The ENS can coordinate many gastrointestinal activities independently of direct CNS commands, although it is modulated by sympathetic and parasympathetic input.

ENS neuron types

Short and long reflexes

• Short reflexes: occur entirely within the ENS and can coordinate local secretion and motility.
• Long reflexes: involve the CNS and autonomic pathways; they may be initiated by GI stimuli or signals from outside the gut.

Autonomic effects

These are general patterns; the exact effect depends on the organ, receptor and enteric circuit.

Receptive Relaxation and Vagal Reflexes

When food enters the stomach, the proximal stomach relaxes to accommodate the meal without a large rise in intragastric pressure.

Mechanism

1. Swallowing and esophageal distension activate sensory afferents.
2. Signals travel through vagal pathways to the brainstem.
3. Vagal efferent signals return to the stomach.
4. Enteric inhibitory neurons release mediators, particularly nitric oxide and VIP.
5. Fundic smooth muscle relaxes, allowing the stomach to accommodate food.

Clinical importance: Impaired accommodation may contribute to early satiety and postprandial discomfort.

Remember: Receptive relaxation is a vagovagal reflex, coordinated through the vagus nerve and enteric inhibitory neurons.

GI Hormones, Paracrines and Neurocrines

GI signaling substances may act through the bloodstream, diffuse locally or function as neurotransmitters.

Regulatory substance categories

Major GI hormones

Hormones (in detail)

CCK

Gastrin

VIP - Vasocative Intestinal Peptide

Secretin

High-yield hormone distinctions

• Gastrin: promotes gastric acid secretion.
• CCK: pancreatic enzymes and gallbladder contraction.
• Secretin: bicarbonate secretion in response to acid.
• GIP and GLP-1: incretin hormones that enhance glucose-dependent insulin secretion.
• Somatostatin: broad inhibitory regulator.
• Motilin: fasting migrating motor complex.

Incretin effect

Oral glucose produces a greater insulin response than an equivalent intravenous glucose load because gut hormones amplify insulin secretion.

MCQ tip: GIP and GLP-1 are responsible for much of the incretin effect.

Oral Phase, Saliva, Swallowing and Esophagus

Salivary Secretion

Saliva lubricates food, supports swallowing, protects oral tissues, buffers acids and begins digestion.

Two-stage model of saliva formation

1. Acinar cells produce an initial fluid containing water and electrolytes, broadly similar to plasma in osmotic concentration.
2. Duct cells modify this fluid by reabsorbing Na⁺ and Cl⁻ and secreting K⁺ and HCO₃⁻.

Because the ducts are relatively impermeable to water, final saliva is usually hypotonic to plasma.

Effect of flow rate

Composition and functions

Autonomic regulation

• Parasympathetic stimulation, mainly through CN VII and CN IX pathways, produces abundant watery saliva.
• Sympathetic stimulation can promote secretion of protein-rich saliva and may contribute to a dry-mouth sensation.
• Salivary secretion is influenced by taste, chewing, smell and conditioned responses.

Clinical relevance

Xerostomia can result from medications, dehydration, salivary gland disorders or radiation injury. Reduced saliva increases the risk of dental caries, oral discomfort, swallowing difficulty and mucosal infection.

Swallowing

Swallowing transfers food from the mouth to the stomach while protecting the airway.

Three phases

Esophageal motility

• Primary peristalsis: follows a swallow.
• Secondary peristalsis: triggered by esophageal distension when material remains in the esophagus.
• The lower esophageal sphincter relaxes ahead of the bolus to permit entry into the stomach.

Sphincter control

The upper esophageal sphincter is normally contracted between swallows, helping prevent air entry and regurgitation into the pharynx.

The lower esophageal sphincter and crural diaphragm help prevent gastric contents from refluxing into the esophagus.

MCQ tip: Achalasia is associated with impaired LES relaxation and loss of normal esophageal peristalsis.

Stomach Physiology

Functional Regions of the Stomach

Gastric Gland Cells

Parietal-cell acid secretion

Inside parietal cells, carbonic anhydrase facilitates the formation of H⁺ and HCO₃⁻ from CO₂ and water.

• H⁺ is secreted into the gastric lumen by the H⁺/K⁺-ATPase.
• Cl⁻ enters the lumen through chloride channels.
• H⁺ and Cl⁻ form gastric hydrochloric acid.
• HCO₃⁻ enters the blood, producing the postprandial alkaline tide.

Remember: The proton pump is the final common pathway for gastric acid secretion.

Regulation of acid secretion

Three major stimulators act synergistically on parietal cells.

Inhibitors of acid secretion

• Somatostatin inhibits gastrin release and parietal-cell activity.
• Prostaglandins reduce acid secretion and support mucus/bicarbonate-mediated mucosal protection.
• Secretin and other intestinal signals help inhibit gastric acid activity when acidic chyme enters the duodenum.

Drugs and their targets

Phases of Gastric Secretion

Clinical correlation: peptic ulcer disease

Ulcers occur when damaging factors overwhelm mucosal defenses. Important contributors include Helicobacter pylori, NSAIDs and gastric acid-pepsin activity.

• NSAIDs reduce protective prostaglandin synthesis.
• H. pylori disrupts mucosal defenses and alters gastrin/somatostatin regulation.
• PPIs reduce acid secretion and support ulcer healing.

Gastric Motility and Emptying

The stomach stores food, mixes it with secretions, reduces particle size and delivers chyme gradually into the duodenum.

Main movements

• Receptive relaxation: allows the proximal stomach to accommodate a meal.
• Mixing waves: propagate toward the antrum.
• Retropulsion: forceful antral contractions drive material backward through the partially closed pylorus, improving grinding.
• Gastric emptying: regulated delivery of chyme into the duodenum.

Factors influencing gastric emptying

Exam tip: Fat entering the duodenum is a strong signal to slow gastric emptying, allowing time for digestion and absorption.

Pancreatic Secretion and Small-Intestinal Digestion

Pancreatic Secretion

The exocrine pancreas produces digestive enzymes and bicarbonate-rich fluid.

Acinar versus duct cells

Pancreatic enzymes

Most pancreatic proteases are secreted as inactive zymogens to prevent autodigestion.

Activation of pancreatic proteases

1. Brush-border enteropeptidase converts trypsinogen to trypsin.
2. Trypsin activates additional trypsinogen.
3. Trypsin activates other pancreatic zymogens.
4. Activated enzymes digest dietary proteins in the intestinal lumen.

Clinical correlation: Premature enzyme activation or impaired pancreatic duct drainage can contribute to pancreatitis.

Regulation

• CCK stimulates acinar enzyme secretion.
• Secretin stimulates bicarbonate-rich ductal secretion in response to acidic duodenal contents.
• Vagal acetylcholine supports pancreatic secretion during feeding.

Bile Secretion and Gallbladder Function

Bile supports fat digestion and absorption. It contains bile salts, phospholipids, cholesterol, bilirubin, electrolytes and water.

Bile salts

Bile salts are amphipathic: they have both hydrophilic and hydrophobic regions.

Their main functions are:

• Emulsification of dietary fats.
• Formation of mixed micelles.
• Delivery of lipids and fat-soluble vitamins to the intestinal surface.
• Facilitation of absorption of vitamins A, D, E and K.

Enterohepatic circulation

1. The liver synthesizes bile acids from cholesterol.
2. The gallbladder stores and concentrates bile between meals.
3. CCK stimulates gallbladder contraction and promotes delivery of bile into the duodenum.
4. Most bile salts are reabsorbed in the terminal ileum.
5. Portal blood returns them to the liver, where they are taken up and secreted again.

Remember: The terminal ileum is the major site of bile salt reabsorption.

Bile salt loss

Terminal ileal disease or resection can reduce bile salt recycling.

• Reduced bile salt availability may impair fat absorption and cause steatorrhea.
• Excess bile acids reaching the colon may stimulate secretion and contribute to diarrhea.

Small-Intestinal Digestion and Absorption

The small intestine is the principal site of nutrient digestion and absorption. Its folds, villi and microvilli greatly increase absorptive surface area.

Carbohydrate digestion

Monosaccharide absorption

The Na⁺ gradient supporting SGLT1 is maintained by basolateral Na⁺/K⁺-ATPase.

Clinical correlation: Oral rehydration solution works because intestinal Na⁺-glucose cotransport remains functional in many diarrheal illnesses, allowing Na⁺ and water absorption.

Protein digestion and absorption

• Gastric pepsin begins protein digestion.
• Pancreatic proteases break proteins into smaller peptides and amino acids.
• Brush-border and intracellular peptidases complete digestion.
• Amino acids use specific transporters, many coupled to Na⁺.
• Di- and tripeptides enter through PEPT1, which uses an H⁺ gradient, and are generally broken down further inside enterocytes.

Most absorbed amino acids enter portal blood.

Lipid digestion and absorption

1. Bile salts help emulsify fat.
2. Pancreatic lipase, aided by colipase, digests triglycerides into monoglycerides and fatty acids.
3. These products enter mixed micelles with bile salts.
4. Micelles deliver lipids to the brush border.
5. Lipids enter enterocytes and are re-esterified into triglycerides.
6. Triglycerides are packaged with cholesterol, phospholipids and apoproteins into chylomicrons.
7. Chylomicrons enter intestinal lymphatics and subsequently reach systemic blood.

Short- and medium-chain fatty acids

Short- and medium-chain fatty acids are more water-soluble than long-chain fatty acids and can enter portal blood directly to a greater extent, often bound to albumin. They do not depend on chylomicron formation to the same degree.

Fat-soluble vitamins

Vitamins A, D, E and K depend on normal fat digestion and absorption. Bile salt deficiency or pancreatic insufficiency can therefore produce fat-soluble vitamin deficiencies.

Vomiting — Neural Pathway and Metabolic Consequences

Vomiting is coordinated by brainstem neural networks that integrate signals from the GI tract, vestibular system, higher centers and chemoreceptor trigger pathways.

Major inputs

• GI irritation and distension activate vagal and visceral afferents.
• Motion-related signals reach the brainstem through vestibular pathways.
• Drugs and toxins can activate the chemoreceptor trigger zone.
• Higher brain centers can contribute to nausea and vomiting.

Metabolic effects

Vomiting causes loss of gastric HCl and fluid.

Exam tip: Persistent vomiting classically causes hypochloremic metabolic alkalosis.