Week 8: Body's Defences 2

The gastrointestinal tract performs six integrated physiological processes: ingestion, secretion, mixing and propulsion, digestion, absorption, and defecation. These processes must occur while maintaining mass balance, preventing auto-digestion, and limiting entry of pathogens and toxins from the lumen.

Mixing and propulsion include chewing, gastric churning, segmentation, and peristalsis. Segmentation is a local mixing pattern generated mainly by circular muscle contractions, while peristalsis is a coordinated propulsive wave that moves luminal contents distally.

Absorption is concentrated in the small intestine, where villi, microvilli, capillaries, and lacteals maximise transport into blood and lymph. Defecation depends on rectal distension, parasympathetic reflex pathways, relaxation of the internal anal sphincter, and voluntary control of the external anal sphincter.

The intrinsic GI barrier consists of epithelial cells, tight junctions, the glycocalyx, mucus, antimicrobial peptides, gastric acid, and the regenerative stem-cell compartment that continually renews the lining. The extrinsic barrier includes GALT, secretory antibodies, broader immune signalling, and neural control of motility that helps remove potentially harmful material.

Goblet cells produce mucins that form the mucus layer. Paneth cells at the base of crypts secrete defensins and help protect the stem-cell niche. M cells transcytose antigens to immune cells in Peyer's patches. IELs are strategically positioned T cells between epithelial cells, providing rapid surveillance at the surface.

Enteroendocrine cells are epithelial sensors that release hormones regulating acid secretion, bicarbonate release, gallbladder contraction, pancreatic enzyme secretion, gastric emptying, and fasting motility. These cells are not just digestive helpers; they are part of how the gut coordinates defence with function.

GALT, as part of mucosal immunity, integrates antigen sampling, immune tolerance, and pathogen defence. Peyer's patches and isolated follicles are supported by diffuse immune cells in the lamina propria, while plasma cells produce secretory IgA for immune exclusion at the mucosal surface.

Receptive relaxation is a reflex-mediated relaxation of the proximal stomach as swallowing begins, and gastric accommodation is the stress-relaxation property that allows the stomach to store a meal without a major increase in intragastric pressure. Rugae assist expansion, but motility control is neural and muscular, not just structural.

Interstitial cells of Cajal serve as GI pacemaker cells that generate slow-wave electrical activity coordinating segmentation and peristalsis. During fasting, the MMC provides cyclical electromechanical activity that sweeps residual contents and bacteria distally, limiting small-intestinal bacterial overgrowth.

Protective removal mechanisms include accelerated transit, diarrhoea, vomiting, and eventual defecation. These responses can limit pathogen colonisation and toxin exposure, but excessive losses may produce hypovolaemia, electrolyte abnormalities, and acid-base disturbances.

Peritoneum: The peritoneum is the largest serous membrane in the body. It has two layers: the parietal peritoneum lining the abdominal cavity and the visceral peritoneum covering abdominal organs. Approximately 50-100 mL of serous fluid lies between these layers, reducing friction and allowing viscera to move freely. The peritoneum also supports abdominal organs and provides a route for blood vessels, lymphatics, and nerves. Peritoneal injury may produce adhesions, creating abnormal attachments between structures that can lead to intestinal obstruction.

Oral microbiome: The oral cavity contains the second largest and most diverse microbiota after the gut. Bacteria, fungi, viruses, and protozoa colonise both hard surfaces such as teeth and soft tissues of the oral mucosa. Biofilm formation on teeth is a normal microbial strategy, but altered microbial balance can contribute to pathology. This means the mouth is both the start of digestion and an important defensive interface.

Vomiting reflex: Vomiting (emesis) is a coordinated protective reflex triggered by mechanical gastrointestinal stimuli, emetogenic chemicals, vestibular disturbance, pain, or central input from the brain. During the pre-ejection phase, retrograde peristalsis moves contents toward the oesophagus, hypersalivation protects teeth, and airway structures close to reduce aspiration risk. During the ejection phase, abdominal and diaphragmatic contraction sharply raise intra-abdominal pressure while the upper oesophageal sphincter dilates, producing forceful expulsion.

Clinical consequences: Prolonged vomiting may be accompanied by diaphoresis, pallor, hypotension, and dizziness. Excess loss of gastric contents commonly causes hypochloraemia, hypokalaemia, and metabolic alkalosis. Loss of upper intestinal contents may instead contribute to metabolic acidosis. Diarrhoea acts as a rapid clearance mechanism for irritating or infectious material, but increased motility and reduced absorption can lead to dehydration, especially in infants and older adults.

GI ageing: Ageing is associated with reduced salivary secretion, impaired dentition, slower oesophageal and colonic transit, and increased prevalence of constipation. Older adults also have greater risk of malnutrition, dehydration, reflux, and complications from reduced mucosal resilience.

Vomiting neural pathway: Emesis is coordinated by medullary vomiting centres receiving input from visceral afferents, higher cortical centres, the area postrema / chemoreceptor trigger zone, and the vestibular apparatus. The area postrema lies outside the usual blood-brain barrier and detects circulating emetogenic drugs and toxins, while vestibular input explains nausea and vomiting in motion sickness.

Vomit colour interpretation: Bilious green vomit indicates bile from the duodenum, bright red haematemesis suggests active upper GI bleeding, and coffee-ground vomit reflects altered blood exposed to gastric acid. Colour is only a clue, but it can quickly guide urgency.

Key GI hormones: Gastrin from G cells stimulates gastric acid secretion and mucosal growth. Secretin from duodenal S cells responds to acid and increases pancreatic bicarbonate secretion. Cholecystokinin (CCK) from I cells responds to fat and amino acids, causing gallbladder contraction, pancreatic enzyme secretion, and slowing gastric emptying. Motilin promotes fasting-phase migrating motor activity.

Intrinsic factor and pernicious anaemia: Intrinsic factor is secreted by gastric parietal cells and binds vitamin B12 so it can be absorbed in the terminal ileum. Autoimmune loss of parietal cells or intrinsic factor causes pernicious anaemia, producing B12 deficiency with megaloblastic change, glossitis, and possible posterior column or peripheral nerve dysfunction.