Lesson 70A: The GI Barrier Function

Physical barriers: Mucus production

Produced by Goblet (mucus) cells, covering the entire stomach and intestinal surface

Gel-like, viscous mucin mixture, bicarbonate-rich

physical barriers: mucus function

Covers the GIT’s surface like a shield, avoiding contact with acids & enzymes.

Protects against mechanical damage by ingesta, Traps pathogens

Tiny channels within the mucus layer allow the HCl to flow into the stomach lumen without touching the mucosa

Physical barriers: Tight Junctions

GI epithelial cells form a continuous monolayer.

Their apical sections are connected via tight junctions, which seal off the paracellular spaces and control the mucosal permeability.

Physical barriers: disruption of tight junctions

Tight junction proteins (claudins, occludins) are downregulated by inflammatory mediators ➔ disruption of the barrier with increased paracellular permeability for ions, acid, toxins and pathogens, aka “ Leaky Gut Syndrome

Chemical barriers: prostaglandins

Produced as paracrines throughout the GIT by various cells.

Physiological = baseline production via COX-1 pathway to maintain GI integrity

Chemical barriers: function of prostaglandins

stimulate mucus and bicarbonate production, regulate blood supply (vasodilators)

limit HCl production, support cell proliferation & healing

Chemical barriers: HCl, GI Enzymes & Bile Acids

Are bactericidal

Induced production during GI irritation via COX-2 pathway to restore protective functions and to heal the mucosa

Immunological Barriers: GALT (gut-associated lymphoid tissue)

Peyers patches, lymphoid follicles, mesenteric lymph nodes

immunological barriers: Immune cells / mucosa & submucosa

Macrophages, T-cells, B-cells, dendritic cells

Immunological barriers: Secretory IgAs

Neutralize pathogens and toxins in the GIT lumen

Microbiological Barriers

Competition for resources

Produce anti-microbials and volatile fatty acids (VFAs), which are the preferred energy source for large intestinal mucosal cells.

Stem Cells

Numerous throughout the intestinal mucosa, in Crypts of Lieberkuehn and tubular glands.

Allows rapid turnover, rapid replacement of damaged cells = great healing capacity

The GI barrier can be disrupted by many things: stress

Stress → Sympathetic tone (vasoconstriction)

Stress → Cortisol (reduces mucus, increases HCL, disrupts tight junctions, reduces PGs)

The GI barrier can be disrupted by many things: other factors

NSAIDS

Inflammations / Infections (tight junctions, injury / destruction of cells )

Ill-perfusion (anemia, GI obstructions)

Dysbiosis

Food & Feeding Pattern

GI disruption leads to?

Mucus reduction

Bicarbonate reduction

PGE2 / PGI2 reduction

Blood perfusion reduction

Permeability increase

Healing capacity reduction

Consequences of disruption:

acute / chronic gastritis, possibly progressing to autodigestion, erosions, ulcerations