Lecture 32: Gastroduodenal Mucosal Protection, Ulcers Flashcards
What is the function of the gastrointestinal barrier
- Allow efficiency transport of nutrients across epithelium
- Protect epithelial cells from destructive acidity, hostile microorganisms, toxins, and digestive activity of pepsin
__cells support the continual repair of GI epithelium
Stem cells
What maintains the H+ gradient in the gastrointestinal barrier
Bicarbonate microenvironment on epithelial cells
What is the function of the mucus gel layer
Provide protection to cells
What are 2 examples of immune cells in the GI tract
- Paneth cells
- Peyers patches
What are the 3 components of the mucosal barrier
- Tight junctions that connect enterocytes
- Mucus layer, unstirred H20 layer
- Immune cells
What layers create the microenvironment separating the lumen and apical membrane
Glycocalyx, mucus, unstirred water layer
What cells secrete mucus in the mucus layer
Goblet
Is the SI mucus layer thick or thin compared to LI
Thin- has buffers to combat acidity
Why is the LI mucus layer thick
To protect from microbial activity
What cells produce mucins
Surface mucous, surface neck and glandular cells
What triggers mucus secretion
- Vagal stimulation
- Stroking causes release of PG—> VIP—> CFTR Cl- channel to release H20 and goblet cells activated
How can acid and pepsinogen pass the mucus layer
Via small channels
What creates the neutral character of the mucus gel layer
- Water layer
- Bicarbonate secretion via surface epithelial cells
What is responsible for stimulating release of bicarbonate at the mucus layer
PGE2
How does PGE2 inhibit gastric acid secretion
- Inhibits AC of parietal cells
- Inhibits histamine
- Inhibits gastrin cells
How does PGE2 impact blood flow
Simulates mucosal blood flow and oxygen delivery by vasodilation
Microbial/pathogen recognition leads to what 3 things
- Activation of immune response
- Production of effector molecules
- Commensal bacteria create hostile environment for pathogenic bacteria
What are paneth cells
Immune cells located in the SI crypts
What are Peyers patches
Mass of lymphatic tissue in the SI, especially the ileum
What is the function of pattern recognition receptors
Recognize and discriminate pathogenic bacteria vs commensal bacteria
What are the two types of PPR’s
- Toll like receptors (transmembrane)
- NOD like receptors (intracellular)
What do PRR’s recognize on pathogenic bacteria
- Lipolysaccharides
- Flagella
- DNA/RNA
PPR recognition leads to production of what effector molecules
IL-18, IL-1B, TNFalpha
What are alpha-Densins (aka cryptidins)
Antimicrobial peptides secreted by paneth cells that have activity against bacteria, some yeast, and giardia trophozoites
How do commensal bacteria provide protection (3)
- Production of inhibitory compounds (stop growth)
- Competing for adhesion sites
- Modulating the immune response
What factors contribute to the development of IBD
- Impaired immunity (cytokines)
- Genetic predisposition (NOD-like receptors)
- Microbial flora dysfunction (metabolites, dysbiosis)
Inflammatory stimuli (HCl injury) induce ___release from mast cells and ____synthesis by epithelial cells
Histamine, prostaglandins
The constant repair of GI epithelium helps prevent defects but bears risk of ___
Malignancy
What causes an ulcer
Excessive exposure to HCl or SCFA
NSAID’s inhibit COX activity which thereby inhibit the production of ___
Prostaglandins
What are the 2 ways in which NSAIDs cause toxic effects
- Inhibit COX and affect in PG synthesis
- Become trapped in epithelial cells causing damage/death
How do NSAIDS effect mucus, bicarbonate, blood flow, cell restitution and inflammation
Decrease all except inflammation which increases
How do NSAIDs become trapped in the epithelial cells
- Carboxylic acids such as NSAIDS are non-ionized in acidic gastric lumen
- Migrate to inside cell lumen which is neutral and become ionized and trapped
- Elevated intracellular NSAID levels cause cell death and injury
How does H. Pylori result in gastritis, peptic ulcers and potentially a higher rate of gastric neoplasia
- Burrow into mucus gel layer
- Adhesins facilitate attachment to mucus layer
- Disturb HCO3- release and digest mucus layer therefore decrease pH causing ulcers and damage to epithelial lining
How do parasites cause damage to GI mucosa/epithelium
- Mechanical damage to mucus gel layer and mucosa
- Chronic exposure of mucosal cells to acidic environment
- Inability of mucosal repair/epithelial proliferation (b/c injury is continuous)
What are the two types of disorders that can cause gastrointestinal ischemia
- Non-occlusive ischemia
- Occlusive ischemia
What is occlusive ischemia and what are some causes
Conditions that directly disrupt gastrointestinal flow
Causes: strangulation, volvulus, thromboembolism, bloat/tympany, FB, herniation
What is non-occlusive ischemia
Ischemia due to reduce capillary flow or shunting blood away from GI tract so that blood bypasses gastric mucosa
Why can stress and Cushings result in non-occlusive ischemia
Both cause an increase in glucocorticoids which results in vasoconstriction
