L32: Gastroduodenal Mucosal Protection, Ulcers Flashcards
functions of the GI barrier
- allow efficient transport of nutrients across epithelium
- protect epithelial cells from destructive acidity, hostile mircoorganisms/toxins & digestive activity of pepsin
what are the 5 components of the gastroduodenal mucosal barrier
- variable osmotic permeability along GI tract
- stem cells for continual repair of GI epithelium
- HCO3 mircoclimate maintains H+ gradient
- mucus gel layer overlays epithelium
- immune defense (paneth cells, peyer’s patches)
3 components of mucosal barrier
- tigh junctions that connect enterocytes-permeable to water/electrolytes-barrier against pathogens
- mucus layer, unstirred water layer
- immune cells
what cells secrete a layer of mucus that covers the mucosa
goblet cells
what is the purpose of the mucus layer
protect cells from dehydration, mechanical damage, low pH
serves as a physical barrier for pathoenic bacteria/viruses/parasites
what does the mucus layer consist of
mucin, phospholipids, electrolytes, water
what cells produce mucin
- surface mucous cells
- surface neck cells
- glandular cells
What triggers mucus secretion
- vagal stimulation
- physical & chemical irritation
stroking of the mucus layer causes the release of _____ which triggers secretomotor neurons to release ______
prostaglandins
VIP
VIP causes Cl- secretion by enterocytes
how can acid and pepsinogen pass through the mucus layer
small channels
what makes the mucus gel layer neutral
- unstirred water layer & HCO3 secretion
- HCO3 trapped in mucus gel layer
PGE2 stimulates the secretion of ____ & inhibits secretion of _____
- HCO3
- gastric acid
PGE2 inhibits adenylyl cyclase of parietal cells; inhibits histamine & gastrin release
this molecule stimulates mucosal blood flow & oxygen delivery by causing vasodilation
PGE2
epithelial granulocytes in crypts of SI
paneth cells
masses of lymphatic tissue throughout GI, especially in ileum
peyer’s patches
how does the mucosal immune system discriminate b/w pathogenic vs commensal bacteria
pattern recognition receptors
- Toll like receptors (transmembrane)
- NOD-like receptors (intracellular)
recognition of pathogens by pattern recognition receptors leads to production of ?
effector molecules via the apical membrane; cytokines are then secreted
synthesize & secrete antimicrobial peptides such as alpha-defensins aka cryptdins
paneth cells
how does commensal bacteria provide protection by creating a hostile environment for pathogenic bacteria
- produce inhibitory compounds
- competition for adhesion sites
- modulation of immune response
pro and con of the constant fast renewal of epithelium lining
pro: helps prevent accumulation of defects
con: risk for malignancy
where do stem cells originate
neck area of crypts
refer to disruptions in mucosal integrity
ulcers
what can cause ulcers
lesions in gastric mucosa from excessive exposure to acid caused by: excess gastric acid production (gastrinoma) or damage to the mucus gel layer
what are prostaglandins produced from
polyunsaturated FAs (linoleic and arahodonic acid)
NSAIDs inhibit ..
COX activity (and therefore production of PGs)
types of NSAID toxicity
- NSAIDs inhibit cyclo-oxygenase activity affecting PG synthesis
- NSAIDs become trapped in epithelial cells causing damage
effects of NSAID toxicity
- decreases: mucus, HCO3, blood flow, cell restituiton
- increases inflammation (neutrophil recruitment)
how can NSAIDs get trapped in epithelial cells
- carboxylic acids are not ionized in the acidic gastric lumen
- once inside cell lumen, at a neutral pH, they get trapped in an ionized form
how does H.pylori get into the mucus gel layer of the stomach
uses its flagella to burrow; chemotaxis towards a higher pH
the presence of parasites in the stomach causes ?
- mechanical damage to the mucus gel layer and mucosa
- chronic exposure of mucosal cells to an acidic environment
- an inability for mucosal repair/epithelial proliferation
what two disorders can result in gastrointestinal ischemia
- non-occlusive ischemia
- occlusive ischemia = conditions that directly disrupt GI blood flow (strangulation, volvulus, thromboembolisms, bloat/tympany, foreign body, herniation)
explain how blood flows through villi
blood enters at the base of the vilus and is carried up to the tip
why does anoxic damage occur at the tip of the villi
due to premature O2 exchange that occurs closer to the base where the blood enters
what is non-occlusive ischemia
ischemia caused by reduced capillary blood flow or shunting or blood away from the GI tract (splanchnic vasoconstriction) that causes blood to by pass the gastric mucosa
ex: stress or cushings
