L32: Gastroduodenal Mucosal Protection, Ulcers

Question 1

functions of the GI barrier

Answer 1

• allow efficient transport of nutrients across epithelium
• protect epithelial cells from destructive acidity, hostile mircoorganisms/toxins & digestive activity of pepsin

Question 2

what are the 5 components of the gastroduodenal mucosal barrier

Answer 2

1. variable osmotic permeability along GI tract
2. stem cells for continual repair of GI epithelium
3. HCO3 mircoclimate maintains H+ gradient
4. mucus gel layer overlays epithelium
5. immune defense (paneth cells, peyer’s patches)

Question 3

3 components of mucosal barrier

Answer 3

1. tigh junctions that connect enterocytes-permeable to water/electrolytes-barrier against pathogens
2. mucus layer, unstirred water layer
3. immune cells

Question 4

what cells secrete a layer of mucus that covers the mucosa

Answer 4

goblet cells

Question 5

what is the purpose of the mucus layer

Answer 5

protect cells from dehydration, mechanical damage, low pH
serves as a physical barrier for pathoenic bacteria/viruses/parasites

Question 6

what does the mucus layer consist of

Answer 6

mucin, phospholipids, electrolytes, water

Question 7

what cells produce mucin

Answer 7

• surface mucous cells
• surface neck cells
• glandular cells

Question 8

What triggers mucus secretion

Answer 8

• vagal stimulation
• physical & chemical irritation

Question 9

stroking of the mucus layer causes the release of _____ which triggers secretomotor neurons to release ______

Answer 9

prostaglandins
VIP
VIP causes Cl- secretion by enterocytes

Question 10

how can acid and pepsinogen pass through the mucus layer

Answer 10

small channels

Question 11

what makes the mucus gel layer neutral

Answer 11

• unstirred water layer & HCO3 secretion
• HCO3 trapped in mucus gel layer

Question 12

PGE2 stimulates the secretion of ____ & inhibits secretion of _____

Answer 12

• HCO3
• gastric acid
  PGE2 inhibits adenylyl cyclase of parietal cells; inhibits histamine & gastrin release

Question 13

this molecule stimulates mucosal blood flow & oxygen delivery by causing vasodilation

Answer 13

PGE2

Question 14

epithelial granulocytes in crypts of SI

Answer 14

paneth cells

Question 15

masses of lymphatic tissue throughout GI, especially in ileum

Answer 15

peyer’s patches

Question 16

how does the mucosal immune system discriminate b/w pathogenic vs commensal bacteria

Answer 16

pattern recognition receptors
- Toll like receptors (transmembrane)
- NOD-like receptors (intracellular)

Question 17

recognition of pathogens by pattern recognition receptors leads to production of ?

Answer 17

effector molecules via the apical membrane; cytokines are then secreted

Question 18

synthesize & secrete antimicrobial peptides such as alpha-defensins aka cryptdins

Answer 18

paneth cells

Question 19

how does commensal bacteria provide protection by creating a hostile environment for pathogenic bacteria

Answer 19

• produce inhibitory compounds
• competition for adhesion sites
• modulation of immune response

Question 20

pro and con of the constant fast renewal of epithelium lining

Answer 20

pro: helps prevent accumulation of defects
con: risk for malignancy

Question 21

where do stem cells originate

Answer 21

neck area of crypts

Question 22

refer to disruptions in mucosal integrity

Answer 22

ulcers

Question 23

what can cause ulcers

Answer 23

lesions in gastric mucosa from excessive exposure to acid caused by: excess gastric acid production (gastrinoma) or damage to the mucus gel layer

Question 24

what are prostaglandins produced from

Answer 24

polyunsaturated FAs (linoleic and arahodonic acid)

Question 25

NSAIDs inhibit ..

Answer 25

COX activity (and therefore production of PGs)

Question 26

types of NSAID toxicity

Answer 26

1. NSAIDs inhibit cyclo-oxygenase activity affecting PG synthesis 2. NSAIDs become trapped in epithelial cells causing damage

Question 27

effects of NSAID toxicity

Answer 27

* decreases: mucus, HCO3, blood flow, cell restituiton * increases inflammation (neutrophil recruitment)

Question 28

how can NSAIDs get trapped in epithelial cells

Answer 28

* 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

Question 29

how does H.pylori get into the mucus gel layer of the stomach

Answer 29

uses its flagella to burrow; chemotaxis towards a higher pH

Question 30

the presence of parasites in the stomach causes ?

Answer 30

* 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

Question 31

what two disorders can result in gastrointestinal ischemia

Answer 31

* non-occlusive ischemia * occlusive ischemia = conditions that directly disrupt GI blood flow (strangulation, volvulus, thromboembolisms, bloat/tympany, foreign body, herniation)

Question 32

explain how blood flows through villi

Answer 32

blood enters at the base of the vilus and is carried up to the tip

Question 33

why does anoxic damage occur at the tip of the villi

Answer 33

due to premature O2 exchange that occurs closer to the base where the blood enters

Question 34

what is non-occlusive ischemia

Answer 34

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