Lecture 32: Gastroduodenal Mucosal Protection, Ulcers

Question 1

What is the function of the gastrointestinal barrier

Answer 1

1. Allow efficiency transport of nutrients across epithelium
2. Protect epithelial cells from destructive acidity, hostile microorganisms, toxins, and digestive activity of pepsin

Question 2

__cells support the continual repair of GI epithelium

Answer 2

Stem cells

Question 3

What maintains the H+ gradient in the gastrointestinal barrier

Answer 3

Bicarbonate microenvironment on epithelial cells

Question 4

What is the function of the mucus gel layer

Answer 4

Provide protection to cells

Question 5

What are 2 examples of immune cells in the GI tract

Answer 5

1. Paneth cells
2. Peyers patches

Question 6

What are the 3 components of the mucosal barrier

Answer 6

1. Tight junctions that connect enterocytes
2. Mucus layer, unstirred H20 layer
3. Immune cells

Question 7

What layers create the microenvironment separating the lumen and apical membrane

Answer 7

Glycocalyx, mucus, unstirred water layer

Question 8

What cells secrete mucus in the mucus layer

Answer 8

Goblet

Question 9

Is the SI mucus layer thick or thin compared to LI

Answer 9

Thin- has buffers to combat acidity

Question 10

Why is the LI mucus layer thick

Answer 10

To protect from microbial activity

Question 11

What cells produce mucins

Answer 11

Surface mucous, surface neck and glandular cells

Question 12

What triggers mucus secretion

Answer 12

1. Vagal stimulation
2. Stroking causes release of PG—> VIP—> CFTR Cl- channel to release H20 and goblet cells activated

Question 13

How can acid and pepsinogen pass the mucus layer

Answer 13

Via small channels

Question 14

What creates the neutral character of the mucus gel layer

Answer 14

1. Water layer
2. Bicarbonate secretion via surface epithelial cells

Question 15

What is responsible for stimulating release of bicarbonate at the mucus layer

Answer 15

PGE2

Question 16

How does PGE2 inhibit gastric acid secretion

Answer 16

1. Inhibits AC of parietal cells
2. Inhibits histamine
3. Inhibits gastrin cells

Question 17

How does PGE2 impact blood flow

Answer 17

Simulates mucosal blood flow and oxygen delivery by vasodilation

Question 18

Microbial/pathogen recognition leads to what 3 things

Answer 18

1. Activation of immune response
2. Production of effector molecules
3. Commensal bacteria create hostile environment for pathogenic bacteria

Question 19

What are paneth cells

Answer 19

Immune cells located in the SI crypts

Question 20

What are Peyers patches

Answer 20

Mass of lymphatic tissue in the SI, especially the ileum

Question 21

What is the function of pattern recognition receptors

Answer 21

Recognize and discriminate pathogenic bacteria vs commensal bacteria

Question 22

What are the two types of PPR’s

Answer 22

1. Toll like receptors (transmembrane)
2. NOD like receptors (intracellular)

Question 23

What do PRR’s recognize on pathogenic bacteria

Answer 23

1. Lipolysaccharides
2. Flagella
3. DNA/RNA

Question 24

PPR recognition leads to production of what effector molecules

Answer 24

IL-18, IL-1B, TNFalpha

Question 25

What are alpha-Densins (aka cryptidins)

Answer 25

Antimicrobial peptides secreted by paneth cells that have activity against bacteria, some yeast, and giardia trophozoites

Question 26

How do commensal bacteria provide protection (3)

Answer 26

1. Production of inhibitory compounds (stop growth) 2. Competing for adhesion sites 3. Modulating the immune response

Question 27

What factors contribute to the development of IBD

Answer 27

1. Impaired immunity (cytokines) 2. Genetic predisposition (NOD-like receptors) 3. Microbial flora dysfunction (metabolites, dysbiosis)

Question 28

Inflammatory stimuli (HCl injury) induce ___release from mast cells and ____synthesis by epithelial cells

Answer 28

Histamine, prostaglandins

Question 29

The constant repair of GI epithelium helps prevent defects but bears risk of ___

Answer 29

Malignancy

Question 30

What causes an ulcer

Answer 30

Excessive exposure to HCl or SCFA

Question 31

NSAID’s inhibit COX activity which thereby inhibit the production of ___

Answer 31

Prostaglandins

Question 32

What are the 2 ways in which NSAIDs cause toxic effects

Answer 32

1. Inhibit COX and affect in PG synthesis 2. Become trapped in epithelial cells causing damage/death

Question 33

How do NSAIDS effect mucus, bicarbonate, blood flow, cell restitution and inflammation

Answer 33

Decrease all except inflammation which increases

Question 34

How do NSAIDs become trapped in the epithelial cells

Answer 34

1. Carboxylic acids such as NSAIDS are non-ionized in acidic gastric lumen 2. Migrate to inside cell lumen which is neutral and become ionized and trapped 3. Elevated intracellular NSAID levels cause cell death and injury

Question 35

How does H. Pylori result in gastritis, peptic ulcers and potentially a higher rate of gastric neoplasia

Answer 35

1. Burrow into mucus gel layer 2. Adhesins facilitate attachment to mucus layer 3. Disturb HCO3- release and digest mucus layer therefore decrease pH causing ulcers and damage to epithelial lining

Question 36

How do parasites cause damage to GI mucosa/epithelium

Answer 36

1. Mechanical damage to mucus gel layer and mucosa 2. Chronic exposure of mucosal cells to acidic environment 3. Inability of mucosal repair/epithelial proliferation (b/c injury is continuous)

Question 37

What are the two types of disorders that can cause gastrointestinal ischemia

Answer 37

1. Non-occlusive ischemia 2. Occlusive ischemia

Question 38

What is occlusive ischemia and what are some causes

Answer 38

Conditions that directly disrupt gastrointestinal flow Causes: strangulation, volvulus, thromboembolism, bloat/tympany, FB, herniation

Question 39

What is non-occlusive ischemia

Answer 39

Ischemia due to reduce capillary flow or shunting blood away from GI tract so that blood bypasses gastric mucosa

Question 40

Why can stress and Cushings result in non-occlusive ischemia

Answer 40

Both cause an increase in glucocorticoids which results in vasoconstriction