Barrier Function

Question 1

what parts of the GI tract are stratified squamous epithelium?

Answer 1

upper digestive tract (through esophagus), then continues in the anal canal

everything in between is simple columnar

Question 2

luminal layer of the stratified squamous epithelium of the esophagus

Answer 2

6-7 layers

functional layer - serving as a barrier…since these layers have tight junctions

Question 3

middle (prickle layer) of the esophageal epithelium

Answer 3

no tight junctions

ion transport

Question 4

lower layer of esophageal epithelium

Answer 4

replication

no tight junctions

Question 5

surface cells of the simple columnar epithelium

Answer 5

mostly comprised of cells that secrete mucus and HCO3-

Question 6

secretion of HCL - general uses, risks

Answer 6

needed for both digestion and absorption of nutrients and for protection against bacterial colonization

risk –> damage to epithelial lining with which it comes in contact

could lead to gastroesophageal reflux disease (GERD) or peptic ulcer disease (PUD)

Question 7

stomach and duodenum pre-epithelial defense system against acid damage

Answer 7

buffer zone at the surface, due to the presence of an adherent mucus coat that is rich in HCO3-

mucus and HCO3- secreted by surface cells

Question 8

esophagus pre-epithelial defense to acid damage

Answer 8

minimal because the squamous epithelium does NOT secrete mucus or HCO3-

Question 9

epithelial defense against acid damage (esophagus –> duodenum)

Answer 9

1. hydrophobic cell membranes
2. apical membrane channels that inhibit cation entry at acidic luminal pH
3. tight junctions
4. intracellular and intercellular bufferes
5. basolateral membrane transporters (cell alkanizers for removal of excess H+ from cell)

Question 10

Na+ entry into epithelial cells (regarding acid defense system)

Answer 10

Na+ entry into cells aids H+ extrusion

occurs along a concentration gradient with extracellular Na+ being high (equilubrated with blood)…

Na+/K+ pumps keep intracellular Na+ low

Question 11

buffers for acid defense in cell

Answer 11

HCO3- (also outside cell)
PO4(2-)
anionic proteins

Question 12

basolateral cell alkanizer transporters

Answer 12

Na+/H+ exchanger (H+ out)

Na+ and HCO3-)/Cl- exchanger (Cl- out

Question 13

basolateral cell acidifier transporters

Answer 13

Cl-/HCO3- exchanger (HCO3- out)

Question 14

post-epithelial acid defense (blood side)

esophagus –> duodenum

Answer 14

interstitial fluid within the wall and epithelium is in equilibrium with the fluid compartment of the blood

therefore…

the post epithelial defense is due to the circulation of blood through the organ’s capillary network

a network that continuously replenishes the tissues O2, nutrients, and HCO3- for acid buffering…while serving to remove waste

Question 15

stomach additional defense system against acid (unlike the duodenum and esophagus)

Answer 15

‘alkaline tide’

refers to the fact that the byproduct of HCL production by gastric parietal cells is prodction of HCO3-

therefore…HCL production by parietal is matched by transportation of HCO3- into capillary circulation

capillary circulation then delivers the HCO3- to the surface cells for buffering of H+

Question 16

how does HCO3- get from the blood –> luminal side of surface cells to buffer the H+ (alkaline tide defense system in stomach)

Answer 16

parietal cell:

H2CO3 –> H + HCO3-

HCO3- leaves via Cl/HCO3- exchanger into blood

surface cell:

HCO3- enters basolateral side via reverse HCO3-/Cl- exchanger

diffuses through cytoplasm to another exchanger into luminal membrane where… H+ + HCO3- –> H2CO3

then…H2CO3 –> CO2 + H20 (CO2 diffuses back into lumen)

Question 17

2 repair mechanisms following injury

stomach and duodenum and esophagus

Answer 17

1. restitution

2. replication

Question 18

‘mucus cap’

only stomach and duodenum

Answer 18

created via the restitution and replication repair mechanisms

results from release of mucus from surface mucus cells to cover the injury site…further entrapping HCO3- at the site

therefore cap also provides a buffer zone to protect the would from acid access and inhibition of repair

Question 19

epithelial restitution

Answer 19

small defects with intact basolateral membrane

no DNA or protein synthesis

rapid 30-60 minutes

migration of adjacent viable cells over defect

Question 20

epithelial replication

Answer 20

large defects

collagen deposition is needed

needs DNA and protein synthesis…thus slow; days to weeks to complete

Question 21

prostaglandin E2

Answer 21

needed for stomach and duodenum repair (not esophagus)

stimulation of the following:

1. mucus secretion
2. HCO3- secretion
3. blood flow
4. promotes epithelial restitution

Question 22

NSAIDS and peptic ulcer disease

Answer 22

NSAIDS inhibit COX1

therefore inhibit prostaglandin E2 in repair mechanisms for acidic damage…

Question 23

Celebrex

Answer 23

COX2 inhibitor

retains anti-inflammatory properties while preserving the ability of prostaglandins to protect epithelium

Question 24

exuberant collagen deposition

Answer 24

can lead to stricture that can obstruct the downstream movement of food through the organ

Question 25

Barrett’s esophagus (BE)

Answer 25

damage squamous epithelium can be replaced by specialized columnar epithelium

more acidic resistant…but comes with risk of becoming an esophageal adenocarcinoma