Secretory functions of small intestines & mechanisms of diarrhea

Question 1

Secretory cells in small intestine crypts

Answer 1

-crypt stem cells
-crypt enterocytes
-goblet cells
-enteroendocrine cells
-Paneth cells
-M cells

Question 2

Secretory cells in small intestine villus

Answer 2

-villous absorptive enterocytes
-goblet cells
-M-cells

Question 3

Crypt stem cells

Answer 3

-pluripotent stem cell population at base of crypts
-give rise to crypt secretory cells, mucus secreting goblet cells, enteroendocrine cells, and Paneth cells

Question 4

Crypt enterocytes

Answer 4

-secrete Cl, Na, and water into lumen
-migrate up the crypt and then up the villus where their phenotype switches to become absorptive enterocyte

Question 5

How do crypt enterocytes move up the crypt?

Answer 5

lamellipodia allow them to walk up the crypt (1-2 days to migrate up, 3-4 to reach tip of villus and then they are sloughed off)

Question 6

Goblet cells

Answer 6

-migrate up villi
-become more numerous from duodenum to ileum
-secrete mucus

Question 7

Enteroendocrine cells

Answer 7

-remain near base of crypt
-contain secretory granules containing the hormone they will secrete (ex. CCK, secretin, ghrelin, serotonin, etc.)

Question 8

Paneth Cells

Answer 8

-do not migrate
-secrete antibacterial substances such as lysozymes, phospholipases and defensins
-not in dogs, cats, pigs

Question 9

M-cells or dome cells

Answer 9

-not derived from crypt stem cells
-associated with Peyer’s patches (immune system)
-mostly present in crypts, few in villus

Question 10

Villous absorptive enterocytes

Answer 10

-derived from crypt secretory enterocytes
-on villi, begin to secrete enzymes within the apical membrane microvilli (brush border) and transport proteins required for absorption

Question 11

Cell characteristics lining mucosal surfaces

Answer 11

-have apical and basolateral membranes
-adjacent cells linked by tight junctions
-impermeable to viruses, bacteria, large molecules,
-also impermeable to water and small ions but it can be overcome if electrochemical gradient is present

Question 12

Brunner’s glands

Answer 12

-Present in submucosa; upper duodenum
-produces a mucus-rich alkaline secretion (bicarbonate)
>acinar cells secrete mucus; ductal cells add K and Na and remove Cl = form alkaline secretion
-stimulated by secretin (from enteroendocrine I cells) in response to low pH

Question 13

Role of crypt enterocytes in diarrhea

Answer 13

-enterocytes secrete Cl, Na, Water
>Na provides the electrochemical force required for transport of AA, sugars, phosphate
>water reduces osmolarity of the digesta

Question 14

Enterocyte crypt cell stimulation

Answer 14

-vagal and enteric nervous systems sensory neurons sense changes within the lumen
>changes include increased osmolarity, stretch, AA’s, or decreased pH
-medulla receives these signals, and initiates parasympathetic efferent stimulation of crypt cells

Question 15

Diarrhea mechanism

Answer 15

1.vagus nerve responds to stretch or osmotic changes and releases acetylcholine.
2. Acetylcholine activates muscarinic receptors. Stimulates G-protein activation of PL-A catalyzing production of IP3
3. IP3 acts on membranes of internal cell organelles that store Ca2+ causing the Ca channels to open
4. Ca binds to calmodulin resulting in its activation. Ca-calmodulin complex interacts with a Cl pump (CFTCR) causing it to open
>ATPase activation also occurs to help create energy to pump Cl against gradient
5. Cl pumped into the lumen and is replaced by Cl from extracellular fluid at the same time
6. Negative Cl and high Na in the extracellular fluid results in the Na ions moving to the lumen across the tight junction opening
7. Water follows through specialized water channels

Question 16

CFTCR

Answer 16

-cystic fibrosis transmembrane conductance regulator protein

Question 17

Diarrhea mechanisms

Answer 17

-Transit disorder
-osmotic diarrhea

Question 18

Transit disorder

Answer 18

-hypermotility- rapid intestinal transit due to rapid peristalsis
-increases volume of fluid into the lumen by increased secretion or decreases/incomplete absorption may accelerate transit time

Question 19

Osmotic disorder

Answer 19

-accumulation of non-absorbable solute in the gut lumen
-poor absorptive pathway for solute (mannitol, sucrase, lactase)
-overwhelmed transport systems (sudden overeating)
-loss of absorptive surfaces, villus shedding

Question 20

Abnormal fluid and electrolyte transport

Answer 20

-affects unidirectional secretion into the intestinal lumen AND unidirectional absorption into intestinal mucosa

Question 21

When does diarrhea occur?

Answer 21

-net fluid absorption exceeds secretion by:
>increase secretion exceeding normal absorption (secretory)
>inhibit absorption, exceeding normal secretion (malabsorptive)
>combination of both (secretory and malabsorptive; but often called secretory)

Question 22

Clinical indicators that help localize diarrhea

Answer 22

-mucus (SI: no; LI: yes)
-blood (SI:digested/dark; LI: fresh/bright red)
-weight loss (SI: no; LI: yes)
-volume (SI: larger; LI:smaller)
-increased frequency (SI: no; LI: yes)

Question 23

Mechanism of diarrhea pathogens

Answer 23

1.increase secretion through direct activation of the secretory cells. Usually through increased activation of phosphorylation pathway, leading to activation of secretory channels
2.activation of ENS leading to indirect activation of secretory cell
3.inhibition of absorptive transporters
4. disruption of the tight junctions
5. reducing the absorptive cells

Question 24

Crypt cell and enteroendocrine/serotonin cell activation through toxins, pathogens, poisons

Answer 24

-crypt cell activated by prostaglandins, G-protein receptors, and IP3. Leads to opening of Ca channels and secretion of Cl, Na, water
-serotonin cells: toxins activate receptors on cells resulting in the cells fusing to membrane and releases serotonin into lamina propria. Serotonin activates crypt cells, opening of Ca channels, and the formation of Ca-calmodulin and activation of Cl transporter. Na and Water follow Cl through tight junction

Question 25

Infectious secretory diarrhea

Answer 25

-increases intracellular cAMP, inducing serotonin release from enterochromaffin cells
-serotonin stimulates secretion
-blood flow enhanced by vasodilation by VIP and NO

Question 26

Cholera toxin and E coli toxins

Answer 26

-results in increased blood flow in the gut wall due to vasodilation by VIP and NO

Question 27

Outcome of infectious secretory diarrhea

Answer 27

-fluid loss
-HCO3- loss
-dehydration
-acidosis
-death