1. GI Part 2 Flashcards
4 routes that secretions of GI tract reach target tissues
- endocrine - deposited close to blood vessels, blood carries them to target tissues
- paracrine - diffuse through interstitial space to affect other nearby cells
- autocrine - substances of a given cell regulate functions of that same cell
- neurocrine - secretions by enteric neurons that affect muscle cells, glands, and blood cells
define a gastric hormone
a hormone must be secreted by one cell and affect another
a hormone must be transported in the blood
a hormone must be stimulated by food and its action must be mimicked by a synthetic analog molecule
5 main GI hormones
Secretin Gastrin CCK GIP Motilin
synthesis site of the 5 main GI hormones
secretin – duodenum, beginning of jejunum
gastrin – antrum (stomach), duodenum
CCK – duodenum, jejunum, ileum
GIP – duodenum, jejunum
Motilin – duodenum, jejunum
actions of the 5 main GI hormones
secretin – stimulate bicarbonate secretion, inhibit acid secretion
gastrin – stimulate acid secretion
CCK – stimulate pancreatic enzyme secretion and gallbladder contraction
GIP – inhibit gastric secretion, stimulate insulin secretion
Motilin – induction of intestinal motility during fasting (MMC)
stimulus of 5 main GI hormones
secretin – acid, fat, protein
gastrin – protein, high pH
CCK – fats, proteins
GIP – fats, glucose
motilin – acetylcholine
three glandular zones of the monogastric stoamch
- cardis –> mucus
- fundus –> HCl, enzymes
- pylorus –> mucus
describe gastric pits
the glandular mucosa of the monogastric stomach has invaginations called gastric pits
gastric pits are lined with mucus secreting cells at the luminal surface called surface mucus cells
each gastric pit leads into a deep gastric gland
describe gastric glands
parietal cells are located in the neck of the gastric glands
chief cells secrete proteolytic enzyme precursors such as pepsinogen
mucous neck cells produce a less viscous secretion, a thin mucus
monogastric stomach cell types
surface mucous cells
parietal cells
mucous neck cells
enteroendocrine cells
chief cells
surface mucous cells
produce a thick mucus to protect the stomach from the acid
function - secretion of mucus
mucins (glycoproteins) secreted by exocytosis
N terminal and C terminal have several cysteine residues –>
disulfide bridges between monomers –>
protection and lubrication of the mucosa
do not live long
parietal cells
secrete intrinsic factor (IF, a glycoprotein) that is essential for vitamin B12 absorption in the ileum
high surface area – lots of intercellular canaliculi
lots of carriers located in canaliculi
carbonic anhydrase – increases rate of reaction
parietal cells release HCl
mucous neck cells
produce a less viscous secretion, a thin mucus
serve as progenitor cells for gastric mucosa
after division they migrate down or up into the pit and differentiate into several types of gastric pit cells
enteroendocrine cells
produce gastric hormones – gastrin, VIP, etc
G cells – gastrin –> mostly produced in the stomach
D cells – somatostatin
I cells – CCK –> mostly produced in the small intestine
thin cytoplasmic projections reach the lumen
secrete granule contents (gastrin, histamine, somatostatin) into lamina propria; some will reach blood capillaries and travel to other parts of the GI tract
chief cells
produce enzymes (pepsinogen)
Pepsinogen (proenzyme)
in acidic pH pepsinogen becomes pepsin (autoproteolysis) –> hydrolysis of proteins
In calves and lambs prochymosin
in acidic pH in the abomasum prochymosin becomes chymosin –> hydrolysis of milk protein
regulation of gastric acid secretion - 3 levels
- neural – mediated by acetylcholine
- hormonal – mediated by gastrin
- paracrine – mediated by histamine (released by enterochromaffin like cells)
regulation of gastric acid secretion - stimulatory and inhibitory substances
stimulatory substances – gastrin, histamine, acetylcholine
inhibitory substances – somatostatin
what does somatostatin do
when the pH goes below 3, D cells stimulated to release somatostatin
somatostatin reduces the activity of G cells
negative feedback
gastric acid secretion - resting state
not eating
few canaliculi
under resting conditions, the H/K ATPase ahs limited access to apical membrane
gastric acid secretion - stimulated state
eating
larger canaliculi
proton pumps and carriers at apical membrane
after stimulation of acid secretion, canaliculi fuse with the apical (luminal) membrane and vesicles containing H/K ATPase are targeted to the apical membrane increasing HCl secretion
secretion of gastric enzymes - stimulation
enzymatic secretion stimulated at 2 levels
neural – acetylcholine, noradrenaline
hormonal – secretin, CCK
gastric enzymes – release of secretin and CCK
release of secretin and CCK form enteroendocrine cells of the small intestine depends on the presence of food particles in the intestinal lumen and the pH
amino acids and fatty acids –> CCK
decreased pH –> secretin
what does secretin do when pH is too low
if pH is too low in the small intestine, secretin is released to reduces gastric acid secretion
reduced gastric acid will then increase the pH
what do acetylcholine and prostaglandin E stimulate
mucus secretion
decreased pH –> acetylcholine and prostaglandin E –> increased mucus
how do NSAIDs affect the mucosa
NSAIDs block the synthesis of prostaglandins as well as several important processes (COX-1 and COX-2) in the gastric mucosa – promoting formation of gastric ulcers
what effects does NSAIDs blocking COX 1 have
reduced mucosal blood flow
reduced mucus and bicarbonate secretion
impaired platelet aggregation
impaired defense
mucosal injury and bleeding
what effects does NSAIDs blocking COX 2 have
reduced angiogenesis
impaired healing
increased leukocyte adherence
leukocyte activation
mucosal injury and bleeding
other effects of NSAIDs
epithelial damage
acid back diffusion
impaired platelet aggregation
impaired healing
mucosal injury and bleeding
how is gastric acid a defense against microorganisms
gastric acid: HCl (pH 1-4) –> defense system (killing microorganisms)
what is the exception for gastric acid defense against microorganisms
Helicobacter pylori
colonization of the mucosa (goes under the mucus layer)
neutralizes acid pH by producing enzyme urease
H2N-CO-NH2 –> 2 NH3 + CO2 –> neutral microenvironment
the ammonia produced acts as a buffer to neutralize the pH
the CO2 produced combines with water to produce bicarbonate and acts as a buffer too
how do NH3 and bicarbonate from urease produced by Helicobacter pylori neutralize pH of the gastric mucosa and how does this cause gastric ulcers
they accept protons (H) to neutralize the pH of the gastric mucosa
gastric mucosa now exposed to gastric acid and can be damaged –> gastric ulcers
gastric ulcers in pigs and horses
pH of 4-6 in proximal part of the stomach
leads to colonization of bacteria
leads to hydrolysis of carbohydrates in short chain fatty acids and lactate
leads to more acidic pH which causes damage to the mucosa
leads to gastric ulcers
what are the 3 phases gastric secretion is said to occur in
cephalic
gastric
intestinal
cephalic phase of gastric secretion
before food enters the stomach
sight, smell, thought, taste
the greater the appetite, the stronger the stimulation
gastric phase of gastric secretion
induced by vasovagal reflexes form the stomach to the brain
through dilation of the stomach
and through the presence of amino acids and peptides in the GI lumen
intestinal phase of gastric secretion
induced by the presence of food in the duodenum
works as a feedback
