Secretions of the GI tract and pancreas Flashcards
Where is saliva produced
salivary glands
Function of saliva
initial digestion of starches and lipis
3 major salivary glands
parotid, submaxillary, sublingual
Which is the largest salivary structure
parotid gland
Parotid gland secretions
serous cells
What percent of daily output of saliva is from parotid gland
25%
Secretions from sublingual and submandibular
mixed- serous and mucous cells
75% daily output of saliva
Blood supply to salivary glands
external carotid artery
4 parts of the structure of salivary glands
acinus, myoepithelial cells, intercalated duct, and striated duct
Acinus function
secrete initial saliva
Myoepithelial cell function
contain actinomycin and contract to eject saliva into the mouth
Intercalated duct function
contains myoepithelial cells and has ionic saliva
Striated duct function
modify initial saliva to produce final saliva and contain columnar epithelial cells
Composition of final saliva product
hypotonic (compared to plasma), increased K+ and HCO3 concentrations, decreased Na and Cl concentrations
What are the components of saliva
H20, electrolytes, a-amylase, lingual lipase, kallikrein, and mucus
A-amylase functon
begins initial digestion of carbohydrates
Lingual lipase function
begins initial digestion of lipids
Kallikrein function
protease involved in production of bradykinin
Bradykinin function
vasodilator
2 main steps in formation of saliva
- Form isotonic and plasma like solution by acinar cells
2. Modification of isotonic solution by the ductal cells fvg
3 transport mechanisms for salivary secretion on luminal side
1.Na/H+ exchange, 2. Cl-/HCO3- exchange, 3. H+/K+ exchange
2 transport mechanisms for salivary secretion on basolateral (blood) side
1.Na+/K+ ATPase, 2. Cl- channels
Net result of salivary secretion mechanism
absorption of Na/Cl, secretion of K/HCO3, net absorption of solute (more NaCl absorbed)
2 options on how HCO3 can leave the cell
1.through cAMP-activated CFTR (cystic fibrosis transmembrane regulator) Cl- channel, 2. Cl-/HCO3 exchanger
Cystic fibrosis patients
lack Cl- transporter (CTFR)
What is elevated in patients with cystic fibrosis
Ca+, Na+ and protein
T/F Ductal cells are permeable to H2O
F- ductal cells are impermeable to water which helps make saliva hypotonic
What does ionic composition depend on?
rate of secretion
An increase flow rate….
- saliva resembles plasma and initial saliva
- less time for ductal cells to be in contact with saliva
A decreased flow rate…
- final saliva has lower concentrations of Na+ and Cl-, and higher concentration of K+
- more time for ductal cells to modify the saliva
“Contact-time” dependent mechanism
amount of time ductal cell is in contact with saliva determines ionic composition
DOES NOT APPLY TO HCO3
HCO3 secretion
selectively stimulated when saliva production is stimulated
Innervation to salivary glands
ANS
Presynpatic nerves origin for parasympathetic innervation to salivary glands
facial and glossopharyngeal nerves
Postsynpatic nerves origin for parasympathetic innervation to salivary glands
autonomic ganglia innervate individual glands
What ganglion and nerves is the facial nerve associated with?
Submandibular ganglion for sublingual and submandibular glands
What ganglion and nerves is the glossopharyngeal nerve associated with
Otic ganglion to the auriculotemporal branch of trigeminal nerve to the parotid gland
Preganglionic nerve origin for sympathetic innervation of salivary glands
cervical ganglion
Postganglionic fibers for sympathetic innervation of salivary glands
glands in the periarterial spaces to thoracic spinal nerves
What can up regulate the parasympathetic innervation to salivary glands
conditioning (?), food, nausea, smell
What can down regulate paraysympathetic innervation to salivary glands
fatigue, dehydration, fear, sleep
Neurotransmitter associated with parasymp salivary innervation
Ach
Neurotransmitter associated with sympath salivary innervation
NE
Receptor on acinar or ductal for parasympath innervation of salivary glands
mAchR
Receptor on acinar or ductal for sympath innervation of salivary glands
Beta- AR
Stimulation of salivary cells results in…
increase saliva production, increase HCO3 and enzyme secretions and contraction of myoepithelial cells
Vasopressin and aldosterone effect on saliva
decrease Na+ concentration and increase K+ concentration
T/F Salivary secretion is increased by only parasympathetic nervous system
F- salivary secretion is increased by both parasymp and sympath stimulation
What do cells of gastric mucosa secrete
gastric juice
5 main components of gastric juice
HCl, pepsinogen, mucus, instrinsic factor, H2O
HCl function in gastric juice
initiate protein digestion, converts pepsinogen to pepsin, and kill bacteria in stomach
Pepsinogen function in gastric juice
inactivates precursor to pepsin
Mucus function in gastric juice
protect stomach from damage, lubrication, with HCO3 it neutralizes acid
Intrinsic factor function in gastric juice
required for absorption of B12 in ileum, and is indispensable (absolutely necessary)
H2O function in gastric juice
solubilized much of ingested material
Location of oxyntic gland
proximal 80% of stomach
Function of oxyntic gland
secretes acid
Location of pyloric gland
distal 20% if the stomach
Function of pyloric gland
synthesized and releases gastrin
Cells in oxynotic gland
parietal cell, mucous neck cell, enterochromaffin like cells, D cells, chief cells
Cells of pyloric gland
mucous neck cells, G cells, D cells
Cells in body of the stomach
parietal cells (intrinsic factor and HCl), Chief cells (pepsinogen)
Cells in antrum of the stomach
G cells (gastrin into circulation ), Mucus cells (mucus, HCO3, and pepsinogen)
What does the number of parietal cells determine
secretory rate
How many L of gastric juices does the stomach secrete everyday
1-2 L/day
Function of low gastric pH
convert pepsinogen to pepsin
Where is HCl formed
villus-like membranes of canaliculi which is continuous with the lumen
Function of Omeprazole
inhibit the H+/K+ ATPase making H+ more concetrated in lumen and Cl- follows H+ so HCl is secreted
“Alkaline tide”
HCO3 is pumped into the blood because Cl- is being pushed out due to the inhibition of the H+/K+ ATPase
Net result of Omeprazole (inhibition of H+/K+ ATPase)
HCl- secretion and HCO3 absorption
Histamine function for HCl secretion
stimulates HCl secretion
What cells secrete histamine
enterochromaffin-like cells
What stimulates histamine release
gastrin and Ach
What receptors does histamine bind to?
H2 receptors on parietal cells
What can block H2 receptors on parietal cells
Cimetidine
End result of histamine
activates cAMP cascade and secretes H+ through the H+/K+ ATPase
Ach function for HCl
stimulates HCl secretion
Where is Ach released from
vagus nerve innervating gastric mucosa
What receptor does Ach bind to
mAchR on parietal cells
Function of Atropine
block the mAchR receptors so Ach can’t bind
End result of Ach
activates IP3 and Ca2+ and secretes H+ through H+/K+ ATPase
Indirect effect of Ach on HCl
stimulates ECL cells (enterochromaffin-like cells) which release histamine
Gastrin function for HCl
stimulates HCl secretion
What secretes gastrin
G cells in antrum of the stomach
What receptor does gastrin bind to?
CCKB receptor on parietal cells
CCKB
has equal binding affinity for gastrin and CCK
CCKA
receptor specific for CCk
End result of gastrin
activates IP3/Ca2+ and secretes H+ through H+/K+ ATPase
Stimuli for gastrin secretion
gastric distention, small peptides and amino acids, stimulation of vagus nerve
Indirect effect of gastrin for HCl
stimulates ECL cells which release histamine
Atropine on gastrin
DOES NOT block vagal stimulation of the G cells
Somatostatin function on HCl
inhibits HCl secretion
What cells release somatostatin
D cells in antrum
What receptor does somatostain bind to?
somatostatin receptors on parietal cells
End result of somatostatin on HCl
inhibits adenylate cyclase and inhibits secretion of H+
Indirect effect of somatostatin on HCl
inhibits histamine release from ECL cells and gastrin release from G cells
Potentiation
combined response to two stimulants exceeds the sum of their individual responses
requires 2 specific receptors
Histamine potentiates with…
Ach and gastrin
Ach potentiates with…
histamine and hastrin
Cimetidine potentiation phenomena
antagonist of H2 receptors block direct action of histamine and Ach and gastrin
Atropine potentiation phenomena
antagonist of mAchRs block direct action of Ach and Ach-potentiated actions of histamine and gastrin
2 pathways of vagus nerve stimulation
- Direct pathway
2. Indirect pathway
Which pathway does atropine block?
direct pathway
3 phases of gastric HCl secretion
1.Cephalic phase, 2. Gastric phase, 3. Intestinal phase
Cephalic phase
1.vagus nerve –> parietal cells, 2. vagus nerve –> gastrin –> parietal cells
Gastric phase
local nervous secretory reflexes, vagal reflexes, gastrin-histamine stimualtion
Intestinal phase
nervous mechanism and hormonal mechanism
Stimuli of cephalic phase
smelling, tasting, chewing, swallowing, and conditioned reflexes
Direct pathway for cephalic phase
1.innervation releasing Ach to parietal cells, 2. Ach stimulates secretion of HCl from parietal cells
Indirect pathway for cephalic phase
1.Innervation releasing gastrin-releasing peptide to G cells, 2. G cells release gastrin into circulation, 3. Gastrin is delivered back to stomach to stimulate HCl secretion from parietal cells
What happens if a vagotomy occurs….
abolishes cephalic phase
Stimuli for gastric phase
distention of the stomach, presence of breakdown of proteins, amino acids and small peptides
4 mechanisms of gastric phase
1.Direct distention, 2. Indirect distention, 3. Distention of antrum, 4. Amino acids and small peptides
Direct distention in gastric phase
vagus nerve–> Ach –> parietal cell –> HCl
Indirect distention in gastric phase
vagus nerve–>gastrin releasing hormone –> G cells –> gastrin in circulation –> gastrin delivered back to stomach –> parietal cells –> HCl
Distention of antrum in gastric phase
local reflex –> pyloropyloric reflex –> gastrin –> parietal cell
Amino acids and small peptides in gastric phase
gastrin –> parietal cell –> HCl
Coffee effect on HCl
stimulates gastric HCl secretion
2 intestinal phase mechanisms
1.Distention of small intestine 2. Digested protein (amino acids)
Distention of small intestine in intestinal phase
stimulates acid secretion
Digestion of protein in intestinal phase
stimulate acid secretion via direct parietal cell activation–> gastrin (intestinal G cells) –> parietal cell
What does gastric juice composition depend on..
secretion rate
Low secretion rate ….
final juice is NaCl solution
Higher secretion rate …
final juice decrease Na concentration and increase in H+ concentration
At peak secretion rate …
final juice is primarily HCl
T/F gastric juice and plasma are isotonic, regardless of secretion rate
T
2 types of gastric juice mixtures
1.Nonparietal 2. Parietal
Nonparietal mixture
alkaline secretion and low volume
Primary components of nonparietal mixture
Na+, Cl-, K+ in same concentration
Parietal mixture
slightly hyperosmotic
Only anion present in parietal mixture is …
Cl-
When is composition of gastric juice knowledge helpful
treatment for patient suffering from vomiting or maintained IV
GRP function
gastrin release
Vagal activation on gastrin release
releasing GRP and inhibiting release of somatostatin
Gastrin association with somatostatin
negative feedback and increase somatostatin
H+ in the lumen association with somatostatin
stimulate release of somatostain
When is pepsinogen secreted
when gastric pH is acidic enough to be converted to pepsin
2 cells that secrete pepsinogen
chief cells and mucus cells in oxyntic glands
Most important stimulus for pepsinogen secretion
vagus nerve stimulation
Pepsin positive feedback on pepsinogen
pepsin converts more pepsinogen to pepsin
What is intrinsic factor
mucoprotein secreted by parietal cells
Failure to secrete intrinsic factor can lead to..
pernicious anemia
What can cause pernicious anemia/failure to secrete intrinsic factor
destruction of gastric parietal cells
Where is vitamin B12 stored
liver
What is secreted by gastric epithelium
HCO3 and mucus to make gel-like mucosal barrier
What do mucus neck cells secrete
mucus
What do gastric epithelial cells secrete
HCO3
Function of mucosal barrier
protects gastric mucosal epithelium against HCl and pepsin
What components can protect gastric mucosa
HCO3, mucus, prostaglandins, mucosal blood flow, and growth factors
What components can damage gastric mucosa
Acid, pepsin, NSAID, H. pylori, aspirin, alcohol, bile, and stress
S/S of Gastrinoma
diarrhea, vomitting, peptic ulcer, increase resting gastrin, weight loss, GERD, epigastric pain
What syndrome are gastrinoma tumors associated with
ZOllinger-Ellison syndrome
How can a peptic ulcer form
loss of protective mucosal layer, excessive H+ and pepsin
Two types of peptic ulcers
Gastric ulcers and duodenal ulcers
What can cause a gastric ulcer
defective mucosal barrier and/or H pylori
H. pylori function on gastric ulcer
release cytotoxins that bkdown mucosal barrier, contain urease that allow bacteria to colonize and convert urea to NH3 which makes basic environment
Diagnostic test for gastric ulcer
urease activity
How can duodenal ulcer form
H+ secretory rate are higher than normal
H. pylori function on duodenal ulcer
indirect effect- inhibits somatostatin from D cells (inhibit inhibition) and gastric H. pylori speads to duodenum and inhibits duodenal HCO3 secretion
Excessive H+ in duodenum
overwhelms buffer of HCO3 in pancreatic juice
Zollinger-Ellison syndrome
tumor, usually pancreas secretes large amt gastrin
Low duodenal pH inactivates..
pancreatic lipases, resulting in steatorrhea
Treatment options for duodenal ulcers
cimetidine, omeprazole, surgical removal of tumor
Components of pancreatic juice
- HCO3 for neutralization
- enzymes to secrete carbs, proteins, lipids
Two main components of exocrine pancreas
1.aqueous solution containing HCO3, 2. Enzymatic secretion
Acinus of exocrine pancreas
lined by acinar cells that secrete enzymatic portion
Ducts of exocrine pancreas
lined by ductal cells that extend into acinus containing centroacinar cells
What do ductal and centroacinar cells secrete
aqueous solution containing HCO3
Parasympathetic innervation of exocrine pancreas
vagus nerve
Preganglionic fibers of exocrine pancreas for parasym
ENS
Postganglionic fibers of exocrine pancreas for sympath
synapse ON exocrine pancreas
Sympathetic innervation of exocrine pancreas
Postganglionis nerves from celiac and superior mesenteric plexus
Difference btwn innervation of salivary gland and exocrine pancreas
in exocrine pancrease- parasymp stimulates pancreatic secretion and sympath activity inhibits pancreatic secretion
Two components of pancreatic secretion
- enzymatic secretion of acinar cells
- aqueous secretion by centroacinar and ductal cells
Enzymatic section by acinar cells
enzymes that digest carbs, proteins, lipids
pancreatic amylase and lipase
Where are pancreatic proteases converted to active form
in the lumen of duodenum
What cells produce initial isotonic solution
centroacinar and ductal cells
Where does modification of initial pancreatic section occur
ductal cells
Net result of pancreatic modification
secretion of HCO3 into pancreatic juice and net absorption of H+
Ionic composition of pancreatic juice depends on…
rate of secretion
Increased flow rate on pancreatic juices
HCO3 is highest and Cl- is lowest
Decreased flow rate on pancreatic juices
HCO3 is lowest and Cl- is highest
How is relationship between HCO3 and Cl- concentrations maintained in pancreatic juice
HCO3-/Cl- exchanger in apical membrane of ductal cells
3 phases of pancreatic secretion
1.Cephalic, 2. Gastric, 3. Intesitnal
Cephalic phase of pancreatic secretion
produces mainly enzymatic secretion, mediated by vagus nerve
Gastric phase of pancreatic secretion
produces mainly enzymatic secretion, mediated by vagus nerve
Intestinal phase of pancreatic secretion
!! most importan phase! - 80% of pancreatic secretion
- both enzymatic and aqueous secretion stimulated
Upregulators of pancreatic secretion in intestinal phase for I cells
phenylalanine, methionine, tryptophan, small peptides, fatty acids
Upregulators of pancreatic secretion in intestinal phase for IScells
H+
How does acute pancreatitis occur?
pancreatic enzymes are activation in pancreas and autodigest the pancreas