Secretions of GI Flashcards
What are the main functions of saliva?
initial digestion of starches and lipids
dilution and buffering of ingested food
Lubrication of ingested food with mucus
Describe parotid glands
largest of the salivary structure located near angle of jaw and ear serous cells Fluids: water, ions, and enzymes with amylase secrete 25% of daily output of saliva
Describe Submaxillary and sublingual glands
mixed glands: serous and mucous cells
secrete aqueous fluid and mucin glycoprotein for lubrication
secrete most of 75% of daily output saliva
What is the salivary’s embryologic origin?
ectodermal
What is the blood supply to the savilary glands?
branches of external carotid artery
Describe the acinus of the salivary gland?
blind end
have acinar cells that secrete initial saliva
Describe the intercalated duct of the salivary gland
contains myoepithelial cells
saliva in the intercalated duct is similar to ionic composition to plasma
what are myoepithelial cells?
Cells that rest on the basement membrane of acinar cells and intercalated ducts
contain actinomycin
have motile extensions
What part of the salivary gland contracts when stimulated by neural input to eject saliva into the mouth?
myoepithelial cells
Describe the striated duct of the salivary gland
lined by columnar epithelial cells (ductal cells)
Ductal cells modify initial saliva to produce final hypotonic saliva
cells alter the concentration of various electrolytes
What is saliva coomposed of?
water electrolytes Alpha-amylase: digest carbs lingual lipase: digest lipids killikrein: protease involved in the production of bradykinin (vasodilator)
Compared to plasma, what are the concentrations of the following ions in saliva?
K, Na, Cl, bicarb
K and bicarb concentrations are higher in saliva than plasma
Na and Cl concentrations are lower
What are the 2 main steps in the formation of saliva?
Formation of isotonic, plasma-like solution by acinar cells
Modification of the isotonic solution by the ductal cells (impermeable to water)
There is net absorption of solute, more ______ is absorbed than ______ is secreted from ducts
NaCl
KHCO3
What are the transport mechanisms on the lumen/apical side of the salivary ductal cell?
On the basolateral side?
Lumen:
Na/H exchange
Cl/HCO3 exchange
H/K exchange
Basolateral: Na/K ATPase and Cl- channels
How does HCO3 leave the ductal cell?
either through cAMP-activated CFTR Cl/HCO3 channel or via the Cl/HCO3 exchanger
both on the apical membrane
In patients with cystic fibrosis, what transporter is lacking? Thus, what is elevated?
CFTR
salivary Ca, Na, and protein are elevated
Also true for bronchial secretions, pancreatic juice, and sweat
Why does saliva become hypotonic as it flows through the ducts?
ductal cells are H2O impermeable
At increased flow rate, final saliva resembles what?
plasma and initial saliva
At decreased flow rate, what is the final saliva concentration?
lower concentration of Na and Cl and higher concentration of K
What is “contact-time” dependent mechanism?
What does it not apply to?
The amount of time that saliva is in contact with ductal cells influences the ionic composition
As flow rate increases, ductal cells have less time to modify saliva and vice versa
Does not apply to bicarb - its secretion is selectively stimulated when saliva production is stimulated
What is the Parasympathetic innervation of salivary glands? What does it lead to the production of?
Facial and glossopharyngeal nerves
PS dominates
Receptors on acinar and ductal cells
Leads to the production of IP3 and increase [Ca] which increases saliva production and bicarb and enzyme secretions
What is the sympathetic innervation of salivary glands?
originate at cervical ganglion whose postganglionic fibers extend to glands in the periarterial spaces
Ne->B-adrenergic receptors on acinar and ductal cells
Increase cAMP and increases salivary volume
What stimulates parasympathetic control of salivary glands?
What inhibits ?
Conditioning food, Nausea, Smell
Fatigue, dehydration, fear and sleep
What can modify the composition of salvia by decreasing its Na concentration and increasing K concentration?
vasopressin and aldosterone
Salivary is _____ under the control of the ANS
exclusively
*other GI secretions are under both neural and hormonal control
Does sympathetic stimulation decrease salivary secretion?
no.
Salivary secretion is increased by both PNS and SNS stimulation
What are the main components of gastric juice?
HCL, pepsinogen, mucus, intrinsic factor, H2O
What is the origin, location, and action of HCL?
Origin: parietal cells
Location: stomach, villus of lumen
Actions: initiates process of protein digestion, converts pepsinogen to pepsin, kills lg # of bacteria in stomach
What are the main actions of mucus?
lines wall of stomach
protects from damage
lubricant
with bicarb, it neurtralizes acid and keeps surface at neutral pH
What are the main actions of intrinsic factor?
needed for absorption of Vit B12 in ileum
released from parietal cells
What is the role of water in gastric juice?
medium for action of HCL and enzymes
solubilizes much of ingested material
Describe oxyntic glands
glands that are located in the proximal 80% of the stomach (Body/fundus)
secretes acids
parietal cells, suface/mucous neck cells, ECL cells, D cell, Chief cell, ECC
Describe pyloric glands
located in distal 20% of stomach (antrum)
synthesizes and release gastrin
surface/mucous neck cell, G cell, D cell, ECC
What determines the maximal secretory rate of HCL?
the # of parietal cells
Where is HCL formed in parietal cells?
at the villus-like membranes of the canaliculi which are continuous with the lumen
What are the metabolic processes and membrane-associated proteins that are involved in HCL secretion?
Apical: H/K exchanger and Cl channel (Cl follows H)
Basolateral: Na/K exchanger and Cl/HCO3 exchanger
Carbonic anhydrase activity
Net secretion of HCL and net absorption of HCO3
What is the alkaline tide?
The bicarb secreted to the blood side of the gastric parietal cell will be alkalytic because of the bicarb being absorbed
What is histamine released from and what are its main actions?
What stimulates its release?
(paracrine) Released from ECL cells in gastric mucosa
Stimulates HCL secretion by binding to H2 receptors on parietal cells and cAMP cascade. H secreted through H/K ATPase
Gastrin and ACh stimualtes
How does ACh stimulate HCL secretion?
From vagus n it binds to M3 mAChR on parietal cells
IP3/Ca cascade
Secretion of H through H/K ATPase
Indirect effect through stimulation of ECL cells that release histamine
How does Gastrin stimulate HCL secretion?
Gastrin is a hormone that is secreted into blood by G cells in the antrum
Bind to CCKB cells on parietal cells
IP3/Ca cascade
Secretion of H through H/K ATPase
Indirectly: stimulation of ECL cells that release histamine
What stimulates gastrin secretion?
gastric distention
presence of small peptides and a.a.
stimulation of vagus nerve
What can atropine block?
What can it not block?
Can block HCL release by blocking ACh from binding to mAChR
Does NOT block vagal stimulation of G cells
How does somatostatin inhibit HCL secretion?
In D cell of antrum, the somatostatin is released and binds to SSTR2 on parietal cells
inhbits adenylate cyclase that inhibits H secretion
Indirect: inhibits histamine release from ECL cells and gastrin release from G cells
What can block the direct effects of histamine?
What is the purpose of the drug?
cimetidine (H2 antagonist) : used to treat duodenal and gastric ulcers, gastroesophageal reflux disease etc
What can block the H/K ATPase? what is the purpose of this drug?
Omeprazole: used in the treatment of ulcers to reduce H secretion
How do PGs inhibit HCL secretion?
inhibits Histamine via Gi pathway
The vagus nerve can stimulate of HCL secretion by parietal cells 2 ways. What are the two pathways and why can atropine only work on one of them?
Direct: vagus nerve ACh action on Parietal cells - atropine blocks ACh from binding
Indirect: Vagus stimulates gastrin secretion via neurotransmitter GRP. atropine cant block
Gastrin HCL secretion is divided into what phases?
Cephalic phase
Gastric Phase
Intestinal phase
Describe cephalic phase
30% of HCL secreted in response to a meal
Stimuli: smelling, tasting, chewing, swallowing
Via vagus -> parietal cells
Vagus->gastrin->parietal cell
Vagotomy abolishes this phase
Describe gastric phase
60% of HCL
Stimuli: distension of stomach, presence of proteins, a.a., and small peptides
Mechanisms:
- Distension activates mechanoreceptors in oxyntic and pyloric glands -> vagus stimulation (2ways)
- Local reflex from distension(pyloropyloric reflex)->gastrin->parietal cell
- aa and small peptides ->G cells->gastrin->parietal cell
What are the non-physiological stimulants of HCL gastric secretion?
Alcohol and caffeine
Describe intestine phase
~10% of HCL
Stimuli: distention of small intestine - stimulates acid secretion
Stimuli: digested proteins - stimulate acid secretion via direct effect on parietal cell: gastrin (intestinal G cells)->parietal cell
What does the gastric juice composition depend on?
secretion rate
Low = NaCl
High = [Na] decreases and [H] increases; primarily HCL
in gastric juice, The concentration of H, K and Cl are (greater than/less) than those in plasma, and the concentration of Na is (greater/less) than that in plasma
greater
less
Gastric juice can be seen as a mixture of two separate secretions: describe the non parietal secretion
basal alkaline secretion of constant and low volume
1* constituents = Na, Cl, K and same concentration as in plasma
Bicarb secreted at concentration of 30 mEq/L
Gastric juice can be seen as a mixture of two separate secretions: describe the parietal secretion
Slightly hyperosmotic
Cl- is only anion present
As secretion rate increases, concentrations of electrolytes begin to approach those of pure parietal cell secretion
What inhibits the release of somatostatin?
vagal stimulation with ACh
What activates somatostatin release?
Increase of gastrin
H in the lumen of the stomach
what is pepsinogen secreted by?
chief cells and by mucus cells in the oxyntic glands
What is the most important stimulus for pepsinogen secretion ? what is another stimulus?
vagus nerve
Low pH - requires H secretion from parietal cells
H+ triggers local cholinergic reflex that stimulates chief cells to secrete pepsinogen
Pepsin degrades food proteins into peptides but can also act as a proteolytic enzyme to what zymogen ?
pepsin can convert more pepsinogen to pepsin
What is the optimal pH for pepsin?
What is the reversibly inactivated pH for pepsin?
what is the irreversibly inactivated pH for pepsin?
Optimal: 1.8-3.5
RI: >pH 5.0
II: >pH 7-8
What is the only secretion by the stomach that is required (essential)?
intrinsic factor: a mucoprotein that is secreted by parietal cells
What does intrinsic factor do? what does the failure to secrete intrinsic factor lead to?
Combines with Vit B12 to form a complex for absorption
Pernicious anemia: destruction of gastric parietal cells
The gastric epithelium secretes bicarb and mucus to form the gel-like mucosal barrier. What cells secrete the bicarb and mucus?
mucous neck cells - mucus
gastric epithelial cells - bicarb
What does the mucosal barrier protect the gastric mucosal epithelium from?
HCL and pepsin
HCO3, mucus, PGs, mucosal blood flow and GFs ______ the gastric mucosa
protect
Acid, pepsin, NSAIDS, H. pylori, aspirin, alcohol, bile, and stress _____ the gastric mucosa
damage
what are the symptoms of gastrinoma?
diarrhea, nausea, peptic ulcer disease, Increase resting gastrin level, weight loss, GERD
What are the predominant causes of peptic ulcer diseases?
H. Pylori infection and NSAIDS
When is a peptic ulcer created?
loss of protective mucosal barrier
excessive H and pepsin secretion
combo of above
What kind of ulcers does H. pylori usually cause? How?
gastric
forms primarily bc mucosal barrier defective
cytotoxins breakdown barrier and underlying cells
Enzyme urease allows bacteria to colonize
Urease converts urea to NH3, alkalinizes local environment
Diagnostic test: urease activity
What types of ulcers form because H secretory rates are higher than normal?
duodenal ulcers
more common than gastric ulcers
H. pylori role indirect: inhibits somatostatin from D cells, Gastric H. pylori infections spreads to duodenum and inhibits bicarb secretion
What is Zollinger-Ellison syndrom
Hypersecretion of gastrin typically from tumor in pancreas
More H in duodenum and overwhelm buffer capacity of bicarb in pancreatic juice and creates an ulcer
Low duodenal pH inactivates pancreatic lipases ->steatorrhea
Tx: cimetidine, omeprazole, and surgical removal of tumor
How much of the pancreas is exocrine?
90%
What are the two main components of pancreas secretion?
aqueous solution of bicarb for neutralization of H from the stomach and enzyme secretion to digest carbs, proteins, and lipids
Anatomically, how is the exocrine pancreas gland organized?
like salivary glands
Acinus: line by acinar cells that secrete enzymatic portion
Ducts: line by ductal epithelial cells, extend to region in the acinus containing centroacinar cells - secrete bicarb solution
What is the exocrine pancreas innervated by?
PNS: vagus nerve; pregang synapse in ENS, postgang synapse on pancreas - STIMULATES
SNS: postgang from celiac and SM plexuses - INHIBITS
What is secreted from acinar cells of exocrine pancreas? When are the components activated?
Enzymes:
pancreatic amylase and lipases secreted as active forms
Pancreatic proteases secreated in inactive forms and converted to active forms in lumen of duodenum
What do centroacinar and ductal cells of exocrine pancreas secrete?
produce initial aqueous solution which is isotonic and contains Na, K, Cl, and bicarb
Then modified by transport processes in ductal epithelial cells
What are the transporters on the luminal and basolateral sides of the pancreatic ductal cells? What is the net result ?
Lumen: HCO3/Cl exchanger
Basolateral: Na/K ATPase and H/Na exchanger
Net result: secretion of bicarb into pancreatic ductal juice and net absorption of H
*inside: carbonic anhydrase
How does salivary and pancreatic secretion differ?
PNS stimulates and SNS inhibits pancreatic secretion and in saliva secretion they both stimulate it
At increased flow rate, what are the concentration of bicarb and Cl in pancreatic juice? What is it at low flow rate?
Explain what this means
Increased: bicarb highest, Cl lowest
Decreased: bicarb lowest, Cl highest
there is a reciprocal releationship btwn Bicarb and Cl concentrations, Maintained by HCO3/Cl exchanger on apical membrane of ductal cells
Describe the phases of pancreatic secretion
Cephalic: initiated by smell, taste and mediated by vagus n. produces mainly enzymatic secretion
Gastric phase: initiated by distention of stomach, vagus n, produces mainly enzymatic secretion
Intestinal phase: most important - 80% of pancreatic secretion. both enzymatic and aqueous secretions stimulated
How are acinar cells stimulated in intestinal phase?
A.a, small peptides, fatty acids stimulate I cells to secrete CCK,
CCK stimulates acinar cells
ACh potentiates acinar cells to do IP3, Ca pathway,
enzymes are secreted
How are ductal cells stimulated in intestinal phase?
H+ stimulates S cells to secrete secretin Secretin acts on ductal cells ACh and CCK potentiate Ductal cells go through cAMP pathway Aqueous sol is secreted
How does acute pancreatitis occur?
when pancreatic enzymes are activated in pancreatic tissue rather than in lumen of the intestine, resulting in autodigestion of pancreatic tissue
