Secretions of the GI & Pancreas Flashcards
Function of the saliva?
What does it do to digest this stuff?
providing the first steps for the digestion of starches and lipids
(done by amylase in the saliva and a lingual lipase)
diluting and buffering particles of the food
lubrication of the ingested food
3 types of salivary glands
Parotid Glands:
biggest ones, composed of serous cells - secrete water, ions, enzymes (rich in amylase)
25% of daily output from parotid
Submaxillary glands (mixed), Sublingual glands (mixed):
- both serous and mucous
- secrete most of the daily output of saliva
aqueous fluid + mucin glycoprotein
75% of daily output
Structure of the salivary glands? (4 parts)
what are each function?
Acinus (blind end) –> composed of aciar cells –> responsible for secreting initial saliva.
myoepithelial cells –> mostly directly outside to the acinus cells in the acinus but can go around the intercalated duct… important for controlling ejection of saliva from the acinus down to the duct through contractions and changing the morphology of the flow.
Intercalated duct –> smaller cells that are extended and go to the striated duct. saliva is going to have a similar composition to that of the plasma at this point (isotonic).. but remember our saliva is usually hypotonic.. this modification happens at the STRIATED DUCT!
Striated Duct lined by columnar cells (ductal cells) –> responsible for producing final saliva
What creates the hypotonic saliva from the isotonic saliva in the intercalated duct?
ductal cells in the striatal duct.
Striated duct?
lined by columnar epithelial cells (ductal cells) –> responsible for producing final saliva.
What is saliva not?
what is it composed of?
not an ultra-filtrate of the plasma
water, electrolytes, alpha amylase, lingual lipase, kvllikrein (important for bradykinin), and mucus.
Saliva is compared to plasma with K, HCO3, Na, Cl
high potassium + bicarbonate (compared to plasma) –> secreted into acinus
low Na and Cl (compared to plasma) –> absorption into blood
Ductal cells do what with Na/Cl and K/HCO3
Na + Cl are shoved out of the saliva at bigger quantities than the absorption of K+ and HCO3 to maintain it!
Na/Cl absorbed (into blood) more than KHCO3 secretion (into acinus)
What’s happening at the lumenal side or the basolateral side of the ductal cell?
On the basolateral side:
1) we have a Na/K ATPase. shoving 3 Na out and 2K in.
2) Cl channels out of the cell
3) HCO3 Na symporters into the ductal cell
on the apical side:
1) Na/H exchangers (Na in, H out)
2) Cl/HCO3 exchanger (Cl out, HCO3 in)
* * also have a chloride channel regulated by cAMP which helps get chloride into the cell or out of the cell (CFTR channel)***
3) H/K exchanger (K in, H out)
How does saliva become hypotonic as it flows through the ducts?
Ductal cells are H2O impermeable.
so we’re not letting water to get into the basolateral side, so we have a lot of water, less solute in the end.
PNS innervation of the salivary glands comes from what?
which one goes to which glands?
facial nerve (CN7) –> submandibular + sublingual
Glossopharyngeal nerves –> to the parotid gland
SNS innervation of salivary glands comes from what?
T1-T3 (sometimes T4) –> superior cervical ganglion –> serves to all 3 glands
what is the main driver of the regulation of the salivary secretions? EXCLUSIVELY
what up regulates the parasympathetic system?
Negative?
ANS (composed of PNS + SNS)
Conditioning (pavlov)
Food
Nausea
Smell
Dehydration
Fear
Sleep
What happens when you up regulate PNS?
stimulates the facial and glossopharyngeal –> ACH binds to muscarinic receptor in the acinar or ductal cells –> increases IP3 and the production of Ca2+ –>
end result = higher saliva production, higher HCO3 and enzyme secretions, contractions of myoepithelial cells
What happens when you upregulate the SNS for salivary glands?
T1-T3 release Norepinephrine –> Beta Adrenergic Receptor (BAR) –> production of cAMP –>
end result = higher saliva production, higher HCO3 and enzyme secretions, contractions of myoepithelial cells
what’s good to know about PNS and SNS with salivary glands? THIS IS IMPORTANT
Parasympathetic and sympathetic are BOTH STIMULATING.. so similar output, but PNS is dominating.
How does ADH and aldosterone modify saliva?
decreasing Na+ concentration and increasing K+ concentration
What does atropine do?
antagonist of muscarinic ACH receptors.
so inhibits saliva production of the PNS. so less Ip3, less Ca2+!
HCl does what? what does it work with?
main goal of acid in the stomach? secondarily?
components of gastric juice?
together with pepsin, initiates protein digestion.
activate pepsinogen to do pepsin
secondarily –> acid kills a ton of bacteria that enter the stomach.
HCl Pepsinogen Mucus Intrinsic Factor H2O
What is pepsinogen?
What is mucus? what does it work with?
What does intrinsic factor do?
what does water do in the gastric juice?
inactive precursor of pepsin
lines the wall of the stomach and protects it from damage, lubricant, and works with HCO3 it helps to neutralize acid and protect the surface to maintaining a neutral pH
glycoprotein and super important for absorption of vitamin B12!
solubilizes much of the material
Oxyntic Gland vs Pyloric gland?
similar?
different cells in each and what do they do?
both similar structures, both have surface mucosal cells. both have enterochromaffin Cells, both have somatostatin (D cells)
different: Oxyntic glands have Parietal Cells (secrete the acid), and Chief cells (secrete pepsinogen), and Enterochromaffin-like Cells (secrete histamine)
Pyloric gland has G cells which secrete Gastrin –> this goes into the blood –> back to the stomach.
What does somatostatin do?
released from D cells inhibits gastric acid release.
Where are oxyntic glands located? Pyloric?
main function?
body + fundus
Antrum
secretes acid (oxyntic) and synthesizes and releases gastrin (Pyloric)
In the stomach, where would you NOT find parietal cells and chief cells?
antrum.
What is the importance of the # of parietal cells?
why do parietal cells have a ton of mitochondria?
where is HCl formed in the parietal cells?
what is the main goal of low gastric pH?
determines the maximal secretion rate.
critical to producing a ton of acid. (stomach has a pH of 1, so a ton of acid is going out).
at the villus like membranes of the canaliculi (little invaginations in the cell)
to convert pepsinogen to pepsin
What’s going on on the luminal side of the parietal cell?
basolateral?
what happens intracellularly?
basolateral:
1) Na/K atpase
2) HCO3/Cl exchanger (HCO3 in, Cl out)
Luminal:
1) H/K ATPase (K+ in, H out)
2) Cl out to lumen (following H to form HCl in the lumen)
the bicarbonate is going to be generated and absorbed and the H is going to be secreted into the lumen to form HCl… all this is made possible by Carbonic Anhydrase!
What happens when we eat?
“alkaline tide”. we have a ton of acid in our stomach so in our blood we’ll have a lot of HCO3 being absorbed into the blood.
What does Omeprazole?
H/K proton pump inhibitor.
Lowers HCL, so helps people with peptic ulcers, acid reflux.
what are the different receptors found on the gastric parietal cell?
There’s different receptors on the gastric parietal cells.
M3 receptors (type 3 muscarinic) –> binds to ach.
CCKb receptors –> bind gastrin.
H2 receptors –> binds histamine that is created by ECL cells (enterochromaffin like)
What do both M3 receptors and CCKb do?
Activate Gq to increase IP3/Ca2+ to increase H/K ATPase to make more acid
What are the three main secretions that increase H+ secretion by gastric parietal cells?
what are the two main secretions that decrease H+ secretions by the gastric parietal cells?
Ach
Gastrin
Histamine
Somatostatin
prostaglandins
What pathway do activated H2 receptors deal with and what’s going to happen?
how is this being inhibited?
Gs –> creates more cAMP –> formation of more H/K ATPase –> more acid
Somatostatin + Prostaglandins work through Gi to inhibit cAMP (the same one that’s unregulated by Gq)
What could inhibit cAMP release other than somatostatin + prostaglandins?
Cimetidine (inhibits H2 receptors)
What are additional things that somatostatin + prostaglandins do for regulation?
prostaglandins negatively regulate ECL cells (which secrete histamine usually)
Somatostatin negatively regulate ECL cells too + inhibiting G cell and the production of gastrin.
What happens to gastrin as the pH falls?
somatostatin is released to inhibit gastrin to prevent gastrin from being secreted.
Cholinergic fibers of the vagus nerve have what effect on parietal cells?
peptinerpic fibers?
which pathway does atropine act on?
direct affect because they directly release ACH…
indirect! release GRP (gastrin releasing peptide), which stimulate G cells to produce gastrin, which indirectly produce acid from parietal cells!
only the direct way!
What affect does more Ach release from the vagus nerve have on somatostatin cells?
but what about if there’s more gastrin?
inhibit them, so up regulating Gastrin cells, making more acid.
more gastrin means more acid, and more acid increases more somatostatin to negatively regulate gastrin.
What affect does more Ach release from the vagus nerve have on somatostatin cells?
but what about if there’s more gastrin?
inhibit them, so up regulating Gastrin cells, making more acid.
more gastrin means more acid (through GRP and indirect acid production from parietal), and more acid increases more somatostatin to negatively regulate gastrin.
so they work on each other!
what is potentiation?
2 examples?
what does this mean with blocking?
when we have a combination of two drugs that when they’re together the response is higher than having one by itself.
1) histamine potentiates the actions of Ach + Gastrin
2) Ach potentiates the actions of histamine + gastrin.
blocking mACHR? block direct effects of ACh + the ACh potentiated effect!
block H2 receptors? block histamine and the potentiating effect too!
What are the three phases of the gastric HCL secretions?
how are each occurring?
What happens to the cephalic phase if you have a vagotomy?
1) Cephalic phase –> via Vagus (vagotomy will abolish cephalic phase completely)
2) Gastric phase –> local secretory reflexes, vagal reflexes, gastrin-histamine stimulation
3) intestinal phase –> nervous + hormonal mechanisms
Cephalic Phase accounts for how much HCL secretion?
stimuli?
2 mechanisms?
30%
smelling + tasting, chewing, swallowing, conditioning
vagus –> directly on the parietal cell
Vagus –> indirectly to the GRP –> G cells –> Gastrin –> activate parietal
Gastric Phase accounts for how much HCL secretion?
stimuli?
4 Mechanisms?
how does distention work??
60%
distention of stomach, presence of digested proteins , amino acids, small peptides
Vagus –> parietal (same as cephalic)
Vagus –> gastrin –> parietal cell (same as cephalic)
distention of antrum –> local reflexes (pyloric reflex or vasovagal reflex ) –> Ach –> Parietal cell & G cell
AAs/small peptides broken down –> stimulate G cells to produce gastrin –> indirectly activate parietal cell
(activates mechanoreceptors in the mucosa of oxyntic and pyloric glands, which then activate the response)
What does coffee, wine, beer, do?
stimulate gastric HCl secretion.
Intestine Phase accounts for how much HCL secreted?
stimuli?
what happens when
5-10%
distention of small intestine –> stimulates gastric secretion
digested protein happening? –> direct effect on parietal cell or through gastrin in duodenum
What’s the optimum pH for pepsin activity?
when the pH is at 3.5-5, what happens to pepsin?
7-8?
1.8-3.5
reversibly inactivated
irreversibly inactivated
if we have a failure to secrete intrinsic factor… i.e. no parietal cells.. what happens?
why is IF so essential for us?
achlorhydria (can’t absorb B12 –> IMPORTANT FOR THE DEVELOPMENT OF RED BLOOD CELLS
Pernicious anemia?
why is it not diagnosed early?
what are the 2 causes?
due to the incapability to produce enough intrinsic factor, so B12 absorption is affected.
we usually are used to having a big store in the liver that lasts for 4 years, so diagnosing doesn’t happen right away
atrophic gastritis –> chronic inflammation that leads to loss of parietal cells
autoimmune metaplastic atrophic gastritis –> immune system attacks IF protein or gastric parietal cells
How does the gastric mucosa grow?
gastric epithelium makes HCO3 + mucus to form the barrier. mucous cells make the mucus
surface epithelial cells secrete the HCO3
this barrier protects the epithelium from HCL and pepsin.
What are some agents that can either promote (6) the growth of the gastric mucosa or negatively impact (7)?
positive: HCO3, Mucus, Prostaglandins (misoprostol), mucosal blood flow, gastrin, growth factors
Acid, pepsin, NSAIDs (aspirin), H. pylori, alcohol, bile, stress
why does gastrin positively help the mucosa?
gastrin is seen as a growth factor. it helps proliferate some of the cells even though it aids in acid production it actually helps develop the mucosa.
What do NSAIDs to do destroy the mucosa?
inhibit prostaglandin formation!!
so that means more acid is being made!
Zollinger-Ellison syndrome?
acid secretion rates are super high.
tumor in the pancreas, secreting large quantities of gastrin
not responsive to regulation
excessive H+ overwhelms the duodenum and this low duodenal pH inactivates the pancreatic lipase –> you see lipids in the stool.
What does secretin do?
inhibits gastrin and a bunch of other acid forming stuff as well
Secretin stimulation test?
what normally happens when you have secretin administered
what’s different about it?
used for diagnosing gastrin-secreting tumors.
normally it inhibits gastrin release
injection of secretin causes a PARADOXICAL increase in gastrin release! (super high release)
What contributes to the cytotoxic effect of H. pylori on gastric mucosa?
H pylori produces ammonia, plus the acid makes ammonium, which makes it super cytotoxic
what are the causes of peptic ulcer diseases?
NSAIDs and H. Pylori
could also be the result of loss of mucosal barrier, excessive H+ and pepsin secretions, combination of both
H. Pylori: how does it damage the mucosa?
diagnostic test?
has urease –> converts urea to ammonia (NH3) –> creates NH4+ ==> causes cytotoxicity and damages the mucosal barrier.
urease activity
What’s the difference between Non-parietal and Parietal gastric juice?
Gastric juice is a mix of these 2
non-parietal = basal alkaline secretion of constant & low volume… primary constituents are Na, Cl… K is the same as plasma. HCl is secreted at 30 mEq/L
Parietal = slightly hyper osmotic… contains 150-160 mEq H+/L and 10-20 mEq K+/L.. Cl is the only anion present. (dominant! this is the one producing acid)
As the secretion rate increases, the concentration of electrolytes begin to approach those of pure parietal cell secretion.
Besides Ach and Gastrin upregulating M3 receptors and CCKb receptors respectively, what else do they up regulate?
Ach and Gastrin up regulate the production of Enterochromaffin-Like cells (which produce histamine)
End goal of having acidic stomach?
pepsinogen is secreted by Chief cells and mucus cells of the oxyntic glands… but it requires secretion of H+ secretion from parietal cells to lower pH of gastric contents to less than 5
so Pepsin is dependent on pH
what are the only secreted element by the stomach that is required?
Intrinsic Factor
Gastric ulcers?
duodenal ulcer?
which is more common?
compromise of the mucosal barrier… as opposed to increased acid secretion
higher level of parietal cells so more acid than normal!
duodenal
H+ secretion, gastrin levels of each:
Gastric Ulcer
Duodenal Ulcer
Zollinger Ellison Syndrome
lower, higher
higher, higher (with response to food ingestion)
way higher, way higher
what’s the difference between pancreatic juice and stomach juice?
pancreatic juice is similar, in that it contains HCO3 for neutralization, but it also has zymogen granules that digest all different stuff, which isn’t in the stomach.
Innervation of exocrine pancreas?
PNS
SNS
how is this different than the stomach?
PNS = vagus (preganglion fibers synapse in ENS, post on exocrine pancreas
SNS = postganglionic nerves from the celiac and superior mesenteric plexus
stomach, both SNS and PNS stimulate. in the pancreas, PNS stimulates, SNS inhibits secretion
what kinds of enzymes are secreted by acinar cells of the pancreas?
enzymes that are already active
proteases that are inactive and converted to the active form in the duodenum lumen
What kind of transport is happening in the pancreatic ductal cells?
apical, basolateral, paracellular
apical: Cl in, HCO3 out to lumen (exchanger)
basolateral: Na/K ATPase, H/Na exchanger (Na in, H out into blood)
paracellular = Na to lumen from blood
What’s the difference between the ductal cells of the pancreas and ductal cells of the salivary glands?
H is going to the lumen in the salivary ductal cells, H is going to the blood in pancreatic
What happens if someone has cystic fibrosis?
there’s a CFTR receptor on the apical membrane that helps shove Cl out of the cell, but CF people do not have this active due to a mutation.
so you have Cl that can’t move with the exchanger that needs to get HCO3 out.
Pancreatic secretion divisions and what is secreted in each?
Cephalic = enzymatic secretion (vagus)
Gastric = Enzymatic Secretion (vagus)
Intestinal = 80% OF PANCREATIC SECRETION… enzymatic and aqueous secretions are stimulated
What releases CCK in the duodenum?
what stimulates CCK?
what’s the end goal of CCK secretion?
I cells.
amino acids, FA’s
releases enzymes!
What releases secretin?
stimulus?
end goal of this?
S cells!
respond to acid!
aqueous secretion (Na, HCO3)
