Salivary, Gastric, Intestinal Secretions - Fan 2/19/16 Flashcards
why secrete in the first place?
-
provide digestive enzymes with optimal working environment
* sm int and pancreas secrete HCO3-rich alkaline fluid to neutralize stomach acid, prevent enzymes from being denatured -
passive secretion of water that is pulled in when influx of sugars, a.a.s, peptides increases osmolality of lumen
* water will diffuse back once these particles are absorbed - protection
- excretion of toxic metabolic wastes
general secretory mechanisms
- enzymes secreted via exocytosis, in response to neuroendocrine factors
- fluids (electrolytes/water) via ion movement into lumen (requires energy, one way or another),osmotic gradient that’s set up
salivary secretions
1500 mL/day
- lubrication
- assists w/ swallowing and speech
- protection
- mucus, bicarb, lysozyme (effective against gram+ bacteria), lactoferrin (effective against gram- bacteria), secretory IgA
- digestion
- amylase (active in oral cavity), lingual lipases (activated by stomach acid)
characteristics of saliva
- four major ions: Na, HCO3, K, Cl
- concentrations vary, but a few major trends…
- always lower in Na and Cl than plasma
- always higher in K than plasma
- usually rich in bicarb
2-stage model of saliva secretion
- acinar cells secrete: Na, Cl, K, bicarb, pours water into lumen [isotonic primary solution]
- secretions move through ductal area, where modifications occur
- Na reabs, Cl reabs
- leads to hypotonicity (because ductal tight junctions are super tight, water won’t be able to follow)
- K secreted, bicarb secreted
- Na reabs, Cl reabs
acinar cell: ion movements (resting)
- Cl moves from serosal side into cell via Na/Cl cotransporter
- Cl moves from cell into lumen via Cl/HCO3 ion channel (leaks both of them)
- both Cl and HCO3 are negatively charged, so K leaks from cell into lumen and from cell to serosal side via K channel
- Na moves from serosal side to lumen through cell-cell jx
- water follows!
sets up isotonic primary secretion that moves down to ductal area
acinar cell: ion movements (stimulated)
salty food will stimulate the acinar cells, lead to increased Ca within acinar cells
- stimulates anion channel (Cl/HCO3) and K channel
increase in metabolism will give you increased water and CO2 → increased HCO3 formation
ductal cells: ion movements
- Na reabs through Na/H exchanger
- Na eventually moves to serosal side via Na/K ATPase
- H reabs through H/K exchanger (K secreted)
- K leaks to either side from cell
- Cl reabs through Cl/HCO3 exchanger
- leads to increased bicarb secretion
- Cl leaks to serosal side via chloride channel (ONLY ON SEROSAL SIDE)
regulation of salivary secretion
almost 100% neurally regulated
-
salivary nucleus of medulla
- + : smell, taste, pressure, nausea
- - : fatigue, no sleep, fear, dehydration
most CNS signals come through PSNS (CN IX, X, FN VII)
-
Ach, VIP
- vasodilation (fluid delivery)
- acinar cell metabolism (more bicarb)
- channel activation (secrete K/Cl/bicarb)
- glandular growth (mainly due to vagal system)
- myoepithelial cell contraction
minor effect through sympathetics T1-T3 by way of superior cervical ganglion
- norepi
- mostly mucus secretion (not really fluid secretion)
gastric secretions
2000 mL/day
two major secretions
1. oxyntic component
- parietal cells: HCl, K, IF
- highly stimulated by feeding
2. non-oxyntic component
- mucous cells: mucus Na, HCO3
- chief cells: pepsinogen
- diffused interstitial fluids
- secreted at relatively constant rate; major component at rest, becomes v diluted by oxyntic component on feeding
gastric secretions: rest vs. stimulated
- resting: non-oxyntic components dominate: isonotic NaCl
- after stimulation: oxyntic components take over: isotonic HCl
general features of gastric secretion (Cl, K)
Cl is always the ion present in greatest quantity in gastric secretions
K concentration is always higher than plasma
functions of gastric secretion
- digestion
- acidic pH activates pepsinogen and lipases
- HCl denatures proteins for digestion by pepsin
- aiding absorption
- HCl solubilizes minerals (Ca, PO4, Fe, etc)
- IF required for B12 abs
- protection
- HCl inactivates microbes (exception: H. pylori in stomach)
- mucus, HCO3, Cl contain acidity of H
mechanism of HCl secretion
parietal cells undergo morphological change to enhance H secretion
- stimulation causes tubulovesicles rich in H pumps that are resting in parietal cell to fuse with intracellular canaliculi which eventaully opens to the lumen of the gastric pit to secrete H
HCl secretion: ion movements in resting cell
parietal cells, resting
- regular metabolism: bicarbonate made
- HCO3/Cl exchanger puts bicarb into blood, brings Cl into cell
- Cl moves into lumen via Cl channel
- Na/K ATPase moves Na out of cell, K into cell
- K moves into blood and into lumen via K channels
generally, you get accumulation of Cl (-70 to -80 mV potential difference) and K in resting lumen
HCl secretion: ion movements in stimulated cell
parietal cell, stimulated (via Ach, histamine, Ghrelin) = increased Ca in cell = increased cAMP
- increases metabolim, bicarb production
- activates H/K ATPase (in tubulovesicle membrane?)
- causes tuberovesicle/intracellular canaliculus fusion
- ultimately pumps H into lumen
- also activates Cl channel
- more bicarb production → more bicarb/Cl exchange → more Cl in cell
- more Cl moved out through activated Cl channel!
- also activates K channel
- more K leaves cell
- makes intracellular environment more negative, more likely for bicarb and Cl to be moved out in their respective directions
potential difference is reduced (-30 to -50 mV, but still have a diff due to the fact that so much Cl is pumped out)
omeprazol
targets H/K ATPase - thereby reducing acid secretion
how?
- reduced H pumped out into gastric lumen
- could also drop blood pH a little bit
- H not secreted from parietal cell neutralizes bicarb, which doesnt move out in the usual alkaline tide!
alkaline tide
sudden increase of pH in gastric vein after stimulation of parietal cell (acid secretion)
how?
increase in metabolism : increase in bicarb synthesis : bicarb moves out to bloodstream via HCO3/Cl exchanger!!
- physiologically: postprandial alkaline tide after a big meal
- pathologically: severe vomiting, sustained alkaline tide, metabolic alkalosis
digestive phases
- % daily HCl
- stimulated by…
- mediated by…
1. interdigestive: 15% HCl
- basal secretion.
- mediated by PSNS (vagus), gastrin, histamine.
2. cephalic: 30% HCl
- stimulated by sight/smell/taste/chewing/swallowing food.
- mediated by PSNS (vagus), gastrin, histamine.
3. gastric: 50% HCl
- stimulated by food in stomach.
- mediated by PSNS (vagus), gastrin, histamine.
4. intestinal: 5% HCl (active inhibition of acid secretion!)
- stimulated by digestion product
- mediated by secretin, CCK, GIP
parietal cell secretory control at the cellular level
stimulated by:
- Ach: M3-R
- histamine : H2 receptor
- gastrin : CCKB receptor (Ca influx via PLC)
- all lead to increased Ca, increased cAMP
collaboration among the stimulators!
- Ach stimulates gastrin production
- Ach and gastrin both stimulate ECL production (precursor of histamine)
inhibited by: secretin, GIP, CCK
- all directly inhibit gastrin secretion
- all also trigger major inhibitory paracrine, somatostatin
- inhibits gastrin secretion
- tells parietal cell to reduce HCl production
***prostaglandins also directly hit parietal cells to inhibit HCl production
mechanisms for containment of HCl
- Cl current (anywhere from -30 to -80 mV gradient)
- mucosal barrier (mucus gel and HCO3)
- prostaglandins: cytoprotection
- inhibition of HCl secretion form parietal cell
- stimulates mucus and bicarb production
clinical correlation: NSAIDs inhibit prostaglandin synthesis, which is why you sometimes see stomach problems
