How much saliva is produced daily?
Main functions?
800 - 1500 ml/day
- initiates digestion of lipids carbs
- lubrication + dilution of food to create bolus
further functions on “constituents of saliva” card
(90% during eating)
Describe the general structure of the salivary glands.
Differentiate.
tubualveolar structure
= consists of acini + ducts
- parotid: purely serous
- sublingual gland: mainly mucous
- s**ub**m**andibular gland: mixed serom**ucous
Generally…
How is the secretory function of the GI tract regulated?
- enteric NS: direct stimulation or action of ENS cells
-
autonomic NS:
- parasymp. → ↑ GI activity
- symp. → ↓ or ↑ GI activity (dep. on tissue)
- secretogogues: substances that cause secr., either holo-/endocrine
⇒ act on slayer of myoepithelium around acini
→ contraction
What are the major constituents of saliva?
- water
- electrolytes (Na+, K+, HCO3-, Cl-)
-
proteins
- α-amylase, lipase → digestion
- IgA, lysosyme → antimicrobial effect
- Ca2+ binding protein → provides ↑[Ca2+] around teeth
- R-protein → vit B12 absorption
Describe the two-stage model of salivary secretion.
Another name for this mechanism?
= sequential secretion
-
primary saliva = isotonic
produced/secreted from acinar cells -
secondary saliva = hypotonic
modified as it passes through duct cells, reabsorb Na+/Cl-, secrete K+, HCO3- → alkaline
Describe the ion transport in acinar cells.
- Cl- diffuses via CFTR into lumen of acinus, causes negative potential
- Na+/H2O follow paracellularly
- Na/K-ATPase and Na/K/Cl cotransporter maintain balance on basolat. surface
- proteins exocytosed
⇒ isotonic primary saliva
Briefly describe the characteristics of the CFTR channel.
cystic fibrosis transmemb. conductance regulator
- Cl- channel
-
ABC transporter → needs ATP
if ATP present: passive transport
Describe the ion transport in duct cells.
- Na+ reabsorbed via ENaC
- HCO3- and K+ secreted
- no aquaporins → impermeable to water
⇒ hypotonic secondary saliva
How does the flow rate affect the ionic composition of saliva?
the higher the flow rate (eating) the less time for compositional modification by duct cells
⇒ ↑ [Na+], ↓[K+]
= more similar to that of plasma
ONLY exception:
[HCO3-] is HIGHEST at HIGH flow rates
bc secreted selectively upon parasymp. stim.
Describe the 3 mechanisms of parasymp. regulation of salivary secretion.
via n. VII, IX
-
ACh binds to m3-R (Gq) on acinar cells
⇒ ↑ fluid and enzyme secretion -
VIP causes vasodilation via Gs
⇒ ↑ secretion due to ↑ blood flow - incr. parasymp. activity (↑ACh) from smelling or seeing food, nausea
Why does atropin only selectively inhibit the saliva production?
only blocks ACh receptors
→ VIP can still enhance saliva prod.
Describe the 2 mechanisms of symp. regulation of salivary secretion.
NE binds to acinar/duct cells via
-
α1-R (Gq)
→ vasoconstriction + ↓ fluid production -
β2-R (Gs)
→ ↑ mucin secretion
How much gastric juice is secreted daily?
Functions w/ to its constituents.
- *1000 - 1500ml/day**
incr. production after meal - mucous/HCO3-: protection of mucosa
- H+: antimicrobial effect, activates pepsinogen to pepsin
- lipase, pepsinogen: digestion
- intrinsic factor: only essential secretion → necessary for absoprption of vit B12
As a summary..
Differentiate btw the most important cell types of the stomach, their location and function.
3 functional regions w/ unique functions:
- LES + cardia
- fundus + body
- antrum + pylorus
Differentiate btw the 2 states of parietal cells.
Function?
resting state - active state
translocation of membranes/transporters to luminal surface for ↑↑ gastric acid secretion
- H+, Cl- secretion
- intrinsic factor production
Describe the mechanism of gastric acid secretion.
initiated by translocation of H/K pump
- CO2 + H2O form H+ + HCO3-
- HCO3- exported, Cl- imported by antiporter on basolateral surface
-
H+/K+ pump on lum. surface exports H+,
Cl- leaves via CFTR - K+ leaves again via channels
NOTE: blood that leaves stomach = alkaline due to ↑[HCO3-]
Which mechanisms regulate the activity of parietal cell secretion?
stimulated by
- neural: ACh by vagus → via m3-R
- hormonal: histamine by ECL cells → via H2-R (Gs)
- paracrine: gastrin by G cells → via CCKB-R, also ECL cells
How is the release of gastrin stimulated?
- distension of stomach → ACh
- ACh from vagus → GRP
- AAs, peptides
- enteric reflexes
- too high symp. tone → β2-R
How is the release of gastrin inhibited?
-
mainly feedback regulation
↑[H+] → D cells produce ↑[somatostatin] (Gi) → ↓[gastrin] → ↓[H+] -
ALSO: inhibited by PGE2
omeprazole for treatment of gastric cancer
Differentiate btw mucous cells of the stomach.
Function?
surface/neck mucous cells
⇒ secrete Na+, Cl-, HCO3-, mucin to buffer HCl
→ cells surface remains near pH 7
Which substances are secreted by chief cells?
What is the necessary stimulus?
ACh, secretin causes
⇒ secretion of pepsinogen, gastric lipase
What can you say about the ionic composition of gastric acid w/r/t its rate of secretion?
ALWAYS isotonic
- ↑[Cl-], [K+] w/ incr. rate of secretion
- ↑↑↑[H+] w/ incr. rate of secretion
- ↓↓↓[Na+] w/ incr. rate of secretion
Values for peak acid output in male and females.
- PAO - male = 25mmol/h
- PAO - female = 16mmol/h
> in males due to higher no. of parietal cells
What are the 3 phases of gastric secretion?
- cephalic phase
- gastric phase
- intestinal phase
As a summary..
What happens during the cephalic phase of gastric secretion?
thought of food, smell, taste, chewing, swallowing
= 40% of total acid secretion
vagus → ACh → GRP → G cells → HCl secretion
(ACh also directly stimulates parietal cells)
NOTE: atropine-resistant pathway bc acting via GRP
As a summary..
What happens during the gastric phase of gastric acid secretion?
food reached stomach, hence gastric distension
= 50% of total gastric acid secretion
What happens during the intestinal phase of gastric acid secretion?
food reaches small intestine
= 10% of total acid secretion
- protein digestion digested in stomach → free AAs
- distension → signals intestinal endocrine cells to secrete enterooxyntin
⇒ stimulus to parietal cells
What are mechanisms other than the pathway using somatostatin to inhibit the release of gastric acid?
Where do they happen?
- antrum: low pH directly inhibits gastrin release
- duodenum: low pH causes release of secretin/neural reflex
- duodenum/jejunum: hyperosmotic sol. and FAs cause release of GIP and CCK
⇒ inhibited rel. of gastrin/HCl rel. by parietal cells
What happens during the small intestinal phase?
food reaches small intestine
→ secretions of pancreas, liver, small intestine
How much pancreatic juice is secreted daily?
Functions?
Tonicity.
700 - 900ml/day
98% exocrine, 2% endocrine
-
exocrine:
- neutralization of acids
- digestive enzymes
- endocrine: regulation of blood sugar
ALWAYS isotonic
<u>NOTE:</u> large reserve, even 10% would be enough
How does the sequential secretion in the pancreas differ from that in salivary glands?
- acini secrete isotonic acinar fluid
and lots of enzymes - intralobular ductal system: spontaneous secretion → incr. [HCO3-], [K+]
- extralobular ductal system: stimulated by secretin to further secrete [HCO3-]
List important enzymes that are produced by the pancreas.
Where?
Examples.
pancreatic acinar cells
- zymogen proteases: chymo-/trypsinogen
- starch-digesting enzymes: amylase
- lipid-digesting enzymes/precursors: lipase
- nucleases
- regulatory factors: procolipase
Describe the main features of ion transport in pancreatic duct cells.
- in apical membr.: Cl-/HCO3− exchanger
- in basolat. membr.: Na/K-ATPase and an Na/H-exchanger
-
carbonic anhydrase
CO2 + H2O → H2CO3 → H+ and HCO3− -
Cl-/HCO3− exchanger
HCO3− secreted into pancreatic juice -
Na/H-exchanger
H+ is transported into the blood
⇒ net secretion of HCO3− into pancreatic ductal juice and net absorption of H+
(acidification of pancr. venous blood)
What is cystic fibrosis?
genetic disease, caused by mutation in CFTR
→ impaired Cl- secretion
⇒ clog secretion (since secretion of mucous is not suspended), hence impaired function of a variety of epithelial organs
if CFTR in pancreas defect, bicarbonate cannot be secr.
Which substance is the most important stimulant for enzyme secretion in acinar cells?
CCK (secreted by I cells of duodenum)
How is the pancreatic secretion regulated?
Mechanisms.
neurally and hormonally
activated by:
- hormonally: CCK/gastrin, secretin
- neurally: VIP, GRP, ACh
inhibited by: somatostatin
What are the 3 phases of pancreatic secretion?
Which one is the most important one?
- cephalic phase = sight, smell, taste of food
- gastric phase = distention of stomach
- intestinal phase (cf. own card)
⇒ 80% of secretion happens in intestinal phase
Which stimuli induce pancreatic secretion in the intestinal phase?
Mediator/mechanism.
- acidic duodenum (pH → secretin stimulates duct cells
-
AAs, FAs, Ca2+
→ CCK stimulates aff. arm of vagovagal reflexes to acinar and duct cells -
distention of duodenum, hypertonicity in duodenum
→ enteropancr. reflexes stimulate both cell types
Describe the feedback loop that responds to a fall in luminal pH in the duodenum.