Secretions of the Gastrointestinal Tract and the Pancreas Flashcards
What is the Function of Saliva? and what is it composed of?
- Initial digestion of starches and lipids
- Dilution and buffering of ingested food
- Lubrication of ingested food with mucus
Saliva is composed of H20, electrolytes, a-amylase, lingual lipase, kallikrein, and mucus
Saliva is hypotonic (compared to plasma)
- higher K+ and HCO3- concentrations
- lower Na+ and Cl- concentrations
What are the 3 major salivary glands and what are they composed of and what do they secrete?
Parotid Glands:
- Composed of serous cells
- secrete fluids composed of water, ions, and enzymes (rich in amylase)
- secrete 25 percent of the daily output of saliva
Submaxillary and sublingual glands (mixed glands)
- composed of serous and mucous cells
- secret aqueous fluid and mucin glycoprotein for lubrication
- Secrete most of the rest 75% of daily output saliva
4 Structures of the Salivary gland, and each of their functions
Acinus (blind end)
-acinar cells secrete initial saliva
Myoepithelial cells
- have motile extensions
- when stimulated by neural input, contract to eject saliva into the mouth
Intercalated duct
-Saliva in the intercalated duct is similar in ionic composition to plasma
Striated duct:
- Lined by columnar epithelial cells (ductal cells)
- Ductal cells modify the inital saliva to produce the final saliva (hypotonic)
- Ductal cells alter the concentration of various electrolytes
What is the mechanism of Salivary secretion?
Two main steps:
- Formation of the isotonic plasma like solution by acinar cells
- Modification of the isotonic solution by the ductal cells
Combined action is absorption of Na+ and Cl- and secretion of K+ and HCO3-
-net absorption of solute, more NaCl is absorbed than KHCO3 is secreted
all this is done via transporters:
- Na/H exchange
- Cl/HCO3 exchange
- H/K exchange
HCO3- leaves the cell to the lumen via cAMP-activated CFTR Cl- channel or via the Cl-/HCO3- exchanger
when saliva first leaves the acinar cells it is isotonic, how does it become hypotonic as it flows through the ducts?
Ductal cells are H2O impermeable
-there is a net absorption of solute (more NaCl is avsorbed than KHCO3 secreted)
What are the Innervations of the salivary glands?
Parasympathetic:
-presynaptic nerves originate at facial and glossophryngeal nerves, postsynpatic fibers in the autonomic ganglia innervate individual glands
Sympathetic:
-Preganglionic nerves originate at the cervical ganglion, whose postganglionic fibers extend to the glands in the periarterial space
how does parasympathetics and sympathetics affect salivary secretion?
Parasympathetics: stimulate salivary cells
- release of ACh on to the mAChR of the Acinar or ductal cells
- rlease of IPs and Ca+ leading to increase saliva production and increase in HCO3- and enzyme secretions
- as well as contraction of myoepithelial cells
Sympathetics: also stimulate the salivary glands
- release of NE on BAR receptors of acinar or ductal cells
- release of cAMP leading to increase in salivary production, increase of HCO3- and enzyme secretion
- contraction of myoepithelial cells
what are some environmental cues for activation and inactivation of the parasympathetic activation of salivary glands?
activation:
- conditioning
- food
- Nausea
- smell
inactivation:
- Dehydration
- fear
- sleep
How does ADH and Aldosterone affect saliva?
ADH and aldosterone modify the composition of saliva by decreasing its Na+ concentration and increasing its K+ concentration
What are the main components of gastric juice?
HCL (H+):
- Together with pepsin it initiates protein digestion
- Necessary for the conversion of pepsinogen to pepsin
- kills a large number of bacteria that enter the stomach
Pepsinogen
-Inactivaate precursor
Mucus
- Lines the wall of the stomach and protects it rom damage
- Lubricant
- Together with HCO3-, it neutralizes acid and maintains the surface of the mucosa at netral pH
Intrinsic factor
-required for the absorption of vitamin B12 in the ileum
H2O
- medium for the action of HCl and enzymes
- Solubilizes much of the ingested material
what are the two different gastric mucosa divided into? and where are there locations and what are the main things they secrete?
Oxyntic Gland:
- Located in the proximal 80% of the stomach (body and fundus)
- Secretes acid
Pyloric Gland:
- Located in the distal 20% of the somach (antrum)
- Synthesizes and releases gastrin
What is a major function of parietal cells?
Secrete HCL
- the number of pariteal cells determines the maximal secretory rate
- the function of the low gastric pH (1-2) is to convert pepsinogen to pepsin
- HCL is formed at the villus-like membranes of the canaliculi
Cellular mechanism of HCL secretion by gastric parietal cells?
Carbonic anhydrase converts CO2 and H20 to H+ and HCO3-
- HCL is secreted since Cl- will follow H+ , this is done via a K+ and H+ transporter that requires ATP
- HCO3- is released into the blood and CL- is brought back into the cell
Na+ is sent into the blood and K+ is brought back in, this requires ATP
What is the two component model of gastric secretion?
Non-Parietal
- Basal alkaline secretion of constant and low volume
- its primary constitutents are Na+ and CL- and K+ is present at the same concentration as plasma
- HCO3- is secreted at a concentration of 30 mEq/L
Parietal
- slightly hyperosmotic
- CL- is the only anion present
- 150-160 mEq H+/L and 10-20 mEq K+/L
knowledge of composition of gastric juice is required in the treatment of patients suffering from vomitting or patients maintained with IV
what is the feedback mechanism for gastrin as pH levels drop?
Gastrin will be inhibited which will decrease HCL secretion
this is done via Somatostatin released from D cells also prostaglandins
what are the 2 pathways for vagus nerve stimuation of HCL secretion by parietal cells
Direct pathway:
- vagus activates parietal cells via ACh
- Atropine blocks the direct pathway of vagal stimulation
indirect pathway:
- act on G cells via GRP which then releases gastrin that will circulate to then activate parietal cells to release HCL
- atropine doesnt affect this pathway because of the use of GRP
How is the regulation of gastrin done?
- Somatostatin acts on G cells to inhibit gastrin release
- Vagal activation stimulates gastrin release by releasing GRP and inhibiting the release of somatostatin
- Negative feedback regulation by gastrin (low pH will then increase somatostatin releease
- H+ in the gastric lumen stimulates release of somatostatin
what is potetiation? and how does it affect the rate of secretion of HCl
Combined response to two stimulants exceeds the sum of their individual response
-requires the presence of separate receptors on the target cell for each stimulant
Ex.
- histamine potentiates the actions of ACh and gastrin
- ACh potentiatses the actions of histamine and gastrin
WHat are the functions of Cimetidine and Omeprazole?
Cimitidine: Antagonist of H2 receptor used to treat duodenal and gastric ulcers, gastroesophageal reflux disease
-helps limit potentiation of ACh and gastrin
Omeprazole: inhibits the H+/K+ ATPase, used in the treatment of ulcers to reduce H+ secretion
What are the three phases of Gastric HCL secretion phase?
Cephalic phase via vagus
Gastric phase
- local nervous secretory reflexes
- Vagal reflexes
- Gastrin-histamine stimulation
Intestinal phase:
- Nervous mechanisms
- Hormonal mechanisms
What occurs in the Cephalic phase?
- Accounts for 30% of the total HCL secreted in response to a meal
- Stimuli: smelling and tasting, chewing, swallowing, and conditioned reflexes
Mechanism:
- Vagus nerve to parietal cell, vagus releases ACh to parietal cells, which causes release of HCl
- Vagus nerve to gastrin to parietal cell, vaguse releases GRP to G cells, which release gastrin to the circulation and the gastrin is then delivered back to the stomach to stimulate HCL secretion from parietal cells
Vagotomy abolishes this phase!
what occurs in the gastric phase?
- Accounts for 60 percent of the total HCL secretion in response to a meal
- Stimuli: distension of the stomach and presence of breakdown or proteins, amino acids, and small peptides
Mechanism:
1) distension activates the mechanoreceptors in the mucosa of oxyntic and pyloric glands
- vagus nerve to parietal cell
- vagus nerve to gastrin to parietal cell
2) Distension of antrum
- local reflexes release ACh that releases on parietal cell and g cell
3) Amino acids and small peptides
- gastrin release to parietal cell
how does coffee affect the HCL secretion?
Coffee (caffeinated and decaffinated) also stimulate gastric HCL secretion
What happens in the intestine phase?
-Accounts for 5-10 percent of the total HCL secreted in response to a meal
Distention of small intestine
-stimulates acid secretion
Digested protein
-stimulates acid secretion via Direct effect on parietal cell and Gastrin via intestinal G cells that then will activate the parietal cells
when and what secrets Pepsinogen? what innervates it?
Pepsinogen is only secreted when the gastric pH is acidic enough to convert pepsin
Pepsinogen is secreted by chief cells and by mucus cells in the oxyntic glands
-requires H+ secretion from parietal cells to lower pH of gastric contents (pH <5)
Vagus nerve stimulation is the most important stimulus for pepsinogen secretion
H+ triggers local cholinergic reflexes that stimulate chief cells to secrete pepsinogen
What does pepsin do?
Pepsin converts more pepsinogen to pepsin
- proteolytic enzyme
- optimal pH is between 1.8-3.5
- reversibly inactivated at > pH 3.5-5.0
- Irreversibly inactivated >pH 7-8
What is Intrinsic factor and what is it used for?
IF (intrinsic factor is required for absorption of vitamin B12 in the ileum
- Mucoprotein secreted by parietal cells
- Binds B12
- Only secretion by the stomach that is required
Failure to secrete IF is associated with achlorhydria and with absence of parietal cells
Mechanism in the absorption of Vitamin B12
in the sotmach, B12 will bind R protein and then when they get down to the duodenum the pancreatic proteases will switch R protein with IF where then the B12 IF complex will be absorbed in the distal ileum via IF receptors
What leads to Pernicious anemia
There is a decrease in B12 due to the fact that the stomach does not produce enough IF
Common causes:
- Atrophic gastritis: chronic inflammation of the stomach mucosa that leads to loss of parietal cells
- Autoimmune metaplastic atrophic gastritis, immune system attacks IF protein or gastric parietal cells
What are some Disruptions in the absorption of Vitamin B12
Gastrectomy: loss of parietal cells (source of IF)
Gastric bypass: Exclusion of the stomach, duodenum, and proximal jejunum alters absorption of vitamin B 12
How is the Gastric Mucosa created? and what is its function?
Gastric epithelium secretes HCO3- and mucus to form the gel like mucosal barrier
- mucosa cells secrete mucus
- surface epithelial cells secrete HCO3-
The mucosal barrier protects the gastric mucosal epithelium against the HCl and pepsin
also the prostoglandins, mucosal blood flow, gastrin, and growth factors protect the gastric mucosa
what can damage the gastroduodenal mucosa?
- H+ and pepsin
- H. pylori
- NSAIDs
- Stress-smoking
- Alcohol
What is Zollinger-Ellison syndrome? and how does it affect the body?
Large secretion of gastrin by duodenal or pancreatic neuroendocrine tumors
- increase H+ secretion by parietal cells
- Increase parietal cell mass
- H+ secretory rates are the highest
- inhibit the absorption of sodium and water by the small intestine (secretory diarrhea)
creates ulcer by overwhelming the HCO3- buffer capacity in pancreatic juice
Low pH of intestinal contents
- inactivates pancreatic digestive enzymes
- interferes with the emulsification of fat by bile acids
- damages intestinal epithelial cells and villi
- leads to maldigestion and malabsorption (both result in steatorrhea
what is a Secretin Stimulation test
Secretin is used in the diagnosis of gastrin-secreting tumors
Under normal conditions, secretin administration inhibits gastrin release
in gastrinomas, injection of secretin causes a paradoxical increase in gastrin release
-basis for the secretin stimulation test
what are the two types of Peptic ulcer disease and what are possible causes?
two types:
- Gastric ulcers
- Duodenal ulcers
In the US, helicobacter pylori infection and the use of NSAIDS are the predominant causes
- loss of protective mucosal barrier
- excessive H+ and pepsin secretions
- combination of the two above
How does Helicobacter pyloru damage the gastric mucosa?
H. pylori releases cytotoxins that breakdown the mucosal barrier and underlying cells
THe enzyme urease allows the bacteria to colonize the gastric mucosa
- urease converts urea to ammonia which alkalinizes the local environment
- the resulting production of ammonium is believed to be a major cause of cytotoxicity and damages epithelial cells and breaks the mucosal barrier
what are the characteristics of Gastric ulcers?
Form on the lining of the stomach
Form mainly because gastric mucosal barrier is edfective, opposed to increased acid secretion
what are the characteristics of Duodenal ulcers
Form on the lining of the duodenum
More common then gastric ulcers
Usually do not become malignant
H+ secretion rates are higher than normal
H+ secretion, Gastrin levels, and comments: Gastric ulcer
H+ secretions: decreased
Gastrin levels: increased (in response to decreased H+)
Causes damage to protective barrier of gastric mucosa
H+ secretion, gastrin levels, comments: Duodenal ulcer
H+ secretion: increased
Gastrin levels: increased in response to food ingestion)
increased parietal cell mass due to increased gastrin levels
H+ secretion, gastrin levels, and comments: Zollinger-ellison syndrome
H+ secretion: major increase
Gastrin levles: major increase
Gastrin is secreted by pancreatic tumor
increase in parietal cell mass due to tropic effect of gastrin levles
What is found in Pancreatic Juice?
contains HCO3- for the neutralization of H+ from the stomach and enzyme secretions to digest carbohydrates, proteins, and lipids into absorbable molecules
What innervates the exocrine pancreas and how does it impact activity
Parasympathetic : vagus nerve
- pregangionic fibers synapse ENS
- POst ganglionic fibers synapse on the exocrine pancreas
- will stimulate the pancreatic secretion
Sympathetics
- Post ganglionic nerves from the celiac and superior mesenteric plexuses
- inhibits pancreatic secretion
What are the two components of the exocrine pancreatic
Enzymatic secretion by acinar cells for digestion
‘-pancreatic amylases and lipases are secreted as active enzymes
-pancreatic proteases are secreted in inactive forms and converted to their active forms in the lumen of the duodenum
Aqueous secretion by centroacinar and ductal cells
- secrete HCO3- rich fluid that alkalinizes and hydrates the protein rich primary secretions of the acinar cell
- initial secretion is modified by transport processes in the ductal epithelial cells
How does HCO3- secrete into the lumen of the pancreatic ductal cell
via CL-/HCO3- exchanger or
cAMP activated CFTR Cl- channel
leads to a net result of secretion of HCO3- and a absorption of H+
Cystic fibrosis and the pancreas
Mutations in the cystic fibrosis transmembrane conductance regulator
-CFTR, regulated Cl- channel in the apical surface of the duct cell
In CF the pancreas is one of the first organs to fail
SOme CFTR mutations can lead to loss of HCO3- secretion
- abillity to flush active enzymes out of the duct may be loss
- may lead to recurrent acute and chronic pancreatitis
What are the three phases of Pancreatic sectretion?
Cephalic phase:
- Initiated by smell, taste and conditioning
- mediated by the vagus nerve
- produces mainly an enzymatic secretion
Gastric phase:
- initiated by distention of the stomach
- mediated by vagus nerve
- produces mainly an enzymatic secretion
Intestinal phase:
- Accounts for 80 percent of pancreatic secretion
- enzymatic and aqueous secretions are stimulated
Regulation of pancreatic secretions
CCK induces the release of pancreatic enzymes into the duodenal lumen
Secretin induces the secretion of HCO3- from pancreatic cells into the duodenum
Process of regulation on I cells
initiated by Phenylalanine, methionine, tryptophan, small peptides, fatty acids
this acts on I cells to release CCK
this acts on Acinar cells with potentiates ACh to decrease IP3 and Ca+ leading to enzyme release from the acinar cell
Process of regulation on S cells
H+ will activate S cells to release secretin to act on Ductal cells that causes a decrease in cAMP that then will increase the aqueous secretion of Na+ and HCO3-
