Secretion of the GI Tract & Pancreas (Physiology) Flashcards
The distribution and importance of the different salivary glands:
Parotid glands- 100% serous fluid (25% of saliva)
submandibular & sublingual glands- mixed serous/mucosal fluid (75% of saliva)
Anatomy of the Salivary Glands:
Acinus- starts saliva secretion
Myoepithelial Cells- finish the complete secretions through extensions into the acinus cells
Intercalated ducts-> creates isotonic environment in between the plasma & salivary fluid
Ductal Cells/Striated Duct-> Simple Columnar Epithelium; HYPOTONIC saliva at this point compared to the blood plasma
What is the final structure of saliva? What is it composed of & osmolarity in relation to the blood plasma?
- hypotonic compared to blood plasma
- HIGH CONCENTRATIONS OF K+ & HCO3-
- LOW CONCENTRATIONS OF NA+ & CL-
Composed of:
H20, electrolytes, alpha-amylase, lingual lipase, kallikrein (mild protease), & mucus
Two main steps in the formation of saliva
- ) Creation of the Isotonic Saliva by the Acinar Cells
2. ) Creation of the Hypertonic Solution by the Ductal Cells
Ductal Cells (overall goal) ***(P.S. it helps that these cells are H20 impermeable)
Create a net absorption of solute:
- Increase in K+ & HCO3- output
- Increase in Na+ & Cl- input
*** The solution becomes isotonic because there is more absorption into the ductal cells of Na+ & Cl- than there is excretion of HCO3- & K+ OUTFLOW
INFLOW»» OUTFLOW–> Thats what makes the solution hypotonic as it becomes secreted!
Sympathetic vs Parasympathetic Innervations of the Salivary Glands
Sympathetic Innervation: T1-T3 Lateral Horn synapses at the superior celiac ganglion where it then acts on the salivary glands
Parasympathetic Innervation: CN 3, 7, 9 all will go to certain ganglions like the pterygpalatine ganglion & submandibular ganglion to synapse and release saliva into the mouth!!!!
What is the effect of the post-ganglionic neuron on the salivary glands when acted on by atropine?
ATROPINE blocks the release of Acetylcholine on to the mAChR that releases the saliva from the mouth!
**THIS IS POST-SYNAPTIC PARASYMPATHETIC
INNERVATION
ADH & Aldosterone also have effects on the release of the saliva. What effects does it have?
The effect that it has is that it creates more absorption of the Na+ & Cl- ions into the blood supply. To support the actions of the ADH & Aldosterone to increase the blood pressure.
The cells of the gastric mucosa secrete gastric juice
Main Components of Gastric Juice:
HCL, Pepsinogen, Mucus, Instrinsic Factor, H20
Main components of the secretion of gastric juice:
Secretions:
HCL- together with pepsin, it initiates digestion
Pepsinogen- pepsinogen broken down into pepsin by HCL (pepsinogen is the precursor for pepsin)
Mucus- lines the wall of the stomach & protects it from damage; lubricant & neutralizes the surface of the stomach lining to protect it (keeping at neutral PH)
Intrinsic Factor- secreted by the gastric cells that is needed to bind to vitamin B12 and allows for the absorption of B12 in the ileum.
H20- medium for the action of HCl & enzymes; “I think it means that it gives it the aqueous environment”
The Stomach Divisions & Secretions
1.) Fundus & Body–>
Oxyntic Gland-
secretes 80% oxyntic gland which is important for HCL secretion from (Parietal Cells & Chief Cells)
Parietal Cells- secrete pepsinogen Chief Cells- secrete HCL
2.) Antrum–>
Pyloric Gland-
secretes 20% Pyloric Gland; releases gastrin enzyme (goes into the blood circulation to bind to the parietal cells+ intrinsic factor)
G Cells- secrete gastrin into circulation
Mucus Cells- secrete mucus, HCO3- ion, pepsinogen
*****Protects the epithelial layer of the gastric mucosa
The Oxyntic Gland (The parietal cells in it & the Chief cells in it)
The Oxyntic Gland (Body & Fundus):
+Parietal Cells- secrete HCL from the cannaliculi along the villi of the parietal cell’s apical membrane
+Chief Cells- secretes pepsinogen to pepsin from the low gastric pH
What is the function of Omeprazole in gastric secretions?
Omeprazole inhibits the K+/H+ Pump which inhibits the parietal cells to secrete acid (H+) into the apical side lumen.
***Inhibition of the Parietal Cells
How does the Parietal Cell Work?
Apical Side:
It uses a H+/K+ Pump (antiporter) to push H+ out into the lumen and K+ into the cell:
* HCO3- gets pushed into the basolateral side of the
blood
- The Breakdown of h20+c02–>h2c03–> h+ +
hco3-
Basolateral Side:
It uses a HC03-/CL- antiporter to push HCO3- to the blood basolaterally while pushing the Cl- ion into the cell.
So on the Basolateral Side of the Gastric Parietal Cell are these receptors:
M3 Receptors- activated by vagus nerve stimulation via acetylcholine release
*SECRETES H+ SECRETION
CCKb Receptors- G cells release gastrin that binds to the CCKb Receptors on the basolateral side of the parietal cells.
*SECRETE H+ SECRETION
H2 Receptors- Enterochromaffin-like cells release histamine to activate h2 receptors–>
*SECRETE H+ SECRETION
What are the Enterochromaffin-like Cells inhibited by which cause them to stop the release of H+ into the lumen of the stomach?
ECL cells that release histamine that activate h2 receptors that cause H+ secretions via H+/K+ Antiporter Pump.
* Somatostatin & Prostaglandins inhibit the ECL cells from RELEASING HISTAMINE that bind H2 Receptors
What inhibits CCKb Receptor binding of gastrin because of an inhibition of the G cell?
G cell is inhibited by somatostatin -> this causes a problem with the release of Gastrin from G-Cells–> problem binding of Gastrin to the CCKB receptors that activates the release of H+/K+ Antiporter.
Explain the Direct & Indirect Pathway of vagal nerve stimulation of the Stomach that causes release of H+ from parietal cells-
Direct Pathway of Vagal Nerve- Direct stimulation of the body and fundus areas of oxyntic gland where parietal cells are. These cells are inhibited by Atropine because it prevents the release of Acetylcholine @ post-synaptic fibers to release HCL.
Indirect Pathway of the Vagal Nerve- Indirect stimulation of the antrum via post ganglionic fiber stimulation of Gastrin Releasing Peptide (GRP). This is NOT INHIBITED BY THE DRUG ATROPINE!!!!!
The function of Somatostatin and its role in regulation of the G Cell.
Somatostatin is secreted from D-cells in the stomach and it causes the inhibition of the G-cells in the Pyloric Gland which inhibits the release of G-Cells into the bloodstream to activate the Parietal Cells.
Explain the negative feedback between the G Cell and the D cells in the stomach.
G cells secretes gastrin to increase the h+ secretion of the stomach.
D cells regulate that G cell release of gastrin when the somatostatin released from D cells
** There is a TON OF H+ in the lumen of the stomach
and that creates a change in the environment of
the stomach
The rate of secretion of HCL is also regulated by the interactions among histamine, Acetylcholine, and Gastrin. But how?
Acetylcholine, Gastrin, and Histamine all have proactive roles in self stimulating each other to get an overall additive effect to the release of H+ into the lumen of the stomach via blood transport!
What are a class of drugs that can inhibit the effect of these potentiating NT effects?
Atropine or MAchR antagonists–> not only effect the direct pathway of the release of H+, but also diminishes the potentiating effects of H+ release into the stomach.
What directly inhibits the H2 receptors from binding histamine to the basolateral side of the gastric parietal cell?
Cimetidine Drug on the basolateral side of the gastric parietal cell
Histamine potentiates:
Gastrin and Acetylcholine release
Ach potentiates:
Gastrin and Histamine release
Cephalic Phase of Gastric HCL Secretion
Stimuli: smelling, tasting, chewing, swallowing, conditioned reflexes
Direct Pathway : Vagus nerve stimulates the release of HCL from Parietal Cells
Indirect Pathway: Vagus nerve stimulates the release of GRP from the G Cells. These G cells secrete gastrin and then will bind to the parietal cells that cause the cell to release HCL.
**30% of Total HCL is secreted in response to a meal
Gastric Phase of HCL Secretion
** 60% of Total HCL is secreted in response to a meal
Stimuli: Distention of the stomach, presence of breakdown of proteins, AAs, & small peptides
Direct Pathway: Vagus nerve stimulates the release of the HCL from the parietal cells
Indirect Pathway: Vagus nerve stimulates the release of GRP & then it causes the release of Acetylcholine to the parietal cells.
Intestinal Phase of HCL Secretion
** 5-10 % of Total HCL is secreted in response to a meal
Distention of small intestine- stimulates acid secretion
Digested protein also causes stimulation of acid secretion:
+ via G-Cells that are activated that causes the release
of Gastrin. That Gastrin acts on parietal cells to
secrete HCL.
How is pepsinogen converted to the pepsin? What is the optimum pH and what is the strongest stimulus for the secretion of H+?
Pepsinogen is secreted only when the gastric pH is acidic enough to convert it to pepsin; Pepsinogen is secreted from the Chief Cells with the HCL from Parietal Cells that are from the oxyntic glands of the body and the fundus of the stomach.
pH< 5 (*BEST AT THIS PH LEVEL)
Pepsin degrades food proteins into peptides
Pepsin converts more pepsinogen to peptides;
a.) proteolytic enzyme–>
Optimal ph- 1.8-3.5
Reversibly inactivated @ x> ph 3.5-5.0
Irreversibly Inactivated @ x> pH 7-8
What is secreted by the parietal cells of the oxyntic glands of the fundus and the body of the stomach?
What is secreted is HCL by the parietal cells of the body and fundus of the stomach
What is pernicious anemia?
Pernicious Anemia is a type of anemia that is developed when you cannot secrete IF with the Parietal Cells.
* That Vitamin B12 is used with IF to take up the combination through the gut and into the liver for storage.
+ because of this reservoir of Vitamin B12, there is an
accumulation that won’t get depleted for several
years
Common Causes of pernicious anemia?
Atrophic Gastritis- chronic inflammation that causes damage to the parietal cells that secrete intrinsic factor causing the pernicious anemia
Autoimmune Metaplastic Atrophic Gastritis- (immune system does its own attack on the parietal cells or the secrete IF of the body and fundus of the stomach)
Growth of the Gastric Mucosa
Gastric Mucosal Barrier–> created from the secretion of the HCO3- ion and the mucus from the gastric epithelium.
+This barrier is there to protect the epithelial lining
from damage by the pepsin or the high acidity/low
pH value
What damages the gastric mucosal barrier?
Acid, Pepsin, NSAIDS, Helicobacter Pylori, Alcohol, Bile, stress damage to the gastric mucosa, Stress, Smoking
What is Zollinger-Ellison Syndrome?
- H+ secretory rates are the highest
- Tumor in the pancreas- secretes large amounts of
gastrin
+ Increased H+ secretion by parietal cells &
Increased Parietal Cell Mass
(Trophic Effect: due to the large tumor in the pancreas secreting Gastrin from the G-Cells)
How is steatorrhea related to Zollinger-Ellison Syndrome?
ZES causes an increase in the H+ secretion from the parietal cells because of the activation of the parietal cells by the release of Gastrin in the Pancreas of G-Cells.
Steatorrhea comes into play when the extremely acidic condition causes a large upbeat overcompensation of the HCO3- ion buffering system from the pancreas causing the low pH to causes ULCERS IN THE DUODENUM.
What is the secretin stimulation test used for and what is its effect on the gastrinomas/ ZES Syndrome?
Secretin stimulation test is a hormone that is released from the duodenum that causes the inhibition of the G cells.
- When this inhibition doesn’t occur, what happens is that secretin actually increases the release of gastrin from the G-CELLS.
Predominant causes of 2 ulcers (gastric ulcers & duodenal ulcers)
Gastric Ulcers and Duodenal Ulcers->
*****caused by H. Pylori & NSAIDS
How does H. Pylori breakdown the gastric mucosa?
Gastric mucosa is broken down by the effects of:
**** urease released from H. pylori
Disorders of the Gastric H+ Secretion
Gastric Ulcer:
Decreased H+ secretion
Increased Gastrin Levels
Damage to mucosal barrier of stomach
Duodenal Ulcer:
Increased H+ Secretion
Increased Gastrin Levels
increased parietal cell mass due to increased gastrin
levels
The exocrine pancreas is innervated by:
parasympathetics
sympathetics
Parasympathetics: vagus nerve
Sympathetics:
post-ganglionic nerves from the celiac & superior mesenteric ganglion
Sympathetic Innervation- inhibits pancreatic secretion
Parasympathetic Innervation- activates pancreatic secretions
Secretory Cells of the Exocrine Pancreas
Acinar Cells-> secrete HCO3- ions & enzymatic secretions
Exocrine Pancreas is organized like salivary glands:
Acinus Cells-> synthesize & secrete major enzymes of
digestion
Ductal & Centroacinar Cells–> secrete ions like HCO3-
aq solution
What type of hormones are secreted from these acinar cells of the pancreas?
pancreatic lipase, pancreatic amylase, and pancreatic proteases (secreted in inactive forms)
***Special Note: those pancreatic proteases are zymogens until they’re converted into active forms in the duodenum
What are the pancreatic ductal cells and how do they secrete HC03- ions from the apical side?
***There is also paracellular travel of Na+ from basolateral side to the apical side of the pancreatic ductal cells!
HC03- ions leave from the apical side into lumen while the Cl- ions come into the cell via the:
*HCO3-/Cl- Antiporter Channel on the Apical Side
Cystic Fibrosis & Pancreas Problems
Cystic Fibrosis- causes a problem with CFTR Cl- Channel to leave through the apical side of the cell. This causes water to follow that would cause enzymes to be able to be washed away.
**Problem comes when the CFTR channel is closed;
when this happens, what happens is that there is a
large amount of Cl- collected within the cell
causing H20 to follow.
Complications of Cystic Fibrosis
Acute & Chronic Pancreatitis
Three similar phases to Pancreatic Secretions like Gastric Secretions:
- ) Cephalic Phase- initiated by smell, taste, conditioning; mediated by vagus nerve; produces mainly by enzymatic secretions
- ) Gastric Phase - produced mainly an enzymatic secretion mediated by the vagus nerve; initiated by the distention of the stomach
- ) Intestinal Phase- accounts for 80% of pancreatic secretions
The mechanism of how these pancreatic enzymes are activated during the INTESTINAL PHASE
I cells are activated by (Phenylalanine, Methionine, Tryptophan, Small Peptides, Fatty Acids)
I Cells–> secrete CCK Hormone–> Acinar Cells of Pancreas (CCK activates the pancreas as well as Ach from Vagus Nerve) –> Release of Pancreatic Enzymes
What is the mechanism that controls the acidity of the stomach based on from the pancreas?
**When there is high H+ concentrations in the lumen of the duodenum, S cells are secreted to activate the Ductal Cells to secrete Aq Solution (Na+, HCO3- ions).
