PHYS - Secretions of GI & Pancreas Flashcards
What is the function of saliva?
- Initial digestion of starches and lipids
- Lubrication of ingested food with mucus
- Dilution and buffering of ingested food
What are the 3 saivary glands?
Parotid Glands
Submaxillary Glands
Sublingual Glands
What is unique about the Parotid Glands?
Produce 25% of saliva
- Secretions rich in amylase
- Secretions contain water, ions, and enzymes (not just amylase)
Composed of serous cells only
What is unique about the Submaxillary and Subingual Glands?
Composed of serous and mucous cells
Produce 75% of saliva
Secrete aqueous fluid and mucin glycoprotein for lubrication
What is the Acinus, what cells are there, and what do the cells do?
Acinus is the blind end of the Salivary gland
Acinar Cells - secrete INITIAL saliva (which is ISOTONIC, and plasma-like)
Myoepithelial Cells - Contract when stimulated by neural input, ejecting the saliva into the mouth
What is the intercalated duct?
Middle portion of the salivary gland between the acinus and the striated duct.
What is the striated duct, what cells are there, and what do the cells do?
The last portion of the salivary gland after the intercalated duct
Simple columnar epithelial cells called Ductal Cells are present
- They alter the concentration of various electrolytes, making the final saliva HYPOTONIC
What is the composition of saliva?
Saliva is HYPOTONIC
It is composed of water, alpha amylase, electrolytes, lingual lipase, kallikrein, and mucous
Saliva has high concentrations of HCO3- and K+, and low concentrations of Na+ and Cl-
What transporters do the ductal cells express, and on which membrane are they found?
Apical Membrane:
- Na+/H+ Exchanger
- H+/K+ Exchanger
- HCO3-/Cl- Exchanger
Basolateral Membrane:
- Na+/K+ ATPase
- Cl- Channel
- HCO3-/Na+ COTRANSPORTER
What is the net movement of electrolytes across the Ductal Cells’ apical membrane?
Na+ and Cl- Absorption
HCO3- and K+ Secretion
How does water move as saliva travels through the Striated Duct?
Water remains in the Salivary Gland lumen as the Ductal Cells are Impermeable to water
How are the salivary glands innervated by the parasympathetic nervous system?
Presynaptic nerves originate in the Glossopharyngeal N. (Parotid Gland) and the Facial N. (Submaxillary & Subingual Glands)
Post synaptic nerves originate in autonomic ganglia which innervate the glands
How are the salivary glands innervated by the sympathetic nervous system?
Presynaptic nerves originate at T1-T3 and synapse at the cervical ganglion
Post synaptic fibers extend to the salivary glands in the periarterial spaces
What effect does atropine have on the salivary glands?
Atropine blocks post-synaptic parasympathetic signaling of the salivary glands, inhibiting salivary secretion
What do sympathetic and parasympathtic innervation do to the salivary glands?
Both Parasympathetic and Sympathetic innervation cause increase in saliva production, increase in HCO3- and enzyme secretion, as well as myoepithelial cell contraction (saliva secretion into mouth)
Which of the two autonomic innervations is dominant?
Parasympathetic effects dominate
What conditions regulate parasympathetic innervation?
Promotes parasympathetic Signaling:
- Conditioning
- Food
- Nausea
- Smell
Inhibits Parasympathetic Signaling:
- Dehydration
- Sleep
- Fear
How are the salivary glands controlled under somatic innervation?
Trick question, only the Autonomic nervous system innervates the salivary glands
What are the main components of secreted gastric juices from the gastric mucosa?
HCl (H+) - Kills bacteria, helps digest food, converts pepsinogen to active form (pepsin)
Intrinsic Factor - Required for absorption of Vitamin B12 in the ileum
Pepsinogen - Inactive precursor of pepsin
Water - Medium for activity of acid and enzymes, solubilizes ingested material
Mucous - Lines wall of stomach to protect lining from acidic damage (with help of HCO3-; neutralizing pH)
What are the two gland types and where in the stomach are they located?
Oxyntic Glands - Found in the proximal 80% of the stomach (body and fundus)
Pyloric Glands - Found in the distal 20% of the stomach (antrum)
What is the function of the Oxyntic Glands and what cell types are found in the gland?
Oxyntic Glands main function is the secrete Acid
Parietal Cells - Secrete Acid (HCl) and Intrinsic Factor
Chief Cells - Secrete Pepsinogen (protein digestion)
D Cells - Secrete Somatostatin (acts on parietal cells to reduce acid secretion)
Enterochromaffin-like Cell (ECL cell) - Secrete histamine (which promotes acid secretion by the parietal cells)
Enterochromaffin Cell - Secrete Serotonin (to induce peristaltic contractions)
What is the function of Pyloric Glands and what cell types are found in the gland?
Pyloric Glands synthesize and secrete Gastrin
G Cells - Secrete Gastrin (promotes Parietal cells to secrete acid)
D Cells - Secrete Somatostatin (inhibits Parietal Cell acid secretion)
Enterochromaffin Cells - Secrete Serotonin (to induce peristaltic contractions)
What cells are primarily found in the Body of the Stomach and what do they do?
Parietal Cells - Secrete HCl and Intrinsic Factor (required for Vitamin B12 absorption) into gastric lumen
Chief Cells - Secrete Pepsinogen into gastric lumen
What cells are primarily found in the antrum of the stomach and what do they do?
Mucus Cells - Secrete Mucus, HCO3-, and Pepsinogen
G cells - Secrete Gastrin into the blood (promoting acid secretion by the parietal cells)
What is omeprazole, and how does it work?
It is a proton pump inhibitor
It prevents the exchange of luminal K+ and cellular H+
What cellular mechanisms allow for HCl secretion?
Na-K ATPase sets the Na+/K+ gradient
HCO3- Buffer system produces H+ and HCO3- in the cell.
H+ leaves cell through K+/H+ ATPase on apical membrane
HCO3- leaves cell through HCO3-/Cl- exchanger on the basolateral membrane
Cl- leaks into stomach lumen through Cl- channel on the apical membrane
H+ and Cl- secretion results in formation of HCl in the gastric lumen
How does vagal stimulation affect parietal cells?
Vagal stimulation ends with acetylcholine secretion at the parietal cell, PROMOTING acid secretion directly
Additionally, Acetylcholine acts on Enterochromaffin-like cells, PROMOTING Histamine secretion (indirectly PROMOTING acid secretion)
How do G cells affect perietal cells?
G cells secrete gastrin, gastrin directly PROMOTES parietal cell acid secretion
Gastrin also PROMOTES Enterochromaffin-like cell histamine secretion (indirectly PROMOTING acid secretion)
How do Prostaglandins affect parietal cells?
Prostaglandins directly INHIBIT parietal cell acid secretion
Prostaglandins also INHIBIT Enterochromaffin-like cell histamine secretion (indirectly INHIBITING acid secretion)
How do D cells affect parietal cells?
D cells secrete Somatostatin, which directly INHIBITS parietal cell acid secretion
Somatostatin INHIBITS G cell gastrin secretion (indirectly INHIBITING acid secretion)
Somatostatin INHIBITS Enterochromaffin-like Cell histamine secretion (indirectly INHIBITING acid secretion)
How do Enterochromaffin-like cells affect parietal cells?
Enterochromaffin-like cells secrete Histamine
Histamine directly PROMOTES acid secretion
What is Atropine, and what does it do?
It is a drug that is capable of blocking Acteylcholine binding to M3 muscarinic ACh receptors found on parietal cells
Blocking ACh activity on parietal cells inhibits vagal stimulation of gastric acid secretion
HOWEVER, vagus nerve also stimulates G cells via the Gastrin Releasing Peptide neurotransmitter, which indirectly promotes acid secretion and cannot be blocked by Atropine
What is Cimetidine and what does it do?
It is a drug tat is capable of blocking the H2 histamine receptor.
Histamine is secreted from Enterochromaffin-like cells, and it promotes parietal cell acid secretion.
Thus cimetidine blocks this activity
How does the vagus nerve stimulate parietal cell acid secretion?
Direct Pathway: ACh neurotransmitter signals parietal cells to secrete HCl
Indirect Pathway: Gastrin Releasing Peptide neurotransmitter signals G cells to secrete Gastrin, which enters the circulation and signals Parietal cells to secrete HCl
How is somtatostatin secretion by D cells regulated?
Increased circulating levels of Gastrin promote D cell somtatstatin secretion
Increased gatric H+ concentration promotes D cell somatostatin secretion
Vagal stimulation results in ACh neurotransmitter signaling D cells to stop secreting Somatostatin
What is potentiation and what does it mean for parietal cell acid secretion?
Potentiation means that a cells response to two stimulants at once is greater than the sum of their individual responses
This means that if a parietal cell is being stimulated to secrete acid by Histamine from ECL cells and Gastrin from D cells, more acid is secreted than if just Histamine and Gastrin were stimulating the parietal cell individually.
What are the three phases Gastric HCl secretion?
Cephalic Phase
Gastric Phase
Intestinal Phase
What is the Cephalic Phase of HCl secretion, what stimulates it, and how does it influence parietal cells?
Cephalic phase is a phase of gastric acid secretion stimulated by Chewing, Swallowing, smell, and taste of food. It is responsible for 30% of HCl secretion.
The above stimuli trigger the vagus nerve to activate parietal cell acid secretion directly via ACh signaling and indirectly via GRP signaling to G cells causing Gastrin secretion, which signals parietal cells to secrete HCl
What is the Gastric Phase of HCl secretion, what stimulates it, and how does it influence parietal cells?
Gastric phase is a phase of gastric acid secretion stimulated by gastric distension (food in stomach), and is responsible for 60% of total HCl secretion
Gastric distension causes vagus nerve to stimulate Parietal cells directly via ACh.
Local reflexes activated by gastric distension cause direct stimulation of parietal cells via ACh signaling.
Same local reflexes also activate G cells via ACh signaling, causing the G cells to secrete Gastrin, which promotes parietal cells to secrete HCl
Presence of amino acids in the stomach also promote Gastrin secretion from G cells, thus promoting parietal cells to secrete acid
What is the Intestinal Phase of HCl secretion, what stimulates it, and how does it influence parietal cells?
Intestinal Phase is a phase of gastric acid secretion stimulated by the presence of digested proteins, and is responsible for 5-10% of total HCl secretion.
The digested proteins promote gastric G cell and intestinal G cell secretion of Gastrin into the blood stream, promoting parietal cells to secrete HCl
Digested proteins are also absorbed into the blood, and the presence of these circulating amino acids promote Parietal cell HCl secretion
If a patient undergoes a vagotomy, which phase(s) of gastric acid secretion would be inhibited?
Cephalic phase would be completely, and permanently, abolished.
What stimulates Chief cells, what do they secrete, and what happens when their secretion enters the gastric lumen?
Chief cells are stimulated primarily by the vagus nerve
In response to vagal stimulation, the chief cells secrete pepsinogen
When pepsinogen enters the gastric lumen, it is converted to its active form Pepsin.
An acidic pH (optimally betwen 1.8-3.5) will cause the partial conversion of Pepsinogen to pepsin. Other pepsin molecules interact with converting Pepsinogen molecules, allowing them to become fully active Pepsin molecules
What is pernicious anemia?
Anemia is when there are not enough red blood cells circulating in the blood.
Pernicious anemia is when vitamin B12 is not absorbed due to lack of Intrinsic factor excretion (IF is required for B12 absorption)
Can either be ATROPHIC (chronic inflammation of stomach causes destruction of parietal cells)
Or AUTOIMMUNE (immune system attacks IF molecules or Parietal cells)
What cells are present in the gastric epithelium, what do they secrete, and what is their purpose?
Mucus Cells - secrete mucous
Surface Epithelial Cells - secrete HCO3-
Mucous and HCO3- together form a protective barrier that keeps the gastric epithelium from being damaged by HCl acid and Pepsin enzymes
What are some examples of agents that can harm the gastric epithelium?
Acid, H pylori bacteria, NSAIDs, Pepsin, alcohol, smoking, bile, and stress
What are some examples of agents that can enhance the gastric epithelium?
HCO3-, Mucus, Prostaglandins, Mucosal blood flow, growth factors
What is Zollinger-ellison syndrome
A Tumor (usually in the pancreas) secretes excessive amounts of gastrin, causing an increase in HCl secretion and an increase in parietal cell size (trophic effect)
Excessive H+ entering the duodenum overwhelm the buffer capacity of HCO3- in pancreatic juices, causing an ulcer
Additionally, the low pH causes lipase enzymes secreted by the pancreas to become deactivated, reducing the ability to digest fats (resulting in fatty stools)
How do you test for a gastrin secreting tumor?
You inject secretin
Secretin inhibits gastrin release by G cells, thus if secretin is injected you would be able to test blood samples and observe a decrease in circulating gastrin levels.
What is Peptic ulcer disease?
Chronic condition that results in the formation of an ulcer.
Most caused by H pylori infection or excessive use of NSAIDs
Result from a decrease in protective mucosal barrier, excessive H+ and pepsin secretions, or a combination
Two types: Gastric ulcers and Duodenal ulcers
How does H pylori affect the gastric epithelium?
H pylori bacteria utilize an enzyme called urease
Urease converts urea into ammonia (NH3), which makes the local environment around the bacteria more alkaline than the rest of the gastric lumen.
NH3 reacts with the H+ in the stomach forming NH4+, which is cytotoxic and breaks down gastric epithelial cells and the mucosal barrier
Thus an ulcer is formed
How is H pylori tested diagnostically?
A test is done to detect urease activity
What are the components of pancreatic juice?
Water, HCO3-, and enzymes that aid in digestion of carbs, proteins,and lipids
How does the sympathetic nervous system innervate the exocrine pancreas?
Post ganglionic nerve fibers travel from the cephalic plexus and the superior mesenteric plexus.
Sympathetic innervation inhibits secretion of pancreatic juices
How does the parasympathetic nervous system innervate the exocrine pancreas?
Via vagus nerve, pre-synaptic nerve fibers synapse at the ENS
Post synaptic nerve fibers synapse on the exocrine pancreas
Parasympathetic innervation promotes the secretion of pancreatic juices
What are the two cells found in the exocrine pancreas and what are their functions?
Acinar Cells - Found at closed end of exocrine gland, secrete pancreatic enzymes into lumen of gland
Ductal Cells - Found at open end of exocrine gland, form the duct of the gland and secrete aqueous solution containing HCO3-
What is the net result in terms of ion movement across ductal cells?
HCO3- is secreted by ductal cells, while H+ are absorbed into the blood
There is no net movement of Na+ as Na-K ATPase pumps Na+ out into the blood while Na+ also leaks into the lumen paracellularly
How does Cystic Fibrosis affect the pancreas?
Cystic Fibrosis occurs when there is mutation resulting in the dysfunction of the CFTR Cl- channel.
This Cl- channel is found on the apical membrane and allows for the HCO3-/Cl- exchanger to function properly on the apical membrane.
Without a Cl- gradient to promote the activity of the HCO3-/Cl- exchanger, HCO3- is not secreted into the lumen of the exocrine gland.
This results in an inability to secrete pancreatic enzymes and can lead to pancreatitis
What are the 3 phases of pancreatic secretion?
Cephalic - Stimulated by smell, taste; mediated by the vagus nerve; produces pancreatic secretion mostly composed of enzymes
Gastric - Stimulated by gastric distention; mediated by the vagus nerve; produces mainly enzymatic secretion
Intestinal - Accounts for 80% of pancreatic secretion; produces enzymatic and aqueous secretion
How are the exocrine pancreas acinar cells regulated?
Parasympathetic signaling via ACh promotes secretion of enzymes from Acinar cells
Presence of amino acids, small peptides, and fatty acids promotes I Cells to secrete CCK; CCK promotes acinar cell enzyme secretion
How are exocrine pancreas ductal cells regulated?
Parasympathetic signaling vis ACh promotes secretion of aqueous solution (w/ HCO3-)
Increased presence of H+ stimulates S cells to secrete Secretin; Secretin promotes ductal cell aqueous solution secretion
Increased presence of amino acids, small peptides, and fatty acids stimulates I Cells to secrete CCK; CCK promotes dutal cells to secrete aqueous solution
