GI secretions: Salivary/Gastric/Pancreatic/Hepatobiliary Flashcards
Describe the composition of saliva. What is the tonicity of saliva relative to the plasma and how is this tonicity maintained? (hint: think of water and ion solubility in acinar/duct cells)
High in K+, HCO3-
Low in Na+ and Cl-
Enzymes: ptyalin (amylase), lingual lipase
The final saliva is hypotonic relative to plasma
In acinar cells: NaCl secreted, water follows and solution is isotonic to plasma
In duct cells (site of final secretion): NaCl reabsorbed, K+ and HCO3- secreted, water not reabsorbed as much b/c duct cells are impermable to water; with increasing rate of flow/secretion, reabsorption of NaCL decreases
Describe the movement of ions in the duct cells
At all flow rates, saliva is ___ to the plasma. There is a higher concentration of __ and __, while more __ and __ are absorbed.
Hypotonic
K+, HCO3-
Na+ and Cl-
Between the sympathetic and parasympathetic systems, which one is the most important for regulation of saliva secretion? Compare the saliva output, temporal responses, saliva content and response to denervation of the 2 systems.
Parasympathetic is the most important for salivary secretion
Unlike other systems, the sympathetic and parasympathetic systems both act to __ saliva secretion. Draw the pathway each system uses to do this. What are the conditioned reflexes that influence saliva secretion? Under which conditions is saliva stimulation inhibited?
Both systems stimulate secretion
Describe Sjogren’s syndrome
Autoimmune disease that causes xerostomia aka dry mouth
What are the components of parietal cell secretions? What about non parietal cell secretions?
What is the major anion at all flow rates?
T/F: K+ concentration is always higher in gastric secretion than in plasma
Chlorine = major anion at all flow rates
T: K+ = always higher in gastric juice than in plasma
Name the functions of the following parts of the stomach:
Fundus
Body
Antrum
Pyloric sphincter
Fundus: receptive relaxation
Body (and fundus): glands for hormone and acid secretion
Antrum: tituration
Pyloric sphincter: separates stomach from duodenum; allows passage of small food particles
Contrast the components of gastric juice in parietal and non parietal cells. What is the significance of Intrinsic factor?
T/F: At all flow rates, bicarbonate is the major anion and K+ is always less in the gastric secretion than in the plasma.
What is the clinical significance of K+?
Parietal cell secretion: Intrinsic factor, H+, water
Non-parietal cell secretion: Pepsinogen, mucus, bicarbonate, sodium, potassium, chloride
Intrinsic factor >> needed for VitB12 absorption
Falsehood: Cl- major anion at all flow rates, and K+ is always higher in gastric secretion than in plasma
In vomiting, patients can become hypokalemic so treatment would require replacement of K+ more than any other ion
Describe the activation process of pepsin. What environment (acidic/alkaline) is needed for pepsin activation? Which cells secrete pepsinogen?
Which important process that occurs in pepsin activation separates pepsin activation from the activation of other enzymes?
How is pepsin activation regulated?
Pepsinogen (has catalytic site with Arg and inhibitory peptide) >> H+ environment >> Pepsin activated via autocatalysis (pepsin clips off inhibitory peptide in the presence of H+,which makes it active)
Pepsinogen secreted by chief cells
Regulation = vagus nerve >> ACh >> M1 and M3 receptors on chief cells >> +cAMP >> pepsinogen secreted >> H+ env >> cleaved to pepsin
Describe the phases of gastric secretion
Inderdigestive phase: basal Na+ absorption, baseline histamine levels, neutral ion transport
Cephalic phase: Stimulated by conditioned reflexes (taste, smell, chewing, swallowing, hypoglycemia); parasympathetic activation of acid secretion via vagus nerve
Gastric phase: stimulated by stretch of stomach due to presence of food (local reflex = stretch receptors); vago-vagal reflex : Vagus n >> Ach >> G cells >> Gastrin >>Parietal cell >> H+ secretion
Intestinal phase: slowing of gastric acid secretion and gastric emptying (secretin, CCK, GIP inhibit gastric acid secretion/emptying)
Specifically, draw a diagram summarizing what happens in the cephalic and gastric phases. Include the stimuli, the response from the vagus n/neurotransmitters and subsequent acid secretion. Which cells are involved in acid secretion?
Draw and describe the feedback regulation of gastric acid secretion
T/F: The primary method of gastrin-mediated acid secretion is by gastrin’s direct effect on parietal cells
Falsehood. Gastrin’s primary effect is not directly on parietal cells. It’s actually its activation of ECL cells to secrete histamine, which then stimulates acid secretion via H2 receptor binding on the parietal cell
Draw and describe the mechanism of acid secretion in parietal cells (so what is the direction of ion movement between the circulation and the lumen?
Co2 and water are converted to H+/HCO3- viacarbonic anhydrase
H+ secreted into lumen via H+/K+ ATPase
Cl- diffuses out via Cl- channels
HCO3- absorbed into bloodstream in exchange for Cl- (increased bicarbonate in the bloodstream = alkaline tide)
K+ recirculates via luminal K+ channels
Explain the significance of Helicobacter pylori in the formation of gastric ulcers.
What is the difference between antral-dominant gastritis and pangastritis?
H. pyloricauses chronic superficial gastritis and gastric lymphoma/carcinoma; alters acid secretion
Antral dominant gastritis: increased acid secretion, results in ulcers
Pangastritis: results in atrophy of epithelial lining; causes reduced acid secretion, results in cancer
How do NSAIDS impact the gastric mucosal barrier?
NSAIDS inhibit cyclooxygenase enzymes >> no prostaglandin synthesis
Results in decreased HCO3- secretion, decreased mucin production and mucosal blood flow
Describe the absorption of Vitamin B12. What are the effects of gastrectomy, pernicious anemia and pancreatitis on B12 absorption?
Haptocorins in the stomach bind B12
B12 freed by pancreatic enzymes
Intrinsic factor binds B12 in the proximal ileum
Allows for B12 absorption
If gastrectomy and pernicious anemia, haptocorins can’t bind B12
If pancreatitis, pancreatic enzymes can’t free B12 from haptocorins (enzymes don’t get secreted?)
Describe the exocrine and endocrine function of the pancreas. T/F: Most of the cells in the pancreas are devoted to endocrine function
Endocrine: islet cells of Langerhans (insulin, glucagon, somatostatin secretion)
Exocrine: HCO3- and digestive enzyme secretion
Draw and describe the secretion of bicarbonate
What’s the first step in digestive enzyme secretion? What are the 3 classes of zymogens/enzymes released by the pancreas and the enzyme/zymogens in each class?
(hint: for one of the categories - ENside the pancreas is ELASTic and CHYM is TRYPIN!
The exos are 3 pros, the rest are fat carbs)
Cleavage of trypsinogen into trypsin by enterokinase
Draw and describe the regulation of pancreatic secretions (hint: draw the thing showing all the peptides and the receptors they bind to and the pathway leading to secretion).
Describe the role of secretin, VIP, cholecystokinin and the vagal eneteropancreatic reflex. (for the peptides, include which cells they are secreted from)
Secretin - released from S cells; stimulated by H+*** and stomach distension; increases bicarbonate and water secretion
VIP - similar to secretin but not as potent
CholecystokInin released from I cells; stimulates acinar enzyme release and gall bladder contraction
Vagal enteropancreatic reflex - food in duodenum >> vagal afferents >> vagal efferents >> fluid and enzyme secretion
Draw and describe the process of bile formation. What is the difference between bile acid dependent and independent flow? Describe the hormonal/neural regulation of either process, if any.
Bile independent flow: driven by secretions from duct cells (HCO3-), and absorption of Na+, Cl-; hormonal regulation by secretin (opposed by somatostatin)
Bile dependent flow: osmotic gradient created by bile acids drags ions and water with the bile acids into the canaliculus. Independent of nerves or hormonal regulation.
Draw and describe the bile acid transport in the ileum and the liver. Describe the roles of NTCP, BSEP, OSTalpha/beta and OTAP transporters on the hepatocyte.
What are the roles of ASBT and OSTalpha/beta on the enterocyte?
What is the significance of the MDR3 transporter?
MDR3 – multi drug resistant
NTCP – major transporter of bile acids from blood to hepatocytes
BSEP - major transporter of bile acids into bile
ASBT – transports bile acids back into the liver
OSTalpha/beta - returns bile acids back into portal circulation
Draw and describe the enterohepatic feedback regulation of bile synthesis
What is the significance of FGF19?
How is this feedback loop changed in patients with irritable bowwl syndrome w/ diarrhea?
In the enterocyte:
cholesterol >> bile acid >> ASBT transport into enterocyte >> bile acid binding to FXR receptor >> stimulation of FGF19 production
In the hepatocyte: FGF19 binding to receptor complex >> upregulation of SHP >> inhibition of Cyp7A1
Alt pathway:
In the enterocyte: cholesterol >> bile acid >> ASBT transport into enterocyte >> export by OSTa/b into portal circulation
In the liver: bile acid binding to liver FXR >> upregulation of SHP >> inhibition of Cyp7A1
IBS w/ diarrhea: bile acids beyond ASBT’s transport capacity >> secreted into colon >> diarrhea develops; FGF19 also lacking
FGF19: suppresses bile acid production
What is the effect of bacterial deconjugation of bile acids in the small intestine?
Describe the mechanism through which bacteria form secondary bile acids
Bacterial deconjugation of bile acids >> enhanced motility >> diarrhea
Bile acids that escape the enterohepatic circulation get converted to 2ndary bile acids
