Pancreas, Gallbladder, and Liver Physiology Flashcards
True or False: Amino acids enter enterocytes along with Na+ ions, using 5 different co-transporters that are selective for neutral aromatic, imino, positively charged and negatively charged amino acids.
True
True or False: Monosaccharides leave the enterocyte by means of a Na+ coupled transporter protein on the basolateral surface of the cell.
False
How does H+ in the duodenum lead to bicarbonate secretion?
- H+ ions in duodenum
- Activates secretin release
- Goes over to pancreas and leads to bicarbonate secretion
How do amino acids/fats in the duodenum lead to decreased motility?
- Amino acids/fats in duodenum
- Triggers release of CCK
- Slows things in your stomach down
- Both inhibit gastric motility as well as gastric secretion
What contraction does CCK control?
Sphincter of Oddi contraction
What is the Pancreas exocrine secretion?
~90% of cells
-Digestive enzymes and bicarbonate into the duodenum
How much exocrine pancreas secretions do we release each day?
1.5 L/day
What do Acinar cells (exocrine pancreas) release?
Secrete digestive enzymes
What do Centroacinar and Duct cells do in the exocrine pancreas?
They dilute pancreatic enzymes and make rich in sodium and bicarbonate.
What proteases are pancreatic acinar cell secretory products?
- Trypsinogen
- Chymotrypsinogen
- Proelastase
- Procarboxypeptidase A
- Procarboxypeptidase B
What amylolytic enzymes are pancreatic acinar cell secretary products?
-Amylase
What Lipases are pancreatic acinar cell secretory products?
- Lipase
- Nonspecific esterase
- Prophospholipase A2
What Nucleases are pancreatic acinar cell secretory products?
- Deoxyribonuclease
- Ribonuclease
What “others” are pancreatic acinar cell secretory products?
- Procolipase
- Trypsin inhibitors
- Monitor peptide
What do Enteropeptidase and Enterokinase do?
Targe trypsinogen to become trypsin
What is the function of Trypsin?
- Activates procolipase to become co-lipase
- Activates co-lipase to become lipase
It’s important for pancreatitis that you’re not getting premature activation of these enzymes.
How are pancreatic enzymes synthesized?
They are synthesized with an N-terminal signal peptide, which targets them for the secretory pathway where they are packaged into zymogen granules and prevents them from being exposed to the cytosol.
What indicates the inactive form of pancreatic enzymes?
-ogen
pro-
During the cephalic/gastric phase, what percent of pancreatic exocrine secretion is enzyme?
30% enzyme, low volume acinar cells activated by parasympathetic efferents (ACh) from vagal centers in the brain and secondary to gastrin release.
During the Intestinal phase, what percent of pancreatic exocrine secretion is enzyme?
70% enzyme, increased enzyme, high volume. Acinar cells are activated by vago-vagal reflex and by fat/amino acids in duodenum.
- I cells release CCK
- H+ ions cause S cells to release secretin activating ductal cell secretion of bicarbonate
What things promotes compound exocytosis in acinar cells?
Secretagogues!
- CCK and vagal stimualtion (ACh, GRP)
- Ca2+ signaling most important with cAMP signaling playing a modifying role
What does vagal stimulation cause during the cephalic and gastric phases?
Vagal stimulation causes release of pancreatic enzymes including Monitor Peptide.
What do amino and fatty acids cause the release of during intestinal phase?
CCK-RP
What do CCK-RP and Monitor Peptide do?
Cause the release of CCK from I cells into the blood.
What does CCK increase the release of?
Monitor peptides and pancreatic enzymes
What happens toward the end of intestinal phase?
- Pancreatic enzymes digest luminal nutrients.
- CCK-RP and Monitor peptide turning off CCK secretion.
What is CCK??
Cholecystokinin - Master regulator of duodenal cluster unit
- Released when fat and protein are in the duodenum
- Satiety signal
- Also alters brain decreasing food intake
What does CCK do to the Gallbladder?
Contraction
What does CCK do to the Pancreas?
Acinar secretion
What does CCK do to the stomach?
Reduced emptying
What does CCK do to the Sphincter of Oddi?
Relaxation
Overall what does CCK promote?
- Protein, carbohydrate, lipid absorption and digestion
- Matching of nutrient to digestive and absorptive capacity
What is the function of Enteropeptidase?
It’s in the duodenal brush boarder membrane and it cleaves trypsinogen to its active form, trypsin.
What does Trypsin activate?
Lipases and Endopeptidases, chymotrysin and elastase.
What causes Hereditary Pancreatitis?
It occurs due to a mutation in the trypsinogen PRSS1 gene causing activation of digestive enzymes in the pancreas which can lead to inflammation.
How is Hereditary Pancreatitis passed on?
Autosomal Dominant
What do S cells do when duodenal pH
Release secretin, which raises the pH by increasing bicarbonate secretion from the pancreatic ducts, biliary ducts and duodenal mucosa.
Do you predict a patient on a PPI will have increased or decreased duodenal bicarbonate secretion postprandially?
Decreased (no longer an acid signal being released)
What is the function of Secretin?
It initiates secretion of bicarbonate solution by pancreatic duct cells.
What transporter provides “power” for the duct cells of the pancreas?
Na+/K+ ATPase on basolateral membrane generates the “power” in the form of a steep sodium gradient.
What does Carbonic Anhydrase do in the duct cells of the pancreas?
Carbonic anhydrase promotes formation of H+ and HCO3- and come bicarbonate from the alkaline tide is taken up from the blood stream by NBC response to depolarization
What exchanger is regulated by Secretin?
CFTR supplies the Cl- for the HCO3-/Cl- exchanger . This exchanger is regulated by secretin activation of cAMP.
What would Cystic Fibrosis do to the Pancreas?
It would cause decreased bicarbonate because you aren’t getting Cl- going into the duct (also not getting water into the ducts). This leads to Pancreatic insufficient (90% reduction in number of ducts being functional/used)
What are Causes of Pancreatitis?
- Cystic fibrosis
- Occlusion of pancreatic duct: gallstones, malignancy
- Alcohol can be metabolized into products that cause hyper stimulation of acinar cells resulting in intracellular trypsin activation and cell death
What are the effects of Pancreatitis?
- Upper abdominal pain from autodigestion of pancreatic tissue can lead to vomiting and sympathetic activation
- Enzymes spill over into circulation - elevated serum amylase and lipase levels
- Malabsorption of fat and fat-soluble vitamins (A, D, E, K) steatorrhea
- Malignancy, Diabetes, and Infections
What does the pancreas provide enzymes for?
To promote digestion and bicarbonate to neutralize gastric acid.
When is pancreatic secretion induced?
During cephalic and gastric phases, but maximal secretion occurs during intestinal phase due to the release of cholecystokinin and secretin.
What do Acini and ducts secrete? What is the function of these products?
Acini - secrete inactive enzymes
Ducts - secrete fluid and bicarbonate to neutralize acid from the stomach
How are pancreatic enzymes activated?
At the brush border by enteropeptidase
Does the GI system maintain a state of homeostasis?
GI does NOT maintain a state of homeostasis, instead it generally assimilates everything presented to it in the diet.
Why is the Hypothalamus important?
It’s important in regulating energy homeostasis by maintaining a balance between food intake and energy expenditure.
What is GLP-1 and what does it do?
GLP-1 is an incretin.
It increases insulin and decreases glucagon.
Why does oral glucose tend to lead to higher insulin than IV glucose?
Since glucose causes a release of glucagon-like peptide-1 (GLP-1) from intestinal L cells and glucose-dependent insulinotropic peptide (GIP) from K cells.
How do some diabetes drugs work?
By increasing GLP-1 stability (glistens) and other are GLP-1 agonists.
What four molecules stimulate insulin secretion of pancreatic beta-cells in the islets of Langerhans?
- GLP-1
- Amino acids
- Cholecystokinin
- ACh
What are negative regulators of insulin?
- Somatostatin secreted from neighboring D cells
- Norepinephrine
When are plasma insulin levels higher?
After consuming glucose/amino acids than IV glucose
What four molecules act as satiety signals at the hypothalamus?
- GLP1
- CCK
- Insulin
- Leptin (adipose tissue)
What do satiety signals do?
They travel to the hypothalamus, decreasing food intake and increasing energy expenditure
What can lack of sleep lower?
Leptin levels. Individuals with dec. leptin often experience hyperphagia or overeating.
What is Ghrelin?
A peptide hormone produced in fundus of stomach during fasting stimulates appetite (orexigenic) and decreases energy expenditure through neuropeptide Y and agouti-related peptide.
What are Ghrelin levels like in individuals with gastric bypass?
Individuals with gastric bypass have relatively flat ghrelin levels.
What would be the consequence of giving gherkin prior to eating a buffet?
You could eat a lot more!
Where is Gastrin secreted?
Stomach, by G cells
What hormones are secreted in the Intestine (five)?
- Cholecystokinin (CCK)
- Secretin
- Motilin
- Gastric inhibitory peptide (GIP)
- Glucagon-like peptide-1 (GLP-1)
What stimulates Gastrin release?
Peptides and amino acids; neural reflexes
What is the target for Gastrin?
ECL cells and parietal cells
What are the effects of gastrin?
Stimulates gastric acid secretion and mucosal growth
What inhibits gastrin release?
Somatostatin
What stimulates the release of CCK?
Fatty acids and some amino acids.
What is the primary target for CCK?
Gallbladder, pancreas, stomach
What are the primary effects of gastrin?
- Stimulates gallbladder contraction and pancreatic enzyme secretion
- Inhibits gastric emptying and acid secretion
What does CCK promotes?
Satiety. Some effects may be due to CCK as neurotransmitter.
What stimulates the release of Secretin?
Acid in small intestine
What is the target for Secretin?
Pancreas, stomach
What is the effect of Secretin?
- Stimulates HCO3- secretion
- Inhibits gastric emptying and acid secretion
What stimulates the release of Motilin?
Fasting: periodic release every 1.5-2 hours
What are the targets of Motilin?
Gastric and intestinal smooth muscle
What are the effects of Motilin?
Stimulates migrating motor complex.
What inhibits Motilin?
Eating a meal
What stimulates the release of Gastric Inhibitory Peptide (GIP)?
Glucose, fatty acids, and amino acids in small intestine
What is the target for Gastric inhibitory peptide (GIP)?
Beta cells of pancreas
What are the effects of GIP (gastric inhibitory peptide)?
- Stimulates insulin release (Feedforward mechanism)
- Inhibits gastric emptying and acid secretion
What stimulates the release of Glucagon-like peptide-1 (GLP-1)?
Mixed meal that includes carbohydrates or fats in the lumen.
What is the primary target for GLP-1 (Glucagon-like peptide-1)?
Endocrine pancreas
What are the primary effects of GLP-1 (glucagon-like peptide-1)?
- Stimulates insulin release
- Inhibits glucagon release and gastric function
What does Glucagon-like peptide-1 (GLP-1) promote?
Satiety
