Pancreatic secretions (Your boy Chou Chou)
Secretin generates an electrical gradient that factors co-transport of what?
-Bicarb (NaHCO3)
What are autoimmine conditions which lead to pancreas issues? (2)
-Celiac disease -Ig64
What is pancreatitis?
-Retention of secretion in pancreas leads to autodigestion of pacreatic tissue
Why is it important to neutralize the acid in the duodenum? (2)
-To stop duodenal ulcers -Pancreatic lipase is inactivated at low pH
What does the pancreas create trace amounts of?
Enzyme inhibitors
Enzyme: Amylase Activator:Cl- Substrate:
Enzyme: Amylase Activator: Cl- Substrate: Starch, glycogen
Enzyme: Chymotrypsinogens-chymotrypsins Activator: Substrate: Proteins, polypeptides
Enzyme: Chymotrypsinogens Activator: Trypsin (endo-peptidase) Substrate: proteins, polypeptides
Enzyme: Activator: None Substrate: DNA
Enzyme: Deoxyribonuclease Activator: None Substrate: DNA
Enzyme: Activator:None Substrate: Triglycerides
Enzyme: Lipase Activator: None Substrate: Triglycerides
Enzyme: Trypsinogen Activator: Substrate: Protein, polypeptides
Enzyme: Trypsinogen Activator: Enterokinase Substrate: protein, polypeptides
Enzyme: Ribonuclase Activator: Substrate: RNA
Enzyme:Ribonuclase Activator: None Substrate: RNA
T/F: Acinar cells secrete protein (enzymes)
True
T/F: ACh and CCK stimulate NaCl secretion through phosphorylation of ion channels
True Image: Only if you reallyyyy care about the deats
When do signs of malabsorption and ingestion appear?
When pancreatic secretions fall below 10%
Overview of hormonal control of pancreatic exocrine secretion
Read it at least once
What hormone stimulates enzyme secretion?
CCK
Secretin acts on which cells to increase bicarb production?
Ductal cells Ductal cells Ductal cells
How does the pancreas protect itself from acid?
-Acid in the duodenum causes release of secretin, which binds to ductal cells leading to the release of bicarb -As the pH rises, the less secretin is secreted
The exocrine pancreas secrets from two types of cells: ductal cells and acinar cells. How are they different?
-Acinar secretions are enzyme-rich secretions that provide the enzymes necessary for digestion for carbohydrates, proteins, nucleic acids, and lipids -Ductal secretions are HCO3 rich and neutralize acidic chyme to allow for proper function of pancreatic enzymes
What enzymes are activated by trypsin? (6)
-Chymotrypsingen -Proelastase -Procarboxypeptidase A -Procarboxypeptidase B -Pro-phospholipase -Procolipase
What are two most common causes of pancreatitis
-ETOH -Gallstones
What is steatorrhea? What is it a sign of?
-Fat in the stool-early sign of pancreatic dysfunction -60% fat and 30-40% proteins and carbohydrates not absorbed -reduced pancreatic enzyme (lipase) and bicarbonate secretion -low pH inactivates lipase
How does the pancreas know when to secrete enzymes for digestion?
-Fats and protein in the duodenal lumen results in CCK being released. CCK binds to acinar cells which leaes to secretion of pancreatic digestive enzymes into the duodenum -As things get digested, the less CCK is released
What drugs and toxins lead to pancreatitis? (3)
-Immunosuppresants -anticonvulsants -thiazides
Clinical correlation: Achlohyrdic -What is it? -Why is this an issue?
-Inability to secrete acid, secondary to disease (on drugs, proton pump inhibitors, bicarbonate) fail to release secretin (can't decrease acidity to secrete secretin) even in the presence of a fatty meal. -Leads to a duodenal ulcer
What are the main ways the pancreas protects itself against auto-digestion? (5)
-Packaging digestive proteins/enzymes as zymogen so they don't have enzymatic activity -Restriction of zymogen interaction -Blocking premature activation of enzymes -Condensation of enzymes at low pH, limits enzyme activity -Degrading active enyzymes
What is the main function of colipase?
-Prevent inhibitory effect of bile salts on lipase
So in total, ACh causes what 3 functions?
-Protein secretion by acinar cells -NaCl secretion -Bicarb secretion Note: Secretin is still the most powerful stimulus for bicarb secretion
ACh, CCK, Secretin, VIP all stimulate secretion of what, by acinar cells? Do these all increase Ca2+ (2nd messenger)?
-Protein, all activate protein kinases which increase acinar cell secretion -Yes Image: Don't need to know secondary messengers
Factors causing secretin release
-S cells in duodenal mucosa acts as pH meters -S cells secretes secretin when pH falls due to entry of acidic chyme -Secretin binds to receptors on: 1) pancreatic ductular cells 2) epithelial cells lining bile ducts 3) duodenum -Cells stimulate to secrete HCO3-in duodenum -Increase in pH will inhibit secretin release Fatty acid meals evoke secretin release -Secretin release is sensitive to pH
Role of secretin in pancreatic exocrine release
-Secretin released from S cells in duodenal mucosa, stimulates pancreatic ductular cells when acidic chyme enters duodenum to neutralize H+ -Pancreatic secretions volume increases from low volume protein rich fluid to high absolute volume -As the secretory rate rises, the pH and bicarbonate concentration also rises concentrations of Cl- and HCO3- are inversely related to those of Na+ and H+ in stomach
Which enzymes are stored and secreted in inactive forms? (7)
-Trypsinogen -Enterokinase -Chymotrypsinogens -Proelastase -Procarboxypeptidase A -Procarboxypeptiase B -Pro-phospholipase A2
In cystic fibrosis, absorption of what macronutrient is affected the most? What is this condition called?
-Usually, fat digestion is affected to the greatest extent, resulting in fatty diarrhea (steatorrhea) in which the feces may float, have an oily appearance, and be particularly foul-smelling. -These patients are often treated with supplementary pancreatic enzymes.
The exocrine pancreas has all kinds of ducts. What is the Wirsung's duct, duct of santorini, ampulla of vater, and the sphicter of oddi in laymens term?
-Wirsung's duct: Pancreatic duct -Duct of santorini: Accessory duct -ampulla of vater: Hepatopancreatic ampulla -Sphicter of oddi: The sphincter of Oddi is located at the junction of common bile duct, main pancreatic duct, and the duodenum. It is a high-pressure zone with phasic contractions that regulate bile and pancreatic juice flow.
What are genetic abnormalties that lead pancreatitis? (4)
-weak SPINK1, CFTR, CTRC genes and insult by alcohol, gallstones, etc may precipitate pancreatitis - both acute and chronic
Label the following as acute or chronic causes of pancreatitis: 1)Obstructive (gallstone occluding pancreatic duct, or a malignancy: 2)Hereditary-expression of a mutated trypsin molecule that is resistant by trypsin inhibitors. Trypsin digests pancreatic tissue 3)Inflammation of the pancreatic tissue (alcohol abuse)
1) Acute 2) Chronic 3) Chronic
1) What is the function of enzymatic component? 2) What leads to the release of CCK?
1)Digests proteins, carbohydrates, lipids and nucleic acids 2)When small peptides, amino acids and fatty acids enter duodenum CCK is released by I cells, stimulating enzyme secretion
So, we have established that the exocrine pancreas has an aqueous (bicarb) component and an enzymatic component. 1) What is the function of aqueous component? 2)Does it deactive/activate pepsin? 3)When, what, and why do do the secrete Secretin?
1)Neutralizes HCl in chyme 2)Deactivates pepsin 3)when H+ enters duodenum, S cells secrete Secretin, which acts on pancreatic ductal cells to increase HCO3- production which prevents damage to duodenal mucosa; buffers pH for maximal enzymatic activity
Once enterokinase activates trypsin, what does trypsin then do?
Activates trypsinogen (positive feedback), and a number of other enzymes
What do alpha cells, beta cells and delta cells, and pp cells in the pancreas produce, respectively?
Alpha: Glucagon Beta: Insulin (amylin) Delta: Somatostatin 8=D: Pancreatic polypeptide
Overview of pancreatic acinar cell secretions
Be happy you don't have to type all this b.s out. -Note which are secreted in inactive form. The "dash" represent what they become after they are activated
Enterokinase is release from where? By what?
Brush border membrane by bile salts
Enzyme: Monitor peptide Activator: Substrate: Feedback-secretion
Enzyme: Monitor peptide Activator: Intestinal conent Substrate: Feedback-secretion
Enzyme: Nonspecific esterase Activator: None Substrate:
Enzyme: Nonspecific esterase Activator: None Substrate: cholesteryl esters
Enzyme: Pro-phospholipase A2- (PLA2) Activator: Substrate: Phospholipids
Enzyme: Pro-phospholipase A2- (PLA2) Activator: Trypsin Substrate: Phospholipids
Enzyme: Procarboxypeptidase A-(Carboxypeptidase A) Activator: trypsin (exo-pepidase) Substrate:
Enzyme: Procarboxypeptidase A-(Carboxypeptidase A) Activator: trypsin (exo-pepidase) Substrate: proteins, polypeptides
Enzyme: Procarboxypeptidase B-(Carboxypeptidase B) Activator: trypsin (exo-peptidase) Substrate:
Enzyme: Procarboxypeptidase B-(Carboxypeptidase B) Activator: trypsin (exo-peptidase) Substrate: proteins, polypeptides
Enzyme: Activator: Trypsin Substrate: Fat Droplets
Enzyme: Procolipase-Colipase Activator: Trypsin Substrate: Fat Droplets
Enzyme: Proelastaste-elastase Activator: Substrate: elastin, other proteins
Enzyme: Proelastase Activator: trypsin (endo-peptidase) Substrate: elastin, other proteins
T/F: Endocrine secretions are only innervated by the sympathetic NS
False, by both. Inhibited by the sympathetic and stimulated bu the parasympathetic
T/F: Bruh bruh, pancreatic secretions are same as the stomach
False, it's opposite of the stomach. My main dawg the pancreas produces 2-3 liters of bicarb a day
What is Cystic fibrosis? Why does it lead to panceatic insufficiency?
Genetic disease, disorder of pancreatic secretion that results from a defect in Cl- channel that is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This results in a thick secretions into the pancreatic duct that may obstruct the duct and cause pancreatic insufficiency
What is the significance of peptide factors regulating CCK release?
In plain english: When too much protein/peptides need to be digested, CCK-RP and MP compete with trypsin so that it doesn't bind to I cells since trypsin is inhibitory. When little protein/peptide need to be digested, trypsin will have enough time to degrade CCK-RP and MP, so some of the trypsin can actually bind to the I cells, which stops CCK secretion. Details: -Monitor peptide (MP) and CCK-RP( releasing peptide) control CCK release -Presence of too much protein in diet, then both protein and peptides (CCK-RP/MP) compete for trypsin and other proteolytic enzymes and both are are degraded slowly -When little or no protein in diet then trypsin degrades the peptides (CCK-RP/MP) and terminates the release of CCK peptides regulate release of CCK so that it can match its need in the duodenum Image: Solid arrows: stimulatory dashed arrows: inhibition
Like anybody actually reads these
LEARNING OBJECTIVES After reviewing the relevant reading and lecture material you should be able to: 1. Lists the components of pancreatic juice and their physiological functions. 2. Describe the physiological mechanisms in pancreatic acinar and duct cells that are responsible for secretion of pancreatic juice. 3. Lists the enzymes for digestion secreted by the exocrine pancreas. 4. Explain the role played by pancreas in digestion and absorption of a mixed meal. 5. Describe the structure of the exocrine pancreas and the cell types that give rise to proteinaceous and fluid components of the pancreatic juice. 6. Identify key constituents of the pancreatic juice & enzymes that are secreted in inactive forms. 7. Describe the ion transport pathways expressed in pancreatic ducts & mechanisms of action. 8. Explain the role of secretin, cholescystokinin (CCK) and gastrin hormones in exocrine secretion of the pancreas. 9. Describe the factors that regulate the release of secretin and the role of this hormone in stimulating pancreatic ductular secretion. 10. Explain the role of CCK and other factors in regulating pancreatic acinar cells secretion. 11. Describe the relative roles of monitor peptide & CCK-releasing peptide in regulating CCK 12. Identify signaling events activated in pancreatic acinar cells by secretagogues. 13. Describe the regulation of pancreatic secretion during the cephalic, gastric & intestinal phases 14. What are the effects of sympathetic & parasympathetic NS on pancreas and its secretion. 15. Describe pancreatitis and explain the causes of acute and chronic pancreatitis.
T/F: Colipase activates lipase
NO!!!! It does not.
Where is enterokinase located?
On intestinal mucosal cells
Regulation of pancreatic secretion
Only thing I'd make sure to remember is that secretin and CCK are released at the same time. Nothing in this slide is in red
Other causes of pancreatitis
Other well established but less common causes include significant hereditary pancreatitis, marked hypercalcemia and hypertriglyceridemia, abdominal trauma, and various drugs such as azathioprine.
What do glycoproteins do?
Protect against protease-mediated mucosal injuries
What do "trypsin inhibitors" do?
Protect against trypsins in acinar and ductal cells
Summary of lecture
SUMMARY pPancreatic secretion consists of an aqueous bicarbonate component from the duct cells and an enzymatic component from the acinar cells. vThe duct cells actively secrete HCO3− into the lumen, and Na+ and H2O follow down electrical and osmotic gradients, respectively. vThe composition of pancreatic juice varies with the rate of secretion. v At low rates Na+ and Cl− predominate; at high rates Na+ & HCO3− predominate. vPancreatic enzymes are essential for the digestion of all major foodstuffs and are stored in zymogen granules of acinar cells before secretion. vThe primary stimulant of the aqueous component is secretin, whose effects are potentiated by CCK and ACh. vDuring the cephalic phase of secretion, vagal stimulation results in a low volume of secretion containing a high concentration of enzymes.This secretion is produced by the acinar cells.
Yet another blurb about secretin
Secretin is released from the duodenum in response to reduced pH to evoke bicarbonate secretion from the pancreatic ducts (as well as from the biliary ducts and the duodenal mucosa, not shown), thereby neutralizing gastric acid in the duodenal lumen
Describe the activation of pancreatic proteolytic enzymes
The process begins in the lumen, the duodenal brush border enzyme, enterokinase cleaves a hexapeptide from trypsinogen, converting it to active enzyme trypsin. -Trypsin then catalyzes the formation of more trypsin and activates: - chymotrypsinogen, - pro-carboxypetidases and - pro-phospholipases.
T/F: Ribonuleases, amylase, and lipase do not exist as pro-enzymes
True, and yes I know Choudary is contradicting himself with other slide and this one
T/F: Proteolytic enzymes are secreted into the duodenum as inactive precurors
True....