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....