PANCREAS Flashcards
Exocrine function of pancreas
- Duct cells - Secrete HCO3- to neutralize acid in chyme
- Excorine acinar cells - secrete digestive enzymes that break down macromolecules for absorption
Endocrine function of pancreas
Islet of langerhans:secrete insulin, glucagon and several other hormones
Describe the pathway of digestive enzymes/exocrine products
Digestive enzymes are stored inside zymogen granules within the pancreatic acinar cell
- Secrete them by exocytosis into the lumen of the acinus
- -> flow into intercalated ducts > intralobular ducts > interlobular ducts
- -> ducts coalesce into the main pancreatic duct
- -> drains directly into the duodenum
the lumen of the acinus communicates directly with __lobular ducts
Intralobular ducts
Epithelial cells of the intralobular ducts project ‘back’ into the lumen of the acinus as centro-acinar cells
All interlobular ducts coalesce into
two pancreatic ducts - Santorini & Wirsung - which drain directly into the duodenum or join w the common bile duct first
How do ACh and CCK promote pancreatic enzyme secretion?
ACh binding to M3 receptors
CCK & gastrin bind to CCK-B receptors
- Elevates IP3 and DAG
- -> increased [Ca2+]cytosol
- -> stimulation of protein kinase C
Secretion of NaCl and water from pancreatic acinar cells
-
Basolateral NCCK transporter takes Na down its gradient and Cl & K against their gradient into the cell.
- Na,K-ATPase maintains the Na+ gradient
- Cl- can now enter the lumen via the apical CFTR Cl- channel
- Lumen is now more negative, attracting Na+ to enter the lumen by traveling across leaky tigh tjunctions
CCK & vagus stimulation ____ enzyme and NaCl secretion from the acinar cells
increase enzyme & NaCl secretion
The CFTR Cl- channel is activated by cAMP & Ca2+
Describe the route of bicarbonate secretion
- Secretin increases cAMP in duct cells
- Opens CFTR Cl- channels so Cl- empties into the duct lumen
- Drives the HCO3/Cl antiporter to send HCO3- into lumen
- Sources of HCO3- in the cell:
- Basolateral NBC-1 symporter takes in Na+ & HCO3-
- Carbonic anhydrase
- Sources of HCO3- in the cell:
Acinar cells & duct cells produce independent secretions.
What does the acinar cell produce?
- Digestive enzymes
- Cofactors:
- Trypsin inhibitor protein
- Co-lipase
- Lactoferrin & IgA (antibacterials)
- Pancreatitis-associated proteins (incresaes in early pancreatic injury)
- Lithostathine - forms protein aggregates; can prevent stone formation
- Glycoprotein-2 (may regulate endocytosis)
Acinar cells and duct cells produce indpenedent secretions.
What do ductal cells secrete?
HCO3- & water
When a meal enters the small intestine, the volume of pancreatic secretions increases rapidly.
What impact does this have on the composition of the pancreatic juice?
Increased flow rate of pancreatic juice will make the juice more alkaline and dilute.
- Increase HCO3-
- Lower Cl-
Name the digestive enzymes of pancreatic juice
-
Trypsin & chymotrypsin (proteases)
- Packaged in secretory vesicles as proenzymes trypsinogen & chymotrypsinogen
- Pancreatic lipase hydrolyzes triglycerides
- Amylase hydrolyzes starch into maltose
- Ribonuclease, deoxyribonuclease, gelatinase, elastase
Orlistat (Xenical)
Pancreatic lipase inhibitor
–> reduces absorption of dietary fat –> weight loss
Activation of trypsinogen & chymotrypsinogen
After release into the lumen of the small intestine,
- Trypsinogen is activated by enterokinase on the brush border –> trypsin
- Trypsin activates chymotrypsinogen & more trypsinogens
Protein digestion
- Chymotrypsin & trypsin digest proteins into smaller and smaller peptides, but not into aa
-
Peptidases on the surface of the small inestine epithelial cells break down peptides into aa
- Carboxypeptidases (pancreatic protease) can also do this, but not as much
Triglyceride breakdown & absorption requires
- Pancreatic lipase
- Bile salts from the liver
What are the primary mechanisms that prevent pancreatic tissue from auto-digestion?
- The enzymes are produced as inactive zymogens that aren’t activated until they’re in the SI
- The enzymes are stored in vesicles until exocytosis
- Pancreas produces a trypsin inhibitor to prevent accidental activation of trypsin in the pancresa
What causes pancreatic exocrine secretion?
-
Acid in the small inestine stimulates secretin secretion –> HCO3- secretion
- Potentiated by dual stimulation from CKK & Ach
- Neutralized acid –> pancreatic secretion slows
- Proteins, starch, and triglycerides in the stomach & small inestine stimulate CKK secretion
Cholecystokinin
- Synthesized & secreted by enteric endocrine cells in the dudoenum
- Stimulated by proteins & fats in the small inestine
- Binds receptors on pancreatic acinar cells to secrete a lot of digestive enzymes
Secretin
- Produced by enteric endocrine cells in the duodenum
- Secreted in response to acid in the duodenum
- Stimulates duct cells to secrete H3O- and water
- –> Flushes the enzymes from acinar cell sout of the pancreas, through the pancreatic duct, and into the duodenum
Gastrin
- Secreted by the stomach
- Produed in response to gastric disenteion & irritation
- Stimulates acid secretion from parietal cells
- Stimualtes pancreatic acinar cells to secrete digestive enzymes
Cephalic phase of pancreatic secretion
- Sight, smell, and taste of food stimulates the vagus
- Ach stimulates acinar & ductal ells
- 25-50% of pancreatic secretions
Gastric phase of pancreatic secretions
- Food in stomach stimulates vagus
- Vagus stimulates Ach & Gastrin, both of which stimulates pancreatic acinar cells
- ~10% of pancreatic secretions
Intestinal phase
-
Digestive products in the duodenum stimulates the vagus
- Ach and CCK –> pancreatic acinar cells release enzymes* & HCO3-
-
Acid in the duodenum stimulates secretin
-
Secretin –> ductal cells release HCO3- & water
- Potentiated by Ach and CCK
-
Secretin –> ductal cells release HCO3- & water
- 50-100% of pancreatic secretions
Causes of pancreatitis
Tests for pancreatitis
- Causes
- Usually *gallstones* or alcohol
- Infections, some medicines
- Blood tests for
- Serum amylase (high)
- Serum lipase (high)
- Cholesterol (very low)
- Bilirubin (high)
- CBC for WBCs (high)
- Liver fxn tests for ALT & alkaline phosphatase
What is pancreatitis?
Digestive enzymes from an inflamed pancreas accidentally get activated before they reach the small intestine. May be acute or chronic
Inflammation may be from gallstones, alcohol abuse, infection, medications, trauma, tumors, etc
Cause of cystic fibrosis
-
Recessive autosomal CFTR gene mutation
-
–> Messed up CFTR channel
- –> decreased HCO3- & water secretion by pancreatic duct cells leaves them vulnerable to the pancreatic proteases
- –> inflammation & tissue destruction
-
–> Messed up CFTR channel
Symptoms of CF patients
- Recurrent pulmonary infection
- Chronic pancreatitis
- Abnormal sweat
- Malaborption
- steatorrhea
- Malnutrition
- Thick, viscous pulmonary secretions
