Lecture 19; Control of pancreatic and biliary secretions Flashcards
What is the role of the duodenum?
- Inhibition of gastric emptying
- Inhibition of acid secretion
- Stimulation of pancreatic and biliary secretion
How does the duodenum detect its contents?
Vagal afferents
Specialised cells
- I cells
- S cells
- Enterochromaffin cells
What do I, S and enterochromaffin cells do?
I cells
- Sample luminal contents FA/AA
- CCK
S cells
- Senses pH
- Releases Secretin
Enterochromaffin cell
- Serotonin cells
What do CCK and Secretin both inhibit?
Inhibit;
- Gastric emptying
- Acid secretion
What does serotonin secretion from enterochromaffin cells do?
- Stimulates gut motility
- High levels in blood can activate vomiting via medulla
Whats the role of exocrine pancreas?
- Ductal cells secrete HCO3
- Acinar cells release digestive enzymes for fat and protein digestion
Describe the ductal cells of the pancreas;
- Intercalated ducts and centeroacinar cells (Duct cells) release HCO3 via pancreatic duct.
What are the 3 mechanisms of pancreatic bicarb secretion;
1) Secretin release causes increased cAMP in ductal cells, CFTR insertion and HCO3 release
2) Direct vagal stimulation via increased iCa2
3) Duodenum secretes Bicarb also
Describe the release from pancreatic enzymes;
- Acinar cells
- Stored as zymogen granules, pro-enzymes that are activated in SI
- CCK controls release in response to FA/AA
How does CCK act?
Acts directly on acinar cells or causes vagal stimulation of acinar cells and enzyme release.
Where does pancreatic enzyme activation take place?
- Activation takes place in the duodenal lumen at the brush border.
Describe the action of trypsin;
Trypsinogen is converted to trypsin by enterokinase.
Trysin in turn cleaves;
- Trypsinogen
- Chymotrypsinogen
- Other pro-enzymes.
What are some other pancreatic enzymes;
Pancreatic lipase
Amylase
Describe how CCK and Secretin act on the pancreas;
- FA/AA in duodenum stimulates I cells to release CCK.
- CCK causes acinar cells to release pancreatic enzymes via 2 pathways
- HCl in the duodenum stimulates S cells to release secretin.
- Secretin stimulates pancreatic ductal cells to release secretions rich in HCO3 for acid neutralisation.
What other factors can stimulate pancreatic exocrine release?
- Gastrin, also stimulates acinar cells to release digestive enzymes
- Vagal stimulation can to a low degree cause release of digestive enzyme and HCO3 release.
Whats the other action of CCK?
Stimulates bile production in liver, gallbladder contraction, and sphincter of oddi relaxation to deliver more bile into the duodenum
Whats the other action of secretin?
Causes the release of HCO3 from bile duct
What can cause inhibition of pancreatic secretions?
- Glucagon, somatostatin, peptide YY and pancreatic polypeptide
Pancreatic polypeptide via vagal inhibition
What happens to the pancreas in CF?
- Pancreatic insufficiency
Defective CFTR;
- Cl accumulates in ductal cells
- Draws Na and water into lumen
- Pancreatic secretions become hyperviscous ( too thick)
What happens to the pancreas when the secretions become hyperviscous?
- Pancreatic ducts become blocked
- Insufficient pancreatic enzymes released
- (autodigestion -> pancreatitis -> Fibrosis) (Cystic fibrosis)
What are the causes of pancreatitis?
Alcohol
Gallstones
Whats the difference between acute and chronic pancreatitis?
Acute
- Acute inflammation, elevated enzymes in serum, self limiting
Chronic
- Chronic inflammation, progressive loss of pancreatic endocrine and exocrine function (alcohol)
Describe pancreatic insufficiency at an endocrine and exocrine level;
Endocrine insufficiency
- Impaired insulin production
- Diabetes
Exocrine insufficiency
- Impaired digestive enzymes production
- Fat malabsorption
How does exocrine pancreatic insufficiency present?
- 90% loss of exocrine function
- Loss of lipase (most critical)
- Fat malabsorption -> weight loss, steatorrhoea.
- Pancreatic enzyme supplements can be taken but issues with gastric degradation.
Whats evident with chronic pancreatitis on a pancreatogram?
Dilated main branches with irregular side branches
Whats in bile?
- Bile acids
- Cholesterol
- Phospholipids
- Bilirubin
= Detergent (Is irritant outside the biliary system)
Whats the function of bile?
Carries bile acids
- Critical for digestion and absorption of fats and fat-soluble vitamins (A,D,E,K)
Elimination of waste products including bilirubin
Describe bile flow through the biliary tree;
Hepatocytes secrete bile (large quantities of bile acids, cholesterol, etc)
- BIle enteres canaliculi and flows into the larger bile ducts. As it flows through watery secretions rich in bicarbonate is added to the bile by ducted epithelial cells
- Bile leaves the liver , flowing down common hepatic duct and enters cystic duct into the gallbladder
Describe the mechanisms that drive bile flow;
Bile flow into canaliculi
Bile acid dependent
- Active transport (draws water, osmotic effect)
- Bilirubin is carried along
Bile acid independant
- Transport of other solutes and electrolytes help drive the flow of bile
( As the bile ducts become larger, more water and electrolytes is removed from the secretion)
What are the two sources of bile acids?
- 5% synthesised
- 95% reabsorbed from terminal ilium i.e enterohepatic circulation via portal vein
Bile lost in faeces = amount synthesised per day , note failure to reabsorb bile salts causes diarrhoea
What happens to bile in the gallbladder?
20x concentrations
What is cholestasis?
- Increased pressure in biliary tree and liver
- Leads to rupture of tight junctions and leakage of bile
- Bile contents spill back into circulation causing jaundice (hyperbillrubinaemia)
What are malignant causes of biliary obstruction?
Pancreatic cancer, cancer in the head of the pancreas can cause narrowing of common bile duct, obstructing bile flow
Whats the effect of prolonged bile duct obstruction?
- Jaundice
- Hyperbilirubinaemia (yellow skin, mucous membranes)
- Itching
- Nausea
- Effects on renal perfusion
- Malabsorption of fat and fat-soluble vitamins
