Pancreas Flashcards
Pancreas anatomy; Pancreas function; Pancreatic regulation; Pancreatitis
What is the embryological origin of the pancreas?
Develops around day 35-39 from two sites:
-Ventral pancreatic bud
-larger dorsal pancreatic bud
day 40-55 duodenum twist to move ventral pancreas towards dorsal pancreas
Endocrine pancreas arises from stem cells at duct branch points
Exocrine pancreas arises from endoderm tubules
Day 56 dorsal and ventral pancreas fuse together, dorsal pancreatic duct fuses with common bile duct and ventral pancreatic duct becomes Ampulla of Vater
Where is the pancreas found?
Head sits in C shaped part of duodenum
Tail sits in hilum of spleen
What are the 5 divisions of the pancreas?
Head, neck, body and tail
Uncinate process
How is the pancreas perfused?
Branches of superior mesenteric artery and coeliac trunk
Drains into hepatic portal vein
What are key features of pancreatic tissue?
Columnar epithelium lining pancreatic ducts
Islets of Langerhans
Acini (pancratic acinus)
What cells are found in the Islets of Langerhans?
α cells that secrete glucagon
β cells that secrete insulin 70%
δ cells that secrete somatostatin
What is the structure of a pancreatic acinus?
circular arrangement of acinar cells connecting to duct cells via centroacinar cells
What is the role of an acinar cell?
Secrete enzyme rich fluid
Low volume very viscous
Lots of RER
Lots of vesicles
What is the role of duct cells?
Modifies the acinar secretions High volume Secrete watery dilute bicarbonate rich fluid to: Neutralise chyme Decrease viscosity
How do pancreatic secretions drain into the duodenum?
pancreatic ducts converge to form larger pancreatic duct
combines with bile duct to form the ampulla of Vater
Drains into major duodenal papilla at the sphincter of Oddi
How is HCO3- produced and secreted from duct cells and how is the concentration of sodium managed?
CO2 diffuses into cell and combines with H2O to form H+ and HCO3- catalysed by carbonic anhydrase
Some Na+ moves down its concentration gradient via the paracellular pathway and some H2O passes by osmosis due to osmotic gradient - produces watery secretion
Cl- moves out of CFTR activated channels and this allows
HCO3- exchange for lumen Cl- via anion exchanger
H+ must be managed in order to prevent it damaging cell actions
H+ pumped out and Na+ pumped in at basolateral membrane
Na+/K+ ATPase used to pump Na+ back out and as K+ concenration inside cell increases, they leave via a K+ channel
How is HCO3- secretion controlled?
Drop in duodenal pH activates S cells spread amongst enterocytes
S cells secrete secretin
Secretin travels in blood all the way round back to pancreas
Secretin then binds to G protein coupled receptors on duct cells
This increases cAMP messenger concentration
Causes activation of Cl- channels in apical membrane and Cl- moves out
This provides concentration gradient for 2 active transport so increased activity of anion exchanger and therefore efflux of HCO3-
How is enzyme secretion controlled?
Fats and peptides are detected by I cells
Causes a Cholecystokinin release from I cells
CCK travels in blood round to pancreas and binds to CCK1 receptors on acinar cells
This activates PLC/IP3 2nd messenger (also activated by ACh released from vagus nerve binding to mucosine receptors)
Causes an increase in cytosolic Ca2+
Causes exocytosis of vesicles containing zymogen, inhibitor and enzyme granules
enzymes activated by enterokinase in duodenum
What are the phases of secretion, their key mediators and target cells?
Cephalic - Vagus nerve, acinar cells
Gastric - vagus nerve, acinar cells
Intestinal - hormones, acinar and duct cells
What stimulates the cephalic phase secretions?
Sight, smell, taste of food
What stimulates the gastric phase secretions?
Stomach distension
What stimulates the intestinal phase secretions?
Acid and nutrient detection in duodenum
What hormones effect HCO3- secretion?
Secretin increases HCO3- secretion but no effect on enzyme secretion
CCK has not much effect on secretion
CCK amplifies the effect of secretin on bicarbonate secretion
What does the pancreas secrete?
Zymogens: -Protease zymogens -Typsinogen -Procolipase Active enzymes: -Lipase -Amylase Trypsin inhibitor
What does the liver secrete?
Bile
What does the duodenum secrete?
Enterokinase
What stimulates the conversion of trypsinogen to trypsin?
Enterokinase
Trypsin
What stimultes the conversion of protease zymogens to proteases?
Trypsin
Enterokinase
What stimulates the conversion of procolipase to colipase?
Trypsin
What does bile do?
Emulsifies fats into triglycerides
What do colipase and lipase do?
Break down triglycerides into fatty acids and monoglycerides
What do trypsin and proteases do?
Break down large peptides into shorter ones
What does amylase do?
Break polysaccharides down into disaccharides
What inhibits the conversion of trypsinogen into trypsin and why?
Trypsin inhibitor in the pancreas
Trypsin activation amplifies all other enzyme activations in the small intestine so it must be controlled
How does pancreatitis occur?
Pancreatic duct obstruction impedes flow of pancreatic juice
causes accumulation of enzymes that cant be controlled by trypsin inhibitor
once inhibitor overwhelmed trypsinogen turns to trypsin without enterokinase
this leads to pancreatic autodigestion
= ACUTE PANCREATITIS
What is acute pancreatitis?
Acute inflammatory process that leads to necrosis of pancreatic parenchyma
What are signs and symptoms of pancreatitis?
Severe abdominal pain nausea vomiting diarrhoea fever shock
What are the main causes of pancreatitis?
Gallstones
Ethanol
Trauma
Steroids Mumps Autoimmune Scorpion bite Hyperlipiaemia/hypercalcaemia/hypothermia ERCP Drugs
What are systemic complications of pancreatitis?
Hypovolaemia Hypoxia Hypocalcaemia Hyperhlycaemia DIC Multiple organ failure
What are localised complications associated with pancreatitis?
Pancreatic necrosis
Fluid collections - mature into pseudocysts
Splenic vein thrombosis/pseudoaneurysm
Chronic pancreatitis
What is the available treatment options for acute pancreatitis?
Supportive treatments fluids painkillers nutrition organ support management of complications
What is chronic pancreatitis?
Progressive fibroinflammatory process of the pancreas that results in permanent structural damage which leads to impairment of exocrine and endocrine function
How can chronic pancreatitis be managed?
Stop alcohol and smoking
Small meals, low fat
Proton pump inhibitors and pancreatic supplements
Analgesia
How is acute pancreatitis investigated?
Chest and abdominal X ray
Ultrasound
CT scan
MRCP- magnetic resonance cholangiopancreatography
ERCP-Endoscopic retrograde cholangiopancreatography
How is chronic pancreatitis investigated?
Plain X ray
CT scan
Faecal elastase
