The Pancreas Flashcards
What is pancreatic embryology?
- The abdominal accessory organs arise as foregut outgrowths
Ventral: liver buds (become liver), gall bladder, ventral pancreatic bund and duct. The tube connecting these to the foregut eventually gets smaller and becomes the bile duct
Dorsal: dorsal pancreatic bud and duct
- The proximal duodenum rotates clockwise (within 11 weeks)
- The ventral and dorsal pancreatic buds and ducts fuse (the ventral pancreatic bud becomes the unicnate process of the pancreas) . The bile and pancreatic ducts join to drain together at the major papilla (this is the main pancreatic duct). The accessory pancreatic duct drains through the minor papilla but in many adults this is degenerated. The common bile duct also drains into the major papilla/ampulla
What is the anatomy of the pancreas?
It is a retroperitoneal structure (doesn’t actually exist in abdomen, is behind the posterior peritoneum)
Sits behind the transverse colon and the stomach
Consists of: head of pancreas, neck of pancreas, body of pancreas, tail of pancreas (from anatomical right to left)
The head of the pancreas fits into the duodenum which is C shaped (D1, D2, D3, D4)
On superior edge is the coeliac axis with the common hepatic artery, the stump of the left gastric artery, and the left splenic artery
Inferiorly, at the neck is the superior mesenteric vein, behind the bancreas this joins with the splenic vein to become the portal vein
Behind the pancreas is the inferior vena cava, the right and the left renal veins
How is an image of the pancreas taken?
Most useful is CT (computed tomography)
Also MRCP (magnetic resonance cholangio pancreatography)
Also angiography, for intervention purposes. You can suu on the superior border the coeliac axis and the right hepatic artery, the left gastric artery and the splenic artery. Inferiorly you can see the superior messnteric artery
What are endocrine and exocrine secretion?
Endocrine - secretion into the blood stream for a systemic effect - ductless glands
Exocrine - secretion into a duct for a direct local effect
What are the main endocrine secretions of the pancreas?
Insulin - anabolic hormone.
promotes glucose transport into cells and storage as glycogen. Decreases blood glucose. Promotes protein synthesis and lipogenesis
Glucagon
Increases gluconeogenesis and glycogenolysis. This increases blood glucose
Somatostatin
“Endocrine cyanide”
What are the (anatomical) differences between the endo and exocrine parts of the pancreas?
Endocrine - 2% of gland
Islets of langerhans, secrete insulin, glucagon and somatostatin into blood. Regulation of flood glucose, metabolism and growth effects
Exocrine - 98% of gland
Secretes pancreatic juice into duodenum via major pancreatic duct/sphincter of oddi/ampulla. Digestive function
What is pancreatic cell differentiation?
Acini:
Ducts
Grape like clusters of secretor units
Acinar cells secrete pro enzymes into ducts
Islets:
Derived from the branching duct system
Lose contact with ducts and become islets
Differentiate into alpha and beta cells secreting into blood
Tail>head (more islets in tail than head)
What is the micro anatomy of the pancreas?
Grape like structures of acinar cells. Around a duct
Between acinar cells are intercellular caniliculi. These drain in to the duct
Duct -> intercalated duct -> intralobular duct
Also centroacinar cells. Between acinar cells and duct
Islets have no connection to duct. Many capillaries in it
What is the composition of the islets?
Alpha cells: form about 15-20% of islet tissue and secrete glucagon
Beta cells: form about 60-70% and secrete insulin
Delta cells: form about 5-10% and secrete somatostatin
Highly vascular ensuring that all endocrine cells have close access to a site for secretion
What is the composition of acini?
Exocrine pancreatic units
Secretory acinar cells: large with apical secretion granules
Duct cells: small and pale
What are the components of pancreatic juice?
Acinar cells: low volume of viscous, enzyme rich fluid
Duct and centroacinar cells: high volume of watery, HCO3- (bicarbonate) rich fluid
What is bicarbonate secretion like?
Produced by duct and acinar cells
Pancreatic juice is high in bicarbonate- around 120 mmol/L (plasma is only around 25). This gives the PJ a pH of 7.5-8.0
It neutralises the acid chyme from stomach. This prevents damage to duodenal mucosa. And raises pH to optimum range for pancreatic enzymes to work
Washes low volume enzyme secretion out of pancreas into duodenum
As acidity increases between pH 5 and 3 there is a linear relation ship as the rate of bicarbonate secretion increases. But below pH 3 the rate cannot increase further
This is because bicarbonate is also secreted in bile, as well as the alkaline fluid secreted by Brunner glands
What is the bicarbonate mechanism?
- Pancreatic bicarbonate secretion
Carbon dioxide enters pancreatic duct cell. Combines with water. Makes hydrogen ions and bicarbonate
CO2 + H2O -> H+ + HCO3-
Catalysed by carbonic anhydrase
The H+ and bicarbonate are separated. Hydrogen into blood, bicarbonate into lumen of duct
Na+ moves down concentration gradient from blood to lumen via para cellular (tight) junctions
H2O follows sodium
Cl-/HCO3- exchange at lumen (anion exchanger)
Na+/H+ exchange at basolateral membrane into bloodstream (sodium hydrogen exchanger (anti Porter) type 1)
These exchanges are driven by electrochemical gradients (higher sodium in blood than duct cell) (higher chlorine in lumen than duct cell)
3.
Sodium gradient into cell from blood is maintained by the Na+/K+ ATPase
- Potassium returns to the blood via potassium Chanel
Chlorine returns to lumen via chloride channel (CFTR - cystic fibrosis transmembrane regulator)
Where else does the reaction to make bicarbonate occur?
Stomach (Gastric parietal cells)
Stomach: H+ -> gastric juice, HCO3- -> blood
Gastric venous blood is alkaline
Pancreas: H+ -> blood, HCO3- -> juice
Pancreatic venous blood is acidic
What are the types of enzymes secreted by acinar cells?
Lipase
Proteases
Amylase (carbohydrate)
These are synthesised and stored in zymogen (pro enzyme) granules
Proteases are released as inactive pro enzymes to protect acini and dicta from auto digestion
Pancreas also contains trypsin inhibitor to prevent trypsin activation
Enzymes are only activated in duodenum
Blockage of MPD may overload protection -> auto digestion (=acute pancreatitis)
How are enzymes secreted by the acinar cells activated?
Duodenal mucosa secreted an enzyme - enterokinase (brush border enzyme)
This converts trypsinogen to trypsin
Trypsin then converts all other proteolytic and some lipolytic enzymes into their active form
(Lipases are secreted in their active form but require colipase) ( they also require the presence of bile salts to work properly)
Pancreatic secretions adapt to diet
Pancreatic enzymes and bile are ESSENTIAL for normal digestion of a meal (lack of these can cause malnutrition even if diet is fine)
How is pancreatic juice secretion controlled?
Cephalic phase:
Reflex response to sight smell taste of food
Enzyme rich viscous component only (low volume)
Gastric phase
Stimulation of pancreatic secretion originating from food arriving in the stomach
Basically same mechanisms involved as for cephalic phase
Intestinal phase (70-80% of pancreatic secretion)
Hormonally mediated when gastric chyme enters the duodenum
Both components of pancreatic juice stimulated (Enzymes and HCO3 juice flows into duodenum)
How are (neurally) the two components of the pancreatic juice controlled?
Enzyme secretion by acini-
- Vagus nerve. Cholinergic. Vagal stimulation of enzyme secretion
- Cholecystokinin. Amino acids and fatty acids have a stimulators effect on this. Trypsin has an inhibitory effect. CCK-RP and GRP also have a stimulating effect. Released from duodenal I cells
Bicarbonate secretion from duct and centroacinar cells-
Secretin (cAMP)
How is HCO3 secretion controlled?
- acinar fluid is isotonic (resembles plasma concentrations of sodium, potassium, chloride and bicarbonate)
The secretion of acinar fluid and proteins it contains is stimulated primarily by cholecystokinin
Secretin stimulates secretion of water and bicarbonate from cells lining extra lobular ducts
Secretin stimulated secretion is richer in HCO3 than acinar secretion because of Cl-/HCO3- exchange
Bicarbonate has a classic negative feedback loop: low pH is duodenal cells -> s cells -> secretin release -> pancreatic dicta bicarbonate secretion -> INHIBTS SECRETION OF MORE SECRETIN
How does stimulation interaction work?
CCK alone has no effect on bicarbonate secretion
Secretin alone has a minor affect
Both together give a much higher rate of bicarbonate secretion
Vagus nerve has a similar effect to CCK
Secretin has NO Effect on enzyme secretion
Give a summary of what happens after a meal?
Food mixed, digested in stomach, pH 2
Chyme squirted into duodenum
H+ ions in duodenum-> increased secretin -> increased pancreatic juice
Plus bile and brunners gland secretion
Peptides and fat induodenum cause large increase in CCK and vagus nerve stimulation
This stimulates pancreatic enzyme release
Peaks by 30 mins, continues till stomach empty
CCK potentials effects of secretin on aqueous component (necessary as most of duodenum is not at a low pH)
