Pancreas

Question 1

What is the embryological origin of the pancreas?

Answer 1

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

Question 2

Where is the pancreas found?

Answer 2

Head sits in C shaped part of duodenum

Tail sits in hilum of spleen

Question 3

What are the 5 divisions of the pancreas?

Answer 3

Head, neck, body and tail

Uncinate process

Question 4

How is the pancreas perfused?

Answer 4

Branches of superior mesenteric artery and coeliac trunk

Drains into hepatic portal vein

Question 5

What are key features of pancreatic tissue?

Answer 5

Columnar epithelium lining pancreatic ducts
Islets of Langerhans
Acini (pancratic acinus)

Question 6

What cells are found in the Islets of Langerhans?

Answer 6

α cells that secrete glucagon
β cells that secrete insulin 70%
δ cells that secrete somatostatin

Question 7

What is the structure of a pancreatic acinus?

Answer 7

circular arrangement of acinar cells connecting to duct cells via centroacinar cells

Question 8

What is the role of an acinar cell?

Answer 8

Secrete enzyme rich fluid
Low volume very viscous
Lots of RER
Lots of vesicles

Question 9

What is the role of duct cells?

Answer 9

Modifies the acinar secretions
High volume
Secrete watery dilute bicarbonate rich fluid to:
Neutralise chyme
Decrease viscosity

Question 10

How do pancreatic secretions drain into the duodenum?

Answer 10

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

Question 11

How is HCO3- produced and secreted from duct cells and how is the concentration of sodium managed?

Answer 11

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

Question 12

How is HCO3- secretion controlled?

Answer 12

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-

Question 13

How is enzyme secretion controlled?

Answer 13

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

Question 14

What are the phases of secretion, their key mediators and target cells?

Answer 14

Cephalic - Vagus nerve, acinar cells
Gastric - vagus nerve, acinar cells
Intestinal - hormones, acinar and duct cells

Question 15

What stimulates the cephalic phase secretions?

Answer 15

Sight, smell, taste of food

Question 16

What stimulates the gastric phase secretions?

Answer 16

Stomach distension

Question 17

What stimulates the intestinal phase secretions?

Answer 17

Acid and nutrient detection in duodenum

Question 18

What hormones effect HCO3- secretion?

Answer 18

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

Question 19

What does the pancreas secrete?

Answer 19

Zymogens:
-Protease zymogens
-Typsinogen
-Procolipase
Active enzymes:
-Lipase
-Amylase
Trypsin inhibitor

Question 20

What does the liver secrete?

Answer 20

Bile

Question 21

What does the duodenum secrete?

Answer 21

Enterokinase

Question 22

What stimulates the conversion of trypsinogen to trypsin?

Answer 22

Enterokinase

Trypsin

Question 23

What stimultes the conversion of protease zymogens to proteases?

Answer 23

Trypsin

Enterokinase

Question 24

What stimulates the conversion of procolipase to colipase?

Answer 24

Trypsin

Question 25

What does bile do?

Answer 25

Emulsifies fats into triglycerides

Question 26

What do colipase and lipase do?

Answer 26

Break down triglycerides into fatty acids and monoglycerides

Question 27

What do trypsin and proteases do?

Answer 27

Break down large peptides into shorter ones

Question 28

What does amylase do?

Answer 28

Break polysaccharides down into disaccharides

Question 29

What inhibits the conversion of trypsinogen into trypsin and why?

Answer 29

Trypsin inhibitor in the pancreas | Trypsin activation amplifies all other enzyme activations in the small intestine so it must be controlled

Question 30

How does pancreatitis occur?

Answer 30

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

Question 31

What is acute pancreatitis?

Answer 31

Acute inflammatory process that leads to necrosis of pancreatic parenchyma

Question 32

What are signs and symptoms of pancreatitis?

Answer 32

``` Severe abdominal pain nausea vomiting diarrhoea fever shock ```

Question 33

What are the main causes of pancreatitis?

Answer 33

Gallstones Ethanol Trauma ``` Steroids Mumps Autoimmune Scorpion bite Hyperlipiaemia/hypercalcaemia/hypothermia ERCP Drugs ```

Question 34

What are systemic complications of pancreatitis?

Answer 34

``` Hypovolaemia Hypoxia Hypocalcaemia Hyperhlycaemia DIC Multiple organ failure ```

Question 35

What are localised complications associated with pancreatitis?

Answer 35

Pancreatic necrosis Fluid collections - mature into pseudocysts Splenic vein thrombosis/pseudoaneurysm Chronic pancreatitis

Question 36

What is the available treatment options for acute pancreatitis?

Answer 36

``` Supportive treatments fluids painkillers nutrition organ support management of complications ```

Question 37

What is chronic pancreatitis?

Answer 37

Progressive fibroinflammatory process of the pancreas that results in permanent structural damage which leads to impairment of exocrine and endocrine function

Question 38

How can chronic pancreatitis be managed?

Answer 38

Stop alcohol and smoking Small meals, low fat Proton pump inhibitors and pancreatic supplements Analgesia

Question 39

How is acute pancreatitis investigated?

Answer 39

Chest and abdominal X ray Ultrasound CT scan MRCP- magnetic resonance cholangiopancreatography ERCP-Endoscopic retrograde cholangiopancreatography

Question 40

How is chronic pancreatitis investigated?

Answer 40

Plain X ray CT scan Faecal elastase