Pancreas

Question 1

Describe generally how the pancreas develops

Answer 1

The pancreas develops from 2 buds. The ventral bud arises from hepatic diverticulum forming lower part of head and uncinated process while dorsal bud arises from dorsal aspect of duodenum and gives rise to upper part of head, neck, body and tail.

Question 2

Describe step by step process of pancreatic embryology

Answer 2

1. Abdominal accessory organs arise as foregut outgrowths. From ventral aspect, liver buds, gallbladder and ventral bud of pancreas arises.
2. Proximal duodenum then rotates
3. Ventral and dorsal ducts and buds then fuse forming main pancreatic bud. Ventral duct joins bile duct at major papilla while dorsal gives rise to accessory pancreatic duct.

Question 3

Describe anatomical location of pancreas

Answer 3

Pancreas is a retroperitoneal organ and doesn’t actually exist within abdomen, is behind posterior peritoneum of abdomen. In front of it is the transverse colon and stomach. Head of pancreas fits into duodenum which is C shaped and divided into D1-D4. On superior edge of pancreas is the coeliac axis. Inferiorly at neck is the superior mesenteric vein and behind pancreas, joins up with the splenic vein forming portal vein. Behind the pancreas is the coeliac axis, renal veins, portal vein etc.

Question 4

How is the pancreas mainly imaged?

Answer 4

Mainly through CT scanning or MRCP (Magnetic Resonance Cholangiopancreatography).

Question 5

What is pancreas divisum?

Answer 5

This is a variation in pancreatic duct anatomy which occurs when the ventral duct and common bile duct are completely separated and this is important as patients can get repeated pancreatitis since it’s the ventral duct which has enough calibre to cope with the repeated pancreatic juice flow. If they are separated, pancreatic secretions have to flow through minor ampulla. Occurs when ventral and dorsal ducts don’t fuse during embryological development.

Question 6

What is angiography and when is it used in imagin g of pancreas?

Answer 6

Is a type of X-ray used to image blood vessels by injecting a dye to allow clear imaging. Angiography used now for interventional purposes particularly in patients that are bleeding. Essentially, involves accessing femoral artery in groin under local anaesthetic, putting needle in and threading wire via femoral artery into aorta and can access coeliac axis. Further down via aorta can access superior mesenteric artery.

Question 7

Why could angiography be used following surgery?

Answer 7

Complications of surgery:
Patient had acute pancreatitis, underwent procedure and started bleeding. Pseudo-aneurysm is a weakening of the arterial wall. Bleeding was then stopped by inserting coils into gastroduodenal artery and blocking it off, thereby stopping bleeding.

Question 8

What is endocrine and exocrine secretion?

Answer 8

Endocrine secretion is secretion into the blood stream to have effect on distant target organ. This can be autocrine/paracrine and is a form of ductless gland secretion. Exocrine secretion is secretion into a duct to have direct local effect.

Question 9

What are the main endocrine secretions of the pancreas & their actions?

Answer 9

Insulin is an anabolic hormone which promotes glucose transport into cells & storage as glycogen and decreases blood glucose. It also promotes protein synthesis & lipogenesis.
Glucagon increases gluconeogenesis and glycogenolysis to increase blood glucose.
Somatostatin has an inhibitory effect on all its receptors.

Question 10

Contrast pancreatic endocrine secretion and exocrine secretion

Answer 10

Endocrine secretion occurs from 2% of glands and occurs in islets of Langerhans. Involves secreting hormones into blood (insulin, glucagon, somatostatin and pancreatic polypeptide). Responsible for regulation of blood glucose, metabolism & growth effects. 98% of the gland is involved in exocrine secretion of pancreatic juice into duodenum via MPD/sphincter of Oddi/ampulla which has a digestive function.

Question 11

What are the 2 types of pancreatic cells?

Answer 11

Acini and islets. Acini are connected by ducts which feed zymogens into main pancreatic ducts. They are grape-like clusters of secretory units. Islets are derived from the branching duct system but lose contact with ducts – become islets. They then differentiate into α- and β-cells secreting into blood and are found more abundantly in the tail region than head region.

Question 12

Describe pancreatic microanatomy

Answer 12

Pancreatic acinar cells form circular bundles with a duct in the centre, into which each cell feeds zymogen granules. These ducts are lined by centroacinar cells., The ducts then converge to form the intercalated duct which then forms the intralobular duct. The islets form isolated circular bundles with capillaries running through the middle and hence have a rich blood supply.

Question 13

Describe the composition of the islets of Langerhans

Answer 13

α-cells (A) form about 15-20% of islet tissue and secrete glucagon
β-cells (B) form about 60-70% of islet tissue and secrete insulin
δ-cells (D) form about 5-10% of islet tissue and secrete somatostatin
The islets are highly vascular, ensuring that all endocrine cells have close access to a site for secretion.

Question 14

What are the 2 components of pancreatic juice?

Answer 14

Acinar cells produce the viscous, enzyme rich secretion in small volumes. The duct/centroacinar cells produce a watery, bicarbonate rich secretion in large quantities.

Question 15

Where is pancreatic bicarbonate produced, how much is produced and what is its function?

Answer 15

It is produced by duct & centroacinar cells. Has a pH of 7.5-8.0.

1. Neutralises acid chyme from stomach - prevents damage to duodenal mucosa and raises pH to optimum range for pancreatic enzymes to work.
2. Washes low volume enzyme secretion out of pancreas into duodenum.

Question 16

How does duodenal pH influence bicarbonate secretion?

Answer 16

When duodenal pH is between 5 and 3, there is a linear increase in bicarbonate secretion as pH falls. However, below pH 3, there is no increase in bicarbonate secretion. This is because bile also contains HCO3- and helps neutralise acid chyme. Brunners glands also secrete alkaline fluid.

Question 17

Describe bicarbonate secretion mechanism - how is bicarbonate formed?

Answer 17

Na+ moves down gradient from blood via paracellular (“tight”) junctions and water follows. Carbon dioxide diffuses into the pancreatic duct cell from the blood and reacts with water forming H+ and HCO3- in a reaction catalysed by carbonic anhydrase. H+ is secreted into the blood while bicarbonate is secreted into the lumen.

Question 18

Describe bicarbonate secretion mechanism - how is bicarbonate secreted and what happens meanwhile?

Answer 18

Bicarbonate is secreted into the lumen via an anion exchanger which transports chlorine into the cell from the lumen. This exchange is driven by electrochemical gradients as there is a higher conc of Cl- in the lumen than cell. H+ is secreted into the blood through a type 1 sodium-hydrogen exchanger antiporter (NHE-1). Driven by high blood Na+ compared to duct cell. Primary active transport used by Na+/K+ pump to maintain sodium gradient.

Question 19

Describe bicarbonate secretion mechanism - how is potassium and chlorine gradients maintained?

Answer 19

K+ returns to blood via K+-channel. Cl- returns to lumen via Cl-channel (cystic fibrosis transmembrane conductance regulator [CFTR]).

Question 20

What reaction occurs in both gastric parietal cells and duct cells?

Answer 20

H20 + CO2 H+ + HCO3-
However, in stomach, H+ is secreted into lumen and bicarbonate into blood so gastric venous return is alkaline. In pancreas, opposite occurs so venous return is acidic.

Question 21

What enzymes does the acinar cell secrete?

Answer 21

Lipases, proteases and amylases. These are synthesised & stored in zymogen granules.

Question 22

What protective mechanisms prevent auto-digestion in the pancreas?

Answer 22

Proteases are released as inactive pro-enzymes to protect acini & ducts from auto-digestion. Pancreas also contains a trypsin inhibitor to prevent trypsin activation and enzymes are only activated in the duodenum. Blockage of MPD may overload protection however and result in auto-digestion known as acute pancreatitis.

Question 23

How are enzymes activated in the duodenum?

Answer 23

Duodenal mucosa secretes an enzyme known as enterokinase (an enteropeptidase). This converts trypsinogen to trypsin. Trypsin then converts all other proteolytic & some lipolytic enzymes. Lipase is secreted in active form but requires colipase (i.e. secreted as precursor). However, lipases require presence of bile salts for effective action.

Question 24

How do pancreatic secretions change with diet?

Answer 24

Enzyme secretion is modified depending on contents of food. These enzymes are particularly important for digestion as lack of these or bile would result in malabsorption regardless of diet contents.

Question 25

What are the 3 stages of pancreatic juice secretion?

Answer 25

1. Cephalic phase
2. Gastric phase
3. Intestinal phase

Question 26

Describe cephalic phase of pancreatic juice secretion

Answer 26

Occurs as a reflex response to sight/smell/taste of food. Enzyme-rich component only released. Low volume of secretion as this “mobilises” enzymes.

Question 27

Describe gastric phase of pancreatic juice secretion

Answer 27

Stimulation of pancreatic secretion originating from food arriving in the stomach. Same mechanisms involved as for cephalic phase.

Question 28

Describe intestinal phase of pancreatic juice secretion

Answer 28

This phase accounts for 70-80% of pancreatic secretion. Hormonally mediated when gastric chyme enters duodenum and both components of pancreatic juice stimulated so enzymes & HCO3- juice flows into duodenum.

Question 29

How is pancreatic juice secretion controlled?

Answer 29

Pancreatic juice enzyme secretion controlled in acini by vagus nerve and cholecystokinin. Vagus nerve is cholinergic and vagal stimulation leads to enzyme secretion as well as communication of this information from gut to brain. Pancreatic juice bicarbonate secretion controlled in duct & centroacinar cells by secretin via cAMP.

Question 30

How is enzyme secretion in acini controlled?

Answer 30

Release of acetylcholine from vagus nerve or binding of GRP stimulates pancreas to produce trypsin which inhibits monitor peptide and lack of monitor peptide binding to duodenal I cells prevents release of CCK from these cells. Proteins in the lumen however, inhibit trypsin production. These are broken down into amino acids which along with fatty acids stimulate CCK Releasing Protein production in I cells, producing a monitor peptide which binds to I-cells facilitating CCK release into bloodstream.

Question 31

Describe control of HCO3- secretion in acini & ducts

Answer 31

Acinar fluid is isotonic and resembles plasma in its concs of Na+, K+, Cl− & HCO3−. Secretion of acinar fluid & proteins it contains is stimulated primarily by CCK. Secretin stimulates secretion of H2O & HCO3- from cells lining extralobular ducts. Secretin-stimulated secretion is richer in HCO3−cf acinar secretion because of Cl−/HCO3−exchange.

Question 32

Describe the Secretin and HCO3−secretion loop

Answer 32

Classic negative-feedback loop. Responds to decrease in luminal pH in duodenum. A decrease in pH stimulates S cells to produce and secrete secretin which then increases pancreatic ductal HCO3- conc leading to increase in pH.

Question 33

Describe CCK and secretin interaction

Answer 33

CCK alone has no effect on HCO3- secretion but can markedly increase HCO3- secretion which has been prompted by secretin. Vagus nerve has a similar effect to CCK. Secretin itself has no effect on enzyme secretion.

Question 34

Summarise what happens after the ingestion of a meal

Answer 34

1. Food mixed, digested in stomach, pH 2 and chyme squirted into duodenum.
2. H+ ions in duodenum increase secretin production and hence pancreatic juice secretion. Bile and Brunner’s gland secretion also increased so pH increases to alkaline.
3. Peptides & fat in duodenum cause sharp ↑ in CCK & vagal nerve stimulation. This stimulates pancreatic enzyme secretion. Peaks by 30 mins, continues until stomach empty.
4. CCK potentiates effects of secretin on aqueous component. Necessary as most of duodenum not at low pH.