Functions and Secretions of the Pancreas

Question 1

Overall functions of the pancreas

Answer 1

• Digestion of nutrients (enzymes)
• Providing appropriate environment for enzymatic digestion in small bowel
• Regulating fed + fasted states (eg. insulin)

Question 2

What is the pancreas arranged into morphologically?

Answer 2

Lobules draining into a ductular network that connects the entire gland to the GIT lumen

Question 3

Types of duct in the pancreatic ductular network

Answer 3

• Intralobular duct
• Interlobular duct
• Main pancreatic duct

Question 4

What does the major pancreatic duct form with the common bile duct in the duodenal wall

Answer 4

Ampulla of Vater

Question 5

Muscular thickening around the ampulla of Vater

Answer 5

Sphincter of Oddi

Question 6

What is the function of the sphincter of Oddi?

Answer 6

Regulate and prevent reflux

Question 7

What do pancreatic secretions empty through and what into?

Answer 7

• Through major duodenal papilla
• Into descending duodenum

Question 8

What is each secretory unit of the pancreas comprised of?

Answer 8

• Acinus
• Small intercalated duct

Question 9

What is an acinus and what does it do?

Answer 9

• Cluster of acinar cells
• Synthesise and secrete zymogens, digestive enzymes + isotonic, plasma-like fluid into lumen of epithelial structure

Question 10

Types of cells in the pancreas and their functions

Answer 10

• Acinar cells
  > Specialised/polarised for production + export of protein
• Duct cells
  > Specialised for transport of electrolytes
• Centroacinar cells
  > First cells of intercalated duct located at junction of acinar + duct cells
• Goblet cells
  > Produce mucous for lubrication, hydration, mechanical protection + immunologic role

Question 11

What mediate stimulation of acinar cells?

Answer 11

• CCK + muscarinic ACh receptors on basolateral membrane
• Signal through phospholipase C (PLC/PKC)/Ca2+ pathway

Question 12

2 routes of activation of acinar cells

Answer 12

• ACh + CCK activate PKC + release of calcium
• VIP + secretin activate adenylyl cyclase, producing cAMP + activating PKA

Question 13

Principle function of pancreatic duct cells

Answer 13

Secrete an HCO3- rich fluid that alkalinises + hydrates primary secretions of acinar cells

Question 14

What type of channel is the cystic fibrosis transmembrane conductance regulator (CFTR) and where is it found?

Answer 14

• cAMP-activated Cl- channel
• Apical membrane of pancreatic duct cells

Question 15

Mechanism of pancreatic duct cells

Answer 15

• Secretin binding simulates adenylyl cyclase, increasing [cAMP]
• cAMP stimulates CFTR, causing Cl- efflux into lumen
• Carbonic anhydrase forms additional HCO3-
• Cl- in lumen (from CFTR + other) exchanged by Cl-/HCO3- exchanger, to secrete HCO3- into lumen
• ACh stimulates HCO3- secretion too by muscarinic receptors, increasing [Ca2+] + activating Ca2+-dependent protein kinases

Question 16

What is secretin secreted by?

Answer 16

S cells in the small bowel

Question 17

What happens in cystic fibrosis

Answer 17

• Mutation in CF gene
• Mutant CFTR prematurely degraded
• Decreases secretion of HCO3- + water by ducts
• Results in protein-rich primary secretion thickening in duct lumen
• Lumen obstruction

Question 18

Consequences of obstructed ductal lumen in cystic fibrosis

Answer 18

• Deficiency of pancreatic enzymes
• Malnutrition of nutrients –> steatorrhea + diabetes

Question 19

Where is CCK secreted from?

Answer 19

Duodenal I cells

Question 20

What stimulates secretion of CCK?

Answer 20

• Response to fatty meal
  > CCKA receptor
  > Parasympathetic NS
• Luminal CCK-releasing factor - LCRF (endogenously produced proteins secreted into gut lumen)

Question 21

Why do LCRFs not stimulate CCK secretion in the fasting state, but do in the fed state?

Answer 21

• Digestive enzymes break them down in fasting state
• Digestive enzymes act on chyme in fed state so LCRFs can stimulate I cells

Question 22

Action of somatostatin on pancreatic secretions

Answer 22

Inhibits release of CCK + secretin (+ therefore pancreatic secretion)

Question 23

What are used clinically to inhibit pancreatic secretions?

Answer 23

Somatostatin analogues

Question 24

3 phases of pancreatic secretion

Answer 24

• Cephalic
• Gastric
• Intestinal

Question 25

What percentage of pancreatic secretion is the cephalic phase, and how does it work?

Answer 25

- 25% - Sight, taste + smell of food causes nervous activation - ACh receptors on acinar cells + duct cells to lesser extent

Question 26

What percentage of pancreatic secretion is the gastric phase, and how does it work?

Answer 26

- 10-20% - Release of hormones (mainly gastrin, stimulated by luminal peptides/AAs, from G cells of antrum) > Signals through CCK receptors on acinar cells - Stimulating neural pathways > Gastric distension stimulates pancreatic secretion through vagovagal gastropancreatic reflex

Question 27

What percentage of pancreatic secretion is the intestinal phase, and how does it work?

Answer 27

- 50-80% - Chyme enters proximal SI + stimulates secretion by 3 mechanisms: > Gastric acid stimulates duodenal S cells to secrete secretin --> HCO3- + fluid from duct cells > Lipids stimulates duodenal I cells to release CCK --> digestive enzymes from acinar cells > Lipids activate vagovagal enteropancreatic reflex --> acinar cells

Question 28

How does the pancreas prevent autodigestion?

Answer 28

- Digestive proteins stored in secretory granules as inactive precursors - Secretory granule membrane impermeable to proteins - Enzyme inhibitors (eg. pancreatic trypsin inhibitor SPINK1) co-packaged into secretory granules - Condensation of zymogens, low pH + ionic conditions limit enzyme activity

Question 29

How are inactive enzymes from the pancreas activated?

Answer 29

- Coming into contact with small bowel brush-border enzyme enterokinase - Converts trypsinogen to trypsin which in turn initiates conversion of all other zymogens

Question 30

Causes of acute pancreatitis

Answer 30

- GET SMASHED: > Gallstones > Ethanol > Trauma (children) > Steroids > Mumps > Autoimmune (SLE, Sjogren's syndrome) > Scorpion sting > Hypercalcaemia, hypertriglyceridaemia, hypothermia > ERCP > Drugs (paracetamol, cisplatin, erhythromycin)

Question 31

What is needed to diagnose acute pancreatitis?

Answer 31

- 2 of following 3: > Characteristic abdominal pain (epigastrium radiating to back) - often associated with nausea + vomiting > Serum amylase and/or lipase >= 3x upper limit of normal > Characteristic findings of acute pancreatitis on CT scan

Question 32

3 phases of pathophysiology of acute pancreatitis

Answer 32

- Phase 1: > Premature activation of trypsin within acinar cells (disruption of calcium signalling, cleavage of trypsinogen by lysosomal hydrolase cathepsin-B or decreased activity of the intracellular pancreatic trypsin inhibitor SPINK 1) > Activates all other enzymes - Phase 2: > Intra-pancreatic inflammation (activation of inflammatory + endothelial cells) - Phase 3: > Extra-pancreatic inflammation including systemic sepsis + multi-organ failure

Question 33

Treatment of acute pancreatitis

Answer 33

- Resting pancreas (IV fluids to combat dehydration) - Hourly fluid balance (input + output due to severe hypovolaemia) - Pain relief

Question 34

What is chronic pancreatitis?

Answer 34

Inflammation of the pancreas that does not heal or improve - gets worse over time + leads to permanent damage

Question 35

Most common and other causes of chronic pancreatitis

Answer 35

- MC = chronic alcohol abuse - Other: > Hereditary disorders of the pancreas > Cystic fibrosis > Hypercalcaemia > Hyperlipidaemia

Question 36

Treatment of chronic pancreatitis

Answer 36

- Hospitalisation for pain management, IV hydration + nutritional support - Supplement resuming of normal diet with synthetic pancreatic enzymes if not enough secreted - Nutritious diet low in fat with small, frequent meals - ERCP: > Enlarge duct openings + drain pseudocysts > Stent placement to keep open narrowed pancreatic/bile duct > Balloon dilation to dilate/stretch narrowed pancreatic/bile duct