Endocrine 1 - Exocrine Pancreas

Question 1

What 4 components comprise the pancreas?

Answer 1

Head, neck, body, tail

Question 2

What % of the pancreas does the exocrine component comprise?

Answer 2

80-85%

Question 3

1. The main pancreatic duct comprises the:

2. What is another important duct?

Answer 3

1. Hepatopancreatic duct (Ampulla of Vater) and hepatopancreatic sphincter (Sphincter of Oddi)
2. Accessory pancreatic duct (abnormalities during development can result in this duct acting as the main duct)

Question 4

What are the 2 main functional units of the exocrine pancreas?

Answer 4

1. Acinar cells

2. Ductal structures

Question 5

What do the ACINAR, CENTRO-ACINAR & COLUMNAR CELLS each secrete?

Answer 5

A: proenzymes (which are digestive enzymes)
C-A: neutralise pH by secreting bicarbonate ions
C: produce mucin which acts as a chemical barrier

Question 6

How are proenzymes activated?

Answer 6

By ENTEROPEPTIDASE in chyme in the upper duodenum. This converts trypsinogen to trypsin which then initiates a cascade in which trypsin activates the other 5 enzymes. Therefore abnormal activation of trypsin = bad

Question 7

Which 6 digestive enzymes comprise the PANCREATIC JUICE? What do they each break down?

Answer 7

1. Trypsinogen – breaks down protein (trypsin = the active form)
2. Chymotrypsinogen - breaks down protein
3. Procarboxypeptidase – breaks down protein
4. Proelastase – breaks down elastin and collagen
5. Kallikreinogen - cleave kininogens to form kinins
6. Prophospholipase A and B – hydrolises lipids

Question 8

What does SPHINK1 code for?

Answer 8

Trypsin inactivators - your bodies defence for when trypsin is activated at the wrong time

Question 9

What 2 things does secretion of cholecystokinin (CCK) from the duodenum do?

Answer 9

1. Stimulates the release of the digestive enzymes from the pancreas
2. Stimulates the release of bile from the gall bladder

Question 10

What does the PDX1 gene do?

Answer 10

Gene present during development involved in the formation of the pancreas.

Question 11

What are 4 congenital abnormalities of the pancreas?

Answer 11

1. Pancreas Divisum: duct systems fail to fuse, accessory duct acts as main duct
2. Pancreatic agenesis: mutations of PDX1 gene during developement —> foetus dies
3. Ectopic Pancreas: stomach, duodenum
4. Annular Pancreas: forms as a ring-shape around duodenum instead of a nice, elongated gland

Question 12

What is PANCREATITIS? What are its 2 subcategories?

Answer 12

• Inflammation and activation of digestive enzymes in pancreas (they should only be activated in the duodenum)
• Acute or Chronic (based on length of inflammation)

Question 13

The body has 4 mechanisms it uses to protect itself when abnormal changes occur in the pancreas. What are these?

Answer 13

• Maintenance of a zymogen granule
• Secretion of a proenzyme (inactive) rather than an active enzyme
• The pH conditions which are maintained by the bicarbonate ions
• The chemical barrier formed by mucin

Question 14

Is acute pancreatitis reversible?

Answer 14

Yes. Restoration of acinar cell mass occurs.

Question 15

______ and _______ account for 80% of acute pancreatitis cases.
What are 5 other causes?

Answer 15

• Alcoholism and Biliary tract disease
• Metabolic (hypercalcemia), genetic (PRSS1 or SPINK1), mechanical (trauma), infectious (mumps), vascular (shock)
• ** All of these cause ACINAR CELL INJURY which is ultimately what causes AP

Question 16

What are 3 symptoms people with AP present with?

Answer 16

1. Acute abdominal pain (URQ)
2. Referred pain to upper back and left shoulder
3. Nausea/vomiting

Question 17

What are 4 measurements used to diagnose AP?

Answer 17

1. Abdominal distention + tenderness
2. Increased WBC count
3. Increased [serum] of pancreatic lipase + pancreatic amylase
4. Fluid exudate as seen in CT scan

Question 18

Name 5 morphological changes seen in the pancreas of a person with AP.

Answer 18

1. Destruction of pancreas parenchyma
2. Oedema
3. Chalky white fat appearance + necrosis
4. Enlarged
5. Interstitial haemorrhage
   * ** Reasons why are on Slide 7

Question 19

What 3 enzymes are inappropriately activated in AP?

Answer 19

1. Trypsin: breakdown of proteins + activation of other pancreatic enzymes
2. Phospholipase: breakdown of fat cells
3. Elastase: breakdown of elastic fibres & vasculature

Question 20

Local inflammation is mediated by the release of PRO-INFLAMMATORY CYTOKINES. Which 4 in particular are released?

Answer 20

TNF-alpha
IL-1beta
IL-6
IL-8

Question 21

If not treated, AP can progress to what syndrome?

Answer 21

Systemic Inflammatory Response Syndrome (SIRS)

Question 22

What 5 things are done as treatment for AP?

Answer 22

1. Fluid resuscitation to correct fluid loss
2. Pain relief
3. Nil by mouth to rest exocrine function
4. Antiemetics for nausea + vomiting
5. Drainage of fluids to relieve pressure

Question 23

Why are serum concentrations of amylase and pancreatic lipase not elevated in Chronic Pancreatitis?

Answer 23

Necrosis occurs in CP. The cells have gone past just apoptosis and are no longer able to perform any function anymore.

Question 24

What are 6 measurements used to diagnose CP?

Answer 24

1. Abdominal distention + tenderness
2. No change in serum amylase and lipase
3. Potential for elevated BGLs and CCK
4. Pancreatic calcifications observed using CT scan
5. ERCP (endoscopy) to look for pancreatic + bile duct deformities
6. Staining of faecal samples to test for steatorhhoea

Question 25

Name 3 morphological changes seen in the pancreas of a person with CP.

Answer 25

1. Parenchymal fibrosis - reduced number and size of acini cells 2. Inter + intra-lobular ducts have protein plugs 3. Inflammatory infiltrate found in ducts with atrophic epithelium

Question 26

What are the 5 suggested causes of CP?

Answer 26

1. Ductal theory (physical clogs and stuff) 2. Acinar theory (more about chemicals/molecules/enzymes that damage the acinar cells) 3. Two-hit theory 4. Multiple cause theory (ischemia) 5. Electrophilic stress (toxic – too much, deficiency – too little of something)

Question 27

______ is a key sign of AP | ______ is a key sign of CP

Answer 27

Inflammation | Fibrosis

Question 28

What 4 steps occur in CP which lead to FIBROSIS occuring?

Answer 28

1. Infiltrate and activation of macrophages 2. Increased collagen synthesis, decreased collagen degradation 3. Release of pro-fibrotic cytokines (TGbeta, PDGF) 4. Release of pro-inflammatory cytokines (TNF-alpha)

Question 29

What 6 things are done as treatment for AP?

Answer 29

1. Pain management 2. Steroids 3. Enzyme therapy (block CCK) 4. Micronutrients (to combat Reactive Oxygen Species) 5. Treatment of protein-energy malnutrition 6. Surgery: lateral pancreaticojejunostomy (Puestow procedure)