Path Notes: Pancreatitis****

Question 1

What is pancreatitis?

Answer 1

Inflammation of the pancreas, associated with injury to the exocrine parenchyma

Question 2

What is Acute Pancreatitis?

Answer 2

Acute pancreatic exocrine parenchyma injury associated with inflammation. Outcome depends on severity which ranges from mild to severe acute pancreatitis

Question 3

Describe the non-hereditary Aetiological causes of acute pancreatitis

Answer 3

1. Idiopathic
2. **Gallstones (more often in females) causing obstruction to the pancreatic duct system - or tumours, etc causing obstruction
3. **Ethanol Abuse (more often in males)
4. Trauma - blunt abdo trauma, or introgenic (caused by medical intervention) traume - e.g. ERCP
5. Drugs
6. Infections such as mumps, Mycoplasma pneumoniae, coxsackieviruses
7. Hypercalcaemia
8. Hypertriglyceridaemia

Question 4

Describe the hereditary aetiology of acute pancreatitis

Answer 4

Cationic Trypsinogen Mutation (PRSS1)

AD syndrome

Characterised by recurrent severe attacks of acute pancreatitis, which start in childhood

Trypsin resistant to inactivation, leading to pancreatic self-digestion and thus more pancreatitis

Question 5

Describe the macroscopic features of acute pancreatitis

Answer 5

1. Oedema
2. Mild-severe necrosis and haemorrhage (can be very extensive)
3. Fat necrosis

Question 6

Describe the microscopic features of pancreatitis:

Difference between mild and severe forms?

Answer 6

1. Microvascular leakage causing oedema
2. Fat necrosis by lipoytic enzymes
3. Acute inflammatory reaction
4. Proteolytic destruction of pancreatic parenchyma (self-digestion)
5. Destruction of blood vessels and subsequent haemorrhage

Mild form:
= Interstitial pancreatitis with oedema and fat necrosis

Severe forms:
= acute necrotising pancreatitis

These can both involve widespread necrosis of pancreatic tissue. This affects acinar and ductal tissues, as well as the islets of langerhans

Haemorrhage into the parenchyma and chalky white fat necrosis indicates the most severe form - haemorrhagic pancreatitis

Question 7

Describe the pathogenesis of pancreatitis:

Answer 7

1. Inappropriately activated pancreatic enzymes undergo self-digestion of pancreatic parenchyma
2. The activation of trypsinogen plays an important role in this
3. Typsinogen activates other proenzymes, including phospholipase (fat necrosis) and proelastase (vascular destruction)
4. This leads to parenchymal digestion/destruction, fat necrosis, haemorrhage
5. Subsequent activation of clotting and compliment pathways

Question 8

How are the pancreatic enzymes activated in pancreatitis? (Just list them)

Answer 8

1. Pancreatic Duct Obstruction
2. Primary Acinar Cell Injury
3. Defective transport of pro-enzymes within acinar cells
4. Alcohol (ethanol)

Question 9

How does pancreatic duct obstruction cause pancreatitis?

Answer 9

1. The increased pressure causes accumulation of enzyme-rich fluid to accumulate
2. Causes necrosis of parenchymal cells
3. Secretion of cytokines - inflammation
4. Inflammation leads to oedema
5. Oedema can in turn compromise blood flow, leading to ischaemia

Question 10

How does Primary acinar cell injury lead to pancreatitis?

Answer 10

Injury may be caused by:

• viruses
• drugs
• trauma
• ischaemia
• shock

Causes cellular dysfunction and/or degradation, releasing enzymes

Question 11

How does defective proenzyme transport within acinar cells lead to pancreatitis?

Answer 11

Leads to inappropriate intracellular activation of pro-enzymes

Question 12

How does alcohol cause pancreatitis?

Answer 12

Mechanism is unknown, but alcohol may cause:
1. Secretion of protein-rich intestinal secretions, leading to protein plug formation which can cause pancreatic duct obstruction

2. Transient increase in pancreatic exocrine secretions, and contraction of the sphincter of oddi (sphincter at ampula of vater)
3. Direct toxic effect on acinar cells

Alcohol could also represent sudden exacerations of chronic pancreatitis

Question 13

Describe the clinical features of acute pancreatitis?

Answer 13

1. Mild-severe abdo pain often referred to the upper back
2. Associated nausea and vomiting
3. Anorexia

Pancreatitis is a medical emergency

Question 14

What are some of the associated things that happen with acute pancreatitis? i.e. why is it a medical emergency, what happens with it?

Answer 14

1. Toxic enzymes, cytokines and other mediators result in:
   - Leukocytosos
   - Haemolysis
   - DIC
   - Fluid sequestration (into bodily spaces, out of circulation)
   - Acute Respiratory Distress Syndrome (ARDS)
   - Diffuse fat necrosis
   - Peripheral vascular collapse
   - Shock
   - Renal tubular necrosis

Question 15

What are some complications of acute pancreatitis?

Answer 15

1. Death - occurs in 5%
2. Death usually due to multi-organ failure-shock, ARDS, acute renal failure, DIC
3. Pancreatic Abscesses
4. Pancreatic pseudocyst
5. Duodenal obstruction
6. Infection of necrotic pancreatic tissue by enteric gram negatives

Question 16

What is used to diagnose acute pancreatitis?

Answer 16

1. Elevated serum amylase and lipase
2. Low glucose may occur
3. Hypocalcaemia may occur
4. Imaging to assess pancreas
5. Clinical presentation