tbl 3 pathology (pancreas)

Question 1

Review of pancreas
- Mainly exocrine, endocrine portion <1% (islets of Langerhans)
- Exocrine pancreas – lobules comprised mainly of ____________, and ducts
o Proenzymes (inactive) – trypsinogen, chymotrypsinogen, amylase, lipase
o Bicarbonate rich fluid

• Ducts are arranged from small to large, eventually draining into the main and accessory pancreatic duct
• Congenital variations include variations of the ductal anatomy, such as ____________
  o Normally, the ventral and dorsal portions of the pancreatic duct fuse to form the __________ (main pancreatic duct), which opens into the ampulla of Vater
  o Pancreas divisum – failure of fusion of the ventral and dorsal portions of the duct, opening separately into the duodenum
  § Pancreatic divisum is important – surgical considerations and is implied in the risk factors of acute pancreatitis

Answer 1

pyramidal acinar cells; pancreas divisum; duct of Wirsung

Question 2

Safety features to prevent autodigestion of pancreas
- Proenzymes that are inactivated in the pancreas – activation occurs at a different site from production
o In the duodenum, ________ on the brush border activates trypsinogen to trypsin, which brings about activation of other pancreatic enzymes
- Protease Inhibitors – produced by acinar cells and ductal cells, preventing activating of proenzymes during passage e.g. ________ (Pancreatic secretory trypsin inhibitor, PSTI)
- Low calcium

Answer 2

enterokinase; SPINK1

Question 3

Acute pancreatitis
Reversible acute inflammatory process of pancreas due to inappropriate activation of pancreatic enzymes

Pathophysiology

1. Duct obstruction – due to biliary stone at ampulla or tumour etc.
   - Bile is refluxed into the pancreatic duct, leading to injury of acinar cells
   - Ductal __________ – increased pressure within the duct results in enzymes leaking into the interstitium and inflammatory changes
   - Lipases are secreted in the active form, leading to ___________ and more inflammation
   - Increased inflammation leads to _____________ - compresses on vasculature leading to ischaemia and acinar cell injuryy
2. Acinar cell injury – release of intracellular proenzymes and ___________ leading to inappropriate activation of proenzymes
3. Defective intracellular transport – mainly observed in experimental animal models only
   - All 3 factors lead to activated enzymes (proteases, lipases, elastases etc.), leading to damaged blood vessels, fat necrosis, proteolysis and interstitial inflammation and oedema – destruction of pancreas

Answer 3

dilatation; fat necrosis; interstitial oedema;

lysosomal hydrolases

Question 4

Aetiology of acute pancreatitis – mnemonic
G \_\_\_\_\_\_\_\_\_\_\_ (35 to 60%)
E \_\_\_\_\_\_\_\_\_
T \_\_\_\_\_\_\_\_\_\_
S Steroids
M Mumps
A Autoimmune – polyarteritis nodosa
S Scorpion bite
H Hyperlipidaemia, hypercalcaemia, hyperthyroidism
E ECRP
D Drugs – tetracyclines, azathioprine

Answer 4

Gallstones; Ethanol; Trauma

Question 5

Acute pancreatitis Histopathology
- Oedema
- Fat necrosis – fatty acids are released, combines with __________ to form insoluble soaps (saponification)
o Chalky white deposits in the _________ and mesentery grossly)
- Acute inflammation
o Necrosis of parenchyma
o Necrosis of blood vessels – interstitial haemorrhage (seen grossly)
- Degree of severity ranges from – mild acute, acute necrotising, acute necrotising and haemorrhagic pancreatitis

Answer 5

calcium; omentum

Question 6

Acute pancreatitis complications

• Pancreatic abscess
• Pancreatic pseudocyst
• Inflammatory mediators such as TNF-α and IL-6 and _____ can be released to the circulation, leading to systemic effects – shock, ARDS
• Trypsin can activate the _________ system, having effects on the vasculature – DIC
• Recurrent attacks can lead to chronic pancreatitis

Answer 6

IL-8; prekallikrein-kinin

Question 7

Chronic pancreatitis
- Chronic inflammation of the pancreas with ________ damage of the exocrine and endocrine components
o ______ and gland atrophy
- More common in middle aged males
- Gland atrophy can lead to pancreatic insufficiency and malabsorption
o Endocrine effects such as DM are only seen in advanced stages of chronic pancreatitis

Causes of chronic pancreatitis

• Chronic alcoholism (most common)
• Biliary tract obstruction
• Idiopathic
• Rarer causes – genetic, cystic fibrosis, autoimmune pancreatitis

Answer 7

irreversible; Fibrosis

Question 8

Chronic Pancreatis Histopathology
- Gross – hard pancreas (fibrosis) with ________ with/without calculi or concretions
- Microscopy – ___________ are usually spared
o Acini – fibrosis, glandular atrophy,
o Ducts – dilatation, periductal chronic inflammation within ducts, stones,
squamous metaplasia
- Complications – pseudocyst, bile duct obstruction (strictures and fibrosis), increased risk of carcinoma

Answer 8

dilated ducts; islets of Langerhans

Question 9

Pseudocyst – cystic collection of necrotic enzyme rich material

• No __________
• Non neoplastic cyst, accounts for 75% of cysts in pancreas (another type of non-neoplastic cyst is congenital cyst)
• Following a bout of acute pancreatitis (alcohol usually or trauma)
• Rarely in chronic pancreatitis due to rupture of dilated duct cysts
• Solitary (rarely multiple) cystic lesion in pancreas or lesser omentum
• Progression – resolve, infected, larger ones can compress on adjacent structures e.g. bile duct, or perforate

Differential diagnosis – abscess (can also present as a cystic lesion), cystic pancreatic neoplasm
o Cystic pancreatic neoplasms – particularly mucin-producing types as mucinous cystic neoplasm and ____________ has a high malignancy potential and need to be excised to prevent further development
§ Correlation with history, radiological findings and examination of cystic fluid
can help in differential diagnosis

Answer 9

true epithelial lining; intraductal papillary mucinous neoplasm (IPMN);