Pancreatic Pathology Flashcards
What is the exocrine function of the pancreas?
What cells/structures are involved?
secretion of digestive enzymes which require activation
- trypsin
- lipase
- phospholipase
- elastase
- amylase (marker of pancreatic inflammation)
involves glands, ducts and the duodenum
Why are exocrine products secreted as enzymatically inert?
How are they activated and suppressed?
if they were not enzymatically inert, the pancreas would digest itself
activation requires conversion of trypsinogen into trypsin in the duodenum
trypsin inhibitors (e.g. SPINK-1) are present in the acinar and ductal cells
What are acinar cells?
pyramidal shaped epithelial cells arranged around a central lumen into which enzymes are secreted
What % of the pancreas is made from endocrine and exocrine cells?
85% of the pancreas is exocrine
1-2% of the pancreas is endocrine
What cells are involved in the endocrine function of the pancreas?
What is this function?
1 million clusters of cells - islets of Langerhans
they secrete peptide hormones into the blood
(e.g. insulin and glucagon)
What is pancreatitis and what is it associated with?
inflammation of the pancreas
associated with injury to the exocrine parenchyma
What is the main difference between acute and chronic pancreatitis?
acute:
- gland reverts to normal if the underlying cause is removed
chronic:
- irreversible loss of the pancreatic tissue
What are the causes (aetiology) of acute pancreatitis?
- gallstones (50% cases)
- alcohol (25% cases)
- rare causes (<5% cases)
- vascular insufficiency
- viral infections - mumps & coxsackie B
- hypercalcaemia
- ERCP
- inherited causes
- idiopathic (10% cases)
What is the male : female ratio like in acute pancreatitis?
How common is it?
male to female ratio varies with cause
1 M : 3F in biliary disease, 6M : 1F in alcoholism
it is relatively common - 10-20 per 100,000 in Western countries
What % of patients with gallstones have acute pancreatitis?
35-60% of patients with acute pancreatitis have gallstones
5% of patients with gallstones have pancreatitis
What is hereditary pancreatitis?
What are the 2 different mutations that can cause it?
recurrent attacks of severe pancreatitis that usually begins in childhood
- PRSS1 inherited mutations - autosomal dominant
- SPINK-1 gene - autosomal recessive
What is the result of having a PSSR1 inherited mutation?
- PRSS1 mutations alter a site on the cationic trypsinogen molecule that is essential for inactivation of trypsin by trypsin itself
- mutations result in trypsin being resistant to cleavage by another trypsin molecule
- small amounts of trypsin activation results in activation of other digestive enzymes causing pancreatitis
What is the SPINK-1 gene?
What is its function?
serine protease inhibitor Kazal type 1
it codes for a trypsin inhibitor which helps prevent autodigesiton of the pancreas by activated trypsin
What are the clinical features of acute pancreatitis?
What is a poor prognostic sign?
usually presents as an emergency requiring hospital admission
- sudden onset of severe abdominal pain, radiating to the back
- nausea & vomiting
- raised serum amylase / lipase (> 3x normal)
it may be mild (recovery within 5-7 days) but can be serious with high mortality
persistent hypocalcaemia is a poor prognostic sign
What is involved in the pathogenesis of acute pancreatitis?
it varies according to aetiology
- leakage and activation of pancreatic enzymes
- amylase released into the blood
e.g. obstruction (stones) damages duct lining resulting in leakage and activation of pancreatic enzymes
hypoxia affects the acinar cells at the periphery of the lobules
What is the difference in pathogenesis in mild and severe acute pancreatitis?
mild pancreatitis:
- swollen gland with fat necrosis
severe pancreatitis:
- swollen, necrotic gland with fat necrosis and haemorrhage
- Grey Turner’s sign - haemorrhage into the subcutaneous tissues of flank
- Cullen’s sign - periumbilicus
Why does fat necrosis occur in pancreatitis?
chalky white material containing calcium salts which have been freed up by lipase-mediated cleavage of fatty acids
What are some other factors involved in the pathogenesis of acute pancreatitis?
- hypocalcaemia (fatty acids bind calcium ions)
- hyperglycaemia
- abscess formation
- pseudocysts
What are the complications of acute pancreatitis?
What do most of them relate to?
- shock
- intravascular coagulopathy
- haemorrhage
- pseudocysts (collections of pancreatic juice secondary to duct rupture)
many of the systemic features are related to the release of toxic enzymes, cytokines and other mediators into the circulation
this results in activation of the systemic inflammatory response
What is chronic pancreatitis?
What does it lead to?
a progressive inflammatory disorder in which parenchyma of the pancreas is destroyed and replaced by fibrous tissue
irreversible destruction of the exocrine tissue, followed by destruction of the endocrine tissue
leads to malnutrition and diabetes
Why are acute and chronic pancreatitis not two distinct diseases but a continuum?
- recurrent acute can develop chronic pancreatitis
- overlap in causative factors
- both genetic and environmental
- experimental protocols can be modified to induce each condition
What are the symptoms of chronic pancreatitis?
What can it mimic?
- intermittent abdominal pain
- back pain
- weight loss
- fibrosis of exocrine tissue can mimic carcinoma macroscopically and microscopically
What are the characteristics of chronic pancreatitis?
- localised, irregular involvement of the gland early on then later global atrophy
- dilated and distorted ducts
- calculi, especially in alcohol induced
- fatty replacement - fibrosis
- pseudocyst formation
What is involved in the progression model for adenocarcinoma of the pancreas?
What is the most common neoplastic precursor?
the most common neoplastic precursor to invasive carcinoma is PanIN
- K-ras mutations occur early on
- p16 inactivation occurs as an intermediate step
- inactivation of suppressor genes occurs later
What is shown here?
pancreatic intraepithelial neoplasia (PanIN)
What are the non-specific symptoms of pancreatic carcinoma?
- epigastric pain, radiating to the back
- weight loss
- painless jaundice
- pruritis
- nausea
- diabetes - both increases risk and can be a presenting complication
Where may distant metastases be seen in pancreatic carcinoma?
liver, peritoneum and lung
What is the survival like for pancreatic carcinoma with and without treatment?
it is almost universally fatal (incidence nearly equals mortality)
mean survival untreated is 3-5 months
survival is 10-20 months post-surgery but only 10-20% are resectable at time of diagnosis
