Gastrointestinal: Pathology - The pancreas Flashcards
What % of the pancreas is endocrine vs exocrine?
80-85% exocrine
1-2% endocrine
How many litres are secreted by the pancreas daily?
2-2.5L/day
What are the cell types of the exocrine and endocrine pancreas?
Exocrine: acinar cells
Endocrine: insulin-secreting B cells, glucocagon-secreting a cells, somatostatin-secreting d cells
What % of cells in the endocrine pancreas are B, a or d?
B (insulin-secreting): 68%
a (glucagon-secreting): 20%
d (somatostatin-secreting): 10%
What is the effect of somatostatin on release of insulin and glucagon from pancreatic B and a cells?
Inhibits
Which pancreatic enzymes are NOT secreted as proenzymes?
Lipase
Amylase
Seven pancreatic proenzymes
Trypsinogen
Chymotrypsinogen
Procarboxypeptidase
Proelastase
Kallikreinogen
Phospholipase A
Phospholipase B
What % of acute pancreatitis is caused by alcohol and biliary tract disease?
80%
Seven broad causes of acute pancreatitis, with specific examples
- Obstruction (e.g. neoplasm, parasites)
- Medications (e.g. furosemide, thiazide diuretics, sulfonamides, azathioprine, methyldopa)
- Infection (e.g. mumps)
- Metabolic disorders (e.g. hypertriglyceridaemia, hypercalcaemia)
- Ischaemia (e.g. due to shock, thrombosis, thromboembolism, vasculitis)
- Trauma (blunt or iatrogenic, e.g. ERCP)
- Hereditary
Three pathogenic mechanisms of acute pancreatitis
- Duct obstruction: accumulation of enzymes in interstitium -> inflammatory response -> interstitial oedema -> impaired blood flow -> ischaemia -> acinar cell injury
- Primary acinar cell injury: e.g. in setting of infection, drugs, trauma -> release of proenzymes and lysosomal hydrolases -> enzyme activation -> acinar cell injury
- Defective intracellular transport of proenzymes: delivery of proenzymes to lysosomal compartment -> intracellular activation -> acinar cell injury
What is the common final pathogenic pathway for acinar cell injury and pancreatic inflammation?
Whether duct obstruction, primary acinar cell injury, or defective intracellular transport of proenzymes: all lead to pancreatic autodigestion via:
- Proteolysis (proteases)
- Fat necrosis (lipase, phospholipase)
- Haemorrhage (elastase)
What is the mechanism of pancreatic injury due to alcohol consumption?
Chronic EtOH causes secretion of protein-rich pancreatic fluid
Forms protein plugs which obstruct small pancreatic ducts
Five morphological features of pancreatitis
- Microvascular leakage causing oedema
- Fat necrosis by lipolytic enzymes
- Acute inflammation
- Proteolytic destruction of pancreatic parenchyma
- Destruction of blood vessels leading to interstitial haemorrhage
What is the difference in histological features seen with increasing severity of pancreatitis?
Mild (acute interstitial pancreatitis): inflammation, oedema, focal areas of fat necrosis
Severe (acute necrotising pancreatitis): acinar, ductal tissues, and islets of Langerhans are necrotic; intraparenchymal haemorrhage
Most severe (haemorrhagic pancreatitis): extensive parenchymal necrosis with dramatic haemorrhage
What are two clinical signs which may be seen in acute necrotising pancreatitis?
Periumbilical bruising (Cullen’s sign)
Flank bruising (Grey Turner’s sign)
Eight early sequelae of acute pancreatitis
- Acute renal tubular necrosis -> acute renal failure
- Hypocalcaemia (due to precipitation of Ca2+ in necrotic fat)
- Fluid sequestration, ARDS
- CV collapse, shock
- Sepsis (usually GNRs from GIT)
- DIC, haemolysis
- Transient hyperglycaemia
- Glycosuria
What % of patients with severe necrotising pancreatitis develop sepsis?
40-60%
Five later (week 2-4) sequelae of acute pancreatitis
- Pancreatic necrosis
- Haemorrhage from erosion into nearby arteries (e.g. UGIB)
- Pancreatic ascites, pleural effusion (fluid high in amylase)
- Pancreatic abscess and pseudocyst
- Fistula
What are the four possible longterm outcomes of acute pancreatitis?
Most commonly there is full recovery with no longterm sequelae
May get recurrence (especially if ductal damage incurred)
Pancreatic insufficiency (both exocrine -> malabsorption, and endocrine -> DM)
Death in 5% of patients with severe necrotising pancreatitis (from shock, within first week of illness)
Outline Ranson’s criteria
> /= 3 of the following, within 48hrs of admission, confers increasing risk of morbidity/mortality:
- Age >55yrs
- BSL >10mmol/L (with no history of diabetes)
- WCC >15 x 10^9 L
- LDH >600IU/L
- AST >200u/L
- Corrected Ca2+ <2.0mmol/L
- BUN >16mmol/L (with no improvement with IVT)
- Decreasing Hct
- Arterial pO2 <60mmHg
- Metabolic acidosis
- Serum albumin <32g/L
Describe the mortality risk with increasing numbers of positive Ranson’s criteria
0-2: <5%
3-4: 20%
5-6: 40%
7-8: 100%
What increases first in acute pancreatitis: serum amylase or lipase levels?
Amylase increases first, within 24hrs
Lipase follows, within 72-96hrs
In what % of cases of acute pancreatitis is glycosuria present?
10%
What defines chronic (as opposed to acute) pancreatitis?
Defined by IRREVERSIBLE loss of exocrine pancreatic parenchyma (and endocrine parenchyma in late stages)
