Pancreatic Pathology Flashcards
What causes a pancreas divisum?
What can it possibly lead to?
The main pancreatic duct joins the common bile duct just proximal to the papilla of Vater, and the accessory pancreatic duct drains into the duodenum through a separate papilla.
It leads to inadequate drainage of pancreatic secretions and may increase the risk for chronic pancreatitis.
It is the most common congenital anomaly of the pancreas.
What is an annular pancreas?
What can it cause?
A band-like ring of pancreatic tissue that encircles the pancreas.
It may cause duodenal obstruction.
What is the definition of acute pancreatitis?
Pancreatic inflammation characterized by reversible pancreatic parenchymal injury.
What are 5 etiologies of acute pancreatitis?
Toxins (EtOH, etc.)
Pancreatic duct obstruction
Inherited defects
Vascular injury
Infection
What is the overall pathogenesis of acute pancreatitis?
Inappropriate release and activation of pancreatic enzymes, which destroy pancreatic tissue and elicit acute inflammation.
What are the 3 major initiating events of acute pancreatitis?
Duct obstruction
Acinar cell injury
Defective intracellular transport
What is the process of duct obstruction leading to acute pancreatitis?
Gallstones, cancers, choledochoceles and parasites cause obstruction.
- enzyme-rich fluid accumulates in the interstitium
- lipase causes local fat necrosis and triggers “danger” signals that stimulate production of cytokines and inflammatory mediators.
This leads to edema, impaired blood flow and ischemic injury to acinar cells.
What is the process of primary acinar cell injury leading to acute pancreatitis?
Injury causes release of digestive enzymes, inflammation and auto-digestion of pancreatic tissue.
- oxidative stress may generate free radicals in acinar cells, leading to lipid oxidation and transcription factor activation (AP1 and NF-kB).
- release of intracellular proenzymes and lysosomal hydrolases.
- activation of enzymes leads to acinar cell injury.
What is the process of defective intracellular transport of proezymes within acinar cells in the development of acute pancreatitis?
Metabolic injury, EtOH and duct obstruction leads to delivery of proenzymes to the lysosomal compartment.
-intracellular activation of enzymes leads to acinar cell injury.
All inciting events of acute pancreatitis, in the end, lead to: (4)
Interstitial inflammation and edema
Proteolysis
Fat necrosis
Vessel wall damage and hemorrhage
What are the 2 major risk factors for acute pancreatitis?
Which patients are most likely to have these risk factors?
Alcoholism: M>F 6:1; younger age of onset
Gallstones: F>M 3:1; older age of onset (not all patients with stones get it)
What 5 features make up the morphology of acute pancreatitis?
Microvascular leak and edema
Fat necrosis
Acute inflammation
Pancreatic parenchymal destruction
Vessel destruction and hemorrhage
What is the morphology of mild vs. severe acute pancreatitis?
Mild - acute interstitial pancreatitis
Severe - acute necrotizing pancreatitis
What genes are risk factors for acute pancreatitis? (6)
- CFTR
- PRSS1
- SPINK1
- CASR
- CTRC
- CPA1
Symptoms of acute acute pancreatitis
Abdominal pain (cardinal sx) which may refer to the left shoulder and is constant
Anorexia, N/V
Increased serum lipase and amylase
Full blown pancreatitis is a…
What processes are occuring during full blown pancreatitis? (4)
What 2 severe complications may occur as a result?
Medical emergency!
Systemic inflammatory response, causing:
- leukocytosis
- DIC
- edema
- ARDS
Renal failure and shock may occur as a consequence.
What is the definition of chronic pancreatitis?
Prolonged inflammation of the pancreas associated with irreversible destruction of the exocrine parenchyma, fibrosis and, in late stages, destruction of the endocrine pancreas.
What are 3 major etiologies of chronic pancreatitis?
Long-standing obstruction of the pancreatic duct
Autoimmune injury
Hereditary pancreatitis (up to 25% of cases)
What is the pathogenesis of chronic pancreatitis?
It develops most often following repeated episodes of acute pancreatitis.
Fibrogenic cytokines (TGF-b and PDGF) lead to activation of periacinar myofibroblasts which results in fibrosis and collagen deposition.
What is autoimmune pancreatits associated with?
What are the symptoms?
IgG4-secreting plasma cells in the pancreas
It may mimic the signs and symptoms of pancreatic adenocarcinoma, but responds to steroid therapy
6 features of chronic pancreatitis
Repeated bouts of abdominal pain
Persistent back pain
Calcifications
Pseudocysts
Pancreatic exocrine insufficiency
DM
What is the morphology of chronic pancreatitis? (2)
Fibrosis, atrophy and dropout of acini
Variable dilation of the pancreatic ducts
What is the outcome of chronic pancreatitis?
Poor - 20-25 year mortality rate is approx. 50%
What is a pseudocyst in the pancreas?
What is the most common precipitating cause?
What is their progression?
A collection of necrotic and hemorrhagic material rich in pancreatic enzymes, but without epithelial lining.
Often occur following a bout of acute pancreatitis, especially one superimposed on chronic alcoholic pancreatitis.
They may resolve on their own, but can also become infected secondarily. Larger pseudocysts can compress of perforate into adjacent structures.
What is the role of CA19-9?
It is often elevated in patient with pancreatic adenocarcinoma. However, it is not sensitive/specific enough for screening, but it is used in evaluating a patient’s response to therapy.
4 risk factors of pancreatic adenocarcinoma
Cigarette smoking
High-fat diets
Chronic pancreatitis
DM
What are the clinical features of pancreatic carcinoma? (5 features)
May remain silent until they invade adjacent structures
-tumors of the body and tail don’t impinge the biliary tract, so they may not be painful
Pain is often the first symptom, but at that time it is often too extensive to cure.
Obstructive jaundice (in cancers of the head of the pancreas)
Weight loss, anorexia and generalized fatigue/malaise are signs of advanced disease
Migratory thrombophlebitis (Troussaeu sign) in 10% of patients
What are the most common locations of cancers of the pancreas?
60% in the head
15% in the body
5% in the tail
20% are diffuse
What morphological feature is characteristic of pancreatic adenocarcinoma?
A dense desmoplastic reaction
What mutations are associated with pancreatic cancer? (4)
KRAS
p16/CDKN2A
SMAD-4
TP53
