Exam III Pancreas PT 2 Flashcards
Acute Pancreatitis
An inflammatory condition of the pancreas characterized clinically by abdominal pain, and elevated levels of pancreatic enzymes in the blood.
Etiology:
-Gallstones and alcohol abuse
Mechanisms of Gallstone pancreatitis:
- Reflux of bile into the pancreatic duct because of transient obstruction of the ampulla with gallstones
- Or obstruction at the ampulla by stone(s) or edema
Alcohol-induced Pancreatitis
Selective Mechanisms:
- Sensitization of acinar cells to cholecystokinin (CCK)-induced premature activation of zymogens
- Generation of Toxic metabolites, such as acetaldehyde (can come from alcohol)
- Activation of pancreatic stellate cells by acetaldehyde and oxidative stress-> increased collagen and other matrix problems.
Pathogenesis of Acute Pancreatitis
Intra-acinar activation of proteolytic enzymes:
-Pancreatic autodigestion, setting up a vicious cycle of active enzymes damaging cells
Microcirculatory injury:
-Vasoconstriction, capillary stasis, progressive ischemia-> increased vascular permeability and edema
Leukocyte chemoattraction, release of cytokines and oxidative stress:
-Rapid worsening of pancreatic damage and necrosis
Systemic Responses in Acute Pancreatitis
The systemic inflammatory response syndrome (SIRS) is mediated by:
- Activated pancreatic enzymes
- Cytokines released into circulation
- Myocardial depression and shock due to vasoactive peptides and a myocardial depressant factor
-Acute renal failure due to hypovolemia and hypotension
-Metabolic complications-> hyperlipidemia, hyperglycemia, hypoglycemia, and diabetic ketoacidosis
Bacterial translocation-> local and systemic infection
Chronic Pancreatitis
A progressive fibro-inflammatory process of the pancreas that results in irreversible destruction of exocrine and endocrine parenchyma and fibrosis
Etiology: The most common Cause of chronic pancreatitis by far is long-term alcohol abuse
- Cigarette smoking
- Hereditary pancreatitis
- Ductal obstruction
- Systemic disease
- Idiopathic pancreatitis
Chronic Pancreatitis Pathogenesis
Hypersecretion of digestive enzymes, which is not neutralized for by an increase in ductal bicarbonate secretion
The inflammatory changes
Pancreatic fibrosis and acinar cell loss
Chronic Pancreatitis Clinical Features
Two primary clinical manifestations:
-Abdominal pain
–The pain is typically epigastric, often radiates to the back
-Pancreatic insufficiency
–Clinically significant protein and fat deficiencies after over 90% of pancreatic function is lost
—Fat malabsorption: steatorrhea usually occurs prior to protein deficiencies
—Pancreatic diabetes – Also alpha cells are affected as well-> an increased risk of hypoglycemia
Pathogenesis of Pain in Pancreatitis
Biological factors such as NGF (nerve growth factor) that are produced in chronic pancreatitis and mast cells can sensitize the nociceptor neuron by upregulating substance P
Inflammatory mediators further sensitize and / or activate neurons
Chronic or Acute Pancreatitis
Chronic Pancreatitis may be:
- Asymptomatic over long periods of time
- Can be present with a fibrotic mass
- The serum amylase and lipase concentrations tend to be normal in chronic pancreatitis, but are almost always elevated with acute disease
Pathogenesis of Pancreatic Cancer
One of the most aggressive of the solid malignancies
Infiltrating ductal adenocarcinoma is the most common type
Arise from well-defined noninvasive precursor lesions known as pancreatic intraepithelial neoplasia (PanIN)
There is a progression in the pancreatic carcinogenesis
Multiple genetic mutations:
-Activation of oncogene KRAS
-Inactivation of tumor suppressor genes such as TP53
-Inactivation of DNA repeair genes
The strongest environmental influence is cigarette smoking.
Pancreatic Cancer Clinical Features
Remains silent until they invade into adjacent structures
The most common presenting symptoms in PTs with exocrine pancreatic cancer
-Pain
-Jaundice
-Weight loss
Pain is usually the first symptom
Obstructive jaundice is associated with the most cases of carcinoma of the head of the pancreas
Weight loss, anorexia, and generalized malaise and weakness: signs of advanced disease
Interactions of Pancreatic Cancer & Adipose Tissue Inflammation
Adipose tissue inflammation, which leads to:
- Systemic Cytokine response
- Abnormal adipokine secretion
- Lipolysis
Eventually, these changes cause peripheral insulin resistance and B cell dysfunction
