Pancreas II Flashcards
Acute pancreatitis is defined as ?
- an inflammatory condition of the pancreas characterized clinically by:
- abdominal pain
- elevated levels of pancreatic enzymes in the blood
What is the etiology of acute pancreatitis ?
gallstones and alcohol abuse
What is the mechanism of gallstone pancreatitis ?
What is the end result?
- Reflux of bile into the pancreatic duct because of transient obstruction of the ampulla with with gallstones
- OR obstruction at the ampulla by stone(s) or edema
End result: Pancreas tissue gets autodigested
What protein gets activated a lot during during acute pancreatitis that leads to all the issues?
Trypsin
Mechanisms of Alcohol Induced Pancreatitis
Selective mechanisms:
• Sensitization of acinar cells due to cholecystokinin (CCK)-induced premature activation of zymogens
• Generation of toxic metabolites, such as acetaldehyde
• Activation of pancreatic stellate cells by acetaldehyde and oxidative stress → increased collagen and other matrix proteins
FYI
-Cholecystokinin (CCK) is the major hormone responsible for gallbladder contraction and pancreatic enzyme secretion.
- Digestive enzymes are released in inactive forms called zymogens. This is necessary to prevent the digestive enzymes from digesting the cells that produce them.
- Pancreatic zymogens are normally only activated after they reach the small intestine. An enzyme, enterokinase, cleaves a peptide from trypsinogen, forming the active enzyme trypsin. Trypsin then activates the other enzymes. A dangerous situation occurs if there is inappropriate formation of trypsin in the pancreas. This can cause pancreatitis, where trypsin digests pancreatic tissue and triggers an inflammatory response
What is Pathogenesis of Acute Pancreatitis ?
What is the role of the active enzymes
- Intraacinar activation of proteolytic enzymes
- pancreatic autodigestion → viscious cycle of active enzymes damaging cells
- Active enzymes (lipase,amylase, protease)
- pancreatic autodigestion → viscious cycle of active enzymes damaging cells
- Microcirculatory Injury:
- vasoconstriction, capillary stasis, progressive ischemia → vascular permeability and edema
- Leukocytle chemoattraction, release of cytokines and oxidative stress:
- rapid worsening of pancreatic damage and necrosis
What are the bodys systemic responses to aucte pancreatitis?
-
The systemic inflammatory response syndrome (SIRS) is mediated by:
- activated pancreatic enzymes
- cytokines released into the circulation(allows inflammation to spread)
- Myocardial depression and shock due to vasoactive peptides and a myocardial depressant factor
- Acute renal failure due to hypovolemia and hypotension
-
Metabolic complications such as:
- hyperlipidemia,
- hyperglycemia,
- hypoglycemia
- diabetic ketoacidosis
-
Bacterial translocation → local and systemic infection (sepsis)
- Gut barrier becomes compromised and bacteria leaks into gut
Chronic pancreatitis is defined as ?
- A progressive fibro-inflammatory process of the pancreas that results in irreversible destruction of exocrine and endocrine parenchyma and fibrosis
What are the causes of chronic pancreatitis?
- Long term alcohol abuse (most common)
- Cigarete smoking
- Hereditary pancreatitis
- Ductal obstruction
- Systemic disease
- Idiopathic pancreatitis
What is the pathogenesis of chronic pancreatitis?
- Hypersecretion of digestive enzymes, which doesn’t become neutralized by an increase in ductal bicarbonate secretion
- The Inflammatory changes
- Pancreatic fibrosis and acinar cell loss
What are the clinical manifestations of Chronic Pancreatitis?
Two primary clinical manifestations:
- abdominal pain (usually occurs 2-3 months beforehand)
- The pain is typically epigastric, often radiates to the back
- pancreatic insufficiency
- Clinically significant protein and fat deficiencies (mal-absorption) after over 90% of pancreatic function is lost
- Fat malabsorption: steatorrhea usually occurs prior to protein deficiencies
- Pancreatic diabetes: alpha cells are affected as well→an increased risk of hypoglycemia
What is the 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 (sub. P is increased)
• inflammatory mediators further sensitize and/or activate neurons
What physical manifestation can chronic pancreatitis present with?
fibrotic mass
Is chronic pancreatitis always active or can it be asymptomatic?
asymptomatic over long periods of time
What is the difference in the serum levels of amylase and lipase in chronic pancreatitis vs. acute?
- the serum amylase and lipase concentrations tend to be normal in chronic pancreatitis, but are almost always elevated with acute disease
- the levels are normal in chronic because its a progressive situation so the body can compensate
In acute pancreatitis what type of inflammation is present?
diffuse spread of inflammation
What is the most common type of pancreatic cancer?
Pancreatic cancer arises from? What happens next?
- Infiltrating ductal adenocarcinoma is the most common type?
- Arises from well-defined noninvasive precursor lesions known as pancreatic intraepithelial neoplasia (PanIN) (treatable at this stage)
- It is a stepwise process - progressive cancer
What are the multiple genetic mutations that can occur that increases your risk for getting pancreatic cancer?
What is the strongest environmental factor that increases your risk for getting pancreatic cancer?
•Activation of oncogene KRAS
•Inactivation of tumor suppressor genes such as
TP53
•Inactivation of DNA repair genes
Environmental factor: cigarette smoke
All patients with pancratic cancer need to be tested for?
- For germ line mutations(BRCA 1 +2) and microstatelliete instability (means your mismatch repair gene isn’t working correctly)
What are the clinical features of pancreatic cancer?
- Remains silent until they invade into adjacent structures
What are the most common presenting symptoms in patients exocrine pancreatic cancer:
-
Pain
- Usually the first symptom
-
Jaundice
- When tumor blocks common bile duct of head of pancreas (about 60%)
- Weight loss
Obstructive jaundice is associated with most cases of carcinoma of what?
Obstructive jaundice is associated with most cases of carcinoma of the head of the pancreas
What are the signs of advanced disease?
- generalized malaise and weakness
Adipose tissue inflammation from pancreatic cancer can lead to?
- Systemic cytokine response
- Abnormal adipokine secretion
- Lipolysis → weight loss
*Eventually these changes can cause peripheral insulin resistance and beta cell dysfuncton
