Pancreas II

Question 1

Acute pancreatitis is defined as ?

Answer 1

• an inflammatory condition of the pancreas characterized clinically by:
  
  • abdominal pain
  • elevated levels of pancreatic enzymes in the blood

Question 2

What is the etiology of acute pancreatitis ?

Answer 2

gallstones and alcohol abuse

Question 3

What is the mechanism of gallstone pancreatitis ?

What is the end result?

Answer 3

• 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

Question 4

What protein gets activated a lot during during acute pancreatitis that leads to all the issues?

Answer 4

Trypsin

Question 5

Mechanisms of Alcohol Induced Pancreatitis

Answer 5

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

Question 6

What is Pathogenesis of Acute Pancreatitis ?

What is the role of the active enzymes

Answer 6

• Intraacinar activation of proteolytic enzymes
  
  • pancreatic autodigestion → viscious cycle of active enzymes damaging cells
    
    • Active enzymes (lipase,amylase, protease)
• 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

Question 7

What are the bodys systemic responses to aucte pancreatitis?

Answer 7

• 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

Question 8

Chronic pancreatitis is defined as ?

Answer 8

• A progressive fibro-inflammatory process of the pancreas that results in irreversible destruction of exocrine and endocrine parenchyma and fibrosis

Question 9

What are the causes of chronic pancreatitis?

Answer 9

• Long term alcohol abuse (most common)
• Cigarete smoking
• Hereditary pancreatitis
• Ductal obstruction
• Systemic disease
• Idiopathic pancreatitis

Question 10

What is the pathogenesis of chronic pancreatitis?

Answer 10

• 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

Question 11

What are the clinical manifestations of Chronic Pancreatitis?

Answer 11

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

Question 12

What is the pathogenesis of Pain in Pancreatitis?

Answer 12

• 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

Question 13

What physical manifestation can chronic pancreatitis present with?

Answer 13

fibrotic mass

Question 14

Is chronic pancreatitis always active or can it be asymptomatic?

Answer 14

asymptomatic over long periods of time

Question 15

What is the difference in the serum levels of amylase and lipase in chronic pancreatitis vs. acute?

Answer 15

• 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

Question 16

In acute pancreatitis what type of inflammation is present?

Answer 16

diffuse spread of inflammation

Question 17

What is the most common type of pancreatic cancer?

Pancreatic cancer arises from? What happens next?

Answer 17

• 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

Question 18

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?

Answer 18

•Activation of oncogene KRAS

•Inactivation of tumor suppressor genes such as
TP53

•Inactivation of DNA repair genes

Environmental factor: cigarette smoke

Question 19

All patients with pancratic cancer need to be tested for?

Answer 19

• For germ line mutations(BRCA 1 +2) and microstatelliete instability (means your mismatch repair gene isn’t working correctly)

Question 20

What are the clinical features of pancreatic cancer?

Answer 20

• Remains silent until they invade into adjacent structures

Question 21

What are the most common presenting symptoms in patients exocrine pancreatic cancer:

Answer 21

• Pain
  
  • ​Usually the first symptom
• Jaundice
  
  • ​When tumor blocks common bile duct of head of pancreas (about 60%)
• Weight loss

Question 22

Obstructive jaundice is associated with most cases of carcinoma of what?

Answer 22

Obstructive jaundice is associated with most cases of carcinoma of the head of the pancreas

Question 23

What are the signs of advanced disease?

Answer 23

• generalized malaise and weakness

Question 24

Adipose tissue inflammation from pancreatic cancer can lead to?

Answer 24

• Systemic cytokine response
• Abnormal adipokine secretion
• Lipolysis → weight loss

*Eventually these changes can cause peripheral insulin resistance and beta cell dysfuncton