Acute & Chronic Pancreatitis

Question 1

Summarize the basic local and systemic pathophysiology of acute pancreatitis.

Answer 1

Acute inflammatory process of the pancreas that may also involve peri-pancreatic tissues and remote organs
Increasing incidence in U.S.
o 20% will have severe acute pancreatitis (necrosis)
o 5% overall mortality

Pathophysiology
Activation of zymogen granules in acinar cells
• Fusion with basolateral membrane (normally released through apical membrane into ductal lumen)
• Release into interstitial space

Recruitment of activated neutrophils
• Also able to convert trypsinogen to trypsin
• Trypsin able to activate elastase and phospholipase

Digestion of pancreatic and peripancreatic tissues
• Result: proteolysis, 3rd spacing, hemorrhage, necrosis
• 3rd spacing: inflamed pancreas → releases enzymes into periphery = causes vessels to be leaky → lose serum into interstitial space → get increased hematocrit relative to plasma
• Decreased intravascular volume (from 3rd spacing) → hypoperfusion → further inflammation and necrosis

Systemic illness due to bradykinin, peptides, vasoactive substances, histamine release
• Leads to vasodilation, increased vascular permeability, 3rd spacing

Result: Systemic inflammatory response syndrome (SIRS)
• Ultimately leads to multi-organ failure

Question 2

Acute pancreatitis: Clinical presentation

Answer 2

o Epigastric pain (radiating to back)
• Get relief by sitting, flexing trunk, and pulling knees up
o Nausea, vomiting

Question 3

Acute pancreatitis: lab findings

Answer 3

Amylase and lipase = initially increase together

Amylase:
• Can be elevated due to other conditions (ex: hypertriglycerides) = low sensitivity
• Returns to normal after 48-72 hours

Lipase:
• Remains elevated for 7-14 days
• More sensitive (85-100%) than amylase
• 3x increase in normal levels + classic abdominal pain = usually diagnostic
• BUT levels do NOT correlate with severity of disease

Question 4

Acute pancreatitis: radiographic findings

Answer 4

o CT & ultrasound: enlarged, edematous pancreas with associated pancreatic fluid
o Use to evaluate extent of damage and to determine cause (ex: gallstones)
• Necrosis usually not seen for 48-72 hours after onset

Question 5

Acute pancreatitis: complications

Answer 5

Local:
Necrosis
• Can be sterile or infected (diagnosed based on percutaneous biopsy)
• Based on CT scan
• Infected necrosis = needs antibiotic treatment; often needs surgical debridement
Pseudocysts
• Localized collection of pancreatic secretions without epithelial lining
• Develop over 4-6 weeks
• Occur in 10% patients
• Usually spontaneously resolve
• May cause pain, nausea/vomiting, become infected or bleed

Systemic (from release of inflammatory mediators and correlated with presence of necrosis)
• Pleural effusion and ARDS → Respiratory failure
• Acute kidney injury (renal failure)
• Hypotension/shock
• Coagulopathy (DIC)
• GI bleeding
• Metabolic disorders: hyperglycemia, hypocalcemia

Question 6

List the etiologies of acute pancreatitis and identify which are most common.

Answer 6

Etiology 
Obstructive:
•	Gallstones (45%)
•	Pancreas divisum
•	Tumors 
•	Choledochoceole 
•	Ascaris infection (worms)
•	Post ERCP
Toxins
•	Alcohol (35%)
•	Aminosalicylates
•	Falfyl
•	Sulfa pentamidine
•	DDI azathioprine 
Idiopathic (10%)

Risk factors
o	Smoking (relative risk 2.1-3.5x)

Question 7

Predict disease outcome of acute pancreatitis based on clinical presentation, laboratory values, and radiographic findings.

Answer 7

Main factors:
o Presence of pancreatic necrosis
o Secondary inflammatory mediators that perpetuate injury
o Renal function
o Hemoconcentration: indicates degree of intravascular hypovolemia from inflammatory cascade
o Number of different grading systems available

Prognosis
o Interstitial or edematous pancreatitis: 80-85%; self limiting, low mortality
o Necrotizing pancreatitis: 15-20%; severe, 20% mortality

Question 8

Describe the treatment of acute pancreatitis.

Answer 8

IV fluids (lots: 250-400 cc/hr)
o	Goal = prevent hypoperfusion and necrosis 

Pain relief

“Resting pancreas” (patient doesn’t eat)
o	Instead = enteral nutrition (because in catabolic state and need increased caloric intake)
o	Decreases infectious complications
o	Decreases hospital stay
o	Decreases mortality 
o	Decreased organ failure 

Prophylactic antibiotics
o Suspected infected necrosis = imipenem/meropenem
o Sterile necrosis = controversial role if needed
o During 1st 7-10 days, most patients meet criteria for Systemic Inflammatory Immune Response (SIRS) = antibiotics appropriate while doing work-up for infection

ERCP (endoscopic retrograde cholangiopancreatography)
o Endoscopic sphincterotomy and stone extraction in patients with obstruction

Question 9

Summarize the basic theories regarding the development of chronic pancreatitis.

Answer 9

Definition:
o Chronic inflammatory process → fibrosis and scarring
o Leads to endocrine and exocrine dysfunction
o Lots of variability in presentation and natural history

Pathophysiology
Sentinel event: toxins (alcohol) → pancreatic juice rich in high viscous protein
• Protein plugs precipitate in small ductules
• Block/damage larger ducts
Decreased production of lithostatin
• Plug and stone formation
Inflammatory response
• Early phase: influx of pro-inflammatory cells
• Second/late phase: cells → cytokines
• Recruits pro-fibrotic stellate cells → collagen
Alcohol is a direct pancreatic toxin

Question 10

Chronic Pancreatitis: clinical presentation

Answer 10

Lots of heterogeneity
Asymptomatic

Pain (85%)
•	 Mid-epigastric with radiation to back
•	Worse with food (post-prandial)
•	Episodic or chronic and steady
•	Chronic inflammation, increased intraductal pressure, noxious stimulation of pancreatic nerves 

Malabsorption = loss of exocrine pancreas
• After 80% of gland destroyed
• Results: weight loss, steatorrhea, vitamin deficiencies

Diabetes = loss of endocrine function
• When <10% of normal function

Nausea, vomiting

Question 11

Chronic Pancreatitis: lab findings

Answer 11

Amylase and lipase often normal (so values not helpful)

Histology = gold standard

Pancreatic function measured by secretin test
• Becomes abnormal when over 60% of exocrine function lost
• Correlates with onset of chronic abdominal pain

Question 12

Chronic Pancreatitis: radiographic findings

Answer 12

Abdominal x-ray: 30% cases have calcifications

Ultrasound
• Dilation of ducts, calcifications, change in pancreatic parenchyma
• 70% sensitivity

CT/MR
• Sensitivity of 75-90%

ERCP: 95% sensitivity
• Abnormal main and side branches, stricture, dilation, stones

Endoscopic ultrasound

Question 13

Chronic Pancreatitis: diagnosis

Answer 13

o Clinical symptoms + changes in pancreas structure/function

Question 14

Chronic Pancreatitis: complications

Answer 14

o	Pseudocysts
o	Bile duct obstruction 
o	Splenic vein thrombosis 
o	Pseudoaneurysms 
o	Pancreatic cancer

Question 15

List the etiologies of chronic pancreatitis and identify which are most common.

Answer 15

• Alcohol (70%)
• Idiopathic (20%)

Other (10%):
Pancreatic duct obstruction (tumor, trauma, pancreas divisum, fibrosis)
Cystic fibrosis
Hereditary pancreatitis
• Autosomal dominant disorder
• Affects gene for trypsinogen and CFTR gene
o Autoimmune pancreatitis
• Can mimic pancreatic cancer by presenting with obstructive jaundice and enlarged pancreatic head
• Often see increased levels of serum IgG4
Tropical pancreatitis
Hyperparathyroidism & hypertriglyceridemia (rare causes)

Question 16

Describe the treatment of chronic pancreatitis.

Answer 16

General:
o Stop ongoing toxins (alcohol and tobacco)
o Small low fat meals and hydration

Correct pancreatic insufficiency
o Pancreatic enzyme replacement (lipase, amylase, protease)
o Vitamin supplementation
o Medium chain TAGs (don’t need pancreas to digest)

Pain management
o Analgesia (narcotics)
o Endoscopy and/or ESWL if obstructive cause = shock waves to deliver pulse of energy to break up stones
o Celiac plexus block (block nerve stimulation)
Surgery
• Dilated main pancreatic duct
• Lateral pancreaticojejunostomy = decreases pressure in pancreatic duct = relieves pain

Monitor for chronic pancreatitis complications (ex: pancreatic cancer)