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Acute and Chronic Pancreatitis¶

Chapter 359 | Part 10: Disorders of the Gastrointestinal System · Part 10 – Gastrointestinal Disorders · Chapter 359

Key Clinical Points¶

Diagnosis requires 2 of 3 criteria: typical epigastric pain, ≥3x upper limit of normal serum lipase/amylase, or confirumatory imaging.
Serum lipase is preferred over amylase due to higher specificity and longer elevation (7-14 days).
Severe acute pancreatitis is defined by persistent organ failure (≥48 hours) involving one or more systems.
Gallstones (30-60%) and alcohol (15-30%) are the primary causes of acute pancreatitis.
Hypertriglyceridemia (>1000 mg/dL) is a significant cause; apolipoprotein CII deficiency leads to recurrence.
Prophylactic antibiotics are no longer recommended for severe acute pancreatitis.
Fecal elastase-1 >200 μg/g is considered normal; <100 μg/g indicates severe exocrine pancreatic insufficiency (EPI).
Necrotizing pancreatitis is identified by a lack of parenchymal enhancement on contrast-enhanced CT.
Type 1 Autoimmune Pancreatitis (AIP) presents with 'sausage-shaped' enlargement and a 'capsule sign' on CT, often with high IgG4.
ERCP is primarily therapeutic; it should not be delayed in cases of suspected biliary obstruction.

DEFINITION & CLASSIFICATION¶

• Acute Pancreatitis: Inflammation of the pancreas. ◦ Evolution in 3 phases: → 1. Intrapancreatic enzyme activation and acinar cell injury → 2. Activation, chemoattraction, and sequestration of leukocytes/macrophages → 3. Effects of activated proteolytic enzymes and cytokines on distant organs ◦ Pathological range: Interstitial (blood supply maintained) to Necrotizing (blood supply interrupted). • Chronic Pancreatitis: Progressive inflammatory disease with irreversible loss of exocrine and endocrine function. ◦ Characterized by: Fibrosis, calcifications, and acinar cell atrophy. • Morphologic Features (Revised Atlanta Criteria): → Interstitial: Inflammation without recognizable tissue necrosis; shows parenchymal enhancement on CT. → Necrotizing: Inflammation with parenchymal/peripancreatic necrosis; lacks parenchymal enhancement on CT. → Acute pancreatic fluid collection: Peripancreatic fluid in interstitial pancreatitis, <4 weeks from onset, no necrosis, no wall. → Pancreatic pseudocyst: Encapsulated fluid collection, >4 weeks after onset of interstitial pancreatitis. → Acute necrotic collection (ANC): Collection with fluid and necrosis; no definable wall; occurs in necrotizing pancreatitis. → Walled-off necrosis (WON): Mature, encapsulated collection of necrosis; >4 weeks after onset of necrotizing pancreatitis.

Table 2: Revised Atlanta Definitions¶

Table 359-2 summarizes the morphologic distinctions: • Interstitial: Enhancement present, no necrosis. • Necrotizing: Lack of enhancement, presence of necrosis. • Acute fluid collection: <4 weeks, no wall, no necrosis. • Pseudocyst: >4 weeks, well-defined wall, minimal/no necrosis. • ANC: No definable wall, contains both fluid and necrosis. • WON: >4 weeks, well-defined wall, contains necrosis.

EPIDEMIOLOGY¶

• Prevalence: One of the most common primary GI diagnoses; \sim300,000 hospitalizations annually in the US. ◦ Incidence: 15-45/100,000 persons globally. • Demographics: → Higher incidence with age. → Higher rates among African Americans. • Costs: Median stay of 4 days; cost \sim6,000; annual cost \sim3 billion.

ETIOLOGY & PATHOPHYSIOLOGY¶

• Common Causes (80-90%): ◦ Gallstones: 30-60% of cases. ◦ Heavy alcohol use: 15-30% of cases. • Other Common Causes: → Hypertriglyceridemia (1-4%). → ERCP (especially after intervention). → Idiopathic. • Pathogenesis: → Theory: Autodigestion due to premature activation of proteolytic enzymes (trypsinogen, chymotrypsinogen) in the acinar cell rather than the intestinal lumen. → Factors facilitating activation: Endotoxins, viral infections, ischemia, oxidative stress, lysosomal calcium, direct trauma. • Genetic Factors: ◦ Primary driver: Control of trypsin activity. ◦ Variants identified: → 1. PRSS1 (Cationic trypsinogen) - Only variant sufficient to cause disease alone. → 2. SPINK1 → 3. CFTR → 4. CTRC → 5. CASR → 6. CLDN2 (Others are considered disease modifiers). • Table 1: Causes of Acute Pancreatitis ◦ Common: Gallstones, Alcohol, Hypertriglyceridemia, ERCP, Idiopathic. ◦ Uncommon: Drugs (azathioprine, 6-mercaptopurine, sulfonamides, estrogens, tetracycline, valproic acid, 5-ASA, DPP4 inhibitors), Connective tissue disorders/TTP, Pancreatic cancer, Hypercalcemia, Periampullary diverticulum, Pancreas divisum, Hereditary pancreatitis, Cystic fibrosis, Renal failure, Infections (mumps, coxsackievirus, etc.), Autoimmune, Trauma, Postoperative. ◦ Recurrent cases: Consider biliary tree disease, alcohol abuse, metabolic issues (hypercalcemia/triglyceridemia), anatomical variants (divisum), IPMN.

CLINICAL FEATURES¶

• Symptoms: → Pain: Primary symptom; steady and boring in the epigastrium; may radiate to back, chest, flanks, or lower abdomen. → Associated: Nausea, vomiting, abdominal distention (due to hypomotility). • Physical Examination: → General: Distressed/anxious patient; low-grade fever, tachycardia, hypotension. → Shock: Common due to hypovolemia (fluid exudation), kinin release, and systemic enzyme effects. → Jaundice: Infrequent; if present, suggests biliary obstruction or mass effect. → Skin: Erythematous nodules (pancreatic panniculitis) from fat necrosis (rare). → Pulmonary: 10-20% have basilar rales, atelectasis, or pleural effusion (mostly left-sided). → Signs of Severity: → Cullen's sign: Periumbilical discoloration (hemoperitoneum). → Turner's sign: Flank discoloration (tissue breakdown of hemoglobin from severe necrosis). • Laboratory Data: → Amylase/Lipase: ≥3x upper limit of normal (Amylase drops after 3-7 days; Lipase remains high for 7-14 days). → Leukocytosis: 15,000-20,000 leukocytes/μL. → Hemoconcentration: Hematocrit >44%. → Prerenal Azotemia: Elevated BUN. → Hyperglycemia: Common. → Hypocalcemia: \sim25% of patients. → Hyperbilirubinemia: >4.0 mg/dL in \sim10% of patients. → ALT: >3 imes upper limit strongly suggests gallstone etiology.

DIFFERENTIAL DIAGNOSIS¶

• Common Mimics: → Perforated Viscus (e.g., peptic ulcer). → Acute Cholecystitis/Biliary Colic (Amylase may be elevated in both; ultrasound helps differentiate). → Mesenteric Vascular Occlusion: Suspected in elderly with leukocytosis, distention, and bloody diarrhea. → Diabetic Ketoacidosis (DKA): Mimics pain and high amylase; however, lipase is usually normal and imaging is normal. • Other Considerations: → Renal colic. → Inferior myocardial infarction. → Dissecting aortic aneurysm. → Connective tissue disorders/Vasculitis (SLE, PAN).

DIAGNOSTIC APPROACH¶

Initial Imaging: • Abdominal Ultrasound: First-line; evaluates gallstones and common bile duct dilation.
Diagnostic Criteria (Need 2 of 3): • Typical epigastric pain radiating to the back. • Serum lipase or amylase ≥3x upper limit of normal. • Confirmatory findings on cross-sectional imaging.
Follow-up Imaging: • CT with IV contrast: Performed 3-5 days into hospitalization if not responding to care; used to assess for necrosis and local complications.
Fecal Elastase (for Chronic Pancreatitis/EPI): • >200 μg/g: Normal. • 100-200 μg/g: Mild-moderate EPI. • <100 μg/g: Severe EPI.
ERCP: • Primarily therapeutic for biliary obstruction; not used as primary diagnostic tool due to risk of complications (EUS and MRI/MRCP preferred). • Most sensitive for detecting bile duct stones.

MANAGEMENT & TREATMENT¶

Fluid Resuscitation: • Primary intervention; most important treatment. • Failure to respond → consider ICU/step-down for hemodynamic monitoring and organ failure management.
Pain Control: • Essential component of care.
Antibiotics: • Prophylactic antibiotics are NOT recommended for severe acute pancreatitis.
Nutrition: • Oral intake: Resume if patient is hungry, has normal bowel function, and no nausea/vomiting. • Initial meal: Clear or full liquid; low-fat solid diet early in mild cases.
ERCP Management: • Biliary pancreatitis: Do not delay ERCP if high clinical suspicion of biliary obstruction exists.
Monitoring Severity (Table 3): • Risk Factors: Age >60, BMI >30, Comorbidities (Charlson index). • Markers at ≤24h: SIRS (2+ criteria), APACHE II (≥8), Hemoconcentration (Hct >44%), BUN (>20 mg/dL), BISAP score (≥3 present). • Organ Failure (Modified Marshall): Cardiovascular (SBP <90, HR >130), Pulmonary (PaO_2 <60), Renal (Creatinine >2.0 mg/dL).

COMPLICATIONS & PROGNOSIS¶

• Local Complications (Table 4): → Fluid collections: Acute necrotic collection, Walled-off necrosis, Pseudocyst. → Structural: Pancreatic duct disruption, Pancreatic ascites, Chylous ascites. → Vascular: Splanchnic thromboses (splenic vein, SMV, portal vein). → Other: Gastric outlet obstruction, Biliary obstruction, Colon perforation. • Systemic Complications (Table 4): → Pulmonary: Pleural effusion, Atelectasis, ARDS. → Cardiovascular: Hypotension, Hypovolemia, Pericardial effusion. → Hematologic: DIC, Gastrointestinal hemorrhage, Hemorrhagic necrosis. → Renal: Oliguria (<300 mL/d), Azotemia, ATN. → Metabolic: Hyperglycemia, Hypertriglyceridemia, Hypocalcemia. → CNS: Encephalopathy, Psychosis, Fat emboli. • Chronic Pancreatitis Complications (Table 7): → Chronic abdominal pain, Exocrine pancreatic insufficiency, Diabetes mellitus, Splanchnic venous thrombosis, Metabolic bone disease (osteoporosis). → Biliary stricture/cirrhosis, Pancreatic duct stricture, Pseudocyst, Pancreatic cancer. → Malnutrition, micronutrient deficiencies.

SPECIAL POPULATIONS¶

• Autoimmune Pancreatitis (AIP) Comparison (Table 6): → Type 1: Mean age \sim70s; 75% male; Serum IgG4 elevated in \sim66%; Associated with IgG4-related disease; Histology shows abundant IgG4 staining (≥10 cells/hpf); Risk of relapse moderate to high (20-60%). → Type 2: Mean age \sim50s; No sex predilection; Serum IgG4 elevated in \sim25%; Idiopathic duct-centric; Histology shows scant IgG4 staining (<10 cells/hpf); Risk of relapse low (<10%). • TIGAR-O System (Table 5/9): → Toxic-metabolic: Alcohol, Tobacco, Hypercalcemia, Hyperlipidemia, Chronic renal failure. → Idiopathic: Early onset, Late onset, Tropical. → Genetic: PRSS1, CFTR, CASR, CTRC, SPINK1. → Autoimmune: Type 1 (IgG4-related), Type 2 (duct-centric). → Recurrent/Severe: Postnecrotic, Recurrent acute, Vascular disease, Radiation induced. → Obstructive: Pancreas divisum, Duct obstruction (tumor), Preampullary cysts, Posttraumatic strictures.

KEY PEARLS & HIGH-YIELD POINTS¶

• Diagnostic Pearls: → Use Lipase for diagnosis; it stays elevated longer than Amylase. → Rule of 2: Need 2 of (Pain, ≥3x Lipase/Amylase, Imaging). → Timing matters: Pseudocysts and WON typically develop after 4 weeks; Acute fluid collections are <4 weeks. • Therapeutic Pearls: → Fluid resuscitation is the cornerstone of management. → No prophylactic antibiotics for severe cases. → ERCP is a 'rescue' or therapeutic tool for biliary obstruction, not a primary diagnostic step.

Reference Tables¶

TABLE 359-1 Causes of Acute Pancreatitis Common Causes Gallstones (including microlithiasis) Heavy alcohol use Severe…¶

Harrison's 22e, p.2744

Common Causes
Gallstones (including microlithiasis)
Heavy alcohol use
Severe hypertriglyceridemia
Endoscopic retrograde cholangiopancreatography (ERCP), especially after
therapeutic intervention
Idiopathic
Uncommon Causes
Drugs (azathioprine, 6-mercaptopurine, sulfonamides, estrogens, tetracycline,
valproic acid, 5-aminosalicylic acid [5-ASA], dipeptidyl peptidase-4 [DPP4]
inhibitors)
Connective tissue disorders and thrombotic thrombocytopenic purpura (TTP)
Pancreatic cancer
Hypercalcemia
Periampullary diverticulum
Pancreas divisuma
Hereditary pancreatitis
Cystic fibrosis
Renal failure
Infections (mumps, coxsackievirus, cytomegalovirus, echovirus, parasites)
Autoimmune (e.g., type 1 and type 2)
Trauma (especially blunt abdominal trauma)
Postoperative (abdominal and nonabdominal operations)
Causes to Consider in Patients With Recurrent Bouts of Acute
Pancreatitis Without an Obvious Etiology
Occult disease of the biliary tree or pancreatic ducts, especially microlithiasis/
biliary sludge
Alcohol abuse
Metabolic: Hypertriglyceridemia, hypercalcemia
Anatomic: Pancreas divisuma
Pancreatic cancer
Intraductal papillary mucinous neoplasm (IPMN)
Hereditary pancreatitis
Cystic fibrosis
Idiopathic

TABLE 359-2 Revised Atlanta Definitions of Morphologic Features of Acute Pancreatitis Types of Acute Pancreatitis…¶

Harrison's 22e, p.2746

	DEFINITION	COMPUTED TOMOGRAPHY FEATURES
Types of Acute Pancreatitis
Interstitial pancreatitis	Acute inflammation of the pancreatic parenchyma and peripancreatic tissues, but without recognizable tissue necrosis	Pancreatic parenchyma enhancement by IV contrast agent and without peripancreatic necrosis
	Inflammation associated with pancreatic parenchymal and/or peripancreatic necrosis
Morphologic Features
Acute pancreatic fluid collection	Peripancreatic fluid associated with interstitial edematous pancreatitis with no associated peripancreatic necrosis. This term applies only to areas of peripancreatic fluid seen within the first 4 weeks after onset of interstitial edematous pancreatitis and without the features of a pseudocyst.	Occurs in the setting of interstitial pancreatitis Homogeneous collection with fluid density Confined by normal peripancreatic fascial planes No definable wall encapsulating the collection Adjacent to pancreas (no intrapancreatic extension)
	An encapsulated collection of fluid with a well-defined wall usually outside the pancreas with minimal or no necrosis. This usually occurs >4 weeks after onset of interstitial edematous pancreatitis.
Acute necrotic collection (ANC)	A collection containing variable amounts of both fluid and necrosis associated with necrotizing pancreatitis; the necrosis can involve the pancreatic parenchyma and/or the peripancreatic tissues.	Occurs in the setting of acute necrotizing pancreatitis Heterogeneous and nonliquid density of varying degrees in different locations (some appear homogeneous early in their course) No definable wall encapsulating the collection Location—intrapancreatic and/or extrapancreatic
	A mature, encapsulated collection of pancreatic and/or peripancreatic necrosis that has developed a well-defined inflammatory wall. WON usually occurs >4 weeks after onset of acute necrotizing pancreatitis.

TABLE 359-3 Severity Assessment of Acute Pancreatitis Risk Factors for Increased Severity • Age >60 years • Obesity…¶

Harrison's 22e, p.2748

Risk Factors for Increased Severity
• Age >60 years
• Obesity, BMI >30 kg/m2
• Comorbid disease (based on Charlson comorbidity index)
Markers of Severity at Admission or Within 24 h
• SIRS—defined by presence of 2 or more criteria:
• Core temperature <36° or >38°C
• Heart rate >90 beats/min
• Respirations >20/min or PCO <32 mmHg
2
• White blood cell count >12,000/μL, <4000/μL, or 10% bands
• APACHE II (≥8 at 24 h)
• Hemoconcentration (hematocrit >44%)
• Admission BUN (>20 mg/dL)
• BISAP score (≥3 present)
• (B) BUN >25 mg/dL
• (I) Impaired mental status
• (S) SIRS: ≥2 of 4 present
• (A) Age >60 years
• (P) Pleural effusion
• Organ failure (Modified Marshall score) (≥1 present):
• Cardiovascular: systolic BP <90 mmHg, heart rate >130 beats/min
• Pulmonary: PaO <60 mmHg
2
• Renal: serum creatinine >2.0 mg/dL
Markers of Severity during Hospitalization
• Elevated C-reactive protein (CRP) (variable thresholds >100 mg/L reported)
• Persistent organ failure (≥48 h)
• Pancreatic or extrapancreatic necrosis

TABLE 359-4 Complications of Acute Pancreatitis Local Pancreatic/peripancreatic fluid collections (Table 359-2):¶

Harrison's 22e, p.2749

Local
Pancreatic/peripancreatic fluid collections (Table 359-2):
Acute necrotic collection (sterile or infected)
Walled-off necrosis (sterile or infected)
Pancreatic pseudocyst
Disruption of main pancreatic duct or secondary branches
Pancreatic ascites
Chylous ascites (secondary to disruption of lymphatic ducts)
Involvement of contiguous organs by necrotizing pancreatitis (e.g., colon
perforation)
Splanchnic thromboses (splenic vein, superior mesenteric vein, and/or portal
vein)
Gastric outlet obstruction
Biliary obstruction (jaundice)
Systemic
Pulmonary
Pleural effusion
Atelectasis
Mediastinal fluid
Pneumonitis
Acute respiratory distress syndrome
Cardiovascular
Hypotension
Hypovolemia
Nonspecific ST-T changes in electrocardiogram simulating myocardial
infarction
Pericardial effusion
Hematologic
Disseminated intravascular coagulation
Gastrointestinal hemorrhage
Peptic ulcer disease
Erosive gastritis
Hemorrhagic pancreatic necrosis with erosion into major blood vessels
Variceal hemorrhage secondary to splanchnic thrombosis
Renal
Oliguria (<300 mL/d)
Azotemia
Renal artery and/or renal vein thrombosis
Acute tubular necrosis
Metabolic
Hyperglycemia
Hypertriglyceridemia
Hypocalcemia
Encephalopathy
Sudden blindness (Purtscher’s retinopathy)
Central nervous system
Psychosis
Fat emboli
Fat necrosis
Subcutaneous tissues (erythematous nodules)
Bone
Miscellaneous (mediastinum, pleura, nervous system)

TABLE 359-5 Classification of Chronic Pancreatitis: The TIGAR-O System Toxic-metabolic Alcoholic Tobacco smoking…¶

Harrison's 22e, p.2750

Toxic-metabolic
Alcoholic
Tobacco smoking
Hypercalcemia
Hyperlipidemia (hypertriglyceridemia)
Chronic renal failure
Idiopathic
Early onset
Late onset
Tropical
Genetic
Cationic trypsinogen (PRSS1)
Cystic fibrosis transmembrane conductance regulator gene (CFTR)a
Calcium-sensing receptor (CASR)a
Chymotrypsin C gene (CTRC)a
Pancreatic secretory trypsin inhibitor gene (SPINK1)a
Autoimmune
Type 1 autoimmune pancreatitis (associated with IgG4-related disease)
Type 2 autoimmune pancreatitis (idiopathic duct-centric chronic pancreatitis)
Recurrent and severe acute pancreatitis
Postnecrotic (severe acute pancreatitis)
Recurrent acute pancreatitis
Vascular diseases/ischemia
Radiation induced
Obstructive
Pancreas divisuma
Duct obstruction (e.g., tumor)
Preampullary duodenal wall cysts
Posttraumatic pancreatic duct strictures

TABLE 359-6 Comparison of the Autoimmune Pancreatitis (AIP) Subtypes Age at diagnosis, mean Male sex Serum IgG4…¶

Harrison's 22e, p.2751

	TYPE 1 AIP	TYPE 2 AIP
Age at diagnosis, mean	Seventh decade	Fifth decade
	75%
Serum IgG4 elevation	~66%	~25%
	50%
Histologic findings:
	++
Periductal inflammation	++	++
	++
Obliterative phlebitis	++	+
	–
IgG4 tissue staining	Abundant (≥10 cells/hpf)	Scant (<10 cells/hpf)
	~100%
Risk for relapse	Moderate to high (20–60%)	Low (<10%)
	Yes

TABLE 359-7 Complications of Chronic Pancreatitis Chronic abdominal pain Exocrine pancreatic insufficiency Diabetes…¶

Harrison's 22e, p.2753

Chronic abdominal pain Exocrine pancreatic insufficiency Diabetes mellitus Splanchnic venous thrombosis Metabolic bone disease (osteoporosis)	Biliary stricture and/or biliary cirrhosis Pancreatic duct stricture Pseudocyst Pancreatic cancer Malnutrition, micronutrient deficiencies