Acute Pancreatitis

Acute Pancreatitis

Acute Pancreatitis is an acute inflammatory process of the pancreas caused by premature activation of pancreatic digestive enzymes leading to autodigestion, inflammation, edema, necrosis, and systemic inflammatory response.

It ranges from:

• Mild self-limiting interstitial edema
  to
• Severe necrotizing pancreatitis with multiorgan failure.

Diagnostic Criteria (Revised Atlanta Classification)

Diagnosis requires 2 of 3 criteria:

Differential Diagnosis

Etiology

Remember:“I GET SMASHED”

Most common causes:

1. Gallstones(~40-70%).
2. Alcohol(~30%).

Common Causes

1. Gallstone Pancreatitis

Most common overall cause.

Mechanism:

• Transient obstruction of ampulla
• Bile reflux
• Pancreatic duct obstruction

Suggestive features:

• Female
• Obesity
• RUQ pain
• Elevated ALT (>150 IU/L strongly suggests biliary cause)

2. Alcoholic Pancreatitis

• Typically occurs after years of drinking.Usually requires >5 years of heavy alcoholism (not binge or social alcohol intake)
• Acute-on-chronic pancreatitis is common in patients with alcoholic chronic pancreatitis. Suspect it when a patient with a history of chronic alcohol use and chronic pancreatitis (calcifications, diabetes, steatorrhea) presents with a new episode of severe epigastric pain. 
• Imaging often shows acute inflammatory changes superimposed on chronic structural pancreatic damage, and serum amylase/lipase may be less elevated than expected or even normal due to loss of functional acinar tissue.

3. Hypertriglyceridemia

Usually TG >500 mg/dL
High risk >1000 mg/dL

Mechanism:Toxic free fatty acid release

Clues:

• Lactescent serum
• Diabetes
• Obesity

4. Drug-Induced Pancreatitis

• Azathioprine
• Valproate
• Didanosine
• Thiazides
• Furosemide
• GLP-1 agonists
• DPP4 inhibitors
• Estrogens

5. Post-ERCP Pancreatitis

Risk factors:

• Difficult cannulation
• Sphincterotomy
• Female sex
• Sphincter of Oddi dysfunction

Prevention:

• Rectal NSAIDs
• Pancreatic duct stent

6. Hypercalcemia

Causes:Hyperparathyroidism,Malignancy

Mechanism:Intrapancreatic trypsin activation

7. Autoimmune Pancreatitis

Associated with:IgG4 disease

Features:

• Painless jaundice
• Diffuse enlargement
• Steroid responsive

Pathophysiology

Central Event:

Premature activation of trypsinogen → trypsin inside pancreas.

Trypsin activates:Elastase/Phospholipase/Lipase

Result:Fat necrosis/Vascular injury/Hemorrhage/Cytokine storm

Systemic Pathophysiology

Massive cytokine release:TNF-α/IL-1/IL-6

Leads to:SIRS/Capillary leakARDS/ShockAKI/MODS

TYPES

1. Interstitial Edematous Pancreatitis(90%)

• Mild inflammation
• Good prognosis

2. Necrotizing Pancreatitis(10%)

• Pancreatic necrosis
• Peripancreatic necrosis
• Infected necrosis possible
• The diagnosis of necrotizing pancreatitis is typically made based on a contrast-enhanced CT scan, which reveals a lack of blood flow to the necrotic areas. (Note, however, that a CT scan shouldn’t be obtained solely for this purpose.)

Clinical Features

Pain(80-95% of patients):

• Sudden severe epigastric pain,(“boring” pain)
• Radiates to back(not always)
• Worse supine,eating(especially fatty meals), drinking
• Better leaning forward, Sitting up(Stretching of the retroperitoneum is reduced,Compression on the pancreas decreases.)Note-Acute pericarditis also relieved on Sitting up, leaning forward 

Associated Symptoms

• Nausea
• Vomiting
• Fever
• Abdominal distension
• Ileus

Examination Findings

Hemorrhagic Signs

Rare but severe.Suggest hemorrhagic pancreatitis.

Laboratory Diagnosis

Macroamylasemia and Macrolipasemia

These are benign biochemical conditions in which pancreatic enzymes bind to large molecules (usually immunoglobulins), forming high-molecular-weight complexes that cannot be easily filtered by the kidneys.

This leads to:

• Persistently elevated serum enzyme levels
• Reduced urinary excretion
• No true pancreatic injury

Other Labs

Imaging

1. Ultrasound

• First imaging in all patients.Must in all patients
• Purpose:Detect gallstones/CBD dilation
• Limitation:Pancreas poorly visualized due to gas

2. Contrast CT Abdomen

• Best for:Necrosis/Complications/Severity assessment
• Not needed routinely at admission.
• Ideal timing:After 2-3days(to allow for delineation of necrotic tissue) if severe/not improving.ACG (2024) Repeat CECT (or MRI) should be obtained only when there is failure to improve or clinical deterioration, or when local complications are suspected.
• Early CT is appropriate when:
• Diagnosis remains uncertain(Differentiate pancreatitis from perforated ulcer, mesenteric ischemia, bowel obstruction, ruptured AAA, etc.)
• Another abdominal emergency is suspected.
• Trauma is present.
• There is concern for complications requiring urgent intervention(Suspected pancreatic hemorrhage)

Why Repeat CT After Several Days?Pancreatic complications evolve over time:

Thus, CT performed later can identify complications that were absent or not apparent initially.

• A CT scan with contrast is safe

CT-Based Severity Assessment in Acute Pancreatitis

Balthazar Grading

Pancreatic Necrosis Scoring (Used in CTSI)

CT Severity Index (CTSI) Formula=Balthazar Score+Necrosis Score

Modified CT Severity Index (MCTSI)

Components

MCTSI Detailed Scoring

Extrapancreatic Complications in MCTSI

Include:

• Pleural effusion
• Ascites
• Vascular complications
• GI involvement
• Parenchymal complications

MCTSI Interpretation

4.Indications for ERCP 

When ERCP is NOT Recommended

• Routine or diagnostic ERCP should be avoided in acute pancreatitis because it may worsen pancreatitis.
• Patients with mild gallstone pancreatitis without cholangitis or persistent biliary obstruction do not require routine ERCP.

If the Need for ERCP is Uncertain

• Serial clinical assessment with repeat LFTs and bilirubin.
• MRCP – non-invasive evaluation of the biliary tree.
• EUS – highly sensitive for detecting occult CBD stones and helps avoid unnecessary ERCP.

4. MRI/MRCP

Useful for:

• Biliary obstruction
• Duct evaluation
• Necrosis characterization

Revised Atlanta Classification

Modified Marshall Scoring System in Acute Pancreatitis

Used in the Revised Atlanta Classification to define organ failure.

• Score ≥2 in any organ system = organ failure
• Persistent organ failure (>48 h) defines severe acute pancreatitis

Severity Scores

BISAP Score

Score ≥3:High mortality risk.

Management

1.Fluid Resuscitation

Controlled Goal-Directed Fluid Therapy(WATERFALL Trial) 

Preferred Fluid: Lactated Ringer’s (LR)

Advantages over normal saline:

• Less hyperchloremic acidosis
• Reduced inflammation
• Better pH balance
• Lower SIRS rates

Typical Regimen

• Bolus 10 mL/kg over 2 hours if hypovolemic
• Maintenance:1.5–3 mL/kg/hr

Assessing Fluid Responsiveness

Patients with pancreatitis are nearly always fluid-responsive; however, the administered fluid may rapidly leak out of the vascular space.

Clinical Parameters

• HR<120 ,BP≥65 mmHg
• Capillary refill <3
• Urine output >0.5ml/kg/hr

Why Avoid Excessive Fluids? Over-resuscitation causes:

• Abdominal compartment syndrome
• Pulmonary edema
• ARDS
• Increased mortality

2.Pain Management

Paracetamol-Scheduled not SOS,opioid-sparing.

Opioids(they promote ileus therefore kip it minimum)

• Commonly used:Fentanyl/Hydromorphone/Morphine
• Old concern:“Morphine causes sphincter of Oddi spasm”
• Current evidence:Clinically insignificant-Morphine acceptable

Multimodal Analgesia

• Ketamine infusion pain dose
• Epidural analgesia (selected ICU patients)

Avoid- NSAID due to the Risk of AKI 

3.Nutrition

Early Enteral Feeding(Within 24–48 hours if possible.)

Benefits:

• Preserves gut barrier
• Reduces infection
• Reduces bacterial translocation

–Diet-Low-fat solid diet(Fat thought to stimulate pancreas excessively.)

TPN only if enteral impossible.

4.Antibiotics

• NOT routinely indicated
• Do NOT give prophylactic antibiotics for sterile necrosis.
• Acute pancreatitis often produces a systemic inflammatory response (SIRS) that mimics sepsis, with:
• Fever
• Leukocytosis
• Tachycardia
• Hypotension/vasodilatory shock

These findings usually reflect sterile inflammation, not bacterial infection.During the first week, fever and leukocytosis are usually due to sterile pancreatic inflammation, as infected necrosis is uncommon in this period.

Indications

Only if:

• Infected necrosis
• Acute Ascending Cholangitis
• Extrapancreatic infection(Pneumonia/UTI/CLABSI)
• Diagnostic uncertainty

Signs of Infected Necrosis

• Recurrent Fever
• sepsis
• Gas in necrosis on CT
• Positive culture
• Procalcitonin of >3.5 ng/mL(sensitivity and specificity of ~90%)

Antibiotics That Penetrate Pancreas

• Carbapenems
• Piperacillin-tazobactam
• Quinolones
• Metronidazole 
• 3rd-4th generation cephalosporins

5.Exocrine Pancreatic Insufficiency (EPI) 

• Transient exocrine pancreatic dysfunction is common after acute pancreatitis, while persistent EPI is more likely after necrotizing or recurrent pancreatitis.
• Results in fat malabsorption, steatorrhea, weight loss, bloating, and deficiency of fat-soluble vitamins (A, D, E, K).

Management

Diagnosis

• Fecal elastase-1 <200 µg/g stool suggests EPI.
• <100 µg/g stool = severe EPI.
• Best performed after recovery or in patients with persistent steatorrhea, weight loss, or malnutrition—not during the acute inflammatory phase.

NOTE-

• Routine pancreatic enzyme supplementation is not indicated for all patients with acute pancreatitis. It is recommended only in patients with symptomatic or confirmed exocrine pancreatic insufficiency, particularly after necrotizing or chronic pancreatitis.

6.IAP Monitoring 

• Periodic measurement of IAP is recommended in all patients with severe acute pancreatitis (WSACS/IAP Guidelines)
•  especially those with:
• Persistent organ failure
• Massive fluid resuscitation
• Increasing abdominal distension
• Oliguria/anuria
• Rising ventilatory pressures or worsening oxygenation
• IAP is measured indirectly via the urinary bladder (gold standard).

7.Gallstone Pancreatitis Management

Urgent ERCP if:Cholangitis OR Persistent biliary obstruction

Not needed routinely in all gallstone pancreatitis.

8. Hypertriglyceridemia Pancreatitis Treatment

• Insulin infusion
• Treat DKA if present
• Fibrates later
• Plasmapheresis in selected severe cases

Complications

Management of Collections

Observation-Most asymptomatic collections require no treatment.

Drainage Indications

• Infection
• Gastric outlet obstruction
• Biliary obstruction
• Persistent pain
• Failure to thrive

Infected Pancreatic Necrosis

incidence of infected necrosis peaks 10-14 days after the onset of pancreatitis.The classic presentation would be a patient who initially improves, but subsequently deteriorates with worsening sepsis.

Major cause of late mortality.

Diagnosis

• Gas in collection on CT
• Clinical sepsis
• FNA(Fine-needle aspiration) rarely needed now

Management: Step-Up Approach

1. Antibiotics(2-4 weeks)
2. Percutaneous(PANTER trial)/endoscopic drainage
3. Minimally invasive necrosectomy if needed

Timing of Intervention

• Delay intervention whenever possible(POINTER trial )
• Ideally:≥4 weeks after onset
• Reason:Allows walling-off of necrosis.

Vascular Complications

Systemic Complications

ARDS in Pancreatitis

Due to:

• Cytokine-mediated lung injury
• Capillary leak

Major mortality contributor.

Abdominal Compartment Syndrome

Causes:Massive fluids/Ileus/Edema

Suspect if:

• Rising airway pressures
• Oliguria
• Tense abdomen

Measure bladder pressure.

 AKI in Pancreatitis

AKI in pancreatitis is usually multifactorial.

Major Mechanisms

1. Hypovolemia (Most Important Early Cause)

Acute pancreatitis causes:

• Massive third spacing
• Vomiting
• Reduced oral intake
• Capillary leak
• Sweating/tachypnea

This leads to:

• Reduced renal perfusion
• Prerenal AKI

2. Systemic Inflammatory Response Syndrome (SIRS)

Result:

• Renal ischemia
• Acute tubular injury

3. Persistent Hypotension/Shock

Shock causes:

• Renal hypoperfusion
• Ischemic ATN

Septic shock may occur later due to:

• Infected necrosis
• Secondary infections

4. Intra-Abdominal Hypertension (IAH)