Epigastric Pain: A Differential Diagnosis Approach for Emergency Department Evaluation

Case Study

A 41-year-old woman arrived at the emergency department experiencing severe and continuous epigastric pain that had persisted for 24 hours. Notably, the pain radiated directly to her back. This was accompanied by progressively worsening nausea and vomiting, with bile-stained vomit, although no blood was present. The patient reported previous, less severe episodes of similar abdominal pain, typically occurring after consuming heavy meals. These prior episodes, however, had always resolved within a few hours. Her medical history included two pregnancies and two live births, with her last menstrual period two weeks prior to presentation. She denied any alcohol consumption.

Upon physical examination, she was afebrile. Her vital signs included a heart rate of 115 beats per minute, blood pressure of 128/86 mmHg, and a respiratory rate of 18 breaths per minute. Her abdomen was not distended, and there were no surgical scars, visible masses, or bruising around her umbilicus or flanks. Bowel sounds were hypoactive. Palpation of the epigastrium revealed marked tenderness, but no guarding or rebound tenderness was elicited. The remainder of her abdomen was soft and non-tender. No organomegaly or masses were appreciated.

Laboratory investigations revealed a significantly elevated white blood cell count of 17.2 × 103 cells/μL (normal range: 4.1–10.9 × 103 cells/uL), an amylase level of 1545 u/L (normal range: 30–110 u/L), and a lipase level of 1134 u/L (normal range: 7–60 u/L). Liver function tests were also abnormal, with an ALT of 245 u/L (normal range: 7–56 u/L) and AST of 263 u/L (normal range: 5–35 u/L). Her serum glucose was elevated at 156 mg/dL (normal range: 65–110 mg/dL), and LDH was 180 u/L (normal range: 0–250 u/L). An abdominal X-ray series showed gas throughout the small and large bowel and a focal dilated loop of proximal small bowel without air-fluid levels. There was no evidence of free air under the diaphragm.

Diagnosis

Differential Diagnosis of Epigastric Abdominal Pain

Epigastric pain, located in the upper central region of the abdomen, is a common presenting complaint in the emergency department. Establishing an accurate differential diagnosis is crucial for timely and appropriate management. The table below outlines a differential diagnosis for epigastric abdominal pain, considering various conditions and their typical clinical presentations.

Table 1: Differential Diagnosis of Epigastric Pain

Condition	History and Physical Examination Findings
Gastroenteritis	Nausea, significant vomiting, diarrhea, myalgia, fever, typically mild abdominal tenderness. Often associated with recent travel or foodborne illness.
Acute Gastritis	Burning or gnawing epigastric pain, history of NSAID use or alcohol consumption, mild abdominal tenderness. May be related to stress or Helicobacter pylori infection.
Acute Cholecystitis	Right upper quadrant or epigastric pain radiating to the right back or shoulder, nausea, vomiting, fever, positive Murphy’s sign. Often associated with fatty food intake.
Peptic Ulcer Disease (PUD)	Intermittent burning epigastric pain, pain relieved by food intake in duodenal ulcer, worsened by food intake in gastric ulcer. Nausea, H. pylori risk factors, NSAID or steroid use.
Perforated Ulcer	Sudden onset of severe epigastric pain, rapidly progressing to diffuse abdominal tenderness, abdominal rigidity, rebound tenderness, signs of peritonitis.
Pancreatitis	Epigastric pain radiating to the back, nausea, vomiting, anorexia, fever, tachycardia. Risk factors include cholelithiasis and alcohol abuse, though other causes exist.
Appendicitis	Initial periumbilical pain migrating to the right lower quadrant (McBurney’s point), nausea, vomiting, anorexia, fever, Rovsing’s sign, psoas sign, obturator sign.
Small Bowel Obstruction	Abdominal distension, crampy intermittent abdominal pain, vomiting (bilious or feculent), high-pitched bowel sounds early, absent bowel sounds late. History of adhesions, hernia, or neoplasms.
Mesenteric Ischemia	Severe abdominal pain often described as “out of proportion to physical exam findings,” nausea, vomiting, risk factors for cardiac emboli (atrial fibrillation), bloody diarrhea in severe cases.
Ruptured Abdominal Aortic Aneurysm (AAA)	Severe abdominal, back, or flank pain, pulsatile abdominal mass, hypotension, elderly male smoker with cardiovascular risk factors. A surgical emergency.
Myocardial Infarction (Referred Pain)	Atypical presentation of chest pain, more common in women, elderly, and diabetics. Epigastric pain, nausea, vomiting, shortness of breath, diaphoresis. Cardiovascular risk factors present.

NSAID = Nonsteroidal Anti-Inflammatory Drugs

Diagnosis for This Patient

The most likely diagnosis for this patient is acute pancreatitis, strongly suspected to be secondary to cholelithiasis (gallstones). Her clinical presentation is highly characteristic of acute pancreatitis: severe epigastric pain radiating to the back, accompanied by nausea and vomiting. The history of similar, though milder, episodes of pain after heavy meals suggests symptomatic gallstones as a potential underlying cause. Given her lack of alcohol consumption, gallstones become the leading etiological factor. Furthermore, the significantly elevated amylase and lipase levels in her laboratory results strongly support the diagnosis of acute pancreatitis.

Diagnostic Criteria for Acute Pancreatitis

The diagnosis of acute pancreatitis is primarily clinical, supported by laboratory and imaging findings. The Atlanta criteria, widely used for diagnosing acute pancreatitis, requires the presence of at least two of the following three features:

1. Abdominal pain consistent with acute pancreatitis: Characteristically sudden onset of severe, persistent epigastric pain, often radiating to the back.
2. Serum lipase or amylase activity at least three times greater than the upper limit of normal. Lipase is generally considered more specific for pancreatitis.
3. Characteristic findings of acute pancreatitis on imaging (CT, MRI, or ultrasound). These findings may include pancreatic enlargement, peripancreatic fluid collections, or the presence of gallstones. In some cases, sentinel loops (dilated small bowel) or a colon cutoff sign may be observed on abdominal radiographs, although these are less specific.

In this patient’s case, she fulfills all three criteria: she presented with sudden, severe epigastric pain radiating to her back, her lipase and amylase levels were significantly elevated, and while initial imaging was plain film, the clinical picture strongly points to pancreatitis, warranting further imaging if needed for confirmation or complication assessment.

History and Physical Examination in Epigastric Pain

Nonsurgical Conditions Mimicking an Acute Abdomen

It is crucial to consider other nonsurgical conditions that can mimic an acute abdomen when evaluating epigastric pain. These conditions, while not requiring immediate surgical intervention, can present with similar symptoms and require prompt medical attention. These include:

• Gastroenteritis
• Acute adrenal insufficiency
• Sickle cell crisis
• Diabetic ketoacidosis (DKA)
• Acute porphyria
• Pelvic inflammatory disease (PID)
• Kidney stones (renal colic)
• Pyelonephritis

A thorough history and physical examination, along with appropriate laboratory and imaging studies, are essential to differentiate these conditions from surgical emergencies and acute pancreatitis.

Significance of Bruising Around the Umbilicus, Flank, and Inguinal Ligament

Bruising in specific abdominal locations can indicate retroperitoneal hemorrhage, particularly in the context of severe hemorrhagic pancreatitis. These are classic but less common signs:

• Cullen’s sign: Blue-red discoloration around the umbilicus, indicating intraperitoneal or retroperitoneal hemorrhage tracking subcutaneously.

Alt text: Clinical photograph showing Cullen’s sign, characterized by bluish discoloration around the umbilicus, suggestive of retroperitoneal hemorrhage, possibly from pancreatitis.

• Grey Turner’s sign: Blue-black discoloration in the flanks, also indicative of retroperitoneal hemorrhage.

Alt text: Medical image illustrating Grey Turner’s sign, marked by ecchymosis or bruising in the flank region, which may signal retroperitoneal bleeding associated with conditions like severe pancreatitis.

• Fox’s sign: Bruising over the inguinal ligament, another sign of retroperitoneal bleeding, though less specific to pancreatitis.

These signs, while suggestive of severe hemorrhagic pancreatitis, are not always present and are relatively late findings. Their absence does not rule out severe disease.

Signs, Symptoms, and Physical Findings of Acute Pancreatitis

The hallmark symptom of acute pancreatitis is epigastric pain radiating to the back. This pain is often described as:

• Severe and persistent: Unlike colicky pain, pancreatitis pain is typically constant and unrelenting.
• Worsened by food intake: Eating, especially fatty foods, can exacerbate the pain.
• Nausea and Vomiting: Present in approximately 90% of cases, often severe and persistent.
• Anorexia or decreased oral intake: Due to pain and nausea.

Physical examination findings in acute pancreatitis may include:

• Epigastric tenderness: Localized tenderness to palpation in the epigastric region.
• Localized guarding: Voluntary muscle contraction in response to palpation in the epigastrium.
• Tachycardia: Elevated heart rate, often due to pain, dehydration, and systemic inflammation.
• Fever: May be present, especially in more severe cases.
• Hypoactive bowel sounds: Resulting from reactive ileus, decreased bowel motility due to inflammation.
• In severe cases, signs of shock such as hypotension may be present.

Structures in the Retroperitoneum

Understanding the retroperitoneal anatomy is relevant in pancreatitis as the pancreas itself and many structures affected by pancreatitis are located in this space. A useful mnemonic to remember the retroperitoneal structures is “SAD PUCKER”:

• Suprarenal (adrenal) glands
• Aorta/IVC (Inferior Vena Cava)
• Duodenum (2nd and 3rd parts)
• Pancreas (except tail)
• Ureters
• Colon (ascending and descending)
• Kidneys
• Esophagus
• Rectum

Pathophysiology of Acute Pancreatitis

Pathophysiology of Pancreatitis

The fundamental mechanism in acute pancreatitis is the inappropriate activation of pancreatic enzymes within the pancreas itself. Normally, pancreatic enzymes are produced in an inactive form and are activated only upon reaching the duodenum, preventing self-digestion of the pancreas. In pancreatitis, premature activation of these enzymes leads to:

• Autodigestion of pancreatic parenchyma: Pancreatic enzymes, such as trypsin, lipase, and amylase, begin to digest the pancreas itself.
• Peripancreatic inflammation: The inflammatory response is triggered by enzyme leakage and cellular damage, extending beyond the pancreas to surrounding tissues and vasculature.
• Systemic inflammatory response: In severe cases, the inflammatory response becomes systemic, leading to complications in distant organs.

This cascade of events results in tissue damage, edema, hemorrhage, and necrosis within and around the pancreas.

Etiologies of Acute Pancreatitis

The mnemonic “GET SMASHED” is a helpful tool to remember the common etiologies of acute pancreatitis:

• Gallstones (Cholelithiasis): Approximately 40% of cases.
• Ethanol (Alcohol): Approximately 30% of cases.
• Tumors: Pancreatic tumors or ampullary tumors causing duct obstruction.
• Scorpion stings: Venom can trigger pancreatitis.
• Mumps or Mycoplasma: Infections, though less common.
• Autoimmune diseases: Lupus, polyarteritis nodosa.
• Surgery or Trauma: Post-ERCP pancreatitis, abdominal trauma.
• Hyperlipidemia/Hypercalcemia: Elevated triglycerides (>1000 mg/dL), hypercalcemia.
• ERCP (Endoscopic Retrograde Cholangiopancreatography) or Embolic/Ischemic events.
• Drugs or Toxins: Certain medications can induce pancreatitis (see Table 2).

The “4 F’s” associated with gallbladder disease (and thus gallstone pancreatitis) are: Female, Fat, Forty, and Fertile. While gallstones are a common cause of pancreatitis, only a small percentage of individuals with gallstones (3-7%) develop pancreatitis.

Medications Associated with Pancreatitis

Certain medications are recognized to be associated with an increased risk of acute pancreatitis. Table 2 lists some of these medications, categorized by the conditions they treat.

Table 2: Medications Associated with Pancreatitis

Disease Treated	Medications
Cardiovascular Disease	Furosemide, Thiazide diuretics
Inflammatory Bowel Disease	Sulfasalazine, 5-Aminosalicylic acid (5-ASA)
Immunosuppression	Azathioprine
Seizures	Valproic acid
Diabetes	Exenatide
HIV Infection	Didanosine, Pentamidine

Mechanism of Gallstone-Induced Pancreatitis

The prevailing theory for gallstone pancreatitis is the “common channel” theory. It proposes that:

1. A small gallstone passes from the gallbladder into the common bile duct.
2. This gallstone causes transient obstruction at the ampulla of Vater, where the common bile duct and pancreatic duct converge and empty into the duodenum.
3. This transient impaction leads to a reflux of bile into the pancreatic duct and/or a sudden increase in pressure within the pancreatic ductal system.
4. These events trigger the premature activation of pancreatic enzymes and initiate the inflammatory cascade of pancreatitis.

Importantly, in gallstone pancreatitis, the obstructing stone is often small and passes spontaneously into the duodenum shortly after causing the initial insult. Therefore, persistent common bile duct stones are not typically found in gallstone pancreatitis, unlike in acute cholangitis where larger stones are more likely to remain impacted and necessitate ERCP for removal.

Differences Between Acute and Chronic Pancreatitis

Acute and chronic pancreatitis represent distinct disease processes with differing etiologies, presentations, and long-term consequences. Table 3 summarizes the key differences.

Table 3: Differences Between Acute and Chronic Pancreatitis

Feature	Acute Pancreatitis	Chronic Pancreatitis
Onset	Severe and sudden	Recurrent episodes, gradual progression
Etiology	Gallstones (40%), alcohol (30%), other causes less common	Alcohol (90%), anatomic defects (pancreas divisum), hereditary, idiopathic
Presentation	Epigastric pain radiating to the back, nausea, vomiting, anorexia	Recurrent epigastric pain, weight loss, diabetes, steatorrhea
Laboratory Findings	Elevated amylase and lipase (lipase more sensitive)	Low fecal elastase levels, amylase and lipase may be normal
Radiology	Dilated loops of bowel near pancreas (sentinel loop) on plain films	Pancreatic calcifications on plain films, ductal changes on CT/MRI

The initial event in acute pancreatitis is the premature activation of trypsin within pancreatic acinar cells. This triggers the cascade of enzyme activation and inflammation.

Classification of Severity in Acute Pancreatitis

The severity of acute pancreatitis is classified into three categories to guide management and prognostication:

• Mild Acute Pancreatitis: Most common (80-90% of cases). Characterized by minimal organ dysfunction and absence of local or systemic complications. Usually resolves within 2-5 days.
• Moderately Severe Acute Pancreatitis: Includes transient organ failure (lasting less than 48 hours) and/or local complications (e.g., peripancreatic fluid collections, pseudocyst) or systemic complications (e.g., exacerbation of pre-existing co-morbidities).
• Severe Acute Pancreatitis: Defined by persistent organ failure (lasting longer than 48 hours). Associated with a higher risk of complications and mortality.

Organ Systems Affected by Acute Pancreatitis

Acute pancreatitis can affect multiple organ systems beyond the pancreas due to the systemic inflammatory response and release of inflammatory mediators. The organ systems commonly involved include:

• Cardiovascular: Hypotension, shock, myocardial dysfunction.
• Pulmonary: Pleural effusions, acute respiratory distress syndrome (ARDS), hypoxemia.
• Renal: Acute kidney injury, electrolyte imbalances.
• Gastrointestinal: Ileus, gastrointestinal bleeding.

Definition of Organ Failure in Acute Pancreatitis

Organ failure in acute pancreatitis is defined based on the Atlanta Symposium criteria, using specific parameters for various organ systems:

• Cardiovascular: Systolic blood pressure ≤ 90 mmHg.
• Respiratory: PaO2 ≤ 60 mmHg (arterial partial pressure of oxygen).
• Renal: Creatinine > 2.0 mg/dL after rehydration.
• Gastrointestinal: Gastrointestinal bleeding > 500 cc/24 hours.
• Hematologic: Disseminated intravascular coagulation (DIC).
• Metabolic: Metabolic disturbances (e.g., hypocalcemia: Calcium < 7.5 mg/dL).

Mechanism of Hypotension in Pancreatitis

Hypotension is a frequent and serious complication of acute pancreatitis. The mechanisms contributing to hypotension include:

• Fluid Sequestration (“Third Spacing”): Inflammation and cytokine release cause endothelial injury and increased vascular permeability in the peripancreatic tissues. This leads to fluid leaking out of the intravascular space into the retroperitoneal space and surrounding tissues, effectively reducing circulating blood volume.
• Vasodilation: Cytokine-mediated systemic vasodilation contributes to a decrease in systemic vascular resistance and blood pressure.
• Decreased Cardiac Output: In severe cases, myocardial depressant factors released during pancreatitis can reduce cardiac contractility and output, further contributing to hypotension.

Pulmonary Complications of Acute Pancreatitis

Pulmonary complications are common and significant in acute pancreatitis, contributing to morbidity and mortality. The main pulmonary complications are:

• Pleural Effusions: Fluid accumulation in the pleural space, often bilateral but more frequently on the left side. Thought to be due to diaphragmatic lymphatic channels and inflammatory exudate.

Alt text: Chest radiograph showing bilateral pleural effusions and diffuse pulmonary infiltrates, consistent with acute respiratory distress syndrome (ARDS) as a complication of pancreatitis.

• Acute Respiratory Distress Syndrome (ARDS): A severe form of lung injury characterized by diffuse alveolar damage, increased pulmonary permeability, and hypoxemia. Mediated by cytokines and pancreatic enzymes (e.g., phospholipase-A2) reaching the lungs via systemic circulation.

Histopathologic Types of Acute Pancreatitis

Histopathologically, acute pancreatitis can be broadly categorized into two main types, which have implications for prognosis and management:

• Interstitial Edematous Pancreatitis: More common (>80% of cases). Characterized by pancreatic enlargement due to inflammatory edema. Minimal pancreatic necrosis. Generally milder clinical course with good prognosis.
• Necrotizing Pancreatitis: Less common (<20% of cases) but more severe. Characterized by necrosis (cell death) of pancreatic parenchyma and/or peripancreatic fat. Higher risk of complications, including infection (infected necrosis) and sepsis.
• Hemorrhagic Pancreatitis: A subtype of necrotizing pancreatitis with extensive bleeding into the pancreatic parenchyma and surrounding tissues. Associated with a particularly severe course and poorer prognosis.

The type of pancreatitis (edematous vs. necrotizing) is a key determinant of prognosis and influences management strategies.

Prognosis in Acute Pancreatitis

Determination of Severity in Pancreatitis

Assessing the severity of acute pancreatitis is crucial for risk stratification and guiding management decisions. Several scoring systems are used to predict severity, including:

• Ranson Criteria: A widely used scoring system that assesses multiple clinical and laboratory parameters at admission and at 48 hours after admission.

Alt text: Ranson criteria scoring system table, detailing admission and 48-hour parameters used to assess the severity of acute pancreatitis and predict prognosis.

• APACHE II (Acute Physiology and Chronic Health Evaluation II) Score: A more complex, general severity scoring system used in intensive care settings.
• BISAP (Bedside Index of Severity in Acute Pancreatitis) Score: A simpler scoring system that has been shown to be comparable to APACHE II in accuracy and easier to use at the bedside. The BISAP score is calculated by assigning one point for each of the following:
  • BUN > 25 mg/dL
  • Impaired mental status
  • Systemic Inflammatory Response Syndrome (SIRS)
  • Age > 60 years
  • Pleural effusion

The Ranson criteria remain a commonly used tool, employing the mnemonic “GA LAW” for parameters assessed on admission and “CHOBBS” for parameters assessed at 48 hours. Each positive criterion receives one point, and the total score correlates with the severity and prognosis.

It’s important to note that the degree of amylase or lipase elevation does not correlate with the severity of acute pancreatitis and should not be used to predict prognosis or guide management decisions.

Drawbacks of Ranson Criteria

A major drawback of the Ranson criteria is that it takes 48 hours to fully calculate the score, as some parameters are assessed only after 48 hours of hospitalization. By this time, the clinical course of many patients may already be apparent. Furthermore, the Ranson criteria variables are not designed for repeated measurement to monitor changes in patient status over shorter time intervals.

Mechanism of Hypocalcemia in Severe Pancreatitis

Hypocalcemia is a common complication of severe acute pancreatitis. The primary mechanism is:

• Saponification: Pancreatic lipase, released in large amounts in pancreatitis, breaks down triglycerides into free fatty acids. These free fatty acids bind to calcium ions in the peripancreatic tissues, forming insoluble calcium soaps. This process, known as saponification, effectively removes calcium from the circulation, leading to hypocalcemia.

Natural Disease Course of Acute Pancreatitis

The majority of patients with acute pancreatitis (80-90%) experience a mild course and recover within 5 days without significant complications. However, approximately 20% of patients develop a severe presentation with local or systemic complications, including organ failure, which can lead to prolonged hospitalization and increased mortality.

Common Causes of Mortality in Acute Pancreatitis

The causes of mortality in acute pancreatitis vary depending on the timing of death in relation to disease onset:

• Early Mortality (First Week): Most often due to multiorgan failure resulting from the severe systemic inflammatory response syndrome (SIRS). This early mortality is driven by the overwhelming inflammatory cascade and its effects on vital organs.
• Late Mortality (Beyond the First Week): Most commonly due to sepsis secondary to infected pancreatic necrosis and peripancreatic abscesses. These infectious complications typically develop in the third and fourth weeks of hospitalization. If a pancreatic abscess is not adequately drained, mortality approaches 100%.

Workup for Epigastric Pain and Suspected Pancreatitis

Key Laboratory Tests for Suspected Acute Pancreatitis

When acute pancreatitis is suspected based on epigastric pain and clinical presentation, the most important initial laboratory tests include:

• Serum Amylase and Lipase: These are the primary diagnostic enzymes. Lipase is generally considered more specific and sensitive for pancreatitis than amylase. In gallstone pancreatitis, amylase levels are often very high (>1000 u/L).
• Liver Function Tests (LFTs): Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), and bilirubin. Elevated ALT levels, particularly if greater than three times the upper limit of normal, are highly suggestive of gallstone pancreatitis. However, normal LFTs do not rule out gallstone etiology.
• Complete Blood Count (CBC): To assess for leukocytosis (elevated white blood cell count), which is common in pancreatitis and can indicate inflammation or infection.
• Electrolytes: Sodium, potassium, chloride, bicarbonate, calcium, magnesium. Electrolyte imbalances are common in pancreatitis and require monitoring and correction.
• Lipid Panel: To rule out hypertriglyceridemia as a cause of pancreatitis. Triglyceride levels >1000 mg/dL are considered a potential etiology.

Most Specific Laboratory Test for Acute Pancreatitis

Lipase is considered the most specific laboratory test for acute pancreatitis. While amylase levels can be elevated in various non-pancreatic conditions (hyperamylasemia), lipase elevation is more specific to pancreatic inflammation. Table 4 lists conditions that can cause hyperamylasemia.

Table 4: Conditions Causing Hyperamylasemia (Elevated Amylase)

Condition Category	Specific Diseases
Pancreatic Disease	Pancreatitis, pancreatic pseudocyst, pancreatic trauma, ERCP, pancreatic carcinoma, cystic fibrosis
Salivary Disease	Parotitis (mumps), salivary gland radiation, ductal obstruction
Gastrointestinal Disease	Peptic ulcer disease, perforated bowel, mesenteric ischemia, appendicitis, cholecystitis, celiac disease
Other Conditions	Alcohol abuse, renal failure (amylase is renally cleared)

In patients with hemorrhagic pancreatitis, the initial hematocrit may not accurately reflect blood loss due to hemoconcentration from fluid shifts. It may take 1-2 days for the hematocrit to equilibrate and reflect true blood loss. Furthermore, in dehydrated patients, hemoconcentration can falsely elevate or normalize the hematocrit, masking underlying blood loss.

Diagnostic Imaging of Choice for Acute Pancreatitis on Admission

The initial diagnostic imaging modality of choice for acute pancreatitis, especially on admission to the emergency department, is right upper quadrant ultrasound. Given that gallstones are the most common cause of acute pancreatitis, ultrasound is used to rapidly assess for the presence of gallstones in the gallbladder and common bile duct. Ultrasound is non-invasive, readily available, and does not involve ionizing radiation.

Classic Abdominal X-ray Findings in Acute Pancreatitis

While abdominal X-rays are not highly sensitive or specific for acute pancreatitis, certain findings may be suggestive:

• Sentinel Loop: Dilated loops of proximal small bowel, typically seen in the left upper quadrant near the pancreas. This represents localized ileus (paralysis of bowel segment) due to pancreatic inflammation.
• Colon Cutoff Sign: Distended proximal colon, often in the right or transverse colon, with abrupt collapse of the colon in the left upper quadrant at the splenic flexure. This is also due to local ileus affecting the colon.

Both sentinel loops and colon cutoff sign are non-specific findings and can be seen in other intra-abdominal inflammatory conditions causing localized ileus.

Delayed development of ileus in a patient with pancreatitis or after abdominal trauma should raise suspicion for retroperitoneal bleeding.

Classic Chest X-ray Finding in Acute Pancreatitis

A common chest X-ray finding in acute pancreatitis is a pleural effusion, classically located on the left side. Pleural effusions are more frequently observed in severe pancreatitis. Approximately 85% of patients with severe pancreatitis have pleural effusions on admission chest X-ray, compared to only 15% of patients with mild pancreatitis. The presence of a pleural effusion on chest X-ray is thus associated with increased severity of pancreatitis.

Role of Abdominal CT Scan on Admission for Acute Pancreatitis

Routine abdominal CT scans are not recommended on admission for most patients with acute pancreatitis. In the majority of cases, CT scans do not change immediate management decisions. While CT can differentiate between mild and severe pancreatitis, clinical criteria and scoring systems (like Ranson or BISAP) are often sufficient for initial risk stratification.

However, abdominal CT scan may be useful on admission in specific situations:

• Diagnostic Uncertainty: When the diagnosis of acute pancreatitis is unclear, and other intra-abdominal pathologies need to be ruled out.
• Severe Presentation: In patients with a diffuse peritonitis-like examination, where differentiating pancreatitis from other surgical emergencies is challenging.

Role of Abdominal CT Scan During Subsequent Hospitalization

Abdominal CT scan becomes more valuable during subsequent hospitalization for acute pancreatitis, particularly if:

• Lack of Clinical Improvement: If a patient is not clinically improving after several days of conservative management, a CT scan can help identify complications such as pancreatic necrosis, peripancreatic fluid collections, or abscess formation that may be hindering recovery.
• Worsening Condition: If a patient develops worsening abdominal pain, fever, or signs of sepsis during hospitalization, a CT scan is indicated to evaluate for local complications such as pseudocyst or pancreatic abscess (which typically develop later in the course of pancreatitis, not on admission).

Figure 1: Axial CT scan showing a normal pancreas in a patient without pancreatitis.

Alt text: Axial computed tomography (CT) scan of the abdomen illustrating a normal pancreas, indicated by black arrows, in a patient without pancreatic pathology.

Figure 2: Axial CT scan demonstrating peripancreatic fluid collections with irregular walls, consistent with abscesses in necrotizing pancreatitis.

Alt text: Axial CT scan of the abdomen revealing peripancreatic fluid collections with thick, irregular walls and fat stranding, consistent with pancreatic abscesses as a complication of necrotizing pancreatitis.

Figure 3: Axial CT scan showing a thin-walled peripancreatic fluid collection, consistent with a pancreatic pseudocyst.

Alt text: Axial CT scan illustrating a thin-walled peripancreatic fluid collection, consistent with a pancreatic pseudocyst, a potential late complication of pancreatitis.

Role of Urgent ERCP in Gallstone Pancreatitis

Urgent ERCP (Endoscopic Retrograde Cholangiopancreatography) is rarely needed in gallstone pancreatitis. The primary indication for urgent ERCP in this setting is suspected concomitant acute cholangitis (infection of the bile ducts). Cholangitis is a more urgent condition requiring biliary decompression.

ERCP itself carries a risk of inducing pancreatitis (post-ERCP pancreatitis). If ERCP is deemed necessary, prophylactic rectal indomethacin suppositories can reduce the risk of post-ERCP pancreatitis.

Management of Acute Pancreatitis

Initial Treatment for Acute Pancreatitis

The initial management of acute pancreatitis is primarily supportive and conservative. Key components of initial treatment include:

• Vigorous Intravenous Fluid Resuscitation: Aggressive fluid replacement is crucial to address fluid losses from vomiting, third spacing, and systemic inflammation. Ringer’s lactate is often the preferred intravenous fluid.
• NPO (Nil Per Os – Nothing by Mouth): Oral intake is withheld to reduce pancreatic stimulation and allow the pancreas to rest and recover.
• Analgesics: Pain management is essential. Opioid analgesics, such as intravenous hydromorphone or fentanyl, are commonly used to control the severe pain associated with pancreatitis.

Routine nasogastric tube (NGT) decompression is not routinely recommended in acute pancreatitis. NGT may be considered in patients with persistent vomiting or severe gastric distension.

Routine use of antibiotics is also not recommended in the initial management of acute pancreatitis, unless there is evidence of infection (e.g., cholangitis, infected necrosis – typically later in the course).

With conservative management, most patients with mild acute pancreatitis experience resolution of symptoms within 3-5 days.

While some historical test questions may suggest meperidine over morphine for pain control in pancreatitis due to concerns about morphine potentially causing sphincter of Oddi contraction, this is not clinically significant. Meperidine also carries a higher risk of seizures and is generally not preferred. Current practice focuses on adequate pain control with appropriate opioid analgesics.

Subsequent Management Plan

The subsequent management plan for acute pancreatitis depends on the etiology and severity.

For Gallstone Pancreatitis:

• Cholecystectomy: If gallstones are identified as the cause and there is no history of alcohol abuse, cholecystectomy (gallbladder removal) should be performed during the same hospitalization to prevent recurrent gallstone pancreatitis. The risk of recurrence is high within 30 days if cholecystectomy is not performed.
• Timing of Cholecystectomy:
  • Mild Pancreatitis: Early cholecystectomy (within 48-72 hours of admission) is recommended once the patient is stable.
  • Moderately Severe or Severe Pancreatitis: Cholecystectomy is typically delayed until after complete resolution of the acute pancreatitis episode, usually weeks later, to allow inflammation to subside and reduce surgical risk.
  • Amylase and lipase levels should not influence the timing of surgery.

For Alcoholic Pancreatitis:

• Alcohol Cessation Counseling: Essential for preventing recurrent episodes.
• Referral to Support Groups: Alcoholics Anonymous or other addiction support programs.

Influence of Severity on Management

The severity of acute pancreatitis significantly impacts management decisions:

• Triage and Monitoring: Severity assessment helps determine the appropriate level of care – ward for mild pancreatitis, monitored step-down unit or ICU for moderately severe or severe pancreatitis. Severe pancreatitis requires closer monitoring for organ failure and complications.
• Timing of Cholecystectomy in Gallstone Pancreatitis: As described above, severity influences the timing of gallbladder surgery.

Figure 4: Management algorithm for acute pancreatitis, based on American College of Gastroenterology guidelines.

Alt text: Algorithm flowchart illustrating the management of acute pancreatitis, including steps for diagnosis, severity assessment, and treatment strategies based on gallstone or non-gallstone etiology and disease severity, according to American College of Gastroenterology guidelines.

Special Situations in Acute Pancreatitis

Pancreatic Abscess in Severe Acute Pancreatitis

If a patient with severe acute pancreatitis develops fever and leukocytosis approximately 4 weeks into hospitalization, pancreatic abscess should be suspected. The diagnostic workup includes:

1. Abdominal CT Scan with Contrast: To assess for necrotic tissue (non-enhancing areas) or abscess formation.
2. CT or Ultrasound-Guided Aspiration: If necrosis or abscess is identified, aspiration is performed to obtain fluid for Gram stain and culture to confirm infection.

Management of Pancreatic Abscess/Infected Necrosis:

• Antibiotics: Broad-spectrum antibiotics are administered if infection is confirmed.
• Surgical Debridement: Infected pancreatic necrosis and pancreatic abscesses often require surgical debridement to remove necrotic tissue and control infection. A “step-up approach” is typically used:
  1. Percutaneous or endoscopic drainage (minimally invasive).
  2. Video-assisted retroperitoneal debridement (VARD).
  3. Open necrosectomy (traditional open surgery) – reserved for cases failing less invasive approaches.

These procedures aim for external drainage of infected material.

Pancreatic Pseudocyst

If a patient with a recent history of pancreatitis presents weeks later (e.g., 6 weeks) with vague abdominal pain, a palpable epigastric mass, and persistently elevated serum amylase, pancreatic pseudocyst should be considered. A pseudocyst is a collection of pancreatic fluid surrounded by a fibrous wall, lacking an epithelial lining. It typically develops after pancreatitis or pancreatic trauma due to disruption of pancreatic ducts.

Clinical Presentation:

• Vague abdominal pain
• Palpable epigastric mass
• Persistently elevated serum amylase

Diagnosis:

• Abdominal CT scan is the diagnostic test of choice to confirm pseudocyst and assess its size and location.

Management:

• Conservative Management: Most pseudocysts can be managed conservatively, as many will resolve spontaneously.
• Intervention: Intervention is considered for:
  • Symptomatic pseudocysts (causing pain, obstruction, etc.)
  • Pseudocysts larger than 6 cm
  • Pseudocysts persisting for more than 6 weeks
• Internal Drainage: Treatment for symptomatic or persistent pseudocysts is usually internal drainage, creating a connection between the pseudocyst and an adjacent intestinal organ, typically the stomach (endoscopic cystogastrostomy). This allows the pseudocyst fluid to drain into the gastrointestinal tract.
• External Drainage: External drainage is generally avoided due to the risk of pancreaticocutaneous fistula formation.
• Pseudoaneurysm Risk: Pseudocysts can erode into nearby arteries, leading to pseudoaneurysm formation and upper gastrointestinal bleeding. This requires urgent management, typically angiographic embolization to stop the bleeding.

Pancreatic cysts without a history of pancreatitis should raise suspicion for pancreatic neoplasms, and biopsy should be considered to rule out malignancy.

Complications of Chronic Pancreatitis

Chronic pancreatitis can lead to several long-term complications:

• Diabetes Mellitus (Type 3 Diabetes): Destruction of insulin-producing beta cells in the pancreas due to chronic inflammation can result in diabetes. This type of diabetes is often difficult to manage and frequently requires insulin therapy.
• Steatorrhea: Malabsorption of fats and fat-soluble vitamins due to pancreatic exocrine insufficiency (reduced lipase and other digestive enzymes). Patients may require pancreatic enzyme supplementation to improve digestion and nutrient absorption.
• Chronic Pain: Persistent and severe abdominal pain is a common and debilitating symptom in chronic pancreatitis. The exact mechanisms are not fully understood, but nerve injury in the pancreas is thought to play a role.

Acute Pancreatitis After Vascular Procedures

Although rare, patients undergoing vascular procedures, particularly endovascular procedures, are at risk of atheroemboli (cholesterol embolism). Dislodged cholesterol plaques from the aorta or other vessels can travel downstream and cause:

• Skin changes: Blue toe syndrome, livedo reticularis.
• Gastrointestinal complications: Acute pancreatitis, mesenteric ischemia.

Pancreatitis can also result from ischemia after cardiac bypass surgery. Pancreatitis due to uncorrectable causes like atheroembolism or ischemia is managed supportively with IV fluids and analgesia.

Surgical Management of Chronic Pancreatitis

The most common indication for surgical management in chronic pancreatitis is persistent and severe pain that is refractory to medical management. The mechanisms of chronic pain in pancreatitis are not fully understood, but nerve injury in the pancreatic head is implicated.

Nonoperative Pain Relief:

• Pancreatic duct stent placement: To improve drainage of pancreatic juices and reduce ductal pressure. Provides temporary pain relief.

Definitive Surgical Treatment:

• Puestow Procedure (Lateral Pancreaticojejunostomy): A surgical procedure for chronic pancreatitis with dilated pancreatic ducts. The pancreatic duct is opened longitudinally from head to tail and anastomosed to the jejunum in a side-to-side fashion. This allows free drainage of pancreatic juices into the small intestine, reducing intraductal pressure and pain.

Areas of Controversy in Pancreatitis Management

Urgent ERCP for Severe Pancreatitis

The role of urgent ERCP in severe acute pancreatitis, specifically in the absence of cholangitis, remains controversial. The theoretical benefit is to remove a potentially impacted gallstone in the distal common bile duct, which might perpetuate pancreatic inflammation. However, clinical trials have not consistently demonstrated a benefit of urgent ERCP in severe pancreatitis without cholangitis. This lack of proven benefit may be due to:

• ERCP-induced pancreatitis risk: ERCP itself carries a ~5% risk of causing pancreatitis.
• Spontaneous stone passage: Most gallstones causing pancreatitis are small and pass spontaneously into the duodenum.

There is evidence supporting ERCP with stone removal and papillotomy if cholangitis is present. Some clinicians may also consider ERCP in cases of obstructive jaundice with persistent and marked bilirubin elevation.

Prophylactic Antibiotics for Severe Acute Pancreatitis

The use of prophylactic antibiotics in severe acute pancreatitis is another area of debate.

• Mild Pancreatitis: There is no role for prophylactic antibiotics in mild pancreatitis, as it is primarily an inflammatory, not infectious, process.
• Severe Pancreatitis: Patients with severe pancreatitis have increased mortality risk from subsequent infections, particularly infected necrosis. Historically, prophylactic antibiotics were often used, based on anecdotal evidence and clinical practice. However, recent clinical trials have largely failed to show a reduction in mortality with prophylactic antibiotics in severe pancreatitis. Current guidelines generally do not recommend routine prophylactic antibiotics. Antibiotics are indicated if infection is confirmed or strongly suspected (e.g., infected necrosis, cholangitis).

Areas Where You Can Get in Trouble in Pancreatitis Management

Missing Hypercalcemia as a Cause of Pancreatitis

In cases of acute pancreatitis where gallstones and alcohol abuse are ruled out, consider less common etiologies, including hypercalcemia. Risk factors for hypercalcemia-induced pancreatitis include:

• Hyperparathyroidism
• Medications: Thiazide diuretics (e.g., hydrochlorothiazide), which can increase calcium reabsorption.

Mechanism of Hypercalcemia-Induced Pancreatitis: Hypercalcemia can cause a secretory block in the pancreatic duct, leading to ductal hypertension and enzyme activation.

Paradoxical Hypocalcemia: While hypercalcemia can cause pancreatitis, pancreatitis itself can cause hypocalcemia (due to saponification). Therefore, the initial hypercalcemia may be missed if only calcium levels during the acute pancreatitis episode are assessed. It is important to consider hypercalcemia as a potential underlying cause, especially in unexplained cases.

Pseudohyponatremia in Hyperlipidemic Pancreatitis

Be aware of pseudohyponatremia in patients with hyperlipidemic pancreatitis (pancreatitis due to hypertriglyceridemia). In severe hyperlipidemia, high levels of lipids in the blood can interfere with sodium measurement in some laboratory assays. The lipids displace water in the blood sample, leading to an artificially low sodium reading. True serum sodium levels are normal in pseudohyponatremia. If pseudohyponatremia is suspected, direct ion-selective electrode (ISE) sodium measurement can be used to obtain accurate sodium levels.

Nutritional Support in Pancreatitis

Nutritional support is important in patients with acute pancreatitis, especially if they are expected to be NPO for an extended period.

• Enteral Nutrition Preferred: If NPO status is expected to exceed 7 days, nutritional support is indicated. Enteral nutrition (feeding via the gastrointestinal tract) is preferred over parenteral nutrition (intravenous feeding). Enteral nutrition is associated with lower rates of infection and other complications compared to parenteral nutrition in pancreatitis.
• Post-Pyloric Feeding Tube Placement: To minimize pancreatic stimulation, the feeding tube should be placed distal to the pylorus, ideally past the ligament of Treitz (into the jejunum). This avoids stimulating pancreatic enzyme release in response to gastric distension and duodenal contents.

Summary of Essentials in Epigastric Pain and Pancreatitis

History and Physical Examination Essentials

• Nonsurgical conditions mimicking acute abdomen: gastroenteritis, acute adrenal insufficiency, sickle cell crisis, DKA, acute porphyria, PID, kidney stones, pyelonephritis.
• Typical pancreatitis presentation: epigastric pain radiating to the back, nausea, vomiting, anorexia, fever, tachycardia.

Pathophysiology Essentials

• Initial event in pancreatitis: inappropriate activation of pancreatic enzymes within the pancreas.
• Most common causes of acute pancreatitis: gallstones and alcohol.

Diagnosis Essentials

• Diagnosis often clinical, based on history, physical exam, and elevated amylase/lipase.
• Ranson criteria: predict severity based on admission and 48-hour parameters.

Workup Essentials

• Amylase/lipase levels do not correlate with pancreatitis severity.
• RUQ ultrasound first-line imaging to rule out gallstones in the absence of alcohol history.

Management Essentials

• Initial management: conservative with IV fluids, NPO, narcotic analgesia.
• Gallstone pancreatitis:
  • Urgent ERCP rarely needed (only with cholangitis suspicion).
  • Early cholecystectomy for mild pancreatitis.
  • Late cholecystectomy for moderately severe/severe pancreatitis.
• No clinical improvement after 3 days conservative management: consider CT scan with contrast for complications (necrosis).
• Enteral nutrition preferred if prolonged NPO or severe pancreatitis.
• Refractory persistent abdominal pain main surgical indication in chronic pancreatitis.

Complications Essentials

• Systemic Complications:
  • Early (first week): Multiorgan failure.
• Local Complications:
  • Late (3 weeks): Pancreatic abscess, pancreatic pseudocyst, pancreatic necrosis.

Contributor Information

Christian de Virgilio, Phone: +113102225101, Email: [email protected].

Areg Grigorian, Phone: +118184389093, Email: [email protected].

Areg Grigorian, Email: [email protected].

Matthew Y. C. Lin, Email: [email protected]

Christian de Virgilio, Email: [email protected].