Tema 1

Pancreatitis Aguda: Causas y Patogenia

Introducción a la pancreatitis aguda

• Se revisarán temas importantes en gastroenterología, comenzando con la pancreatitis aguda, un tema frecuentemente preguntado.

• Otros temas incluyen úlcera péptica, hemorragia digestiva alta y baja.

Etiología de la pancreatitis aguda

• La causa más frecuente de pancreatitis aguda es la colitiasis (patología biliar), especialmente en mujeres.

• Los cálculos menores de 5 mm pueden obstruir el conducto cístico y colédoco, provocando inflamación del páncreas.

Otras causas comunes

• La ingestión crónica de alcohol es la segunda causa más común, causando toxicidad directa al páncreas.

• La hipertrigliceridemia (triglicéridos > 1000 mg/dl) puede inducir pancreatitis aguda; se debe tener cuidado con este factor.

Medicamentos asociados

• Varios fármacos están relacionados con un alto riesgo de pancreatitis aguda: diuréticos (furosemida), antibióticos (tetraciclinas), quimioterapia y anticonvulsivantes como valproato.

Trauma y otras causas

• El trauma abdominal directo puede causar pancreatitis; procedimientos como CPRE también son riesgosos por su potencial para provocar lesiones.

• Infecciones como parotiditis en niños pueden llevar a pancreatitis; se deben descartar complicaciones asociadas.

Patogenia de la pancreatitis aguda

• La obstrucción del conducto biliar genera edema intersticial que altera el flujo sanguíneo, llevando a isquemia del páncreas.

• Esto provoca activación prematura de enzimas digestivas dentro del páncreas, lo que resulta en inflamación.

Consecuencias celulares

• La lesión a los asinos pancreáticos afecta las enzimas digestivas necesarias para procesar lípidos, proteínas y carbohidratos.

• Finalmente, esto lleva a una activación prematura de las enzimas que contribuyen al desarrollo de la pancreatitis aguda.

Pancreatitis: Pathogenesis and Diagnosis

Understanding the Pathogenesis of Pancreatitis

• The activation of trypsinogen to trypsin by enteropeptidase in the intestine is crucial for food digestion. However, premature activation of pancreatic enzymes leads to complications such as edema and inflammation.

• Premature enzyme activation results in interstitial edema, proteolysis, steatonecrosis due to lipase activation, and hemorrhage from elastase activity affecting blood vessels. This can lead to interstitial pancreatitis or severe necrohemorrhagic pancreatitis.

• The key takeaway is that early enzyme activation is a primary cause of acute pancreatitis. Understanding this pathogenesis is essential for diagnosis and treatment.

Clinical Presentation and Diagnosis

• Patients with acute pancreatitis typically present with intense abdominal pain located in the epigastric region or upper abdomen, necessitating immediate evaluation for potential pancreatitis.

• Acute pancreatitis is the most common medical cause of an acute abdomen; it should be considered alongside surgical causes like appendicitis when evaluating patients in emergency settings.

• Symptoms may include paralytic ileus (nausea, vomiting), hemodynamic instability, and multi-organ failure due to systemic inflammatory response syndrome (SIRS). These signs indicate a serious condition requiring urgent attention.

Key Signs and Symptoms

• Pain characteristics are critical; if pain radiates to the back or presents as a band-like sensation around the torso, it suggests retroperitoneal involvement typical of pancreatic issues. Past medical history may reveal gallstones or alcohol consumption as contributing factors.

• Severe cases may exhibit signs indicating necrohemorrhagic pancreatitis: Cullen's sign (periumbilical ecchymosis) and Grey Turner’s sign (flank ecchymosis), which suggest bleeding into the peritoneal cavity from various causes including trauma or ruptured ectopic pregnancy.

Diagnostic Confirmation

• To confirm clinical suspicion of pancreatitis, serum levels of amylase and lipase are measured; elevations more than three times normal indicate diagnosis but do not correlate with severity or prognosis. Amylase has good sensitivity but low specificity compared to lipase which is more reliable for diagnosis especially in alcoholic cases or hypertriglyceridemia-induced pancreatitis where amylase might be normal.

• Lipase rises earlier than amylase (4–6 hours post-onset) and remains elevated longer (10–14 days), making it a better marker for late-presenting patients with suspected acute pancreatitis who may have normal amylase levels despite significant symptoms.

Understanding Acute Pancreatitis and Its Classifications

Late Presentation of Patients

• Typical Peruvian patients often arrive late to emergency services, usually after 72 hours of illness. In such cases, lipase tests are preferred over amylase since amylase levels drop by the third or fifth day.

Importance of Lipase in Diagnosis

• When pancreatitis is caused by alcohol or triglycerides, or if the patient presents late (over 72 hours), lipase becomes crucial for diagnosis as amylase may be normal.

Classification of Acute Pancreatitis

• Approximately 80% of acute pancreatitis cases are interstitial edematous, which typically do not lead to local or systemic complications. The remaining 20% are necrohemorrhagic, indicating serious conditions that can lead to increased mortality.

• Necrohemorrhagic pancreatitis shows heterogeneous areas on imaging and does not capture contrast well. This type has a general mortality rate of 30% when infected necrosis occurs.

Atlanta Classification System

• The Atlanta classification categorizes pancreatitis into mild, moderate, severe, and critical based on complications and organ failure duration:

• Mild: No local/systemic complications or organ failure.

• Moderate: Local complications with transient organ failure (less than 48 hours).

• Severe: Persistent organ failure lasting more than 48 hours.

Petrov Classification System

• Petrov's classification includes four categories based on the severity of local complications:

• Mild: No necrosis or organ failure.

• Moderate: Sterile necrosis with transient organ failure.

• Severe: Either infected necrosis or persistent organ failure (>48 hours).

• Critical status arises when both infected necrosis and persistent organ failure are present. Management should occur in intensive care units for moderate to critical cases due to high mortality risk.

Complications Associated with Acute Pancreatitis

Local Complications

• Common local complications include pseudocysts, abscesses, and infected necrosis. Pseudocysts are fluid collections that can become symptomatic weeks after an episode of acute pancreatitis.

Pseudocyst Characteristics

• Pseudocysts appear as homogeneous liquid collections without epithelial lining; they may cause pain or distension if large enough. They typically manifest around four weeks post-pancreatitis.

Management Strategies for Pseudocysts

• If a pseudocyst is asymptomatic and uncomplicated, it can be monitored ("watchful waiting"). However, complicated pseudocysts require drainage procedures.

• Surgical intervention is indicated for pseudocysts larger than six centimeters that persist beyond six weeks or if they become complicated through infection or rupture.

Understanding Pancreatitis and Its Complications

Clinical Presentation of Pancreatitis

• Abdominal pain typically presents around the third or fourth week, often accompanied by fever and abdominal discomfort. The presence of pus may indicate an abscess characterized by a homogeneous collection with air.

Necrosis in Pancreatitis

• Necrosis is associated with ischemia of pancreatic parenchyma, appearing as a heterogeneous area on tomography that does not absorb contrast, indicating necrotic tissue rather than fluid collection.

Diagnosing Infective Necrosis

• Determining if necrosis is sterile or infected is crucial for prognosis and treatment. Key indicators include clinical signs (fever, poor patient evolution), tomographic findings (air presence), and microbiological tests (positive culture from fine needle aspiration).

Risks Associated with Infective Necrosis

• An infected necrosis represents the most severe local complication of acute pancreatitis, linked to a 30% mortality rate. Systemic complications can arise, including respiratory failure and hemodynamic instability.

Initial Management Strategies

• Initial treatment focuses on medical management: patients should be NPO (nothing by mouth) to rest the pancreas while aggressive fluid therapy is initiated due to significant fluid loss into the third space.

Fluid Therapy Considerations

• Lactated Ringer's solution is preferred over normal saline for fluid resuscitation due to its anti-inflammatory properties. Patients may require 3-4 liters per day initially, monitored closely for urine output.

Pain Management Protocol

• Effective analgesia is essential; opioids such as pethidine or tramadol are recommended for managing severe abdominal pain associated with pancreatitis.

Nutritional Support in Severe Cases

• In cases of severe pancreatitis where prolonged NPO status occurs, enteral nutrition via nasojejunal tube is preferred over total parenteral nutrition to reduce infection risk through better gut function.

Infection Prevention Strategies

• Adequate hydration and nutritional support are critical in preventing infections during acute pancreatitis. Antibiotic prophylaxis has not been proven effective unless infection has been confirmed through clinical or imaging criteria.

Antibiotic Use and Surgical Interventions in Acute Pancreatitis

Antibiotic Administration

• Antibiotics are administered only after confirming an infection, typically occurring two weeks post-injury. The choice of antibiotic for infections in acute pancreatitis is carbapenems, specifically imipenem combined with silastatin to prevent inactivation.

Endoscopic Interventions

• Endoscopic interventions like CPRE (Endoscopic Retrograde Cholangiopancreatography) are crucial depending on the presence of cholangitis. If cholangitis is present, CPRE should be performed within 24 hours; otherwise, it can be done between 24 to 48 hours for severe cases.

Surgical Indications

• Surgery is considered a last resort and indicated primarily when there is an infection associated with pancreatitis or if the patient shows no response to medical management. Conditions warranting surgery include infected necrosis or complications from pseudocysts.

Surgical Techniques

• The preferred approach is a "step-up" technique that starts with minimally invasive methods such as drainage (percutaneous or transgastric), followed by debridement if necessary. Laparotomy is reserved for extreme cases due to its higher complication rates.

Recovery and Prognosis

• Oral tolerance can be resumed once clinical criteria are met: appetite returns, bowel sounds are present, and pain subsides. Persistent elevation of amylase may indicate complications like pancreatic pseudocysts.

Mortality Causes and Prognostic Scoring

Mortality Causes in Acute Pancreatitis

• Mortality can occur early (within two weeks), primarily due to multi-organ failure, while late mortality (after two weeks) often results from pancreatic infections or infected necrosis.

Ranson's Score for Prognosis

• Ranson's score evaluates prognosis based on 11 criteria—five assessed at admission and six after 48 hours—to predict outcomes in patients with acute pancreatitis effectively.

Pancreatitis Scoring Systems and Prognostic Indicators

Mnemonic for Initial Assessment

• The mnemonic "Llega" is introduced to remember key parameters for assessing pancreatitis severity: leukocytes > 16,000, LDH > 350, age > 55 years, glucose > 200, and transaminase TGO > 250.

• Each altered parameter scores one point; a maximum of five points can be assigned at admission based on these criteria.

Additional Parameters for Evaluation

• After the initial assessment, six additional parameters are evaluated at 48 hours: hematocrit decrease, increased IA (inflammatory activity), hypocalcemia (low calcium), oxygen pressure drop (hypoxemia), base deficit, and fluid deficit.

• If any of these six parameters are altered, they also contribute one point to the total score.

Ranson Criteria

• A total score above three indicates severe pancreatitis. The limitation of Ranson's criteria is that it requires waiting 48 hours to assess the complete picture.

BISAP Score

• The BISAP score includes five parameters: blood urea nitrogen (BUN), altered mental status, age over 60 years, pleural effusion (usually left-sided in acute pancreatitis).

• Two or more alterations in these parameters indicate a poor prognosis.

Organ Failure Assessment

• The Marshall scoring system evaluates organ failure in pancreatitis through respiratory failure (PAFI), renal failure (creatinine levels), and hemodynamic instability (blood pressure).

Prognostic Biomarkers

• Elevated C-reactive protein (CRP) is identified as an ideal non-invasive biomarker for predicting outcomes in pancreatitis due to its availability and cost-effectiveness.

Imaging Studies for Severity Assessment

• At 72 hours post-admission for potentially severe cases of pancreatitis, a CT scan is recommended to evaluate severity indices such as edema and necrosis using the Balthazar scoring system.

Balthazar Scoring System Explained

• Balthazar scores range from A to E based on findings:

• A = normal pancreas (0 points)

• B = pancreatic edema (1 point)

• C = peripancreatic fat inflammation (2 points)

• D = fluid collection present (3 points)

• E = two or more fluid collections or gas presence indicating infection.

Understanding Pancreatitis Severity Scoring

Key Components of the Scoring System

• The scoring system for pancreatitis includes assessing air bubbles, pancreatic edema, peripancreatic fat, and fluid collections. A minimum of two fluid collections or one gas collection is necessary for evaluation.

• The necrosis percentage is crucial in determining severity:

• Less than 3% necrosis yields 2 points.

• Between 30% to 50% necrosis gives 4 points.

• More than 50% necrosis also results in a score of 4 points.

Calculating the Severity Index

• The total severity index combines the Baltazar score with the necrosis percentage score. An index of greater than or equal to 6 indicates severe pancreatitis.

• This scoring method emphasizes that both components (Baltazar score and necrosis percentage) are essential for accurate assessment and management decisions regarding pancreatitis severity.