Acute pancreatitis


Acute pancreatitis a gallstone impacted in the common bile duct beyond the point where the pancreatic duct joins it; 2) heavy alcohol use; 3) systemic disease; 4) trauma; 5) and, in minors, mumps. Acute pancreatitis may be a single event; it may be recurrent; or it may progress to chronic pancreatitis.
Mild cases are usually successfully treated with conservative measures: hospitalization, pain control, nothing by mouth, intravenous nutritional support, and intravenous fluid rehydration. Severe cases often require admission to an intensive care unit to monitor and manage complications of the disease. Complications are associated with a high mortality, even with optimal management.

Signs and symptoms

Common

Although these are common symptoms, frequently they are not all present; and epigastric pain may be the only symptom.

Uncommon

The following are associated with severe disease:
Locoregional complications include pancreatic pseudocyst and phlegmon/abscess formation, splenic artery pseudoaneurysms, hemorrhage from erosions into splenic artery and vein, thrombosis of the splenic vein, superior mesenteric vein and portal veins, duodenal obstruction, common bile duct obstruction, progression to chronic pancreatitis, pancreatic ascites, pleural effusion, sterile/infected pancreatic necrosis.
Systemic complications include ARDS, multiple organ dysfunction syndrome, DIC, hypocalcemia, hyperglycemia and insulin dependent diabetes mellitus, malabsorption due to exocrine failure

Most common

Pathogenesis

Acute pancreatitis occurs when there is abnormal activation of digestive enzymes within the pancreas. This occurs through inappropriate activation of inactive enzyme precursors called zymogens inside the pancreas, most notably trypsinogen. Normally, trypsinogen is converted to its active form in the first part of the small intestine, where the enzyme assists in the digestion of proteins. During an episode of acute pancreatitis, trypsinogen comes into contact with lysosomal enzymes, which activate trypsinogen to trypsin. The active form trypsin then leads to further activation of other molecules of trypsinogen. The activation of these digestive enzymes lead to inflammation, edema, vascular injury, and even cellular death. The death of pancreatic cells occurs via two main mechanisms: necrosis, which is less organized and more damaging, or apoptosis, which is more controlled. The balance between these two mechanisms of cellular death is mediated by caspases which regulate apoptosis and have important anti-necrosis functions during pancreatitis: preventing trypsinogen activation, preventing ATP depletion through inhibiting polyADP-ribose polymerase, and by inhibiting the inhibitors of apoptosis. If, however, the caspases are depleted due to either chronic ethanol exposure or through a severe insult then necrosis can predominate.

Pathophysiology

The two types of acute pancreatitis are mild and severe, which are defined based on whether the predominant response to cell injury is inflammation or necrosis. In mild pancreatitis, there is inflammation and edema of the pancreas. In severe pancreatitis, there is necrosis of the pancreas, and nearby organs may become injured.
As part of the initial injury there is an extensive inflammatory response due to pancreatic cells synthesizing and secreting inflammatory mediators: primarily TNF-alpha and IL-1. A hallmark of acute pancreatitis is a manifestation of the inflammatory response, namely the recruitment of neutrophils to the pancreas. The inflammatory response leads to the secondary manifestations of pancreatitis: hypovolemia from capillary permeability, acute respiratory distress syndrome, disseminated intravascular coagulations, renal failure, cardiovascular failure, and gastrointestinal hemorrhage.

Histopathology

The acute pancreatitis is characterized by acute inflammation and necrosis of pancreas parenchyma, focal enzymic necrosis of pancreatic fat and vessel necrosis. These are produced by intrapancreatic activation of pancreatic enzymes. Lipase activation produces the necrosis of fat tissue in pancreatic interstitium and peripancreatic spaces as well as vessel damage. Necrotic fat cells appear as shadows, contours of cells, lacking the nucleus, pink, finely granular cytoplasm. It is possible to find calcium precipitates. Digestion of vascular walls results in thrombosis and hemorrhage. Inflammatory infiltrate is rich in neutrophils. Due to the pancreas lacking a capsule, the inflammation and necrosis can extend to include fascial layers in the immediate vicinity of the pancreas.

Diagnosis

The differential diagnosis includes:
Regarding selection on these tests, two practice guidelines state:
Most, but not all individual studies support the superiority of the lipase. In one large study, there were no patients with pancreatitis who had an elevated amylase with a normal lipase. Another study found that the amylase could add diagnostic value to the lipase, but only if the results of the two tests were combined with a discriminant function equation.
While often quoted lipase levels of 3 or more times the upper-limit of normal is diagnostic of pancreatitis, there are also other differential diagnosis to be considered relating to this rise.

Computed tomography

Regarding the need for computed tomography, practice guidelines state:
CT is an important common initial assessment tool for acute pancreatitis. Imaging is indicated during the initial presentation if:
CT is recommended as a delayed assessment tool in the following situations:
CT abdomen should not be performed before the first 12 hours of onset of symptoms as early CT may result in equivocal or normal findings.
CT Findings can be classified into the following categories for easy recall:
The principal value of CT imaging to the treating clinician is the capacity to identify devitalised areas of the pancreas which have become necrotic due to ischaemia. Pancreatic necrosis can be reliably identified by intravenous contrast-enhanced CT imaging, and is of value if infection occurs and surgical or percutaneous debridement is indicated.

Magnetic resonance imaging

While computed tomography is considered the gold standard in diagnostic imaging for acute pancreatitis, magnetic resonance imaging has become increasingly valuable as a tool for the visualization of the pancreas, particularly of pancreatic fluid collections and necrotized debris. Additional utility of MRI includes its indication for imaging of patients with an allergy to CT's contrast material, and an overall greater sensitivity to hemorrhage, vascular complications, pseudoaneurysms, and venous thrombosis.
Another advantage of MRI is its utilization of magnetic resonance cholangiopancreatography sequences. MRCP provides useful information regarding the etiology of acute pancreatitis, i.e., the presence of tiny biliary stones and duct anomalies. Clinical trials indicate that MRCP can be as effective a diagnostic tool for acute pancreatitis with biliary etiology as endoscopic retrograde cholangiopancreatography, but with the benefits of being less invasive and causing fewer complications.

Ultrasound

On abdominal ultrasonography, the finding of a hypoechoic and bulky pancreas is regarded as diagnostic of acute pancreatitis.

Treatment

Initial management of a patient with acute pancreatitis consists of supportive care with fluid resuscitation, pain control, nothing by mouth, and nutritional support.

Fluid replacement

Aggressive hydration at a rate of 5 to 10 mL/kg per hour of isotonic crystalloid solution to all patients with acute pancreatitis, unless cardiovascular, renal, or other related comorbid factors preclude aggressive fluid replacement. In patients with severe volume depletion that manifests as hypotension and tachycardia, more rapid repletion with 20 mL/kg of intravenous fluid given over 30 minutes followed by 3 mL/kg/hour for 8 to 12 hours.
Fluid requirements should be reassessed at frequent intervals in the first six hours of admission and for the next 24 to 48 hours. The rate of fluid resuscitation should be adjusted based on clinical assessment, hematocrit and blood urea nitrogen values.
In the initial stages of acute pancreatitis, fluid replacement has been associated with a reduction in morbidity and mortality.

Pain control

Abdominal pain is often the predominant symptom in patients with acute pancreatitis and should be treated with analgesics.
Opioids are safe and effective at providing pain control in patients with acute pancreatitis. Adequate pain control requires the use of intravenous opiates, usually in the form of a patient-controlled analgesia pump. Hydromorphone or fentanyl may be used for pain relief in acute pancreatitis. Fentanyl is being increasingly used due to its better safety profile, especially in renal impairment. As with other opiates, fentanyl can depress respiratory function. It can be given both as a bolus as well as constant infusion.
Meperidine has been historically favored over morphine because of the belief that morphine caused an increase in sphincter of Oddi pressure. However, no clinical studies suggest that morphine can aggravate or cause pancreatitis or cholecystitis. In addition, meperidine has a short half-life and repeated doses can lead to accumulation of the metabolite normeperidine, which causes neuromuscular side effects and, rarely, seizures.

Bowel rest

In the management of acute pancreatitis, the treatment is to stop feeding the patient, giving them nothing by mouth, giving intravenous fluids to prevent dehydration, and sufficient pain control. As the pancreas is stimulated to secrete enzymes by the presence of food in the stomach, having no food pass through the system allows the pancreas to rest. Approximately 20% of patients have a relapse of pain during acute pancreatitis. Approximately 75% of relapses occur within 48 hours of oral refeeding.
The incidence of relapse after oral refeeding may be reduced by post-pyloric enteral rather than parenteral feeding prior to oral refeeding. IMRIE scoring is also useful.

Nutritional support

Acute pancreatitis is frequently understood in a catabolic state, characterized by profound metabolic, cardiovascular, pulmonary, hemodynamic, hematological and renal abbretions.
Recently, there has been a shift in the management paradigm from TPN to early, post-pyloric enteral feeding. The advantage of enteral feeding is that it is more physiological, prevents gut mucosal atrophy, and is free from the side effects of TPN. The additional advantages of post-pyloric feeding are the inverse relationship of pancreatic exocrine secretions and distance of nutrient delivery from the pylorus, as well as reduced risk of aspiration.
Disadvantages of a naso-enteric feeding tube include increased risk of sinusitis and a still-present risk of accidentally intubating the trachea even in intubated patients.

Oxygen

Oxygen may be provided in some patients if Pao2 levels fall below 70mm of Hg.

Antibiotics

Up to 20 percent of people with acute pancreatitis develop an infection outside the pancreas such as bloodstream infections, pneumonia, or urinary tract infections. These infections are associated with an increase in mortality. When an infection is suspected, antibiotics should be started while the source of the infection is being determined. However, if cultures are negative and no source of infection is identified, antibiotics should be discontinued.
Preventative antibiotics are not recommended in people with acute pancreatitis, regardless of the type or disease severity

ERCP

If a gallstone is detected, Endoscopic retrograde cholangiopancreatography, performed within 24 to 72 hours of presentation with successful removal of the stone, is known to reduce morbidity and mortality. The indications for early ERCP are:
The risks of ERCP are that it may worsen pancreatitis, it may introduce an infection to otherwise sterile pancreatitis, and bleeding.

Surgery

Surgery is indicated for infected pancreatic necrosis and diagnostic uncertainty and complications. The most common cause of death in acute pancreatitis is secondary infection. Infection is diagnosed based on 2 criteria
Surgical options for infected necrosis include:
Acute pancreatitis patients recover in majority of cases.
Some may develop abscess, pseudocyst or duodenal obstruction.
In 5 percent cases, it may result in ARDS, DIC
Acute pancreatitis can be further divided into mild and severe pancreatitis.
Mostly the Ranson Criteria are used to determine severity of acute pancreatitis. In severe pancreatitis serious amounts of necrosis determine the further clinical outcome. About 20% of the acute pancreatitis are severe with a mortality of about 20%. This is an important classification as severe pancreatitis will need intensive care therapy whereas mild pancreatitis can be treated on the common ward.
Necrosis will be followed by a systemic inflammatory response syndrome and will determine the immediate clinical course. The further clinical course is then determined by bacterial infection. SIRS is the cause of bacterial translocation from the patients colon.
There are several ways to help distinguish between these two forms. One is the above-mentioned Ranson Score.
In predicting the prognosis, there are several scoring indices that have been used as predictors of survival. Two such scoring systems are the Ranson criteria and APACHE II indices. Most, but not all studies report that the Apache score may be more accurate. In the negative study of the APACHE-II, the APACHE-II 24-hour score was used rather than the 48-hour score. In addition, all patients in the study received an ultrasound twice which may have influenced allocation of co-interventions. Regardless, only the APACHE-II can be fully calculated upon admission. As the APACHE-II is more cumbersome to calculate, presumably patients whose only laboratory abnormality is an elevated lipase or amylase do not need assessment with the APACHE-II; however, this approach is not studied. The APACHE-II score can be calculated at .
Practice guidelines state:

Ranson score

The Ranson score is used to predict the severity of acute pancreatitis. They were introduced in 1974.

At admission

The criteria for point assignment is that a certain breakpoint be met at any time during that 48 hour period, so that in some situations it can be calculated shortly after admission. It is applicable to both gallstone and alcoholic pancreatitis.
Alternatively, pancreatitis can be diagnosed by meeting any of the following:

Alternative Ranson score

of ≥ 8
Organ failure
Substantial pancreatic necrosis
Interpretation
If the score ≥ 3, severe pancreatitis likely.
If the score < 3, severe pancreatitis is unlikely
Or
Score 0 to 2 : 2% mortality
Score 3 to 4 : 15% mortality
Score 5 to 6 : 40% mortality
Score 7 to 8 : 100% mortality

APACHE II score

"Acute Physiology And Chronic Health Evaluation" score > 8 points predicts 11% to 18% mortality
Developed in the early 1990s by Emil J. Balthazar et al., the Computed Tomography Severity Index is a grading system used to determine the severity of acute pancreatitis. The numerical CTSI has a maximum of ten points, and is the sum of the Balthazar grade points and pancreatic necrosis grade points:
Balthazar grade
Balthazar gradeAppearance on CTCT grade points
Grade ANormal CT0 points
Grade BFocal or diffuse enlargement of the pancreas1 point
Grade CPancreatic gland abnormalities and peripancreatic inflammation2 points
Grade DFluid collection in a single location3 points
Grade ETwo or more fluid collections and / or gas bubbles in or adjacent to pancreas4 points

Necrosis score
Necrosis percentagePoints
No necrosis0 points
0 to 30% necrosis2 points
30 to 50% necrosis4 points
Over 50% necrosis6 points

CTSI's staging of acute pancreatitis severity has been shown by a number of studies to provide more accurate assessment than APACHE II, Ranson, and C-reactive protein level. However, a few studies indicate that CTSI is not significantly associated with the prognosis of hospitalization in patients with pancreatic necrosis, nor is it an accurate predictor of AP severity.

Glasgow score

The Glasgow score is valid for both gallstone and alcohol induced pancreatitis, whereas the Ranson score is only for alcohol induced pancreatitis. If a patient scores 3 or more it indicates severe pancreatitis and the patient should be considered for transfer to ITU. It is scored through the mnemonic, PANCREAS:
Predicts mortality risk in pancreatitis with fewer variables than Ranson's criteria. Data should be taken from the first 24 hours of the patient's evaluation.
Patients with a score of zero had a mortality of less than one percent, whereas patients with a score of five had a mortality rate of 22 percent. In the validation cohort, the BISAP score had similar test performance characteristics for predicting mortality as the APACHE II score. As is a problem with many of the other scoring systems, the BISAP has not been validated for predicting outcomes such as length of hospital stay, need for ICU care, or need for intervention.

Epidemiology

In the United States, the annual incidence is 18 cases of acute pancreatitis per 100,000 population, and it accounts for 220,000 hospitalizations in the US. In a European cross-sectional study, incidence of acute pancreatitis increased from 12.4 to 15.9 per 100,000 annually from 1985 to 1995; however, mortality remained stable as a result of better outcomes. Another study showed a lower incidence of 9.8 per 100,000 but a similar worsening trend over time.
In Western countries, the most common cause is alcohol, accounting for 65 percent of acute pancreatitis cases in the US, 20 percent of cases in Sweden, and 5 percent of those in the United Kingdom. In Eastern countries, gallstones are the most common cause of acute pancreatitis. The causes of acute pancreatitis also varies across age groups, with trauma and systemic disease being more common in children. Mumps is a more common cause in adolescents and young adults than in other age groups.