This 70 year old lady has presented with severe, persistent right upper abdominal pain, in association with mild fever, nausea, and vomiting. Examination reveals her to be febrile, with tenderness and guarding in the right hypochondriac region; in a nutshell, this is an acute abdomen. The potential differential diagnoses include gallbladder disease, acute pancreatitis, perforation of a duodenal ulcer, right lower lobar pneumonia, hepatitis, and perhaps, a subphrenic abscess. Note that the pain radiates towards the back; this is suggestive of a retroperitoneal origin, and favors choledocolithiasis, acute pancreatitis or a perforated duodenal ulcer. A liver profile, pancreatic enzyme assay, and ultrasound scan of the abdomen are essential next steps; the last reveals a normal hepatobiliary tract, making gallstones very unlikely. Unfortunately, the pancreas is not visualized, most likely due to bowel shadows. Note also that while the liver profile is within normal parameters, both serum amylase and serum lipase levels are elevated more than 3-fold; this is highly suggestive of exocrine involvement of the pancreas. Thus, when the clinical presentation and elevated pancreatic enzymes are considered together, moderate acute pancreatitis appears to be the diagnosis. Early and aggressive hydration is key in the management of moderate acute pancreatitis, and should be initiated as soon as intravenous access is established. Suitable analgesia is also very important; an opiate should be administered for pain relief. Following alleviation of symptoms, the next step should be to identify the etiology underlying the episode. Alcohol abuse and gallstones are the commonest causes of acute pancreatitis, but are excluded by the history and preceding investigations. Her unremarkable surgical history excludes acute pancreatitis associated with manipulation of sphincter of Oddi through endoscopic retrograde cholangiopancreatography (ERCP), or post cardiac surgery; the absence of a suggestive family history excludes hereditary pancreatitis. Drug and toxin associated acute pancreatitis is also ruled out by the history; nor are there any preceding symptoms which would support an infection precipitating the episode. Given that the common causes of acute pancreatitis are mostly excluded, it behooves us to consider some of the less common etiologies - particularly pancreatic cancer and autoimmune pancreatitis. Considering the age of the patient, it is crucial to exclude the possibility of a pancreatic malignancy causing exocrine failure (and thus giving rise to high pancreatic enzyme levels); further imaging of the abdominal structures should be considered. In this respect, note that the National Comprehensive Cancer Network (NCCN) guidelines (version 1.2013) recommend computed tomography (CT) of the abdomen as the investigation of choice. However, this patient's CT scan excludes this possibility; instead, it merely reveals changes compatible with acute pancreatitis. The CT findings can also be used to exclude autoimmune pancreatitis, given the absence of diffuse narrowing of the pancreatic duct or irregularities of the wall (which are a key diagnostic criterion for the disease). Dyslipidemia can also give rise to acute pancreatitis, making a lipid profile important; while this demonstrates an elevated triglyceride level of 203 mg/dL, this is unlikely to be the cause, as values >1000 mg/dL are usually seen in such patients. Hypercalcemia is another potential etiology; and in this patient, assessment of serum calcium reveals both total and ionized calcium levels to be elevated. Thus, this might be very well be acute pancreatitis associated with hypercalcemia; she needs further assessment as to the underlying etiology, with both primary hyperparathyroidism and hypercalcemia of malignancy being important considerations; the possibility of excessive use of over-the-counter supplements containing calcium and/or Vitamin D should not be forgotten either. Considering the remaining aspects of her acute management, note that the American College of Gastroenterology (ACG) recommends against the routine use of prophylactic antibiotics in patients with moderate acute pancreatitis, unless there is evidence of sepsis or a septic focus. The fever in this patient is most likely secondary to inflammation, rather than infection or Vitamin D intoxication; this is supported by the unremarkable complete blood count. Thus, IV antibiotic therapy is probably best avoided for now. The ACG also recommends that oral intake be severely limited in the initial period; total parenteral nutrition (TPN) is only indicated if the patient remains nil per oral for 5 to 7 days or more. ERCP is definitely not indicated, given that her biliary tree appears pristine. The lady in this case subsequently underwent further investigation for the cause of the hypercalcemia; she was found to have a parathyroid adenoma, which was surgically resected.
Pancreatitis is an inflammatory process which results in autodigestion of the pancreatic gland. The sequelae are either healing without any morphological changes or functional impairment, a process known as acute pancreatitis; or an intermittent recurrence of symptoms contributing to functional and morphological loss of gland, which is referred to as chronic pancreatitis. Note that the remainder of this monograph pertains to acute pancreatitis alone; chronic pancreatitis (despite the similar sounding name), is a very different clinical entity. The incidence of acute pancreatitis ranges from 5 to 80 per 100,000 population; this has risen over the last few decades. Currently, the exact pathophysiologic insult triggering the episode of pancreatitis is unclear; however, both extracellular factors (such as neural and vascular responses) and intracellular factors (including increased calcium signalling, and activation of digestive enzymes and heat shock protein) are believed to play a role. Following initiation of the cellular injury pattern, inflammatory mediators (IL-6, IL-8, TNF-α) are released, resulting in increased pancreatic vascular permeability, with subsequent hemorrhage, edema, and pancreatic necrosis; this may culminate in the systemic inflammatory response syndrome (SIRS), and shock. The initial stage of the disease is characterized by parenchymal edema and peripheral fat necrosis; in severe episodes, hemorrhage and glandular dysfunction may follow, giving rise to hemorrhagic or necrotizing pancreatitis. Alcohol abuse, biliary tract disease, endoscopic retrograde cholangiopancreatography (ERCP), abdominal trauma and drugs are the etiologies most frequently implicated; less common causes (accounting for less than 1% of presentations) include infections, autoimmune pancreatitis, hereditary pancreatitis, toxins such as scorpion venom, surgical procedures, hypertriglyceridemia, hypercalcemia, hypothermia, tumours, developmental anomalies of the pancreas, and vascular abnormalities. A sudden onset, characteristically dull, and persistent abdominal pain is the cardinal sign of acute pancreatitis; radiation to the back is reported in half of all cases. Nausea and vomiting are often present, along with anorexia; an associated diarrhoea may also be seen. Physical examination may reveal fever and tachycardia, while upper abdominal tenderness, guarding and distension are observed in most patients; bowel sounds are often either diminished or absent. Note that only a minority of patients (28%) exhibit jaundice. Clinical findings associated with complicated disease include dyspnea, pleural effusions, tachypnea (in patients with associated acute respiratory distress syndrome), hematemesis, melena, and hemodynamic instability. Note that the Cullen sign, Grey-Turner sign, and erythematous skin nodules are uncommon findings associated with severe necrotizing pancreatitis. Key complications include intra abdominal infections, acute pseudocyst formation, pancreatic abscess formation, common bile duct obstruction, pancreatic necrosis, hemorrhage into the gastrointestinal tract, intestinal obstruction, fistulation, and multi organ failure. The diagnosis of acute pancreatitis is mainly clinical, with support from laboratory investigations such as as serum amylase and lipase (with three-fold elevations being more specific for the condition). Other investigations typically carried out include a complete blood count, liver profile, renal profile, serum electrolytes, c-reactive protein levels, random plasma glucose, and lipid profile. Note that arterial blood gas assays, lactic dehydrogenase levels, immunoglobulin G4 levels, and levels of trypsin and its precursor trypsinogen-2 are less frequently ordered; they are mainly of use in detecting the development of complications, and in evaluating the potential etiologies associated with the disease. Abdominal ultrasonography is the investigation of choice for the detection of potential underlying gallstones; however, the sensitivity is only 70% to 80% in the setting of acute pancreatitis. Note also that the most recent (2013) guidelines issued by the American College of Gastroenterology (ACG) state that abdominal computed tomography (CT) is not indicated in patients with mild acute pancreatitis, unless there is suspicion of a pancreatic tumour. However, CT is considered the imaging technique of choice for the assessment of complications in patients with severe disease, if there is absence of clinical improvement within the first 48 to 72 hours of hospitalisation, or in patients in whom the diagnosis is unclear. While not sensitive as ERCP, magnetic resonance cholangiopancreatography (MRCP) is playing an increasingly important role in the diagnosis of duct obstruction (both biliary and pancreatic) associated with pancreatitis. Note that ERCP should never be used as the first line diagnostic tool in patients with acute pancreatitis, and should be performed only if the patient has severe disease secondary to choledocholithiasis as observed on radiographic studies, or in the setting of biliary pancreatitis with clinical deterioration or worsening jaundice, even with maximal supportive therapy. Various staging methods have been used to predict the severity and likely outcome of episodes; these include the Ranson, Acute Physiology and Chronic Health Evaluation (APACHE) II, Glasgow, and Imrie scoring systems; note that none of these have been accepted as a universal standard. The medical management of mild acute pancreatitis includes intravenous hydration with fluids and adequate analgesia; the patient is kept nil per mouth until the pain and anorexia resolve. In patients with moderate to severe pancreatitis, nutritional support may be considered; this varies from enteral feeding via nasojejunal tubes, to total parenteral nutrition. Antibiotics are not routinely required even if the patient is febrile; they are generally used only if infected pancreatic necrosis occurs. Several studies have also evaluated the role of prophylactic empirical antibiotics in patients with severe acute necrotizing pancreatitis; however, this still remains a controversial topic. Note also that individuals with severe pancreatitis should be treated in an intensive care setting, as complications may potentially develop within hours. Surgical intervention should be considered in patients with gallstone pancreatitis, pancreatic duct disruption, pseudocyst formation, infected pancreatic necrosis, or pancreatic abscess formation. Avoidance of further episodes of acute pancreatitis depends on the causative etiology; in most patients, treatment of the underlying condition prevents recurrence. Note also that following discharge, a careful followup is essential to detect and treat any potential long term complications.