Overview
Acute pancreatitis describes the acute inflammation of the pancreas with varying involvement of the surrounding tissues or more remote organ systems. It is not possible to classify the severity of acute pancreatitis based on clinical features at presentation. Severity can broadly be classified as:
- Mild acute pancreatitis – most common:
- Inflammation of the pancreas with resolution in the first week
- There are no associated local or systemic complications
- Moderately severe acute pancreatitis:
- Inflammation of the pancreas with local complications and/or transient organ failure that resolves within 48 hours
- Severe acute pancreatitis:
- Inflammation of the pancreas with persistent single or multiorgan failure for more than 48 hours
A patient cannot be classified as having mild acute pancreatitis until 48 hours have passed after the onset of symptoms. This is because many patients may go on to develop severe disease later.
Pathophysiology
Initiation
Abnormal activation and secretion of digestive enzymes (particularly trypsinogen) within the pancreas lead to digestion of the pancreatic tissue (autodigestion). This leads to inflammation and oedema in the pancreas, which can result in necrosis.
Local complications
Inflammation and damage of the pancreas can lead to local complications:
- Pancreatic necrosis:
- Can lead to systemic complications and infection
- 80% of deaths from acute pancreatitis are due to infected pancreatic necrosis
- Pseudocysts:
- Inflammation leads to thick-walled collections of pancreatic fluid, usually at least 4 weeks after the onset of acute pancreatitis
- Pancreatic abscesses
- Pancreatic fistulae which can extend from the pancreatic ducts to the:
- Abdominal cavity, causing ascites
- Pleural cavity, causing pleural effusion
- Pericardial cavity, causing pericardial effusion
Systemic complications
Damage to the pancreatic tissue leads to the release of danger-associated molecular patterns (DAMPs) which results in a systemic inflammatory response and recruitment of neutrophils to the pancreas.
The systemic inflammatory response leads to the systemic complications seen in acute pancreatitis:
- Increased capillary permeability which can lead to:
- Hypovolaemia and shock: fluid shifts out of the intravascular compartment (‘third spacing)
- Systemic inflammation which can lead to:
- Disseminated intravascular coagulopathy:
- Leads to thrombosis throughout the body, impairing blood flow to organs such as the kidneys causing acute kidney injury. If severe enough, this can cause multiorgan failure
- This can also cause retroperitoneal haemorrhage which gives rise to the following signs:
- Cullen’s sign – periumbilical discolouration
- Grey-Turner’s sign – flank discolouration
- Fat necrosis and hypocalcaemia:
- Lipases released from the pancreas can digest surrounding lipids into free fatty acids which bind with serum calcium to form chalky, insoluble, deposits in fatty tissue, leading to hypocalcaemia.
Causes
Overview
The most common causes of acute pancreatitis are gallstones and alcohol misuse, making up around 75% of cases.
- Gallstones can block the pancreatic duct, triggering autodigestion and pancreatitis
- Alcohol is thought to be directly toxic to the pancreas
The mnemonic I GET SMASHED is often used to remember the causes of acute pancreatitis:
- Idiopathic (10%)
- Gallstones (50%)
- Ethanol (alcohol, 25%)
- Trauma
- Steroids
- Mumps
- Autoimmune pancreatitis
- Scorpion stings
- Hyperlipidaemia, hypercalcaemia, hypothermia
- Hypercalcaemia can cause pancreatitis and pancreatitis can cause hypocalcaemia
- Endoscopic retrograde cholangiopancreatography (ERCP)
- Drugs – azathioprine, mesalazine, bendroflumethiazide, furosemide, corticosteroids, sodium valproate
Epidemiology
- Acute pancreatitis is one of the most common gastrointestinal disorders requiring hospital admission
- Incidence in the UK is around 56 per 100,000 per year and is thought to be increasing
Presentation
Overview
- Acute, severe, epigastric, constant pain that radiates to the back – mostcommon:
- Usually increases in severity over hours before plateauing
- Often described as sharp or ‘being stabbed with a knife’
- Often worsened with movement and eased when in the foetal position
- The intensity of pain is not correlated with disease severity as in rare cases, people can present without abdominal pain
- Nausea – very common in up to 80% of cases
- Vomiting may also be present
- Anorexia – commonly seen
Examination findings
An examination may show:
- Signs of shock/hypovolaemia – tachycardia, tachypnoea, hypotension
- Fever
- Abdominal distention – common and due to fluid leakage in the peritoneum
- Abdominal tenderness and features of Peritonitis
- Reduced/absent bowel sounds – suggests ileus has developed
- Reduced air entry and dullness to percussion – suggest pleural effusion (50%)
- Haemorrhagic features, generally rare:
- Cullen’s sign – periumbilical discolouration (bluish)
- Grey-Turner’s sign – flank discolouration (bluish)
Investigations
Initial tests and diagnosis
All patients with suspected acute pancreatitis require urgent admission to hospital for investigations and management.
If a patient has characteristic signs and symptoms (epigastric pain, fever, tachycardia etc.), then acute pancreatitis can be diagnosed using lipase/amylase without imaging:
- Serum lipase or amylase:
- >3 times the upper limit of normal in acute pancreatitis
- Lipase levels remain elevated for longer (up to 14 days compared to 5 for amylase), allowing for detection in people who present later
- The accuracy of lipase/amylase decreases over time
- Lipase/amylase values do not correlate with the prognosis
- Up to ¼ of people may have normal lipase/amylase results, do not use lipase/amylase only and consider the full clinical picture
- Abdominal CT with contrast – not necessary in most patients:
- Most patients do not need imaging to confirm a diagnosis of acute pancreatitis.
- An abdominal CT with contrast may be used if lipase/amylase is not elevated enough to confirm pancreatic inflammation
- Investigations for the underlying cause (e.g. abdominal ultrasound):
- Although imaging is not needed for diagnosis of acute pancreatitis in all patients, early ultrasound imaging is important to look for an underlying cause (e.g. gallstones or biliary obstruction)
In summary, if a patient presents with characteristic features of acute pancreatitis and lipase/amylase is >3 times the upper limit of normal, they can be diagnosed with acute pancreatitis without the need for a CT scan. If lipase/amylase is not elevated enough, the CT scan can confirm pancreatic inflammation. In all patients diagnosed with acute pancreatitis, an early abdominal ultrasound is performed to look for gallstones and other causes.
Do not assume that someone’s acute pancreatitis is due to alcohol just because they drink alcohol.
Other tests
Other non-diagnostic tests may be performed to help with identifying complications and prognostication:
- Full blood count (FBC):
- Leukocytosis with a left shift is often seen
- Thrombocytopenia may be seen in severe pancreatitis
- Dehydration may result in an elevated haematocrit, which is associated with a poorer prognosis
- C-reactive protein (CRP):
- Non-specific marker of inflammation, may be elevated, suggesting pancreatic necrosis
- Urea and electrolytes (U&Es):
- May show renal dysfunction due to hypovolaemia or disseminated intravascular coagulation
- Serum calcium:
- Hypercalcaemia can cause acute pancreatitis
- Acute pancreatitis can cause hypocalcaemia and is a poor prognostic factor
- Liver function tests (LFTs):
- If deranged, gallstones may be the likely cause
- Chest X-ray:
- May show pleural effusions, atelectasis, or an elevated hemidiaphragm, or infiltrates
Scoring and Prognostication
Overview
Commonly used scoring systems include the Glasgow Prognostic Score, Ranson’s Criteria, and the Acute Physiology and Chronic Health Evaluation II (APACHE) score which can indicate prognosis.
They have differing criteria, however, the following factors are common to most of them, suggesting severe pancreatitis and a poorer prognosis:
- Age >55 years old
- White cell count >15 x 109/L
- Hypocalcaemia
- Hyperglycaemia
- Hypoxia
- Elevated lactate dehydrogenase (LDH)
- Elevated AST
Management
Initial treatment
Initial treatment is supportive and aims at stabilising the patient, giving analgesia, and managing local and systemic complications. Important aspects include:
- IV fluids – aggressive fluid resuscitation with crystalloids, the most important step:
- Large amounts of fluid loss can occur in acute pancreatitis, even if mild
- Early and aggressive fluid resuscitation reduces the effects of hypovolaemia, hypoperfusion, and end-organ damage
- Urine output should be monitored and people with severe pancreatitis may require catheterisation
- Oxygen:
- Monitor oxygen saturations and treat hypoxia accordingly
- Analgesia – pain in acute pancreatitis is severe:
- The pain in acute pancreatitis is severe. Breathing may exacerbate pain which can worsen acute pancreatitis.
- IV opioids are often needed
- Nutrition:
- Patients should not be made nil-by-mouth routinely unless there is an obvious reason to (e.g. nausea, vomiting, or ileus)
- Enteral feeding (either orally or by a feeding tube such as a nasogastric tube) is beneficial in acute pancreatitis as it is thought to continually move bacteria through the gastrointestinal tract and reduce the risk of pancreatic tissue infection
- If enteral feeding is contraindicated or unsuccessful, parenteral nutrition is used as a last resort as it is associated with an increased risk of pancreatic necrosis and mortality
- Do not give prophylactic antibiotics routinely:
- They should only be given to those with confirmed or clinically suspected pancreatic/extra-pancreatic infection (such as infected pancreatic necrosis, pneumonia, acute cholangitis, or sepsis)
- There is no good evidence to support their use routinely to prevent infection
- Some patients may require treatment in an intensive care unit or high-dependency unit
Treating local complications
- Pancreatic necrosis:
- In cases of infected pancreatic necrosis or continued deterioration, drainage or necrosectomy (removal of necrotic tissue)/debridement may be necessary
- Signs of infected pancreatic necrosis include: worsening fever, increasing inflammatory markers, new/persistent organ failure, or imaging showing gas within the areas of necrosis
- Pancreatic head pseudocysts:
- If symptomatic (e.g. pain, vomiting, weight loss): treat with endoscopic ultrasound-guided drainage or endoscopic transpapillary drainage
- If asymptomatic: consider treating if associated with pancreatic duct disruption, they apply pressure on blood vessels or the diaphragm, they are at risk of rupture, or infection is suspected
- Laparoscopic/open surgery may be necessary if endoscopic techniques are unsuitable or have failed
Treating the underlying cause
After patients are resuscitated and stabilised, the underlying cause should be sought and treated:
- Gallstones and cholecystectomy:
- All patients with acute pancreatitis should have an abdominal ultrasound to screen for gallstones
- If present, cholecystectomy should be performed to reduce the risk of recurrence
- For people with mild pancreatitis, this is done during the initial admission, but for more severe disease, this is often delayed until inflammation has resolved (often around 6 weeks)
- Gallstones and ERCP:
- Patients with gallstones and coexisting bile duct obstruction and/or cholangitis should undergo ERCP
- Alcohol-related acute pancreatitis:
- Manage alcohol withdrawal if necessary and offer alcohol abstinence counselling if appropriate
Monitoring and Patient Advice
Overview
Upon discharge, patients should be given advice and support with modifying risk factors where possible, such as excess alcohol consumption and hypertriglyceridaemia. They should also be given safety-netting advice to recognise acute pancreatitis and seek immediate help should it occur again.
Complications
The complications of acute pancreatitis and how they arise are described above under ‘Pathophysiology’.
Prognosis
- Around 80% of patients have mild acute pancreatitis and recovery without complications after 3-7 days with conservative management
- The mortality rate is around 5% in mild cases and increases up to 30% in severe cases
- Some studies suggest that up to 10% of people (mainly men) can go on to develop chronic pancreatitis
