Acute Pancreatitis

What is Acute Pancreatitis?

Acute pancreatitis is a serious medical condition that needs to be treated urgently. In this condition the pancreas becomes inflamed over a short period of time.

What is the pancreas and what does it do?

The pancreas is a small elliptical organ that is shaped like a tadpole. It is located behind the stomach and below the ribcage.

Its main functions are to secrete enzymes and digestive juices that help the gastrointestinal tract digest food.

The pancreas also releases hormones that regulate various biochemical parameters. For example, the pancreas secretes the insulin hormone. Insulin regulates the levels of sugar (glucose) in the blood.

Symptoms of acute pancreatitis

Acute pancreatitis is typically characterized by a sudden onset severe pain in the centre of the abdomen. The pain may be excruciating and most patients also complain of feeling sick (nauseous) or may even vomit.

Types of acute pancreatitis

Acute pancreatitis may be of two types – mild or severe. The mild form affects most of patients and the severe form is rare.

Those with mild acute pancreatitis have inflammation of their pancreas that improves within three to five days. Mild acute pancreatitis is still severe and may need urgent treatment.

The difference between mild and severe forms is that in mild forms the person recovers without complications. Those with severe acute pancreatitis have severe inflammation of their pancreas and this may lead to life threatening complications like spread of the inflammation throughout the body leading to multiple organ failure.

Who gets acute pancreatitis?

Pancreatitis worldwide occurs commonly among people who suffer from gall bladder stones and those who take in excessive alcohol. In some persons the inflammation may persist for many years giving rise to chronic pancreatitis.

Acute pancreatitis is an uncommon condition. In the United Kingdom, around 1 in every 2,500 people will develop acute pancreatitis annually. Acute pancreatitis is responsible for around 25,000 hospital admissions and 950 deaths each year in England.

With the rise of obesity and alcohol consumption the rates of acute pancreatitis has risen sharply over the last few decades.

Treatment of acute pancreatitis

At present there is no cure for acute pancreatitis. Treatments are based on alleviating symptoms and control the inflammation. Acute pancreatitis will require admission to hospital.

Mild acute pancreatitis can be treated in a general hospital ward but severe form will require admission to a high dependency unit or an intensive care unit (ICU).

Prognosis

The outlook or prognosis of mild acute pancreatitis is good and most people are well enough to be discharged from the hospital in a week or two. However, precautions like stopping or reducing alcohol intake should be taken to reduce the risk of a repeat attack.

Those with severe acute pancreatitis are more at risk for complications. The risk of death is as high as 1 in 3. It could be several months before the patient is discharged from the hospital in case of a recovery.

Acute Pancreatitis Causes

The causes of acute pancreatitis are not well understood. There are several risk factors that are associated with acute pancreatitis. The actual cause that sets in the inflammation inside the pancreas are not clear.

Enzyme secretion

Trypsin is an enzyme secreted by the pancreas. This enzyme helps to break down the proteins in food to help digest food. This is a very strong enzyme and while within the pancreas, it stays in an inactive form and has no digestive properties.

Once it moves out of the pancreas and into the intestines, it becomes active and starts to break down proteins.

In pancreatitis this trypsin may become active while still within the pancreas leading to damage to the pancreas and inflammation.

Presence of gall bladder stones

This is one of the commonest risk factors associated with acute pancreatitis. Gall bladder stones are hard stones that can form if the bile within the gall bladder has too much cholesterol and other minerals. Presence of gall bladder stones is called cholelithiasis.

These gall stones can also block the openings (ducts) to the pancreas. The blockage of the pancreatic ducts may lead to premature the activation of trypsin inside the pancreas and lead to acute inflammation.

Excessive alcohol consumption

Alcohol is normally metabolized by the liver. There are studies that suggest that alcohol may affect the normal workings of the cells of the pancreas and this may lead to a premature activation of the enzyme trypsin that damages the pancreas cells to lead to inflammation.

Alcohol is a direct risk factor for acute pancreatitis. Binge drinking or drinking large amounts of alcohol at one sitting also raises the risk of acute pancreatitis significantly.

Damage to the pancreas

Damage to the pancreas and its ducts during a type of surgery known as endoscopic retrograde cholangiopancreatography (ERCP). ERCP is generally used for the removal of the gall bladder stones.

Medications

Some medications may cause acute pancreatitis as their side effect. These include diuretics (water pills) like thiazides, furosemide, anticancer drugs like azathioprine, mercaptopurine, L-Asparaginase hormonal drugs like oestrogens (oral contraceptives), heart drugs like procainamide, ACE inhibitors, losartan, and antibiotics like  sulphonamides, erythromycin, tetracycline, pentamidine, metronidazole, nucleoside-analogue reverse transcriptase inhibitors, anti-seizure drugs valproic acid, pain relievers like paracetamol, salicylates and general anesthetics like propofol.

Poisons

Some poisons may also cause pancreatitis. These include methyl alcohol, poisoning with organophosphates, scorpion venom etc.

Infections

Some infections like measles virus, coxsackie B virus, ascariasis, mycoplasma, viral hepatitis (Hepatitis A, B and C), HIV, varicella virus, cytomegalovirus, Epstein-Barr virus, adenovirus, echo virus, leptospirosis, legionella, campylobacter jejuni,   tuberculosis, mycobacterium avium and mumps virus may lead to pancreatic inflammation.

Obesity

Obesity with a body mass index (BMI) of over 30 is a risk factor for pancreatitis.

Smokers

Smokers and those over the age of 70 are at a greater risk of pancreatic inflammation.

Genetics

Studies have shown that those with a specific genetic mutation, known as the MCP-1 mutation, are eight times more likely to develop severe acute pancreatitis than others with no such mutation.

Cholesterol levels

Those with high blood levels of a special type of cholesterol called triglycerides especially while pregnant are at a greater risk of pancreatitis.

Metabolic conditions

Other metabolic conditions that raise risk of pancreatitis include:-

  • high blood calcium
  • high levels of chylomicrons (special fat particles in blood)
  • diabetic ketoacidosis
  • high levels of ureas in blood
  • low body temperature (hypothermia)
  • advanced stages of pregnancy etc.

Lack of blood to the pancreas

Conditions leading to deprivation of blood to the pancreas may also lead to pancreatitis. These include systemic lupus erythematosus, polyarteritis nodosa, thrombotic thrombocytopaenic purpura, cardiopulmonary bypass, duodenal ulcer etc.

Idiopathic

There may be no reason or cause or presence of a risk factor in some patients presenting with acute pancreatitis. These cases are termed idiopathic.

Acute Pancreatitis Pathogenesis

Acute pancreatitis is generally considered to occur in three phases.

First phase

This phase involves a premature activation of the powerful enzyme called trypsin. Normally the pancreas contains trypsin in an inactive form within the acinar cells. Once it is released in the gut this enzyme breaks down proteins present in the food.

The pancreatic cells are protected from this enzyme by its presence as an inactive form within the pancreas. In the first phase of pancreatitis there is premature activation of this enzyme called trypsin.

There are several mechanisms by which this premature activation may take place. There may be a disruption of calcium signaling in acinar cells or breakdown of trypsinogen to trypsin by the enzyme lysosomal hydrolase cathepsin-B or decreased activity of the intracellular pancreatic trypsin inhibitor.

Once activated trypsin in turn activates several pancreatic digestive enzymes. These enzymes bring in the process of self digestion of the pancreatic cells.

Second phase

In this phase the activated trypsin causes inflammation within the pancreas.

Third phase

In this phase the inflammation within the pancreas spreads to other organs for example acute respiratory syndrome (ARDS).

Both the second and third phase of inflammation is medicated by cytokines and other inflammatory mediators. These mediators lead to activation of inflammatory cells and this set in a chain of events. The other inflammatory cells are activated and these bind to the cells lining the blood vessels.

There is activation blood coagulation or clotting factors. These spread to other organs as well via blood. The blood vessel walls become leaky and begin to release the inflammatory cells. In addition to inflammatory cells, free radicals are also released along with other chemical mediators of inflammation like cytokines (tumor necrosis factor (TNF), interleukins, arachidonic acid metabolites, platelet activator factor, leukotrines, prostaglandins, substance P, mitogen-activated protein kinase, P-selectin or E-selectin, heat shock proteins etc.

In most patients acute pancreatitis is mild. In around 10 to 20% patients there may be severe inflammation. This may lead to systemic inflammatory response syndrome (SIRS). Gall bladder stone and alcohol consumption are linked to acute pancreatitis.

Acute Pancreatitis Treatment

Pain control

Originally it was thought that analgesia should not be provided by morphine because it may cause spasm of the sphincter of Oddi and worsen the pain, so the drug of choice was meperidine. However, due to lack of efficacy and risk of toxicity of meperidine, more recent studies have found morphine the analgesic of choice. Meperidine may still be used by some practitioners in more minor cases, or where morphine is contraindicated.

Bowel rest

In the management of acute pancreatitis, the treatment is to stop feeding the patient, giving him or her 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.. However, the one study in the meta-analysis that used a quinolone, and a subsequent randomized controlled trial that studied ciprofloxacin were both negative .

Carbapenems

An early randomized controlled trial of imipenem 0.5 gram intravenously every eight hours for two weeks showed a reduction in from pancreatic sepsis from 30% to 12%.

Another randomized controlled trial with patients who had at least 50% pancreatic necrosis found a benefit from imipenem compared to pefloxacin with a reduction in infected necrosis from 34% to 20%

A subsequent randomized controlled trial that used meropenem 1 gram intravenously every 8 hours for 7 to 21 days stated no benefit; however, 28% of patients in the group subsequently required open antibiotic treatment vs. 46% in the placebo group. In addition, the control group had only 18% incidence of peripancreatic infections and less biliary pancreatitis that the treatment group (44% versus 24%).

Summary

In summary, the role of antibiotics is controversial. One recent expert opinion (prior to the last negative trial of meropenem

ERCP

Early ERCP (endoscopic retrograde cholangiopancreatography), performed within 24 to 72 hours of presentation, is known to reduce morbidity and mortality. The indications for early ERCP are as follows :

  • Clinical deterioration or lack of improvement after 24 hours
  • Detection of common bile duct stones or dilated intrahepatic or extrahepatic ducts on CT abdomen

The disadvantages of ERCP are as follows :

  • ERCP precipitates pancreatitis, and can introduce infection to sterile pancreatitis
  • The inherent risks of ERCP i.e. bleeding

It is worth noting that ERCP itself can be a cause of pancreatitis.

Surgery

Surgery is indicated for (i) infected pancreatic necrosis and (ii) diagnostic uncertainty and (iii) complications. The most common cause of death in acute pancreatitis is secondary infection. Infection is diagnosed based on 2 criteria

  • Gas bubbles on CT scan (present in 20 to 50% of infected necrosis)
  • Positive bacterial culture on FNA (fine needle aspiration, usually CT or US guided) of the pancreas.

Surgical options for infected necrosis include:

  • Minimally invasive management - necrosectomy through small incision in skin (left flank) or stomach
  • Conventional management - necrosectomy with simple drainage
  • Closed management - necrosectomy with closed continuous postoperative lavage
  • Open management - necrosectomy with planned staged reoperations at definite intervals (up to 20+ reoperations in some cases)

Other measures

  • Pancreatic enzyme inhibitors are not proven to work.
  • The use of octreotide has not been shown to improve outcome.

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Acute Pancreatitis Diagnosis

Acute pancreatitis is a medical emergency and needs to be diagnosed immediately upon admission with severe abdominal pain.

Significant history of risk factors like obesity, alcohol use, gall bladder stones are obtained and acute pancreatitis is suspected. The abdomen feels tender or painful to touch.

Tests for acute pancreatitis

Several diagnostic, laboratory and imaging studies are prescribed. These include:-

Blood tests

The pancreas during its inflamed state produces high levels of two chemicals called amylase and lipase. Testing the levels of these two chemicals can help detect pancreatitis.

Other blood tests prescribed within the first 24 hours of onset of symptoms include assessment of liver biochemistry, calcium levels and blood triglycerides.

Imaging studies

Initially the first imaging study performed is an abdominal ultrasound scan. This can help detect presence of gall bladder stones.

A computerized tomography (CT scan) can show the picture of the damaged pancreas in details.

During early stages of acute pancreatitis symptoms alone cannot determine the severity of the inflammation. An X ray or CT scan helps in detecting the extent of inflammation.

The role of magnetic resonance imaging (MRI) in the diagnosis of acute pancreatitis and establishment of severity is not yet established.

An endoscopic retrograde cholangiopancreatography (ERCP) ERCP involves the use of a narrow, flexible tube, known as an endoscope. The endoscope has a camera on one end. It will be guided into the intestines using an ultrasound as guidance. ERCP detects gall bladder, bile duct and pancreas pathologies.

Characteristic symptoms of acute pancreatitis

Characteristic symptoms that are often diagnostic of acute pancreatitis include two of the three features including:-

1 - Characteristic pain in the abdomen

2 - Rise of serum amylase or lipase levels of over three times the upper limit of normal value. Generally both amylase and lipase are elevated during the course of acute pancreatitis. The serum lipase may remain elevated slightly longer than amylase.

This said, the extent of rise or peak levels of amylase and lipase are not directly associated with the severity of acute pancreatitis. Serum lipase may remain normal in some nonpancreatic pathologies whereas serum amylase may be raised in several non-pancreatic pathologies. This includes macroamylasemia, parotitis, and some cancers.

Although routine and daily monitoring of these enzymes is of little value in determining the gradual recovery, it has been seen that is serum amylase and/or lipase remain elevated for several weeks, there may be persisting pancreatic inflammation, blockage of the pancreatic duct or presence of a pseudocyst.

3 - Specific findings related to pancreatic inflammation on CT scan. A CT scan along with special contrast dyes can clearly delineate areas of the pancreas that have been damaged by the inflammation.

Contrast CT scan also helps in diagnosing the cause of pancreatic inflammation including presence of common bile duct stones, pancreatic calcifications, chronic pancreatitis caused by excessive alcohol consumption or pancreas cancers.

Acute Pancreatitis Symptoms

Acute pancreatitis is an emergency that needs to be treated urgently. There are a few warning symptoms that may occur suddenly and the patient needs to seek help immediately if these symptoms occur.

The symptoms of acute pancreatitis include:-

  • The commonest symptom of acute pancreatitis is sudden onset of a severe pain in the center of the upper abdomen. The pain is dull in nature and is located at the top of the abdomen.

  • The pain gets worse over time and there is a constant pain.

  • The pain may radiate or travel from the abdomen to the back and worsens after a meal. The pain may especially be worse after a large meal for persons who have developed acute pancreatitis due to presence of gall bladder stones.

  • The pain is eased to a certain extent when the patient curls up into a fetal position or curls up into a ball.

  • If the acute pancreatitis is brought about by alcohol, the pain often develops 6 to 12 hours after a drinking a large amount of alcohol.

  • Nausea and vomiting. Nausea is more common and may be accompanied by retching.

  • Diarrhea

  • Loss of appetite

  • There may be a high rise of temperature over 38°C or 100.4°F.

  • Some patients may also present with liver damage. This is called jaundice and is typically manifested by yellowing of the whites of the eyes, nail beds and skin.

  • There may be excessive sweating and there is a rapid heart rate or palpitation

  • Some patients may experience abnormal bloating of the abdomen.

  • In very severe cases the patient may lose consciousness or collapse

  • Symptoms are often confused with other emergencies like heart attack, gall bladder stones, biliary colic, and perforation of a stomach or duodenum ulcer.