Pancreatitis

Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes (especially trypsin) that digest food are activated in the pancreas instead of the small intestine. It may be acute beginning suddenly and lasting a few days, or chronic occurring over many years. It has multiple causes and symptoms. Signs and symptoms The most common symptoms of pancreatitis are severe upper abdominal pain radiating to the back, nausea, and vomiting that is worsened with eating. The physical exam will vary depending on severity and presence of internal bleeding. Blood pressure may be elevated by pain or decreased by dehydration or bleeding. Heart and respiratory rates are often elevated. The abdomen is usually tender but to a lesser degree than the pain itself. As is common in abdominal disease, bowel sounds may be reduced from reflex bowel paralysis. Fever or jaundice may be present. Chronic pancreatitis can lead to diabetes or pancreatic cancer. Unexplained weight loss may occur from a lack of pancreatic enzymes hindering digestion. Causes Eighty percent of pancreatitis is caused by alcohol and gallstones. Gallstones are the single most common etiology of acute pancreatitis. Alcohol is the single most common etiology of chronic pancreatitis. Some medications are commonly associated with pancreatitis, most commonly corticosteroids such as prednisolone, but also including the HIV drugs didanosine and pentamidine, diuretics, the anticonvulsant valproic acid, the chemotherapeutic agents Lasparaginase and azathioprine, estrogen by way of increased blood triglycerides, cholesterollowering statins and the antihyperglycemic agent sitagliptin. There is an inherited form that results in the activation of trypsinogen within the pancreas, leading to autodigestion. Involved genes may include Trypsin 1, which codes for trypsinogen, SPINK1, which codes for a trypsin inhibitor, or cystic fibrosis transmembrane conductance regulator. Other common causes include trauma, mumps, autoimmune disease, scorpion stings, high blood calcium, high blood triglycerides, hypothermia, and endoscopic retrograde cholangiopancreatography (ERCP). Pancreas divisum is a common congenital malformation of the pancreas that may underlie some recurrent cases. Pregnancy can be a cause, possibly by increasing blood triglycerides. Diabetes mellitus type 2 is associated with a 2.8-fold higher risk. Less common causes include pancreatic cancer, pancreatic duct stones, vasculitis (inflammation of the small blood vessels in the pancreas), coxsackievirus infection, and porphyriaparticularly acute intermittent porphyria and erythropoietic protoporphyria. Infectious causes A number of infectious agents have been recognized as causes of pancreatitis.

Viruses

Coxsackie virus Cytomegalovirus Hepatitis B Herpes simplex virus Mumps

Varicella-zoster virus Bacteria Legionella Leptospira Mycoplasma

Salmonella Fungi

Aspergillus Parasites

Ascaris Cryptosporidium

Toxoplasma Diagnosis Diagnosing pancreatitis requires two of the following:

Characteristic abdominal pain Blood amylase or lipase will be 4-6 times higher than the normal variations, but this will be dependent on the laboratory that is testing the blood. Abdominal ultrasound is generally performed first, which is advantageous for the diagnosis of the causes of the pancreas, for example, detecting gallstones, and diagnosing alcoholic fatty liver (combined with history of alcohol consumption). They are both the main causes of pancreatitis. Abdominal ultrasound also shows an inflamed pancreatitis clearly. It is convenient, simple, non-invasive and inexpensive. Characteristic CT scan

Amylase or lipase is frequently part of the diagnosis; lipase is generally considered a better indicator, but this is disputed. Cholecystitis, perforated peptic ulcer, bowel infarction, and diabetic ketoacidosis can mimic pancreatitis by causing similar abdominal pain and elevated enzymes. The diagnosis can be confirmed by ultrasound and/or CT. Treatment The treatment of pancreatitis is supportive and depends on severity. Morphine generally is suitable for pain control. There is a claim that morphine may constrict the sphincter of Oddi, but this is controversial. There are no clinical studies to suggest that morphine can aggravate or cause pancreatitis or cholecystitis. Oral intake, especially fats, is generally restricted at first. Fluids and

electrolytes are replaced intravenously. However there is also evidence showing that earlier nutrition and feeding contributes to better recovery. The underlying cause should also be treated (targeting gallstones, discontinuing medications, cessation of alcohol etc.) The patient is monitored for complications. Prognosis Severe acute pancreatitis has high mortality rates, especially where necrosis of the pancreas has occurred. Several scoring systems are used to predict the severity of an attack of pancreatitis. They each combine demographic and laboratory data to estimate severity or probability of death. Examples include APACHE II, Ranson, and Glasgow. Apache II is available on admission; Glasgow and Ranson are simpler but cannot be determined for 48 hours. One form of the Glasgow criteria suggests that a case be considered severe if at least three of the following are true:

Age > 55 years Blood levels:

P02 Oxygen < 60mmHg or 7.9kPa White blood cells > 15 Calcium < 2 mmol/L Urea > 16 mmol/L Lactate dehydrogenase (LDH) > 600iu/L Aspartate transaminase (AST) > 200iu/L Albumin < 32g/L Glucose > 10 mmol/L

This can be remembered using the mnemonic PANCREAS: P02 Oxygen < 60mmHg or 7.9kPa Age > 55 Neutrophilia White blood cells > 15 Calcium < 2 mmol/L Renal Urea > 16 mmol/L Enzymes Lactate dehydrogenase (LDH) > 600iu/L Aspartate transaminase (AST) > 200iu/L Albumin < 32g/L Sugar Glucose > 10 mmol/L Complications Early complications include shock, infection, systemic inflammatory response syndrome, low blood calcium, high blood glucose, and dehydration. Blood loss, dehydration, and fluid leaking into the abdominal cavity (ascites) can lead to kidney failure. Respiratory complications are often severe. Pleural effusion is usually present. Shallow breathing from pain can lead to lung collapse. Pancreatic enzymes may attack the lungs, causing inflammation. Severe inflammation can lead to intra-abdominal hypertension and abdominal compartment syndrome, further impairing renal

and respiratory function and potentially requiring management with an open abdomen (laparostomy) to relieve the pressure]. Late complications include recurrent pancreatitis and the development of pancreatic pseudocysts collections of pancreatic secretions that have been walled off by scar tissue. These may cause pain, become infected, rupture and bleed, block the bile duct and cause jaundice, or migrate around the abdomen. Acute necrotizing pancreatitis can lead to a pancreatic abscess, a collection of pus caused by necrosis, liquefaction, and infection. This happens in approximately 3% of cases, or almost 60% of cases involving more than two pseudocysts and gas in the pancreas.

Chronic pancreatitis Chronic pancreatitis is a long-standing inflammation of the pancreas that alters its normal structure and functions. It can present as episodes of acute inflammation in a previously injured pancreas, or as chronic damage with persistent pain or malabsorption. Symptoms Patients with chronic pancreatitis usually present with persistent abdominal pain or steatorrhea resulting from malabsorption of the fats in food. Diabetes is a common complication due to the chronic pancreatic damage and may require treatment with insulin. Some patients with chronic pancreatitis look very sick, while others don't appear to be unhealthy at all. Considerable weight loss, due to malabsorption, is evident in a high percentage of patients, and can continue to be a health problem as the condition progresses. The patient may also complain about pain related to their food intake, especially those meals containing a high percentage of fats and protein. Some chronic pancreatitis patients do not experience pain while others suffer from constant, debilitating pain. Weight loss can also be attributed to a reduction in food intake in patients with severe abdominal pain. Causes

Alcohol Tropical (nutritional) Hereditary Trypsinogen and inhibitory protein defects Cystic fibrosis Idiopathic Trauma Hypercalcaemia

Calcific stones

In developed countries, the most common causes of chronic pancreatitis are alcohol and idiopathic. Across the rest of the world malnutrition and associated dietary factors have been implicated. In a small group of patients chronic pancreatitis has been shown to be hereditary, inherited as an autosomal dominant condition with variable penetrance. Almost all patients with cystic fibrosis have established chronic pancreatitis, usually from birth. Cystic fibrosis gene mutations have also been identified in patients with chronic pancreatitis but in whom there were no other manifestations of cystic fibrosis. Obstruction of the pancreatic duct because of either a benign or malignant process may result in chronic pancreatitis. Congenital abnormalities of the pancreatic duct, in particular pancreas divisum, have been implicated. Diagnosis The diagnosis of chronic pancreatitis is typically based on tests on pancreatic structure and function, as direct biopsy of the pancreas is considered excessively risky. Serum amylase and lipase may or may not be moderately elevated in cases of chronic pancreatitis, owing to the uncertain levels of productive cell damage, though elevated lipase is the more likely found of the two. Amylase and lipase are nearly always found elevated in the acute condition along with an elevated CRP inflammatory marker that is broadly in line with the severity of the condition. A secretin stimulation test is considered the gold standard functional test for diagnosis of chronic pancreatitis but not often used clinically. The observation that bi-carbonate production is impaired early in chronic pancreatitis has led to the rationale of use of this test in early stages of disease (sensitivity of 95%). Other common tests used to determine chronic pancreatitis are faecal elastase measurement in stool, serum trypsinogen, Computed tomography (CT), ultrasound, EUS, MRI, ERCP and MRCP. Pancreatic calcification can often be seen on plain abdominal X-rays, as well as CT scans. There are other non-specific laboratory studies useful in diagnosis of chronic pancreatitis. Serum bilirubin and alkaline phosphatase can be elevated, indicating stricturing of the common bile duct due to edema, fibrosis or cancer. When the chronic pancreatitis is due to an autoimmune process, elevations in ESR, IgG4, rheumatoid factor, ANA and antismooth muscle antibody may be seen. The common symptom of chronic pancreatitis, steatorrhea, can be diagnosed by two different studies: Sudan chemical staining of feces or fecal fat excretion of 7 grams or more over a 24hr period on a 100g fat diet. To check for pancreatic exocrine dysfunction, the most sensitive and specific test is the measurement of fecal elastase, which can be done with a single stool sample, and a value of less than 200 ug/g indicates pancreatic insufficiency.

Treatment The different treatment modalities for management of chronic pancreatitis are medical measures, therapeutic endoscopy and surgery. Treatment is directed, when possible, to the underlying cause, and to relieve pain and malabsorption. Insulin dependent diabetes mellitus may occur and need long term insulin therapy. The abdominal pain can be very severe and require high doses of analgesics, sometimes including opiates. Disability and mood problems are common, although early diagnosis and support can make these problems manageable. Alcohol cessation and dietary modifications (low-fat diet) are important to manage pain and slow the calcific process. Recent research indicates smoking may be a high-risk factor. Pancreatic Enzyme Supplementation Replacement pancreatic enzymes are often effective in treating the malabsorption and steatorrhea. However, the outcome from 6 randomized trials has been inconclusive regarding pain reduction. While the outcome of trials regarding pain reduction with pancreatic enzyme replacement is inconclusive, some patients do have pain reduction with enzyme replacement and since they are relatively safe, giving enzyme replacement to a chronic pancreatitis patient is an acceptable step in treatment for most patients. Treatment may be more likely to be successful in those without involvement of large ducts and those with idiopathic pancreatitis. Patients with alcoholic pancreatitis may be less likely to respond. Surgery Traditional Surgery for Chronic Pancreatitis tends to be divided into two areas - resectional and drainage procedures. New and proven transplantation options prevent the patient from becoming diabetic following the surgical removal (resection) of their pancreas. This is achieved by transplanting back in the patient's own insulin-producing beta cells.