Chapter 3 Acute pancreatitis
The pancreas is a gland located in the upper, posterior abdomen and is responsible for insulin production and the manufacture and secretion of digestive enzymes leading to carbohydrate, fat, and protein metabolism. Approximately 80% of the gross weight of the pancreas supports exocrine function, while the remaining 20% is involved with endocrine function.
In acute pancreatitis there are not only symptoms of acute inflammation in the pancreas are present. There are the signs of haemorrhages and necrotic processes, which are caused by autodigestion of tissues by pancreatic enzymes. Secondary infection and multiorgan system failure may be associated with autodigestion process.
The overall mortality rate of patients with acute pancreatitis is 10–15%. In patients with severe disease (necrosis and/or organ failure), the mortality rate is approximately 30%.
Anatomy of hepato-pancreato-duodenal region is demonstrated at fig. 14.
Bile and digestive – pancreatic reflux.
Obstruction and hypertension of biliary and pancreatic ducts.
Blood supply disturbance of pancreas.
Allergic and toxic process.
Peptic ulcer disease.
A number of factors are capable of initiating acute pancreatitis although their mechanism of action is not known. Alcoholism and biliary tract disease are the processes most commonly associated with pancreatitis: together they account for 80% of acute cases.
The most common cause of acute pancreatitis is gallstones passing into the bile duct and temporarily lodging at Oddi’s sphincter. The risk of a stone causing pancreatitis is inversely proportional to its size.
Alcohol. Most commonly, the disease develops in patients whose alcohol ingestion is habitual over 5–15 years. Alcoholics are usually admitted with an acute exacerbation of chronic pancreatitis.
Acute pancreatitis may be the first manifestation of a tumor causing pancreatic duct obstruction: pancreatic carcinoma should be considered in non-alcoholic patients in whom no biliary disease is identified.
Infectious agents which have been implicated as a course of pancreatitis include mumps virus, coxsackie virus, Mycoplasma and parasites.
Many drugs are capable of causing acute pancreatitis: these include thiazide diuretics, 6-mercaptopurine, azathioprine, oestrogens, frusemide, methyldopa, sulphonamides, tetracycline, pentamidine, enalapril, and procainamide.
Patients with types I and V hypertriglyceridaemia frequently suffer from pancreatitis, usually associated with extremely high levels of serum triglycerides. However, hypertriglyceridaemia can also be the result rather than the cause of pancreatitis.
Postoperative pancreatitis can be fatal and is often due to iatrogenic pancreatic trauma. Pancreatitis following cardiopulmonary bypass is being recognized with increasing frequency. The majority of cases are mild or even subclinical, but evidence of severe pancreatitis is found in 25% of patients who die following cardiac surgery.
Abdominal trauma causes an elevation of amylase and lipase levels in 17% of cases and clinical pancreatitis in 5% of cases. Pancreatic injury occurs more often in penetrating injuries (e.g., from knives, bullets) than in blunt abdominal trauma (e.g., from steering wheels, horses, bicycles). Blunt injury may crush the gland across the spine, leading to a ductal injury in that location.
Toxins. Exposure to organophosphate insecticide can cause acute pancreatitis. In Trinidad, the sting of the scorpion Tityus trinitatis is the most common cause of acute pancreatitis.
Hypercalcemia cause can lead to acute pancreatitis. Causes include hyperparathyroidism, excessive doses of vitamin D, familial hypocalciuric hypercalcemia and total parenteral nutrition.
Developmental abnormalities of the pancreas. Two developmental abnormalities are associated with pancreatitis: anomaly of pancreatic ducts and annular pancreas.
Oddi’s sphincter dysfunction can lead to acute pancreatitis by causing increased pancreatic ductal pressures.
Acute pancreatitis may occur when factors involved in maintaining cellular homeostasis are out of balance. The initiating event may be anything that injures the acinar cell and impairs the secretion of zymogen granules, such as alcohol use, gallstones and certain drugs. In addition, acute pancreatitis can develop when ductal cell injury leads to delayed or absent enzymatic secretion.
Once a cellular injury pattern has been initiated, cellular membrane trafficking becomes chaotic, with the following deleterious effects:
1) lysosomal and zymogen granule compartments fuse, enabling activation of trypsinogen to trypsin;
2) intracellular trypsin triggers the entire zymogen activation cascade;
3) secretory vesicles are extruded across the basolateral membrane into the interstitium, where molecular fragments act as chemoattractants for inflammatory cells.
Activated neutrophils then exacerbate the problem by leasign superoxide or proteolytic enzymes (cathepsins B, D, and G; collagenase; and elastase).
Finally, macrophages release cytokines that further mediate local (and, in severe cases, systemic) inflammatory responses. The early mediators defined to date are tumor necrosis factor-alpha, interleukin-6, and interleukin-8.
These mediators of inflammation cause an increase of pancreatic vascular permeability, leading to haemorrhage, oedema, and eventually pancreatic necrosis. As the mediators are excreted into the circulation, systemic complications can arise, such as bacteremia due to gut flora translocation, acute respiratory distress syndrome, pleural effusions, gastrointestinal haemorrhage and renal failure.
In mild pancreatitis the inflammatory response is well controlled. There may be oedema, usually confined to the pancreas, but tissue necrosis is uncommon. In severe pancreatitis the response is uncontrolled, leading to more widespread tissue injury and the many systemic manifestations of the disease. An inflammatory exudate rich in proteolytic enzymes, kinins, and vasoactive substances escapes from the pancreas into the lesser sac, retroperitoneum and peritoneal cavity. It can then be absorbed into the systemic circulation leading to shock, respiratory failure and renal failure.
The aetiology of shock in the early phase of acute pancreatitis is multifactorial. Sequestration of fluid in the interstitium, or the third space (intestinal tract), results in intravascular fluid depletion. However, restoration of euvolaemic status, as indicated by central venous pressure and pulmonary capillary wedge pressure measurements may not restore normal blood pressure and haemodynamic. Kinins, serotonin and vasoactive amines have been implicated as mediators of diminished peripheral vascular resistance and increased vascular permeability. Patients have high concentration of these substances in the peritoneal fluid during acute pancreatitis. Removal of this fluid by peritoneal lavage reverses the haemodynamic alterations.
A failure of system vascular resistance increases appropriately in the face of hypovolaemia and inability of the myocardium to compensate appropriately for this loss of peripheral resistance by increasing cardiac output. This is attributed to a myocardial depressant factor.
Circulated lipases and phospholipases destroy surfactant. Development of atelectasis and pneumonia is possible. Plevritis may occur as a result of pleura injuries by enzymes.
The mechanisms underlying the development of renal failure are: hypotension and hypovolaemia, reductions in glomerular filtration, toxic injuries of renal cells.
Savelyev V. S. (1983)
Clinical and anatomical forms
Period of haemodynamic disturbances and pancreatogenic shock.
Period of functional insufficiency of parenchymatous organs.
Period of degenerative and purulent complications.
Toxic: pancreatogenic plevritis, “pancreatic lung”, hepatic and kidney necrosis, erosive haemorrhagic gastropathy, delirium, coma.
Necrotic: pancreatic mass, pancreatic abscess, abdominal abscess, phlegmon of retroperitoneal fatty tissue, pseudocyst of pancreas.
Visceral: external and internal fistulas.
Atlanta classification, Beger H. G., 1991
Pancreonecrosis (aseptical, inflectional).
Parapancreatitis (fluid in parapancretical fatty tissue).
Pseudocyst of pancreas.
Abscess of pancreas.
Clinical diagnostic of acute pancreatitis
The cardinal symptom of acute pancreatitis is abdominal pain, which is characteristically dull, boring, and steady. Usually, the pain is sudden in onset and gradually intensifies in severity until reaching a constant ache. Most often, it is located in the upper abdomen, usually in the epigastric region, but it may be perceived more on the left or right side, depending on which portion of the pancreas is involved. The pain radiates directly through the abdomen to the back in approximately one half of cases. The duration of pain varies but typically lasts more than a day.
Nausea and vomiting are often present.
Positioning can be important, because the discomfort frequently improves with the patient in the supine position.
Atypical acute pancreatitis may be misdiagnosed. In a study of patients with pancreatitis discovered at autopsy, 13% presented with abdominal pain, 19% had disease that occurred in the postoperative setting, and 68% presented with various cardiac, pulmonary, hepatic, renal, abdominal and metabolic disturbances.
The following physical examination findings vary with the severity of the disease.
Fever and tachycardia are common abnormal vital signs.
Abdominal tenderness, muscular guarding and distension are observed in most patients. Bowel sounds are often hypoactive due to gastric and transverse colonic ileus. Guarding tends to be more pronounced in the upper abdomen.
A minority of patients exhibit jaundice.
Some patients experience dyspnea, which may be caused by irritation of the diaphragm (resulting from inflammation), pleural effusion, or a more serious condition, such as acute respiratory distress syndrome.
In severe cases, haemodynamic instability is evident and haematemesis or melena sometimes develops (erosive haemorrhagic gastropathy). In addition, patients with severe acute pancreatitis are often pale, diaphoretic and listless.
Cullen’s sign – bluish discolouration around the umbilicus.
Grey-Turner’s sign – reddish-brown skin discolouration along the flanks resulting from retroperitoneal space blood dissecting.
Mondor’s sign – violet sports on the body and face.
Holsted’s sign – cyanosis of skin of abdominal wall.
Grunvald’s sign – petechial skin rash in the navel region.
Korte’s sign – regional tension of anterior abdominal wall in epigastria region, along the projection of pancreas.
Mayo–Robson's sign – palpation pain in the left costal-vertebral angle.
Gobye’s sign – abdominal distension in upper region.
Voskresensky’s sign – absence of pulsation of abdominal aorta in epigastria region (sign of parapancreatical infiltration).
Patients may have a ruddy erythema in the flanks secondary to extravasated pancreatic exudate.
Erythematous skin nodules may result from focal subcutaneous fat necrosis. These are usually not more than 1 cm in size and are typically located on extensor skin surfaces. In addition, polyarthritis is occasionally seen.
The main tasks of special investigations are:
Differential diagnosis with other abdominal and extraabdominal diseases.
Detection of the form (pancreatitis or pancreonecrosis).
Detection of the previous system disorders for immediate correction.
Amylase and lipase. Serum amylase and lipase levels are typically elevated in persons with acute pancreatitis. Amylase or lipase levels at least 3 times above the reference range are generally considered diagnostic of acute pancreatitis.
The level of serum amylase or lipase does not indicate whether the disease is mild, moderate, or severe, and monitoring levels serially during the course of hospitalization does not offer insight into prognosis.
Liver-associated enzymes. Determine alkaline phosphatase, total bilirubin, aspartate aminotransferase and alanine aminotransferase levels to search for evidence of gallstone pancreatitis.
Calcium, cholesterol and triglycerides. Determine these levels to search for aetiology of pancreatitis (hypercalcemia or hyperlipidemia) or complications of pancreatitis (hypocalcemia resulting from saponification of fats in the retroperitoneum). However, be wary of the fact that baseline serum triglyceride levels can be falsely lowered during an episode of acute pancreatitis.
Serum electrolytes, creatinine, and glucose. Measure these to look for electrolyte imbalances, renal insufficiency, and pancreatic endocrine dysfunction.
CBC. Haemoconcentration at admission (an admission hematocrit value greater than 47%) has been proposed as a sensitive measure of more severe disease. Leukocytosis may represent inflammation or infection.
C-reactive protein. A C-reactive protein (CRP) value can be obtained 24–48 hours after presentation to provide some indication of prognosis. Higher levels have been shown to correlate with a propensity toward organ failure. A CRP value in double figures (i.e., >10 mg/dL) strongly indicates severe pancreatitis. CRP is an acute-phase reactant that is not specific for pancreatitis.
Arterial blood gases. Measure ABGs if a patient is dyspneic. Whether tachypnea is due to acute respiratory distress syndrome or diaphragmatic irritation must be determined.
Trypsin and its precursor trypsinogen-2 in both the urine and the peritoneal fluid have been evaluated as possible markers for acute pancreatitis but are not widely used.
Abdominal radiography. This modality has a limited role in acute pancreatitis. These radiographs are primarily used to detect free air in the abdomen, indicating a perforated viscus, as would be the case in a perforated ulcer. In some cases, the inflammatory process may damage peripancreatic structures, resulting in a colon cut-off sign, a sentinel loop, or an ileus. The presence of calcifications within the pancreas may indicate chronic pancreatitis.
Chest radiography can help to detect lung and pleural complications.
Abdominal ultrasonography. This is the most useful initial test in determining the aetiology of pancreatitis and is the technique of choice for detecting gallstones. In the setting of acute pancreatitis, sensitivity is reduced to 70–80%. In addition, the ability to identify choledocholithiasis is limited. Ultrasonography cannot measure the severity of disease. Some complications (pancreatical mass, pancreatical abscess, abdominal or retroperitoneal abscess, pseudocyst of pancreas, peritonitis) can be diagnosed.
Abdominal CT scanning. This is generally not indicated for patients with mild pancreatitis unless a pancreatic tumor is suspected (usually in elderly patients). CT scanning is always indicated in patients with severe acute pancreatitis and is the imaging study of choice for assessign complications. Scans are seldom needed within the first 72 hours, because inflammatory changes are often not radiographically present until this time.
Contrast-enhanced CT of the pancreas is diagnostic and can show (fig. 15, 16):
enlargement of pancreas due to oedema;
peripancreatic inflammation: linear strands in the peripancreatic fat;
haemorrhagic: enlarged pancreas with increased density due to haemorrhage;
necrosis: on contrast enhanced phases the necrotic pancreatic parenchyma will show decreased or no enhancement when compared with normally enhancing viable tissue;
fluid in the paracolic gutter;
fluid collections: a simple peripancreatic fluid collection will not have a well-defined capsule;
pseudocysts: as liquifaction of necrotic pancreatic tissue progresses it will gradually take on the appearance of localized fluid collection pseudocyst;
abscesses: diffusely enlarged pancreas with air pockets.
Post Contrast CT findings reveal diffusely enlarged pancreas with low density from oedema. C – colon, St – stomach,
P – pancreas
Note the nonenhancing pancreatic body anterior to the splenic vein. Also present is peripancreatic fluid extending anteriorly from the pancreatic head
Abdominal CT scans also provide prognostic information based on the following grading scale developed by Balthazar:
A – normal.
B – enlargement.
C – peripancreatic inflammation.
D – signle fluid collection.
E – multiple fluid collections.
The chances of infection and death are virtually nil in grades A and B but steadily increase in grades C through E. Patients with grade E pancreatitis have a 50% chance of developing an infection and a 15% chance of dying.
Dynamic spiral CT scanning is used to determine the presence and extent of pancreatic necrosis. Focal or diffuse regions of unenhanced parenchyma on the second study suggest pancreatic necrosis.
Magnetic resonance cholangiopancreatography (MRCP) has an emerging role in the diagnosis of suspected biliary and pancreatic duct obstruction.
Endoscopic ultrasonography (EUS) is an endoscopic procedure that allows a high-frequency Ultrasonic transducer to be inserted into the gastrointestinal tract. EUS is often helpful in evaluating the cause of severe pancreatitis, particularly microlithiasis and biliary sludge, and can help identify periampullary lesions better than other imaging modalities.
Endoscopic retrograde cholangiopancreatography is dangerous in patients with acute pancreatitis and should never be used as a first-line diagnostic tool in this disease.
The indications for this procedure are:
1) if a patient has severe acute pancreatitis that is believed, and is seen on other radiographic studies, to be secondary to choledocholithiasis;
2) if a patient has biliary pancreatitis and is experiencing worsening jaundice and clinical deterioration despite maximal supportive therapy.
CT-guided needle aspiration. This procedure is used to differentiate infected necrosis and sterile necrosis in patients with severe necrotizing pancreatitis.
Treatment of acute pancreatitis
For acute pancreatitis, initial treatment is conservative.
Analgesics, spasmolytics. Narcotic analgetics are dangerous in patients with acute pancreatitis because of Oddi’s sphincter constriction.
Relief of vomiting. Drainage of the stomach with a probe, metaclopramid (cerucal, reglan) 10–20 mg; osetron (ondansetron, navoban, tropisetron).
Fluid replacement. The most important requirement in the early treatment of pancreatitis is maintenance of adequate hydration. If the patient becomes hypovolaemic, and the splainchnic circulation is compromised, the pancreas may become ischaemic, with the potential for the development of complicated pancreatitis.
With considerable reduction of arterial blood pressure – dopamine 5–7 mkg/kg of the body weight; for relief of angiospasm – benzohexamethonium 0.15 mg / kg of the body weight or pentamine 0.25 – 0.3 mg/kg of the body weight every 6 hours; for reduction of vascular permeability – hydrocortisone 1000–1500 mg/day.
Treatment of hypoxaemia. Fluid replacement, normalization of peripheral microcirculation is adequate in majority of patients. In the most severely ill patients intubation and ventilatory support is indicated.
Minimizing of pancreatic secretion
Bowel rest, nasogastric tube.
H2-receptor or H-pomp blockers. They are useful for inhibition of pancreatic enzymes secretion and prevention of acute upper digestive tract ulcerations.
5-ftoruracyl (500 mg /d).
Nutritional support. Patients with severe acute pancreatitis often cannot be fed for several days. Once severe pancreatitis has developed total parenteral nutrition should be instituted. Intravenous fat emulsions do not exacerbate pancreatitis in patients with normal triglyceride levels. If triglyceride levels are raised, however, fat emulsion should not be used. Total parenteral nutrition should be continued until the patient appears clinically well.
Antibiotic therapy. Antibiotics are generally ineffective in preventing the late septic complications of acute pancreatitis, and their use may even promote selection of organisms that are more difficult to treat later on. The best variants are:
third and fourth generations of cephalosporin;
quinolones and metronidazole;
Antiprotease therapy. Gordox, Contrical. They are useful and effective only as inhibitors of kinins.
Treatment of metabolic disturbansis includes correction of hypocalcaemia, hypoalbuminaemia, hypomagnesaemia, hypokalaemia, control of blood glucose.
In patients with acute pancreatitis common indications for surgery are:
Progressive multiorgan system failure.
Gallstones pancreatitis without effect of conservative treatment during 24–48 h.
Gallstones pancreatitis: cholecystectomy and, if still necessary, common bile duct tube.
Surgycal management in necrotizing process into the retroperitoneum, perirenal spaces, and mesentery.
Drainage by percutaneous aspiration of peripancreatic fluid collections.
Percutaneous drainage of pancreatic abscesses (under CT or US control).