© Borgis - Postępy Nauk Medycznych 8/2014, s. 574-580
*Agnieszka Białas, Wiesław Tarnowski
Ostre zapalenie trzustki – przegląd piśmiennictwa
Acute pancreatitis – papers review
Department of General, Oncologic and Gastrointestinal Surgery, Medical Centre of Postgraduate Education, Professor Witold Orłowski Independent Public Clinical Hospital, Warszawa
Head of Department: prof. Wiesław Tarnowski, MD, PhD
Ostre zapalenie trzustki (OZT) jest ostrą niebakteryjną chorobą zapalną trzustki, która przebiega z dużą różnorodnością postaci klinicznych. Może występować jako pojedynczy epizod bądź mieć charakter nawracający. OZT ma wiele czynników etiologicznych a jego przebieg może być od łagodnego przez ciężki do zagrażającego życiu. Diagnoza OZT wymaga minimum 2 z następujących: typowy ból w nadbrzuszu, podwyższenie poziomu amylazy lub lipazy w surowicy > 3 razy górna granica normy oraz potwierdzenia w badaniach obrazowych. Jak dotychczas, nie ma precyzyjnej metody prognozowania ciężkości OZT, aczkolwiek w praktyce klinicznej stosowane są różne kryteria. Optymalne leczenie pacjentów z OZT, obejmujące resuscytację płynową, leczenie przeciwbólowe, antybiotyki, żywienie czy interwencję chirurgiczną w odpowiednich przypadkach, jest kluczowe w celu zmniejszenia śmiertelności i chorobowości związanej z tą chorobą.
Acute pancreatitis (AP) is an acute nonbacterial inflammatory condition of the pancreas, with extremely different clinical expressions. It may occur as an isolated attack or may be recurrent. It has a variety of causes and can range in severity from mild to severe and life threatening. The diagnosis of acute pancreatitis requires at least 2 of the following: typical upper abdominal pain, serum levels of amylase or lipase > 3 times the upper limit of normal, and confirmatory findings from imaging analysis. So far, there has been no precise method for predicting the severity of AP, although in daily practice a number of criteria are being used. Optimal management of patients with acute pancreatitis, including fluid resuscitation, analgesia, antibiotics, nutrition, or surgical intervention when necessary, is essential in order to reduce mortality and morbidity associated with this disease.
Acute pancreatitis (AP) is defined as the acute nonbacterial inflammatory condition of the pancreas. It is derived from the early activation of digestive enzymes found inside the acinar cells, with variable compromise of the gland itself, nearby tissues and other organs. Although the disease process may be limited to pancreatic tissue, it also can involve peripancreatic tissues or more distant organ sites. AP is a disease with extremely different clinical expressions. It may occur as an isolated attack or may be recurrent (1). It has a variety of causes and can range in severity from mild to severe and life threatening. Most patients suffer a mild and limited disease but about one fifth of cases develop multiple organ disfunction syndrome (MODS), accompanied by high mortality (1). The correct diagnosis of acute pancreatitis should be made in all patients within 48 hours of admission. Mild acute pancreatitis has a very low mortality rate (less than 1 percent), whereas the death rate for severe acute pancreatitis can be 10 to 30 percent depending on the presence of sterile versus infected necrosis. This great variability in presentation, clinical course and complications has given rise to the confusion related to AP related terminology. However, consensus meetings (Atlanta and later working groups) have provided more uniform definitions. For the last 25 years, there has been a global increase in incidence of AP, along with many advances in diagnosis and treatment. This increase was associated with a parallel increase in gallstone and alcohol-related pancreatitis.
Acute pancreatitis is a disease with an overall mortality of approximately 4-6% (which increases to 17-39% in severe disease) and substantive morbidity (2, 3). New mortality data in AP confirm that mortality rates are similar in gallstone and alcohol-induced AP, that mortality is 20% in those hospitalized more than 1month with severe AP (SAP), and that increased mortality occurred in those with hospital-acquired infection and those at least 70 years old (4).
The most common risk factors for acute pancreatic are gallbladder disease (often caused by choledocholithiasis) and chronic alcohol consumption. The etiology factors for acute pancreatitis are listed in table 1 (3, 5, 6). The etiology of acute pancreatitis should be determined in at least 80% of cases and no more than 20% should be classified as idiopathic (7).
Table 1. Etiology of acute pancreatitis (1).
|Toxic – metabolic||Alcohol|
Drugs and pills (azathioprine, didanosine, estrogen, furosemide, salicylates, sulfonamide, pentamidine)
Organophosphorus and other toxic substances
Venoms (scorpion, spiders)
|Mechanical||Biliary: lithiasis, microlithiasis, sludge|
– Duodenal duplication
– Duodenal diverticulum
– Choledochal cyst
Ampullary dysfunction and stenosis
Trauma or post-procedure (ERCP, surgery)
Autoimmune associated to other autoimmune disorders
Primary sclerosing cholangitis
– Virus: mumps, Coxsackie A, HIV, CMV
– Bacteria: Mycobacterium tuberculosis
– Parasites: Ascaris
– Other: Mycoplasma
Cigarette smoking is an independent risk factor for AP and total exposure correlates with overall risk (4). Sex is strongly associated with the risk of acute pancreatitis: the incidence of alcoholic pancreatitis is higher in men, and the incidence of gallstone pancreatitis is higher in women. Multivariate analyses showed that acute pancreatitis was associated with a stone diameter of less than 5 mm and with mulberry-shaped gallstones.
The hallmark symptom of acute pancreatitis is the acute onset of persistent upper abdominal pain, usually with nausea and vomiting. The usual locations of the pain are the epigastric and periumbilical regions. The pain may radiate to the back, chest, flanks, and lower abdomen. Patients are usually restless and bend forward (the knee-chest position) in an effort to relieve the pain because the supine position may exacerbate the intensity of symptoms (5). Physical examination findings are variable but may include fever, hypotension, severe abdominal tenderness, guarding, respiratory distress, and abdominal distention. Accurate diagnosis is important because many other conditions have similar symptoms, including acute cholecystitis, choledocholithiasis, and penetrating duodenal ulcers. Potentially lifethreatening conditions to consider include a perforated viscus, an ischemic bowel, bowel obstruction, or myocardial infarction (6, 8).
Two types of pancreatitis were defined at the Atlanta symposium in 1992: one light form, usually auto limited; and the other severe, where local complications may appear, such as necrosis and distant organ failure (OF). Fortunately, these complications are uncommon, occurring in approximately 15% of the cases. The situation’s severity will be determined by clinical, analytical and radiological criteria. Because some complications do not appear immediately (necrosis or pseudocysts), a severity definition will be made adequately at the end of the process (9).
Clinical features (abdominal pain and vomiting) together with elevation of plasma concentrations of pancreatic enzymes are the cornerstones of diagnosis. The diagnosis of acute pancreatitis requires at least 2 of the following: typical upper abdominal pain, serum levels of amylase or lipase > 3 times the upper limit of normal, and confirmatory findings from cross-sectional imaging analysis (10, 11). But there is no single laboratory or clinical sign which is pathognomonic for acute pancreatitis; many biomarkers and inflammatory mediators for predicting the severity of acute pancreatitis are being evaluated (5, 12).
The initial laboratory evaluation should include amylase and lipase levels, complete blood count with differential, metabolic panel (blood urea nitrogen, creatinine, glucose, and calcium levels), triglyceride level, urinalysis and arterial blood gases. Amylase and lipase, secreted by the acinar cells of the pancreas, are the most common laboratory markers used to establish the diagnosis of acute pancreatitis. Elevated amylase and lipase levels can be nonspecific, depending on the time since onset of pain, other intra-abdominal processes, and concomitant chronic diseases such as renal insufficiency. Pancreatic enzymes are released into the circulation during an acute attack. Levels peak early, and decline over 3-4 days. An important concept derives from this: the diagnosis of acute pancreatitis should not rely on arbitrary limits of values 3 or 4 times greater than normal, but values should be interpreted in light of the time since the onset of abdominal pain (7). The half life of elevated amylase is shorter than that of lipase. Because it persists longer after the onset of the attack and because the pancreas is the only source of lipase, estimation of plasma lipase has slightly superior sensitivity and specificity and greater overall accuracy than amylase. Amylase levels may be normal in patients with alcoholism who present with acute pancreatitis, especially if they have had previous attacks of alcoholic pancreatitis; thus, serial testing may not be helpful. Plasma lipase is more sensitive and specific than plasma amylase. Recent research has examined potential biologic markers for predicting the severity and prognosis of pancreatitis. Trypsinogens and pancreatic protease involved in the autodigestive processes of acute pancreatitis appear promising. Other investigational serologic markers include trypsinogen activation peptide, C-reactive protein, procalcitonin, phospholipase A2, and the cytokines interleukin-6 and interleukin-8. Currently, these markers have limited clinical availability, but there is significant interest in better understanding markers of immune response and pancreatic injury because these could be valuable tools for reliably predicting the severity of acute pancreatitis (12, 13).
Plain radiographs contribute little to the diagnosis of acute pancreatitis. The recommended initial examination is ultrasonography. Ultrasound may show pancreatic swelling but the pancreas is visualised in only 25-50% of patients with acute pancreatitis. The value of ultrasonography lies in its ability to demonstrate gall bladder stones and dilatation of the common bile duct, as well as other pathology unrelated to the pancreas such as abdominal aortic aneurysm. The sensitivity of the US in the detection of gallstones is > 95% in uncomplicated cases; however in the setting of acute pancreatitis, sensitivity for gallstone detection is only 67-78% due to the ileus and bowel distension. Furthermore, sensitivity in the detection of common bile duct stones is between 25-90% (12, 14).
CT is occasionally indicated for diagnosis, if clinical and biochemical findings are inconclusive, especially when abdominal signs raise the possibility of an alternative abdominal emergency, such as a perforation or infarction of the bowel.
Liver biochemistry is helpful for the diagnosis of biliary pancreatitis. A meta-analysis found that a 3-fold increase of serum alanine transaminase (> 60 μ/l < 48 hours of symptoms) will identify gallstones as the cause in patients with pancreatitis with a positive predictive value of 95%. It should be kept in mind that around 10-15% of patients with biliary pancreatitis present with normal serum liver enzyme and bilirubin levels (14).
Contrast enhanced computed tomography must be performed > 72 h from onset of symptoms to allow delineation of the necrosis. Magnetic resonance imaging is also a reliable staging method with similar sensitivity and specificity to that of contrast enhanced computed tomography.
The revised Atlanta Classification recognizes 3 degrees of severity. Mild disease is defined as acute pancreatitis not associated with organ failure, local complications, or systemic complications. Most patients with mild acute pancreatitis do not require pancreatic imaging analysis and are usually discharged within 3 to 5 days of onset of illness. Moderately severe acute pancreatitis is defined by the presence of transient organ failure, local complications, or systemic complications. Transient organ failure is defined by organ failure that is present for < 48 hours. Patients with moderately severe acute pancreatitis frequently require extended hospitalization but have lower mortality rates than patients with severe acute pancreatitis. Severe acute pancreatitis is defined by the presence of persistent organ failure. Persistent organ failure is defined by organ failure that is present for > 48 hours. Most patients with persistent organ failure have pancreatic necrosis (8-10).
Prediction of severity
There is agreement that there is still a need for an early objective measure of severity. So far, there has been no precise method for this purpose, although in daily practice, following several clinical guidelines, a number of criteria are being used.
Clinical examination in the first 24 hours of admission although specific lacks sensitivity and hence is unreliable and should be supported by objective measures. Immediate assessment should include clinical evaluation, particularly of any cardiovascular, respiratory, and renal compromise, body mass index, chest x ray. The presence of any organ failure should be documented. After 24 hours in hospital, clinical assessment and documentation of organ failure are required (tab. 2).
Table 2. Features that may predict a severe attack, present within 48 hours of admission to hospital (7).
|Initial assessment |
|Clinical impression of severity|
Body mass index > 30
Pleural effusion on chest radiograph
APACHE II score > 8
|24 h after admission |
|Clinical impression of severity|
APACHE II score > 8
Glasgow score 3 or more
Persisting organ failure, especially if multiple
C-reactive protein 150 mg/l
|48 h after admission |
|Clinical impression of severity|
Glasgow score 3 or more
C-reactive protein > 150 mg/l
Persisting organ failure for 48 h
Multiple or progressive organ failure
The Glasgow and Ranson scales have been and still are being used; they are easy to use, although they require 48 h for a complete evaluation. The Acute Physiology and Chronic Health Evaluation APACHE II scale and its modification for obese patients, is currently the most commonly used scale; a score higher than 8 indicates severe illness. The problem is that 14 variables must be recorded, but it can be useful to assess severity of illness at patient’s admission. More recently, the bedside index for severity in AP system has been developed with a predictive value similar to APACHE II, but much simpler to implement because it only reflects five variables (tab. 3).
Table 3. Clinical Criteria Used in Prognostic Scoring Systems for Acute Pancreatitis (5).
|APACHE II scale|
|Equation includes the following factors: age, rectal temperature, mean arterial pressure, heart rate, PaO2, arterial pH, serum potassium, serum sodium, serum creatinine, hematocrit, white blood cell count, Glasgow Coma Scale score, chronic health status|
|CT Severity Index|
A is normal pancreas (0 points)
B is edematous pancreas (1 point)
C is B plus mild extrapancreatic changes (2 points)
D is severe extrapancreatic changes plus one fluid collection (3 points)
E is multiple or extensive fluid collections (4 points)
None (0 points)
> One third (2 points)
< One third but less than one half (4 points)
> One half (6 points)
Scoring: CT grade + necrosis score
|Imrie scoring system|
|Age > 55 years|
White blood cell count > 15 000 per mm3 (15.0 × 109 per L)
Blood glucose > 180 mg per dL (10 mmol per L) in patients without diabetes
Serum lactate dehydrogenase > 600 U per L
Serum AST or ALT > 100 U per L
Serum calcium < 8 mg per dL
PaO2 < 60 mmHg
Serum albumin < 3.2 g per dL (32 g per L)
Serum urea > 45 mg per dL (16.0 mmol per L)
Scoring: One point for each criterion met 48 hours after admission
|At admission or diagnosis:|
Age > 55 years
White blood cell count > 16 000 per mm3 (16.0 × 109 per L)
Blood glucose > 200 mg per dL (11.1 mmol per L)
Serum lactate dehydrogenase > 350 U per L
AST > 250 U per L
During initial 48 hours:
Hematocrit decrease > 10 percent
Blood urea nitrogen increase > 5 mg per dL (1.8 mmol per L)
Serum calcium < 8 mg per dL (2 mmol per L)
Base deficit > 4 mmol per L (4 mEq per L)
Fluid sequestration > 6000 mL
PaO2 < 60 mmHg
Scoring: One point for each criterion met
APACHE II – Acute Physiology and Chronic Health Evaluation; PaO2 – partial arterial oxygen tension; CT – computed tomography; AST – aspartate transaminase; ALT – alanine transaminase
Powyżej zamieściliśmy fragment artykułu, do którego możesz uzyskać pełny dostęp.
Płatny dostęp do wszystkich zasobów Czytelni Medycznej
1. Cruz-Santamaría DM, Taxonera C, Giner M: Update on pathogenesis and clinical management of acute pancreatitis. World J Gastrointest Pathophysiol 2012 June 15; 3(3): 60-70.
2. Brag JD, Cox KR, Despins L et al.: Improvements in Care in Acute Pancreatitis by the Adoption of an Acute Pancreatitis Algorithm. JOP. J Pancreas (Online) 2010 Mar 5; 11(2):183-185.
3. Sekimoto M, Takada T, Kawarada Y et al.: Epidemiology of acute pancreatitis. J Hepatobiliary Pancreat Surg 2006; 13: 10-24.
4. DiMagno MJ, Wamsteker EJ, DeBenedet AT et al.: Advances in managing acute pancreatitis. F1000 Medicine Reports 2009; 1: 59.
5. Carroll JK, Herrick B, Gipson T et al.: Acute Pancreatitis: Diagnosis, Prognosis, and Treatment. Am Fam Physician 2007; 75: 1513-1520.
6. Stevenson K, Carter CR: Acute pancreatitis. Surgery 2013 Jun; 31: 6.
7. UK Working Party on Acute Pancreatitis: UK guidelines for the management of acute pancreatitis. Gut 2005; 54 (suppl. 3): iii1-iii9.
8. Wu BU, Banks PA: Clinical Management of Patients With Acute Pancreatitis. Gastroenterology 2013; 144: 1272-1281.
9. Scheper NJ, Besselink MGH, van Santvoort HC et al.: Early management of acute pancreatitis. Best Practice & Research Clinical Gastroenterology 2013; 27: 727-743.
10. Dupuis CS, Baptista V, Whalen G et al.: Diagnosis and management of acute pancreatitis and its complications. Gastrointestinal Intervention 2013; 2(1): 36-46.
11. Working Group IAP/APA Acute Pancreatitis Guidelines: IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology 2013; 13: e1ee15.
12. Koizumi M, Takada T, Kawarada Y et al.: JPN Guidelines for the management of acute pancreatitis: diagnostic criteria for acute pancreatitis. J Hepatobiliary Pancreat Surg 2006; 13: 25-32.
13. Huang W, Altaf K, Jin T et al.: Prediction of the severity of acute pancreatitis on admission by urinary trypsinogen activation peptide: A meta-analysis. World J Gastroenterol 2013 July 28; 19(28): 4607-4615.
14. Alexakis N, Neoptolemos JP: Algorithm for the diagnosis and treatment of acute biliary pancreatitis. Scandinavian Journal of Surgery 2005; 94: 124-129.
15. Park JY, Jeon TJ, Ha TH et al.: Bedside index for severity in acute pancreatitis. Hepatobiliary Pancreat Dis Int 2013; 12: 645-650.
16. Yang CJ, Chen J, Phillips ARJ et al.: Predictors of severe and critical acute pancreatitis: A systematic review. Digestive and Liver Disease 2014; 46: 446-451.
17. Hirota M, Takada T, Kawarada Y et al.: JPN Guidelines for the management of acute pancreatitis: severity assessment of acute pancreatitis. J Hepatobiliary Pancreat Surg 2006; 13: 33-41.
18. Pezzilli R, Fantini L, Morselli-Labate AM et al.: New Approaches for the Treatment of Acute Pancreatitis. JOP. J Pancreas (Online) 2006; 7(1): 79-91.
19. Takeda K, Takada T, Kawarada Y et al.: JPN Guidelines for the management of acute pancreatitis: medical management of acute pancreatitis. J Hepatobiliary Pancreat Surg 2006; 13: 42-47.
20. Maraví Poma E, Laplaza Santos C, Gorraiz Loprez B et al.: Clinical pathways for acute pancreatitis: Recommendations for early multidisciplinary management. Med Intensiva 2012; 36(5): 351-357.
21. Laguna LB, Cárdenas CL, Escribano JA: Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus SEMICYUC-SENPE: Severe acute pancreatitis. Nutr Hosp 2011; 26 (suppl. 2): 32-36.
22. Petrov MS, McIlroy K, Grayson L et al.: Early nasogastric tube feeding versus nil per os in mild to moderate acute pancreatitis: A randomized controlled trial. Clinical Nutrition 2013; 32: 697e703.
23. Kimura Y, Takada T, Kawarada Y et al.: JPN Guidelines for the management of acute pancreatitis: treatment of gallstone-induced acute pancreatitis. J Hepatobiliary Pancreat Surg 2006; 13: 56-60.
24. Gooszen HG, Besselink MG, van Santvoort HC, Bollen TL: Surgical treatment of acute pancreatitis. Langenbecks Arch Surg 2013; 398: 799-806.