Akut Pankreatit Etiyolojisi ve Etiyopatogenezi
Özet
Akut pankreatit, pankreasın kendi sindirim enzimlerince sindirilmesi sonucu gelişen, peripankreatik dokuları etkileyen ve sistemik komplikasyonlara yol açabilen ciddi bir inflamatuar hastalıktır. Hastalığın dünya genelinde sindirim sistemi kaynaklı hastaneye yatışların en sık nedenlerinden biri olduğu, yaklaşık %20 oranında şiddetli seyrederek mortalite riski taşıdığı belirtilmektedir. Etiyolojide en yaygın faktörler %75-90 oranla safra yolu taşları ve alkol kullanımı iken; hipertrigliseridemi, hiperkalsemi, ilaçlar, travma, ERCP sonrası gelişen komplikasyonlar, genetik mutasyonlar ve otoimmün süreçler de önemli rol oynamaktadır. Patogenez, esas olarak tripsinojenin vaktinden önce aktif tripsine dönüşmesi ve bu durumun diğer zimojenleri de aktive ederek doku hasarını, iskemi ve inflamasyonu tetiklemesi üzerine kuruludur. Bu süreç elastaz ve fosfolipaz gibi enzimlerin etkisiyle vasküler hasara ve nekroza ilerleyerek, sitokin salınımı yoluyla sistemik inflamatuar yanıt sendromu (SIRS), çoklu organ yetmezliği ve ARDS gibi hayati tehlike arz eden tablolara zemin hazırlayabilir. Tedavi ve yönetimde etiyolojik faktörün belirlenmesi nükslerin önlenmesi açısından kritik önem taşır.
Acute pancreatitis is a serious inflammatory disease characterized by the autodigestion of the pancreas by its own digestive enzymes, affecting peripancreatic tissues and potentially leading to systemic complications. It is one of the most frequent causes of gastrointestinal-related hospitalizations worldwide, with approximately 20% of cases progressing severely and carrying a risk of mortality. While biliary tract stones and alcohol consumption are the most common etiological factors, accounting for 75-90% of cases, other significant causes include hypertriglyceridemia, hypercalcemia, certain medications, trauma, post-ERCP complications, genetic mutations, and autoimmune processes. The pathogenesis primarily involves the premature activation of trypsinogen into active trypsin, which triggers a cascade activating other zymogens, leading to tissue damage, ischemia, and inflammation. This process, fueled by enzymes like elastase and phospholipase, progresses to vascular damage and necrosis, potentially resulting in life-threatening conditions such as systemic inflammatory response syndrome (SIRS), multi-organ failure, and ARDS through cytokine release. Identifying the specific etiological factor is crucial in clinical management to prevent recurrence.
Referanslar
1 Spanier BW, Dijkgraaf MG, Bruno MJ: Epidemiology, aetiology and outcome of acute and chronic pancreatitis: an update. Best Pract Res Clin Gastroenterol 2008; 22: 45–63.
2 American Gastroenterological Association (AGA) Institute on “Management of Acute Pancreatits” Clinical Practice and Economics Committee; AGA Institute Governing Board: AGA Institute medical position statement on acute pancreatitis. Gastroenterology 2007;132: 2019–2021.
3 Lee JK, Enns R: Review of idiopathic pancreatitis. World J Gastroenterol 2007; 13: 6296–313.
4 Sekimoto M, Takada T, Kawarada Y, Hirata K, Mayumi T, Yoshida M, et al: JPN Guidelines for the management of acute pancreatitis: epidemiology, etiology, natural history, and outcome predictors in acute pancreatitis. J Hepatobiliary Pancreat Surg 2006; 13: 10–24.
5 Al-Haddad M, Wallace MB: Diagnostic approach to patients with acute idiopathic and recurrent pancreatitis, what should be done? World J Gastroenterol 2008; 14: 1007–1010.
6 Steer ML, Perides G: Pathogenesis and pathophysiology of acute pancreatitis; in: Beger HG, Matsuno S, Cameron JL: Diseases of the Pancreas: Current Surgical Therapy. Berlin Heidelberg, Springer-Verlag, 2008; pp 153–162.
7 Wang GJ, Gao CF, Wei D, Wang C, Ding SQ: Acute pancreatitis: etiology and common pathogenesis. World J Gastroenterol 2009; 15: 1427–1430.
8 Pongprasobchai S, Thamcharoen R, Manatsathit S: Changing of the etiology of acute pancreatitis after using a systematic search. J Med Assoc Thai 2009; 92:S38–S42.
9 Working Group IAP/APA Acute Pancreatitis Guidelines: IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology 2013; 13:e1–e15.
10 Banks PA, Freeman ML; Practice Parameters Committee of the American College of Gastroenterology: Practice guidelines in acute pancreatitis. Am J Gastroenterol 2006; 101: 2379–2400.
11 Working Party of the British Society of Gastroenterology; Association of Surgeons of Great Britain and Ireland; Pancreatic Society of Great Britain and Ireland; Association of Upper GI Surgeons of Great Britain and Ireland: UK guidelines for the management of acute pancreatitis. Gut 2005; 54:iii1–iii9.
12 Kapetanos DJ: Endoscopic management of acute recurrent pancreatitis. Ann Gastroenterol 2010; 23: 31–37.
13 Mariani A, Arcidiacono PG, Curioni S, Giussani A, Testoni PA: Diagnostic yield of ERCPand secretin-enhanced MRCP and EUS in patients with acute recurrent pancreatitis of unknown aetiology. Dig Liver Dis 2009; 41: 753–758.
14 Forsmark CE. Acute Pancreatitis. In: Goldman L, Schafer AI, Goldman-Medicine 25th ed. Philadelphia: Saunders, Elsevier 2016,p.959-63.
15 Petrov M, Yadav D. Global epidemiology and holistic prevention of pancreatitis. Nature Reviews-Gastroenterology and Hepatology 2018
16 Conwell DL, Banks P, Greenberger NJ. Acute and chronic pancreatitis. In: Kasper DL, Hauser SL, Lameson JL, Fauci AS, Longo DL, Loscalzo J, eds. Harrison's Principles of internal Medicine. 19th ed. Newyork: Mc Graw Hill;2015.p. 2090-102.
17 Bruno MJ: Current insights into the pathogenesis of acute and chronic pancreatitis. Scand J Gastroenterol 2001; 36: 103–108.
18 Mayer J, Rau B, Gansauge F, Beger HG: Infl ammatory mediators in human acute pancreatitis: Clinical and pathophysiological implications. Gut 2000; 47: 546–552.
19 Pandol SJ. Acute pancreatitis. Curr Opin Gastroenterol 2006; 22: 481-486
20 Grendell J H. Acute pancreatitis. In Current Diagnosis and Treatment in gastroenterology. Ed. Friedman S. L., McQuaid K. R. , Grendell J. H. 2nd ed. , Lange Medical Boks/Mc Graw-Hill, NewYork, 2003; 489-95.
21 Frossard JL, Steer ML, Pastor CM. Acute pancreatitis. Lancet 2008; 371: 143-152
22 Spanier BW, Dijkgraaf MG, Bruno MJ. Epidemiology, aetiology and outcome of acute and chronic pancreatitis: An update. Best Pract Res Clin Gastroenterol 2008; 22: 45-63
23 Samuel I, Toriumi Y, Zaheer A, Joehl RJ. Mechanism of acute pancreatitis exacerbation by enteral bile-pancreatic juice exclusion. Pancreatology 2004; 4: 527-532
24 McKay CJ, Buter A: Natural history of organ failure in acute pancreatitis. Pancreatology 2003; 3: 111–114.
25-Bhatia M, Brady M, Shokuhi S, Christmas S, Neoptolemos JP, Slavin J: Infl ammatory mediators in acute pancreatitis. J Pathol 2000; 190: 117–125.
26 Naruse S: Molecular pathophysiology of pancreatitis. Intern Med 2003; 42: 288–289.
27 Bhatia M: Novel therapeutic targets for acute pancreatitis and associated multiple organ dysfunction syndrome: An update. Medicinal Chemistry Reviews – Online 2004; 1: 25–26.
28-Hruban RH, lazobuzio-Donahue CA. The Pancreas In Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease 9th ed. Philadelphia: Saunders, Elsevier 2015;p.884-8.
29-Sonneday CJ. Disorders of the Exocrine Pancreas. In Hammer GD, McPhee S. Pathophysiology of Disease: An Introduction of Clinical Medicine. 7th ed.New York: Mc Graw Hill; 2015;p.2090-102.
30-Doig. AK, Huether SE. Alterations of digestive functions. In: McCance KL, Huether SE, eds. Pathophysiology: The Biologic Basis for Disease in Adults and Children. Missouri:Mosby, Elsevier 2014.p.1464-6.
