Acute pancreatitis

Japanese: 急性膵炎

Definition and Concept Acute pancreatitis is an acute lesion in which pancreatic enzymes are pathologically activated within the pancreas for some reason, causing autodigestion of the pancreas and surrounding tissues.
In mild cases of pancreatitis, inflammation is limited to the pancreas, there is a strong tendency for the condition to improve naturally, and the fatality rate is low. On the other hand, if inflammation does not remain localized in the pancreas but spreads widely into the abdominal cavity, multiple organ failure (MOF), including circulatory failure, renal failure, and respiratory failure, is likely to occur early in the onset of the disease, and the frequency of severe infections, such as sepsis, increases after two weeks from the onset of the disease. This condition is called severe acute pancreatitis, and has a poor prognosis.
ClassificationClinically , it is classified into mild and severe cases. Pathologically and morphologically, it is divided into edematous pancreatitis (Figure 8-9-2), which is characterized by interstitial edema without pancreatic blood flow disorder, and necrotizing pancreatitis (Figure 8-9-3), which is characterized by intrapancreatic bleeding and necrosis due to pancreatic blood flow disorder, the latter of which tends to become severe. According to the cause, it is classified into alcoholic, gallstone-related, and idiopathic, with an unknown cause.
Causes and EtiologyAlcoholic causes account for 32% of all cases of acute pancreatitis, gallstones for 25%, and idiopathic for 17%, accounting for over 70% of the total (Ministry of Health, Labour and Welfare Research Project to Overcome Intractable Diseases, Research Group on Intractable Pancreatic Diseases, 2008). Alcoholic causes account for 43% of cases in men, but the frequency of alcoholic cases in women is less than 10%, with gallstones and idiopathic cases accounting for 35% and 25%, respectively. Other less common causes include postoperative pancreatitis, cases associated with diagnostic ERCP and endoscopic papillary procedures, pancreaticobiliary maljunction, hyperlipidemia, pancreatic tumors, drug-induced, and pancreatic duct nonfusion.
Epidemiology, incidence, and statisticsThe number of patients receiving medical treatment for acute pancreatitis in 2007 is estimated to be 57,560, and has been increasing rapidly in recent years. The male to female ratio is 2:1, with more men than women, and the average age at onset was 59.3±18.0 years. The peak age for onset is older, with men in their 50s and women in their 70s. Severe cases accounted for 21.6% of all acute pancreatitis cases (Ministry of Health, Labor and Welfare Research Project to Overcome Intractable Diseases, Research Group on Intractable Pancreatic Diseases, 2008).
In pathological mild pancreatitis, as a rule, there is no necrosis of the pancreatic parenchyma, and the main findings are peripancreatic fat necrosis, interlobular edema, and infiltration of polymorphonuclear leukocytes. In severe cases, severe fat necrosis inside and outside the pancreas, as well as necrosis and hemorrhage of the pancreatic parenchyma, are observed. Pathological findings do not necessarily correspond to clinical severity. Once the acute inflammation subsides, a repair mechanism is initiated around the necrotic focus through a mesenchymal reaction, and pseudocysts encapsulating pancreatic exudate, necrotic material, and hemorrhage are often formed.
Pathophysiology: Pancreatic acinar cells produce pancreatic enzymes, many of which are stored in an inactive form within zymogen granules. Upon food ingestion, pancreatic enzymes are secreted into the duodenum via the pancreatic duct, where they are physiologically activated to digest food. In this way, inactive pancreatic enzymes in the pancreas become pathologically activated, resulting in acute pancreatitis, a chemical inflammation that autodigests the pancreas and surrounding organs. Trypsin, a proteolytic enzyme, plays a central role in activating various pancreatic enzymes. Causes of pancreatic enzyme activation are diverse, including excessive alcohol intake, impaction of gallstones in the duodenal papilla, reflux of duodenal juice into the pancreatic duct, overstimulation of exocrine pancreatic secretions, trauma, viral infection, hypertriglyceridemia, pancreatic ischemia, and increased intraductal pressure due to pancreatic duct stenosis.
In mild acute pancreatitis, inflammation is limited to the pancreas, and in most cases, it improves naturally within about a week, and the patient returns to normal both functionally and morphologically. On the other hand, if inflammation does not remain in the pancreas but spreads widely into the abdominal cavity, a large amount of activated pancreatic enzymes autodigest the surrounding organs, producing various inflammatory mediators. These, along with the activated pancreatic enzymes, escape into the blood and lymph, and reach important organs far from the pancreas. In such a pathological condition, vascular permeability is increased throughout the body, plasma components leak out, causing dehydration within the blood vessels, and blood coagulation ability is increased, impairing organ blood flow. In addition, activated neutrophils accumulate in important organs, damaging the tissues, causing shock, respiratory failure, renal failure, etc. in the early stages of the disease. On the other hand, after two weeks from the onset, mainly intestinal bacteria migrate throughout the body, making it easier to develop severe infections such as infection of pancreatic necrotic foci and sepsis. Acute pancreatitis that develops such severe systemic complications is called severe acute pancreatitis.
Clinical manifestations
1) Symptoms:
Typically, the disease begins with upper abdominal pain. The pain gradually increases, reaching its peak within a few hours. The pain increases when the patient is in the supine position, and is often alleviated by bending forward strongly (pancreatic posture). The initial symptoms of acute pancreatitis are abdominal pain in 90% of cases, nausea and vomiting in approximately 20%, and back pain in approximately 10%, with fever/chills, loss of appetite, and abdominal distension being seen in 2-5% of cases. In elderly patients, the disease may rarely progress as a painless event, so caution is required.
2) Objective symptoms:
Tenderness is observed mainly in the upper abdomen. Early after onset, it is localized to the upper abdomen, but gradually spreads throughout the abdomen and is often accompanied by peritoneal irritation symptoms. Early after onset, abdominal findings may be mild despite complaints of severe abdominal pain, so caution is required. Other initial symptoms reported to occur include fever in 5.0% of cases, jaundice in 1.2%, and intestinal obstruction in 0.8%. Fever and jaundice are more common in gallstone pancreatitis. Although uncommon at around 3%, characteristic skin findings may be observed as a sign of a bleeding tendency. These are Cullen's sign, in which hemorrhagic exudate from the abdominal cavity spreads around the umbilicus and causes subcutaneous hemorrhagic spots, and Grey-Turner sign, in which subcutaneous hemorrhagic spots spread mainly to the flank. These signs appear 2 to 3 days after onset.
Test results
1) General Inspection:
a) Blood count and coagulation: White blood cell count increases, and the hematocrit value increases early on, reflecting intravascular dehydration. In severe cases, abnormalities in the blood coagulation system and a decrease in platelet count may be observed.
b) Pancreatic enzyme deviation: Pancreatic enzymes such as amylase, lipase, and trypsin increase in the blood from the early stages of the disease. Blood amylase begins to increase within a few hours of the onset of the disease, peaking 20 to 30 hours later, and in mild cases, levels often return to normal within five days. Elevated urinary amylase levels persist for 10 to 20 days. For diagnosis, it is recommended to measure blood amylase in combination with other pancreatic enzymes that are highly specific to the pancreas, such as blood lipase. Note that the degree of increase in blood pancreatic enzymes does not reflect the severity of acute pancreatitis.
c) Blood biochemistry and serum: Increases in blood glucose, lactate dehydrogenase (LDH), blood urea nitrogen (BUN), and creatinine, as well as decreases in serum calcium and platelet count, are correlated with the prognosis of pancreatitis and are prognostic factors for determining the severity of the condition (Table 8-9-1). Abnormalities in AST, ALT, and total bilirubin levels are frequent in gallstone pancreatitis.
As an inflammatory response, blood C-reactive protein (CRP) levels rise. If CRP is 15 mg/dL or higher 48 hours after the onset of symptoms, the possibility of the condition becoming severe should be considered.
d) Arterial blood analysis: Perform arterial blood gas analysis to diagnose respiratory failure early.
e) SIRS symptoms: Evaluate the presence or absence of each item according to the SIRS diagnostic criteria.
2) Imaging tests:
a) Chest and abdominal plain X-ray: These are essential for evaluating the clinical course of patients with acute pancreatitis and for differential diagnosis. Abdominal X-ray findings may include ileus, localized arch-like small intestinal dilation in the left upper abdomen (sentinel loop sign) due to localized jejunal paralysis caused by the spread of inflammation, transverse colon dilation and sudden interruption at the splenic flexure (colon cut-off sign), retroperitoneal gas, calcified gallstones, and pancreatic stones. Chest X-ray findings include pleural effusion, ARDS, and pneumonia. b) Abdominal ultrasound (US): This is one of the first tests to be performed in all cases suspected of acute pancreatitis. In addition to pancreatic enlargement and inflammatory changes around the pancreas, it can also detect abnormal findings related to the cause and pathology of acute pancreatitis, such as the presence or absence of ascites, bile duct stones, and common bile duct dilation. c) X-ray CT: These findings include pancreatic enlargement, inflammatory changes around the pancreas, fluid accumulation, and uneven concentration of the pancreatic parenchyma. While paying attention to deterioration of renal function and allergic reactions, contrast CT or dynamic CT should be performed as soon as possible to determine the presence and extent of pancreatic necrosis, which correlates with the severity of the condition, and the spread of inflammatory changes (Table 8-9-2).
Diagnosis: 1) There is an attack of acute abdominal pain and tenderness in the upper abdomen, 2) There is an increase in pancreatic enzymes in the blood or urine, and 3) There are abnormal findings in the pancreas associated with acute pancreatitis on ultrasound, CT, or MRI. Acute pancreatitis is diagnosed when two or more of these three criteria are met and other pancreatic diseases and acute abdominal conditions are excluded. Acute exacerbation of chronic pancreatitis is included in acute pancreatitis.
Since the treatment plan differs greatly between mild and severe cases, the severity of the disease should be assessed within 48 hours of onset according to the "Criteria for Assessing the Severity of Acute Pancreatitis (Ministry of Health, Labor and Welfare Research Group on Specific Diseases and Intractable Pancreatic Diseases, 2008) (Tables 8-9-1, 8-9-2)" to accurately grasp the patient's condition. This severity assessment criteria is independent of the severity assessment based on nine prognostic factors and the severity assessment based on contrast CT grade, and if either is judged to be severe, the diagnosis of severe acute pancreatitis is confirmed. The severity assessment based on prognostic factors is designed to be able to be made using clinical signs and a minimum number of blood test items, and is used to assess the severity at the first visit to acute pancreatitis and for follow-up observation after hospitalization. Because the pathology of acute pancreatitis changes from moment to moment, it is important to frequently check clinical signs and test data and repeatedly assess the severity to diagnose the progression to severe disease early.
Differential diagnosis Diseases that are often accompanied by elevated blood and urinary amylase levels and whose main symptom is abdominal pain include perforated peptic ulcer, intestinal obstruction or rupture, dissecting aortic aneurysm, postoperative hyperamylasemia, diabetic ketoacidosis, cholelithiasis, and juxtapapillary diverticulitis. In addition, acute pancreatitis may be the initial symptom of pancreatic cancer due to pancreatic duct stenosis, so caution is required with acute pancreatitis in elderly patients. When severe epigastric pain is accompanied by shock, other possibilities such as ruptured thoracic and abdominal aortic aneurysm, dissecting aortic aneurysm, and myocardial infarction should also be kept in mind.
Complications of severe acute pancreatitis include early complications such as shock, respiratory failure, renal failure, and multiple organ failure, which occur frequently within two weeks of onset, and late complications such as severe infections such as sepsis, infected pancreatic necrosis, and pancreatic abscess, which become more frequent after two weeks, and resulting multiple organ failure, pseudocysts, gastrointestinal bleeding due to infection or gastrointestinal perforation of the pseudocyst, intraperitoneal bleeding, intestinal bleeding, and liver failure.
The prognosis for mild cases is good, with abdominal pain subsiding within 2-5 days and subjective and objective symptoms improving within 2-3 weeks. There is often no residual pancreatic dysfunction.
The overall fatality rate for acute pancreatitis is 2.6%. The fatality rate for mild cases with two or fewer prognostic factors was 0%, whereas the fatality rate for severe cases with three or more points was 19%, and for those with five or more points the fatality rate reached 50% (prospective study by the Ministry of Health, Labour and Welfare research team in 2006). When the severity of the disease was assessed using contrast CT, there were no deaths in cases with CT grade 1, but the fatality rate for cases with CT grade 2 or higher was 14.8%, and the fatality rate for cases judged to be severe based on both prognostic factors and contrast CT grade reached 30.8%. It is important to perform contrast CT in cases with three or more prognostic factors to detect cases with a poor prognosis.
Treatment : As a rule, hospitalization is required. The key to treatment is to start initial treatment promptly, improve and maintain hemodynamics through adequate fluid infusion to prevent the onset of multiple organ failure, and in severe cases or those with the potential for severe disease, administer antibiotics prophylactically from an early stage to prevent infectious complications. Severe cases with prognostic factors of 3 or more points are transferred to a facility that is equipped with ICU management, interventional radiology (IVR), continuous hemodiafiltration (CHDF), endoscopic treatment for cholelithiasis, surgical treatment, a nutritional support team, and other facilities that can handle severe acute pancreatitis. Even if the initial prognostic factor score is 2 or less, the severity of the disease should be assessed repeatedly, and if the patient is determined to be severe, transfer should be considered (Figure 8-9-4).
1) Initial treatment:
a) Fluid therapy: Even in mild cases, sufficient fluid therapy should be administered, aiming for at least 3,000 mL/day, using lactated Ringer's solution or acetate Ringer's solution as the basis, while monitoring the response of blood pressure, pulse, and urinary volume to fluid therapy.
In severe cases or cases of acute pancreatitis where there is concern that the condition may worsen, the initial fluid infusion volume is set at 60-160 mL/kg/day, with 1/2-1/3 of the daily volume administered within the first 6 hours. The state of consciousness, blood pressure, pulse rate, respiratory rate, oxygen saturation, body temperature, and urine volume are monitored over time, and hemodynamics is evaluated to ensure that the hourly urine volume is at least 0.5 mL/kg/hr. b) Protease inhibitors: In order to inhibit activated pancreatic enzymes and suppress the progression of pancreatitis and prevent the condition from worsening, intravenous infusion of protease inhibitors such as gabexate mesilate (FOY), nafamostat mesilate (FUT), and urinastatin (UR) is initiated. Severe pancreatitis is often complicated by DIC and shock, and so protease inhibitors are administered continuously in large doses or in combination with two drugs, such as FOY and UR or FUT and UR.
c) Pain treatment: Ensure sufficient pain control. The administration of buprenorphine or pentazocine is recommended, but because these drugs have a contracting effect on the sphincter of Oddi, atropine sulfate should be used in combination if they are used frequently. Narcotic preparations such as Opatto and Panatto are used for stronger analgesia. For mild pain, diclofenac or indomethacin suppositories are used. d) Suppression of gastric acid secretion: _H2 receptor antagonists are administered to cases with or at risk of acute gastric mucosal lesions or gastrointestinal bleeding.
2) Infection prevention measures:
Prophylactic administration of antibiotics is not necessary in mild cases. In severe cases or cases predicted to become severe, there is a high incidence of pancreatic and peripancreatic infections, which are fatal complications, so broad-spectrum antibiotics with high pancreatic transferability should be administered prophylactically from an early stage. Carbapenem antibiotics are recommended. If there is a concomitant biliary tract infection, administration of second-generation or later cephalosporin antibiotics is recommended, taking into account their ability to transfer into the bile.
3) Nutritional Management:
Total parenteral nutrition is not useful in mild cases. Oral intake is possible from a relatively early stage. If symptoms persist, enteral nutrition should be attempted. Total parenteral nutrition is often used in severe cases, but early enteral nutrition via a feeding tube placed in the jejunum is recommended. In patients with impaired glucose tolerance, insulin should be used in combination.
4) Gallstone pancreatitis:
In cases where gallstone pancreatitis is evident and there is obstructive jaundice due to cholangitis or stone impaction, emergency endoscopic papillotomy is performed to remove the stone and place a naso-biliary drainage tube (ENBD) (Figure 8-9-5). In cases of gallstone pancreatitis, cholecystectomy is recommended after the pancreatitis has subsided to prevent recurrence.
5) Special treatment for severe acute pancreatitis:
In an attempt to improve prognosis, the following special therapies are used. In cases where diuresis is not achieved due to unstable hemodynamics despite adequate initial fluid infusion, continuous hemodiafiltration (CHDF) is performed. In severe cases, it is also expected to be effective in removing MOF-inducing factors from the blood. For severe necrotizing pancreatitis, local pancreatic arterial infusion therapy with protease inhibitors and antibiotics is performed to increase the concentration of drugs in pancreatic tissue and strongly suppress pancreatic inflammation and infection. As an infection control measure, selective digestive tract decontamination (SDD) is also performed, in which non-absorbable antibiotics are administered through a tube placed in the intestine to selectively eradicate intestinal bacteria.
6) Surgical treatment:
Even in severe pancreatitis, the principle of treatment is conservative, and early surgery is no longer performed. If infected pancreatic necrosis is suspected during the course of conservative treatment, a localized pancreatic puncture (FNA) is performed under CT or ultrasound guidance, and a bacteriological test is performed on the aspirate. If infected pancreatic necrosis is confirmed, necrotic pancreatic tissue must be removed by necrotic surgery.
In cases of pancreatic abscess, enlarging pseudocyst, or symptomatic cases, or pseudocyst complicated by intracystic bleeding or infection, endoscopic drainage, percutaneous drainage, or surgical fistula should be considered. [Hirota, Eihisa, Shimosegawa, Toru]
■ References <br /> Ministry of Health, Labour and Welfare Research Project to Overcome Intractable Diseases, Research Group on Intractable Pancreatic Diseases: Consensus on Initial Treatment for Acute Pancreatitis, Arc Media, Tokyo, 2008. Publication Committee for Revised Guidelines for Treatment of Acute Pancreatitis 2010: Guidelines for Treatment of Acute Pancreatitis 2010, 3rd Edition, Kanehara Publishing, Tokyo, 2009. Shimosegawa Toru: Research Group on Intractable Pancreatic Diseases, Ministry of Health, Labour and Welfare, Comprehensive Research Report for FY2008-2010, 2011.

Table 8-9-1
Criteria for assessing the severity of acute pancreatitis (Ministry of Health, Labor and Welfare, Research Group on Intractable Pancreatic Diseases, 2008)

Table 8-9-1

Table 8-9-2
Criteria for assessing the severity of acute pancreatitis (Ministry of Health, Labor and Welfare, Research Group on Intractable Pancreatic Diseases, 2008 )

Table 8-9-2

Fig. 8-9-4
Basic medical treatment policy for acute pancreatitis ">

Fig. 8-9-4

Fig. 8-9-5
Treatment policy for gallstone pancreatitis ">

Fig. 8-9-5

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

定義・概念
　急性膵炎とは，膵酵素が何らかの原因によって膵内で病的な活性化を受け，膵臓と周囲組織を自己消化する急性病変である．
　軽症の膵炎では炎症は膵に限局し，自然軽快傾向が強く致命率は低い．一方，炎症が膵局所にとどまらず，腹腔内に広く進展すると，発症早期には循環不全，腎不全，呼吸不全などの多臓器不全（multiple organ failure：MOF）を合併しやすく，発症2週以降には敗血症などの重症感染症の合併頻度が高まる．このような病態が重症急性膵炎であり，予後が悪い．
分類
　臨床的には，軽症と重症に分類される．病理・形態学的には，膵の血流障害を伴わず間質の浮腫を主体とする浮腫性膵炎（図8-9-2）と，膵の血流障害によって膵内に出血や壊死を伴う壊死性膵炎（図8-9-3）に分けられ，後者は重症化しやすい．成因別には，アルコール性，胆石性，原因が明らかでない特発性などに分類される．
原因・病因
　アルコール性が急性膵炎全体の32％，胆石性が25％，特発性が17％であり，これらで全体の70％以上を占める（厚生労働省難治性疾患克服研究事業難治性膵疾患に関する調査研究班，2008）．男性では成因の43％がアルコール性であるが，女性ではアルコール性の頻度は10％弱と少なく，胆石性と特発性がそれぞれ35％，25％を占める．その他，頻度は少ないが，術後膵炎や診断的ERCP，内視鏡的乳頭処置に伴うもの，膵胆管合流異常，高脂血症，膵腫瘍，薬剤性，膵管癒合不全などがあげられる．
疫学・発生率・統計的事項
　2007年1年間の急性膵炎受療患者数は57560人と推定されており，近年急速に増加している．男女比は2：1で男性に多く，平均発症年齢は59.3±18.0歳だった．発症のピークは男性では50歳代に，女性では70歳代とより高齢層にみられる．重症例は急性膵炎全体の21.6％を占めた（厚生労働省難治性疾患克服研究事業難治性膵疾患に関する調査研究班，2008）．
病理
　軽症膵炎では，原則として膵実質の壊死はなく，膵周囲の脂肪壊死と小葉間の浮腫，多核白血球の浸潤がおもな所見である．重症例では，膵内外の高度な脂肪壊死と膵実質の壊死や出血が認められる．病理所見と臨床的重症度は必ずしも一致しない．　急性炎症が終息すると，壊死巣周囲に間葉系の反応による修復機転が働き，膵の滲出液，壊死物質や出血を被包した仮性囊胞をしばしば形成する．
病態生理
　膵腺房細胞は膵酵素を産生し，その多くはチモーゲン顆粒内で不活性な形で貯蔵される．膵酵素は食物摂取時に膵管を経て十二指腸に分泌され，生理的には十二指腸内で活性化され食物を消化する．このように膵内では不活性な膵酵素が病的に活性化され，膵および周囲臓器を自己消化する化学的炎症が急性膵炎である．蛋白分解酵素であるトリプシンが各種膵酵素の活性化に中心的な役割を演じる．膵酵素活性化の原因としては，アルコールの過剰摂取，胆石の十二指腸乳頭部への嵌頓，十二指腸液の膵管内逆流，膵外分泌の過剰刺激，外傷，ウイルス感染，高中性脂肪血症，膵虚血，膵管狭窄による膵管内圧の上昇など多様である．
　軽症の急性膵炎では炎症が膵に限局し，多くは１週間前後で自然軽快し，機能的にも形態的にも元に復する．一方，炎症が膵にとどまらずに腹腔内に広く進展すると，大量の活性化膵酵素が周囲臓器を自己消化してさまざまな炎症性メディエーターが産生される．これらは活性化膵酵素とともに血中やリンパに逸脱して膵から離れた重要臓器に及ぶ．このような病態では，全身の血管透過性が亢進し血漿成分が漏出して血管内は脱水となり，血液凝固能が亢進して臓器血流は障害される．また，活性化好中球が重要臓器に集積して組織を障害し，発症早期にはショック，呼吸不全，腎不全などを起こす．一方，発症2週以降には，おもに腸内細菌が全身へ移行し，膵壊死巣の感染や敗血症などの重篤な感染症が発症しやすくなる．このように重篤な全身性合併症を発症する急性膵炎が，重症急性膵炎（severe acute pancreatitis）である．
臨床症状
1）自覚症状：
典型例は上腹部痛で発症する．疼痛は徐々に増強して数時間でピークに達する．背臥位で増強し，強い前屈位（pancreatic posture）で軽減することが多い．急性膵炎の初発症状の頻度としては，腹痛が90％，悪心・嘔吐が約20％，背部痛が約10％で，そのほか発熱・悪寒，食欲不振，腹部膨満感などが2〜5％にみられる．高齢者ではまれに無痛性に経過することがあり，注意を要する．
2）他覚症状：
上腹部を中心とする圧痛がみられる．発症早期には上腹部に限局するが次第に腹部全体に広がり，腹膜刺激症状を伴うことが多い．発症後早期には，腹部激痛を訴えるわりに腹部所見が軽いことがあり注意が必要である．ほかの初発症状として発熱が5.0％，黄疸が1.2％，腸閉塞の頻度が0.8％と報告されている．発熱や黄疸は胆石性膵炎で頻度が高い．3％程度と頻度は低いが，出血傾向の徴候として特徴的な皮膚所見が認められることがある．腹腔内の出血性滲出液が臍周囲に及び皮下出血斑を起こすCullen徴候，側腹部を中心に皮下出血斑が広がるGrey-Turner徴候である．発症後2〜3日経ってから出現する．
検査成績
1）一般検査：
a）血算・凝固：白血球数が増加し，血管内脱水を反映して早期からヘマトクリット値が上昇する．重症例では，血液凝固系の異常や血小板数の低下がみられることがある．
b）膵酵素逸脱：発症早期から血中でアミラーゼ，リパーゼ，トリプシンなどの膵酵素が上昇する．血中アミラーゼは発症後，数時間で上昇しはじめ20〜30時間でピークとなり，軽症例では多くが5日以内に正常化する．尿中アミラーゼの上昇は，10〜20日持続する．診断には血中アミラーゼに，血中リパーゼのような膵に特異性の高い他の膵酵素の測定を併用することが推奨される．なお，血中膵酵素の上昇の程度は急性膵炎の重症度を反映しない．
c）血液生化学・血清：血糖，乳酸脱水素酵素（LDH），血液尿素窒素（blood urea nitrogen：BUN），クレアチニンの上昇，血清カルシウムや血小板数の低下が膵炎の予後と相関し，重症度判定の予後因子となる（表8-9-1）．AST，ALT，総ビリルビン値の異常は胆石膵炎で頻度が高い．
　炎症反応として，血中C反応性蛋白（CRP）が上昇する．発症後48時間のCRPが15 mg/dL以上の場合，重症化の可能性を考慮する．
d）動脈血分析：動脈血ガス分析を行い，呼吸不全を早期に診断する．
e）SIRS徴候：SIRS診断基準に従って，各項目の有無を評価する．
2）画像検査：
　a）胸・腹部単純X線：急性膵炎患者の臨床経過の評価や，鑑別診断のために必須である．腹部X線所見として，イレウス像，炎症の波及による限局性空腸麻痺のため，左上腹部の局所的なアーチ状の小腸拡張像（sentinel loop sign）や，横行結腸の拡張と脾湾曲部での急激な途絶像（colon cut-off sign），後腹膜ガス像，石灰化胆石，膵石像などが認められることがある．胸部X線所見として胸水貯留像，ARDS像，肺炎像などがある．　b）腹部超音波（US）：急性膵炎が疑われるすべての症例に対し，最初に行われるべき検査の1つである．膵腫大や膵周囲の炎症性変化のほかに，腹水の有無，胆管結石や総胆管拡張のチェックなど，急性膵炎の原因や病態に関連した異常所見がとらえられる．　c）X線CT：膵腫大，膵周囲の炎症性変化，液体貯留，膵実質濃度の不均一などを認める．腎機能の悪化やアレルギー反応等に留意しながら，可能な限り早期に造影CTやダイナミックCTを行い，重症度と相関する膵壊死の有無やその範囲，炎症性変化の広がりを判定する（表8-9-2）．
診断
　①上腹部に急性腹痛発作と圧痛がある，②血中または尿中に膵酵素の上昇がある，③超音波，CTまたはMRIで膵に急性膵炎に伴う異常所見がある．これら3項目のうち2項目以上を満たし，ほかの膵疾患および急性腹症を除外したものを急性膵炎と診断する．慢性膵炎の急性増悪は急性膵炎に含める．
　軽症と重症では治療方針が大きく異なるため，発症後48時間以内に「急性膵炎の重症度判定基準（厚生労働省特定疾患難治性膵疾患に関する調査研究班，2008）（表8-9-1，8-9-2）に従って重症度を判定し，患者の病状を正確に把握する．この重症度判定基準は，9項目の予後因子による重症度判定と造影CTグレードによる重症度判定が独立しており，いずれかで重症と判定されれば，重症急性膵炎の診断が確定する．予後因子による重症度判定は，臨床徴候や最小限の血液検査項目によって判定できるよう工夫されており，急性膵炎初診時の重症度判定および入院後の経過観察に用いられる．急性膵炎の病態は時々刻々変化するため，臨床徴候や検査データを頻回にチェックし，重症度判定を繰り返し行って重症化を早期に診断することが大切である．
鑑別診断
　血中や尿中アミラーゼの上昇をしばしば伴い，腹痛を主症状とする疾患として，穿孔性消化性潰瘍，腸閉塞や腸破裂，解離性大動脈瘤，術後高アミラーゼ血症，糖尿病性ケトアシドーシス，胆石症，傍十二指腸乳頭憩室炎などがあげられる．また，膵癌が膵管狭窄などにより急性膵炎を初発症状とすることがあり，高齢者の急性膵炎では注意を要する．心窩部激痛でショックを伴う場合，胸腹部の大動脈瘤破裂，解離性大動脈瘤や心筋梗塞なども念頭におく．
合併症
　重症急性膵炎では，発症2週以内に頻度が高いショック，呼吸不全，腎不全や多臓器不全などの早期合併症と，2週以降に頻度が増加する敗血症や感染性膵壊死，膵膿瘍などの重症感染症やこれらによる多臓器不全，仮性囊胞，仮性囊胞の感染や消化管穿破による消化管出血，腹腔内出血，腸管出血，肝不全などの後期合併症がある．
経過・予後
　軽症例の予後は良好で，2〜5日で腹痛は軽減し，2〜3週で自他覚的にもほぼ改善する．膵機能障害も残さないことが多い．
　急性膵炎全体の致命率は2.6％である．予後因子2点以下の軽症例の致命率は0％であったが，3点以上の重症例は19％，5点以上では致命率が50％に達した（厚生労働省研究班の2006年度前向き調査）．造影CTによる重症度判定では，CT grade 1の症例には死亡例がなかったが，CT grade 2以上の致命率は14.8％であり，予後因子および造影CT gradeの両方で重症と判定された症例の致命率は30.8％に達した．予後因子3点以上の症例では造影CTを行い，予後不良例を検出することが大切である．
治療
　入院治療を原則とする．治療の要点は，速やかに初期治療を開始し，十分な輸液によって循環動態を改善・維持して多臓器不全の発症を予防すること，重症例やその可能性のあるものでは，早期より予防的に抗菌薬を投与して感染性合併症を予防することである．予後因子3点以上の重症例は，ICU管理，IVR（interventional radiology），持続的血液濾過透析（CHDF），胆石症に対する内視鏡治療，外科的治療，栄養サポートチームなどを備え，重症急性膵炎に対応可能な施設へ転送を行う．初期に予後因子スコアが2点以下であっても，重症度判定を繰り返し行い，重症と判定されれば搬送を考慮する（図8-9-4）．
1）初期治療：
　a）輸液：軽症例でも血圧，脈拍，尿量の輸液への反応をみながら，乳酸リンゲル液や酢酸リンゲル液を基本として3000 mL/日以上を目安に十分な輸液を行う．
　重症例や重症化が懸念される急性膵炎症例には，初期輸液量として60〜160 mL/kg/日を設定し，最初の6時間に1日量の1/2〜1/3を投与する．意識状態，血圧，脈拍数，呼吸数，酸素飽和度，体温，尿量を経時的にモニタリングし，循環動態を評価して，時間尿量として最低0.5 mL/kg/hr以上を確保する．　b）蛋白分解酵素阻害薬：活性化膵酵素を阻害して膵炎の進展を抑え，重症化を予防するために，ガベキサートメシル酸塩（FOY），ナファモスタットメシル酸塩（FUT），ウリナスタチン（UR）などの蛋白分解酵素阻害薬の点滴静注を開始する．重症膵炎ではDICやショックを合併することが多く，蛋白分解酵素阻害薬の大量持続投与やFOYとUR，FUTとURなどの2剤併用投与が行われる．
　c）疼痛治療：十分な疼痛の抑制をはかる．ブプレノルフィンやペンタゾシンの投与が推奨されるが，Oddi括約筋の収縮作用があるため，頻回に用いるときは硫酸アトロピンを併用する．より強力な鎮痛にはオピアトやパンアトなどの麻薬製剤も使用される．軽度の疼痛には，ジクロフェナクやインドメタシンの坐薬を用いる．　d）胃酸分泌抑制：急性胃粘膜病変や消化管出血の合併例や合併する可能性がある症例に対してはH₂受容体拮抗薬を投与する．
2）感染対策：
軽症例には抗菌薬の予防的投与は必要とされない．重症例や重症化が予測される症例では致命的な合併症である膵および膵周囲の感染症の発生頻度が高いため，膵移行性の高い広域スペクトラムをもつ抗菌薬を早期から予防的に投与する．カルバペネム系抗菌薬が推奨される．　胆道感染症の合併があれば，胆汁移行性を考慮して第2世代以降のセフェム系抗菌薬の投与が推奨される．
3）栄養管理：
軽症例には中心静脈栄養の有用性は認められない．比較的早期から経口摂取が可能である．症状が長引く場合，経腸栄養を試みる．　重症例には中心静脈栄養が行われることが多いが，空腸に留置した栄養チューブを介して早期から経腸栄養を行うことが推奨されている．耐糖能障害がある場合は，インスリンを併用する．
4）胆石性膵炎：
胆石性膵炎が明らかで，胆管炎や結石嵌頓による閉塞性黄疸がみられる症例では，緊急に内視鏡的乳頭切開術を行い，結石の除去，経鼻胆道ドレナージチューブの留置（ENBD）などの処置を行う（図8-9-5）．胆石性膵炎では，再燃を予防するために，膵炎鎮静化後の胆囊摘出術が奨められる．
5）重症急性膵炎に対する特殊療法：
生命予後を改善する試みとして，以下に述べる特殊療法が行われている．十分な初期輸液にもかかわらず，循環動態が不安定で利尿が得られない症例には持続的血液濾過透析（CHDF）が行われる．重症例では，MOF惹起因子を血中から除去する効果も期待される．重症の壊死性膵炎に対しては，薬剤の膵組織濃度を高め，膵の炎症と感染を強力に抑制する目的で蛋白分解酵素阻害薬・抗菌薬膵局所動注療法が行われている．感染対策として，腸管内に留置したチューブから非吸収性抗菌薬を投与し，腸内細菌を選択的に根絶する選択的消化管除菌（SDD）も行われる．
6）外科的治療：
重症膵炎でも治療の原則は保存的治療であり，早期に外科手術が行われることはなくなった．保存的治療の経過中に，感染性膵壊死が疑われる場合には，CTあるいは超音波ガイド下に膵局所を穿刺し（FNA），吸引液の細菌学的検査を行う．感染性膵壊死が確認された場合，膵壊死組織を除去するネクロゼクトミーが必要となる．
　膵膿瘍，増大する仮性囊胞や症状を伴うもの，仮性囊胞で囊胞内出血や感染を合併した場合には，内視鏡的ドレナージや経皮的ドレナージ，外科的内瘻術を考慮する．［廣田衛久・下瀬川　徹］
■文献
厚生労働省難治性疾患克服研究事業難治性膵疾患に関する調査研究班編：急性膵炎における初期診療のコンセンサス，アークメディア，東京，2008.急性膵炎診療ガイドライン2010改訂出版委員会：急性膵炎診療ガイドライン2010 第3版，金原出版，東京，2009.下瀬川　徹：厚生労働省難治性膵疾患に関する調査研究班，平成20～22年度　総合研究報告書，2011.

表8-9-1
急性膵炎の重症度判定基準（厚生労働省難治性膵疾患に関する調査研究班，2008）">

表8-9-1

表8-9-2
急性膵炎の重症度判定基準（厚生労働省難治性膵疾患に関する調査研究班，2008">

表8-9-2

図8-9-4
急性膵炎の基本的診療方針">

図8-9-4

図8-9-5
胆石性膵炎の診療方針">

図8-9-5

出典　内科学第10版内科学第10版について　情報

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