胆石症の病態
胆石症とは胆道に胆石が存在することによって引き起こされる様々な病態の総称である。
胆石症は胆石が存在する部位によって3つに分類される。
胆嚢に胆石ができた場合は胆嚢結石症、総胆管に胆石ができた場合は総胆管結石症、肝内に胆石ができた場合は肝内結石症と呼ばれる。
「胆石症に関する2013年度全国調査結果報告」では重複例を含めて胆嚢結石症:74.5%,総胆管結石症:25.6%,肝内結石症:3.7%の割合だったと報告されている。
胆石症は急性胆嚢炎や急性胆管炎を発症して存在が明らかになることが多いものの、検診などで偶然発見されて自覚症状を伴わない「無症状胆石」も存在する。「無症状胆石」に対しては定期的な腹部超音波検査による経過観察が行われる。
代表的なリスクファクター
胆石症の代表的なリスクファクターとしては、5Fと呼ばれる［Forty:年齢, Female:女性, Fatty:肥満, 白人:Fair, Fecund・Fertile:多産・経産婦］が有名である。
合併しやすい状態と胆石の種類
高脂血症では胆汁中のコレステロールが飽和することによってコレステロール胆石が発生しやすい。コレステロール胆石はX線陰性結石であり、胆嚢結石で最多を占める。
完全経静脈栄養・胃切除後などでは胆嚢収縮能が低下して胆汁うっ滞が生じる。胆汁うっ滞が生じると胆汁感染が起こって、細菌が分泌する酵素が不溶性ビリルビンカルシウムを析出させてビリルビンカルシウム胆石が発生する。
総胆管結石と肝内結石は胆汁うっ滞による胆道感染を起因とすることが多く、ビリルビンカルシウム胆石は肝内結石と総胆管結石で最多を占める。
溶血性貧血・肝硬変(脾機能亢進)などの溶血性因子によって胆汁中のビリルビンが増加すると黒色胆石が発生する。
ビリルビンカルシウム胆石と黒色胆石はX線陽性結石であり、色素胆石と呼ばれている。
急性胆嚢炎と急性胆管炎の病態
胆石の存在によって胆嚢管が閉塞すると急性胆嚢炎が発症して、胆管が閉塞すると急性胆管炎が発症する。
これは胆道閉塞によって胆汁感染が起こることが原因である。
起因菌としてはグラム陰性桿菌(Escherichia coli, Klebsiella spp.)と嫌気性菌が多い。
細菌増殖による急性炎症と胆道内圧上昇によって細菌またはエンドトキシンが血流内に逆流することで症状が起こる。
胆石症では右上腹部痛(右季肋部痛)・心窩部痛に右肩甲部の関連痛を伴う胆道仙痛と呼ばれる腹痛が特徴となる。これは食後に多く、高脂肪食が誘発因子になる。
また、腹膜刺激症状として筋性防御やBlumberg徴候(反跳痛)を呈することも多い。
細菌が血流に逆流することによって発熱・悪寒も呈する。
急性胆嚢炎と急性胆管炎の違い
急性胆嚢炎と急性胆管炎の症状は似ているものの、急性胆嚢炎は胆嚢内にできた結石が胆嚢管に嵌頓して引き起こされるのに対して、急性胆管炎は総胆管内にできた結石が総胆管を閉塞した結果として起こるという違いがある。
急性胆嚢炎の特徴
急性胆嚢炎では胆嚢が炎症を起こして腫大するため、触診において右上腹部で腫瘤(腫大した胆嚢)を触知できる。
また、Murphy徴候が陽性となるのが大きなポイントである。
Murphy徴候とは右上腹部に手を差し込んで圧迫しながら患者に深呼吸をさせると、痛みのために途中で吸気が止まる現象を指す。
これは吸気時は横隔膜の動きに伴って胆嚢も下がり手に触れるために起こる現象である。
急性胆管炎の特徴
急性胆管炎は総胆管結石によって総胆管が閉塞するため、胆汁が十二指腸に排出されなくなり黄疸が引き起こされることが大きなポイントである。
急性胆管炎ではCharcot 3徴と呼ばれる腹痛・発熱・黄疸という症状が特徴となり、昔は診断基準にも用いられていた。
Charcot 3徴にショック(血圧低下)・意識障害を加えたReynolds 5徴を呈したものは「重症」の急性胆管炎を示唆するものだとして急性閉塞性化膿性胆管炎と概念的な用語が用いられてきたが、その定義が曖昧なため現在では臨床用語としては用いられなくなってきている。
胆石症の検査と治療
胆石症の検査
胆石症は臨床症状に加えて、特徴的な画像所見を確認することで確定診断を行う。
胆石症を臨床症状によって疑った場合にはまず腹部超音波検査を行う。
腹部超音波検査を行った後により詳細な情報を得るために内視鏡的逆行性膵胆管造影法:Endoscopic Retrograde Cholangiopancreatography(ERCP)や腹部CTやMR胆管膵管撮影:Magnetic Resonance Cholangio Pancreatography(MRCP)を行う。
急性胆嚢炎では腹部超音波検査で音響陰影(acoustic shadow)を伴う高エコー域として胆嚢結石を認めることが多い。
音響陰影(acoustic shadow)とは結石の後方に出現する無エコー域を指す。
急性胆管炎ではERCPで総胆管に詰まった総胆管結石を認めることが多い。
胆石症の治療
胆石症の治療は炎症が強い場合に炎症を抑えるためにまず行われる治療とその後で次に根治を目指して行われる治療に分けられる。
まず行う治療
胆石症(急性胆嚢炎・急性胆管炎)の治療において、炎症が強い場合はまずドレナージ＋抗菌薬を行う。
ドレナージでうっ滞した胆汁を排液することに加えて、抗菌薬を静脈投与することで炎症を抑える。
ある程度炎症が落ち着いてから次に行う治療に移る。
急性胆嚢炎に対して行うドレナージ
急性胆嚢炎では経皮経肝ドレナージ:Percutaneous Transhepatic Gallbladder Drainage(PTGBD)が行われることが多い。
経皮経肝ドレナージでは肝臓と胆嚢が接する肝床(胆嚢床)を経由して穿刺することがポイントとなる。
また、内視鏡的経鼻胆嚢ドレナージ:Endoscopic Nasogallbladder Drainage(ENGBD)が腹水貯留例や出血傾向といった経皮的アプローチ困難な症例に対して行われることがあるものの限られた施設でしか行われておらず一般的な方法とはいえない。
急性胆管炎に対して行うドレナージ
急性胆管炎では内視鏡的逆行性膵胆管造影法:Endoscopic Retrograde Cholangiopancreatography(ERCP)のついでに内視鏡的胆管ドレナージ:Endoscopic Biliary Drainage(EBD)が行われることが多い。
内視鏡的胆管ドレナージには内視鏡的経鼻胆管ドレナージ:Endoscopic Nasobiliary Drainage(ENBD)と内視鏡的胆管ステント留置術:Endoscopic Biliary Stenting(EBS)がある。
また、経皮経肝胆管ドレナージ:Percutaneous Transhepatic Cholangiodrainage(PTCD)が行われることもあるが、出血傾向の患者に対しては行えないことに注意する必要がある。
次に行う治療
急性胆嚢炎の治療
急性胆嚢炎の治療では基本的には胆嚢を外科的に除去する。
胆嚢は胆汁の貯蔵庫という役割を果たしているだけに過ぎない臓器であるため、実は胆嚢が無くなっても生命維持の観点からみるとあまり影響が出ることはないものの手術後には下痢などをきたすことがある。
胆嚢摘出後は胆汁の腸肝循環の回数が増加することに伴って二次胆汁酸の生成が増加する。二次胆汁酸は大腸粘膜からの水分泌を増加させるため、結果として糞便の水分量が増えて下痢をきたすのである。
回腸末端の切除術後にも同じ機序で下痢が起こることがあるのだが、これは通常回腸末端で吸収されるはずの一次胆汁酸が大腸で二次胆汁酸に変換されるために起こるのである。
急性胆嚢炎の有症状時の第一選択は腹腔鏡下胆嚢摘出術である。
ただし、術前や術中に胆嚢癌の合併が明らかとなった場合には開腹胆嚢摘出術へと移行する。
体外衝撃波結石破砕術(ESWL)と経口胆石溶解薬は一部のコレステロール胆石で適応となる。
急性胆管炎の治療
急性胆管炎の治療では胆管石を内視鏡的に除去することが日本では主な治療法となっている。
内視鏡的総胆管結石除去術には内視鏡的乳頭括約筋切開術:Endoscopic Sphincterotomy(EST)と内視鏡的乳頭バルーン拡張術:Endoscopic Papillary Balloon Dilation(EPBD)がある。
総胆管結石に胆嚢結石を合併している場合は内視鏡的総胆管結石除去術を行った後で腹腔鏡下胆嚢摘出術を行う。
治療上の注意点
胆石症の患者に対して塩酸モルヒネは慎重投与しなければいけない。
塩酸モルヒネのOddi括約筋収縮作用によって胆道痙攣が引き起こされる恐れがあるためである。
Oddi括約筋の収縮・弛緩作用のメカニズムは未だ完全には明らかとなっておらず、Oddi括約筋は副交感神経によって収縮するという従来型の考えと、非アドレナリン性抑制ニューロンの働きで副交感神経によって弛緩するという近来型の考えが存在する。
近来型の考えに従うと迷走神経刺激で胆嚢は収縮してOddi括約筋は弛緩するという考えが成り立つ。
また、従来型の考えに従うと抗コリン薬にはOddi括約筋収縮を抑制する働きがあるため、急性膵炎の疼痛時に塩酸モルヒネと抗コリン薬を併用して投与することがあるという理由を説明できる。
一見矛盾しているようにも思えるが、Oddi括約筋の収縮メカニズムというのは副交感神経の働きのみによっては説明できず、他にも様々な要因が関わっているためにこのようなことが起こっていると考えられる。
参考文献
第Ⅸ章 急性胆嚢炎に対する胆嚢ドレナージの適応と手技:https://minds.jcqhc.or.jp/docs/minds/TG/CPGs_TG2013_Ch09.pdf
日本消化器病学会 胆石症診療ガイドライン2016(改訂第2版):https://www.jsge.or.jp/guideline/guideline/pdf/GS2_re.pdf
無石性胆嚢炎:http://hospi.sakura.ne.jp/wp/wp-content/themes/generalist/img/medical/jhn-cq-teine-170920.pdf
第Ⅵ章 急性胆嚢炎の診断基準と重症度判定基準・搬送基準:https://minds.jcqhc.or.jp/docs/minds/TG/CPGs_TG2013_Ch06.pdf
第Ⅴ章 急性胆管炎の診断基準と重症度判定基準・搬送基準:https://minds.jcqhc.or.jp/docs/minds/TG/CPGs_TG2013_Ch05.pdf
急性胆嚢炎・急性胆管炎の病態・診断・治療:https://www.jsgs.or.jp/cgi-html/edudb/pdf/20101041.pdf
第Ⅳ章 急性胆管炎・胆嚢炎 診療フローチャートと基本的初期治療:https://minds.jcqhc.or.jp/docs/minds/TG/CPGs_TG2013_Ch04.pdf
急性閉塞性化膿性胆管炎の外科的治療ーとくにDICとの関連においてー:http://journal.jsgs.or.jp/pdf/011010100.pdf
胆石の種類と成因:https://www.jstage.jst.go.jp/article/tando/27/4/27_672/_pdf
黄疸の臨床:診断と治療の進歩:https://www.jstage.jst.go.jp/article/naika1913/86/4/86_4_538/_pdf
輸液に伴う合併症:https://www.jspm.ne.jp/guidelines/glhyd/2013/pdf/02_05.pdf
良性術後肝内胆汁うっ滞症の一例:https://www.jstage.jst.go.jp/article/kanzo1960/19/4/19_4_383/_pdf/-char/ja
胆嚢総胆管結石症術後のOddi括約筋運動とその神経支配に関する臨床的研究:https://www.jstage.jst.go.jp/article/jsmr1991/30/4/30_4_177/_pdf
第Ⅹ章 急性胆嚢炎ー手術法の選択とタイミングー:https://minds.jcqhc.or.jp/docs/minds/TG/CPGs_TG2013_Ch10.pdf
胆石症に関する2013年度全国調査結果報告:https://www.jstage.jst.go.jp/article/tando/28/4/28_612/_pdf/-char/ja
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