diarrhea

Japanese: 下痢

Concept Diarrhea was the most important symptom along with trauma throughout most of human history. Before cancer or arteriosclerosis became an issue, most people died from infectious diseases, and among diseases, enteritis (dysentery, cholera, typhoid, etc.) was the biggest cause of death. With the development of human society in the past few decades, the threat of infectious diseases has decreased significantly, and now diarrhea is just one of many symptoms. In diarrhea, the stool is liquid or muddy and does not have any shape, so the amount of stool per day and the frequency of bowel movements often increase. To understand the mechanism, it is easiest to understand the normal dynamics of water ingested orally (Figure 2-12-1). About 2 L of water is ingested orally per day, and about 0.1 to 0.2 L is excreted as feces. Numerically, 90 to 95% is absorbed, but in reality it is not so simple. In other words, when water ingested orally enters the digestive tract, it is immediately absorbed by the mucous membrane and begins to move into the extracellular fluid, and is also actively secreted from the digestive tract mucosa into the lumen. The amount of water absorbed reaches about 9 L per day, and about 7 L is secreted per day. Water circulates between the extracellular fluid and the digestive tract many times. Normally, most water is excreted through the kidneys and insensible perspiration, and even if the intake is high, there is ample absorption capacity and the renal system can keep up, so diarrhea does not occur. If water is not absorbed sufficiently from the digestive tract (malabsorptive diarrhea, osmotic diarrhea) or if there is increased secretion and seepage from the digestive tract mucosa (secretory diarrhea), the amount of stool increases and diarrhea occurs.
Pathophysiology: When the osmotic pressure of the intestinal contents increases, water is secreted from the intestinal mucosa to bring the intestinal mucosa closer to isotonicity, but if the solute is non-absorbable, a large amount of water is drawn into the intestinal tract. In such cases, osmotic diarrhea occurs. Diarrhea can also occur when absorption is insufficient due to short bowel syndrome, intestinal bypass, or increased intestinal peristalsis. Osmotic diarrhea can occur even when absorption is insufficient due to mucosal lesions (Crohn's disease, amyloidosis, etc.), but these diseases also have a secretory diarrhea aspect. Polyethylene glycol and magnesium salts used in pretreatment for colon examinations take advantage of osmotic diarrhea, and sorbitol is also used as a laxative. Bile acid preparations also cause diarrhea through this mechanism, and intestinal bacterial overgrowth causes diarrhea due to deconjugation of bile acids. Diarrhea occurs in people with lactose intolerance because non-absorbable lactose cannot be broken down, and in people with pancreatic insufficiency because fats and other substances cannot be broken down.
Secretory diarrhea can be caused by increased secretion from epithelial cells (secretory diarrhea in the narrow sense), or by secretion of exudate due to damage to the mucosa caused by inflammation, etc. (exudative diarrhea). The most prominent example of secretory diarrhea is cholera, in which cholera toxin induces large amounts of cAMP through the abnormal activation of G protein, causing copious secretion of intestinal fluids even in the absence of inflammation. Bloody diarrhea occurs when mucosal damage is also present, i.e., in the case of exudative diarrhea. In fact, there are many conditions in which osmotic diarrhea and secretory diarrhea coexist (infectious enteritis, Crohn's disease, etc.).
Differential diagnosis In practice, the key to differentiating diarrhea is whether it is acute or chronic (or recurrent). In addition, the location of the lesion can be roughly determined by questioning and physical examination (Table 2-12-1).
1) Acute diarrhea (Table 2-12-2):
If an intestinal infection or food poisoning is suspected, such as acute diarrhea with fever, abdominal pain, bloody diarrhea, or similar symptoms seen in the surrounding area, a stool test (culture and toxins) should be performed. Norovirus, rotavirus, adenovirus, and other viral enteritis are the most common, so the current epidemic situation can be used as a reference. Bloody diarrhea is rare among viral causes. Among bacterial enteritis, enterohemorrhagic E. coli (EHEC O157:H7, etc.) requires the same attention as dysentery due to the severity of the condition and high infectiousness, and if this is suspected, a diagnosis should be made promptly using verotoxins and stool culture. In cases of diarrhea after the administration of antibiotics, pseudomembranous enteritis and antibiotic-induced hemorrhagic enteritis should be kept in mind. Pseudomembranous enteritis in particular occurs in those with low physical strength and is prone to becoming serious, so CD toxins and other conditions should be checked early. Cryptosporidiosis is characterized by acute severe diarrhea and abdominal pain, and caution is required immediately after returning from a developing country. Diagnosis is made by detecting the protozoa in the stool. It is also important to ask about medications (laxatives, bile acid preparations, colchicine, anticancer drugs, etc.) and stimulants (cold water, large amounts of alcohol, etc.). In ischemic intestinal disease, bloody diarrhea, sudden onset accompanied by abdominal pain, advanced age, and a history of constipation are useful indicators. Enteritis caused by cytomegalovirus, herpes simplex virus, candida, etc. can also occur in patients with AIDS, cancer, and those receiving immunosuppressants or after organ transplants, and in other immunocompromised situations. In addition, caution is required after surgery, especially after gastrectomy, for severe MRSA enteritis. In patients with severe leukopenia due to anticancer drugs for hematological malignancies, neutropenic enterocolitis may develop, accompanied by a sudden deterioration of the patient's overall condition due to bacterial infection. In addition, after bone marrow transplantation, diarrhea caused by intestinal graft-versus-host disease (GVHD) must be differentiated from infection.
2) Chronic (recurrent) diarrhea (Table 2-12-3):
In chronic (recurrent) diarrhea, irritable bowel syndrome is common, and can be roughly diagnosed through medical history. There are no systemic symptoms such as weight loss or fever. Chronic bloody diarrhea may be due to ulcerative colitis, and in young people with persistent diarrhea accompanied by weight loss, Crohn's disease may be considered. Patients with immunodeficiency or ulcerative colitis often suffer from colitis caused by cytomegalovirus or Clostridium difficile. In middle-aged or older patients with abdominal pain and weight loss, the possibility of colon cancer should be kept in mind. In these cases, colon and small intestine examinations (endoscopy, biopsy, contrast, CT) are useful. Liver failure, malnutrition, food allergies, lactose intolerance, and hyperthyroidism can be diagnosed through medical history, physical examinations, and general examinations. In practice, when chronic diarrhea is not typical of irritable bowel syndrome and the cause is unclear, it is common to perform intestinal endoscopy or contrast examinations. If Crohn's disease is suspected, not only colonic examinations but also small intestinal examinations are necessary. AIDS patients can suffer from various types of infectious enteritis as well as non-infectious diarrhea. Recently, microscopic colitis (including collagenous colitis and lymphocytic colitis), which is common in elderly women, has been much talked about, and causes chronic watery diarrhea. Many cases are drug-induced by NSAIDs or lansoprazole. Endoscopic examinations are characterized by very long longitudinal ulcers, but these are often asymptomatic. Collagenous colitis is characterized by a thickened collagen band just below the covering epithelium in biopsies, and is more often prominent in the right colon than in the lower colon. Lymphocytic colitis has extensive intraepithelial lymphocytic infiltration into the epithelial layer. The mechanism of microscopic colitis has not been elucidated, but if the causative drug is clear, treatment is to discontinue the drug. [Matsuhashi Nobuyuki]

Table 2-12-1
Diarrhea lesions ">

Table 2-12-1

Table 2-12-2
Causes of acute diarrhea (* indicates that the diarrhea may become bloody)

Table 2-12-2

Table 2-12-3
Causes of chronic diarrhea (* indicates conditions that may cause bloody diarrhea )

Table 2-12-3

Figure 2-12-1
Water balance (per day)

Figure 2-12-1

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

Japanese:

概念
　下痢は人類史の大部分を通じて外傷と並んで最も重要な症候だった．癌や動脈硬化が問題になる前に感染症で命を落とすことがほとんどで，病気の中では腸炎（赤痢，コレラ，チフスなど）が最大の死因だった．ここ数十年の人類社会の発展に伴い感染症の脅威は大幅に減り，いまでは下痢といっても数ある症候の1つにすぎなくなった．下痢は便が形をなさず液状～泥状であることで，1日の便の量，排便回数も増加していることが多い．その機序を知るには経口摂取された水分の正常の動態を理解するのが早い（図2-12-1）．経口摂取される水分は1日約2 Lで，糞便として排出されるのは約0.1～0.2 Lである．数字の上では90～95％が吸収されたことになるが，実際には単純なものではない．すなわち，経口摂取された水分は消化管内に入ると直ちに粘膜から吸収されて細胞外液に移行しはじめるとともに，消化管粘膜からの内腔への分泌もさかんに行われる．この水分吸収は1日に約9 Lに及び，分泌も1日約7 Lに及ぶ．水分は細胞外液と消化管内の間を何度も循環するのである．水分の排出は正常では大部分が腎臓，不感蒸泄によっており，摂取量が多くても吸収力には余裕があって腎臓の系が対応して下痢にはならない．消化管からの水分の吸収が十分でないか（吸収不良性下痢，浸透圧性下痢），消化管粘膜からの分泌・浸出が多くなれば（分泌性下痢）便の量が増えて下痢となる．
病態生理
　腸管内容物の浸透圧が上がると腸粘膜から水が分泌されて等張に近づけようとするが，溶質が非吸収性だと腸管内に多量の水分を引き込むことになる．そのようなとき浸透圧性下痢となる．あるいは短腸症候群，腸管のバイパス，腸管蠕動運動の亢進などで十分な吸収ができない場合も下痢となる．粘膜病変（Crohn病，アミロイドーシスなど）のため吸収が十分できなくても浸透圧性下痢が起きうるが，これらの疾患では分泌性下痢の側面もある．大腸検査前処置のポリエチレングリコールやマグネシウム塩などは浸透圧性下痢を利用したものであり，ソルビトールも下剤として使われる．胆汁酸製剤もこの機序で下痢を起こし，腸管内細菌異常増殖では胆汁酸の脱抱合で下痢を起こす．乳糖不耐症では非吸収性の乳糖が分解されないため，膵機能不全では脂肪などの分解ができないために下痢となる．
　分泌性下痢には上皮細胞からの分泌の亢進によるもの（狭義の分泌性下痢）と炎症などにより粘膜が傷害されて浸出液が分泌されることによるもの（浸出性下痢）がある．分泌性下痢の最たるものはコレラで，コレラ毒素はG蛋白の異常活性化を介して多量のcAMPを誘導し，炎症はないのにおびただしい腸液の分泌を起こす．血性下痢がみられるのは粘膜障害を伴うとき，すなわち浸出性下痢の場合である．実際には浸透圧性下痢と分泌性下痢の混在した病態も多い（感染性腸炎，Crohn病など）．
鑑別診断
　下痢の鑑別は，実践的には急性か慢性（ないし反復性）かが大きな鍵となる．また，病変部位については問診，診察で大体の見当がつく（表2-12-1）．
1）急性下痢（表2-12-2）：
急性下痢で発熱，腹痛，血性下痢，周囲に同様の症状を呈する例がみられるなど腸管感染症や食中毒が疑わしいときは，検便（培養，毒素）を行う．数の上ではノロウイルス，ロタウイルス，アデノウイルスなどのウイルス性腸炎が多く，流行状況が参考になる．ウイルス性では血性下痢はまれ．細菌性腸炎の中では，腸管出血性大腸菌（enterohemorrhagic E. Coli， EHEC．O157：H7など）は病態の重篤さと感染性の高さの点で赤痢と同様の注意が必要であり，これが疑われる場合はベロ毒素や便培養で早急に診断をつける必要がある．抗菌薬投与後の下痢では偽膜性腸炎や抗菌薬による出血性腸炎を念頭におく．特に偽膜性腸炎は体力のない者に発生して重篤化しやすいので，早期にCDトキシンなどを調べる．クリプトスポリジウム症では急性の激しい下痢，腹痛が特徴で，発展途上国からの帰国直後では注意が必要であり，便中の原虫を検出して診断する．薬剤（下剤，胆汁酸製剤，コルヒチン，抗癌薬など）や刺激物（冷水，多量の酒など）についても問診が重要．虚血性腸疾患では血性下痢であること，発症が突然で腹痛を伴うこと，高齢，便秘歴などが参考になる．AIDS，坦癌患者，免疫抑制薬投与中や臓器移植後などの免疫能低下の状況下では，サイトメガロウイルス，単純ヘルペスウイルス，カンジダなどによる腸炎も起こりうる．また，手術後，特に胃切除後では重篤なMRSA腸炎に注意が必要．血液悪性腫瘍などで抗癌薬により高度の白血球減少がある場合に，細菌感染による急激な全身状態の悪化を伴う好中球減少性腸炎（neutropenic enterocolitis）が発症することがある．また，骨髄移植後では腸のGVHD（graft-versus-host disease，移植片対宿主病）による下痢も感染との鑑別が必要である．
2）慢性（反復性）下痢（表2-12-3）：
慢性（反復性）下痢では過敏性腸症候群が多く，問診でだいたい見当がつくし，体重減少や発熱などの全身症状を欠く．血性下痢が慢性的に続くのは潰瘍性大腸炎などが考えられ，若年者で体重減少を伴う下痢が続くときはCrohn病などを考える．免疫不全状態や潰瘍性大腸炎患者ではサイトメガロウイルスやClostridium difficileによる腸炎の合併も少なくない．中年以降で腹痛，体重減少などを伴う場合は大腸癌の可能性を念頭におく．これらの場合は大腸，小腸の検査（内視鏡，生検，造影，CT）が有用．肝不全，低栄養状態，食物アレルギー，乳糖不耐症，甲状腺機能亢進症などはおのおの問診，理学所見，一般検査などで見当をつける．実践的には，慢性下痢で典型的な過敏性腸症候群でなく，原因が明らかでない場合は，腸の内視鏡ないし造影検査を行うのが一般的である．Crohn病が疑われる場合は大腸検査だけでなく小腸検査も必要．AIDSでは諸種の感染性腸炎のほか，非感染性の下痢もみられる．最近話題になることが多いのが高齢女性に多いmicroscopic colitis（collagenous colitisとlymphocytic colitisを含む）で，慢性の水様の下痢をきたす．NSAIDsやランソプラゾールによる薬剤誘起性のものが多い．内視鏡的には非常に長い縦走潰瘍が特徴的だが無所見のことも多い．collagenous colitisでは生検で被蓋上皮直下の肥厚したcollagen bandを特徴とし，下部大腸より右側大腸により顕著なことが多い．lymphocytic colitisでは上皮層への上皮内リンパ球浸潤が高度である．このmicroscopic colitisの機序は未解明だが，原因薬剤がはっきりしている場合はそれを中止するのが治療になる．［松橋信行］

表2-12-1
下痢の病変部位">

表2-12-1

表2-12-2
急性下痢の原因（＊は血性下痢を呈しうるもの）">

表2-12-2

表2-12-3
慢性下痢の原因（＊は血性下痢を呈しうるもの">

表2-12-3

図2-12-1
水分の出納（1 日あたり）">

図2-12-1

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