消化道病理(二)

1、炎癥性腸病的臨床病理炎癥性腸病的臨床病理 THE CLINICO-PATHOLOGY OF INFLAMMATORY BOWEL DISEASE (IBD)2015-11-24潰瘍性結(jié)腸炎（潰瘍性結(jié)腸炎（Ulcerative colitis）克羅思?。肆_思病（Crohns disease）未定型結(jié)腸炎（未定型結(jié)腸炎（Indeterminate colitis）IBM一詞主要是指兩種腸?。嚎肆_思病和潰瘍性結(jié)腸炎。兩者臨床病一詞主要是指兩種腸?。嚎肆_思病和潰瘍性結(jié)腸炎。兩者臨床病程與病史不同，病變有別，但某些特點相同，而治療原則不同。程與病史不同，病變有別，但某些特點相同，而治療原則不同。 In

2、flammatory bowel disease is a term that describes two diseases: Crohn disease and ulcerative colitis. Although these two disorders have different clinical courses as well as natural histories and are usually clearly distinguishable, they have certain common features.無特異性實驗室檢測指標(biāo)（無特異性實驗室檢測指標(biāo)（No specif

3、ic laboratory tests）抗中性粒細(xì)胞胞質(zhì)抗體抗中性粒細(xì)胞胞質(zhì)抗體 pANCA (anti-neutrophil cytoplasmic antibody) 60-75%的潰瘍性結(jié)腸炎病例（的潰瘍性結(jié)腸炎病例（Ulcerative colitis: 60-75%） 10-40%的克羅思病病例（的克羅思病病例（Crohns disease: 10-40%）抗釀酒酵母菌抗體抗釀酒酵母菌抗體 ASCA (anti-Saccharomyces cerevisiae antibody) 40-80%的潰瘍性結(jié)腸炎病例（的潰瘍性結(jié)腸炎病例（Crohns disease: 40-80%） 10

4、%的克羅思病病例（的克羅思病病例（Ulcerative colitis: 10%）基因檢測：基因檢測： NOD2 和其他的和其他的IBD 基因基因 （Genetic testing for NOD2 and other IBD genes）IBD的實驗室檢測的實驗室檢測克羅恩病克羅恩?。–rohn Disease） 克羅恩病（克羅恩?。–rohn Disease） 腸炎特點（腸炎特點（Features of Inflammation of the Intestine） 慢性，節(jié)段性，透壁性慢性，節(jié)段性，透壁性（Chronic, Segmental, Transmural） 病變以病變以小腸遠(yuǎn)端

5、為主，右半結(jié)腸可受累小腸遠(yuǎn)端為主，右半結(jié)腸可受累，可有消化道甚至腸，可有消化道甚至腸外組織受累外組織受累 （Crohn disease occurs principally in the distal small intestine but may involve any part of the digestive tract and even extraintestinal tissues. The colon, particularly the right colon, may be affected.）2022-3-26克羅恩病的流行病學(xué)（克羅恩病的流行病學(xué)（Epidemiology）

6、全球發(fā)生克羅思病，每年發(fā)病率為全球發(fā)生克羅思病，每年發(fā)病率為0.5 - 5 人人/ 每每10萬人群萬人群。過去。過去30年來，來自各國的報道表明，全球的克羅思發(fā)病年來，來自各國的報道表明，全球的克羅思發(fā)病率急劇增加。率急劇增加。 （Crohn disease occurs worldwide, with an annual incidence of 0.5 to 5 per 100,000. Reports from various countries indicate that the incidence has increased dramatically over the past 30

7、 years. ） 歐洲的該病病例最常見于青少年或年輕成人歐洲的該病病例最常見于青少年或年輕成人,猶太人群呈猶太人群呈高發(fā)病率，女性較男性稍微多見高發(fā)病率，女性較男性稍微多見(1.6:1). The disease usually appears in adolescents or young adults and is most common among persons of European origin, with a considerably higher frequency in the Jewish population. There is a slight female pred

8、ominance (1.6:1).2022-3-26發(fā)病機(jī)制（發(fā)病機(jī)制（Pathogenesis） 家族性遺傳性體質(zhì)家族性遺傳性體質(zhì) Concordance rates in twin pairs and siblings strongly implicate a genetic predisposition to Crohn disease. A family history of inflammatory bowel disease is more common for Crohn disease than for ulcerative colitis. A putative suscep

9、tibility locus for Crohn disease has been assigned to the centromeric region of chromosome 16 where it is associated with the NOD2/CARD15 locus, which codes for an intracellular receptor for bacterial products involved in innate immunity. 自身免疫機(jī)制自身免疫機(jī)制 The possibility that Crohn disease reflects immu

10、nologically mediated damage to the intestine is suggested by (1) the chronic and recurrent nature（慢性反復(fù)發(fā)作） of the inflammation and (2) its association with systemic manifestations（全身損害） that are suggestive of autoimmune disease. Most recent immunologic studies focus on the possible role of cell-media

11、ted cytotoxicity.2022-3-26 腸道糞便流的作用腸道糞便流的作用 The fecal stream appears to be of prime importance in the pathogenesis of Crohn disease, as evidenced by：(1) the beneficial effects of surgical bypass（腸旁路吻合的好處）（腸旁路吻合的好處）(2) the pattern of preanastomotic recurrence in patients with side-to-end anastomotic

12、sites（側(cè)（側(cè)-端吻合處前段復(fù)發(fā)）端吻合處前段復(fù)發(fā)）, and (3) the frequency of early inflammatory lesions (aphthoid erosions) in the epithelium in association with mucosal lymphoid tissue（淋巴組織增生之（淋巴組織增生之上皮處早期炎癥上皮處早期炎癥-口瘡樣糜爛）口瘡樣糜爛）.2022-3-26病理變化（病理變化（Pathology） 克羅思病有兩大病變特征，以此與其他的炎癥性腸病相鑒別：克羅思病有兩大病變特征，以此與其他的炎癥性腸病相鑒別： Two majo

13、r characteristics of Crohn disease differentiate it from other GI inflammatory diseases. 第一，嚴(yán)重通常累及腸壁全層，故稱之為第一，嚴(yán)重通常累及腸壁全層，故稱之為透壁性炎癥透壁性炎癥。 First, the inflammation usually involves all layers of the bowel wall and is, therefore, referred to as transmural inflammatory disease. 第二，第二，腸壁病變是間斷性的腸壁病變是間斷性的，即

14、節(jié)段性腸炎病變，間有未受累，即節(jié)段性腸炎病變，間有未受累及的正常腸組織及的正常腸組織 Second, the involvement of the intestine is discontinuous; that is, segments of inflamed tissue are separated by apparently normal intestine.2022-3-26克羅恩病病變分布的四大部位特征克羅恩病病變分布的四大部位特征(1)回盲部回盲部病變?yōu)橹?，占病變?yōu)橹?，?0% mainly the ileum and cecum in about 50% of cases(2)僅

15、有僅有小腸小腸病變，占病變，占15% only the small intestine in 15%(3)僅有僅有大腸大腸病變，占病變，占20% only the colon in 20%(4)肛門直腸肛門直腸區(qū)病變?yōu)橹鳎紖^(qū)病變?yōu)橹?，?5% 女性肛門直腸區(qū)克羅恩病可蔓延到外陰部女性肛門直腸區(qū)克羅恩病可蔓延到外陰部 mainly the anorectal region in 15%. In women with anorectal Crohn disease, the inflammation may spread to involve the external genitalia.202

16、2-3-26大體觀大體觀(Grossly )腸壁與鄰近腸系膜增厚，水腫，腸系膜脂肪環(huán)繞腸周（腸壁與鄰近腸系膜增厚，水腫，腸系膜脂肪環(huán)繞腸周（爬行脂肪爬行脂肪） The bowel and adjacent mesentery are thickened as well as edematous, and mesenteric fat often wraps around the bowel (Creeping fat). 腸系膜淋巴結(jié)腸系膜淋巴結(jié)常常腫大，變硬，相互融合常常腫大，變硬，相互融合 Mesenteric lymph nodes are frequently enlarged, fi

17、rm, and matted together. 腸腔狹窄腸腔狹窄（水腫與纖維化共同作用所致），可見鵝卵石狀外觀（因結(jié)（水腫與纖維化共同作用所致），可見鵝卵石狀外觀（因結(jié)節(jié)狀腫脹、腸壁纖維化和粘膜潰瘍所致）節(jié)狀腫脹、腸壁纖維化和粘膜潰瘍所致） The intestinal lumen is narrowed by a combination of edema and fibrosis. Nodular swelling, fibrosis, and mucosal ulceration lead to a cobblestone appearance . 潰瘍特點：潰瘍特點：早期早期的潰瘍呈的

18、潰瘍呈口瘡狀口瘡狀或葡行狀；或葡行狀；晚期晚期的潰瘍變深呈的潰瘍變深呈線狀線狀裂縫或裂紋狀裂縫或裂紋狀 In early cases, ulcers have either an aphthous or a serpiginous appearance; later, they become deeper and appear as linear clefts or fissures (see Fig. 13-23B).2022-3-26圖片圖片A.A.末端回腸遠(yuǎn)端腸壁明顯增厚末端回腸遠(yuǎn)端腸壁明顯增厚，伴有回盲瓣變形。可見一，伴有回盲瓣變形?？梢娨豢v向潰縱向潰瘍瘍 ( (箭頭所示箭頭所示) )

19、圖片圖片B. B. 該回腸節(jié)段另一該回腸節(jié)段另一縱向潰瘍縱向潰瘍。受損粘膜水腫，形成圓形。受損粘膜水腫，形成圓形/ /卵圓卵圓形結(jié)節(jié)狀隆起，使病變腸段粘膜呈形結(jié)節(jié)狀隆起，使病變腸段粘膜呈鵝卵石樣外觀。右下側(cè)局部粘膜部鵝卵石樣外觀。右下側(cè)局部粘膜部分未受累分未受累2022-3-26 克羅恩病腸切除標(biāo)本大體觀克羅恩病腸切除標(biāo)本大體觀大體切面觀大體切面觀 The cut surface of the bowel wall shows the transmural （透壁性）nature of the disease, with thickening（增厚）, edema（水腫）, and fibro

20、sis（纖維化） of all layers. Involved loops of bowel are often adherent（粘連）, and fistulas（瘺管瘺管） between such segments are frequent. These fistulas may also penetrate from the bowel into other organs（腸壁瘺管穿入其它器官）, including the bladder, uterus, vagina, and skin. Lesions in the distal rectum and anus may cr

21、eate perianal fistulas（肛旁瘺）, a well-known presenting feature.2022-3-26Microscopically, Crohn disease appears as a chronic inflammatory process. During early phases of the disease, the inflammation may be confined to（局限于） the mucosa and submucosa. Small, superficial mucosal ulcerations (aphthous ulce

22、rs口瘡樣潰瘍) are seen. Later, long, deep, fissure-like（裂隙狀） ulcers are seen, and vascular hyalinization and fibrosis become apparent.The microscopic hallmark of Crohn disease is transmural, nodular, lymphoid aggregates (Fig. 13-24). Discrete（散在的）, noncaseating（非干酪樣） granulomas（肉芽腫）, mostly in the submuc

23、osa, may be present. Although the presence of granulomas is strong evidence in favor of Crohn disease, less than half of the cases show these lesions. The pathologic features of Crohn disease are summarized in Figure 13-25.2022-3-26正常的結(jié)腸粘膜組織結(jié)構(gòu)正常的結(jié)腸粘膜組織結(jié)構(gòu)Figure 13-24. 克羅恩病克羅恩病. 圖片圖片A顯示潰瘍至粘膜下層；淋巴組織聚集在

24、粘膜下顯示潰瘍至粘膜下層；淋巴組織聚集在粘膜下、鄰近肌層和漿膜下。圖片、鄰近肌層和漿膜下。圖片B顯示粘膜活檢，可見小灶上皮樣肉芽腫位于兩顯示粘膜活檢，可見小灶上皮樣肉芽腫位于兩個無損的腺隱窩之間。個無損的腺隱窩之間。 A. The colon involved with Crohn disease shows an area of mucosal ulceration, an expanded submucosa with lymphoid aggregates, and numerous lymphoid aggregates in the subserosal tissues immedi

25、ately adjacent to the muscularis externa. B. This mucosal biopsy in Crohn disease shows a small epithelioid granuloma (arrows) between two intact crypts.2022-3-26克羅恩病的肉芽腫病變克羅恩病的肉芽腫病變克羅恩病肉芽腫的高倍鏡下觀克羅恩病肉芽腫的高倍鏡下觀大腸腺上皮隱窩結(jié)構(gòu)變形大腸腺上皮隱窩結(jié)構(gòu)變形克羅恩病回腸炎克羅恩病回腸炎下圖見裂縫狀潰瘍下圖見裂縫狀潰瘍逆流性回腸炎逆流性回腸炎克羅恩病腸道活檢克羅恩病腸道活檢H-E染色切片組織學(xué)觀察

26、染色切片組織學(xué)觀察箭頭所示克羅恩病的透壁性炎癥箭頭所示克羅恩病的透壁性炎癥臨床特點臨床特點(Clinical Features) 克羅恩病的臨床表現(xiàn)與病史各自不同，與發(fā)病部位相關(guān)克羅恩病的臨床表現(xiàn)與病史各自不同，與發(fā)病部位相關(guān) The clinical manifestations and natural history of Crohn disease are highly variable and relate to the anatomical sites involved by the disease. 最常見癥狀：最常見癥狀：75%病人腹痛腹瀉；病人腹痛腹瀉；50%病人回歸熱病人回歸

27、熱The most frequent symptoms are abdominal pain and diarrhea, which are seen in more than 75% of patients, and recurrent fever, evident in 50%. 吸收不良和營養(yǎng)不良；腹瀉和腸出血；以直腸肛門病變?yōu)槲詹涣己蜖I養(yǎng)不良；腹瀉和腸出血；以直腸肛門病變?yōu)橹鞯目煞磸?fù)發(fā)生肛瘺主的可反復(fù)發(fā)生肛瘺 When the small intestine is diffusely involved, malabsorption and malnutrition may be ma

28、jor features. Crohn disease of the colon leads to diarrhea and sometimes colonic bleeding. In a few patients, the major site of involvement is the anorectal region, and recurrent anorectal fistulas may be the presenting sign.2022-3-26克羅恩病的繼發(fā)病變克羅恩病的繼發(fā)病變腸道阻塞、瘺管和腸穿孔腸道阻塞、瘺管和腸穿孔Intestinal obstruction and

29、 fistulas are the most common intestinal complications of Crohn disease. Occasionally, free perforation of the bowel occurs. 發(fā)生腸癌發(fā)生腸癌 Small bowel cancer is at least threefold more common in patients with Crohn disease, and the disease also predisposes to colorectal cancer.No cure for Crohn disease i

30、s available. Several medications suppress the inflammatory reaction, including corticosteroids, sulfasalazine, metronidazole, 6-mercaptopurine, cyclosporine, and anti-TNF antibodies. Surgical resection of obstructed areas or of severely involved portions of intestine and drainage of abscesses caused

31、 by fistulas are often required.2022-3-26克羅恩病小腸節(jié)段性病變特征模式圖克羅恩病小腸節(jié)段性病變特征模式圖2022-3-26潰瘍性結(jié)腸炎潰瘍性結(jié)腸炎（ Ulcerative Colitis ） 潰瘍性結(jié)腸炎（潰瘍性結(jié)腸炎（Ulcerative Colitis） 是結(jié)直腸發(fā)生的慢性淺表性炎癥是結(jié)直腸發(fā)生的慢性淺表性炎癥 Ulcerative Colitis is a Chronic Superficial Inflammation of the Colon and Rectum 臨床表現(xiàn)慢性腹瀉，直腸出血。是有加重和緩解，可伴有臨床表現(xiàn)慢性腹瀉，直腸出血。

32、是有加重和緩解，可伴有局部和全身并發(fā)癥局部和全身并發(fā)癥 Ulcerative colitis is characterized by chronic diarrhea and rectal bleeding, with a pattern of exacerbations and remissions and with the possibility of serious local and systemic complications.2022-3-26流行病學(xué)（流行病學(xué)（Epidemiology） In Europe and North America, the incidence of

33、ulcerative colitis is 4 to 7 per 100,000 population, and its prevalence is 40 to 80 per 100,000. It usually begins in early adult life, with a peak incidence in the third decade. However, it also occurs in childhood and old age. In the United States, whites are affected more commonly than blacks.202

34、2-3-26發(fā)病機(jī)制（發(fā)病機(jī)制（Pathogenesis）原因不清，可能與遺傳相關(guān)原因不清，可能與遺傳相關(guān) The cause of ulcerative colitis is unknown. In some families as many as six patients with this disease have been described, and concordance has been reported in monozygotic twins. However, available family studies do not suggest any distinct mode

35、 of genetic transmission.自身免疫病機(jī)制自身免疫病機(jī)制 The possibility that an abnormal immune response may be involved has been studied extensively. There is abundant lymphoid tissue throughout the colon, and ulcerative colitis may occur with autoimmune-like conditions, such as uveitis, erythema nodosum, and vasc

36、ulitis. Increased circulating antibodies against antigens in colonic epithelial cells and against cross-reacting antigens in enterobacteria may occur. Antineutrophil cytoplasmic antibodies are found in 80% of patients with ulcerative colitis. However, these abnormalities are neither unique for ulcer

37、ative colitis, nor are they a prerequisite for the development of the disease.2022-3-26病理變化（Pathology）Ulcerative colitis is a diffuse disease. It usually extends from the most distal part of the rectum（遠(yuǎn)端直腸） for a variable distance proximally (Fig. 13-26). Sparing of the rectum or involvement of the

38、 right side of the colon alone is rare and suggests the possibility of another disorder, such as Crohn disease.Inflammation in ulcerative colitis is generally limited to the colon and rectum. It rarely involves the small intestine, stomach, or esophagus.Ulcerative colitis is essentially a mucosal di

39、sease. Deeper layers are uncommonly involved, mainly in fulminant cases and usually in association with toxic megacolon.2022-3-26三大主要病變?nèi)笾饕∽僒hree major pathologic features characterize ulcerative colitis and help to differentiate it from other inflammatory conditions:Figure 13-26. Ulcerative coliti

40、s. Prominent erythema and ulceration of the colon begin in the ascending colon and are most severe in the rectosigmoid area.2022-3-26The following morphologic sequence may develop rapidly or over a course of years.EARLY COLITIS: Early in the evolution of the disease, the mucosal surface is raw, red,

41、 and granular. It is frequently covered with a yellowish exudate and bleeds easily. Later small, superficial erosions or ulcers may appear. These occasionally coalesce to form irregular, shallow, ulcerated areas that appear to surround islands of intact mucosa.The microscopic features of early ulcer

42、ative colitis include (1) mucosal congestion, edema, and microscopic hemorrhages; (2) a diffuse chronic inflammatory infiltrate in the lamina propria; and (3) damage and distortion of the colorectal crypts, which are often surrounded and infiltrated by neutrophils. Suppurative necrosis of the crypt

43、epithelium gives rise to the characteristic crypt abscess, which appears as a dilated crypt filled with neutrophils (Fig. 13-27).2022-3-26Figure 13-27. Ulcerative colitis. A. A full-thickness section of colon resected for ulcerative colitis shows inflammation affecting the mucosa with sparing of the

44、 submucosa and muscularis propria. B. Sections of a mucosal biopsy from a patient with active ulcerative colitis show expansion of the lamina propria and several crypt abscesses (arrows). C. Chronic ulcerative colitis shows significant crypt distortion and atrophy.2022-3-26 PROGRESSIVE COLITIS: As t

45、he disease continues, mucosal folds are lost. Lateral extension and coalescence of crypt abscesses can undermine the mucosa, leaving areas of ulceration adjacent to hanging fragments of mucosa. Such mucosal excrescences are termed inflammatory polyps. Granulation tissue develops in denuded areas. Im

46、portantly, the strictures characteristic of Crohn disease are absent. Microscopically, colorectal crypts may appear tortuous, branched, and shortened in the late stages, and the mucosa may be diffusely atrophic.2022-3-26 ADVANCED COLITIS: In long-standing cases, the large bowel is often shortened, e

47、specially in the left side. Mucosal folds are indistinct and are replaced by a granular or smooth mucosal pattern. Microscopically, advanced ulcerative colitis is characterized by mucosal atrophy and a chronic inflammatory infiltrate in the mucosa and superficial submucosa. Paneth metaplasia is comm

48、on.2022-3-26Clinical Features The clinical course and manifestations are very variable. Most patients (70%) have intermittent attacks, with partial or complete remission between attacks. A small number (10%) have a very long remission (several years) after their first attack. The remaining 20% have

49、continuous symptoms without remission.2022-3-26 MILD COLITIS: Half of patients with ulcerative colitis have mild disease. Their major symptom is rectal bleeding, sometimes accompanied by tenesmus (rectal pressure and discomfort). The disease in these patients is usually limited to the rectum but may

50、 extend to the distal sigmoid colon. Extraintestinal complications are uncommon, and in most patients in this category, disease remains mild throughout their lives.2022-3-26 MODERATE COLITIS: About 40% of patients have moderate ulcerative colitis. They usually have recurrent episodes of loose bloody

51、 stools, crampy abdominal pain, and frequently low-grade fever, lasting days or weeks. Moderate anemia is a common result of chronic fecal blood loss.2022-3-26 SEVERE COLITIS: About 10% of patients have severe or fulminant ulcerative colitis, often during a flare of activity. They may have more than

52、 6 and sometimes more than 20 bloody bowel movements daily, often with fever and other systemic manifestations. Blood and fluid loss rapidly leads to anemia, dehydration, and electrolyte depletion. Massive hemorrhage may be life-threatening. A particularly dangerous complication is toxic megacolon,

53、which is characterized by extreme dilation of the colon and an associated high risk for perforation. Fulminant ulcerative colitis is a medical emergency requiring immediate, intensive medical therapy, and, in some cases, prompt colectomy. About 15% of patients with fulminant ulcerative colitis die o

54、f the disease.2022-3-26The distinction between ulcerative colitis and Crohn colitis is based on different anatomical localization and histopathology (Table 13-1). The medical treatment of ulcerative colitis depends on the sites involved and the severity of the inflammation. The 5-aminosalicylate鈥揵as

55、ed compounds are the mainstays of treatment for patients with mild-to-moderate ulcerative colitis. Corticosteroids and immunosuppressive and immunoregulatory agents (azathioprine or mercaptopurine) are used in patients who have severe and refractory disease.2022-3-26Extraintestinal Manifestations Ar

56、thritis is seen in 25% of patients with ulcerative colitis. Eye inflammation (mostly uveitis) and skin lesions develop in about 10%. The most common cutaneous lesions are erythema nodosum and pyoderma gangrenosum; the latter is a serious, noninfective disorder characterized by deep, purulent, necrot

57、ic ulcers in the skin. Liver disease occurs in about 4% of patients, most commonly primary sclerosing cholangitis. Thromboembolic phenomena, usually deep vein thromboses of the lower extremities, occur in 6% of ulcerative colitis patients.2022-3-26Ulcerative Colitis and Colorectal Cancer People with

58、 long-standing ulcerative colitis have a higher risk of colorectal cancer than the general population. Colorectal epithelial dysplasia is a neoplastic epithelial proliferation and precursor to colorectal carcinoma in patients with long-term ulcerative colitis. High-grade epithelial dysplasia reflect

59、s a significant risk for the development of colorectal cancer, and when identified in a biopsy, it is a strong indication for colectomy.2022-3-26TABLE 13-1 Comparison of the Pathologic Features in the Colon of Crohn Disease and Ulcerative Colitis2022-3-26LesionCrohn DiseaseUlcerative ColitisMacrosco

60、pIcThickened bowel wallTypicalUncommonLuminal narrowingTypicalUncommon透壁性 lesionsCommonAbsentRight colon predominanceTypicalAbsentFissures and fistulasCommonAbsentCircumscribed ulcersCommonAbsentConfluent linear ulcersCommonAbsentPseudopolypsAbsentCommonMICROSCOPIcTransmural inflammationTypicalUncom