消化道病理(二).ppt

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1、炎症性肠病的临床病理炎症性肠病的临床病理 THE CLINICO-PATHOLOGY OF INFLAMMATORY BOWEL DISEASE(IBD)王军臣王军臣2015-11-24溃疡性结肠炎（溃疡性结肠炎（Ulcerative colitis）克罗思病（克罗思病（Crohns disease）未定型结肠炎（未定型结肠炎（Indeterminate colitis）IBM一词主要是指两种肠病：克罗思病和溃疡性结肠炎。两者临床病一词主要是指两种肠病：克罗思病和溃疡性结肠炎。两者临床病程与病史不同，病变有别，但某些特点相同，而治疗原则不同。程与病史不同，病变有别，但某些特点相同，而治疗原则不

2、同。Inflammatory 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.IBD的类型的类型无特异性实验室检测指标（无特异性实验室检测指标

3、（No specific laboratory tests）抗中性粒细胞胞质抗体抗中性粒细胞胞质抗体 pANCA(anti-neutrophil cytoplasmic antibody)60-75%的溃疡性结肠炎病例（的溃疡性结肠炎病例（Ulcerative colitis:60-75%）10-40%的克罗思病病例（的克罗思病病例（Crohns disease:10-40%）抗酿酒酵母菌抗体抗酿酒酵母菌抗体 ASCA(anti-Saccharomyces cerevisiae antibody)40-80%的溃疡性结肠炎病例（的溃疡性结肠炎病例（Crohns disease:40-80%）1

4、0%的克罗思病病例（的克罗思病病例（Ulcerative colitis:10%）基因检测：基因检测：NOD2 和其他的和其他的IBD 基因基因 （Genetic testing for NOD2 and other IBD genes）IBD的实验室的实验室检测检测克克罗恩病恩病（Crohn Disease）克克罗恩病（恩病（Crohn Disease）肠炎特点（炎特点（Features of Inflammation of the Intestine）慢性，慢性，节段性，透壁性段性，透壁性（Chronic,Segmental,Transmural）病病变以以小小肠远端端为主，右半主，右半结

5、肠可受累可受累，可有消化道甚至，可有消化道甚至肠外外组织受累受累 （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.）2022/12/1克克罗恩病的流行病学（恩病的流行病学（Epidemiology）全球全球发生克生克罗思病，每年思病，每年发病率病率

6、为0.5-5 人人/每每10万人群。万人群。过去去30年来，来自各国的年来，来自各国的报道表明，全球的克道表明，全球的克罗思思发病率病率急急剧增加。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 years.）欧洲的欧洲的该病病例最常病病例最常见于青少年或年于青少年或年轻成

7、人成人,犹太人群呈高犹太人群呈高发病率，女性病率，女性较男性稍微多男性稍微多见(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 predominance(1.6:1).2022/12/1发病机制（病机制（Pathogenesis）家族性家

8、族性遗传性体性体质 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 susceptibility locus for Crohn disease has been assigned to the c

9、entromeric 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.自身免疫机制自身免疫机制 The possibility that Crohn disease reflects immunologically mediated damage to the intestine is suggested by(

10、1)the chronic and recurrent nature（慢性反复发作）of the inflammation and(2)its association with systemic manifestations（全身损害）that are suggestive of autoimmune disease.Most recent immunologic studies focus on the possible role of cell-mediated cytotoxicity.2022/12/1肠道道粪便流的作用便流的作用 The fecal stream appears to

11、 be of prime importance in the pathogenesis of Crohn disease,as evidenced by：(1)the beneficial effects of surgical bypass（肠旁路吻合的好旁路吻合的好处）(2)the pattern of preanastomotic recurrence in patients with side-to-end anastomotic sites（侧-端吻合端吻合处前段复前段复发）,and(3)the frequency of early inflammatory lesions(apht

12、hoid erosions)in the epithelium in association with mucosal lymphoid tissue（淋巴（淋巴组织增生之上增生之上皮皮处早期炎症早期炎症-口口疮样糜糜烂）.2022/12/1病理病理变化（化（Pathology）克克罗思病有两大病思病有两大病变特征，以此与其他的炎症性特征，以此与其他的炎症性肠病相病相鉴别：Two major characteristics of Crohn disease differentiate it from other GI inflammatory diseases.第一，第一，严重通常累及重通常累

13、及肠壁全壁全层，故称之，故称之为透壁性炎症透壁性炎症。First,the inflammation usually involves all layers of the bowel wall and is,therefore,referred to as transmural inflammatory disease.第二，第二，肠壁病壁病变是是间断性的断性的，即，即节段性段性肠炎病炎病变，间有未受累有未受累及的正常及的正常肠组织 Second,the involvement of the intestine is discontinuous;that is,segments of infla

14、med tissue are separated by apparently normal intestine.2022/12/1克克罗恩病病恩病病变分布的四大部位特征分布的四大部位特征(1)回盲部回盲部病病变为主，占主，占50%(2)mainly the ileum and cecum in about 50%of cases(2)仅有有小小肠病病变，占，占15%(3)only the small intestine in 15%(3)仅有有大大肠病病变，占，占20%(4)only the colon in 20%(4)肛肛门直直肠区病区病变为主，占主，占15%(5)女性肛女性肛门直直肠区克

15、区克罗恩病可蔓延到外阴部恩病可蔓延到外阴部(6)mainly the anorectal region in 15%.In women with anorectal Crohn disease,the inflammation may spread to involve the external genitalia.2022/12/1大体大体观(Grossly)肠壁与壁与邻近近肠系膜增厚，水系膜增厚，水肿，肠系膜脂肪系膜脂肪环绕肠周（周（爬行脂肪爬行脂肪）The bowel and adjacent mesentery are thickened as well as edematous,an

16、d mesenteric fat often wraps around the bowel(Creeping fat).肠系膜淋巴系膜淋巴结常常常常肿大，大，变硬，相互融合硬，相互融合 Mesenteric lymph nodes are frequently enlarged,firm,and matted together.肠腔狭窄腔狭窄（水（水肿与与纤维化共同作用所致），可化共同作用所致），可见鹅卵石状外卵石状外观（因（因结节状状肿胀、肠壁壁纤维化和粘膜化和粘膜溃疡所致）所致）The intestinal lumen is narrowed by a combination of ede

17、ma and fibrosis.Nodular swelling,fibrosis,and mucosal ulceration lead to a cobblestone appearance.溃疡特点：特点：早期早期的的溃疡呈呈口口疮状状或葡行状；或葡行状；晚期晚期的的溃疡变深呈深呈线状裂状裂缝或裂或裂纹状状 In early cases,ulcers have either an aphthous or a serpiginous appearance;later,they become deeper and appear as linear clefts or fissures(see

18、 Fig.13-23B).2022/12/1图片片A.A.末端回末端回肠远端端肠壁明壁明显增厚，增厚，伴有回盲瓣伴有回盲瓣变形。可形。可见一一纵向向溃疡 (箭箭头所示所示)图片片B.B.该回回肠节段另一段另一纵向向溃疡。受受损粘膜水粘膜水肿，形成，形成圆形形/卵卵圆形形结节状隆起，使病状隆起，使病变肠段粘膜呈段粘膜呈鹅卵卵石石样外外观。右下。右下侧局部粘膜部分未局部粘膜部分未受累受累2022/12/1 克罗恩病肠切除标本大体观克罗恩病肠切除标本大体观大体切面大体切面观The cut surface of the bowel wall shows the transmural（透壁性）natur

19、e of the disease,with thickening（增厚）,edema（水肿）,and fibrosis（纤维化）of all layers.Involved loops of bowel are often adherent（粘连）,and fistulas（瘘管瘘管）between such segments are frequent.These fistulas may also penetrate from the bowel into other organs（肠壁瘘管穿入其它器官）,including the bladder,uterus,vagina,and ski

20、n.Lesions in the distal rectum and anus may create perianal fistulas（肛旁瘘）,a well-known presenting feature.2022/12/1Microscopically,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,superfi

21、cial mucosal ulcerations(aphthous ulcers口疮样溃疡)are seen.Later,long,deep,fissure-like（裂隙状）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（非干酪样）granulomas（肉芽

22、肿）,mostly in the submucosa,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 13-25.2022/12/1正常的结肠粘膜组织结构正常的结肠粘膜组织结构Figure 13-24.克克罗恩病恩病.图片片A显示

23、示溃疡至粘膜下至粘膜下层；淋巴；淋巴组织聚集在粘膜下、聚集在粘膜下、邻近肌近肌层和和浆膜下。膜下。图片片B显示粘膜活示粘膜活检，可，可见小灶上皮小灶上皮样肉芽肉芽肿位于两个位于两个无无损的腺的腺隐窝之之间。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 immediately adj

24、acent to the muscularis externa.B.This mucosal biopsy in Crohn disease shows a small epithelioid granuloma(arrows)between two intact crypts.2022/12/1克罗恩病的肉芽肿病变克罗恩病的肉芽肿病变克罗恩病肉芽肿的高倍镜下观克罗恩病肉芽肿的高倍镜下观大肠腺上皮隐窝结构变形大肠腺上皮隐窝结构变形克罗恩病回肠炎克罗恩病回肠炎下图见裂缝状溃疡下图见裂缝状溃疡逆流性回肠炎逆流性回肠炎克罗恩病肠道活检克罗恩病肠道活检H-E染色切片组织学观察染色切片组织学观察箭头所示

25、克罗恩病的透壁性炎症箭头所示克罗恩病的透壁性炎症临床特点床特点(Clinical Features)克克罗恩病的恩病的临床表床表现与病史各自不同，与与病史各自不同，与发病部位相关病部位相关 The clinical manifestations and natural history of Crohn disease are highly variable and relate to the anatomical sites involved by the disease.最常最常见症状：症状：75%病人腹痛腹泻；病人腹痛腹泻；50%病人回病人回归热The most frequent symp

26、toms are abdominal pain and diarrhea,which are seen in more than 75%of patients,and recurrent fever,evident in 50%.吸收不良和吸收不良和营养不良；腹泻和养不良；腹泻和肠出血；以直出血；以直肠肛肛门病病变为主的可反复主的可反复发生肛瘘生肛瘘 When the small intestine is diffusely involved,malabsorption and malnutrition may be major features.Crohn disease of the co

27、lon 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.2022/12/1克克罗恩病的恩病的继发病病变肠道阻塞、瘘管和道阻塞、瘘管和肠穿孔穿孔Intestinal obstruction and fistulas are the most common intestinal compl

28、ications of Crohn disease.Occasionally,free perforation of the bowel occurs.发生生肠癌癌 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 is available.Several medications suppress the inflamm

29、atory 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 by fistulas are often required.2022/12/1克克罗恩病小恩病小肠节段性病段性病变特

30、征模式特征模式图2022/12/1溃疡性性结肠炎炎（Ulcerative Colitis）溃疡性性结肠炎（炎（Ulcerative Colitis）是是结直直肠发生的慢性浅表性炎症生的慢性浅表性炎症 Ulcerative Colitis is a Chronic Superficial Inflammation of the Colon and Rectum临床表床表现慢性腹泻，直慢性腹泻，直肠出血。是有加重和出血。是有加重和缓解，可伴有解，可伴有局部和全身并局部和全身并发症症 Ulcerative colitis is characterized by chronic diarrhea an

31、d rectal bleeding,with a pattern of exacerbations and remissions and with the possibility of serious local and systemic complications.2022/12/1流行病学（流行病学（Epidemiology）In Europe and North America,the incidence of ulcerative colitis is 4 to 7 per 100,000 population,and its prevalence is 40 to 80 per 10

32、0,000.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.2022/12/1发病机制（病机制（Pathogenesis）原因不清，可能与原因不清，可能与遗传相关相关 The cause of ulcerative colitis is unknown.In

33、 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 of genetic transmission.自身免疫病机制自身免疫病机制 The possibility that an abnormal immune response may be involve

34、d 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 vasculitis.Increased circulating antibodies against antigens in colonic epithelial cells and against cross-react

35、ing antigens in enterobacteria may occur.Antineutrophil cytoplasmic antibodies are found in 80%of patients with ulcerative colitis.However,these abnormalities are neither unique for ulcerative colitis,nor are they a prerequisite for the development of the disease.2022/12/1病理变化（Pathology）Ulcerative c

36、olitis is a diffuse disease.It usually extends from the most distal part of the rectum（远端直肠）for a variable distance proximally(Fig.13-26).Sparing of the rectum or involvement of the right side of the colon alone is rare and suggests the possibility of another disorder,such as Crohn disease.Inflammat

37、ion 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 disease.Deeper layers are uncommonly involved,mainly in fulminant cases and usually in association with toxic megacolon.2022/

38、12/1三大主要病变三大主要病变Three major pathologic features characterize ulcerative colitis and help to differentiate it from other inflammatory conditions:Figure 13-26.Ulcerative colitis.Prominent erythema and ulceration of the colon begin in the ascending colon and are most severe in the rectosigmoid area.202

39、2/12/1The 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,and granular.It is frequently covered with a yellowish exudate and bleeds easily.Later small,superficial erosions or ulcers may ap

40、pear.These occasionally coalesce to form irregular,shallow,ulcerated areas that appear to surround islands of intact mucosa.The microscopic features of early ulcerative colitis include(1)mucosal congestion,edema,and microscopic hemorrhages;(2)a diffuse chronic inflammatory infiltrate in the lamina p

41、ropria;and(3)damage and distortion of the colorectal crypts,which are often surrounded and infiltrated by neutrophils.Suppurative necrosis of the crypt epithelium gives rise to the characteristic crypt abscess,which appears as a dilated crypt filled with neutrophils(Fig.13-27).2022/12/1Figure 13-27.

42、Ulcerative colitis.A.A full-thickness section of colon resected for ulcerative colitis shows inflammation affecting the mucosa with sparing of the submucosa and muscularis propria.B.Sections of a mucosal biopsy from a patient with active ulcerative colitis show expansion of the lamina propria and se

43、veral crypt abscesses(arrows).C.Chronic ulcerative colitis shows significant crypt distortion and atrophy.2022/12/1PROGRESSIVE COLITIS:As the disease continues,mucosal folds are lost.Lateral extension and coalescence of crypt abscesses can undermine the mucosa,leaving areas of ulceration adjacent to

44、 hanging fragments of mucosa.Such mucosal excrescences are termed inflammatory polyps.Granulation tissue develops in denuded areas.Importantly,the strictures characteristic of Crohn disease are absent.Microscopically,colorectal crypts may appear tortuous,branched,and shortened in the late stages,and

45、 the mucosa may be diffusely atrophic.2022/12/1ADVANCED COLITIS:In long-standing cases,the large bowel is often shortened,especially 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

46、mucosal atrophy and a chronic inflammatory infiltrate in the mucosa and superficial submucosa.Paneth metaplasia is common.2022/12/1Clinical FeaturesThe clinical course and manifestations are very variable.Most patients(70%)have intermittent attacks,with partial or complete remission between attacks.

47、A small number(10%)have a very long remission(several years)after their first attack.The remaining 20%have continuous symptoms without remission.2022/12/1MILD COLITIS:Half of patients with ulcerative colitis have mild disease.Their major symptom is rectal bleeding,sometimes accompanied by tenesmus(r

48、ectal pressure and discomfort).The disease in these patients is usually limited to the rectum but may extend to the distal sigmoid colon.Extraintestinal complications are uncommon,and in most patients in this category,disease remains mild throughout their lives.2022/12/1MODERATE COLITIS:About 40%of

49、patients have moderate ulcerative colitis.They usually have recurrent episodes of loose bloody stools,crampy abdominal pain,and frequently low-grade fever,lasting days or weeks.Moderate anemia is a common result of chronic fecal blood loss.2022/12/1SEVERE COLITIS:About 10%of patients have severe or

50、fulminant ulcerative colitis,often during a flare of activity.They may have more than 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