1、Inflammatory Bowel DiseaseZHOU QiDepartment of Gastroenterology and HepatologyInflammatory bowel disease refers to two chronic diseases that cause inflammation of the intestines: ulcerative colitis and Crohns disease. Although the diseases have some features in common, there are some important diffe
2、rences.Inflammatory bowel disease Medical research hasnt determined yet what causes inflammatory bowel disease. But researchers believe that a number of factors may be involved, such as environment diet possibly geneticsInflammatory bowel disease Current evidence suggests that theres likely a geneti
3、c defect that affects how our immune system works and how the inflammation is turned on and off in those people with inflammatory bowel disease, in response to an offending agent, like: bacteria a virus or a protein in foodEpidemiology of IBDUlcerative colitisCrohns diseaseIncidence (US)11/100 0007/
4、100 000Age of onset15-30 & 60-8015-30 & 60-80Male:female ratio 1:1 1,1-1,8:1SmokingMay prevent diseaseMay cause diseaseOral contraceptiveNo increased riskRelative risk 1,9AppendectomyNot protectiveProtectiveMonozygotic twins8% concordance67% concordanceUlcerative colitis microscopic features Process
5、 is limited to the mucosa and submucosa with deeper layer unaffected Two major histologic features: - the crypt architecture of the colon is distorted - some patients have basal plasma cells and multiple basal lymphoid aggregatesUlcerative colitis is an inflammatory disease of the large intestine, a
6、lso called the colon. In ulcerative colitis, the inner lining - or mucosa - of the intestine becomes inflamed and develops ulcers is often the most severe in the rectal area, which can cause frequent diarrhea. Ulcerative colitis macroscopic features 40-50% of patients have disease limited to the rec
7、tum and rectosigmoid 30-40% of patients have disease extending beyond the sigmoid 20% of patients have a total colitis Proximal spread occurs in continuity without areas of uninvolved mucosaUlcerative colitis macroscopic features Mucosa is : - erythematous, has a granular surface that looks like a s
8、and paper In more severe diseases: - hemorrhagic, edematous and ulcerated In fulminant disease a toxic colitis or a toxic megacolon may develop ( wall become very thin and mucosa is severly ulcerated) Diarrhea: number of stools may vary from only a few episodes (1 or 2) to very frequently (20 or 30)
9、 per day, blood and mucus may be present; Abdominal pain: in the left iliac fossa and cramping that usually subsides after a bowel movement; Abdominal sounds: borborygmus, a gurgling or splashing sound heard over the intestine Tenesmus (里急后重里急后重) Nausea and vomiting Ulcerative colitis clinical prese
10、ntationSymptoms- extraintestinal Fever Anemia Weight loss Loss of appetite Fatigue Arthralgia or arthritis Eye involvement: uveitis(葡萄膜炎葡萄膜炎) Erythema nodosum In fulminating disease the presentation may be of abdominal distension, catastrophic diarrhoea, fever and collapse (虚脱虚脱)Signs pallor, dehydr
11、ation, mouth ulcers, abdominal tenderness Signs of toxic dilatation or perforation Classification of Severity of UCmildmoderate severeStool frequencyBleeding FeverTachycardiaweight losshemoglobinESRAlbumin 100g/Lnormalnormal4-6Profuse37.5ModerateSlight 100-76g/L6Continuous=37.5Severe10%=30mm/h30g/LR
12、adiologic change of UC Fine mucosal granularity Mucosa become thickenned and superficial ulcers are seen (collar-button ulcers) Loss of haustrationInvestigations FBC - anaemia; leukocytosis ESR - increased; correlates with active disease CRP - raised; but less so than in CD Biochemistry - in active
13、disease, biochemical abnormalities may include hypokalaemia, hyponatraemia, hypomagnesaemia, hypocalcaemia, and hyoalbuminaemia. Abnormal LFTs due to associated chronic active hepatitis - increased ALT - or sclerosing cholangitis - increased AKP ANCA - found in HLA-DR2 associated form of UCUlcerativ
14、e colitis - complication Hemorrhage Perforation Stricture Toxic megacolon (transverse colon with a diameter of more than 5,0 cm to 6,0 cm with loss of haustration)UC disease presentationMILDMODERATESEVEREBOWEL MOVEMENTS6 per dayBLOOD IN STOOLsmallmoderateSevereFEVERnone 37,5C TACHYCARDIAnone90 mean
15、pulseColonic pseudopolyps Normal colonGrade 1Grade 2Grade 3Remission stages of UC: the eliminated contours of the vessels and the fragmented light reflections are characteristicAdditionally shows loss of haustration in an illness of longer durationScar stages of UC with formation of pseudopolyps Hem
16、orrhagic colitis with moderate musal bleedingHemorrhagic colitis with heavier musal bleeding (=small pseudopolyp)Acute UC with spontaneous bleeding and ulcerationsComplications Massive colonic haemorrhage: 3% Toxic megacolon: 5% Colon stricture formation - rare Fistula formation - rare Perforation o
17、f the colon Increased risk of malignancy - lymphoma, carcinomaDiagnosisl Careful history and examination is very important for the diagnosis of UC. The hallmark is bloody diarrhoea with mucus, usually of gradual onset, but it can be abrupt.l The diagnosis of UC is based on: Exclusion of other causes
18、 of diarrhoea like bacillary or amoebic dysentery (痢疾痢疾) Colonoscopy and biopsy - histological characteristics, and endoscopic features Differentiation from CD诊断标准诊断标准 1. 1. 临床表现临床表现有持续或反复发作的腹泻、黏液脓血便伴腹痛、里急后重和有持续或反复发作的腹泻、黏液脓血便伴腹痛、里急后重和不同程度的全身症状。病程多在不同程度的全身症状。病程多在4 46 6周以上。可有关节、皮周以上。可有关节、皮肤、眼、口及肝、胆等肠外
19、表现。肤、眼、口及肝、胆等肠外表现。 2. 2. 结肠镜检查结肠镜检查病变多从直肠开始病变多从直肠开始, , 呈连续性、弥漫性分布呈连续性、弥漫性分布, , 表现为表现为: :. .黏黏膜血管纹理模糊、紊乱、充血、水肿、易脆、出血及脓性分膜血管纹理模糊、紊乱、充血、水肿、易脆、出血及脓性分泌物附着。亦常见黏膜粗糙泌物附着。亦常见黏膜粗糙, , 呈细颗粒状；病变明显处可呈细颗粒状；病变明显处可见弥漫性多发糜烂或溃疡；慢性病变者可见结肠袋囊变浅、见弥漫性多发糜烂或溃疡；慢性病变者可见结肠袋囊变浅、变钝或消失变钝或消失, , 假息肉及桥形黏膜等。假息肉及桥形黏膜等。 3. 3. 钡剂灌肠检查钡剂灌肠
20、检查 主要改变主要改变: :黏膜粗乱及黏膜粗乱及( (或或) )颗粒样改变颗粒样改变; ;肠管边缘呈锯齿肠管边缘呈锯齿状或毛刺样状或毛刺样, , 肠壁有多发性小充盈缺损肠壁有多发性小充盈缺损; ; 肠管短缩肠管短缩, ,袋囊袋囊消失呈铅管样。消失呈铅管样。 诊断标准诊断标准 4. 4. 黏膜病理学检查黏膜病理学检查 活动期活动期固有膜内弥漫性、慢性炎细胞及中性粒细胞、嗜酸性粒细固有膜内弥漫性、慢性炎细胞及中性粒细胞、嗜酸性粒细胞浸润胞浸润; ; 隐窝急性炎细胞浸润隐窝急性炎细胞浸润, ,尤其上皮细胞间中性粒细尤其上皮细胞间中性粒细胞浸润、隐窝炎胞浸润、隐窝炎, , 甚至形成隐窝脓肿甚至形成隐窝
21、脓肿, ,可有脓肿溃入固有膜可有脓肿溃入固有膜; ; 隐窝上皮增生隐窝上皮增生, , 杯状细胞减少杯状细胞减少; (4); (4)可见黏膜表层糜烂可见黏膜表层糜烂, , 溃疡形成溃疡形成, , 肉芽组织增生。肉芽组织增生。 缓解期缓解期中性粒细胞消失中性粒细胞消失, ,慢性炎性细胞减少慢性炎性细胞减少; ; 隐窝大小形态不隐窝大小形态不规则规则, , 排列紊乱。腺上皮与黏膜肌层间隙增大排列紊乱。腺上皮与黏膜肌层间隙增大; ; 潘氏细潘氏细胞化生。胞化生。 诊断标准诊断标准 5. 5. 手术切除标本见手术切除标本见UCUC的肉眼和组织学特征。的肉眼和组织学特征。 强调在排除细菌性痢疾、阿米巴痢疾
22、、慢性血吸虫病、肠结强调在排除细菌性痢疾、阿米巴痢疾、慢性血吸虫病、肠结核等感染性结肠炎及结肠克罗恩病、缺血性结肠炎、放射性核等感染性结肠炎及结肠克罗恩病、缺血性结肠炎、放射性结肠炎等的基础上结肠炎等的基础上, ,可按下列诊断标准诊断可按下列诊断标准诊断: :根据临床表现和结肠镜检查根据临床表现和结肠镜检查3 3项中之项中之1 1 项及黏膜活检可肯项及黏膜活检可肯定诊断定诊断; ; 根据临床表现和钡灌肠检查根据临床表现和钡灌肠检查3 3项中之项中之1 1项可诊断本项可诊断本病病; ; 临床表现不典型而有典型的结肠镜或钡灌肠改变者可临床表现不典型而有典型的结肠镜或钡灌肠改变者可以拟诊为本病以拟诊
23、为本病; ; 临床表现典型而结肠镜和钡灌肠检查并无临床表现典型而结肠镜和钡灌肠检查并无典型改变典型改变, ,应列为疑诊随访应列为疑诊随访; ; 初发病例、临床表现与结肠初发病例、临床表现与结肠镜改变均不典型者镜改变均不典型者, ,暂不诊断暂不诊断UC,UC,可随访可随访3 36 6个月。个月。诊断内容诊断内容 完整的诊断应包括临床类型、严重程度、病变范完整的诊断应包括临床类型、严重程度、病变范围、病情分期、肠外表现及并发症。围、病情分期、肠外表现及并发症。 临床类型临床类型: 可分为初发型、暴发型、慢性复发型、可分为初发型、暴发型、慢性复发型、慢性持续型。慢性持续型。初发型指无既往史而首次发作
24、初发型指无既往史而首次发作; 暴发型指症状严重，血便每天暴发型指症状严重，血便每天10次以上，伴全身次以上，伴全身中毒性症状中毒性症状, 可伴中毒性巨结肠、肠穿孔、脓毒可伴中毒性巨结肠、肠穿孔、脓毒血症等并发症。血症等并发症。除暴发型外除暴发型外, 各型可相互转化。各型可相互转化。 临床严重程度临床严重程度: 分为轻度、中度和重度分为轻度、中度和重度诊断内容诊断内容 病变范围病变范围: 可为直肠、直乙结肠、左半结肠可为直肠、直乙结肠、左半结肠(脾曲脾曲以远以远)、广泛结肠（脾曲以近）、全结肠、广泛结肠（脾曲以近）、全结肠 肠外表现肠外表现: 可有关节、皮肤、眼部、肝、胆等系可有关节、皮肤、眼部
25、、肝、胆等系统受累统受累; 并发症：可有大出血、穿孔、中毒性巨结肠、癌并发症：可有大出血、穿孔、中毒性巨结肠、癌变等。变等。诊断步骤诊断步骤 1大便常规与大便培养不少于大便常规与大便培养不少于3次次, 根据流行病学特点，为根据流行病学特点，为除外阿米巴痢疾、血吸虫病等疾病应做相关的检查；除外阿米巴痢疾、血吸虫病等疾病应做相关的检查； 2结肠镜检查结肠镜检查, 兼做活检。重症患者或暴发型患者可暂缓检兼做活检。重症患者或暴发型患者可暂缓检查或者仅做直、乙状结肠检查，以策安全；查或者仅做直、乙状结肠检查，以策安全； 3钡剂灌肠检查可酌情使用；重度患者不推荐。钡剂灌肠检查可酌情使用；重度患者不推荐。
26、4常规的实验室检查常规的实验室检查, 血常规、血浆蛋白、血沉、血常规、血浆蛋白、血沉、C-反应蛋反应蛋白、腹部平片、超声检查有助于确定疾病严重程度和活动度。白、腹部平片、超声检查有助于确定疾病严重程度和活动度。 诊断举例诊断举例 溃疡性结肠炎初发型、中度、直乙结肠受溃疡性结肠炎初发型、中度、直乙结肠受累、活动期累、活动期 。Histology Mucosal inflammationProportionedCrypt abscessesContinuous lesionsContinuous polymorphonuclear infiltration, limited to the muco
27、sa, crypt abscesses, goblet cell mass reducedLocalization of UC 50% of cases presented UC extending up to the left flexure of the colonContrast radiograph in advanced ulcerative colitisUlcerative Colitis Differential diagnosis infective colitis is often a cause of one episode of colitis which is mis
28、labelled as ulcerative colitis e.g. salmonellosis, shigellosis (志贺氏细菌性痢疾志贺氏细菌性痢疾), campylobacter, amoebiasis (阿米巴肠炎阿米巴肠炎), schistosomiasis (血吸虫病血吸虫病). In the immunosuppressed patient then one must consider opportunistic infections e.g. cytomegalovirus, herpes virus, Cryptosporidium, Mycobacterium av
29、ium intracellulare. colonic carcinoma, adenoma - diagnosed on endoscopy, particularly important in the elderly. diverticulitis - not in childhood irritable bowel disease (肠易激综合征肠易激综合征), which would tend to occur in the young, and has early morning explosiveness, not tending to be bothered at night.
30、ischaemic colitis - these patients may have a history of vascular disease with sudden onset of pain, and thumb printing on plain abdominal radiography or barium enema. It does not occur in childhood. post-radiation colitis, the diagnosis of which is based on the history Crohns disease Coeliac diseas
31、e: is an autoimmune disorder of the small bowel that occurs in genetically predisposed people of all ages from middle infancy. Symptoms include chronic diarrhoea, failure to thrive (in children) and fatigue, but these may be absent and symptoms in all other organ systems have been described. Coeliac
32、 disease is caused by a reaction to gliadin(麸朊), a gluten protein found in wheat. Diverticulitis with mottled redness in the vicinity of the viverticulumMelanosis coli following laxative abusePseudomembranous colitis after administration of antibiotics. The membrane-like deposits are characteristic.
33、 Diffuse hemorrhagic colitis in Salmonella infection (S. enteridis)Chronic schistosomiasisManagement There have been massive improvements in the management of UC in the past 40 or 50 years, as evidenced by the death rates in severe attacks:before 1952, 45% now, 1 to 2 % The management has been impro
34、ved by:corticosteroids better understanding of fluid balance and electrolytes in severely ill patients better understanding of indicators of severity of the disease The goals of treatment are to control the acute attacks, prevent recurrent attacks, promote healing of the colon, and decrease the comp
35、lications. Medications that may be used to decrease the frequency of attacks include 5-aminosalicylates such as mesalamine and immunomodulators such as azathioprine (硫唑硫唑嘌呤嘌呤) and 6-mercaptopurine (6-巯基嘌呤巯基嘌呤). Surgery to remove the colon will cure UC and removes the threat of colon cancer. Patients
36、 may need an ostomy (造瘘术造瘘术) or an ileal pouch-anal anastomosisMedical management of UC Medical management of UC varies with respect to disease severity: Considered in terms of:acute attacksmaintenance of remission of UC疗效标准疗效标准 1. 完全缓解完全缓解: 临床症状消失临床症状消失, 结肠镜检查黏膜大致结肠镜检查黏膜大致正常正常; 2. 有效有效: 临床症状基本消失临床症
37、状基本消失, 结肠镜复查黏膜轻度结肠镜复查黏膜轻度炎症或假息肉形成炎症或假息肉形成; 3. 无效无效: 经治疗后临床症状、内镜及病理检查无经治疗后临床症状、内镜及病理检查无改善。改善。Therapy conceptsCrohns disease Crohns disease differs from ulcerative colitis in the areas of the bowel it involves - it most commonly affects the last part of the small intestine and parts of the large intes
38、tine. Crohns disease isnt limited to these areas and can attack any part of the digestive tract Crohns disease generally tends to involve the entire bowel wall Crohns disease macroscopic features Can affect any part of GI tract from the mouth to the anus 30-40% of patients have small bowel disease a
39、lone 40-55% of patients have both small and large intestines disease 15-25% of patients have colitis alone In 75% of patients with small intestinal disease the terminal ileum in involved in 90%Crohns disease macroscopic features CD is a transmural process CD is segmental with skip areas in the midst
40、 of diseased intestine In one third of patients with CD perirectal fistulas, fissures, abscesses, anal stenosis are presentPathological featuresMacroscopically in CD there may be a swollen, reddened and rubbery bowel with: Skip lesions - discontinuous sites of pathology along the GI Cobblestone ulce
41、ration; a result of apthous ulceration progressing to oedema and nodular thickening Lead pipe thickening - thickened, stiff bowel Narrowed lumen Strictures Rose-thorn narrow-mouthed ulcers which lead to fistulae Fistulae, often between adherent bowel and/or bladder, vagina, other abdominal organs or
42、 the abdominal wall Enlarged mesenteric nodesMicroscopically, there is: Non-caseating granulomas - not always present Transmural inflammation and lymphocyte infiltrationHistology Transmural inflammation Asymmetric, discontinuous, granulomasLymphocyte infiltration, tramsmural, distrinution pattern di
43、scontinuous; focal lymphoid hyperplasia; fibrosing of all layers of the wall; fissures; epitheloid cell granulomas in the submucosa; seldom crypt abscesses, goblet cells preserved.CD may involve any part of the bowel from the mouth to the anus: the terminal ileum is involved in nearly 50% of cases j
44、ejunoileitis is also seen, but most ileal inflammation usually ends abruptly at the ileocaecal junction caecal and right colonic involvement is more common than lesions in the stomach and duodenumLocalizition of CDClinical features This is a chronic, relapsing and remitting disease that has symptoma
45、tology dependent on the site of involvement of the GI tract. The commonest site at presentation is the terminal ileum and proximal colon. Various symptoms occur in most patients:abdominal pain weight loss diarrhoeaintestinal Abdominal pain Diarrhea Loss of appetite Bleeding Abdominal mass Anal fistu
46、lae Foul-smelling stools Tenesmus里急后重里急后重 Constipation Abdominal fullness and gas Anal Incontinence Weight loss Fever Fatigue Anemia Malnutrition Arthralgia Eye involvement Erythema nodosumextraintestinal In addition to the bowel abnormalities, CD can also affect other organs in the body, causing: S
47、kin rash Fistulas (abnormal connections between bowel and adjacent organs or skin) Liver inflammation Joint disease (arthritis) Eye inflammation Kidney stones Clotting problems (deep vein thrombosis)Extraintestinal manifestationsSpecial note must be taken that: CD may present with an acute onset of
48、abdominal pain that may mimic acute appendicitis or yersinia耶尔森菌耶尔森菌属属 ileitis. Common features in active disease are lassitude疲乏疲乏 , anorexia, malaise, and fever. In adolescents, a presentation with weight loss alone (without abdominal pain or diarrhoea) may be misdiagnosed as anorexia nervosa.n A
49、physical examination may reveal an abdominal mass or tenderness, skin rash, swollen joints or mouth ulcers.Complications intestinal obstruction haemorrhage perforation with abscess stricture formation; common perianal abscess fistula fistulae to the bowel, bladder, vagina toxic megacolon-rare increa
50、sed risk of malignancy but less than that of UC.Crohns disease sign and symptoms Ileocolitis - right lower quadrant pain and diarhhea - palpable mass, fever and leucocytosis - pain is colickly and relieved by defecation Jejunoileitis - inflammatory disease is associated with loss of digestive and ab
