肝臟病理_ppt精編版課件

1、Welcome肝臟疾病病理學(xué)診斷Outline of GuidelinesClassification of liver diseases LIVERLiver BiopsyLiver Biopsy Confirm the diagnosis Serological blood tests Establish degree of fibrosis Serology Biopsy not representative Identify cirrhosis Determine optimum therapyLiver biopsy adequacy“Most hepatopathologists

2、are satisfied with a biopsy specimen containing at least six to eight portal tracts”.Bravo AA et al NEJM 344, 495; 2001.We should not be primarily concerned with the size of biopsy that “satisfies” the pathologist.The correct question is:What size of biopsy will provide a reliable assessment for the

3、 patients management?Liver biopsy adequacyGuido M and Rugge M. Semin Liv Dis 24, 89; 2004.In most diffuse liver diseases examination of 12-15 complete portal tracts is necessary.20mm of a 1.4mm diameter (17 gauge) needle biopsy.Progressively longer samples of thinner biopsies are needed.36-1 肝臟活檢標(biāo)本的

4、評(píng)價(jià)整體情況 -低倍鏡匯管區(qū) 中、高倍鏡肝小葉 中、高倍鏡中央靜脈 中、高倍鏡LOBULE VS ACINUS肝小葉肝板、肝竇肝臟,EM肝臟,EM (cont.)匯管區(qū)和中央靜脈36-2 常用診斷名詞的定義 嗜酸性小體氣球樣變性Ductule葉間膽管碎宵狀壞死灶狀壞死帶狀壞死融合性壞死大片壞死橋接壞死 Acidophil bodyBallooning DegenerationFatty Degeneration Alcoholic liver diseaseDuctuleInterlobular bile ductNecrosis, piecemealNecrosis, focalNecros

5、is, ZonalNecrosis, ConfluentNecrosis, MassiveNecrosis, BridgingDrug and Toxin- Induced Liver Disease36-3 肝小葉淋巴細(xì)胞浸潤(rùn)伴有或不伴有肝細(xì)胞變性或壞死急性醫(yī)源性急性病毒性 (HAV, HBVB,HCV, CMV, EBV etc)自身免疫性癌髓外造血白血病/淋巴瘤原發(fā)性膽管性肝硬化36-4 肝小葉多形核細(xì)胞浸潤(rùn)伴有或不伴有肝細(xì)胞變性或壞死酒精性肝炎細(xì)菌/真菌感染醫(yī)源性反應(yīng)敗血癥“手術(shù)性”肝炎病毒感染（CMV)Autoimmune Hepatitis 36-5 肝細(xì)胞壞死伴輕微炎癥反應(yīng)急性病

6、毒感染纖維化性膽汁淤積性肝炎肝靜脈血液外溢缺血嗜肝病毒引起的大片壞死醫(yī)源或毒素反應(yīng)創(chuàng)傷腫瘤36-6 匯管區(qū)淋巴細(xì)胞或和漿細(xì)胞浸潤(rùn)急性病毒性肝炎自身免疫性肝炎膽管阻塞移植物抗宿主反應(yīng)淋巴瘤/白血病肝小葉炎癥或變性或壞死輕微肉芽腫或腫瘤原發(fā)性膽汁性肝硬化原發(fā)性硬化性膽管炎排斥反應(yīng)病毒性肝炎Wilson病Primary biliary cirrhosis Antimitochondrial antibody36-7 匯管區(qū)多形核細(xì)胞浸潤(rùn) -肝小葉炎癥或變性或壞死輕微順行性膽管炎膽道阻塞高營(yíng)養(yǎng)醫(yī)源性病毒性肝炎,“膽管溶解性”36-8 匯管區(qū)嗜酸性粒細(xì)胞浸潤(rùn)自身免疫性肝炎髓外造血醫(yī)源反應(yīng)寄生蟲(chóng)感染原發(fā)性

7、膽汁性肝硬化原發(fā)性硬化性膽管炎排斥反應(yīng)Liver biopsy from a 25 y-o Laotian showing a granulomatous reaction against the ovum (HE).36-9 肉芽腫性炎癥兒童慢性肉芽腫病克隆氏病異物反應(yīng)原發(fā)性肝臟肉芽腫病免疫性膽管炎細(xì)菌、真菌、立克次氏體、病毒感染脂肪性肉芽腫惡性腫瘤醫(yī)源性反應(yīng)原發(fā)性膽汁性肝硬化肉瘤樣病36-10 肝纖維化淀粉樣橋接性纖維化中央透明變性纖維化先天性肝纖維化先天性梅毒囊性纖維化灶性結(jié)節(jié)狀增生肝臟門(mén)脈區(qū)纖維化肝臟靜脈性血液外溢，慢性阻塞性代謝性疾病中央靜脈周?chē)w維化腫瘤肝纖維化肝硬化 = 肝細(xì)胞再

8、生 + 纖維化36-11 膽汁淤積良性家族性膽汁淤積妊娠性膽汁淤積醫(yī)源性手術(shù)后性膽汁淤積敗血癥細(xì)胞內(nèi)淤膽Intrahepaptic CholestasisExtrahepaptic Cholestasis36-12 淤血或出血伴有肝竇擴(kuò)張肝靜脈血外溢靜脈阻塞性疾病心力衰竭醫(yī)源反應(yīng)腫瘤壓迫結(jié)節(jié)性再生性增生和回管區(qū)硬化門(mén)脈阻塞肝淤血肝出血36-13 色素沉積膽色素鐵脂褐素其它外源性色素福爾馬林色素膽色素 bile pigmentHemochromatosisPrussian blue iron stain Lipofuscin36-14 細(xì)胞內(nèi)包含體腺病毒抗胰靡蛋白酶缺乏支鏈淀粉血癥大泡脂肪變微泡

9、脂肪變“糖原性”胞核巨線粒體“毛玻璃”細(xì)胞HSVMallory hyalineALPHA-1-ANTITRYPSIN STORAGE MEGAMITOCHONDRIA GROUND GLASS CELLS Alpha-1-antitrypsin deficiencyCMV hepatitis Glycogen NucleiA 30-year-old woman in the 30th week of pregnancy with Fulminant hepatic failure herpes simplex virusMallory hyaline36-15 脂肪變顯著不伴有或輕微壞死酒精性

10、脂肪性肝炎妊娠脂肪肝灶性脂肪變肝細(xì)胞腺瘤、癌醫(yī)源、毒素反應(yīng)代謝性疾病非酒精性脂肪性肝炎非特異性脂肪變Wilson病36-16 組織中出現(xiàn)不常見(jiàn)細(xì)胞髓外造血巨核細(xì)胞轉(zhuǎn)移瘤儲(chǔ)備細(xì)胞（肝、Kupffer或Ito)髓外造血36-17 “幾乎正?！钡母位顧z肝匯管區(qū)纖維化醫(yī)源性反應(yīng)Missed lesion結(jié)節(jié)狀再生或增生蓄積或代謝性疾病36-18 缺少(觀察不到)正常結(jié)構(gòu)膽管中央靜脈肝細(xì)胞匯管區(qū)匯管靜脈肝竇36-19 肝臟代謝性疾病的光鏡診斷類(lèi)型診斷性LM診斷性EMa-抗胰糜蛋白酶缺乏匯管區(qū)周肝細(xì)胞內(nèi)PAS陽(yáng)性球滴擴(kuò)張內(nèi)質(zhì)網(wǎng)內(nèi)出現(xiàn)顆粒狀物囊性纖維化灶性膽管性纖維化膽管纖維狀物Gaucher病Kupffe

11、r增大，匯管區(qū)巨噬細(xì)胞， “Crinkled paper”胞漿溶酶體內(nèi)管狀包含體糖原沉積癥 IV嗜堿性細(xì)胞內(nèi)包含物, PSA +絲狀物粘多糖貯積癥肝細(xì)胞, Kuppfer 膠體鐵染色溶酶體內(nèi)“羊毛”狀物遲發(fā)性皮膚卟啉癥肝細(xì)胞內(nèi)針狀包含物肝細(xì)胞內(nèi)針狀包含物紅細(xì)胞生成性原卟啉癥膽素色(毛細(xì)核小膽管)“Starburst” 狀排列的結(jié)晶36-20 肝臟代謝性疾病的電鏡和非特異性光鏡診斷類(lèi)型LMEM糖原沉積, II細(xì)胞內(nèi)糖原增加結(jié)合溶酶體, 糖原GM2神經(jīng)節(jié)苷脂沉積癥正常膜性層狀包含體Niemann-Pick 病泡沫狀肝、Kupffer細(xì)胞溶酶體內(nèi)“myelin”樣包含體Wolman病泡沫狀肝、Kup

12、ffer細(xì)胞肝、Kupffer細(xì)胞內(nèi)脂滴Zellweger綜合癥非特異性肝細(xì)胞改變?nèi)狈^(guò)氧化小體(peroxisomes)36-21 肝臟代謝性疾病非診斷的光鏡和電鏡特點(diǎn)類(lèi)型LMEM半乳糖血癥Galactosemia同高酪氨酸血癥同高酪氨酸血癥糖原沉積(I, III)Glycogen storage肝細(xì)胞大,竇受壓, 鋪轉(zhuǎn)排列,脂肪變, 高糖原核仁糖原分隔細(xì)胞器, 脂滴, 高糖原核仁遺傳性果糖不耐癥Hereditary fructose intolerance同高酪氨酸血癥“fructose holes” 同心排列內(nèi)質(zhì)網(wǎng), 糖原顆粒高酪氨酸血癥Tyrosinemia肝細(xì)胞變性伴脂肪變(灶性),

13、 淤膽, 纖維化, 肝硬化淤膽, 脂滴, 內(nèi)質(zhì)網(wǎng)增加, 異常線粒體高酪氨酸血癥肝臟Glycogen storage, Liver, LMGlycogen storage, Liver, EM肝臟疾病診斷病因?qū)W形態(tài)（LM & EM)組化和免疫組化血清學(xué)、酶學(xué)檢查臨床表現(xiàn)Alcoholic Fatty LiverAlcoholic Fatty LiverCirrhosisFibrosisRegenerating NoduleMicronodular cirrhosisMicronodular cirrhosis:Hepatic AdenomaHepatocellular CarcinomaHepa

14、tic metastasis:Hepatic metastasis:Amoebic Liver Abscess:Hepar Lobatum (cong. Syphilis):HCC- The Global Perspective The Big Five CancersThe Major Etiological FactorsChronic hepatitis - types B or CCirrhosis/chronic liver disease of any type Aflatoxin exposureMales, increasing age8% - High 2-7% - Inte

15、rmediate 2% - LowData from CDC Chronic HBV Infection - Geographic DistributionProspective Study of HCC Development in HBsAg Seropositive Male Chinese HCC DEVELOPMENT 19,223 (HBsAg -ve) 9 22,707 Mean follow-up = 8.9 years Male Chinese 3,454 (HBsAg +ve) 152 Relative risk = 98.4 (50.2-193)Beasley, 1982Beasley 1986“The lifetime risk of developing Hepatocellular carcinomaIn a Chinese male carrier Of the hepatitis B virusIs between 40 and 50%”Chronic Viral Hepatitis & HCCOkuda , 1999Anti-HCV Prevalence5% - High 1.1-5% - Intermediate 0.2-1% -