肝膽胰疾病下

1、肝臟、膽道、外分泌部胰腺疾?。―iseases of the Liver, Gall Bladder and Exocrine Pancreas）,Lu ChangliDepartment of PathologyWest China Medical School,病毒性肝炎酒精性肝病肝代謝性疾病肝硬化原發(fā)性肝癌膽石癥、膽管炎和膽囊炎，膽道腫瘤胰腺炎，胰腺癌,,病毒性肝炎酒精性肝病肝代謝性疾病肝硬化原發(fā)性肝癌膽

2、石癥、膽管炎和膽囊炎，膽道腫瘤胰腺炎，胰腺癌,肝豆?fàn)詈俗冃?（Wilson’s Disease）,13q14-21，ATP7B常染色體隱形遺傳病多為兒童及青少年膽小管上銅輸出的ATP酶失活銅離子過量肝、CNS、腎角膜kayser-Fleischer 環(huán),Micronodular cirrhosis in Wilson disease,Micronodular cirrhosis in Wilson disease,Near

3、ly all patients with neurologic involvement develop eye lessionKayser-Fleischer rings result from a buildup of copper in the eyes and are the most unique sign of Wilson disease. They appear in each eye as a rusty-bro

4、wn ring around the edge of the iris and in the rim of the cornea.,,,M/56. This patient died from liver failure. The cirrhotic nodules are clearly seen. The liver is a dark brown color because of the heavy iron depositi

5、on within the hepatocytes,,Prussian blue-stained,A Prussian blue iron stain demonstrates the blue granules of hemosiderin in hepatocytes and Kupffer cells.,The Prussian blue iron stain,Pancreas:Microscopically, islet c

6、ells and stroma iron deposition is blue in Prussian blue –stained slide.Grossly, diffuse interstitial fibrosis is present.,血色病 (hemochromatosis),常染色體隱性遺傳病發(fā)病率1/300~1/400多見于男性，約40~60歲出現(xiàn)癥狀鐵攝入正常，但鐵在胃及小腸中過量吸收 致鐵鹽在肝和

7、相關(guān)器官實質(zhì)細胞中過量沉積肝受累最早肝功能異常，進行性門靜脈性肝硬化¼肝性腦病、上消化道出血、15%HCC,繼發(fā)性含鐵血黃素沉積癥（seconderay hemosiderosis),體內(nèi)紅細胞破壞過多 溶血性貧血、重型β海洋性貧血 多次輸血長期大量服用鐵劑,病毒性肝炎酒精性肝病肝代謝性疾病肝硬化原發(fā)性肝癌膽石癥、膽管炎和膽囊炎，膽道腫瘤胰腺炎，胰腺癌,,肝硬化Liver c

8、irrhosis,Rene Laënnec,Greek κιρρ?? [kirrhós] meaning yellowish, tawny,肝硬化（liver cirrhosis）,,肝細胞彌漫性變性壞死纖維組織增生肝細胞結(jié)節(jié)狀再生,反復(fù)交錯,肝臟彌漫變形、變硬血液循環(huán)改建,,,,Gross appearance,basic pathologic change 纖維組織增生

9、 假小葉（pseudolobule） 原有肝臟病變,假小葉（pseudolobule） 廣泛增生的纖維組織分割包繞肝細胞（包括原有的肝小葉和再生的肝細胞結(jié)節(jié)）而形成的大小不等的肝細胞團。 假小葉內(nèi)中央靜脈可缺如、偏位或兩個以上，可以出現(xiàn)匯管區(qū)。,Histopathology,Pathogenesis,Schematic of stell

10、ate cell activation and liver fibrosis in comparison to the normal liver.,發(fā)病機制： 病因 肝細胞彌漫性壞死 、炎癥 網(wǎng)狀纖維支架塌陷 纖維組織增生 分割包繞肝小葉、結(jié)節(jié)狀再生的肝細胞

11、 假小葉 肝小葉結(jié)構(gòu)破壞,,,,,,,,,,,肝星狀細胞-肌纖維母細胞匯管區(qū)成纖維細胞等產(chǎn)生膠原,異常血管吻合,血液循環(huán)途徑改建,小血管堵塞（炎癥）中大血管（血栓）,臨床病理聯(lián)系： 1. 門脈高壓癥 portal hypertension 2. 肝功能不全

12、 hepatic in-sufficiency hepatic failure,門靜脈高壓癥,肝A,小葉間A,門V,小葉間V,（匯管區(qū)）,血竇,中央靜脈,終末門微V,終末肝微A,小葉下V,肝V,下腔V,,,,,,,,,,,門脈壓力增高原因,1、肝血竇閉塞，竇周纖維化（竇性阻塞）,2、假小葉壓迫小葉下靜脈→中央靜脈→肝血竇→門靜脈回流受阻（竇后性阻塞）,門脈壓力增高原因,3、肝動脈與門靜脈間異常吻合→動脈血流入

13、門靜脈→門靜脈壓力↑(竇前性),門脈壓力增高原因,,,,Causes of portal hypertension,Pre-hepatic Post-hepatic Intra-hepatic,Post-hepatichepatic vein thrombosisright heart failureconstrictive pericarditis,Pre-hepatic stenosis of portal vei

14、n thrombosis,Intra-hepatic Schistosomiasis severe diffuse fatty change sarcoidosis TB diffuse liver cirrhosis nodular regenerative hyperplasia,淤血性脾腫大（Congestive splenomagely）,Portal Hypertension,

15、Clinical Features1、 Congestive splenomagely,脾功能亢進,血液淤滯,單核-巨噬細胞 吞噬↑,外周血細胞減少,,,,,,2、Ascites腹水，腹膨隆 淡黃色透明漏出液,原因：（1）門靜脈壓力↑，肝竇流體靜壓↑ ，管壁通透性↑（2）肝臟合成蛋白↓，低蛋白血癥，血漿膠體滲透壓↓（3）肝滅活醛固酮、抗利尿激素功能↓，水鈉潴留,3.Portosystemic Shunts

16、 食管下段靜脈叢 臍周及腹壁靜脈叢 直腸靜脈叢,,歪 門 邪 道,,奇靜脈,上腔靜脈,,下腔靜脈,髂內(nèi)靜脈,臍周及腹壁靜脈叢曲張（海蛇頭,Caput Medusae）,Seen here is the anus and perianal region with prominent prolapsed true hemorrhoids. Chronic constipation, chronic diarrhea, pregnan

17、cy, and portal hypertension enhance hemorrhoid formation. Hemorrhoids can itch and bleed slowly(usually bright red blood, during defaecation).,4、胃腸瘀血、水腫,消化、吸收功能↓,腹脹食欲不振,,,肝功能不全 hepatic insufficiency,,,,,,黃疸（jaundice）,男

18、子乳腺發(fā)育Gynecomastia due to alcoholic cirrhosis - A 32 year old male patient with normal secondary sex characteristics, no testicular mass, no history of drug ingestion, no other endocrine abnormalities and a normal neurol

19、ogical examination. Nevertheless, he had a history of more than 15 years of large amounts of alcohol intake and a liver biopsy confirm alcoholic cirrhosis.,肝掌Palmar erythema蜘蛛狀痣Spider angiomas (upper trunk),出血傾向 (Sp

20、ontaneous bleeding),,Clinical manifestation,The classification of cirrhosis,According to the gross morphologyMicronodular （ 3mm）Mixed nodularIncompleted separated,The descriptive terms should not be used as primary cl

21、assification,The classification of cirrhosis,According to the causesAlcoholic Viral hepatitisCardiacBiliaryParasiticPigmentalCryptogenic,M/39. with hepatitis B infection. The liver is greatly enlarged and weighted

22、 1720 g. Its surface is coarsely nodular.,Here is an example of alcoholic cirrhosis. Note that the liver also has a yellowish hue, indicating that fatty change is present.,Schistosomiasis Cirrhosis,膽汁性肝硬化Biliary cirrhos

23、is,原發(fā)性 (少見） 90%女性自身免疫性損傷 肝內(nèi)小膽管慢性非化 膿性破壞性膽管炎慢性進行性膽汁淤積不全分割型,繼發(fā)性 肝外膽管堵塞、膽道上行性感染,Feathery degeneration,,Bile lakes,Nutmeg liver,,Cardiac cirrhosis,The classification of cirrhosis,Integrated classificatonPortal

24、 (micronodular） Postnecrotic (macronodular or mixed）Biliary (Incompleted separated)CongestiveParasitic …,1、病毒性肝炎： HBV HCV （我國最常見的原因）2、慢性酒精中毒： （歐、美國家最常見原因）3、營養(yǎng)缺乏： 膽堿、蛋氨酸；合成磷脂障礙

25、 脂肪肝4、化學(xué)毒物： 殺蟲劑、CCl4等,病因,門脈性肝硬化（portal cirrhosis）,壞死后性肝硬化（postnecrotic cirrhosis）,肝實質(zhì)發(fā)生大片壞死的基礎(chǔ)上形成的較嚴重的病毒性肝炎 亞急性重型肝炎 重度慢性肝炎+壞死嚴重藥物及化學(xué)物質(zhì)中毒,,,病理特點：大體：體積小，重量輕，質(zhì)硬，表面及切面結(jié)節(jié)狀(＞1cm)，纖維間隔厚，厚薄不均鏡

26、下：假小葉形態(tài)懸殊 肝細胞不同程度變性、壞死 寬大的纖維間隔 膽管增生和炎細胞浸潤顯著,postnecrotic cirrhosis,臨床肝功能障礙 出現(xiàn)早，重 門脈高壓 出現(xiàn)晚，輕惡變率 高,postnecrotic cirrhosis,Summary,In cirrhosis th

27、e liver is diffusely replaced by nodules of hepatocytes separated by fibrosisThe most common causes of cirrhosis are diseases of alcohol abuse and viral hepatitis Cirrhosis is best classified according to the cause of

28、liver damage,Summary,The most common and dangerous complications of cirrhosis Fatal bleeding of lower esophageal plexusHepatic coma (hepatic encephalopathy)Hepatocellular carcinoma, especially for the case from chroni

29、c hepatitis B and C,病毒性肝炎酒精性肝病肝代謝性疾病肝硬化原發(fā)性肝癌膽石癥、膽管炎和膽囊炎，膽道腫瘤胰腺炎，胰腺癌,,,原發(fā)性肝癌( primary carcinoma of the liver ),原發(fā)于肝細胞或肝內(nèi)膽管上皮細胞的惡性腫瘤。,肝癌發(fā)病率大國，發(fā)病率占全球45%高發(fā)年齡40~50歲起病隱匿（40%診斷時沒有癥狀）確診時多數(shù)已達到中晚期5年生存率2%-16%病因 病毒性肝

30、炎 肝硬化 黃曲霉素,高危人群 乙肝表面抗原陽性者 慢性肝炎患者 有肝癌家族史早期發(fā)現(xiàn)肝癌——定期體檢 每半年做一次肝功能、AFP、B超,病 變 肉眼類型： 早期肝癌 （小肝癌） 中晚期肝癌 ：巨塊型 多結(jié)節(jié)型 彌漫型,多合并肝硬化,,Massive

31、 type of HCC in a 17-year-old patient without cirrhosis,Massive type of HCC,The liver showing an unifocal massive neoplasm with cirrhosis; some satellite tumor nodules is directly adjacent.,Mutifocal type of HCC,Diffusel

32、y infiltrative type of HCC,HCC with intrahepatic metastasis,tumor thrombosis,Adenocarcinoma arising from the bile ducts in the porta hepatis.F/78. The patient died from the effect of obstructive jaundice.,cholangiocarc

33、inoma,,HCC,cholangiocarcinoma,Combined hepatocellular and cholangiocarcinoma,肝臟其他常見腫瘤,1. 原發(fā) 2. 繼發(fā)（轉(zhuǎn)移）更常見,良性惡性,海綿狀血管瘤肝細胞腺瘤 等,肝母細胞瘤血管肉瘤 等,,,,Cavernous haemangioma in the liver. This was an incidental finding. O

34、ccasionally these haemangiomas may bleed, but mostly they are asymptomatic.,Most liver-cell adenomas arise in women of child-bearing age,usually after prolonged use of oral contraceptives. Subcapsular adenomas are at ris

35、k for rupture.,metastatic carcinomas from the stomach,Metastatic carcinoma in liver,,The liver may be involved by secondary tumors, presenting multiple hepatic metastases.,病毒性肝炎酒精性肝病肝代謝性疾病肝硬化原發(fā)性肝癌膽石癥、膽管炎和膽囊炎，膽道腫瘤胰腺

36、炎，胰腺癌,正常膽囊（normal gallbladder）,pigment stones are predisposed by increased hepatic secretion of bilirubin. cholesterol stones are predisposed by changes in cholesterol solubility in bile.,Chronic cholecystitis. F/48. T

37、he gall bladder shows the features of chronic cholecystitis and it is packed with small multifaceted mixed gall stones.,Acute superimposed on chronic cholecystitis. F/38. The gall bladder is distended. Both serosal and m

38、ucosal surfaces are reddened and inflamed. The wall of the gall bladder is thickened and there are a few mixed calculi within it.,Cholesterolosis. F/36. The gall bladder showschronic cholecystitis. There are multiple

39、yellowspots on its mucosal surface. This is due to the accumulation of lipid in thelamina propria.,肝內(nèi)膽管結(jié)石,膽道腫瘤,膽囊和肝外膽管癌 (carcinoma of the gallbladder and extrahepatic bile ducts) 膽囊和肝外膽管上皮細胞發(fā)生的惡性腫瘤,Carcinoma of

40、 the gallbladder.Adenocarcinoma of the gallbladder is seen as a raised area in fundus. Most tumors have invaded through the wall at the time of diagnosis.,,,胰腺外分泌部（Exocrine pancreas）,胰腺實質(zhì)由外分泌部和內(nèi)分泌部組成外分泌部占90%，分泌胰液，經(jīng)導(dǎo)管排

41、入十二指腸，有重要的化學(xué)性消化作用 急性胰腺炎（Acute pancreatitis）慢性胰腺炎（Chronic pancreatitis） 胰腺假性囊腫（Pseudocyst of the pancreas） 腫瘤（Tumors）,Normal common bile duct and pancreatic duct,急性水腫性（間質(zhì)性）胰腺炎acute edemous pancreatitis,暴飲暴食（酗

42、酒）；膽道結(jié)石間質(zhì)充血水腫炎細胞浸潤（中性粒細胞和單核細胞）可局灶性脂肪壞死預(yù)后好,Acute hemorrhagic pancreatitis,Hemorrhage and necrosis,Lipase released from the pancreatic acini causes the development of foci of fat necrosis. This is seen as white spot

43、s.,Histologically these spots are composed of necrotic adipose tissue, with adjacent reactive inflammation.,特點：發(fā)病急，病情重病理：胰腺腫大，結(jié)構(gòu)模糊； 廣泛壞死，出血休克和腎功能衰竭，20%死亡,急性出血性胰腺炎Acute hemorrhagic pancreatitis,Pathogene

44、sis,胰腺壞死胰液外溢,大量出血劇烈腹痛,休克、急性腎衰,腹膜炎,淀粉酶、脂酶入血、尿,血尿淀粉酶、脂酶升高,胰高血糖素↑,降鈣素↑骨鈣釋放↓,血鈣↓,炎癥刺激,脂肪壞死,吸收鈣,持續(xù)嘔吐,血鉀、鈉↓,,,,,,,,,,,,,急性胰腺炎反復(fù)發(fā)作膽道系統(tǒng)疾病，慢性酒精中毒輕-中度的腹部疼痛,慢性胰腺炎Chronic pancreatitis,Chronic pancreatitis. F/43. The pancreas is a

45、trophic and fibrotic. The main pancreatic duct is dilated and there are calculi in the ducts of the pancreas. The patient was an alcoholic.,,Chronic pancreatitis. The exocrine pancreas has been replaced by fibrous tissue

46、.,Pseudocyst in the body and tail of the pancreas. F/67. This is a well-recognized complication of pancreatitis.,胰腺癌(carcinoma of pancreas),15%,5%,Carcinoma of the head of pancreasTumor appears as gritty, grey, hard

47、nodules, irregularlyinvading the adjacentstructures.Histologically they areusually moderatedifferentiated adeno-carcinomas.,Summary,Key PiontsViral hepatitisAlcoholic liver diseaseCirrhosis,Key Terms,liver cir