1、肝脏、胆道、外分泌部胰腺疾病（Diseases 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谢性疾病肝硬化原发性肝癌胆石症、胆管炎和胆囊炎，胆道肿瘤胰腺炎，胰腺癌,病毒性肝炎酒精性肝病肝代谢性疾病肝硬化原发性肝癌胆石症、胆管炎和胆囊炎，胆道肿瘤胰腺炎，胰腺癌,肝豆状核变性 （Wilsons Disease）,13q14-21，ATP7B常染色体隐形遗传病多为儿童及青少年胆小管上铜输出的ATP酶失活铜
2、离子过量肝、CNS、肾角膜kayser-Fleischer 环,Micronodular cirrhosis in Wilson disease,Micronodular cirrhosis in Wilson disease,Nearly 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
3、 appear in each eye as a rusty-brown 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 deposition within the hepatocytes,Prussian blue-stained,A
4、Prussian blue iron stain demonstrates the blue granules of hemosiderin in hepatocytes and Kupffer cells.,The Prussian blue iron stain,Pancreas:Microscopically, islet cells and stroma iron deposition is blue in Prussian blue stained slide.Grossly, diffuse interstitial fibrosis is present.,血色病 (hemoch
5、romatosis),常染色体隐性遗传病发病率1/3001/400多见于男性，约4060岁出现症状铁摄入正常，但铁在胃及小肠中过量吸收 致铁盐在肝和相关器官实质细胞中过量沉积肝受累最早肝功能异常，进行性门静脉性肝硬化肝性脑病、上消化道出血、15%HCC,继发性含铁血黄素沉积症（seconderay hemosiderosis),体内红细胞破坏过多 溶血性贫血、重型海洋性贫血 多次输血长期大量服用铁剂,病毒性肝炎酒精性肝病肝代谢性疾病肝硬化原发性肝癌胆石症、胆管炎和胆囊炎，胆道肿瘤胰腺炎，胰腺癌,肝硬化Liver cirrhosis,Rene Lannec,Greek kirrhs meanin
6、g yellowish, tawny,肝硬化（liver cirrhosis）,肝细胞弥漫性变性坏死纤维组织增生肝细胞结节状再生,反复交错,肝脏弥漫变形、变硬血液循环改建,Gross appearance,basic pathologic change 纤维组织增生 假小叶（pseudolobule） 原有肝脏病变,假小叶（pseudolobule） 广泛增生的纤维组织分割包绕肝细胞（包括原有的肝小叶和再生的肝细胞结节）而形成的大小不等的肝细胞团。 假小叶内中央静脉可缺如、偏位或两个以上，可以出现汇管区。,Histopathology,Pathogenesis,Schematic of ste
7、llate cell activation and liver fibrosis in comparison to the normal liver.,发病机制： 病因 肝细胞弥漫性坏死 、炎症 网状纤维支架塌陷 纤维组织增生 分割包绕肝小叶、结节状再生的肝细胞 假小叶 肝小叶结构破坏,肝星状细胞-肌纤维母细胞汇管区成纤维细胞等产生胶原,异常血管吻合,血液循环途径改建,小血管堵塞（炎症）中大血管（血栓）,临床病理联系： 1. 门脉高压症 portal hypertension 2. 肝功能不全 hepatic in-sufficiency hepatic failure,门静脉高压症,肝A,小
8、叶间A,门V,小叶间V,（汇管区）,血窦,中央静脉,终末门微V,终末肝微A,小叶下V,肝V,下腔V,门脉压力增高原因,1、肝血窦闭塞，窦周纤维化（窦性阻塞）,2、假小叶压迫小叶下静脉中央静脉肝血窦门静脉回流受阻（窦后性阻塞）,门脉压力增高原因,3、肝动脉与门静脉间异常吻合动脉血流入门静脉门静脉压力(窦前性),门脉压力增高原因,Causes of portal hypertension,Pre-hepatic Post-hepatic Intra-hepatic,Post-hepatichepatic vein thrombosisright heart failureconstrictive
9、pericarditis,Pre-hepatic stenosis of portal vein thrombosis,Intra-hepatic Schistosomiasis severe diffuse fatty change sarcoidosis TB diffuse liver cirrhosis nodular regenerative hyperplasia,淤血性脾肿大（Congestive splenomagely）,Portal Hypertension,Clinical Features1、 Congestive splenomagely,脾功能亢进,血液淤滞,单核-
10、巨噬细胞 吞噬,外周血细胞减少,2、Ascites腹水，腹膨隆 淡黄色透明漏出液,原因：（1）门静脉压力，肝窦流体静压 ，管壁通透性（2）肝脏合成蛋白，低蛋白血症，血浆胶体渗透压（3）肝灭活醛固酮、抗利尿激素功能，水钠潴留,3.Portosystemic Shunts 食管下段静脉丛 脐周及腹壁静脉丛 直肠静脉丛,歪 门 邪 道,奇静脉,上腔静脉,下腔静脉,髂内静脉,脐周及腹壁静脉丛曲张（海蛇头,Caput Medusae）,Seen here is the anus and perianal region with prominent prolapsed true hemorrhoids.
11、Chronic constipation, chronic diarrhea, pregnancy, and portal hypertension enhance hemorrhoid formation. Hemorrhoids can itch and bleed slowly(usually bright red blood, during defaecation).,4、胃肠瘀血、水肿,消化、吸收功能,腹胀食欲不振,肝功能不全 hepatic insufficiency,黄疸（jaundice）,男子乳腺发育Gynecomastia due to alcoholic cirrhosi
12、s - 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 neurological examination. Nevertheless, he had a history of more than 15 years of large amounts of alcohol intake and a liver biop
13、sy confirm alcoholic cirrhosis.,肝掌Palmar erythema蜘蛛状痣Spider angiomas (upper trunk),出血倾向 (Spontaneous bleeding),Clinical manifestation,The classification of cirrhosis,According to the gross morphologyMicronodular （ 3mm）Mixed nodularIncompleted separated,The descriptive terms should not be used as pri
14、mary classification,The classification of cirrhosis,According to the causesAlcoholic Viral hepatitisCardiacBiliaryParasiticPigmentalCryptogenic,M/39. with hepatitis B infection. The liver is greatly enlarged and weighted 1720 g. Its surface is coarsely nodular.,Here is an example of alcoholic cirrho
15、sis. Note that the liver also has a yellowish hue, indicating that fatty change is present.,Schistosomiasis Cirrhosis,胆汁性肝硬化Biliary cirrhosis,原发性 (少见） 90%女性自身免疫性损伤 肝内小胆管慢性非化 脓性破坏性胆管炎慢性进行性胆汁淤积不全分割型,继发性 肝外胆管堵塞、胆道上行性感染,Feathery degeneration,Bile lakes,Nutmeg liver,Cardiac cirrhosis,The classification o
16、f cirrhosis,Integrated classificatonPortal (micronodular） Postnecrotic (macronodular or mixed）Biliary (Incompleted separated)CongestiveParasitic ,1、病毒性肝炎： HBV HCV （我国最常见的原因）2、慢性酒精中毒： （欧、美国家最常见原因）3、营养缺乏： 胆碱、蛋氨酸；合成磷脂障碍 脂肪肝4、化学毒物： 杀虫剂、CCl4等,病因,门脉性肝硬化（portal cirrhosis）,坏死后性肝硬化（postnecrotic cirrhosis）,肝实
17、质发生大片坏死的基础上形成的较严重的病毒性肝炎 亚急性重型肝炎 重度慢性肝炎+坏死严重药物及化学物质中毒,病理特点：大体：体积小，重量轻，质硬，表面及切面结节状(1cm)，纤维间隔厚，厚薄不均镜下：假小叶形态悬殊 肝细胞不同程度变性、坏死 宽大的纤维间隔 胆管增生和炎细胞浸润显著,postnecrotic cirrhosis,临床肝功能障碍 出现早，重 门脉高压 出现晚，轻恶变率 高,postnecrotic cirrhosis,Summary,In cirrhosis the liver is diffusely replaced by nodules of hepatocytes sepa
18、rated by fibrosisThe most common causes of cirrhosis are diseases of alcohol abuse and viral hepatitis Cirrhosis is best classified according to the cause of liver damage,Summary,The most common and dangerous complications of cirrhosis Fatal bleeding of lower esophageal plexusHepatic coma (hepatic e
19、ncephalopathy)Hepatocellular carcinoma, especially for the case from chronic hepatitis B and C,病毒性肝炎酒精性肝病肝代谢性疾病肝硬化原发性肝癌胆石症、胆管炎和胆囊炎，胆道肿瘤胰腺炎，胰腺癌,原发性肝癌( primary carcinoma of the liver ),原发于肝细胞或肝内胆管上皮细胞的恶性肿瘤。,肝癌发病率大国，发病率占全球45%高发年龄4050岁起病隐匿（40%诊断时没有症状）确诊时多数已达到中晚期5年生存率2%-16%病因 病毒性肝炎 肝硬化 黄曲霉素,高危人群 乙肝表面抗原阳性
20、者 慢性肝炎患者 有肝癌家族史早期发现肝癌定期体检 每半年做一次肝功能、AFP、B超,病 变 肉眼类型： 早期肝癌 （小肝癌） 中晚期肝癌 ：巨块型 多结节型 弥漫型,多合并肝硬化,Massive 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 ty
21、pe of HCC,Diffusely 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.,cholangiocarcinoma,HCC,cholangiocarcinoma,Combined hepatocellular and cholang
22、iocarcinoma,肝脏其他常见肿瘤,1. 原发 2. 继发（转移）更常见,良性恶性,海绵状血管瘤肝细胞腺瘤 等,肝母细胞瘤血管肉瘤 等,Cavernous haemangioma in the liver. This was an incidental finding. Occasionally these haemangiomas may bleed, but mostly they are asymptomatic.,Most liver-cell adenomas arise in women of child-bearing age,usually after prolonged
23、 use of oral contraceptives. Subcapsular adenomas are at risk 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谢性疾病肝硬化原发性肝癌胆石症、胆管炎和胆囊炎，胆道肿瘤胰腺炎，胰腺癌,正常胆囊（normal gallbladd
24、er）,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. The gall bladder shows the features of chronic cholecystitis and it is packed with small multifaceted mixed ga
25、ll stones.,Acute superimposed on chronic cholecystitis. F/38. The gall bladder is distended. Both serosal and mucosal 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 cholec
26、ystitis. There are multiple yellowspots on its mucosal surface. This is due to the accumulation of lipid in thelamina propria.,肝内胆管结石,胆道肿瘤,胆囊和肝外胆管癌 (carcinoma of the gallbladder and extrahepatic bile ducts) 胆囊和肝外胆管上皮细胞发生的恶性肿瘤,Carcinoma of the gallbladder.Adenocarcinoma of the gallbladder is seen as
27、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）,胰腺实质由外分泌部和内分泌部组成外分泌部占90%，分泌胰液，经导管排入十二指肠，有重要的化学性消化作用 急性胰腺炎（Acute pancreatitis）慢性胰腺炎（Chronic pancreatitis） 胰腺假性囊肿（Pseudocyst of the pancreas） 肿瘤（Tumors）,Normal common bile duct and pa
28、ncreatic duct,急性水肿性（间质性）胰腺炎acute edemous pancreatitis,暴饮暴食（酗酒）；胆道结石间质充血水肿炎细胞浸润（中性粒细胞和单核细胞）可局灶性脂肪坏死预后好,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 spots.,Histologically these spo
29、ts are composed of necrotic adipose tissue, with adjacent reactive inflammation.,特点：发病急，病情重病理：胰腺肿大，结构模糊； 广泛坏死，出血休克和肾功能衰竭，20%死亡,急性出血性胰腺炎Acute hemorrhagic pancreatitis,Pathogenesis,胰腺坏死胰液外溢,大量出血剧烈腹痛,休克、急性肾衰,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,降钙素骨钙释放,血钙,炎症刺激,脂肪坏死,吸收钙,持续呕吐,血钾、钠,急性胰腺炎反复发作胆道系统疾病，慢性酒精中毒轻-中度的腹
30、部疼痛,慢性胰腺炎Chronic pancreatitis,Chronic pancreatitis. F/43. The pancreas is atrophic 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.,Pseu
31、docyst 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 nodules, irregularlyinvading the adjacentstructures.Histologically they areusually moderatedifferentiated adeno-carcinomas.,Summary,Key PiontsViral hepatitisAlcoholic liver diseaseCirrhosis,Key Terms,liver cirrhosispseudolobuleportal hypertensionSmall (early) hepatocellular carcinoma,Thank you!,
