第八章++消化系统2

null消化系统疾病(2) 消化系统疾病(2) Disease of digestive system肝脏的概述肝脏的概述肝是人体最大的腺体，具有极复杂多样的生物化学功能，被称为机体的化工厂。 肝小叶是肝的基本结构单位，呈多角棱柱体，成人有50~100万个肝小叶。包括中央静脉、肝索和肝血窦。 肝板即肝细胞单层排列成凹凸不平的板状结构；相邻肝板吻合连接，形成迷路样结构，其断面呈索状，称肝索。 肝细胞相邻面的质膜局部凹陷，形成微细的胆小管 肝巨噬细胞又称库普弗细胞（Kupffer cell），定居于肝血窦内null病毒性肝炎 viral hepatitis病毒性肝炎 viral hepatitis是一组由肝炎病毒引起的以肝实质细胞变性坏死为主要病变的传染病 世界各地均有发病和流行，且发病率有不断升高的趋势，如乙型肝炎病毒携带者达3亿人以上，我国约占人口的10%。nullnullnull二、发病机制二、发病机制 肝细胞损伤的机制（以HBV为例） 病毒侵入机体 整合入肝细胞内复制 “出芽”释出肝细胞入血 在肝细胞表面遗留病毒Ag 刺激机体免疫系统 细胞免疫 体液免疫 免疫活性细胞 Ab 损伤肝细胞 杀灭病毒 二、发病机制二、发病机制各型肝炎的发病机制 细胞免疫反应的强弱是决定病毒性肝炎病变轻重的重要因素，若病毒毒力相同 免疫反应过强→重型肝炎 免疫反应正常→急性普通型肝炎 免疫反应低下→慢性普通型肝炎 免疫缺陷或耐受→病毒携带者三、基本病变三、基本病变 以肝细胞的变性、坏死为主，伴有不同程度的炎性细胞浸润、肝细胞再生和纤维组织增生—变质性炎 肝细胞变性 细胞水肿：胞质疏松化和气球样变 脂肪变 嗜酸性变:胞质水分脱失、浓缩，嗜酸性增强，故红染 三、基本病变三、基本病变肝细胞坏死 分嗜酸性坏死和溶解性坏死 嗜酸性坏死 溶解性坏死 点状坏死 (spotty necrosis) 碎片状坏死(piecemeal necrosis) 桥接坏死(bridging necrosis) 大片坏死(massive necrosis) 三、基本病变三、基本病变炎症细胞浸润 浸润部位—汇管区、肝小叶、坏死区 浸润细胞—T淋巴细胞、单核细胞 肝细胞再生：双核、胞浆略呈嗜碱性 间质反应性增生和小胆管增生 Kupffer细胞增生肥大 肝星状细胞及成纤维细胞增生 小胆管增生 四、临床病理类型及各型主要病变特点四、临床病理类型及各型主要病变特点普通型病毒肝炎 急性普通型肝炎—最常见，有黄疸型和无黄疸型两种，我国以后种多见 病理：肝细胞广泛变性，点状坏死，慢性炎细胞浸润 临床：急性炎症变化：发热、消化不良等 肝大、压痛、SGPT增高 预后：多数在6月内治愈 乙型约5%～10%转为慢性，丙型70%转为慢性 0.1%～1%转为重型null②慢性普通型肝炎（依不同程度的炎症变化、坏死及纤维化分三类） 轻度—点状坏死，肝小叶结构完整，汇管区周围纤维增生 中度—中度碎片状坏死及特征性的桥接坏死，肝小叶结构大部分保存，肝小叶内有纤维间隔形成 重度—重度碎片状坏死及大范围桥接坏死，坏死区肝细胞不规则再生，小叶内外坏死区间纤维增生相连分割肝小叶，晚期可形成假小叶 毛玻璃样肝细胞 null重型病毒性肝炎 急性重型肝炎：又称暴发型肝炎。起病急，病变发展迅猛、剧烈，病死率高。 肉眼：急性黄色( 红色)肝萎缩：体积显著缩小，重 量减轻仅600～800g, 质地软，表面皱缩；切 面呈黄褐色，充血出血。 镜下：肝细胞大片坏死，仅小叶周围残存少量变性 肝细胞，Kupffer细胞增生活跃，淋巴细胞、 巨噬细胞为主的炎细胞浸润，小叶网状支架 数日后塌陷，增生及再生均不明显。null临床：严重肝功能障碍：GPT800～1100,黄疸, 出血倾向，肝性脑病，肝肾综合症，DIC 预后：多在二周内死亡（肝昏迷、肾功能衰 竭、消化道出血） 少数转变成亚急性重型肝炎或慢性肝炎 null亚急性重型肝炎--病程 1～数月，由急性重型迁延而来或从开始即为亚急性过程，也可由急性普通型、慢性恶化而来。 亚急性黄色肝萎缩） 肉眼：肝脏体积缩小，表面不平，结节状，切 面呈黄绿色，质地略硬。 病理：肝细胞的大片坏死，网状支架塌陷，病变新旧不等; 肝细胞结节状再生; 纤维组织的增生，小胆管增生，炎细胞浸润。 结局：病变有停止并治愈可能，多数转变为坏死后性肝硬化nullnull肝硬化 liver cirrhosis肝硬化 liver cirrhosis 各种原因引起肝细胞弥漫性变性坏死、纤维组织增生和肝细胞结节状再生，这三种病变反复交错进行，肝小叶结构和血液循环途径被改建，肝脏变形、变硬而形成肝硬化 分类方法较多 国际纯形态分类（大结节型、小结节型、大小结节型及不全分割型） null我国结合病因、病变特点以及临床表现的综合分类 门脉性肝硬化 坏死后性肝硬化 胆汁性肝硬化 其它（如淤血性肝硬化、色素性肝硬化） 引起肝硬化的病因引起肝硬化的病因病毒性肝炎：70%～80%，HBV,HCV 慢性酒精中毒： 药物及化学物质中毒：砷、黄磷、四氯化碳等 营养缺乏：甲硫氨酸、光氨酸、蛋白质、胆硷等 胆道阻塞、胆汁淤积：结石、肿瘤、总胆管囊肿，先天性狭窄等慢性非化脓性破坏性胆管炎 寄生虫：血吸虫等 黄曲霉素一、发病机制一、发病机制 成纤维细胞 肝细胞变性坏死 胶原纤维增生 肝星状细胞 网状纤维支架塌陷 形成纤维间隔 肝细胞不规则 结节状再生 肝小叶结构未改建 假小叶形成 肝纤维化 肝小叶结构和血液循环途径改建 肝硬化二、两种肝硬化比较二、两种肝硬化比较三、临床病理联系三、临床病理联系门脉高压症 形成原因 肝内广泛的结缔组织增生，肝血窦闭塞或窦周纤维化，使门静脉循环受阻（窦性阻塞） 假小叶压迫小叶下静脉，使肝窦内血流流出受阻，进而影响门静脉血流入肝血窦（窦后性阻塞） 肝动脉与门静脉之间形成异常吻合支，使高压力的动脉血流入门静脉内。null临床表现 慢性淤血性脾肿大→脾功能亢进 腹水 胃肠淤血、水肿→食欲不振、消化不良 侧支循环形成 门V→胃冠状V→食管下端V丛→奇V→上腔V 门V→肠系膜下V→（直肠V）痔V丛→髂内V→下腔V 门V→脐旁V→脐周及腹壁V丛→腹壁上、下V→上、下腔V 肝脏正常血液循环途径及门脉高压形成原因肝脏正常血液循环途径及门脉高压形成原因 门静脉 肝动脉 小叶间静脉 小叶间动脉 肝血窦 中央静脉 小叶下静脉 肝静脉 下腔静脉 回心腹 水腹 水形成原因 门脉系统毛细血管流体静力压↑致管壁通透性↑ 低蛋白血症致血浆胶体渗透压↓ 醛固酮、ADH ↑致水钠潴留三、临床病理联系三、临床病理联系肝功能不全 蛋白质合成障碍 出血倾向 胆色素代谢障碍 对激素的的灭活作用减弱 肝性脑病（肝昏迷）null胆汁性肝硬化胆汁性肝硬化是因胆道阻塞淤胆而引起的肝硬化，较少见，可分为继发性和原发性（更少）两类。 肝体积常增大，表面平滑或呈细颗粒状，硬度中等，呈绿色或绿褐色，切面结节较小，结节间纤维间隔亦细。 镜下肝细胞胞浆内胆色素沉积，肝细胞因而变性坏死。网状或羽毛状坏死；毛细胆管淤胆、胆栓形成，坏死区胆管破裂，胆汁外溢，形成胆汁湖。汇管区胆管扩张及小胆管增生。色素性肝硬化色素性肝硬化多见于血色病(hemochromatosis)患者，由于肝细胞内有过多的含铁血黄素沉着而发生坏死，继而有纤维组织增生形成肝硬化。胆石症 cholelithiasis胆石症 cholelithiasis 胆管结石 胆囊结石病因和发病机制病因和发病机制胆汁理化性质改变 胆汁淤滞 细菌感染 胆汁的某些成分(胆色素、胆固醇、粘液、钙)析出，凝集 胆石的种类和特点胆石的种类和特点色素性胆石 胆固醇性胆石 混合性胆石病案讨论病案讨论病史摘要： 患者舒×，男，47岁。浮肿、腹胀3个月，近一周加重。现病史：患者于4年前罹患肝炎，屡经治疗，反复多次发病。近两年全身疲乏，不能参加体力劳动，并时有下肢浮肿。近3个月腹部逐渐膨胀，一周前因过度劳累同时大量饮酒，腹胀加重。患者食欲不振，大便溏泻，每日3-4次，小便量少而黄。 既往史：患者常年嗜酒，除4年前罹患肝炎外无其它疾病。 体检：面色萎黄，巩膜及皮肤轻度黄染，颈部两处有蜘蛛痣，心肺未见异常。腹部膨隆，腹围94cm，有中等腹水，腹壁静脉曲张，肝脏于肋缘未触及，脾大在左肋缘下1.5cm。下肢有轻度浮肿。 null化验：RBC 3.27×1012/L，Hb 70g/L；血清总蛋白52.3g/L，白蛋白24.2g/L (40~55g/L) ，球蛋白28.1g/L (20~30g/L) ；黄疸指数18单位，谷丙转氨酶102单位(<40)。 X线食管静脉造影提示食管下段静脉曲张。 临床诊断：肝硬化（失代偿期） 讨论： 1．你是否同意本病的临床诊断？为什么？若不同意，又作何诊断及诊断依据。 2．患者为何会出现腹壁静脉和食管下段曲张？请用病理学知识解释。 3．本例患者的黄疸、腹水、浮肿和脾肿大是怎样产生的？ 4．本例肝脏可能会出现哪些大体和镜下改变？ null The left is an in-situ photograph of the chest and abdominal contents. The liver is the largest parenchymal organ, lying just below the diaphragm. The right lobe is larger than the left lobe. The right is the external surface of a normal liver. The color is brown and the surface is smooth. A normal liver is about 1200 to 1600 grams. nullNormal lobules of liverCVnull This photomicrograph is a high magnification of liver plates (LP). Observe that individual hepatocytes (H) are polygonal in shape. Each hepatocyte possesses one or two nuclei, although occasionally some have three nuclei. Plates of hepatocytes enclose hepatic sinusoids (Si) that are lined by sinusoidal lining cells (SC); therefore, hepatocytes do not come into direct contact with the bloodstream. The space between the sinusoidal lining cells and the hepatocytes, the space of Disse (arrows), is at the limit of resolution of the light microscope.null Liver is divided histologically into lobules. The center of the lobule is the central vein. At the periphery of the lobule are portal triads. Functionally, the liver can be divided into three zones, based upon oxygen supply. Zone 1 encircles the portal tracts where the oxygenated blood from hepatic arteries enters. Zone 3 is located around central veins, where oxygenation is poor. Zone 2 is located in between. Kupffer cell (KC), are found interspersed among the endothelial lining cells of liver sinusoids (Si). These macrophages are larger than the epithelial cells and may be recognized by the presence of phagocytosed material within them. Kupffer cells may be demonstrated by injecting an animal intravenously with India ink, as in this specimen. Observe that some cells appear as large black smudges because they are filled with phagocytosed ink (arrows), whereas other cells possess only small quantities of the phagocytosed material (arrowheads). Note also that much of the sinusoidal lining is devoid of ink, indicating that the endothelial cells are probably not phagocytic. Kupffer cell (KC), are found interspersed among the endothelial lining cells of liver sinusoids (Si). These macrophages are larger than the epithelial cells and may be recognized by the presence of phagocytosed material within them. Kupffer cells may be demonstrated by injecting an animal intravenously with India ink, as in this specimen. Observe that some cells appear as large black smudges because they are filled with phagocytosed ink (arrows), whereas other cells possess only small quantities of the phagocytosed material (arrowheads). Note also that much of the sinusoidal lining is devoid of ink, indicating that the endothelial cells are probably not phagocytic. nullnullLiver cell degenerationLiver cell degenerationIndividual hepatocytes are affected by viral hepatitis. Viral hepatitis A rarely leads to signficant necrosis, but hepatitis B can result in a fulminant hepatitis with extensive necrosis. A large pink cell undergoing "ballooning degeneration" is seen below the right arrow. At a later stage, a dying hepatocyte is seen shrinking down to form an eosinophilic "councilman body" below the arrow on the left. Individual hepatocytes are affected by viral hepatitis. Viral hepatitis A rarely leads to signficant necrosis, but hepatitis B can result in a fulminant hepatitis with extensive necrosis. A large pink cell undergoing "ballooning degeneration" is seen below the right arrow. At a later stage, a dying hepatocyte is seen shrinking down to form an eosinophilic "councilman body" below the arrow on the left. nullFatty changenullFatty change, stain of Oil Red OAcidophilic bodyAcidophilic bodynullnullnullSpotty necrosis Acidophilic changenullnull Viral hepatitis leads to liver cell destruction. A mononuclear inflammatory cell infiltrate extends from portal areas and disrupts the limiting plate of hepatocytes which are undergoing necrosis, the so-called "piecemeal" necrosis of chronic active hepatitis. In this case, the hepatitis B surface antigen (HbsAg) and hepatitis B core antibody (HbcAb) were positive.null桥接坏死nullmassive necrosisnullnullInflammatory cells infiltrating　in portal areanullHigher magnification shows proliferating bile ductsAcute hepatitisAcute hepatitisnull皮疹nullChronic hepatitisChronic hepatitisClouded glassis hepatocyteClouded glassis hepatocytenull毛玻璃样细胞nullnullnullNormal bile canaliculi subacute severe hepatitis bile canaliculi cholestasisNormal bile canaliculi subacute severe hepatitis bile canaliculi cholestasissubacute severe hepatitissubacute severe hepatitisnull This is an example of a micronodular cirrhosis. The regenerative nodules are quite small, averaging less than 3 mm in size. The most common cause for this is chronic alcoholism. The process of cirrhosis develops over many years. null Here is another example of macronodular cirrhosis. Viral hepatitis (B or C) is the most common cause for macronodular cirrhosis. Wilson's disease and alpha-1-antitrypsin deficiency also can produce a macronodular cirrhosis. nullnullPortal cirrhosisnullpostnecrotic　cirrhosisnullnullEarly fibrosis, Masson stainnullBridging fibrosis，early stage of liver cirrhosisnullnullLiver cirrhosis, Masson’s stainPortal and postnecrotic cirrhosisPortal and postnecrotic cirrhosisnullnullnullPostnecrotic cirrhosis, later stagenullnullnullLiver cirrhosis and splenomegalynullnullnullnull Portal hypertension results from the abnormal blood flow pattern in liver created by cirrhosis. The increased pressure is transmitted to collateral venous channels. Sometimes these venous collaterals are dilated. Seen here is "caput medusae" which consists of dilated veins seen on the abdomen of a patient with cirrhosis of the liver. null A much more serious problem produced by portal hypertension results when submucosal veins in the esophagus become dilated. These are known as esophageal varices. Varices are seen here in the lower esophagus as linear blue dilated veins. There is hemorrhage around one of them. Such varices are easily eroded, leading to massive gastrointestinal hemorrhage. nullnullnull泰利氏指甲Terry‘s nail：指甲床近端80%是白色，远端是正常的粉紅色——代表肝硬化 另外一个硬化现象是"杵状指（clubbing finger）", 特别是酒精肝的硬化患者 nullBiliary cirrhosisBiliary cirrhosisnullbiliary cirrhosisnull The left is an example of intrahepatic obstruction with a small stone in an intrahepatic bile duct. This could produce a localized cholestasis, but the serum bilirubin would not be increased, because there is plenty of non-obstructed liver to clear the bilirubin from the blood. The right is to see the yellowish-green accumulations of pigment. Most often this is due to extrahepatic biliary tract obstruction. However, bile may also accumulate in liver (called cholestasis) when there is hepatocyte injury. null The hepatocytes and Kupffer cells here are full of granular brown deposits of hemosiderin from accumulation of excess iron in the liver. The term "hemosiderosis" is used to denote a relatively benign accumulation of iron. The term "hemochromatosis" is used when organ dysfunction occurs. The iron accumulation may lead to a micronodular cirrhosis (so called "pigment" cirrhosis). nullnullnullnullnull