《陶小红cirrh》PPT课件.ppt

CIRRHOSIS of LIVER,Xiaohong Tao The First Affiliated Hospital Chongqing University of Medical Sciences,Introduction,一种或几种病因长期或反复作用引起的慢性进行性肝病的后期阶段。(Its the end result of hepatocellular injury resulted from different causes, ERLD ) 病理有广泛肝细胞变性坏死、肝细胞结节性再生、结缔组织增生及纤维化，正常肝小叶结构破坏和假小叶形成、肝逐渐变形、变硬。The histologic feature is degeneration, regeneration(nodular) and fibrosis. According to the following sequence: INJURY DEGENERATION and necrosis regeneration FIBROSIS FORMATION OF FIBRO-VASCULAR MEMBRANES PARENCHYMAL DISSECTION INTO NODULES REARRANGEMENT OF BLOOD CIRCULATION CIRRHOSIS REARRANGEMENT OF BLOOD CIRCULATION CIRRHOSIS,Introduction,临床肝功能损害和门脉高压为主、晚期常出现消化道出血、肝性脑病等并发症。(The clinical manifestations can be broadly classified into those resulting from hepatocellular dysfunction, such as jaundice and coagulopathy and portal hypertension. The complication often appear in late phase, such as hemmorrage, hepatic encephalopathy. 世界性疾病，所有种族、不论国籍、年龄或性别、均可罹患。 年龄3548岁最多，男：女为368：1。,Cirrhosis is the third most common cause of death, after heart disease and cancer. killing about 25,000 people each year.,Introduction,HISTORY,In 1761, This peculiar transformation of the liver was identified by the first anatomic pathologist, Gianbattista Morgagni in his 500 autopsies.,HISTORY,In 1826 (65years latter), the name of cirrhosis was given by Laennec because of the yellowish-tan color of the cirrhotic liver. “cirrhosis“ (greek=orange color).,HISTORY,Only in 1930, one hundred years later, the first theory as to the pathogenesis of this disorder was advanced by Roessle: parenchymal degeneration, regeneration and scarring which is now understood according to the following sequence:,HISTORY,INJURY DEGENERATION FIBROSIS FORMATION OF FIBRO-VASCULAR MEMBRANES PARENCHYMAL DISSECTION INTO NODULES REARRANGEMENT OF BLOOD CIRCULATION CIRRHOSIS REARRANGEMENT OF BLOOD CIRCULATION CIRRHOSIS,其他病因 寄生虫感染 血吸虫、华枝睾吸虫 胆汁淤积 肝内淤胆或肝外胆管梗阻 循环障碍 慢性充血性心力衰竭、缩窄性心包炎 肝静脉和（或）下腔静脉梗阻 工业毒物 四氰化碳、磷、砷、双醋酚丁、四环素 代谢障碍 血色病（铁质沉积）、肝豆状核变性（铜沉积） 营养障碍 慢性炎症性肠病、食物中缺乏蛋白质、维生素、抗脂肝物质 原因不明,病因,ETIOLOGY (CAUSES),ETIOLOGY,2.Alcohol abuse 14 3. Bile duct obstruction (PBC, PSC) 4. Exposure to certain chemicals Use of certain drugs (CCI4) 13 5.Persistent obstruction to outflow of blood from the liver (such as occurs in the Budd-Chiari syndrome) Heart and blood vessel disturbances,ETIOLOGY,6. Hereditary disease, High blood tyrosine levels at birth (congenital tyrosinosis) Glycogen storage disease , Alpha1-antitrypsin deficiency Hereditary accumulation of too much copper (Wilsons disease) 7. Autoimmune diseases (including autoimmune chronic hepatitis) 12 8. Schistosoma hematobium,CAUSES,Iron overload (hemochromatosis) 9. Unknown ( NASH, Cryptogenic),发病机制 Stellate cell, extracellular matrix,PATHOLOGY,Classification of cirrhosis According to World Health Organization (Anthony P.P. et al. J.Clin.Pathol. 31:395,1978) MORPHOLOGIC: Macronodular Micronodular Mixe HISTOLOGIC: Portal, Post-necrotic, Post Hepatitic, Biliary, Congestive ETIOLOGIC AGENTS: Genetic, Toxic, Infectious, Biliary, Vascular, Cryptogenic,MACRONODULAR CIRRHOSIS: Larger nodules separated by wider scars and irregularly distributed throughout the liver usually due to an infectious agent such as viral hepatitis which does not diffuse uniformly throughout the liver.,DISSECTION NODULES: contain remnants of portal tracts an central veins. are separated by wide scars but contain thin fibrous septa. contain dilated sinusoids especially at their periphery looking like multiple central veins obviously produced by the inflow of arterial blood coming from the surrounding wide scars. the portal tracts within large nodules may be hypoplastic containing portal venule and arteriole but no bile ducts giving the impression of a disappearing bile duct disorder. within wide scars regenerative nodules may develop.,REGENERATIVE NODULES: these occur in micro and macro nodular cirrhosis. they arise in the midst of scars favored by the rich arterial blood of scar tissue. they are round nodules with a fibrous pseudo capsule with bile ductules due to obstruction of bile flow. they have embryonal type of cell plates. they often show focal cholestasis. they may undergo dysplastic and malignant changes. they compress the vessels of the capsule contributing to the perpetuation of the cirrhosis.,大体形态 肝逐渐变形、变硬变小、包膜增厚、结节出现而致肝硬化。,病理,组织学改变 假小叶形成,1小结节性 结节的直径3-5mm, 1cm，大小均匀，纤维间隔较窄，结节中可有门脉管道。常见于酒精性肝硬化。,病理分型,2大结节性 结节直径大小不等1-3cm，大者直径可达5cm，结节由纤维隔分开，其中可含正常肝小叶。多见于肝炎后肝硬化。,病理,3混合性 大小结节均有，兼有大、小结节两型的病理特点，临床上绝大多数肝硬化均为此型。,病理,4不完全分隔型 肝小叶由纤维围成结节，纤维间隔可向小叶延伸，但分隔小叶不完全，再生结节不明显。Schistosoma Japonica Schistosomiasis: egg implanted in portal venules lead to periportal fibrosis and granuloma, not cirrhosis,病理,全身改变 脾 胃 肺,临床表现clinical presentation,代偿期 症状较轻，缺乏特异性。可有乏力、纳差、恶心、上腹不适、腹胀、腹泻等，查体见一般情况较好，肝脏轻度肿大，质地结实或偏硬。脾脏轻度或中度肿大。肝功能正常或轻度异常。,SYMPTOMS,About one third of cirrhosis are compensated and, do not produce any clinical sign and symptoms and are accidentally discovered during a medical examination or an operation or at autopsy (Asymptomatic). The rest are decompensated and produce complications mainly due to liver failure and portal hypertension.,The two major problems that eventually cause symptoms are loss of functioning liver cells and distortion of the liver caused by scarring. General Fatigue, Malaise Weakness Weight loss Poor appetite, anorexia Nausea Fever,临床表现,失代偿期decompensated 一、肝功能损害表现： loss of functioning liver cells 1.全身症状：消瘦、乏力及低热等。 2.消化道症状：纳差、恶心、腹胀Abdominal fullness, gaseous及腹泻。 Jaundice 3.出血倾向A tendency to bleed (coagulopathy)及贫血：鼻、牙龈、皮肤、胃肠出血等，不同程度的贫血。 Nosebleed, bleeding gums , Decreased number of red blood cells (anemia) ,Gastrointestinal bleeding from varices,4.内分泌系统失调： 蜘蛛痣、肝掌、皮肤颜面色素沉着、男性乳房发育、睾丸萎缩及女性月经失调。,Skin Spiderlike blood vessels (Spider angioma ) Red palms (palmar erythema ) Florid complexion Itching Other Urine output, decreased Swelling, overall,Hormones,High levels of insulin but poor response to it Cessation of menstrual periods and decreased fertility (in women) Impotence and feminization (in men),This very large spider nevus with its central arteriole developed in a patient with hepatic cirrhosis. Spider nevi develop through deficient estrogen metabolism, and a few can be seen in pregnancy or in patients taking the oral contraceptive. They occur in the distribution of the drainage of the superior vena cava and are therefore seen on the face, arms and upper trunk. Spider nevi will disappear following hepatic function improving.,Here multiple vascular spiders have coalesced to form a network on the anterior chest wall. This appearance has been termed paper money skin. Vascular spiders and palmar erythema are traditionally attributed to estrogen excess. It is not clear why these tend to occur in the upper half of the body (the distribution of the superior vena cava).,Gynaecomastia in alcoholic liver disease. This male patient with alcoholic liver disease has gynaecomastia. Males with liver dysfunction have features of feminization with raised serum estrogen levels and reductions in testosterone levels, while estrogen receptors in tissue increase in number. Gynaecomastia is especially common in alcoholic liver disease, probably because alcohol increases the hepatic metabolism of testosterone. Spironolactone (an aldosterone antagonist) is also associated with gynaecomastia, especially in patients with chronic liver disease.,临床表现失代偿期 二、门脉高压 （Portal Hypertension）,portal hypertension,Normally, blood from the intestines and spleen is carried to the liver through the portal vein. But cirrhosis slows the normal flow of blood through the portal vein, which increases the pressure inside it. This condition is called portal hypertension.,1. Splenomegaly,This splenomegaly is congestive One of the most common findings with portal hypertension is splenomegaly, as seen here. The spleen is enlarged from the normal 300 grams or less to between 500 and 1000 gm.,1. Splenomegaly,Hypersplenism Blood Decreased number of red blood cells (anemia) Decreased number of white blood cells (leukopenia) Decreased number of platelets (thrombocytopenia) A tendency to bleed (coagulopathy),食管静脉曲张 （Oesophageal Varices ） 腹壁静脉曲张 痔静脉曲张rectal hemorroid,临床表现 失代偿期 二、门脉高压 2.侧枝循环建立 Collateral shunting,The enlarged blood vessels, called varices, have thin walls and carry high pressure, and thus are more likely to burst. If they do burst, the result is a serious bleeding problem in the upper stomach or esophagus that requires immediate medical attention.,Oesophageal varices. Normal oesophageal mucosa shows long, thin, evenly spaced lines. Varices show as filling defects in the regular contour of the oesophagus, with the “corkscrew sign“ (arrow), most often in the lower third but the entire oesophagus may be involved. Hepatic cirrhosis is the commonest cause of portal hypertension. Blood from gastro-oesophageal collaterals reaches the superior vena cava system. Hypertension in the gastro-oesophageal venous vessels lead to gastro-oesophageal varices. Haemorrhages following varices rupture may be a slow ooze with melena or a sudden haematemesis. The mortality of bleeding varices is about 40% with each episode.,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.,B. Distention of Abdominal wall vein,C. Rectal hemorrhiod,二、门脉高压 3.腹水(Ascitis)形成原因： A.门脉压力高10mmHg B.低蛋白血症 plasma colloid osmotic pressure decrease C.肝淋巴循环障碍Increased hepatic lymph(5 more) D. Arteriolar visodilatation:This stimulate reninangiotetion and antidureitc hormone,Ascites and umbilical hernia. This patient with alcoholic cirrhosis presented with massive abdominal distension due to ascites. Other noteworthy features here include the umbilical hernia with a bluish tinge (almost certainly due to porto-systemic collateral circulation) and profound muscle-wasting.,二、门脉高压,4.门脉高压胃肠病 5.胸水 hepatic hydrothorax 6.肝肺综合征：hepatopulmonary syndrome无肺部疾病、肺内血管短路、肺内血管扩张,低氧血症/肺泡-动脉氧梯度增加三联症.,Sumarry for portal hypertetion,Portal hypertention: sac Collateral shunting or collateral circulation: ear,Complications,Bleeding esophageal varices(Variceal bleeding) Hepatic encephalopathy Abdominal fluid retention (ascites) and infection of the fluid (bacterial peritonitis) Liver cancer (hepatocellular carcinoma) Kidney failure (hepatorenal syndrome) Dilutional hyponatremia,varices have thin walls and carry high pressure, and thus are more likely to burst. If they do burst, the result is a serious bleeding problem in the upper stomach or esophagus that requires immediate medical attention.,Symptoms,vomiting vomiting blood black, tarry stools decreased urine output symptoms of cirrhosis paleness lightheadedness,肝性脑病Hepatic encephalopathy The liver of a person with cirrhosis also has trouble removing toxins, which may build up in the blood. These toxins can dull mental function and lead to personality changes and even coma Early signs of toxin accumulation in the brain may include neglect of personal appearance, unresponsiveness, forgetfulness, trouble concentrating, or changes in sleeping habits.,Hepatorenal syndrome occurs when there is a decrease in kidney function in a person with a liver disorder. This is often exhibited by: Absent or low urine production, less than 400 cc/day Very low urine sodium concentration Low serum sodium Fluid retention in the abdomen or extremities Increased BUN (Azotemia) and creatinine levels,实验室及特殊检查,一、实验室检查(Lab Test) 1血常规 贫血、脾亢时白细胞和血小板减少。 2尿常现 胆红素、蛋白、管型。 3肝功能 失代偿期 liver function test 血清胆红素 凝血酶原时间、 the time needed for blood to clot. 白蛋白及白球比例 转氨酶 染料排泄功能 如靛青绿（ICG）滞留。 前胶原III肽（ PIIIP ）,一、实验室检查,4免疫功能检查 （l）细胞免疫 半数以上T淋巴细胞低于正常，CD3、CD4和CD8细胞均有降低。 （2）体液免疫 免疫球蛋白 IgG、IgA、IgM 增高。 （3）非特异性自身抗体 如抗核抗体、抗平滑肌抗体、抗线粒伴抗体等出现。 （4）病因为病毒性肝炎者，乙型、丙型或乙型加丁型肝炎病毒标记呈阳性反应。,一、实验室检查 5腹水检查,The serum ascites albumin gradient (SAAG), calculated by subtracting the ascites albumin concentration from the serum value, is the most accurate method of classifying ascites. An SAAG value of greater than 1.1 g/dL predicts a portal hypertensive cause with more than 95% accuracy. Values less than 1.1 g/dL are associated with neoplasms, tuberculosis, pancreatitis, or bile leak; the ascitic fluid should be tested, as indicated, for amylase, cytology, and mycobacterial culture.,腹水检查,If the absolute polymorphonuclear (PMN) count is greater than 250/mm3 (percent PMN times total white blood count WBC), a presumptive SBP diagnosis should be made, and empirical antibiotic therapy (e.g., cefotaxime, 1 to 2 g intravenously every 6 to 8 hours, or ceftriaxone, 500 to 1000 mg intravenously every 12 hours) should be given for 5 to 7 days.,二、特殊检查(Special test),US,钡餐,CT,Cryptogenic cirrhosis. Spiral CT in an elderly male patient with progressive abdominal distension. The liver is small and a large volume of ascites is present. However, contact is maintained between the posterior surface of the liver and the diaphragm (arrows), the bare area since this region is not peritonealized.,A CT scan of the upper abdomen showing an widespread (disseminated) carcinoma of the liver (hepatocellular carcinoma). The liver is the large organ on the left side of the picture. Note the moth-eaten appearance.,胃静脉曲张,内镜,食管静脉曲张,a b 食管静脉曲张红色征（CR） a ：食管曲张静脉表面CR+: 表现为樱桃红点 b：食管曲张静脉表面CR+：表现为蚯蚓状扩张的红色血管。,门脉高压胃病(gastripathy in portal hypertension),内镜,a b,门脉高压性大肠病,内镜,超声内镜(Endoscopic ultrasound),超声内镜,腹腔镜(celioscope),肝穿刺,诊断,病史 肝功能损害 门脉高压 肝脏改变 化验或特殊检查 病理特点,鉴别诊断,伴肝大的其他疾病 伴脾大的其他疾病 伴腹水的其他疾病 与肝硬化并发症相似的其他疾病,Child-pugh分级 项目 1 2 3 肝性脑病（期） 无 1-2 3-4 腹水 无 易消退 难消退 胆红素（mol/L） 51 白蛋白（gL） 35 28-35 28 凝血酶原时间（秒) 14 15-17 18 注：根据5项的总分判断分级，A级 6 分，B级7-9分，C级10分。,Child Pugh Classification,治疗 MANAGEMENT,Treatment,Liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications. Treatment depends on the cause of cirrhosis and any complications a person is experiencing.,Cirrhosis caused by alcohol abuse is treated by abstaining from alcohol. Treatment for hepatitis-related cirrhosis involves medications used to treat the different types of hepatitis, such as interferon for viral hepatitis corticosteroids for autoimmune hepatitis. In all cases, regardless of the cause, following a healthy diet and avoiding alcohol are essential because the body needs all the nutrients it can get, and alcohol will only lead to more liver damage.,Dietary changes that may be helpful: people with liver cirrhosis may be unable to tolerate normal amounts of dietary protein because the cirrhotic liver is less able to detoxify ammonia, a major product of protein digestion.,Lifestyle changes that may be helpful: Avoidance of alcohol is strongly recommended for people with liver cirrhosis. Alcohol is directly toxic to the liver. In people with alcohol-ind