1、HepaticCirrhosisDr.Liping TangDepartment of Gastroenterology,the first affiliated hospital of Chongqing University of Medical SciencesDiagnosisEtiologyComplicationsprognosis evaluationCirrhosis is a serious and irreversible disease and is the tenth leading cause of death in the USA,with an age-adjus
2、ted death rate of 9.2 per 100,000 per year.It is one of the most common non-neoplastic causes of death among hepatobiliary and digestive diseases in our country.SinusoidsPortal veinCentral veinHepatic arteryschistosomiasis)veno-occlusive disease)n schistosomiasis(血吸虫病)n idiopathic(先天性)portal fibrosi
3、sn drugs and toxins:e.g.alcohol,methotrexate(甲氨蝶呤),isoniazid(异烟肼)n infections:chronic hepatitis B or C,brucellosis(布鲁氏菌病)n autoimmunen vascular abnormalities:e.g.right-sided heart failuren metabolic/genetic diseases:e.g.Wilsons diseasen biliary obstructionn idiopathic(先天)/miscellaneous(各种各样的)n veno-
4、occlusive diseaseIn chronic HBV infection,the rate of progression to cirrhosis is influenced by the replicative activity of the virus and whether there has been superinfection by hepatitis delta virus(HDV).Concurrent liver injury from other causes(e.g.alcohol)may also hasten the onset of cirrhosis.a
5、lcohol ingestion gender hepatitis B or C infection genetic factors nutritional statusnPrimary biliary cirrhosisnSecondary(mechanical)biliary cirrhosisPrimary sclerosing cholangitisNeoplasm of bile ducts or pancreasIatrogenic（医源性）or inflammatory biliary stricturenCystic(胆囊的)fibrosisnBiliary atresia(闭
6、塞，不通)/neonatal(新生的)hepatitisnCongenital(先天的)biliary cysts(囊肿)Schistosomiasis(l metabolic/genetic disease:e.g.Wilsons disease(in which copper铜 build up in organ),hemochromatosis(A genetic disorder involving increased absorption of iron铁),porphyria(卟啉症),lipid(脂)disorders,amino acid disorderslChronic i
7、mmune hepatitisl many drugs and toxins:e.g.methotrexate(氨甲喋呤）,isoniazid(异烟肼),vitamin A,alpha-methyldopal cryptogenic(隐源性)cirrhosis:Indian childhood cirrhosis,polycystic(多囊)liver disease Normal liver Cirrhotic liver正常肝脏组织切片肝硬化组织切片Micronodular cirrhosisMacronodular cirrhosisMixed form cirrhosis Early
8、cirrhosis n In the early stage there may be no symptoms at all and the disease may be discovered as a result of an investigation for another illness.When disease progresses,the symptoms may develop:食管静脉曲张胃底静脉曲张腹水男性乳房发育肝掌l General symptoms:Fatigue or even exhaustionWeaknessWeight loss and muscle wast
9、ingFever Itching Abdominal painIncrease sensitivity to drugs Frequent infectionEdema l Digestive disorders:Nausea(恶心)Loss of appetite VomitingDiarrheaJaundicel bleeding and anemia(贫血)Bruising(撞伤)easilySkin bleedingBleeding from gums(齿龈)or noseGastrointestinal bleedinganemial Endocrine(hormone)disord
10、ers:Loss of sexual desire.In men:a fall in testosterone(睾丸激素)levels,reduced testicle(睾丸)size,gynaecomastia(男子女性乳房),impotence(阳萎).In women:menstrual(月经)irregularities,increased menstrual pain and menopausal(更年期)symptoms.Spider veins(蜘蛛痣)Palmar erythema(肝掌)Hyperpigmentation(色素沉着）Fluid retention蜘蛛痣色素沉着
11、及黄疸男性乳房发育l Splenomegaly（脾大）n Hepatic cirrhosis resulting in congestive splenomegaly is a cause of hypersplenism(脾亢）.It is a type of disorder which causes the spleen to rapidly and prematurely destroy blood cells.splenomegalyAnemia(贫血),leukopenia(白细胞减少),thrombocytopenia correction of the cytopenia by
12、 splenectomy(脾切除术).l Varices:1.gastroesophageal varices 2.Abdominal Vein varices3.Hemorrhoids（痔）vein varicesl Ascites:Occurring in advanced cirrhosis,the accumulation of fluid in the abdominal cavity,or ascites,is related to portal hypertension,significant reduction in serum albumin,and renal retent
13、ion of sodium.Pathogenesis of ascites:Ascites:Sinusoidal hypertensionHypoalbuminemia(低白蛋白血症)Fixed capacity to resorb ascitesIncreased sodium and water reabsorption by the Kidneys(due to humoral factors)Splanchnic(内脏)arteriolar vasodilation(血管舒张)increasing sympathetic tone（交感紧张）lA palpable,firm liver
14、 with a blunt（钝，硬）edge is typical,but at times the liver is small and difficult to palpate.lRegenerating nodules are only occasionally palpable.l Upper gastrointestinal tract bleeding l hepatic encephalopathy l infectionsl Hepatorenal syndromel Hepatopulmonary syndromel Hepatocellular carcinomal flu
15、id and electrolyte（电解质）disordersl Upper gastrointestinal tract bleeding may occur from gastroesophageal varices,portal hypertensive gastropathy,or gastroduodenal ulcer.Hemorrhage（出血）may be massive,resulting in fatal exsanguination or portosystemic encephalopathy.Cirrhosis can cause immune system dys
16、function,leading to infection:Spontaneous bacterial peritonitis(SBP),pneumonia,urinary infection or bile duct infection.nSpontaneous bacterial peritonitis(SBP)is an ominous（不详的）complication of late-stage liver disease,it is often heralded by Abdominal pain,increasing ascites,fever.nIt is believed to
17、 reflect altered gut wall permeability to bacteria,impaired capacity of hepatic and splenic macrophages to clear portal bacteremias,and/or the presence of a large volume of peritoneal fluid conductive to bacterial growth.l Hepatorenal syndromeHepatorenal syndrome,also known as functional renal failu
18、re,is defined as renal failure associated with severe liver disease without an intrinsic abnormality of the kidney.l Hepatorenal syndromeType 1 HRS is characterized by rapidly progressive kidney failure,with a doubling of serum creatinine to a level greater than 226 mol/L(2.5 mg/dL)or a halving of t
19、he creatinine clearance to less than 20 mL/min over a period of less than two weeks.The prognosis of individuals with type 1 HRS is particularly grim,with a mortality rate exceeding 50%after one month.Type 2 HRS is slower in onset and progression.It is defined by an increase in serum creatinine leve
20、l to 133 mol/L(1.5 mg/dL)or a creatinine clearance of less than 40 mL/min,and a urine sodium 10 mol/L。l Hepatopulmonary syndromeliver diseasepulmonary vascular dilation reduced arterial oxygenationl Hepatocellular carcinoma is an epithelial tumor arising from malignant transformation of the hepatocy
21、te.It is observed characteristically as a complication of cirrhosis.especially related to chronic viral infections(HBV or HCV).nIt presents as persisting abdominal pain,a palpable abdominal mass,and/or constitutional symptoms in patients with cirrhosis.nThe diagnosis must be considered in cirrhosis
22、with sudden decompensation or in those who develop bloody ascites.of Low ingestion of sodium for a long timeLoss sodium by diuretics(利尿剂)and paracentesis(放液)Elevated antidiuretic hormone to conserve body waterInadequate intake and vomiting or diarrheaRenal losses:drugs(diuretics),hyperaldosteronism(
23、高醛固酮血症)Hypokalemia may induce metabolic alkalosis or encephalopathyClotting or obstruction of blood flow along the veins from the intestines and spleen and into the liver.This causes blood to back up and results various problems such as enlarged spleen and abdominal pain.The obstruction can occur ac
24、utely(over a short space of time)or chronically(over a longer period of time)l Enlarged spleen l Enlarged abdomenl Abdominal painl Diarrhea l Nauseal Blood in stooll Vomitingl Portal hypertensionsymptomsa form of venous thrombosis affecting the hepatic portal vein,which can lead to portal hypertensi
25、on and reduction in the blood supply to the liver.Laboratory findingsl Laboratory findings and other examinationsAnemia,causes include suppression of erythropoiesis红细胞生成 by alcohol as well as folate deficiency,hemolysis溶血,hypersplenism,and insidious潜在的 or overt blood loss from the gastrointestinal t
26、ract.White blood cell count may be low,elevated,or normal,reflecting hypersplenism or infection.Thrombocytopenia(血小板减少症)may be secondary to alcoholic marrow suppression,sepsis,folate叶酸 deficiency,or splenic sequestration.l In patients with cirrhosis,bilirubin(胆红素)and urobilinogen(尿胆原)may be measured
27、 during a urine test when jaundice is present.sometimes,protein,casts or blood cell could be found.Modest elevations of AST,ALT,alkaline phosphatase(碱性磷酸酶)and progressive elevation of the bilirubin.Serum albumin(白蛋白)is low,gamma globulin is increased.Prolongation of the prothrombin time(凝血时间)may res
28、ult from failure of synthesis of clotting constituents by the liver.T cell count decreases in more than 50%of patients with cirrhosis,CD3,CD4 and CD8 cells are all reduced.Serum IgG and IgA levels are elevated,especially for IgG,coinciding with the increasing level of gamma globulin In some patients
29、,the antinuclear antibody could be detected in serum.In those patients whose pathogenie are HBV,HCV,or HDV superimposed on HBV,the viral detection may be positive.Barium(钡)studies of the upper gastrointestinal tract may reveal the presence of esophageal or gastric varices,though endoscopy(内窥镜)is mor
30、e sensitive.Ultrasound or CT is helpful for assessing liver or splenic size,detecting ascites or hepatic nodules,including small hepatocellular carcinomas.Together with Doppler studies,ultrasound is used to evaluate patency of the splenic,portal,and hepatic veins.Hepatic nodules may be characterized
31、 further by intravenous cntrast-enhanced spiral CT scan or MRI along with serum AFP levels.Endoscopic test demonstrates the presence of varices and detects specific causes of bleeding in the esophagus,stomach,and proximal duodenum.Liver biopsy remains to be the gold standard for documenting cirrhosi
32、s,identifying the cause,and assessing the extent of scar formation.In some centers,liver biopsy is performed by laparoscopy,which may be helpful in judging the type of cirrhosis.DiagnosisEtiologyComplicationsprognosis evaluationMeasure1 point2 points3 pointsunitsBilirubin(total)34(50(3)mol/l(mg/dL)S
33、erum albumin3528-3528mg/LINR（or PT prolongation)2.20(18)no unit(seconds)AscitesNoneSuppressed with medicationRefractoryno unitHepatic encephalopathyNoneGrade I-II(or suppressed with medication)Grade III-IV(or refractory)no unit82%C12-1530%B9-1110%A5-8Perioperative mortality and prognosisClassPointsp
34、oorbest/General measures:l l There are no drugs to reverse cirrhosis which have the especially good effect,vitamins or digestive enzyme may be prescribed.some chinese herbal（草药）medicine treatment may improve the liver function and symptoms.The goal of weight loss should be no more than 0.5-0.7 kg/da
35、yIn patients with massive ascites and respiratory(呼吸）compromise,ascites refractory（难控制）to diuretics,or intolerable diuretic side effects,large-volume paracentesis(4-6 L)is effective when this is done,it is often the practice to give intravenous(静脉内的)albumin concomitantly（伴随）at a dosage of 10g/L of a
36、scites fluid removed to protect the intravascular volume.l This technique is designed to provide one way flow of sterile(消毒)ascitic fluid from the abdomen to the vascular system.)Mechanical tamponade(压塞)with specially designed nasogastric tubes containing large gastric and esophageal balloons provid
37、es initial control of active variceal hemorrhage in 60-90%of patients.lPortal decompressive procedure TIPS:it can control acute hemorrhage in over 90%of patients actively bleeding from gastric or esophageal varices.Emergency portosystemic shunt surgery lSpontaneous bacterial peritonitis(Hepatorenal
38、syndrome is characterized by azotemia（氮质血症）（氮质血症）,oliguria（少尿）（少尿）,hyponatremia（低血钠）（低血钠）,low urinary sodium（低尿钠）（低尿钠）Complication of Hepatic Cirrhosis are _，_，_，_，_，_，_。How to explain the Hepatic Cirrhosis?What are the most common causes of cirrhosis in our country and in western country?What are t
39、he clinical manifestations of late cirrhosis?_，_，_，_.The clinical manifestations of Portal hypertension include _，_，_.What are the pathogenesis of ascites of cirrhosis?How to treat the cirrhosis patients with ascites or gastroesophageal varices bleeding?How to diagnose the hepatic cirrhosis correctly?
