620 likes | 811 Views
Hepatic Cirrhosis (肝硬化). Yu Baoping. Introduction. CIRRHOSIS Term was 1st coined by Laennec in 1826 Many definitions but common theme is injury, repair, regeneration and scarring NOT a localized process; involves entire liver Primary histologic features: Marked fibrosis
E N D
Hepatic Cirrhosis(肝硬化) Yu Baoping
Introduction CIRRHOSIS • Term was 1st coined by Laennec in 1826 • Many definitions but common theme is injury, repair, regeneration and scarring • NOT a localized process; involves entire liver • Primary histologic features: • Marked fibrosis • Destruction of vascular & biliary elements • Regeneration • Nodule formation
Definition • Cirrhosis is a pathological diagnosis. It is characterized by widespread fibrosis with nodular regeneration. Its presence implies previous or continuing hepatic cell damage
Alcohol (>70%) Chronic infections hepatitis C, B, B+D brucellosis, syphilis Chr. biliary obstruction PBC, PSC, stricture, stones, cystic fibrosis, cong.b. atresia,~cysts Autoimmune Cardiovascular heart failure, pericarditis, Budd-Chiary-sy Metabolic/genetic errors Fe, Cu, α1-AT, lipids, Drugs and chemicals NASH Cryptogenic Combined Etiologic classification of cirrhosis
Pathogenesis: • Diffuse liver injury leading to necrosis. • (Alcohol, virus, drugs, toxins, genetic etc.) • Chronic inflammation & healing (hepatitis). • Bridging fibrosis – loss of architecture. • Regeneration nodules. • Obstruction to blood flow & shunts. • Portal hypertension spleen, varices • Liver failure – Debilitation, Jaundice, Ascitis, edema, bleeding, jaundice. • Hormone imbalance – spider nevi, testes atrophy etc..
Classification of Cirrhosis • WHO divided cirrhosis into 3 categories based on morphological characteristics of the hepatic nodules • Micronodular • Macronodular • Mixed
Micronodular Cirrhosis • Nodules are <3 mm in diameter • Relatively uniform in size • Distributed throughout the liver • Rarely contain portal tracts or efferent veins • Liver is of uniform size or mildly enlarged • Reflect relatively early disease
Macronodular & Mixed Cirrhosis • Nodules are >3 mm in diameter and vary considerably in size • Usually contain portal tracts and efferent veins • Liver is usually normal or reduced in size • Mixed pattern if both type of nodules are present in equal proportions
Cirrhosis Fibrosis Regenerating Nodule
Pathology (others) • gastrointestinal tract varicose veins,hemorrhage,congestion • Kidney glomerulonephritis • Endocrine muscular atrophy,degeneration(testis, ovary, thyroid,adrenal cortex)
Cirrhosis: Pathophysiology • Primary event is injury to hepatocellular elements • Triggering inflammatory response with cytokine release-toxic substances • Destruction of hepatocytes, bile duct cells, vascular endothelial cells • Repair thru cellular proliferation and regeneration • Formation of fibrous scar
Cirrhosis: Pathophysiology • Stellate cell is activated in response to injury and lead to expression of fibril-forming collagen • Above process is also influenced by Kupffer cells which activate stellate cells by eliciting production of cytokines • Sinusoidal fenestrations are obliterated because of collagen
Cirrhosis: Pathophysiology • Prevents normal flow of nutrients to hepatocytes and increases vascular resistance • Initially, fibrosis may be reversible if inciting events are removed • With sustained injury, process of fibrosis becomes irreversible and leads to cirrhosis
Pathophysiology Protal hypertension Ascites endocrine respiratory systemhepatic hydrothorax hepatopulmonary syndrome the urinary system : hepatorenal syndrom, HRS hematological system nervous system : HE
Portal Hypertension (PH) • Portal vein pressure above the normal range of 5 to 8 mm Hg • Portal vein - Hepatic vein pressure gradient greater than 5 mm Hg (>12 clinically significant) • Represents an increase of the hydrostatic pressure within the portal vein or its tributaries
Pathophysiology of PH • Cirrhosis results in scarring (perisinusoidal deposition of collagen) • Scarring narrows and compresses hepatic sinusoids (fibrosis) • Portal vein thrombosis, or hepatic venous obstruction also cause PH by increasing the resistance to portal blood flow • Progressive increase in resistance to portal venous blood flow results in PH
Pathophysiology of PH • As pressure increases, blood flow decreases and the pressure in the portal system is transmitted to its branches • Results in dilation of venous tributaries • Increased blood flow through collaterals and subsequently increased venous return cause an increase in cardiac output and total blood volume and a decrease in systemic vascular resistance • With progression of disease, blood pressure usually falls
Portal Vein Collaterals • Coronary vein and short gastric veins -> veins of the lesser curve of the stomach and the esophagus, leading to the formation of varices • Inferior mesenteric vein -> rectal branches which, when distended, form hemorrhoids • Umbilical vein ->epigastric venous system around the umbilicus (caput medusae) • Retroperitoneal collaterals ->gastrointestinal veins through the bare areas of the liver
Ascites • Sodium and water retention occur due to renin-angiotensin release secondary to arterial vasodilatation, caused by vasoactive substances such as nitric oxide • Portal hypertension per se causes fluid to accumulate in the peritoneal cavity due to increased hydrostatic pressure, hence further reduces intravascular volume and stimulates sodium and water retention via aldosterone. • Low albumin in plasma
Clinical presentation • There may be no abnormal clinical or biochemical features of liver disease in initial times • Features of hepatocellular failure, portal hypertension, or both may appear in advanced times.
Fatique, weakness Nausea, vomiting and loss of appetite Weight loss, muscle wasting Jaundice, dark urine Spider naevi, caput Medusae Bloody, black stools or unusually light-colored stools Vomiting of blood Abdominal swelling Swollen feet or legs Liver palms Gynecomastia Loss of sex drive Menstrual changes in women Generalized itching Sleep disturbances, confusion,desorientation,tremor, asterixis Symptoms of advanced cirrhosis
Clinical Features • Hepatocellular failure. • Malnutrition, low albumin & clotting factors, bleeding. • Hepatic encephalopathy. • Portal hypertension. • Ascites, Porta systemic shunts, varices, splenomegaly.
Visible signs of advanced liver cirrhosis Gynecomastia Ascites Caput Medusae Umbilical hernia
Complications • Upper gastrointestinal hemorrhage • Hepatic encephalopathy • Infection • Hepatorenal syndrome • Hepatopulmonary Syndrome • Primary carcinoma of the liver • Disturbance of electrolyte and acid-base balance
laboratory tests and investigations • Blood-RT anaemia;hypersplenia:WBC ,Plt • Urine-RTurine bilirubin,urobilinogen;sometimes albumen,haematuria • Stool-RT melena
laboratory tests and investigations liver function tests • Compensation normal or abnormal slightly • Decompensation transaminase : ALT AST cholesterol albumin and globulin prothrombin time bilirubin PⅢP, and so on Quantitation- liver function testsIGG
laboratory tests and investigations • Biochemistry can be surprisingly normal but some abnormality will often be present with slightly raised transaminases and alkaline phosphatases. In severe cases, all live enzymes will be abnormal. Low sodium and albumin are also seen. • Coagulopathy is a very sensitive indicator of liver dysfunction and is reflected in the prolonged prothrombin time.
laboratory tests and investigations • immunologic function test AFP virus hepatitis markers antinuclear antibody, ANA non-specificity antismooth muscle antibody autoantibody anti-mitochondrial antibody
laboratory tests and investigations • Imaging examination Barium meal CT or MRI Ultrasound demonstrates fatty change, size, and fibrosis as well as hepatocellular carcinoma
MRI Cirrhosis laboratory tests and investigations
laboratory tests and investigations Special test • Endoscope • Biopsy • Laparoscope • Hydroperitoneum test • Measure the Pressure of Portal Vein