Vascular Disorders of the Liver

• • • • • • • • • Vascular disorders of the liver Large flow of blood through the liver Dual blood supply → hepatic artery blood and portal vein blood from the GIT Sinusoids Outflow through hepatic vein and its branches Ischaemic injury usually requires more than one component to be compromised Impaired blood flow into the liver → portal vein and hepatic artery o Hepatic artery compromise o Portal vein obstruction and thrombosis o Cardiac failure shock Impaired blood flow through the liver → sinusoidal disease o Acute sinusoidal obstruction syndrome (Hepatic veno-occlusive disease) Hepatic venous outflow obstruction o Hepatic vein thrombosis (Budd Chiari syndrome) o IVC thrombosis o Passive venous congestion (cardiac failure) o Obliterative hepatic venopathy (many conditions) Cirrhosis Metabolic disorders and storage diseases • Some are genetically determined → storage disorders o Genetic defect may result in abnormal metabolic function within liver or outside of liver (secondarily affecting the liver) • Haemosiderosis – iron overload o Acquired e.g. due to ▪ Ineffective erythropoiesis with increased erythroid activity ▪ Parenteral iron overload – iron dextran, blood transfusion – Oral iron overload (African Bantu siderosis) o o o o ▪ Chronic liver disease esp. alcoholic liver disease Hereditary: genetically determined abnormality of iron receptor in GIT → haemochromatosis ▪ Liver macroscopic • Normal in early disease • Enlarge, chocolate brown, fibrotic or cirrhotic ▪ Microscopic • Iron seen in hepatocytes, Kupffer cells, bile duct epithelium (Perl stain) • Early – periportal with gradient to central vein • Later – Diffuse across acinus, associated fibrosis • Cirrhosis Excessive iron directly toxic by lipid peroxidation via iron-catalysed free radical reactions Interactions of reactive oxygen species and of iron with DNA → stimulation of collagen formation Is reversible in cells not fatally injured Cirrhosis • Diffuse process: conversion of normal liver architecture into nodules separated by fibrous septa • Anatomic definition with functional consequences resulting in symptoms, signs, lab + imagine abnormalities • End stage of many liver injuries • Only certain liver insults will result in cirrhosis i.e. chronic low level injury with gradual progression of fibrosis • Acute submassive necrosis resulting in death, transplantation, regen of normal liver or scarring with nodules • Not a fixed/permanent state: represents a balance of processes as cirrhosis can progress or regress • Pathogenesis: o Collagen deposition ▪ Portal tracts/periportal ▪ Sinusoidal o Arterialization of sinusoids o Obliteration of small portal vein branches and hepatic veins o Parenchymal extinction o Various additional vascular changes: congestion, thrombosis, shunt formation o Regeneration o Resorption of fibrous tissue • • • • • o Reversal Causes: o Viral hepatitis o Fatty liver disease: alcoholic, non-alcoholic o Autoimmune diseases: autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis o Other biliary disease e.g. biliary strictures o Metabolic diseases e.g. Haemochromatosis, Wilson’s disease, alpha-1antitrypsin deficiency o Drugs, toxins o Unknown: cryptogenic cirrhosis Presentation: o Insidious onset o May present only with the late effects o Laboratory results may be normal o Portal hypertension ▪ Bleeding from oesophageal varices ▪ Peritoneal fluid – ascites ▪ Splenomegaly o Liver synthetic failure Macroscopic: o Liver at most slightly enlarged but may be variably shrunken as cirrhosis progresses o Diffuse disease ▪ Generalised fibrosis ▪ Abnormal nodules • <3mm micronodular • >3mm macronodular • Large coarse nodules – post necrotic scarring • Large nodules, >10mm, bulging or pale - suspicious for malignancy Microscopic: o Nodules widely varying in size, composed of hepatocytes o Separated by fibrous tissue, variable amount ▪ Narrow bands (septa) connecting portal tracts to portal tracts, portal tracts to terminal hepatic veins, terminal hepatic veins to terminal hepatic veins ▪ Large areas of fibrous tissue with embedded nodules o Beginning of cirrhosis is not clear cut or sharply defined – the liver is not entirely transformed into nodules at a specific point in time Complications: o Liver failure – synthetic function, metabolic disturbance o Effects of portal hypertension – bleeding varices etc. o Portal vein thrombus o Malignancy – mostly hepatocellular carcinoma