Cirrhosis

Cirrhosis

Key features:The parenchymal injury & consequent fibrosis are diffuse.The nodularity is part of the diagnosis  reflects balance between regeneration and scarring.Vascular architecture is re-organized by the parenchymal damage and scarring  formation of abnormal interconnections

Pathogenesis: Progressive fibrosis & re-organization of vascular micro-architecture of liver
Collagen deposition (types I & III) in the lobule
Loss of fenestration of sinusoidal endothelial cells
New vascular channels in the septae
Create delicate or broad septal tracts
Impaired hepatocellular protein secretion (albumin, clotting factors, lipoproteins)
Shunting of blood around the parenchyma


Main characteristics Bridging fibrous septae link portal tracts with one another & portal tracts with terminal hepatic vein Parenchymal nodules contain proliferating hepatocytes encircled by fibrosis micronodules - < 3 mm diameter macronodules - > 3 mm to several cm Disruption of architecture of entire liver


Complications associated with cirrhosis:Hepatic failure ( called decompensation)Multiple coagulation defectsHypoalbuminemia due to decreased albumin synthesis  pitting edema and ascitesHepatic encephalopathyIncreased serum ammonia due to defective urea cycle

Complications associated with cirrhosis: Portal hypertension Ascites Congestive splenomegaly Esophageal varices Hemorrhoids, periumbilical collateral circulation

Cirrhosis

Complications associated with cirrhosis: Hepatorenal syndrome due to decreased renal blood flow Hyperestrinism in males Gynecomastia Spider angiomas Female distribution of hair


Criteria for Diagnosis: liver biopsy or at least three of the following:Hyperglobulinemia, esp. with hypoalbuminemiaLow protein (<2.5 g/dL) ascitesEvidence of hypersplenism (usu. Thrombocytopenia, often with leukopenia)Evidence of portal hypertension (e.g. varices)Characteristic “corkscrew” hepatic arterioles on celiac arteriographyShunting of blood

Bridging fibrous septae

Nodules

HEPATORENAL SYNDROME

HEPATOPULMONARY SYNDROME AND PORTOPULMONARY HYPERTENSION
Cirrhosis and portal hypertension are accompanied by alterations in the vascular beds of multiple organ systems. In the pulmonary circulation, two distinct clinical entities, termed the hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH), have been recognized. HPS is characterized by microvascular alterations and dilatation in the precapillary and capillary pulmonary arterial circulation. In human HPS, the production of vasodilatory substances within the pulmonary vasculature, most notably NO, is increased. Although increased circulating and pulmonary NO levels appear to be features of human HPS, improvement in oxygenation in response to acute inhibition of NO is variable. Classic clinical manifestations of HPS include platypnea (dyspnea worsened by an erect position and improved by a supine position), orthodeoxia (exacerbation of hypoxia and hypoxemia in an upright position), an insidious onset and slow progression of dyspnea, clubbing, and distal cyanosis.