1. 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

2. 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
Impaired hepatocellular protein secretion (albumin, clotting factors, lipoproteins)
Shunting of blood around the parenchyma
Create delicate or broad septal tracts

3. 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

4. Complications associated with cirrhosis:
Hepatic failure ( called decompensation)
Multiple coagulation defects
Hypoalbuminemia due to decreased albumin synthesis  pitting edema and ascites
Hepatic encephalopathy
Increased serum ammonia due to defective urea cycle

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

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

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

8. Bridging fibrous septae
Nodules

10. HEPATORENAL SYNDROME
HRS was found to be part of a cascade of events associated with intense dilatation of the splanchnic arterial vasculature in the setting of cirrhosis or acute liver injury and resulting in profound renal arterial vasoconstriction and progressive renal failure.
The diagnostic criteria for HRS( type 2 HRS usually) :(1) cirrhosis with ascites; (2) serum creatinine level higher than 1.5 mg/dL (133 mmol/L); (3) lack of improvement in the serum creatinine level to 1.5 mg/dL (133 mmol/L) or less after at least two days of diuretic withdrawal and volume expansion with albumin (1 g/kg of body weight/day, up to a maximum of 100 g/day); (4) absence of shock, (5) lack of current or recent treatment with nephrotoxic drugs; and (6) absence of parenchymal kidney disease as indicated by proteinuria of more than 500 mg/day, microhematuria (>50 red blood cells/high power field), or abnormal renal ultrasonographic findings .
Acute hepatorenal syndrome ( type 1 HRS) can occur in severe acute liver disease and acute liver failure even without ascites.

11. 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.