PATH.ANATOMY PPT

Definition
Cirrhosis, which can be the final stage of any chronic liver disease, is a diffuse process characterized by fibrosis and conversion of normal architecture to structurally abnormal nodules.
These “regenerative” nodules lack normal lobular organization and are surrounded by fibrous tissue. The process involves the whole liver and generally is considered irreversible.

MAIN FACTORS CAUSING CIRRHOSIS
Chronic hepatitis C
Alcoholic liver disease
Nonalcoholic fatty liver disease
Chronic hepatitis B
Metabolic disorders
Hemochromatosis
Wilson disease
α1-Antitrypsin deficiency
Glycogen storage diseases
Abetalipoproteinemia
Porphyria
Hepatic venous outflow obstruction
Budd-Chiari syndrome
Veno-occlusive disease
Right-sided heart failure
Drugs and toxins
Intestinal bypass
Indian childhood cirrhosis
OTHER CAUSES OF CIRRHOSIS
(<2% OF ALL CASES)
Cholestatic and autoimmune liver diseases
Primary biliary cirrhosis
Primary sclerosing cholangitis
Autoimmune hepatitis
Intrahepatic or extrahepatic biliary obstruction
Mechanical obstruction
Biliary atresia
Cystic fibrosis
CAUSES OF CIRRHOSIS

PATHOBIOLOGY & PATHOGENESIS
Liver Fibrosis and Cirrhosis

1. The key pathogenic feature underlying liver fibrosis and cirrhosis is activation of hepatic stellate cells.
2. Hepatic stellate cells, which are known as Ito cells or perisinusoidal cells, are located in the space of Disse between hepatocytes and sinusoidal endothelial cells. (vitamin A storage).
3. In response to injury, hepatic stellate cells become activated, as a result of which they lose their vitamin A deposits, proliferate, develop a prominent rough endoplasmic reticulum, and secrete extracellular matrix (collagen types I and III, sulphated proteoglycans, and glycoproteins).
4. They become contractile hepatic myofibroblasts.

5. Liver cells undergo necrosis, the hepatic lobules collapse and this leads to the formation of diffuse fibrous septa.
6. As a compensatory mechanism nodular regeneration of hepatocytes occurs.
7. When the necrosis is associated with collapse of the reticulin framework cirrhosis results.
If the reticulin framework is not collapsed but preserved, hepatocytes regrow and reproduce the normal histological pattern.
Damage to the reticulin framework results in the formation of abnormal nodules which derive nourishment from the hepatic artery, but without portal and biliary connections.
The nodules vary in size from a few millimeters to several centimeters.

10. The liver surface becomes nodular.
11. Hepatic vascular bed is distorted, truncated and obstructed, the obstruction being maximal at the level of sinusoids.
Causes several vascular abnormalities ,they are;
a. Generalized arterialisation of the liver.
b. Formation of shunts between the branches of the hepatic artery, portal vein and hepatic vein.
c. Formation of arteriovenous shunts also in the pulmonary circulation.
d. Development of a hyperdynamic circulatory state with increased cardiac output and reduced peripheral vascular resistance.

12. Obstruction to portal venous flow results in the development of portal hypertension.
13. As the nodules grow, their centers are rendered ischemic. Once the disease process is initiated, other factors such as autoimmunity,
continuing necrosis, and chronic effect of toxins lead to the progression of the pathological lesions.
14. Basement membrane forms in the Disse’s space and this interferes with the metabolic functions of the liver.
15. The necrotic foci stimulate the proliferation of fibroblasts and collagen and fibrous septae develop in the portal zones and hepatic lobules.

Hepatic
sinusoid
Hepatic
sinusoid
Spleen
Spleen
Liver
Liver
Portal
vein
Portal
vein
Porto-systemic
collaterals

Morphological Classification
The morphological types are:
a. micronodular,
b. macronodular, and
c. mixed.

In this stage, cirrhosis is mostly asymptomatic and is diagnosed either during the evaluation of chronic liver disease or fortuitously during routine physical examination, biochemical testing, imaging for other reasons, endoscopy showing gastroesophageal varices, or abdominal surgery in which a nodular liver is detected. Nonspecific fatigue, decreased libido, or sleep disturbances may be the only complaints.
Compensated Cirrhosis

At this stage, there are signs of decompensation: ascites, variceal hemorrhage, jaundice, hepatic encephalopathy, or any combination of these findings.
Ascites, which is the most frequent sign of decompensation, is present in 80% of patients with decompensated cirrhosis
Decompensated Cirrhosis

C/C Liver
Cirrhosis
Compensated
Cirrhosis
Decompensated
Cirrhosis
Death
Complications develops
H.C.C

Early stages of the disease are asymptomatic.
Vague illhealth,
anorexia,
loss of weight,
loss of libido,
impotence,
abdominal distention,
dependent edema
Night blindness (impairment of metabolism of vitamin A).
Ascites
CLINICAL FEATURES

In the compensated phase, liver synthetic function is mostly normal, and portal pressure, although increased, is below the threshold level required for the development of varices or ascites.
As the disease progresses, portal pressure increases and liver function worsens, thereby resulting in the development of ascites, portal hypertensive gastrointestinal bleeding, encephalopathy, and jaundice.
The development of any of these clinically detectable complications marks the transition from a compensated to a decompensated phase. Progression to death may be accelerated by the development of other complications, such as recurrent gastrointestinal bleeding, renal impairment (refractory ascites, hepatorenal syndrome), hepatopulmonary syndrome, and sepsis (spontaneous
bacterial peritonitis). The development of hepatocellular carcinoma may accelerate the course of the disease at any stage

Variceal Hemorrhage
Ascites and Hyponatremia
Spontaneous Bacterial Peritonitis
Hepatic Encephalopathy
Pulmonary Complications
Complications