Bannu Jayallan

0710714004

LIVER CIRRHOSIS

Definition Cirrhosis is a complication of many liver diseases that is characterized by abnormal structure and function of the liver. The diseases that lead to cirrhosis do so because they injure and kill liver cells, and the inflammation and repair that is associated with the dying liver cells causes scar tissue to form. Many forms of liver injury are marked by fibrosis. Fibrosis is defined as an excess deposition of the components of extracellular matrix (ex; collagens, glycoproteins, proteoglycans) within the liver. The liver cells that do not die multiply in an attempt to replace the cells that have died. This results in clusters of newly-formed liver cells (regenerative nodules) within the scar tissue.

Etiology

Chronic viral hepatitis: the two important viruses are hepatitis B and hepatitis C. Alcohol excess: Half of all cases of cirrhosis are due to alcohol excess. Primary biliary cirrhosis: this is an uncommon disease mainly affecting women. For some reason the body mounts an attack on the liver in patients with primary biliary cirrhosis. Autoimmune chronic active hepatitis: another uncommon condition that results in the body's immune system attacking and destroying liver cells. Drugs and chemicals: a number of drugs and chemicals can cause liver damage but few cause cirrhosis. Metabolic and inherited disorders: These are a number of uncommon conditions that allow the accumulation of toxins in the liver. The commonest is haemochromatosis, which causes excess deposits of iron in the liver. Pathophysiology The development of hepatic fibrosis reflects an alteration in the normally balanced processes of extracellular matrix production and degradation. Extracellular matrix, the normal scaffolding for hepatocytes, is composed of collagens (especially types I, III, and V), glycoproteins, and proteoglycans. Stellate cells, located in the perisinusoidal space, are essential for the production of extracellular matrix. Stellate cells become activated into collagenforming cells by a variety of paracrine factors. Such factors may be released by hepatocytes, Kupffer cells, and sinusoidal endothelium following liver injury. As an example, increased levels of the cytokine transforming growth factor beta1 (TGF-beta1). TGF-beta1, in turn, stimulates activated stellate cells to produce type I collagen.

Bannu Jayallan

0710714004

Increased collagen deposition in the space of Disse (the space between hepatocytes and sinusoids) and the diminution of the size of endothelial fenestrae lead to the capillarization of sinusoids. Activated stellate cells also have contractile properties. Both capillarization and constriction of sinusoids by stellate cells contribute to the development of portal hypertension.

Symptoms Many people with cirrhosis have no symptoms in the early stages of the disease. However, as the disease progresses, the following symptoms may occur; weakness fatigue loss of appetite nausea vomiting weight loss abdominal pain and bloating when fluid accumulates in the abdomen itching spiderlike blood vessels on the skin

Complication 1) Portal hypertension Increased resistance across the sinusoidal vascular bed of the liver is caused by both fixed factors and dynamic factors. Two thirds of intrahepatic vascular resistance is explained by fixed changes in the hepatic architecture. Such changes include the formation of regenerating nodules and the production of collagen by activated stellate cells. Collagen, in turn, is deposited within the space of Disse. Dynamic factors account for one third of intrahepatic vascular resistance. Stellate cells serve as contractile cells for adjacent hepatic endothelial cells. The nitric oxide produced by the endothelial cells, in turn, controls the relative degree of vasodilation or vasoconstriction produced by the stellate cells. In cirrhosis, decreased local production of nitric oxide by endothelial cells permits stellate cell contraction, with resulting vasoconstriction of the hepatic sinusoid. (This contrasts with the peripheral circulation where there are high circulating levels of nitric oxide in cirrhosis.) Increased local levels of vasoconstricting chemicals, like endothelin, may also contribute to sinusoidal vasoconstriction.

2) Ascites Ascites is defined as an accumulation of excessive fluid within the peritoneal cavity and may be a complication of both hepatic and nonhepatic diseases.ascites was classified as being a transudate or an exudate.

Bannu Jayallan

0710714004

In transudative ascites, fluid was said to cross the liver capsule because of an imbalance in Starling forces. In general, ascites protein was less than 2.5 g/dL. Classic causes of transudative ascites are portal hypertension secondary to cirrhosis and congestive heart failure. Intrahepatic portal hypertension Cirrhosis, Fulminant hepatic failure Extrahepatic portal hypertension - Hepatic vein obstruction,Congestive heart failure Hypoalbuminemia - Nephrotic syndrome, Protein-losing enteropathy Malnutrition

In exudative ascites, fluid was said to weep from an inflamed or tumor-laden peritoneum. In general, ascites protein was greater than 2.5 g/dL. Examples included peritoneal carcinomatosis and tuberculous peritonitis. Malignant ascites - Primary peritoneal mesothelioma,Secondary peritoneal carcinomatosis Granulomatous peritonitis - Tuberculous peritonitis Fungal and parasitic infections (eg, Candida Histoplasma, Cryptococcus, Schistosoma mansoni) Vasculitis - Systemic lupus erythematosus, Henoch-Schnlein purpura

Attributing ascites to diseases of nonperitoneal or peritoneal origin is more useful. Serum-ascites albumin gradient (SAAG) has come into common clinical use for differentiating these conditions. Nonperitoneal diseases produce ascites with a SAAG greater than 1.1 g/dL. The formation of ascites in cirrhosis depends on the presence of unfavorable Starling forces within the hepatic sinusoid and on some degree of renal dysfunction. Patients with cirrhosis are observed to have increased hepatic lymphatic flow. Fluid and plasma proteins diffuse freely across the highly permeable sinusoidal endothelium into the space of Disse. Fluid in the space of Disse, in turn, enters the lymphatic channels that run within the portal and central venous areas of the liver. Because the transsinusoidal oncotic gradient is approximately zero, the increased sinusoidal pressure that develops in portal hypertension increases the amount of fluid entering the space of Disse. When the increased hepatic lymph production observed in portal hypertension exceeds the ability of the cisterna chyli and thoracic duct to clear the lymph, fluid crosses into the liver interstitium. Fluid may then extravasate across the liver capsule into the peritoneal cavity.

3) Esophageal varices The scar tissue blocks the flow of blood returning to the heart from the intestines and raises the pressure in the portal vein (portal hypertension). When pressure in the portal vein becomes high enough, it causes blood to flow around the liver through veins with lower

Bannu Jayallan

0710714004

pressure to reach the heart. The most common veins through which blood bypasses the liver are the veins lining the lower part of the esophagus and the upper part of the stomach.As a result of the increased flow of blood and the resulting increase in pressure, the veins in the lower esophagus and upper stomach expand and then are referred to as esophageal and gastric varices; the higher the portal pressure, the larger the varices and the more likely a patient is to bleed from the varices into the esophagus or stomach. Bleeding from varices usually is severe and, without immediate treatment, can be fatal. Symptoms of bleeding from varices include vomiting blood (thevomitus can be red blood mixed with clots or "coffee grounds" in appearance, the latter due to the effect of acid on the blood), passing stool that is black and tarry due to changes in the blood as it passes through the intestine (melena), and orthostatic dizziness or fainting (caused by a drop in blood pressure especially when standing up from a lying position).

4) Spontaneous bacterial peritonitis (SBP) Fluid in the abdominal cavity (ascites) is the perfect place for bacteria to grow. Normally, the abdominal cavity contains a very small amount of fluid that is able to resist infection well, and bacteria that enter the abdomen (usually from the intestine) are killed or find their way into the portal vein and to the liver where they are killed. In cirrhosis, the fluid that collects in the abdomen is unable to resist infection normally. In addition, more bacteria find their way from the intestine into the ascites. Therefore, infection within the abdomen and the ascites, referred to as spontaneous bacterial peritonitis or SBP, is likely to occur. SBP is a life- threatening complication. Some patients with SBP have no symptoms, while others have fever, chills,abdominal pain and tenderness, diarrhea, and worsening ascites.

5) Hepatic encephalopathy Some of the protein in food that escapes digestion and absorption is used by bacteria that are normally present in the intestine. While using the protein for their own purposes, the bacteria make substances that they release into the intestine. These substances then can be absorbed into the body. Some of these substances, for example, ammonia, can have toxic effects on the brain. Ordinarily, these toxic substances are carried from the intestine in the portal vein to the liver where they are removed from the blood and detoxified. When cirrhosis is present, liver cells cannot function normally .The result of these abnormalities is that toxic substances cannot be removed by the liver cells, and, instead, the toxic substances accumulate in the blood. When the toxic substances accumulate sufficiently in the blood, the function of the brain is impaired, a condition called hepatic encephalopathy. Sleeping during the day rather than at night (reversal of the normal sleep pattern) is among the earliest symptoms of hepatic encephalopathy. Other symptoms include irritability, inability to concentrate or perform calculations, loss of memory, confusion, or depressed levels of consciousness. Ultimately, severe hepatic encephalopathy causes coma and death.

Bannu Jayallan 6) Hypersplenism

0710714004

The spleen normally acts as a filter to remove older red blood cells, white blood cells, and platelets (small particles that are important for the clotting of blood.). The blood that drains from the spleen joins the blood in the portal vein from the intestines. As the pressure in the portal vein rises in cirrhosis, it increasingly blocks the flow of blood from the spleen. The blood "backs-up" and accumulates in the spleen, and the spleen swells in size, a condition referred to as splenomegaly. As the spleen enlarges, it filters out more and more of the blood cells and platelets until their numbers in the blood are reduced. Hypersplenism is the term used to describe this condition, and it is associated with a low red blood cell count (anemia), low white blood cell count (leucopenia), and/or a low platelet count (thrombocytopenia). The anemia can cause weakness, the leucopenia can lead to infections, and the thrombocytopenia can impair the clotting of blood and result in prolonged bleeding.

Treatment

Bleeding varices -- upper endoscopy with banding and sclerosis Excess abdominal fluid (ascites) -- take diuretics, restrict fluid and salt, and remove fluid (paracentesis) Coagulopathy -- blood products or vitamin K Confusion or encephalopathy -- lactulose medication and antibiotics Infections antibiotics Cirrhosis progresses to end-stage liver disease - liver transplant.