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Cirrhosis

From Academic Kids

Cirrhosis is a chronic disease of the liver in which liver tissue is replaced by connective tissue, resulting in the loss of liver function. Cirrhosis is caused by damage from toxins (including alcohol), metabolic problems, chronic viral hepatitis or other causes. Cirrhosis is sometimes referred to by its obsolete eponym Laennec's cirrhosis after Ren Lannec. Cirrhosis is irreversible but treatment of the causative disease will slow or even halt the damage.

Cirrhosis may refer to chronic interstitial inflammation of any tissue, but is rarely used for other diseases than cirrhosis of the liver.

Contents

Symptoms

Initial symptoms

Early symptoms include red palms, spider angioma (red spots on the upper body), hypertrophy of the parotid glands, and fibrosis of tendons in the hands. Clubbing may develop.

Many people with cirrhosis have no symptoms in the early stages of the disease. However, as scar tissue replaces healthy cells, liver function starts to fail and a person may experience the following symptoms:

Complications

As the disease progresses, complications may develop. In some people, these may be the first signs of the disease.

  • Bruising and bleeding due to decreased production of coagulation factors.
  • Jaundice due to decreased processing of bilirubin.
  • Itching due to bile products deposited in the skin.
  • Hepatic encephalopathy - the liver does not clear ammonia and related nitrogenous substances from the blood, which affect cerebral functioning: neglect of personal appearance, unresponsiveness, forgetfulness, trouble concentrating, or changes in sleep habits.
  • Sensitivity to medication due to decreased metabolism of the active compounds.
  • Insulin resistance and type 2 diabetes.
  • Hepatocellular carcinoma is primary liver cancer, commonly caused by cirrhosis. It has a high mortality rate.
  • Portal hypertension - blood normally carried from the intestines and spleen through the portal vein flows more slowly and the pressure increases; this leads to the following complications:
    • Ascites - fluid leaks through the vasculature into the abdominal cavity.
    • Esophageal varices - collateral portal blood flow through vessels in the stomach and esophagus. These blood vessels may become enlarged and are more likely to burst.
  • Problems in other organs. Cirrhosis can cause immune system dysfunction, leading to infection. Fluid in the abdomen (ascites) may become infected with bacteria normally present in the intestines (spontaneous bacterial peritonitis). Cirrhosis can also lead to impotence, kidney dysfunction and renal failure (hepatorenal syndrome) and osteoporosis.

Causes

Cirrhosis has many possible causes; sometimes more than one cause are present in the same patient. In the Western World, chronic alcoholism and hepatitis C are the most common causes.

  • Alcoholic liver disease (ALD). Alcoholic cirrhosis develops after more than a decade of heavy drinking in 15% of all alcoholics. There is great variability in the amount of alcohol needed to cause cirrhosis (3-4 drinks a day in some men and 2-3 in some women). Alcohol seems to injure the liver by blocking the normal metabolism of protein, fats, and carbohydrates.
  • Chronic hepatitis B (with or without D agent). The hepatitis B virus is probably the most common cause of cirrhosis worldwide, especially South-East Asia, but it is less common in the United States and the Western world. Hepatitis B causes liver inflammation and injury that over several decades can lead to cirrhosis. Hepatitis D is dependant on the presence of hepatitis B, but accelerates cirrhosis in co-infection.
  • Chronic hepatitis C. The hepatitis C virus ranks with alcohol as a major cause of chronic liver disease and cirrhosis. Infection with this virus causes inflammation of and low grade damage to the liver that over several decades can lead to cirrhosis.
  • Autoimmune hepatitis. This disease is caused by the immune system attacking the liver and causing inflammation, damage, and eventually scarring and cirrhosis.
  • Inherited diseases. These interfere with the way the liver produces, processes, and stores enzymes, proteins, metals, and other substances the body needs to function properly.
  • Non-alcoholic steatohepatitis (NASH). In NASH, fat builds up in the liver and eventually causes scar tissue. This type of hepatitis appears to be associated with diabetes, protein malnutrition, obesity, coronary artery disease, and treatment with corticosteroid medications.
  • Diseases that lead to chronic obstruction of the bile ducts. Accumulated bile damages liver tissue:
    • In babies, blocked bile ducts are most commonly caused by biliary atresia, a disease in which the bile ducts are absent or injured.
    • In adults, the most common cause is primary biliary cirrhosis, a disease in which the ducts become inflamed, blocked, and scarred.
    • Secondary biliary cirrhosis can happen after gallbladder surgery if the ducts are inadvertently tied off or injured.
  • Drugs or toxins.
  • Repeated bouts of heart failure with liver congestion.
  • Certain parasitic infections (like schistosomiasis).

Diagnosis

The doctor may diagnose cirrhosis on the basis of symptoms, the medical history, a physical examination and laboratory tests. For example, during a physical examination, the doctor may notice that the liver feels harder or larger than usual and order blood tests that can show whether liver disease is present.

If looking at the liver is necessary to check for signs of disease, the doctor might order a computerized axial tomography (CAT) scan, ultrasound, magnetic resonance imaging (MRI), or a scan of the liver using a radioisotope (a harmless radioactive substance that highlights the liver).

A liver biopsy will confirm the diagnosis. For a biopsy, the doctor uses a needle to take a tiny sample of liver tissue, then examines it under the microscope for scarring or other signs of disease.

Pathology

Macroscopically, the liver is initially enlarged, but with progression of the disease, it becomes smaller. Its surface is irregular, the consistency is firm and the color is often yellow (if associates steatosis). Depending on the size of the nodules there are three macroscopic types: micronodular, macronodular and mixed cirrhosis. In micronodular form (Laennec's cirrhosis or portal cirrhosis) regenerating nodules are under 3 mm. In macronodular cirrhosis (post-necrotic cirrhosis), the nodules are larger than 3 mm. The mixed cirrhosis consists in a variety of nodules with different sizes. Microscopically, cirrhosis is characterized by regeneration nodules, surrounded by fibrous septa. In these nodules, regenerating hepatocytes are disorderly disposed. Biliary tract, central vein and the radiar pattern of hepatocytes are absent. Fibrous septa are important and may present inflammatory infiltrate (lymphocytes, macrophages) If it is a secondary biliary cirrhosis, biliary ducts are damaged, proliferated or distended - bile stasis. These dilated ducts contain inspissated bile which appear as bile casts or bile thrombi (brown-green, amorphous). Bile retention may be found also in the parenchyma, as the so called "bile lakes". 1 (http://www.pathologyatlas.ro/Cirrhosis.html)

Pathophysiology

The liver plays a vital role in synthesis of proteins (e.g. albumin, clotting factors and complement), detoxification and storage (e.g. vitamin A). In addition, it participates in the metabolism of lipids and carbohydrates.

Cirrhosis is often preceded by hepatitis and fatty liver (steatosis), independent of the cause. If the cause is removed at this stage, the changes are still fully reversible.

The pathological hallmark of cirrhosis is the development of scar tissue that replaces normal parenchyma, blocking the portal flow of blood through the organ and disturbing normal function. Iredale (2003) summarises the pivotal role of stellate cell, a cell type that normally stores vitamin A, in the development of cirrhosis. Damage to the hepatic parenchyma leads to activation of the stellate cell, which becomes contractile and obstructs blood flow in the circulation. In addition, it secretes TGF-β1, which leads to a fibrotic response and proliferation of connective tissue. Furthermore, it disturbs the balance between matrix metalloproteinases and the naturally occurring inhibitors (TIMP 1 and 2), leading to matrix breakdown and replacement by connective tissue-secreted matrix.

The fibrous tissue forms nodes, which eventually replace the entire liver architecture, leading to decreased blood flow throughout. The spleen becomes congested, which leads to hypersplenism and increased sequestration of platelets. Portal hypertension is responsible for most severe complications of cirrhosis.

Treatment

Liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications. Close follow-up is often necessary. Alcohol and acetaminophen, as well as other potentially damaging substances, are discouraged. A healthy diet is encouraged, as cirrhosis may be an energy-consuming process. Salt restriction is often necessary, as cirrhosis leads to accumulation of salt (sodium retention). High-protein food increases the nitrogen balance and may increase encephalopathy; this is therefore eliminated as much as possible from the diet.

Treatment exists of elimination of the causes and preventing complications:

  • Elimination of causes: alcoholic cirrhosis caused by alcohol abuse is treated by abstaining from alcohol. Treatment for hepatitis-related cirrhosis involves medications used to treat the different types of hepatitis, such as interferon for viral hepatitis and corticosteroids for autoimmune hepatitis. Cirrhosis caused by Wilson's disease, in which copper builds up in organs, is treated with medications to remove the copper.
  • Preventing complications. Diuretics may be necessary to suppress ascites. Antibiotics will be prescribed for infections, and various medications can help with itching. Laxatives decrease risk of encephalopathy. For portal hypertension, propranolol is a commonly used agent to lower blood pressure over the portal system.

In severe complications from portal hypertension, transjugular intrahepatic portosystemic shunting is occasionally indicated to relieve pressure on the portal vein.

If complications cannot be controlled or when the liver ceases functioning, a liver transplant is necessary. Survival from liver transplantation has been improving over the 1990s and is now around 90%, depending largely on the severity of disease in the recipient. Transplantation necessitates the use of immune suppressants (cyclosporine or tacrolimus).

Epidemiology

In the United States, cirrhosis is the twelfth leading cause of death by disease, killing about 26,000 people each year. As it is a chronic disease with often frequent and severe complications, the cost of cirrhosis in terms of quality of life, hospital admissions, and lost productivity is high.

References

  • National Digestive Diseases Information Clearinghouse (NDDIC) article Cirrhosis of the Liver NIH Publication No. 04-1134 (http://digestive.niddk.nih.gov/ddiseases/pubs/cirrhosis), December 2003
  • Iredale JP. Cirrhosis: new research provides a basis for rational and targeted treatments. BMJ 2003;327:143-7. Fulltext. (http://bmj.bmjjournals.com/cgi/content/full/327/7407/143)PMID 12869458
  • Photos at: Atlas of Pathology (http://www.pathologyatlas.ro/Cirrhosis.html)


Health science - Medicine - Gastroenterology
Diseases of the esophagus - stomach
Halitosis - Nausea - Vomiting - GERD - Achalasia - Esophageal cancer - Esophageal varices - Peptic ulcer - Abdominal pain - Stomach cancer - Functional dyspepsia
Diseases of the liver - pancreas - gallbladder - biliary tree
Hepatitis - Cirrhosis - NASH - PBC - PSC - Budd-Chiari syndrome - Hepatocellular carcinoma - Pancreatitis - Pancreatic cancer - Gallstones - Cholecystitis
Diseases of the small intestine
Peptic ulcer - Intussusception - Malabsorption (e.g. celiac disease, lactose intolerance, fructose malabsorption, Whipple's disease) - Lymphoma
Diseases of the colon
Diarrhea - Appendicitis - Diverticulitis - Diverticulosis - IBD (Crohn's disease and Ulcerative colitis) - Irritable bowel syndrome - Constipation - Colorectal cancer - Hirschsprung's disease - Pseudomembranous colitis
de:Leberzirrhose

es:Cirrosis it:Cirrosi ja:肝硬変 nl:Levercirrose sl:Ciroza jeter tr:Siroz

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