Jaundice

Definition:
Jaundice, also known as icterus (attributive adjective: “icteric”), is yellowish discoloration of the skin, sclerae (whites of the eyes) and mucous membranes caused by hyperbilirubinemia (increased levels of bilirubin in the blood). This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluids. Typically, the concentration of bilirubin in the plasma must exceed 1.5 mg/dL, three times the usual value of approximately 0.5mg/dL, for the coloration to be easily visible. Jaundice comes from the French word jaune, meaning yellow.

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Jaundice is not a disease but rather a sign that can occur in many different diseases. Jaundice is the yellowish staining of the skin and sclerae (the whites of the eyes) that is caused by high levels in blood of the chemical bilirubin. The color of the skin and sclerae vary depending on the level of bilirubin. When the bilirubin level is mildly elevated, they are yellowish. When the bilirubin level is high, they tend to be brown.

Normal Physiology
In order to understand how jaundice results, it is important to understand where the pathological processes that cause jaundice take their effect. It is also important to further recognize that jaundice itself is not a disease, but rather a symptom of an underlying pathological process that occurs at some point along the normal physiological pathway of the metabolism of bilirubin.

Pre-hepatic events
When red blood cells have completed their life span of approximately 120 days, or when they are damaged, their membranes become fragile and prone to rupture. As the cell traverses through the reticuloendothelial system, their cell membranes rupture and the contents of the red blood cell is released into the blood. The component of the red blood cell that is involved in jaundice is hemoglobin. The hemoglobin released into the blood is phagocytosed by macrophages, and split into its heme and globin portions. The globin portion, being protein, is degraded into amino acids and plays no further role in jaundice. Two reactions then take place to the heme molecule. The first reaction is the oxidation of heme to form biliverdin.This reaction is catalyzed by microsomal enzyme heme oxygenase and it results in biliverdin (green color pigment), iron and carbon monoxide. Next step is reduction of biliverdin to yellow color tetrapyrol pigment bilirubin by cytosolic enzyme biliverdin reductase. This bilirubin is known as “unconjugated”, “free” or “indirect” bilirubin. Approximately 4 mg per kg of bilirubin is produced each day. The majority of this bilirubin comes from the breakdown of heme from expired red blood cells in the process just described. However approximately 20 per cent comes from other heme sources, including ineffective erythropoiesis, breakdown of other heme-containing proteins, such as muscle myoglobin and cytochromes.

Hepatic events
The unconjugated bilirubin then travels to the liver through the bloodstream. Because this bilirubin is not soluble, however, it is transported through the blood bound to serum albumin. Once it arrives at the liver, it is conjugated with glucuronic acid (to form bilirubin diglucuronide, or just “conjugated bilirubin”) to become more water soluble. The reaction is catalyzed by the enzyme UDP-glucuronide transferase.

Post-hepatic events
This conjugated bilirubin is excreted from the liver into the biliary and cystic ducts as part of bile. Intestinal bacteria convert the bilirubin into urobilinogen. From here the urobilinogen can take two pathways. It can either be further converted into stercobilinogen, which is then oxidized to stercobilin and passed out in the faeces, or it can be reabsorbed by the intestinal cells, transported in the blood to the kidneys, and passed out in the urine as the oxidised product urobilin. Stercobilin and urobilin are the products responsible for the coloration of faeces and urine, respectively.

Symptoms:-
In jaundice, the skin and whites of the eyes appear yellow. Urine is often dark because excess bilirubin is excreted through the kidneys. People may have itching, light-colored stools, or other symptoms, depending on the cause of jaundice. For example, acute inflammation of the liver (acute hepatitis) may cause loss of appetite, nausea, vomiting, and fever. Blockage of bile may result in abdominal pain and fever.
Causes:

Bilirubin comes from red blood cells. When red blood cells get old, they are destroyed. Hemoglobin, the iron-containing chemical in red blood cells that carries oxygen, is released from the destroyed red blood cells after the iron it contains is removed. The chemical that remains in the blood after the iron is removed becomes bilirubin.

The liver has many functions. One of the liver’s functions is to produce and secrete bile into the intestines to help digest dietary fat. Another is to remove toxic chemicals or waste products from the blood, and bilirubin is a waste product. The liver removes bilirubin from the blood. After the bilirubin has entered the liver cells, the cells conjugate (attaching other chemicals, primarily glucuronic acid) to the bilirubin, and then secrete the bilirubin/glucuronic acid complex into bile. The complex that is secreted in bile is called conjugated bilirubin. The conjugated bilirubin is eliminated in the feces. (Bilirubin is what gives feces its brown color.) Conjugated bilirubin is distinguished from the bilirubin that is released from the red blood cells and not yet removed from the blood which is termed unconjugated bilirubin.

Jaundice occurs when there is 1) too much bilirubin being produced for the liver to remove from the blood. (For example, patients with hemolytic anemia have an abnormally rapid rate of destruction of their red blood cells that releases large amounts of bilirubin into the blood), 2) a defect in the liver that prevents bilirubin from being removed from the blood, converted to bilirubin/glucuronic acid (conjugated) or secreted in bile, or 3) blockage of the bile ducts that decreases the flow of bile and bilirubin from the liver into the intestines. (For example, the bile ducts can be blocked by cancers, gallstones, or inflammation of the bile ducts). The decreased conjugation, secretion, or flow of bile that can result in jaundice is referred to as cholestasis: however, cholestasis does not always result in jaundice.
When a pathological process interferes with the normal functioning of the metabolism and excretion of bilirubin just described, jaundice may be the result. Jaundice is classified into three categories, depending on which part of the physiological mechanism the pathology affects.

The three categories are:

*Pre-hepatic: The pathology is occurring prior the liver

*Hepatic: The pathology is located within the liver

*Post-Hepatic: The pathology is located after the conjugation of bilirubin in the liver

Pre-hepatic
Pre-hepatic jaundice is caused by anything which causes an increased rate of hemolysis (breakdown of red blood cells). In tropical countries, malaria can cause jaundice in this manner. Certain genetic diseases, such as sickle cell anemia, spherocytosis and glucose 6-phosphate dehydrogenase deficiency can lead to increased red cell lysis and therefore hemolytic jaundice. Commonly, diseases of the kidney, such as hemolytic uremic syndrome, can also lead to coloration. Defects in bilirubin metabolism also present as jaundice. Jaundice usually comes with high fevers.

Laboratory findings include:
*Urine: no bilirubin present, urobilirubin > 2 units (except in infants where gut flora has not developed).

*Serum: increased unconjugated bilirubin.

Hepatic
Hepatic jaundice causes include acute hepatitis, hepatotoxicity and alcoholic liver disease, whereby cell necrosis reduces the liver’s ability to metabolise and excrete bilirubin leading to a buildup in the blood. Less common causes include primary biliary cirrhosis, Gilbert’s syndrome (a genetic disorder of bilirubin metabolism which can result in mild jaundice, which is found in about 5% of the population), Crigler-Najjar syndrome, metastatic carcinoma and Niemann Pick Type C disease. Jaundice seen in the newborn, known as neonatal jaundice, is common, occurring in almost every newborn as hepatic machinery for the conjugation and excretion of bilirubin does not fully mature until approximately two weeks of age.

Laboratory Findings include:
Urine: Conjugated bilirubin present, Urobilirubin > 2 units but variable (Except in children)

Post-hepatic
Post-hepatic jaundice, also called obstructive jaundice, is caused by an interruption to the drainage of bile in the biliary system. The most common causes are gallstones in the common bile duct, and pancreatic cancer in the head of the pancreas. Also, a group of parasites known as “liver flukes” live in the common bile duct, causing obstructive jaundice. Other causes include strictures of the common bile duct, biliary atresia, ductal carcinoma, pancreatitis and pancreatic pseudocysts. A rare cause of obstructive jaundice is Mirizzi’s syndrome.

The presence of pale stools and dark urine suggests an obstructive or post-hepatic cause as normal feces get their color from bile pigments.

Patients also can present with elevated serum cholesterol, and often complain of severe itching or “pruritus”.

Laboratory Tests
No one test can differentiate between various classifications of jaundice. A combinations of liver function tests is essential to arrive at a diagnosis.

Neonatal jaundice(jaundice in newborn infants)
Neonatal jaundice is usually harmless: this condition is often seen in infants around the second day after birth, lasting until day 8 in normal births, or to around day 14 in premature births. Serum bilirubin normally drops to a low level without any intervention required: the jaundice is presumably a consequence of metabolic and physiological adjustments after birth. In extreme cases, a brain-damaging condition known as kernicterus can occur; there are concerns that this condition has been rising in recent years due to inadequate detection and treatment of neonatal hyperbilirubinemia. Neonatal jaundice is a risk factor for hearing loss.

Click to see as per Ayurveda-> Yellow Jaundice, Newborn Jaundice, Causes & Symptoms

Jaundiced eye
It was once believed persons suffering from the medical condition jaundice saw everything as yellow. By extension, the jaundiced eye came to mean a prejudiced view, usually rather negative or critical. Alexander Pope, in ‘An Essay on Criticism’ (1711), wrote: “All seems infected that the infected spy, As all looks yellow to the jaundiced eye.” Similarly in the mid 19th century the English poet Lord Alfred Tennyson wrote in the poem ‘Locksley Hall’: “So I triumphe’d ere my passion sweeping thro’ me left me dry, left me with the palsied heart, and left me with a jaundiced eye.”

Problems Jaundice Cause :

Jaundice or cholestasis, by themselves, causes few problems (except in the newborn, and jaundice in the newborn is different than most other types of jaundice, as discussed later.) Jaundice can turn the skin and sclerae yellow. In addition, stool can become light in color, even clay-colored because of the absence of bilirubin that normally gives stool its brown color. The urine may turn dark or brownish in color. This occurs when the bilirubin that is building up in the blood begins to be excreted from the body in the urine. Just as in feces, the bilirubin turns the urine brown.

Besides the cosmetic issues of looking yellow and having dark urine and light stools, the symptom that is associated most frequently associated with jaundice or cholestasis is itching, medically known as pruritus. The itching associated with jaundice and cholestasis can sometimes be so severe that it causes patients to scratch their skin “raw,” have trouble sleeping, and, rarely, even to commit suicide.

It is the disease causing the jaundice that causes most problems associated with jaundice. Specifically, if the jaundice is due to liver disease, the patient may have symptoms or signs of liver disease or cirrhosis. (Cirrhosis represents advanced liver disease.) The symptoms and signs of liver disease and cirrhosis include fatigue, swelling of the ankles, muscle wasting, ascites (fluid accumulation in the abdominal cavity), mental confusion or coma, and bleeding into the intestines.

If the jaundice is caused by blockage of the bile ducts, no bile enters the intestine. Bile is necessary for digesting fat in the intestine and releasing vitamins from within it so that the vitamins can be absorbed into the body. Therefore, blockage of the flow of bile can lead to deficiencies of certain vitamins. For example, there may be a deficiency of vitamin K that prevents proteins that are needed for normal clotting of blood to be made by the liver, and, as a result, uncontrolled bleeding may occur.

Diseases cause jaundice:-
Increased production of bilirubin
There are several uncommon conditions that give rise to over-production of bilirubin. The bilirubin in the blood in these conditions usually is only mildly elevated, and the resultant jaundice usually is mild and difficult to detect. These conditions include: 1) rapid destruction of red blood cells (referred to as hemolysis), 2) a defect in the formation of red blood cells that leads to the over-production of hemoglobin in the bone marrow (called ineffective erythropoiesis), or 3) absorption of large amounts of hemoglobin when there has been much bleeding into tissues (e.g., from hematomas, collections of blood in the tissues).

Acute inflammation of the liver
Any condition in which the liver becomes inflamed can reduce the ability of the liver to conjugate (attach glucuronic acid to) and secrete bilirubin. Common examples include acute viral hepatitis, alcoholic hepatitis, and Tylenol-induced liver toxicity.

Chronic liver diseases
Chronic inflammation of the liver can lead to scarring and cirrhosis, and can ultimately result in jaundice. Common examples include chronic hepatitis B and C, alcoholic liver disease with cirrhosis, and autoimmune hepatitis.

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Infiltrative diseases of the liver
Infiltrative diseases of the liver refer to diseases in which the liver is filled with cells or substances that don’t belong there. The most common example would be metastatic cancer to the liver, usually from cancers within the abdomen. Uncommon causes include a few diseases in which substances accumulate within the liver cells, for example, iron (hemochromatosis), alpha-one antitrypsin (alpha-one antitrypsin deficiency), and copper (Wilson’s disease).

Inflammation of the bile ducts
Diseases causing inflammation of the bile ducts, for example, primary biliary cirrhosis or sclerosing cholangitis and some drugs, can stop the flow of bile and elimination of bilirubin and lead to jaundice.

Blockage of the bile ducts
The most common causes of blockage of the bile ducts are gallstones and pancreatic cancer. Less common causes include cancers of the liver and bile ducts.

Drugs:-
Many drugs can cause jaundice and/or cholestasis. Some drugs can cause liver inflammation (hepatitis) similar to viral hepatitis. Other drugs can cause inflammation of the bile ducts, resulting in cholestasis and/or jaundice. Drugs also may interfere directly with the chemical processes within the cells of the liver and bile ducts that are responsible for the formation and secretion of bile to the intestine. As a result, the constituents of bile, including bilirubin, are retained in the body. The best example of a drug that causes this latter type of cholestasis and jaundice is estrogen. The primary treatment for jaundice caused by drugs is discontinuation of the drug. Almost always the bilirubin levels will return to normal within a few weeks, though in a few cases it may take several months.

Genetic disorders:-
There are several rare genetic disorders present from birth that give rise to jaundice. Crigler-Najjar syndrome is caused by a defect in the conjugation of bilirubin in the liver due to a reduction or absence of the enzyme responsible for conjugating the glucuronic acid to bilirubin. Dubin-Johnson and Rotor’s syndromes are caused by abnormal secretion of bilirubin into bile.

The only common genetic disorder that may cause jaundice is Gilbert’s syndrome which affects approximately 7% of the population. Gilbert’s syndrome is caused by a mild reduction in the activity of the enzyme responsible for conjugating the glucuronic acid to bilirubin. The increase in bilirubin in the blood usually is mild and infrequently reaches levels that cause jaundice. Gilbert’s syndrome is a benign condition that does not cause health problems.

Developmental abnormalities of bile ducts:-
There are rare instances in which the bile ducts do not develop normally and the flow of bile is interrupted. Jaundice frequently occurs. These diseases usually are present from birth though some of them may first be recognized in childhood or even adulthood. Cysts of the bile duct (choledochal cysts) are an example of such a developmental abnormality. Another example is Caroli’s disease.

Jaundice of pregnancy :-

Most of the diseases discussed previously can affect women during pregnancy, but there are some additional causes of jaundice that are unique to pregnancy.

Cholestasis of pregnancy. Cholestasis of pregnancy is an uncommon condition that occurs in pregnant women during the third trimester. The cholestasis is often accompanied by itching but infrequently causes jaundice. The itching can be severe, but there is treatment (ursodeoxycholic acid or ursodiol). Pregnant women with cholestasis usually do well although they may be at greater risk for developing gallstones. More importantly, there appears to be an increased risk to the fetus for developmental abnormalities. Cholestasis of pregnancy is more common in certain groups, particularly in Scandinavia and Chile, and tends to occur with each additional pregnancy. There also is an association between cholestasis of pregnancy and cholestasis caused by oral estrogens, and it has been hypothesized that it is the increased estrogens during pregnancy that are responsible for the cholestasis of pregnancy.

Pre-eclampsia. Pre-eclampsia, previously called toxemia of pregnancy, is a disease that occurs during the second half of pregnancy and involves several systems within the body, including the liver. It may result in high blood pressure, fluid retention, and damage to the kidneys as well as anemia and reduced numbers of platelets due to destruction of red blood cells and platelets. It often causes problems for the fetus. Although the bilirubin level in the blood is elevated in pre-eclampsia, it usually is mildly elevated, and jaundice is uncommon. Treatment of pre-eclampsia usually involves delivery of the fetus as soon as possible if the fetus is mature.

Acute fatty liver of pregnancy. Acute fatty liver of pregnancy (AFLP) is a very serious complication of pregnancy of unclear cause that often is associated with pre-eclampsia. It occurs late in pregnancy and results in failure of the liver. It can almost always be reversed by immediate delivery of the fetus. There is an increased risk of infant death. Jaundice is common, but not always present in AFLP. Treatment usually involves delivery of the fetus as soon as possible.

Diagnosis:-
Many tests are available for determining the cause of jaundice, but the history and physical examination are important as well.

History
The history can suggest possible reasons for the jaundice. For example, heavy use of alcohol suggests alcoholic liver disease, whereas use of illegal, injectable drugs suggests viral hepatitis. Recent initiation of a new drug suggests drug-induced jaundice. Episodes of abdominal pain associated with jaundice suggests blockage of the bile ducts usually by gallstones.

Physical examination
The most important part of the physical examination in a patient who is jaundiced is examination of the abdomen. Masses (tumors) in the abdomen suggest cancer infiltrating the liver (metastatic cancer) as the cause of the jaundice. An enlarged, firm liver suggests cirrhosis. A rock-hard, nodular liver suggests cancer within the liver.

Blood tests
Measurement of bilirubin can be helpful in determining the causes of jaundice. Markedly greater elevations of unconjugated bilirubin relative to elevations of conjugated bilirubin in the blood suggest hemolysis (destruction of red blood cells). Marked elevations of liver tests (aspartate amino transferase or AST and alanine amino transferase or ALT) suggest inflammation of the liver (such as viral hepatitis). Elevations of other liver tests, e.g., alkaline phosphatase, suggest diseases or obstruction of the bile ducts.

Ultrasonography
Ultrasonography is a simple, safe, and readily-available test that uses sound waves to examine the organs within the abdomen. Ultrasound examination of the abdomen may disclose gallstones, tumors in the liver or the pancreas, and dilated bile ducts due to obstruction (by gallstones or tumor).

Computerized tomography (CT or CAT scans)
Computerized tomography or CT scans are scans that use x-rays to examine the soft tissues of the abdomen. They are particularly good for identifying tumors in the liver and the pancreas and dilated bile ducts, though they are not as good as ultrasonography for identifying gallstones.

Magnetic resonance imaging (MRI)
Magnetic Resonance Imaging scans are scans that utilize magnetization of the body to examine the soft tissues of the abdomen. Like CT scans, they are good for identifying tumors and studying bile ducts. MRI scans can be modified to visualize the bile ducts better than CT scans (a procedure referred to as MR cholangiography), and, therefore, are better than CT for identifying the cause and location of bile duct obstruction.

Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound
Endoscopic retrograde cholangiopancreatography (ERCP) provides the best means for examining the bile duct. For ERCP an endoscope is swallowed by the patient after he or she has been sedated. The endoscope is a flexible, fiberoptic tube approximately four feet in length with a light and camera on its tip. The tip of the endoscope is passed down the esophagus, through the stomach, and into the duodenum where the main bile duct enters the intestine. A thin tube then is passed through the endoscope and into the bile duct, and the duct is filled with x-ray contrast solution. An x-ray is taken that clearly demonstrates the contrast-filled bile ducts. ERCP is particularly good at demonstrating the cause and location of obstruction within the bile ducts. A major advantage of ERCP is that diagnostic and therapeutic procedures can be done at the same time as the x-rays. For example, if gallstones are found in the bile ducts, they can be removed. Stents can be placed in the bile ducts to relieve the obstruction caused by scarring or tumors. Biopsies of tumors can be obtained.

Ultrasonography can be combined with ERCP by using a specialized endoscope capable of doing ultrasound scanning. Endoscopic ultrasound is excellent for diagnosing small gallstones in the gallbladder and bile ducts that can be missed by other diagnostic methods such as ultrasound, CT, and MRI. It also is the best means of examining the pancreas for tumors and can facilitate biopsy through the endoscope of tumors within the pancreas.

Liver biopsy
Biopsy of the liver provides a small piece of tissue from the liver for examination under the microscope. The biopsy most commonly is done with a long needle after local injection of the skin of the abdomen overlying the liver with anesthetic. The needle passes through the skin and into the liver, cutting off a small piece of liver tissue. When the needle is withdrawn, the piece of liver comes with it. Liver biopsy is particularly good for diagnosing inflammation of the liver and bile ducts, cirrhosis, cancer, and fatty liver.

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Treatment:

A doctor uses laboratory tests and imaging studies to determine the cause of the jaundice. If the problem is a disease of the liver, such as acute viral hepatitis, the jaundice usually disappears gradually as the condition of the liver improves. If the problem is blockage of a bile duct, surgery or surgical endoscopy (using a flexible viewing tube with surgical instruments attached: Endoscopy) is usually performed as soon as possible to reopen the affected bile duct. Itching caused by jaundice can be treated with cholestyramine Some Trade Names QUESTRAN taken by mouth. Usually, the itching gradually disappears as the liver’s condition improves.

With the exception of the treatments for specific causes of jaundice mentioned previously, the treatment of jaundice usually requires a diagnosis of the specific cause of the jaundice and treatment directed at the specific cause, e.g., removal of a gallstone blocking the bile duct.

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Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://en.wikipedia.org/wiki/Jaundice
http://www.medicinenet.com/jaundice/page2.htm
http://merck.com/mmhe/au/sec10/ch135/ch135b.html

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