Jaundice

Jaundice



Definition of Jaundice

Jaundice (also known as icterus) is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae (whites of the eyes), and othermucous membranes caused by hyperbilirubinemia (increased levels of bilirubin in the blood). This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid. Concentration of bilirubin in blood plasma does not normally exceed 1 mg/dL (>17µmol/L). A concentration higher than 1.8 mg/dL (>30µmol/L) leads to jaundice. The term jaundice comes from the French word jaune, meaning yellow.

Jaundice is often seen in liver disease such as hepatitis or liver cancer. It may also indicate leptospirosis or obstruction of the biliary tract, for example by gallstones or pancreatic cancer, or less commonly be congenital in origin (e.g., biliary atresia).

Yellow discoloration of the skin, especially on the palms and the soles, but not of the sclera and mucous membranes (i.e. oral cavity) is due to carotenemia—a harmless condition important to differentiate from jaundice.

Cause of 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

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, thalassemia 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, as in Gilbert’s syndrome (a genetic disorder of bilirubin metabolism which can result in mild jaundice, which is found in about 5% of the population) and Crigler-Najjar syndrome.

In jaundice secondary to hemolysis, the increased production of bilirubin, leads to the increased production of urine-urobilinogen. Bilirubin is not usually found in the urine because unconjugated bilirubin is not water-soluble, so, the combination of increased urine-urobilinogen with no bilirubin (since, unconjugated) in urine is suggestive of hemolytic jaundice.

Laboratory findings include:

  • Urine: no bilirubin present, urobilinogen > 2 units (i.e., hemolytic anemia causes increased heme metabolism; exception: infants where gut flora has not developed).
  • Serum: increased unconjugated bilirubin.
  • Kernicterus is associated with increased unconjugated bilirubin, neonates are especially vulnerable to this due to increase permeability of the blood brain barrier.

Hepatocellular

Hepatocellular (hepatic) jaundice can be caused by acute or chronic hepatitis, hepatotoxicity, cirrhosis, drug induced hepatitis and alcoholic liver disease. Cell necrosis reduces the liver’s ability to metabolize and excrete bilirubin leading to a buildup of unconjugated bilirubin in the blood. Other causes include primary biliary cirrhosis leading to an increase in plasma conjugated bilirubin because there is impairment of excretion of conjugated bilirubin into the bile. The blood contains abnormally raised amount of conjugated bilirubin and bile salts which are excreted in the urine. Jaundice seen in the newborn, known as neonatal jaundice, is common in newborns as hepatic machinery for the conjugation and excretion of bilirubin does not fully mature until approximately two weeks of age. Rat fever (leptospirosis) can also cause hepatic jaundice. In hepatic jaundice, there is invariably cholestasis.

Laboratory findings depend on the cause of jaundice.

  • Urine: Conjugated bilirubin present, urobilirubin > 2 units but variable (except in children). Kernicterus is a condition not associated with increased conjugated bilirubin.
  • Plasma protein show characteristic changes.
  • Plasma albumin level is low but plasma globulins are raised due to an increased formation of antibodies.

Bilirubin transport across the hepatocyte may be impaired at any point between the uptake of unconjugated bilirubin into the cell and transport of conjugated bilirubin into biliary canaliculi. In addition, swelling of cells and oedema due to inflammation cause mechanical obstruction of intrahepatic biliary tree. Hence in hepatocellular jaundice, concentration of both unconjugated and conjugated bilirubin rises in the blood. In hepatocellular disease, there is usually interference in all major steps of bilirubin metabolism—uptake, conjugation and excretion. However, excretion is the rate-limiting step, and usually impaired to the greatest extent. As a result, conjugated hyperbilirubinaemia predominates.

The unconjugated bilirubin still enters the liver cells and becomes conjugated in the usual way. This conjugated bilirubin is then returned to the blood, probably by rupture of the congested bile canaliculi and direct emptying of the bile into the lymph leaving the liver. Thus, most of the bilirubin in the plasma becomes the conjugated type rather than the unconjugated type, and this conjugated bilirubin which did not go to intestine to become urobilinogen gives the urine the dark color.

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” can live in the common bile duct, causing obstructive jaundice. Other causes include strictures of the common bile duct, biliary atresia, cholangiocarcinoma, pancreatitis and pancreatic pseudocysts. A rare cause of obstructive jaundice is Mirizzi’s syndrome.

In complete obstruction of the bile duct, no urobilinogen is found in the urine, since bilirubin has no access to the intestine and it is in the intestine that bilirubin gets converted to urobilinogen to be later released into the general circulation. In this case, presence of bilirubin (conjugated) in the urine without urine-urobilinogen suggests obstructive jaundice, either intra-hepatic or post-hepatic.

The presence of pale stools and dark urine suggests an obstructive or post-hepatic cause as normal feces get their color from bile pigments. However, although pale stools and dark urine are a feature of biliary obstruction, they can occur in many intra-hepatic illnesses and are therefore not a reliable clinical feature to distinguish obstruction from hepatic causes of jaundice.

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

No single test can differentiate between various classifications of jaundice. A combination of liver function tests is essential to arrive at a diagnosis.

Neonatal jaundice

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. Typical causes for neonatal jaundice include normal physiologic jaundice, jaundice due to breast feeding, and hemolytic disorders that include hereditary spherocytosis, glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, ABO/Rh blood type autoantibodies, or infantile pyknocytosis. 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 cases where bilirubin rises higher, a brain-damaging condition known as kernicterus can occur, leading to significant lifelong disability; there are concerns that this condition has been rising in recent years due to inadequate detection and treatment of neonatal hyperbilirubinemia. A Bili light is often the tool used for early treatment, which often consists of exposing the baby to intensive phototherapy. However, in third world countries where procuring such treatment is prohibitively expensive, parents often subject their children to regular daily sunbathing. Bilirubin count is lowered through bowel movements and urination so regular and proper feedings are especially important.

Signs and Symptoms of Jaundice

The main symptom of jaundice is a yellow discoloration of the white part of the eyes and of the skin.

The conjunctiva of the eye are one of the first tissues to change color as bilirubin levels rise in jaundice. This is sometimes referred to as scleral icterus. However, the sclera themselves are not “icteric” (stained with bile pigment) but rather the conjunctival membranes that overlie them. The yellowing of the “white of the eye” is thus more properly termed conjunctival icterus. The term “icterus” itself is sometimes incorrectly used to refer to jaundice that is noted in the sclera of the eyes, however its more common and more correct meaning is entirely synonymous with jaundice.

Risk Factors for Jaundice

Major risk factors for jaundice include:

  • Premature birth
  • Bruising during birth
  • Blood type
  • Breast-feeding
  • Alcohol Abuse and Alcoholism
  • Drug Abuse and Drug Addiction
  • Medicines that may harm the liver
  • Hepatitis A (through contaminated food or water), Hepatitis B , or Hepatitis C (through contaminated needles or unsafe sex)
  • Industrial chemicals

Diagnosis of Jaundice

Most patients presenting with jaundice will have various predictable patterns of liver panel abnormalities, though significant variation does exist. The typical liver panel will include blood levels of enzymes found primarily from the liver, such as the aminotransferases (ALT, AST), and alkaline phosphatase (ALP); bilirubin (which causes the jaundice); and protein levels, specifically, total protein and albumin. Other primary lab tests for liver function include gamma glutamyl transpeptidase (GGT) and prothrombin time (PT).

Some bone and heart disorders can lead to an increase in ALP and the aminotransferases, so the first step in differentiating these from liver problems is to compare the levels of GGT, which will only be elevated in liver-specific conditions. The second step is distinguishing from biliary (cholestatic) or liver (hepatic) causes of jaundice and altered laboratory results. The former typically indicates a surgical response, while the latter typically leans toward a medical response. ALP and GGT levels will typically rise with one pattern while aspartate aminotransferase (AST) and alanine aminotransferase (ALT) rise in a separate pattern. If the ALP (10–45 IU/L) and GGT (18–85) levels rise proportionately about as high as the AST (12–38 IU/L) and ALT (10–45 IU/L) levels, this indicates a cholestatic problem. On the other hand, if the AST and ALT rise is significantly higher than the ALP and GGT rise, this indicates an hepatic problem. Finally, distinguishing between hepatic causes of jaundice, comparing levels of AST and ALT can prove useful. AST levels will typically be higher than ALT. This remains the case in most hepatic disorders except for hepatitis (viral or hepatotoxic). Alcoholic liver damage may see fairly normal ALT levels, with AST 10x higher than ALT. On the other hand, if ALT is higher than AST, this is indicative of hepatitis. Levels of ALT and AST are not well correlated to the extent of liver damage, although rapid drops in these levels from very high levels can indicate severe necrosis. Low levels of albumin tend to indicate a chronic condition, while it is normal in hepatitis and cholestasis.

Lab results for liver panels are frequently compared by the magnitude of their differences, not the pure number, as well as by their ratios. The AST:ALT ratio can be a good indicator of whether the disorder is alcoholic liver damage (10), some other form of liver damage (above 1), or hepatitis (less than 1). Bilirubin levels greater than 10x normal could indicate neoplastic or intrahepatic cholestasis. Levels lower than this tend to indicate hepatocellular causes. AST levels greater than 15x tends to indicate acute hepatocellular damage. Less than this tend to indicate obstructive causes. ALP levels greater than 5x normal tend to indicate obstruction, while levels greater than 10x normal can indicate drug (toxic) induced cholestatic hepatitis or Cytomegalovirus. Both of these conditions can also have ALT and AST greater than 20× normal. GGT levels greater than 10x normal typically indicate cholestasis. Levels 5–10× tend to indicate viral hepatitis. Levels less than 5× normal tend to indicate drug toxicity. Acute hepatitis will typically have ALT and AST levels rising 20–30× normal (above 1000), and may remain significantly elevated for several weeks. Acetaminophen toxicity can result in ALT and AST levels greater than 50x normal.

Prevention from Jaundice

Due to the wide range of potential causes, it’s not possible to prevent all cases of jaundice. However, there are four main precautions that you can take to minimise your risk of developing jaundice. 

More information about each precaution is provided below.

  • stick to the recommended daily amount (RDA) for alcohol consumption
  • Be careful in mixing drugs, especially alcohol, with over-the-counter and prescription medicines.
  • Maintain a healthy weight
  • Avoid exposure to industrial chemicals.
  • Do not use illegal drugs.
  • Do not share needles or nasal snorting equipment.
  • Practice safe sex.
  • To minimize your risk of exposure to hepatitis A, get the hepatitis A vaccine.
  • To minimize your risk of exposure to hepatitis B, get the hepatitis B vaccine.

 

Treatment Of Jaundice

Mild Newborn Jaundice is common and usually clears without treatment. If bilirubin levels rise above a certain level, the baby may receive phototherapy , which is treatment with a special ultraviolet light. In Gilbert’s syndrome, jaundice tends to occur during stressful periods and clears without treatment.  In cases where bilirubin rises higher, a brain-damaging condition known as kernicterus can occur, leading to significant lifelong disability; there are concerns that this condition has been rising in recent years due to inadequate detection and treatment of neonatal hyperbilirubinemia. A Bili light is often the tool used for early treatment, which often consists of exposing the baby to intensive phototherapy. However, in third world countries where procuring such treatment is prohibitively expensive, parents often subject their children to regular daily sunbathing. Bilirubin count is lowered through bowel movements and urination so regular and proper feedings are especially important.

In most other types of jaundice, the specific condition causing it must be treated. There are many treatments that may be used for liver and gallbladder problems depending on the exact condition. They include:

  • Addressing the cause of anemia
  • Taking medicines to treat causative infectious diseases
  • Avoiding a substance (alcohol or a medicine) that is causing the condition
  • Relieving bile duct obstructions by:
    • Excising tumors
    • Extracting gallstones
    • Removing the gallbladder
    • Treating inflammation of the pancreas (Pancreatitis)

Treatment should include correction of coagulopathy, fluid/electrolyte anomaly, antibiotics and biliary drainage with ERCP where available or trans-hepatic drainage or surgery.