Introduction of Jaundice:
Jaundice is a condition in which a person’s skin and the whites of the eyes are discolored yellow due to an abnormally increased level of bile pigments, bilirubin in the blood and body tissue resulting from liver diseases such as cirrhosis, hepatitis, or gallstones.
Causes of Jaundice:
The liver breaks down old, inefficient red blood cells in a process (hemolysis) and releases large amounts of bilirubin. The excess amount of bilirubin results in toxicity and can cause jaundice. The liver also manufactures the other components of bile. Normally, the liver metabolizes and excretes the bilirubin in the form of bile. However, if there is disruption due to infection or damage in this normal metabolism and production of bilirubin, jaundice may result.
The excess amount of bilirubin can be toxic and it is important to eliminate it from the body as fast as it is produced. There are three basic ways this process can go wrong and can cause jaundice:
- The liver itself can be temporarily or permanently damaged, reducing its ability to break down bilirubin (mix it with bile) and move it into the gallbladder.
- The gallbladder or its bile ducts can become blocked, preventing the excretion of bilirubin into the intestine. Bilirubin will then back up into the liver and then into the bloodstream.
- Any condition that leads to the very rapid destruction of red blood cells can create too much bilirubin for even a healthy liver to handle. Again, the excess is carried into the bloodstream.
Some Causes of Jaundice due to Poor Liver Function include:
Viral hepatitis: Hepatitis A, B, C, D, and E can all cause temporary liver inflammation.
Types B and C can also cause chronic, lifelong inflammation.
Medication-induced hepatitis: This may be caused by alcohol, erythromycin, methotrexate, amiodarone, statins (e.g., lovastatin, pravastatin, rosuvastatin), nitrofurantoin, testosterone, oral contraceptives, acetaminophen, and many other medications.
Autoimmune hepatitis: In this condition, the body’s immune system attacks its liver cells. Autoimmune hepatitis is more common in people and families with other autoimmune diseases, such as lupus, thyroid disease, diabetes, or ulcerative colitis. Primary biliary cirrhosis is another autoimmune condition of the liver and involves inflammation of the bile ducts.
Gilbert’s syndrome: This harmless inherited condition is quite common, affecting about 2% of the population. Minor defects in the liver’s metabolism of bilirubin cause jaundice to appear in times of stress, exercise, hunger, or infection.
Some Causes of Jaundice due to Obstruction (Blockage) include:
Gallstones: Formed in the gallbladder, gallstones can block the bile ducts, preventing bile (and bilirubin) from reaching the intestine. Sometimes, the bile ducts may become infected and inflamed.
Cholestasis: A condition in which the flow of bile from the liver is interrupted. The bile containing conjugated bilirubin remains in the liver instead of being excreted.
Newborn jaundice: Jaundice in newborn babies can be caused by several different conditions, although it is often a normal physiological consequence of the newborn’s immature liver. Even though it is usually harmless under these circumstances, newborns with excessively elevated levels of bilirubin from other medical conditions (pathologic jaundice) may suffer devastating brain damage (kernicterus) if the underlying problem is not addressed. Newborn jaundice is the most common condition requiring medical evaluation in newborns.
The following are some common causes of newborn jaundice:
Physiological jaundice: This form of jaundice is usually evident on the second or third day of life. It is the most common cause of newborn jaundice and is usually a transient and harmless condition. Jaundice is caused by the inability of the newborn’s immature liver to process bilirubin from the accelerated breakdown of red blood cells that occurs at this age. As the newborn’s liver matures, jaundice eventually disappears.
Maternal-fetal blood group incompatibility (Rh, ABO): This form of jaundice occurs when there is an incompatibility between the blood types of the mother and the fetus. This leads to increased bilirubin levels from the breakdown of the fetus’ red blood cells (hemolysis).
Breast milk jaundice: This form of jaundice occurs in breastfed newborns and usually appears at the end of the first week of life. Certain chemicals in breast milk are thought to be responsible. It is usually a harmless condition that resolves spontaneously.
Types of Jaundice:
Jaundice is classified into three categories, depending on which part of the physiological mechanism the pathology affects. The three categories are:
Pre-hepatic jaundice: If an infection or medical condition makes the red blood cells break down sooner than usual, bilirubin levels rise. This is known as pre-hepatic jaundice. Conditions that may trigger this include malaria, sickle cell anemia, thalassemia, Gilbert’s syndrome, hereditary spherocytosis, and Crigler-Najjar syndrome.
Table: Type of jaundice
| Category | Definition |
| Pre-hepatic/ hemolytic | The pathology is occurring before the liver. |
| Hepatic/ hepatocellular | The pathology is located within the liver. |
| Post-hepatic/ Cholestatic | The pathology is located after the conjugation of bilirubin in the water |
Intra-hepatic: If the liver is damaged, it may be less able to process bilirubin and reduces the liver’s ability to metabolize and excrete bilirubin leading to a buildup of unconjugated bilirubin in the blood which causes intra-hepatic jaundice. The liver damage may be a result of causes that include hepatitis, alcoholic liver disease, glandular fever, liver cancer, illegal drug use, and paracetamol overdose. Obesity and non-alcoholic fatty liver disease can be a cause of cirrhosis of the liver and jaundice.
Post-hepatic: Gallstones, pancreatitis, pancreatic cancer, and cancers of the gallbladder or bile duct may also disrupt the bilirubin removal process leading to jaundice. This is called post-hepatic jaundice.
Eating a high-fat diet can raise cholesterol levels and increase the risk of gallstones.
Pathophysiology:
Conjugated hyperbilirubinemia results from reduced secretion of conjugated bilirubin into the bile, such a condition occurs in patients with hepatitis, or it results from impaired flow of bile into the intestine, such condition occurs in patients with biliary obstruction. Bile formation is sensitive to various hepatic insults, including high levels of inflammatory cytokines, such as may occur in patients with septic shock.
High levels of conjugated bilirubin may secondarily elevate the level of unconjugated bilirubin. Although the mechanism of this effect is not fully defined, one likely cause is reduced hepatic clearance of unconjugated bilirubin that results from the competition with conjugated bilirubin for uptake or excretion.
Symptoms of Jaundice:
Common signs and symptoms seen in individuals with jaundice include:
- Yellow discoloration of the skin, mucous membranes, and the whites of the eyes,
- Light-colored stools,
- Dark-colored urine,
- Itching of the skin,
- Nausea and vomiting,
- Abdominal pain,
- Fever,
- Weakness,
- Loss of appetite,
- Confusion,
- Swelling of the legs and abdomen.
Newborn jaundice: In newborns, as the bilirubin level rises, jaundice will typically progress from the head to the trunk, and then to the hands and feet.
Additional signs and symptoms that may be seen in the newborn include:
- Poor feeding,
- Lethargy,
- Changes in muscle tone,
- High-pitched crying and seizures.
Diagnosis:
Physical Examination: The physical examination should focus primarily on signs of liver disease other than jaundice, including bruising, spider angiomas, gynecomastia, testicular atrophy, and palmar erythema. An abdominal examination to assess liver size and tenderness is important. The presence or absence of ascites also should be noted.
Urine Test: Urine can be tested for urobilinogen, which is produced when bilirubin is broken down. Finding high or low levels can help pinpoint the type of jaundice.
Serum Testing: First-line serum testing in a patient presenting with jaundice should include a complete blood count (CBC) and determination of bilirubin (total and direct fractions), aspartate transaminase (AST), alanine transaminase (ALT), γ-glutamyl transpeptidase, and alkaline phosphatase levels.
Imaging Studies:
Ultrasound: It is very useful for detecting gallstones and dilated bile ducts. It can also detect abnormalities of the liver and the pancreas.
Computerized tomography (CT) scan: A CT scan is an imaging study that provides more details of all the abdominal organs, useful in distinguishing an obstructing lesion from hepatocellular disease in the evaluation of a jaundiced patient.
Magnetic resonance imaging (MRI): MRI is an imaging study that uses a magnetic field to examine the organs of the abdomen. It can be useful for detailed imaging of the bile ducts.
Endoscopic retrograde cholangiopancreatography (ERCP): ERCP is a procedure that involves the introduction of an endoscope (a tube with a camera at the end) through the mouth and into the small intestine. A dye is then injected into the bile ducts while X-rays are taken. It can be useful for identifying stones, tumors, or narrowing of the bile ducts.
Liver Biopsy: Liver biopsy can be particularly helpful in diagnosing autoimmune hepatitis or biliary tract disorders. Patients with primary biliary cirrhosis are almost always positive for antimitochondrial antibody, and the majority of those affected by primary sclerosing cholangitis have antineutrophil cytoplasmic antibodies.
Laparoscopy: It allows direct inspection of the liver and gallbladder, without the trauma of a full laparotomy. Unexplained cholestatic jaundice warrants laparoscopy occasionally and diagnostic laparotomy rarely.
Treatment of Jaundice:
Treatment of jaundice typically requires a diagnosis of the specific cause to select suitable treatment options. Treatment would target the specific cause, rather than jaundice itself.
Pre-hepatic jaundice: In treating pre-hepatic jaundice, the objective is to prevent the rapid breakdown of red blood cells that is causing bilirubin levels to build up in the blood.
In cases of infections, such as malaria, the use of medication to treat the underlying infection is usually recommended. For genetic blood disorders, such as sickle cell anemia or thalassemia, blood transfusions may be required to replace the red blood cells.
Intra-hepatic jaundice: In cases of intra-hepatic jaundice, the objective is to repair any liver damage, although the liver can often repair itself over time. The treatment is therefore to prevent any further liver damage from occurring.
If the damage is caused by exposure to harmful substances such as alcohol or chemicals, avoiding any further exposure to the substance is recommended.
In severe cases of liver disease, a liver transplant is another possible option.
Post-hepatic jaundice: In most cases of post-hepatic jaundice, surgery is recommended to unblock the bile duct system. During surgery, it may also be necessary to remove:
- the gallbladder,
- a section of the bile duct system,
- a section of the pancreas to prevent further blockages from occurring.
In certain cases of newborn jaundice, exposing the baby to special colored lights (phototherapy) or exchange blood transfusions may be required to decrease elevated bilirubin levels.
Complication:
Complications include sepsis, especially cholangitis, biliary cirrhosis, pancreatitis, coagulopathy, renal and liver failure.
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 commit suicide.
Most complications that arise are a result of the underlying cause of jaundice, not from jaundice itself. For example, it caused by a bile duct obstruction may lead to uncontrolled bleeding due to a deficiency of vitamins needed for normal blood clotting.
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