Jaundice is the yellowish discoloration of the skin, mucous membranes, and sclera. This yellowish discoloration is imparted by a chemical in the blood called Bilirubin.

Bilirubin is the end product of heme which is produced when red blood cells are destroyed. After red blood cell lysis, the heme is converted to bilirubin which is then transported to the liver and is made water soluble.

This water-soluble bilirubin is then excreted through the biliary channels to the gut some of the bilirubin is excreted in the stools as stercobilin while some of it is reabsorbed and excreted by the Kidneys as Urobilinogen.


What causes jaundice?

Jaundice is a symptom and not a disease. The following are some of the major causes of jaundice.

  • Hemolysis:

Since bilirubin is made from heme so increased red cells lysis can lead to an increase in bilirubin in the blood and imparts yellowish discoloration to the skin and sclera.

Rapid turnover of the red cells is called hemolysis. Patients with hemolysis can present with anemia or progressive pallor along with Jaundice and splenomegaly.

The spleen may not be enlarged in certain types of hemolysis also called as intravascular hemolysis. Liver in patients with hemolysis is normal.

Since the liver is normal the levels of bilirubin does not rise above 6 mg/dl and is mostly unconjugated bilirubin.


  • Liver Disease may manifest as Jaundice

liver
liver diseases

Inflammation of the liver also called hepatitis can also lead to an elevation in bilirubin in the blood. Hepatitis can be acute or chronic.

Acute hepatitis:

Acute hepatitis is usually caused by hepatitis A virus, Hepatitis E virus and sometimes Hepatitis B virus.

Other viruses like cytomegalovirus, Epstein-bar virus and Herpes simplex virus can also lead to acute hepatitis especially in pregnant females and those who are immunocompromised like patients with HIV infections, AIDS, those patients on chemotherapy and diabetic patients.


Chronic hepatitis:

Chronic hepatitis can be caused by viruses like Hepatitis B and most importantly Hepatitis C virus. Jaundice is mild or sometimes maybe absent.

Patients with chronic hepatitis are usually diagnosed on screening or after they develop certain complications because of liver failure.

These complications include Ascites (accumulation of fluid in the abdomen) leading to abdominal distension, hematemesis (blood in vomitus), hepatic encephalopathy (patients become drowsy, unconscious or may have just a mild change in sensorium reflected initially by altered sleep pattern).


Other Liver-related causes of Jaundice:

Other causes of chronic hepatitis include alcoholic hepatitis which occurs in patients who are heavy drinkers for a long time and nonalcoholic steatohepatitis or NASH.

NASH occurs specifically in patients who have a metabolic syndrome that is patients who have diabetes, hypertension, obesity, and hyperlipidemia.

Initially, there is fatty infiltration of the liver also called a fatty liver this is followed by inflammation of the liver and is called non-alcoholic steatohepatitis or NASH.

Patients can progress from NASH to compensated liver disease and later on decompensated chronic liver disease.


Metabolic disorders causing Jaundice:

Metabolic diseases which lead to jaundice are hemochromatosis, Wilson’s disease, and Alpha 1 anti-trypsin deficiency.

Hemochromatosis:

It can be primary or secondary. In primary hemochromatosis patients have a genetic defect leading to increased iron in the body because of an increase absorption of iron.

In secondary hemochromatosis patients develop iron overload secondary to excessive blood transfusions or iron therapy for anemia.

The features and complications of both the conditions that are primary and secondary hemochromatosis are the same. Patients have liver disease leading to chronic hepatitis-like state followed by decompensated liver disease.

Patients in these conditions may also develop diabetes, hypothyroidism, hypoparathyroidism, hypogonadism, hypoadrenalism, arthritis also called pseudo-gout, hyperpigmentation of the skin and cardiomyopathy.


Wilsons disease:

In Wilson’s disease patients have increased copper in the body which is deposited in the liver, pancreas and the brain. This is also a congenital disorder and patients may develop neurological symptoms like movement disorders, spasticity, rigidity and Parkinson’s like features.

These patients may also have diabetes apart from liver disease. Patients with Wilson’s disease may have a copper deposition in the cornea that is called as Kayser-Fleisher or KF rings.

These patients may also have renal disease manifested is Fanconi syndrome and Renal tubular acidosis. Hemolysis and more specifically Coombs-negative hemolytic anemia are also one of the features.


Autoimmune liver diseases and granulomatous liver disease:

Other liver-related disorders include autoimmune hepatitis and primary biliary cirrhosis. Both these conditions are more common in females especially with a history of other autoimmune disorder as well.

Primary biliary cirrhosis patients can present with intense itching or pruritis, hyperlipidemias and clinical features of fat-soluble vitamin deficiency. Granulomatous diseases include sarcoidosis, tuberculosis, and fungal infections.


Congenital disorders of the liver:

These disorders include Gilbert syndrome which is manifested by unconjugated hyperbilirubinemia especially in states of stress and fasting.

Dubin Johnson Syndrome and rotor syndrome manifested by conjugated hyperbilirubinemia and Crigler Najjar syndrome which is the severe form of congenital liver diseases.


Obstructive jaundice:

Apart from hemolysis and liver-related diseases, jaundice can also occur in patients who have problems with their biliary channels. Bile which contains bilirubin is transported to the gall bladder and is stored and released in pulses, to be excreted via the gut.

A stone in the biliary duct or a mass/ tumor in the pancreas, gall bladder or the gut can obstruct the flow of bile and lead to jaundice.

Other disorders of obstructive jaundice include sclerosing cholangitis which is usually associated with ulcerative colitis.

Patients may have liver cancer or hepatocellular carcinoma as a cause of jaundice. Tumors/ cancers elsewhere in the body can also metastasize to the liver and manifest as jaundice.


Veno-occlusive diseases and other causes:

Patients with a veno-occlusive disease like Budd-Chiari syndrome can present with jaundice. This is due to a clot in the hepatic veins.

Patients with heart diseases can have jaundice due to the congestive liver. Certain drugs like anti-tuberculosis drugs can also cause jaundice this is called as toxic hepatitis.


How to Investigate a patient with Jaundice?

jaundice investigations
investigations in jaundiced patients

In patients with hemolytic anemia causing jaundice, the blood complete picture may show anemia and macrocytosis.

Reticulocytes may be raised and depending on the type of hemolytic anemia the patients may have a positive Coombs test (autoimmune hemolytic anemia).


Liver function tests:

Liver function tests include ALT (alanine aminotransferase), AST (aspartate aminotransferase), alkaline phosphatase and gamma Glutamyl transferase.

ALT and AST are specifically raised in patients with Jaundice due to liver disease while alkaline phosphatase and gamma Glutamyl Transferase is raised in patients with obstructive jaundice.

Raised bilirubin may be conjugated in liver disease and obstructive jaundice while unconjugated in hemolytic anemia. Prothrombin time, albumin and total proteins are usually low when the liver synthetic function is compromised.


Investigations to find the underlying cause:

Urine examination may show bilirubin in case of obstructive jaundice and urobilinogen in case the jaundice is due to hemolytic anemia.

Other investigations which are required include an ultrasound of the abdomen to look for the liver architecture, splenomegaly, Ascites (fluid in the abdomen), hepatic veins flow and portal vein pressure. Hepatitis B and C serology should always be done in the case of chronic hepatitis.

For hemochromatosis, serum iron, transferrin binding capacity, transferrin saturation, and ferritin may be advised. Genetic screening should also be done in these patients. In Wilson’s disease serum copper, ceruloplasmin and urinary copper may be advised.

The gold standard investigation for patients with hemochromatosis and Wilson’s disease is the liver biopsy.

Patients may be advised CT scan of the abdomen in case a tumor in the liver, gallbladder pancreas or the gut is suspected. Other investigations include MRCP and ERCP to look for the biliary channels.

Alpha-fetoprotein may be recommended for patients with hepatocellular carcinoma or liver cancer. Similarly, other tumor markers like CA 19-9 may be done for pancreatic cancer and CEA levels for patients with gut malignancy metastasizing to the liver.


What if jaundice is left untreated

Since jaundice is a symptom of an underline liver or biliary disease, complications depend on the underlying disease.

Patients with acute hepatitis, Gilbert syndrome and Dubin Johnson Syndrome may not need any treatment at all.

Patients with chronic hepatitis may need antiviral therapy or abstinence from alcohol or correcting the metabolic causes so that liver disease may not progress to decompensated chronic liver disease.

The liver is said to be decompensated when patients develop ascites, upper GI bleed, hepatic encephalopathy, and jaundice. Similarly not treating a stone in the gall bladder can lead to recurrent infections of the gallbladder and the channels.

Patients with pancreatic, gut, Liver tumors or other tumors metastasizing to the liver may be deadly if not treated well on time. This is also true for hemolytic anemia which may lead to severe anemia and heart failure.


How to prevent yourself from Jaundice?

vaccination
vaccination

One can prevent self from getting infected with hepatitis A or E by drinking clean water and eating hygienic food. Vaccination is available for hepatitis B and is very effective.

It is recommended by the WHO and is in the EPI program as well. One should keep vaccination status up to date and get a booster every 5 to 10 years.

Hepatitis B and C can be prevented via proper screening prior to transfusion, avoiding needle sticks, avoiding contaminated instruments, blades and proper sterilization of hospital equipment.

Secondary hemochromatosis may be avoided by using iron chelation therapy and avoid eating iron-rich food items or supplements. This is also true for patients with primary hemochromatosis.

Treatment of Wilson’s disease may improve neurological and hepatobiliary symptoms. Treatment of chronic hepatitis B may alleviate the chances of hepatocellular carcinoma.

Similarly avoiding excessive use of alcohol and correcting metabolic abnormalities like hyperlipidemia and obesity with healthy diet, weight loss, and exercise are essential.


danger signs in jaundice
warning signs

What signs should alert you to see a doctor?

All patients with Jaundice should consult a physician.

Specific signs of liver failure include:

    • Altered sensorium or encephalopathy,
    • Worsening abdominal distension indicator of Ascites (fluid in the abdomen),
    • Hematemesis (blood in vomitus),
    • Weight loss (patients who have jaundice and weight loss may indicate advanced liver disease, hepatocellular carcinoma, biliary or pancreatic carcinoma, and metastatic disease) and
    • Patients with marked skeletal pains (suggestive of metastatic liver disease).

In conclusion:

Jaundice is not a disease. The patients must be investigated for an underlying disease. Warning signs of advanced liver disease and liver failure, if missed, can be fatal.

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