Jaundice is a symptom complex that is characterized by the yellow coloration of tissues and body fluids due to an increase in bile pigment bilirubin and related products.
For understanding the causes of jaundice, first, we need to learn about the metabolism of bilirubin.
Jaundice is also known as icterus.
Bilirubin Metabolism
Breakdown
Hemoglobin released by the breakdown of aged cells is broken down into globin and heme. The heme is further broken into iron and bilirubin. Bilirubin attaches to serum albumin and is transported to the liver where it is taken up.
Conjugation
In the liver, bilirubin is separated from albumin and conjugated to glucuronide by glucuronyl transferase. The conjugated bilirubin is water-soluble and can be excreted by kidneys.
Alimentary Phase
The conjugated bilirubin is excreted through the bile canaliculi and reaches the intestines where it is converted to stercobilinogen and urobilinogen by the intestinal bacteria. About 70% of this is absorbed in the colon and brought back to the liver and re-excreted (enterohepatic circulation). Unabsorbed stercobilinogen gives a brown color to the faces.
Excretion phase
Circulating urobilinogen is carried to the kidneys for excretion in the urine as urobilinogen.
Why does Jaundice Occur?
A disease or process which causes an increase in bilirubin levels would result in jaundice. Hyperbilirubinemia may arise due to
- Increased bile pigment load to the liver.
- Affection of bilirubin diffusion into the liver cells.
- Defective conjugation.
- Defective excretion.
Normal values of bilirubin are
- Total bilirubin – <1 mg%
- Direct bilirubin – < 0.25 mg%
- Urinary bilirubin is present if direct bilirubin is greater than 0.4 mg% in serum.
- Urine Urobilinogen – 100-200 mg/day
- Fecal stercobilinogen – 300 mg/day
High concentration of bilirubin (hyperbilirubinemia), the bile product and its congeners are responsible for yellow discoloration of skin in jaundice. They bind with circulating proteins.
Bilirubin has more affinity for nervous tissue like basal ganglia and elastic tissues such as skin, sclera and blood vessels.
Causes of Jaundice
Infections
Viral hepatitis
Hepatitis means inflammation of the liver. Viral hepatitis means inflammation of the liver resulting from viral infection. Viral hepatitis could be acute or chronic.
Hepatitis A, B, C, D, and E are viruses that commonly affect the liver. Other viruses that can affect the liver are cytomegalovirus, Epstein-Barr virus, and yellow fever.
The viral infections can occur through the oral route or parenteral route.
Vaccinations are available for Hepatitis A and B.
Weil’s disease (Leptospirosis)
Leptospirosis is an infection by spirochetes of the genus Leptospira and is transmitted from animals [zoonosis].
In fact, it is considered the most common zoonosis in the world mostly occurring from rodents, agricultural occupations, or soil exposure.
Leptospirosis is characterized by sudden onset fever, rigors, headache, retro-orbital pain, and photophobia. There is also back and calf pain, conjunctival suffusion, dry cough, nausea, vomiting, and diarrhea.
It is a multisystem disease that involves the liver when it is severe and could lead to jaundice. The treatment involves supportive measures and antibiotics.
Septicemia
Septicemia or sepsis is a serious complication that occurs when bacteria enter the bloodstream to spread throughout the body. It can quickly lead to tissue damage, organ failure, and death.
It can occur in any infection.
The condition occurs more readily in immunocompromised, old and very young people.
Other Infections
The liver may get involved in many other infections. most prominent of them are
- Yellow fever
- Dengue
- Typhoid
- Salmonella
- Mycobacterium
- Tuberculosis
- Brucellosis
Toxic Injury
Drugs and other toxic agents may cause liver injury. The liver plays an important role in the metabolism of drugs and other chemicals and becomes susceptible to injury from these agents. The injury can occur in the therapeutic ranges or when in overdose.
Apart from drugs, other chemicals may cause hepatotoxicity.
Common agents that may cause hepatic injury are
- Alcohol
- Acetaminophen and other NSAIDs
- Glucocorticoids
- Anti-tubercular drugs
- Rifampicin
- P.A.S
- Isoniazid
- Thiacetazone
- Amanita mushrooms
- Industrial toxins
- Arsenic
- Carbon tetrachloride
- Vinyl chloride
- Benzene Hexachloride
- Anesthetic agents
- Halothane
- Anticoagulants
- Phenindione
- Metals
- Arsenic
- Mercury
- Gold
- Bismuth
- Irradiations
Cirrhosis
It is a gradually progressive disease and can occur because of many reasons including hepatitis, alcoholism, etc.
The only common factor across all the causes is continuous damage to the liver. When the fibrosis becomes extensive, it blocks the circulation causing portal hypertension. Jaundice also develops when the liver is not able to perform the required functions.
Obstruction
Extra Hepatic Obstruction
Extra-hepatic obstruction refers to an obstruction to the flow of biliary fluid from the liver to the intestine.
This results in bile building up in the liver leading to jaundice and other features.
Common causes of extrahepatic biliary obstruction are
- Stone within the biliary system (gallstones)
- Stricture of the ducts
- Acute cholecystitis
- Carcinoma of the head of the pancreas
- Neoplasm of bile ducts, gallbladder, and ampulla of Vater
- Biliary atresia
Intra Hepatic Obstruction
Intrahepatic obstruction is an obstruction to the bile flow within the liver parenchyma.
This is caused by
- Cholestatic phase of infective hepatitis
- Drugs –
- Steroids
- Chlorpromazine
- Sulfonamides
- Chlorpropamide tolbutamide
- Methyltestosterone
Hemolytic Causes
Hemolysis can lead to anemia because there is increased destruction of red blood cells which causes an increase in the production of bilirubin.
Hemolysis may occur due to various reasons. Apart from various congenital and hereditary causes following can cause hemolysis –
- Infections like Malaria, Clostridium welchi
- Drugs like L. Methyldopa, quinine, phenacetin, sulfonamides
- Burns
- Irradiation
- Snakebite
- Mismatched blood-transfusion
- Paroxysmal Cold Hemoglobinuria
- Lymphoma
- Leukemia
- Systemic lupus erythematosus
- Uremia
Congenital Hyperbilirubinemia
This occurs because of the hereditary defect of enzymes taking part in the metabolism of bilirubin. They are divided into two groups, unconjugated and conjugated
- Unconjugated hyperbilirubinemia
- Gilbert’s syndrome
- Crigler-Najjar syndrome
- Conjugated hyperbilirubinemia
- Dubin Johnson syndrome
- Rotor’s syndrome