Jaundice overview

# Overview
Jaundice is  yellowish discoloration of the skin, conjunctiva (a clear covering over the sclera, or whites of the eyes) and mucous membranes caused by hyperbilirubinemia (increased levels of bilirubin in red blooded animals). Usually the concentration of bilirubin in the blood must exceed 23 mg/dL for the coloration to be easily visible.

# Historical Perspective
Jaundice comes from the French word jaune, meaning yellow. It was once believed persons suffering from the medical condition jaundice saw everything as yellow, but this is not true. In 1885, Luhrman noted jaundice as an adverse effect of vaccination. In 1935, A. O. Whipple, an American surgeon first described obstructive jaundice. Many viruses that cause hepatitis and jaundice was discovered in 1950-2000.

# Classification
Jaundice is classified in two categories including unconjugated hyperbilirubinemia and conjugated hyperbilirubinema. Unconjugated hypebilirubinemia can be caused by either increased production, reduced reuptake or defects in conjugation of bilirubin. While conjugated hyperbilirubinemia is further classified into obstruction of biliary tract, interahepatic cholestasis, injury to hepatocellular parenchyma, and defects of hepatocellular canalicular excretion or re-uptake in sinusoids.

# Pathophysiology
Bilirubin is the catabolic product of the heme which is the main component of the red blood cells. Bilirubin is formed in the liver and spleen then it passes through several process in order to be metabolized. Metabolism processes include hepatic uptake, conjugation, clearance and excretion of the bilirubin in the bile. Jaundice develops due to increase the level of bilirubin and deposition under the skin and cause the yellow discoloration of the skin. Pathogenesis of neonatal jaundice includes physiologic process of bilirubin accumulation or pathological mechanism. The pathological jaundice may be acquired or inherited. Acquired neonatal jaundice include Rh hemolytic disease, ABO incompatibility disease, and hemolytic disease due to G6PD enzyme deficiency. Inherited neonatal jaundice is due to defect of one of the processes of bilirubin metabolism and it concludes some inherited syndromes. Inherited neonatal jaundice include Gilbert's syndrome, Crigler-Najjar syndrome type I and II, Lucey-Driscoll syndrome, Dubin-Johnson syndrome, and Rotor syndrome.

# Causes
Common causes of jaundice are classified under conjugated and unconjugated hyperbilirubinemia. Unconjugated hyperbilirubinemia is caused by either increased bilirubin production in the body, impaired hepatic bilirubin uptake in the liver or impaired bilirubin uptake in the liver, all of which causes pooling of unconjugated bilirubin in the body leading to unconjugated hyperbilirubinemia. On the other hand, intra or extra hepatic cholestasis lead to accumulation of conjugated bilirubin causing conjugated hyperbilirubinemia.

# Differential Diagnosis
Jaundice is yellowish discoloration of the skin, conjunctiva, and mucous membranes caused by hyperbilirubinemia. Usually, the concentration of bilirubin in the blood must exceed 23 mg/dL for the coloration to be easily visible.

# Epidemiology and Demographics
The incidence of jaundice is approximately 40,000 per 100,000 individuals of intensive care unit patients. Neonatal jaundice is more common among Asian and mixed Asian/white infants than white infants. Hepatocellular jaundice mainly from viral hepatitis commonly affects  young patients. Cholestatic jaundice mainly from liver cancer, hepatitis, and liver cirrhosis commonly affects older patients. Male are more commonly affected by hepatocellular jaundice and liver cancer than female. Female are more commonly affected by hemolytic jaundice mainly from cholangiocarcinoma than male.

# Risk Factors
Common risk factors in the development of jaundice are classified under conjugated and unconjugated hyperbilirubinemia. The most common risk factors for unconjugated hyperbilirubinemia includes neonatal period, drugs like rifampin and probenecid, syndromes like Gilbert and Crigler-Najjar syndrome types I and II, steroids and chronic liver diseases. The most common risk factors for conjugated hyperbilirubinemia includes viral hepatitis, alcohol, non-alcoholic fatty liver disease, chronic hepatitis, primary biliary cirrhosis, drugs, and toxins (eg, alkylated steroids, chlorpromazine, herbal medications, arsenic), sepsis and hypoperfusion states, infiltrative diseases (eg, amyloidosis, lymphoma, sarcoidosis, and tuberculosis), pregnancy, cirrhosis, choledocholithiasis, intrinsic and extrinsic tumors of biliary tracts, primary sclerosing cholangitis, acute and chronic pancreatitis.

# Screening
There is insufficient evidence to recommend routine screening for jaundice.

# Natural History, Complications, and Prognosis
Natural history of jaundice varies greatly and symptoms can manifest at any age of life depending on the underlying cause. The type and the severity of complications depends on the underlying cause leading to jaundice. Certain individuals may not suffer any long-term complications and recovers fully, while for others the appearance of jaundice may be the first indication of a life-threatening situation.

# Diagnosis

## Diagnostic Study of Choice
Bilirubin plasma level is the gold standard test for the diagnosis of jaundice. Usually the concentration of bilirubin in the blood must exceed 23 mg/dL for the coloration to be easily visible.

## History and Symptoms
Common symptoms of jaundice that the patient will notice, is yellowing of the skin, nausea, and vomiting. Specific symptoms will depend on the underlying factor that caused jaundice to occur. Patients may present with fever, anorexia, dark urine, fatigue, pruritis, right upper quadrant pain. A detailed history of alcohol use, blood transfusions, history of viral hepatitis and family history of liver disease must be taken in all patients.

## Physical Examination
Jaundice is a yellowish discoloration of the skin and sclerae that is an important symptom of elevated serum bilirubin. Physical examination of patients with jaundice is based on underlying disease, include Cervical lymphadenopathy, hepatomegaly, splenomegaly, and peripheral edema.

## Laboratory Findings
An elevated concentration of serum total bilirubin is diagnostic for jaundice. The upper limit of normal is >1 mg/dL or >1.3 mg/d in some laboratories. Hyperbilirubinemia can be further categorized as conjugated or unconjugated. Serum conjugated bilirubin concentration >0.4 mg/dL (6.8 micromol/L) revealed conjugated hyperbilirubinemia. In unconjugated hyperbilirubinemia conjugated bilirubin is 5 mg/dL (85 micromol/L).

## Electrocardiogram
There are no ECG findings associated with jaundice.

## X-ray
There are no x-ray findings associated with jaundice.

## CT
Abdominal CT scan may be helpful in the diagnosis of cirrhosis in patient with jaundice. Findings on CT scan suggestive of cirrhosis include cirrhotic liver, as shrinkage and atrophy in liver, dilated portal vein and/or splanchnic veins, esophageal varices, collaterals in any abdominal organ, splenomegaly, and ascites.

## MRI
Abdominal MRI may be helpful in the diagnosis of jaundice caused by cirrhosis. Findings on MRI suggestive of cirrhosis include re-canalized umbilical vein, dilated portal vein and/or splanchnic veins, esophageal varices, collaterals in any abdominal organ, splenomegaly, and ascites.

## Echocardiography or Ultrasound
Ultrasonography may be helpful in the diagnosis of jaundice due to cirrhosis. Findings on an abdominal ultrasonography suggestive of cirrhosis include splenomegaly, ascites, re-canalization of umbilical vein -- pathognomonic of portal hypertension, and porto-systemic collaterals.

## Other imaging studies
Endoscopic retrograde cholangiopancreatography (ERCP) is an alternative imaging modality for diagnosing the cause of cholestasis in patients with jaundice.

## Other Diagnostic Studies
The gold standard diagnostic test for jaundice caused by cirrhosis is liver biopsy, although it is rarely necessary for diagnosis or treatment. Sample of the liver is obtained bypercutaneous approach, transjugular approach, and laparoscopic radiographically- guided fine-needle approach. A biopsy is not necessary if the clinical, laboratory, and radiologic data suggest cirrhosis. There is a small but significant risk associated with liver biopsy, and cirrhosis itself predisposes to the complications of liver biopsy.

# Treatment

## Medical Therapy
The mainstay of treatment for jaundice is to conjugate the unconjugated bilirubin or excretion and clearance of bilirubin from the circulation. Jaundice is treated mainly through treating underlying diseases, such as viral hepatitis, alcoholic hepatitis, or cirrhosis.

## Surgery
Surgery is not the first-line treatment option for patients with jaundice. Surgery is usually reserved for patients with either cirrhosis, cholestasis, and liver failure. The surgical procedures which are used to treat jaundice include transjugular intrahepatic portosystemic shunting (TIPS), cholecystectomy, and liver transplantation.