Jaundice- Clinical correlation and management: Dr. YK Amdekar
M3 India Newsdesk May 25, 2020
Dr. Amdekar elaborates on the basic concepts of jaundice, its clinical correlates and diagnosis of different types based on physical and laboratory evaluation.
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What is jaundice?
Jaundice is the yellow discoloration of sclera, skin and mucous membranes. It is visible in sclera as icterus (Icterus is a bird with yellow beak), only when serum bilirubin exceeds 2 mg%. Normal serum bilirubin level varies between 0.2 to 1 mg% and hence jaundice is not visible early in the course of rising bilirubin until it crosses 2 mg%.
Clinical correlates of jaundice
Patients report yellow-coloured urine before icterus is visible in their eyes. However, urine is high-coloured in many other conditions such as in concentrated urine due to dehydration, haematuria and drug-induced states. The shade of high-coloured urine is different in all these conditions, urine is dark yellow in jaundice.
The yellow colour of urine is due to excretion of water-soluble conjugated bilirubin while unconjugated bilirubin being not water-soluble, cannot be excreted in urine and so, urine is not yellow in hemolytic jaundice even when sclera is yellow. Thus urine color differentiates haemolytic jaundice from hepatobiliary jaundice.
Mild icterus is not easy to make out as sclera may appear muddy due to environmental exposure in non-jaundiced individuals and is often confused with icterus. Skin and mucous membranes appear yellow only when jaundice becomes severe. In fact, common cause of yellow skin is carotenemia (due to consumption of carrots in normal individuals) wherein eyes are not yellow and so it cannot be confused with jaundice.
Physiology of jaundice
During the breakdown of RBCs at the end of their life span of about 120 days, haemoglobin is released. Haemoglobin consists of haeme and globin. Haeme is iron and biliverdin. The protein, globin and iron are stored in the body while biliverdin is converted to bilirubin that is bound to albumen and transported to the liver where it is conjugated to the water-soluble form. It is excreted in the duodenum via bile and then excreted in stools and urine. On an average, 1% of RBCs break down each day and the amount of bilirubin formed can be easily handled by metabolic processes in the liver. In fact, liver has lots of functional reserve but to a limit. So when this limit is exceeded, jaundice develops due to accumulated bilirubin.
Types of jaundice
Excessive breakdown of RBCs results in large amounts of bilirubin that cannot be handled by the normal liver. Hence, unconjugated bilirubin accumulates in the body. Unconjugated bilirubin is not water-soluble and so cannot be excreted. Thus, urine is not high coloured in haemolytic jaundice. Unconjugated bilirubin may accumulate in the brain leading to dysfunction (bilirubin encephalopathy) especially in a newborn baby or if a large amount is produced. It typically happens in severe haemolysis due to Rh blood group incompatibility in a neonate. Besides blood group incompatibility in a neonate, increased haemolysis occurs due to congenital defects as in case of Thalassemia, sickle cell disease, spherocytosis, and G6PD deficiency. Jaundice occurs with exposure to some of the drugs and also in acquired autoimmune haemolysis.
It occurs as a result of hepatic cell damage. The liver has lots of reserve and only 15% of liver cells are enough to handle normal amount of bilirubin. Thus, when more than 85% of liver cells are involved, even a small amount of unconjugated bilirubin produced by normal RBCs breakdown, resulting in jaundice. Depending upon the degree of conjugation defect, part of the bilirubin that gets conjugated is excreted in the urine and so urine is high-coloured. As liver cells are damaged, other liver functions (production and metabolism) are also affected.
Hepatocellular jaundice due to isolated specific defect
In this type, the deficient enzyme responsible for conjugation fails to convert normal amount of unconjugated bilirubin that accumulates in the body (simulating haemolytic jaundice) and as it is not water-soluble, urine is not high-coloured (Criggler-Najjar or Gilbert syndrome). The deficient enzyme responsible for bilirubin excretion results in accumulation of conjugated bilirubin that colours urine yellow (Dubin-Johnson and Rotor syndrome).
Normal amount of bilirubin produced is conjugated by the liver, but due to obstruction to excretion into the intestines, conjugated bilirubin accumulates in the body. However as conjugated bilirubin is water-soluble, it is excreted in urine and so urine is high-coloured. As bilirubin cannot enter the intestines, stool is clay-coloured. Normal stool is brownish or yellowish in color due to presence of stercobilin – excretory form of conjugated bilirubin in intestines. Biliary obstruction may be due to congenital defect such as biliary atresia or acquired conditions such as biliary calculus, cholangitis or malignancy.
Hepatobiliary or biliary hepatic jaundice
The liver cell – hepatocyte disease if not controlled in time spreads to the biliary tract and often patients present with hepatobiliary disease – meaning both the components of liver – hepatocyte and biliary tract are involved. A similar situation arises when primary biliary tract disease spreads to hepatocytes thus involving both the structures. Thus, it is clear that timely intervention of hepatocyte or biliary tract disease may prevent spread of disease to other parts of the liver.
Clinical approach to jaundice
Mild degree of jaundice may not be easily discernable unless one examines the eyes against natural sunlight. At times, muddy sclera may be mistaken for jaundice. Mild jaundice does not give yellow hue to the skin or mucous membranes. Yellowish skin without yellow eyes suggests carotenemia and not jaundice.
High colorued urine may also be due to other causes and urine is not high-coloured in haemolytic jaundice. Similarly, clay-coloured stools may be due to fat malabsorption or giardiasis. Once clinical jaundice is confirmed, high-coloured urine suggests either hepatocyte or biliary tract disease. Clay-coloured stools and itching favour biliary obstruction though may also be seen in severe hepatocyte disease.
Normal urine color in jaundice indicates haemolytic jaundice that is also characterised by pallor. However, pallor and yellowish tinge may look similar and may be mistaken for one or the other. In haemolytic jaundice pallor is more prominent than in jaundice that is mild. Hepatocyte or biliary tract disease may also look pale due to co-morbid conditions.
In a short duration of jaundice, (hepatitis A or E infection) more sickness disproportionate to degree of jaundice favours hepatocyte disease while a high degree of jaundice with reasonably maintained health status indicates biliary disease.
In a long duration jaundice as in the case of hepatitis B or C infection, metabolic liver diseases (Wilson’s diseae), cirrhosis and autoimmune hepatitis, nutrition and growth are affected. Hepatomegaly with or without splenomegaly are seen in almost all of these cases of jaundice.
In chronic hepatocyte disease such as cirrhosis, there may not be jaundice until late stages, at which time ascites is also often present. However, absence of hepatosplenomegaly in the presence of jaundice suggests specific enzyme deficiency and such patients are otherwise healthy without any liver dysfunction or pallor.
Portal hypertension is seen in chronic liver diseases and manifests as hepatosplenomegaly with ascites. Liver cell failure is characterised by encephalopathy and bleeding.
Serum bilirubin – direct (conjugated) and indirect (unconjugated) components
Direct bilirubin more than 2 mg% is considered as conjugated bilirubinemia irrespective of total and indirect bilirubin. When total bilirubin is small in amount, direct component more than 20% of total is also considered as conjugated bilirubinemia.
SGPT (ALT) and SGOT (AST)
There are intracellular enzymes and so liver cell destruction leads to increase in enzyme level in blood. SGPT is more specific to liver pathology as SGOT also increases in other diseases such as heart or skeletal muscle affection. SGPT is higher than SGOT in primary liver disease while SGOT is more than SGPT in systemic diseases with secondary liver involvement. Hence, it is ideal to order both enzymes in assessment of liver disease.
SGPT is very high in acute destruction of liver cells as seen in acute viral A hepatitis, in which SGPT may be in thousands. Per se, it does not suggest any serious illness, but indicates acute disease.
Serum proteins – albumen and globulin
Albumen level goes down in chronic liver cell disease but not in acute liver cell disease as half-life of albumen is three weeks and takes time to go down. Serum globulins are often increased in immune mediated disorders.
Levels of alkaline phosphatase increase in biliary obstruction. However, it is not specific to biliary disease as it is also increased in muscle disease.
GammaGT – gamma glutamyl transferase
High level of this enzyme is more specific in biliary obstruction as it is not increased in muscle disease.
As hepatocyte produces coagulation factors, prothrombin time is increased in severe liver disease and hence it is a measure of severity of disease. It indicates liver cell failure.
In suspected viral hepatitis (A,B.C,E), viral markers may help in confirming diagnosis. Hepatitis B virus has surface, core and E antigen and the host responds with antibodies to the surface and E antigen. Core antigen is present only in liver cells and so no antibodies are seen in blood. Other viruses may also affect the liver such as CMV or HIV.
Presence of bile salts and pigments confirms diagnosis of conjugated bilirubinemia. CBC is not very useful except in cases where one suspects acute bacterial infection as in acute cholangitis.
USG helps in delineating patency of bile ducts and presence of bile in gall bladder. It also may suggest echo-structure of liver that may be corroborative.
Histopathology of liver
Liver biopsy is reserved for diagnosis of cirrhosis and chronic hepatitis.
Most of liver diseases are treated with symptomatic therapy and there is no specific intervention except for hepatitis B and C which can be treated with drugs and should be best managed by specialists. Biliary tract disorders may be surgically treated. Liver transplant is now possible for many diseases.
Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.
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