JAUNDICE[ PRE-HEPTIC JAUNDICE/    HEPTIC JAUNDICE/ POST-HEPTIC     JAUNDICE]

 

       Jaundice is a yellow discoloration of the skin, mucous membrane, and the whites of the eyes caused by increased amounts of bilirubin in the blood. Serum bilirubin level is normally below 1.0 mg/dl, and levels over 2-3 mg/dl, typically results in jaundice.


                                                   Bilirubin metabolism

           Destruction of senescent red blood cells in the tissue macrophages [in spleen, liver, bone marrow, etc.] results in catabolism of haemoglobin to haeme (and globin) and subsequently to bilirubin. Bilirubin released from the tissue macrophages is called unconjugated bilirubin. It is a lipid soluble pigment transported in blood tightly bound to albumin. In the liver, the hepatocytes take up unconjugated bilirubin from the blood, convert it into water-soluble compounds called conjugated bilirubin (bilirubin mono-and di-glucuronide ), and excrete it into bile canaliculi. Bile duct excretes conjugated bilirubin into small intestine 
           Conjugated bilirubin cannot be absorbed in the intestine. In the  large gut, bacterial degradation converts it to stercobilinogen(=urobilinogen ) ,a water soluble colourless product. Some of the urobilinogen is absorbed into the portal blood to reach the systemic circulation. Being water soluble, it is excreted into the urine by the kidneys. The remaining stercobilinogen is excreted in the faeces. On exposure to air, stercobilinogen is oxidized to stercobilin which gives brown color to the faeces .
            In obstructive jaundice, since bilirubin does not reach the intestine, stercobilinogen and urobilinogen excretion in the faeces and urine is very low. That accounts for the pale chalky-color of the stools of such patients.
             conjugated bilirubin is water-soluble; is present in the blood, it is excreted by the kidneys into the urine (bilirubinuria). Bilirubin imparts brown color to the urine, important clinical sign of conjugated hyperbilirubinemias (hepatic and post-hepatic jaundice). Classification of jaundice based on the pathophysiology of bilirubin metabolism is given below;

      Jaundice type
       
1. Pre-hepatic\haemolytic;
                    The pathology is occurrring prior to the liver in bilirubin metabolism. It can be due to either:
                 A. Increased haemolysis due to intrinsic (congenital) defects in red blood cells 
                 B. Extrinsic causes of increased  haemolysis
2. Hepatic\hepato-cellular;
                      The pathology is located within the liver due to disease of parenchymal cells of liver
3. Post-hepatic;
                        The pathology is located after the conjugated of bilirubin in the liver, due to obstruction in the biliary passage.  

PRE-HAPATIC JAUNDICE 
                  Pre-hepatic jaundice is caused by an increased rate of haemolysis due to a congenital (sickle cell anemia, spherocytosis, thalassemia) or an acquired defect in the structure of red cells. The increased breakdown of red blood cells leads to an increase in the production of unconjugated bilirubin. Presence of excess of unconjugated bilirubin in blood causes its deposition into various tissues causing jaundice. Increased production of unconjugated bilirubin leads to increased production and increased excretion of stercobilinogen and urobilinogen in stools and urine respectively. Bilirubin is not found in the urine because unconjugated bilirubin is not water-soluble.
           laboratory finding include:
                  *urine: excess of urobilinogen, absent bilirubin.
                  *serum: Increased unconjugated bilirubin

HEPTIC JAUNDICE 
        Hepatocellular(hepatic) jaundice results from an acute or chronic injury to hepatocytes(viral hepatitis, cirrhosis, alcoholic liver disease), cell necrosis reduces the liver's ability to take up, conjugate and excrete bilirubin. Therefore, level of both unconjugated and conjugated type of bilirubin rises in the blood. The conjugated type of bilirubin, When present in the blood is excrete in the urine.
          Laboratory findings include;
              *Urine: Bilirubin present.
              *Serum contains excess of both conjugated and unconjugated bilirubin.
              *Elevated levels of certain enzymes in the blood indicative of hepatocellular injury.  

POST-HEPATIC JAUNDICE
          Post-hepatic jaundice, also called obstructive jaundice, is caused by an interruption to the drainage of bile, containing conjugated bilirubin, in the system. The most common causes are gallstones in the common bile duct, and cancer in the head of the pancreas, through which the bile duct passes. The back pressure on bile causes regurgitation of conjugated bilirubin and bile salts into blood circulation.
          In complete obstruction of the bile duct, bile does not reach the intestine, stercobilinogen and urobilinogen are not found in the faeces and urine, restively.
          Hence faeces have a pale chalky appearance
             *urine: Bilirubin present, urobilinogen absent
             *Serum contains excess of conjugated bilirubin.