Bilirubin Hemolytic jaundice

In jaundice secondary to hemolysis, the increased production of bilirubin leads to increased production of urobilinogen, which appears in the urine in large amounts. Bilirubin is not usually found in the urine in hemolytic jaundice (because unconjugated bihmbin does not pass into the urine), so that the combination of increased urobilinogen and absence of bihmbin is suggestive of hemolytic jaundice. Increased blood destruction from any cause brings about an increase in urine urobilinogen. 

Alterations in the metabolism of heme. A. Hemolytic jaundice. B. Neonatal jaundice. [Note The enterohepatic circulation of urobilinogen is omitted for simplicity.] BG = bilirubin glucuronide B = bilirubin U = urobilinogen S = stercobilin. 

Definition and causes of jaundice Jaundice (icterus) refers to the yellow color of the skin, nail beds, and sclerae caused by deposition of bilirubin, secondary to increased bilirubin levels in the blood. There are three major forms of jaundice hemolytic jaundice, caused by massive lysis of red blood cells, releasing more heme than can be handled by the reticuloendothelial system obstructive jaundice, resulting from obstruction of the bile duct and hepatocellular jaundice, caused by damage to liver cells that decreases the liver s ability to take up and conjugate bilirubin. In addition, neonatal jaundice is caused by the low activity of hepatic glucuronylation of bilirubin, especially in premature infants. 

It is generally accepted that in normal subjects, most, but not necessarily all, of the bilirubin formed results from the breakdown of hemoglobin in the reticuloendothelial system. The bilirubin is then conjugated in the liver and excreted into the bile as a water-soluble pigment. The capacity of the liver to conjugate bilirubin is limited (W6), so that in cases of overproduction (e.g., hemolytic jaundice) free bilirubin will appear in the plasma. A similar result will be obtained if the ability of the liver to conjugate bilirubin is diminished (e.g., in the newborn infant). On the other hand, if the excretion of the bile is for some reason... 

A15. Arias, I. M., Studies of chronic familial non-hemolytic jaundice with conjugated bilirubin in the serum with and without an unidentified pigment in the liver cells. Am. /. Med. 31, 510-518 (1961). 

In addition, there are some hepatic metabolic uses. Because hepatic glucuronyl transferase and the bilirubin-binding Y protein are increased by the barbiturates, phenobarbital has been used successfully to treat hyperbilirubinemia and kernicterus in the neonate. The nondepressant barbiturate phetharbital (A-phenylbarbital) works equally well. Phenobarbital may improve the hepatic transport of bihrubin in patients with hemolytic jaundice. 

The anemia is essentially hemolytic, i.e., the heme pigment is synthesized at normal rates but it is not used. The excess pigment is destroyed to yield bilirubin, and hemolytic jaundice develops. Consequently, the clinicopathological picture is that of a hypochromic hemolytic anemia. 

According to Siedel S/t-l) about one-tenth of the urobilinogen and stercobilinogen in the lower intestinal tract may be reabsorbed into the blood stream and re-excreted throu the bile. Only a small amount, 0.5-2 mg per day escapes into the urine where autoxidation to urobilin and stercobilin occurs. Gray S44) believes that reabsorption of these compounds is not a prominent process in man. The finding of urobilin in urine and plasma under abnormal conditions (e.g., in hemolytic jaundice, or partial obstruction of bile secretion) is conadered to be due either to the liver having the capacity to reduce bilirubin fiu ther (S40) or to reabsorption of urobilinogen and a limited ability of the liver to secrete it into the bile (34 ). 

Knowledge of the biochemistry of the porphyrins and of heme is basic to understanding the varied functions of hemoproteins (see below) in the body. The porphyrias are a group of diseases caused by abnormalities in the pathway of biosynthesis of the various porphyrins. Although porphyrias are not very prevalent, physicians must be aware of them. A much more prevalent clinical condition is jaundice, due to elevation of bilirubin in the plasma. This elevation is due to overproduction of bilirubin or to failure of its excretion and is seen in numerous diseases ranging from hemolytic anemias to viral hepatitis and to cancer of the pancreas. 

The commonest causes of obstructive (posthepatic) jaundice are cancer of the head of the pancreas and a gallstone lodged in the common bile duct. The presence of bilirubin in the urine is sometimes referred to as choluria—therefore, hepatitis and obstruction of the common bile duct cause choluric Jaundice, whereas the Jaundice of hemolytic anemia is referred to as acholuric. The laboratory results in patients with hepatitis are variable, depending on the extent of damage to parenchymal cells and the extent of micro-obstruction to bile ductules. Serum levels of ALT and AST are usually markedly elevated in hepatitis, whereas serum levels of alkaline phosphatase are elevated in obstructive liver disease. 

There are several conditions that mimic the laboratory picture of acute hepatitis. Hemolytic anemia can cause jaundice, increased LD, and slight increases in AST and ALT. In contrast to hepatitis, the increase in bilirubin is predomi-... 

---