Bilirubin accumulation

In a small proportion of cases of hemolytic disease of the newborn (inspissated bile syndrome), large amounts of conjugated bilirubin as well as free bilirubin accumulate in the plasma due to obstruction (J3, L2, S16). Conjugated bilirubin is apparently nontoxic to the brain so that exchange transfusions in such infants are indicated only if the free bilirubin and not the total bile pigment concentration is rising above 20 mg/100 ml plasma. 

Nakayama M, Takahashi K, Komura T, et al, Increased expression of heme oxygenase-1 and bilirubin accumulation in foam cells of rabbit atherosclerotic lesions. Arterioscler Thromb Vase Biol 2001 21(8) 1373-1377. 

One such example is the use of ultraviolet (UV) light to treat infant jaundice. Infant jaundice is a condition in which the skin and the whites of the eyes appear yellow because of high levels of the bile pigment bilirubin in the blood. BUirubin is a breakdown product of the oxygen-carrying blood protein hemoglobin. If bilirubin accumulates in the body, it can cause brain damage and death. The immature liver of the baby cannot remove the bilirubin. 

Jaundice is a yellow discoloration involving the sclerae (the "whites " of the eyes) and skin. It is caused by the deposition of bilirubin, a yellow degradation product of heme. Bilirubin accumulates in the blood under conditions of liver injury, bile duct obstruction, and excessive degradation of heme. 

When the amount of bilirubin produced is greater than the amount excreted, bilirubin accumulates in the blood and stains the tissue, leading to yellow discoloration called jaundice. The mechanism by which bilirubin stains tissue is not clear. It is assumed that bilirubin is transferred from plasma proteins to tissue proteins, and, as can be expected, some proteins have a greater affinity for bilirubin than others. For example, elastic tissue avidly picks up bilirubin. Direct bilirubin is more readily fixed by tissues than indirect bilirubin, except in brain of the newborn, where unconjugated bilirubin is more easily picked up by the brain than conjugated bilirubin. 

Cytochrome p450 then removes the iron centre from the hiliverdin structure hy reducing it to iron(ii). Biliverdin reductase then reduces a double bond in the structure introducing another pyrrole ring to giving the unconjugated bilirubin. If unconjugated bilirubin accumulates it can cause jaundice, particular in babies, which can cause serious health problems and can be potentially fatal. 

When bifimbin in the blood exceeds 1 mg/dL (17.1 lmol/L), hyperbifimbinemia exists. Hyperbilirubinemia may be due to the production of more bilirubin than the normal fiver can excrete, or it may result from the failure of a damaged fiver to excrete bilirubin produced in normal amounts. In the absence of hepatic damage, obstmction of the excretory ducts of the fiver—by preventing the excretion of bilirubin—will also cause hyperbilirubinemia. In all these situations, bifimbin accumulates in the blood, and when it reaches a certain concentration (approximately 2-2.5 mg/dL),... 

The sinusoids transport both portal and arterial blood to the hepatocytes. The systemic blood delivered to the liver contains nutrients, drugs, and ingested toxins. The liver processes the nutrients (carbohydrates, proteins, lipids, vitamins, and minerals) for either immediate use or for storage, while the drugs and toxins are metabolized through a variety of processes known as first-pass metabolism. The liver also processes metabolic waste products for excretion. In cirrhosis, bilirubin (from the enzymatic breakdown of heme) can accumulate this causes jaundice (yellowing of the skin), scleral icterus (yellowing of the sclera), and tea-colored urine (urinary bilirubin excretion). 

The over-production of bilirubin to the point at which the liver s capacity to metabolize is exceeded or if there is dysfunction of the liver itself due to damage or metabolic immaturity, can lead to a yellow discolouration of tissues called jaundice. The accumulation of unconjugated bilirubin in neonates, often as a result of antibody-mediated destruction of the baby s red cells is dangerous as serious and irreversible brain damage can occur. Acute or chronic damage to the adult liver (hepatitis) may cause jaundice but not brain damage. 

Jaundice (yellow color of skin, whites of the eyes) may occur when blood levels of bilirubin exceed normal (icterus). Jaundice may be characterized by an increase in unconjugated (indirect) bilirubin, conjugated (direct) bilirubin, or both. Accumulation of bilirubin (usually unconjugiated) in the brain (kernicterus) may result in death. When conjugated bilirubin increases, it may be excreted, giving a deep yeUow-red color to the urine. Examples of conditions associated with increased bilirubin and jaundice include the following. 

Conjugation with glucuronyl residues is of great importance for the metabolic fate of bilirubin (S3), steroids (L5, M2, R8), catecholamines (W17) and other hydrophobic compounds (D8, D9). Neonatal accumulation of bilirubin in man and rats may trigger maturation of UDP-glucuronyltransferase (Bl, B2, T6). Delayed maturation of the enzyme, or its partial or total deficiency, are critical factors in the development of kernicterus (P6). Compared to other species partial deficiency of the... 

Failure to conjugate bilirubin to glucuronic acid causes accumulation of bilirubin in the unconjugated form in the blood. 

Types of jaundice Jaundice can be classified into three major forms described below. However, in clinical practice, jaundice is often more complex than indicated in this simple classification. For example, the accumulation of bilirubin may be a result of defects at more than one step in its metabolism. 

The Treatment of the Jaundice of New-born Infants. This disease results from the accumulation of bilirubin in the blood, when the liver is not yet able to function with its full efficiency. It takes its name from the yellowish colour of the skin, due to the relatively high concentration of bilirubin which absorbs in the violet and blue regions of VIS light. 

When the red blood cells die after their average lifetime of some 120 days, their haemoglobin is degraded to bilirubin which is then filtered by the liver. In new-born infants this process cannot take place often for several days, while the liver becomes fully functional. The accumulation of bilirubin in the... 

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