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					Neonatal jaundice
1-Bilirubin production.
2-Transport in blood.
3-Hepatocellular uptake.
4-Intracellular transport in hepatocytes.
5-Conjugation with glucuronic acid.
6-Secretion into bile ducts.
7- Intestinal metabolism.
8- Renal excretion of bilirubin
9- Renal excretion of urobilinogen
– Bilirubin is the terminal product of heme
  metabolism. Heme is present in hemoglobin
  and in other oxidative compounds such as
  hepatic mitochondrial and microsomal
  cytochromes (P-450).
– Thus plasma bilirubin is part erythropoietic
  and part non-erythropoietic.
– Approximately, 85 % erythropoietic and 15%
                     Cont ..
– The erythropoietic fraction originates from two
  sources: the circulating normal aging red cells and the
  immature defective red cells of the bone marrow.
– The daily production of bilirubin is 250 to 350 mg.
– Shunt bilirubin is called that portion that does not
  originate from circulating red cells but originates from
  immature and defective red cells (7%) and from non-
  hemoglobin heme compounds, particularly from
  hepatic cytochromes and from myoglobin.
  – pathologic states: sideroblastic anemia,
    megaloblastic anemia, erythroleukemia, lead
    poisoning and a congenital disorder called
    "idiopathic dyserythropoietic jaundice".
  – The patients affected by this condition do not
    have hemolysis. They have
    hyperbilirubinemia and jaundice.
  – The hyprbilirubinemia is due to shunt

  – Bilirubin from erythropoietic heme is produced
    by monocytic macrophages, reticulo-
    endothelium, in every organ but especially in
    the spleen, liver and bone marrow.
  – The bilirubin from non-erythropoietic hepatic
    heme is produced in the hepatocytes.

HEME + Heme oxygenase = OXY- HEME ( closed
tetrapyrrolic ring with iron)
OXY- HEME + heme reductase = BILIVERDIN (open
tetrapyrrolic ring without iron)
BILIVERDIN + biliverdin reductase = BILIRUBIN
Pathology of bilirubin production
– Hyperbilirubinimia with jaundice occurs in increased
  destruction of red blood cells namely: hemolysis.
– It occurs in : -
– 1)congenital disorders of red cells (sickle cells,
  thalassemia, spherocytosis),
– 2) immune hemolysis (erythroblastosis fetalis)
– 3) acquired diseases of red cells (dyserythropoiesis), etc.
– In the adult, even a marked hemolysis does not produce
  significant increase of serum bilirubin if the hepatic bilirubin
  clearance is normal.
– In the newborn, a marked hemolysis will be catastrophic.
  At levels of 20mg/dl of serum bilirubin the infant will be
  deeply jaundiced and will develop kernicterus (Nuclear
  jaundice: a grave form of yellow staining and degeneration
  of intracranial gray matter especially of lenticular nucleus
  and subthalamic area).

• Bilirubin is toxic to tissues, therefore, it is
  transported in the blood bound to albumin. Only a
  minute amount of free form is present in the
• Pathology of bilirubin transport in blood.
  – If the free fraction increases, bilirubin will invade and
    damage the tissues. It will cross the blood -brain barrier
    and cause kernicterus in the neonate.
• Free plasma bilirubin can increase in the following
  pathologic conditions:
  – -1- overproduction.
  – -2- defective conjugation in the hepatocyte.
  – -3- presence of substances interfering with bilirubin-
    albumin binding: sulphonamides

  – Bilirubin is taken up by hepatocytes at their
    sinusoidal surface. The albumin-bilirubin bond
    is broken. Albumin remains in the plasma.
    The free molecule of bilirubin enters the
    hepatocyte.This uptake is very rapid.
• Pathology of bilirubin uptake by
• The impairment of uptake will result in
  unconjugated hyperbilirubinemia.

• In the hepatocye bilirubin is bound to cytoplasmic
  proteins: ligandins and Z protein.
• Ligandins are a group of enzymes that represent 2%
  of cytosolic proteins.
• Z proteins bind fatty acids.
• The primary function of these proteins is that of
  avoiding the reflux of free bilirubin into the blood.
• Pathology of intracellular transport.
• No hyperbilirubinemia and jaundice is known due to
  deficiency of ligandins.
• One way for cells to neutralize unwanted compounds is to
  conjugate them with a modified sugar, a glycosyl. The sugars
  used for this reaction are xylose, glucose or glucuronic acid.
• Glucose is normally present in the cell , xylose and glucuronic
  acid are formed from glucose by UDP-glucose
  dehydrogenase. Xylosidation is predominant in plants,
  glucosidation in bacteria and glucuronidation in mammals.
• Unconjugated bilirubinin is lipophilic. Its conjugation with
  glucuronic acid renders it hydrophilic, thus, it can be
  eliminated in the bile.
• Many other agents are eliminated by conjugation with
  glucuronic acid: steroids, thyroid hormone, catecholamines,
  estradiol, testosterone, bile acids, phenols, morphine, which
  can be conjugated by other cells besides hepatocytes
 glucuronidation of bile proceeds in two steps:
– The first glucuronic acid (GA) is synthesized from
  cytosolic glucose that is complexed with
  uridinediphosphate (UDP) and forms udpglucuronic acid
  (UDPGA). From this compound, the glucuronic acid is
  transferred to blirubin. The first reaction is catalyzed by a
  UP- glucose dehydrogenate,
– the second reaction is catalyzed by bilirubin--
  transferase that is synthesized by microsomes. Any
  deficiency of these two enzymes will result in defective
  conjugation and elimination of bilirubin.
– On the other end, administration of microsomal enzyme
  inducers such as phenobarbital, glutethimide and
  antipyrine favour bilirubin conjugation and elimination by
  increasing blirubin transferase activity.
• Conjugation occurs in the endoplasmic reticulum and consists of
  forming an ester between glucuronic acid and one or both propionic
  side-chains of bilirubin. The result will be formation of bilirubin
  mono and di-glucuronides. In general, about 80% of the di and
  less than 20% of the mono are formed.
• Human bile contains also small amounts of unconjugated bilirubin.

• GLUCOSE + UDP-Glucose-dehydrogenase = UDP-GLUCURONIC
• UDPGA + BILIRUBIN + Glucuronyl transferase = BILIRUBIN
  MONO &
    Pathology of bilirubin conjugation

  – Is due to a very mild deficiency of glucuronyl transferase.
    It affects 5 to 7% of the general population. More
    common in males. It consists of mild fluctuating jaundice
    due to non- hemolytic unconjugated hyperbilirubinemia in
    the range of 5 to 7mg/dl or rarely higher.
  – The liver is morphologically normal. State of health and
    life-span are normal. Hemolysis, low caloric diet, nicotinic
    acid will increase the jaundice.
  – A lipid diet will decrease the jaundice.
  – Phenobarbital and other enzyme inducing agents are
  – Is due to a severe deficiency of glucuronyl tranferase.
    Deep jaundice develops at birth, High serum
    unconjugated hyperbilirubinemia, >20 mg/dl., not
    responding to phenobarbital. Absent formation of
    diglucuronides. Death usually in the first year or two
    with kernicterus. Phototherapy, plasmaferesis and
    albumin exchange are beneficial. Liver transplantation
    may be life-saving. The liver is histologically normal.
  – It is apparently a hereditary autosomal recessive trait.

– Is due to a moderate deficiency of glucuronyl
  transferase. Milder unconjugated hyperbilirubinemia
  responding to enzyme inducing agents:
  phenobarbital, gltethimide, phenazone,
  chlorpromazine. Both, mono and di-glucuronides
  are formed. Patients develop normally but some
  may suffer bilirubin encephalopathy, kernicterus.
  They will have unremitting jaundice for the whole
  life. It is a familial disorder.
– defect of bilirubin uptake by hepatocytes.
         THE NEWBORN
It is due to a very transient insufficiency of glucuronyl
    transferase. During the first few days of life there is
    an overproduction of bilirubin and an
    underdeveloped mechanism of the liver to dispose
    of bilirubin.
• Together with deficient conjugation, bilirubin
    production, blood transport, hepatic uptake and
    secretion are all deficient. Sometimes extrahepatic
    factors exist to aggravate the situation: infections,
    drugs competing for binding sites of bilirubin and
    breast feeding. The long chains of fatty acids of the
    breast milk interfere with bilirubin-albumin binding

• The liver is an endocrine and an exocrine gland. It
  secretes synthesized products internally into the
  blood through the sinusoidal surface such as blood
  proteins, coagulation factors etc. and secretes
  external into the biliary tract and the intestine bile
  and many other substances, the terminal products of
  detoxifying function.
• The mechanism of this external secretion is the least
  clear in the physiology of the liver.
• It seems that many cellular organelles are involved in
  this process: vesicles, Golgi complexes, lysosomes,
  plasma membranes, mitochondria, cytoskeleton,
  plasma membranes, canalicular villi.
      Pathology of bile secretion

  – The syndrome consists of chronic benign jaundice due to
    conjugated hyperbilirubinemia without pruritus or elevation
    of serum alkaline phosphatase or histological evidence of
  – The hepatocytes contain an abundance of coarse dark-
    brown pigment similar to melanin . The liver is black but
    normal. Serum bilirubin ranges between 2 and 20mg/dl,
    60% conjugated.
  – Jaundice appears in the first 3 decades of life and is
    intermittent. Sometimes the onset is acute,. The prognosis
    is excellent. The disease is inherited as autosomal
    recessive trait.
  – The diagnosis is made by needle biopsy.

– Bilirubin in the intestine is reduced to urobilins:-
  BILIRUBIN GLUCURONIDE + bacterial or intestinal
  beta-glucuronidase = FREE BILIRUBIN
– FREE BILIRUBIN + bacterial dehydrogenase =
  UROBILINOGEN (colorless)
– UROBILINOGEN + dehydrogenase = UROBILIN
– The bulk of bilirubin, urobilinogen and urobilin is excreted
  in the feces.
– Small amounts of bilirubin and urobilinogen are
  reabsorbed by the intestine and return to the liver.
– The bilirubin is recunjugated in the liver and re-excreted
  in the feces. The reabsorbed urobilinogen is excreted in
  the urine, about 4 mg/ day
Pathology of biliary excretion into the intestine

• The bile does not reach the intestine therefore the feces are acholic.
  There is conjugated hyperbilirubinemia and bilirubinuria.
  Urobilinogen is not formed in the intestine and there is no
  urobilinogen in the urine. because since the bile does not reach the
  intestine, urolinogen is not formed.
• Less bile reaches the intestine. Urobilinogen is formed but in smaller
  amounts. There is less conjugated hyperbilirubinemia, absent
  bilirubinuria and small amounts of urobilinogen in the urine.
• Hemolysis causes unconjugated hyperbilirubinemia. There is no
  bilirubinuria because unconjugated bilirubin is not hydrophilic and
  cannot be excreted in the urine.
• There is increased urobilinogen in the urine because more bilrubin
  reaches the intestine and more urobilinogen is formed an

• Only conjugated bilirubin (the direct fraction) is excreted
  in the urine when its level in the plasma is increased
  above normal. It not present in the urine of normal
  subjects and it is not eliminated in the urine in cases of
  unconjugated hyperbilirubinemia, such as in cases of
• Only the small fraction of non-protein bound bilirubin in
  the plasma passes in the urine.
• Some drugs and bile salts which compete for protein
  binding (salicylates, sofosoxazole) increase the
  threshold of elimination.
• Conjugated bilirubin can be demonstrated in the
  proximal renal tubules.

• Urobilinogen is formed by bacteria in the small intestine and
  in the colon.
• It is then reabsorbed by the small intestine and the colon
  and re-excreted by the liver into the intestine almost entirely.
  A very small amount is therefore excreted into the urine: 0-4
• This amount will increase when more urobilinogen is
  formed or when the liver is sick and unable to re-excrete it.
• This amount will decrease when its formation in the intestine
  is decreased such as in the case of complete bile duct
  obstruction when the bile cannot flow to the intestine where
  urobilinogen is formed by the specific bacteria.
• The urobilinogen formed by bacteria in the small intestine is
  re-absorbed better than that formed in the colon.
   Neonatal jaundice
• Neonatal jaundice is a yellowing of the skin and
  other tissues of a newborn infant. A bilirubin level of
  more than 5 mg/dL manifests clinical jaundice in
  neonates whereas in the adults 2 mg/dL would look
• In newborns , jaundice is detected by blanching
  the skin with digital pressure so that it reveals
  underlying skin and subcutaneous tissue. Jaundice
  newborns have an apparent icteric sclera, and
  yellowing of the face, extending down onto the
• In neonates the dermal icterus is first noted in the
  face and as the bilirubin level rises proceeds
  caudal to the trunk and then to the extremities
• In accurate rules of thumb have been applied to
  the physical exam of the jaundiced infant. Some
  include estimation of serum bilirubin based on
• One such rule of thumb includes infants whose
  jaundice is restricted to the face and part of the
  trunk above the umbilicus, have the bilirubin less
  than 12 mg/dL (less dangerous level).
• Infants whose palms and soles are yellow, have
  serum bilirubin level over 15 mg/dL (more
  serious level).
• In infants jaundice can be measured using
  invasive or non-invasive methods.
• In non invasive method Ingram icterometer and
  Transcutaneous bilirubinometer are used.
    • Levels of neonatal
.     jaundice
           – I - Bilirubin quantity
             between 5 and 8 mg/dl.
           – II - Bilirubin quantity
             between 8 and 10
           – III - Bilirubin quantity
             between 10 and 13
           – IV - Bilirubin quantity
             between 13 and 16
           – V - Bilirubin quantity
             arround 20 mg/dl.
Correlation of dermal zones and levels of jaundice
   Physiological jaundice
• Most infants develop visible jaundice due to elevation of
  unconjugated bilirubin concentration during their first week.
  This common condition is called physiological jaundice.
• This pattern of hyperbilirubinemia has been classified into two
  functionally distinct periods.
   – Phase one
• Term infants - jaundice lasts for about 5 days with a rapid rise
  of serum bilirubin up to 12 mg/dL.
• Preterm infants: For preterm infants jaundice lasts for about a
  week, with a rapid rise of serum bilirubin up to 15 mg/dL.
   – Phase two - bilirubin levels decline about 2 mg/dL for 2 weeks.
• Preterm infants - phase two can last more than 1 month.
• In babies who receive exclusive breast feedings, phase two
  can last more than 1 month.
• Possible mechanisms involved in Physiological
    – Increase bilirubin load on liver cells
•   Increased red blood cell (RBC) volume
•   Increased labeled bilirubin
•   Increased circulation of bilirubin in the liver
•   Decreased RBC survival
    – Defective hepatic uptake of bilirubin from blood plasma
• Decreased ligadin (Y protein)
• Increased binding of Y proteins by other anions
• Decreased liver uptake
    – Defective billirubin conjugation
• Decreased UDPG activity
    – Defective bilirubin excretion
 Pathological Jaundice of Neonates(syn.
Unconjugated pathological hyberbilirubinemia)
Any of the following features characterizes
pathological jaundice:
 – Clinical jaundice appearing in the first 24
 – Increases in the level of total bilirubin by more
   than 0.5 mg/dL per hour or 5 mg/dL per 24
 – Total bilirubin more than 19.5 mg/dL
 – Direct bilirubin ( conjugated ) more than 2.0
 Causes of Pathological Jaundice of Neonates

• Increased production
  – Fetomaternal blood group incompatibility: Rh, ABO
  – Hereditary spherocytosis.
  – Non-spherocytic hemolytic anemia: G-6-PD
    deficiency, a-thalassemia, Vitamin K induced
    hemolysis, pyruvate kinase deficiency.
  – Sepsis.
  – Increased enterohepatic circulation: Pyloris stenosis,
    or large bowel obstruction.
• Decreased clearance
  – Inborn errors of metabolism: Criggler-Najjar syndrome
    type I and II
  – Drugs and Hormones: Hypothryoidism, breast milk
  Differentiation between Physiological and
             Pathological jaundice
• The sign which helps to differentiate pathological
  jaundice of neonates from physiological jaundice of
  neonates are presence of intrauterine retardation,
  stigma of intrauterine infections (e.g. cataracts,
  microcephaly, hepatosplenomegaly etc),
• History of illness is significant.
   Suggestive of pathological jaundice in neonates.
  – Family history of jaundice and anemia,
  – family history of neonatal or early infant death due to liver
  – maternal illness suggestive of viral infection (fever, rash or
  – Maternal drugs (e.g. Sulphonamides, anti-malarials causing
    hemolysis in G-6-PD deficiency)
             Causes of jaundice
• In neonates, benign jaundice tends to develop because of
  two factors –
• the breakdown of fetal hemoglobin as it is replaced with
  adult hemoglobin and the relatively immature hepatic
  metabolic pathways which are unable to conjugate and so
  excrete bilirubin as quickly as an adult.
• This causes an accumulation of bilirubin in the blood
  (hyperbilirubinemia), leading to the symptoms of jaundice.
• If the neonatal jaundice does not clear up with simple
  phototherapy, other causes such as biliary atresia, other
  pediatric liver diseases should be considered.
• Severe neonatal jaundice may indicate the presence of
  other conditions contributing to the elevated bilirubin levels,
  of which there are a large variety of possibilities .These
  should be detected or excluded as part of the differential
  diagnosis to prevent the development of complications.
• They can be grouped into the following categories:
                       Neonatal jaundice

     Unconjugated                     Conjugated bilirubin

•                                         Hepatic            Posthepatic-

•   Pathologic     Physiological jaundice of Neonates

• Hemolytic      Nonhemolytic-

• Intrinsic causes Extrinsic causes
   Intrinsic causes of hemolysis
• Membrane conditions
  – Spherocytosis
  – Hereditary elliptocytosis
• Systemic conditions
  – Splenomegaly
  – Sepsis
  – Arteriovenous malformation
• Enzyme conditions
  – Glucose-6-phosphate dehydrogenase deficiency (also
    called G6PD deficiency)
  – Pyruvate kinase deficiency
• Globin synthesis defect
  – sickle cell disease
  – Alpha-thalassemia
 Extrinsic causes of hemolysis

• Alloimmunity (The neonatal or cord blood
  gives a positive direct Coombs test and the
  maternal blood gives a positive indirect
  Coombs test)
  – Hemolytic disease of the newborn (ABO)
  – Rh disease
  – Hemolytic disease of the newborn (anti-Rh)
  – Other blood type mismatches causing hemolytic
    disease of the newborn
  – Breast milk feeding.
• Non-hemolytic causes
  – Cephalohematoma
  – Polycythemia
  – Sepsis
  – Hypothyroidism
  – Gilbert's syndrome
  – Crigler-Najjar syndrome

• Post-hepatic
  – Biliary atresia
  – Bile duct obstruction
                         Cont …
• Hepatic causes
• Infections
   – Hepatitis B
   – TORCH infections
   – Sepsis
• Metabolic
   – Galactosemia
   – Alpha-1-antitrypsin deficiency
   – Cystic fibrosis
• Drugs
• Total parenteral nutrition
• Idiopathic
Non-organic causes
• Breast feeding jaundice
  – "Breastfeeding jaundice or "lack of
    breastfeeding jaundice," is caused by
    insufficient breast milk intake, resulting in
    inadequate quantities of bowel movements to
    remove bilirubin from the body. This can
    usually be ameliorated by frequent
    breastfeeding sessions of sufficient duration
    to stimulate adequate milk production.
  – Passage of the baby through the vagina
    during birth helps milk production in the
    mother's body, so infants born by cesarean
    section are at higher risk for this condition
Breast milk jaundice
– Whereas breast feeding jaundice is a mechanical
  problem, breast milk jaundice is more of a
  biochemical problem.
– The term applies to jaundice in a newborn baby
  who is exclusively breastfed and in whom other
  causes of jaundice have been ruled out.
– The jaundice appears at the end of the first week
  of life and hence overlaps physiological jaundice.
  It can last for up to two months.
• Several factors are thought to be
  responsible for this condition.
  – First:-
     • in exclusively breastfed babies the establishment of
       normal gut flora is delayed. The bacteria in the adult
       gut convert conjugated bilirubin to stercobilinogen
       which is then oxidized to stercobilin and excreted in the
     • In the absence of sufficient bacteria the bilirubin is de-
       conjugated and reabsorbed. This process of re-
       absorption is called entero-hepatic circulation.
• Second : -
  – the breast-milk of some women contains a
    metabolite of progesterone called 3-alpha-20-
    beta pregnanediol. This substance inhibits the
    action of the enzyme uridine diphosphoglucuronic
    acid (UDPGA) glucuronyl transferase responsible
    for conjugation and subsequent excretion of
  – Reduced conjugation of bilirubin leads to
    increased level of bilirubin in the blood.
• Third : -
   – an enzyme in breast milk called lipoprotein lipase
     produces increased concentration of nonesterified free
     fatty acids that inhibit hepatic glucuronyl transferase which
     again leads to decreased conjugation and subsequent
     excretion of bilirubin.
• Breast-milk jaundice does not usually cause any
  complication (like kernicterus) if the baby is
  otherwise healthy.
• The serum bilirubin level rarely goes above 20 mg
  /dL. It is usually not necessary to discontinue breast-
  feeding as the condition resolves spontaneously.
• Adequate hydration should be maintained by giving
  extra fluids if necessary.
 Non-invasive measurement of jaundice

• This method is more accurate and less subjective
  in estimating jaundice.
• Ingram icterometer: In this method a piece of
  transparent plastic known as Ingram icterometer
  is used. Ingram icterometer is painted in five
  transverse strips of graded yellow lines. The
  instrument is pressed against the nose and the
  yellow colour of the blanched skin is matched with
  the graded yellow lines and biluribin level is
• Transcutaneous
  bilirubinometer: This is hand
  held, portable and rechargable.
  When pressure is applied to the
  photoprobe, a xenon tube
  generates a light; and this light
  passes through the
  subcutaneous tissue. The
  reflected light returns through
  the second fiber optic bundle to
  the spectrophotometric module.
  The intensity of the yellow color
  in this light, after correcting for
  the hemoglobin, is measured
  and instantly displayed in units.
• Exchange Transfusion (ExTx)
• INTRODUCTION: This procedure, used
  most commonly to treat severe
• hyperbilirubinemia, removes the infant’s
  circulating blood and replaces it with
  donorblood. The amount of blood
  exchanged is expressed as multiples of
  the infant’s blood
    PROCEDURE: several possible methods
    Method and types of catheters: -
    A. Continuous Exchange is performed by two operators,
    one infuses blood and theother simultaneously withdraws it.
    The best method is : -
•   withdrawal from an umbilical arterial catheter (UAC) and
    infusion into an umbilical venous catheter (UVC) with tip
    in IVC or right atrium.
•   Flush withdrawal catheter with heparinized saline every 10-
    15 min to prevent clotting.
•   Alternatives are:
•   withdrawal from a peripheral arterial catheter and
    infusion into a centralvenous catheter. However, this is
    slow and the arterial catheter frequently clots.
•   withdrawal from a central venous catheter and infusion
    into a peripheral vein.
•   Flush the central catheter frequently to prevent clotting.

B. Push-Pull Method can be done through:
  – a single UVC with tip in IVC or right
  – a single UAC with tip in lower aorta (below
    3rd lumbar vertebra)
  – Caution: Do not perform ExTx through a
    UVC if the tip is in the portal circulation.
  – This may cause necrotizing enterocolitis by
    markedly decreasing bowel blood flow.
Cont ..
 Important reminders:
• Monitor ECG, blood pressure, O2
  saturation, and temperature during ExTx.
• Measure pH at mid-point and at end of
  ExTx (more frequently in a “sick” baby.
• Measure glucose and electrolytes at end
  of ExTx, and glucose at 10, 30, 60 min
• Warm blood to 34-35º C. Warming blood
  to >37º C causes hemolysis.
     Complications of ExTx
• Problem with Effect on Donor Blood and
  Effect on Infant and Treatment
• Blood is cold – Hypothermia ------ Warm
  donor blood to 34 - 35o C
• High K+ ------     Hyperkalemia,------ Use fresh
  blood,     monitor ECG
• Low pH ---------Acidosis-------- Consider
  buffering blood
• No platelets------Thrombocytopenia ----Consider
  platelet Tx at end of ExTx.
Normal Bilirubin Metabolism and Bilirubin
   Metabolism during Phototherapy.
       Normal Bilirubin Metabolism and Bilirubin
          Metabolism during Phototherapy.

• normal metabolism, lipophilic bilirubin, which results
  predominantly from the catabolism of red cells,
  circulates in blood mainly as a noncovalent
  conjugate with serum albumin. After uptake by the
  liver, it is converted into two isomeric
  monoglucuronides and a diglucuronide (direct
  bilirubin) by the enzyme
  uridinediphosphoglucuronosyltransferase 1A1
• The water-soluble glucuronides are excreted in bile
  with the aid of a canalicular multidrug-resistance–
  associated transport protein, MRP2. Without
  glucuronidation, bilirubin cannot be excreted in bile
  or urine.

• In neonates, hepatic UGT1A1 activity is deficient
  and the lifetime of red cells is shorter than in
  adults, leading to accumulation and increased
  formation of bilirubin, with eventual jaundice.
• Phototherapy converts bilirubin to yellow
  photoisomers and colorless oxidation products
  that are less lipophilic than bilirubin and do not
  require hepatic conjugation for excretion.
• Photoisomers are excreted mainly in bile, and
  oxidation products predominantly in urine.
Mechanism of Phototherapy.
Mechanism of Phototherapy
– The absorption of light by the normal form of
  bilirubin (4Z,15Z-bilirubin) generates transient
  excited-state bilirubin molecules.
– These fleeting intermediates can react with
  oxygen to produce colorless products of lower
  molecular weight, or
– they can undergo rearrangement to become
  structural isomers (lumirubins) or
– isomers in which the configuration of at least one
  of the two Z-configuration double bonds has
  changed to an E configuration.
• Only the two principal photoisomers formed in
  humans are shown : -
• Configurational isomerization is reversible and
  much faster than
• structural isomerization, which is irreversible.
• Both occur much more quickly than photooxidation.
  The photoisomers are less lipophilic than the 4Z,15Z
  form of bilirubin and can be excreted unchanged in
  bile without undergoing glucuronidation.
• Lumirubin isomers can also be excreted in urine.
• Photooxidation products are excreted mainly in
  urine. Once in bile, configurational isomers
  revert spontaneously to the natural 4Z,15Z form
  of bilirubin.
• The graph, a high-performance liquid
  chromatogram of serum from an infant
  undergoing phototherapy, shows the presence
  of several photoisomers in addition to the
  4Z,15Z isomer.
• Photoisomers are also detectable in the blood
  of healthy adults after sunbathing.
Important Factors in the Efficacy of
• Bilirubin absorbs light maximally in the blue
  range ( 420 – 500 nm )
• Daylight ( 550 – 600 nm )
• Distance : - 45 cm
  Complication : -
• Retinal damage
• Increase in body temperature ( dehydration )
• Bronze baby syndrome : -
  – skin urine and serum become brownish black after
    several days of phototherapy.
  – Recover fully after several days once the
    phototherapy is discontinued