Post on 12-Apr-2017
Fetal hemoglobin ( Hb F )
Hb 2 Alpha (α )chains & 2 Gamma(γ ) or Delta (δ ) chains ( delta chain 146 amino acids , 39amino acids differ from beta chain –embryonic hemoglobin)
Physical chemical properties of Hb F :
1. Increased solubility of Deoxy HbF
2. slower electrophoretic mobility
3. Increased resistance of Hb F to alkali denaturation
4. Decreased interaction with 2,3 BPG
5. Hereditary persistence of HbF ( HPF ) increased HbF without Thalassemia, no DELTA BETA gene switching
6. Kleihauer staining for Hb F detection
Fetal hemoglobin ( HbF )
• HbF has two γ globin chains carrying less positively charged amino acids.
• Therefore HbF exhibits weak binding affinity towards 2,3 BPG ( negatively charged ).
• HbF has higher affinity for O₂ compared to adult Hb.
• Binding affinity for O₂ of HbF > HbA (This property of HbF helps to transfer of O₂ from maternal blood to fetus as HbFO ₂)
• Delivery of O₂ to fetus is important function of fetal hemoglobin .
Embryonic Hb - 3-8 weeks
Grover I -zeta ₂ Epsilon ₂ (ζ₂ ε₂ )
Grover II -Alpha ₂ zeta ₂ ( α₂ ε₂ )
Kleihauer staining for detection of fetal cells
Electrophoretic pattern of fetal hemoglobin
Rh- incompatibility
Rh- incompatibility• This condition results from incompatibility between maternal & fetal blood
group. Antigen D existing on membrane of fetal RBC (Rh positive fetus) induces synthesis of antibodies (anti –D ) in Rh negative mother . In Rh incompatibility ,the first child often escapes . But in second pregnancy , Rh antibodies will pass from mother to the fetus. Rh antibodies start destroying fetal red cells even before birth.
• Sometimes ,the child is born with severe hemolytic disease referred to as Erythroblastosis Fetalis .
• When bilirubin levels are more than 20 mg/dl ,the capacity of albumin to bind to bilirubin is exceeded.
• Free bilirubin passes through blood brain barrier and enters the brain. (Kerniecterus)
• Bilirubin gets deposited in brain leading to mental retardation,fits ,toxic encephalitis & spasticity.
Rh- incompatibility• If the newborn develops hemolytic disease ( HDN ),the child may be
given exchange transfusion along with phototherapy and barbiturates ( induce bilirubin metabolizing enzymes in liver).
• Phototherapy with blue light ( 440nm wavelength ) isomerize insoluble bilirubin to more soluble non toxic isomer ( Lumirubin ). These can be easily excreted through urine without conjugation.( in contrast to bilirubin which cannot be excreted without conjugation )
This condition results from incompatibility between maternal & fetal blood group. Antigen D existing on membrane of fetal RBC(Rh positive fetus) induce synthesis of antibodies (anti –D ) in Rh negative mother .In Rh incompatibility ,the first child often escapes .But in second pregnancy , Rh antibodies will pass from mother to the fetus. Rh antibodies start destroying fetal red cells even before birth.
Rh- incompatibility:1
In Rh positive fetus:RBC carry Antigen D on their membrane.
Rh- incompatibility:1a
In Rh negative mother :RBC don’t carry Antigen D on their membrane.
Rh- incompatibility:1b
Rh- incompatibility:2
Rh- incompatibility:3Fetal RBC carrying Antigen D enter the mother circulation through placenta .
Rh- incompatibility:4
In Rh incompatibility : Antigens D on membrane of fetal RBC(Rh positive ) induce synthesis of antibodies ( anti –D ) in Rh negative mother .
Rh- incompatibility:5
In Rh incompatibility Rh antibodies pass from mother to the fetus through placenta.
Rh- incompatibility :6In Rh incompatibility, Rh antibodies start destroying fetal red cells even before birth.
Rh- incompatibility:7
In Rh incompatibility, Rh antibodies start destroying fetal red cells even before birth.
Rh- incompatibility:8: Erythroblastosis Fetalis
Hemolytic Disease of Newborn (HDN )
Rh antibodies will pass from mother to the fetus. Rh antibodies start destroying fetal red cells even before birth.
Hemolytic Disease of Newborn (HDN) unconjugated HyperbilirubinemiaIncompatibility between maternal & fetal blood groups
Anti antibodies ABO(IgM type cannot be transferred to placenta)
Rh incompatibilityFetus mother
Rh ( +ve ) Rh ( -ve )
RBC RBC elicit immune response Anti-D ( IgG )
Destruction Anti-D ( IgG )
Of fetal
RBC ← Placenta
Second pregnancy ( before birth of fetus –destruction of fetal RBC ) child is born with severe hemolytic disease Erythroblastosis fetalis
Erythroblastosis Fetalis
• Serum Bilirubin > 20 mg/dl no more bound to Albumin
• Bilirubin Brain (Kernicterus-deposition of bilirubin in brain )
• Basal ganglia mental retardation
• ↓ ATPase mitochondria fits ,spasticity ,toxic encephalitis
• Treatment : (1) phototherapy before age < 1 year
isomerization ZZ ZE
(2 ) Blood transfusion
• Hemolytic Jaundice
• Causes –Rh- incompatibility Hemolysis due to Malaria Mismatched blood transfusion, sickle cell anemia,
• Liver fails to conjugate excess of Bilirubin
• Therefore ↑unconjugated bilirubin ↑Urobilinogen↑ stercobilinogen(brown color stool )
• SGPT / ALP -Normal
• Absence of bilirubin inUrine
• Hepatic Jaundice
• Causes –dysfunction of Liver Hepatitis al infection poisons/toxins cirrhosis/CCF
• ↑unconjugated bilirubin ↑conjugated bilirubin ↑Urobilinogen↑ stercobilinogen(brown color stool ) ↑SGPT / ALP
• Obstructive Jaundice
• Gall stone stool contains fat unavailability of bile salts
• ↑conjugated bilirubin ↑Urobilinogen↓ stercobilinogen(pale color stool ) ↑SGPT / ALP
Physiological /Neonatal Jaundice
• Not a truly genetic defect
• Causes : increased hemolysis of RBC with HbF and immature liver enzyme system for conjugation of bilirubin
• The activity of the enzyme UDP- glucuronyl transferase is low in the new born.
• The enzyme deficiency is more serious with increasing degree of prematurity.
Fetal hemoglobin ( Hb F )
• Normal Hb F – (2 α 2 γ )
• If α globin not synthesized then synthesis γ & β chain continues Tetramers (γ ₄ )—Hb Bart
• β ₄ Tetramers (β ₄ )—Hb H
• HbH lack Heme –Heme interaction
Hb H & Hb Bart
Hb lack Heme –Heme interaction
Oxygen dissociation curve -Hyperbolic
No delivery of sufficient oxygen to tissue
Fetal death
Hereditary persistent fetal Hb( HPFH )
1. Increase in HbF
2. no clinical symptoms
3. Failure to switch over γ gene to β gene