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