Hemoglobin

DR. SEJIL TV
Learning Objectives
❑Normal values of Hemoglobin
❑Structure of hemoglobin
❑Synthesis of hemoglobin
❑Functions of hemoglobin
❑Destruction of hemoglobin
❑Derivatives of hemoglobin
❑Normal varieties of hemoglobin
❑Abnormal varieties of hemoglobin
Introduction
Hemoglobin is synthesized by the
precursors of the RBC and not by the
mature RBCs
Hemoglobin constitutes 95% of the dry
weight of RBCs

Why is hemoglobin packed in RBCs?

❑Increase in plasma osmotic pressure
❑Rapid destruction of the Hb by the
reticuloendothelial cells
❑Excretion of Hb (molecular wt 68000) by the
kidneys
❑Hemoglobin increases blood viscosity
Normal Values of Hb
❑Adults
❑Male: 14 -18 g/dl
❑Female: 12 – 16 g/dl

❑Children: usually higher if the diet is not deficient in nutrients

❑Newborn : 20-23g/dl
❑Effect of hormones
❑Testosterone has a stimulatory effect of erythropoiesis, while the estrogens
and progesterones inhibit it
 Structure of hemoglobin
Hemoglobin

Heme
[4 pyrrole rings (tetra- Globin
pyrrole), 1 Fe2+] 2 alpha chains
One set for each globin 2 beta chains
chain
Synthesis of Hemoglobin
Takes place in the mitochondria and Glycine Succinyl-CoA
cytosol
Globin chain synthesized by α-amino β ketoadipic acid
ribosomes
α-amino β levulinic acid
Requires:
◦ Proteins Porphobilinogen
◦ Iron
◦ Copper Protoporphyrin –IX
◦ Vitamins – B12, C, folic acid Ferrous
Heme
Globin
Hemoglobin
Functions
Transport of Oxygen
◦ 1gm of Hb – 1.34ml of O2 (OxyHb)
◦ One molecule of O2 to each iron atom, total of 4 molecules of O2 for one Hb

Transport of Carbon dioxide

Control of blood pH - buffer
Catabolism of Hemoglobin
Old RBCs are destroyed in the spleen.
Hemoglobin
Macrophages engulf the Hb and degrade it.
Alteration of hemoglobin catabolism - Choleglobin
jaundice

Iron Biliverdin Globin

(pyrrole rings)

Amino
Bilirubin
acids
 Liver
Spleen
Conjugation
Blood Destruction of old
Bilirubin + glucuronic
Unconjugated bilirubin RBCs, release of
acid=bilirubin
(bilirubin+albumin) bilirubin
diglucuronide)
Conjugated bilirubin

Portal Circulation
Bile Duct

Urobilinogen

Intestine Kidney
Urobilinogen formed
Urobilinogen Bilirubin

Stercobilinogen Urobilin
Stercobilin
Urine
Feces (Stool)
Derivatives of hemoglobin
❑Oxyhemoglobin: hemoglobin with oxygen in the lungs
❑Reduced or deoxygenated hemoglobin: in venous blood
❑Carbaminohemoglobin – carbon dioxide with hemoglobin
❑Carboxy hemoglobin – carbon monoxide with hemoglobin
❑Methemoglobin – iron in ferric form
❑Glycosylated hemoglobin – glucose with hemoglobin
Normal (Physiological)
Varieties of Hemoglobin
Adult hemoglobin
◦ Hemoglobin A (HbA): 2 alpha chains and 2 beta chains (α2β2)
◦ Hemoglobin A2 (HbA2) : 2 alpha chains and 2 delta chains (α2δ2)

Fetal Hemoglobin (HbF)

◦ Contains 2 alpha chains and 2 gamma chains (α2γ2)
◦ Strong affinity to oxygen
◦ RBCs containing HbF – 10-14 days
◦ Changes over to adult hemoglobin by 1 year of age

Embryological hemoglobin
◦ Gowers type 1: 2 zeta chains and 2 epsilon chains
◦ Gowers type 2: 2 alpha chains and 2 epsilon chains
Abnormal (pathological)
varieties of hemoglobin
Called hemoglobinopathies
Alterations in chain structure
Sickle cell anemia
◦ Substitution of glutamate with valine at position 6 of beta chain.
◦ Oxygenated Hb – No issues
◦ Deoxygenated Hb undergoes precipitation and polymerizes
◦ Deforms the RBCs to sickle form – undergo lysis – anemia
◦ Blocks microcirculation
◦ Protection against malaria
Alteration in chain production rate (thalassemia)
Suppression of alpha or beta chain production (α and β thalassemia)
 MUST KNOW
Functions of hemoglobin
Destruction of hemoglobin
Derivatives of hemoglobin
Normal varieties of hemoglobin
Abnormal varieties of hemoglobin
Normal values of Hemoglobin

NICE TO KNOW
Structure of hemoglobin
Synthesis of hemoglobin
Differences between HbF and HbA
Importance of glycosylated Hb
Treatment of sickle cell anemia