Hematology 1
Hemoglobin
- (Hgb; Hb) is the oxygen-binding protein in red blood cells
- Approximately 65% of hemoglobin is produced during the nucleated stages of a developing RBC; the rest is
synthesized during the early reticulocyte stages
- Accounts for approximately 1/3 of the RBC content
- Composed of: (1) 4 heme molecules – each heme molecule has one iron molecule in the ferrous (Fe2+) state and a
protoporhyrin ring;
(2) 2 pairs of globin chains – the protein portion of hemoglobin; and
(3) a 2,3-DPG molecule which may sometimes be present
- Carries oxygen from the lungs to the peripheral tissues and carbon dioxide from the tissues to the lugs for excretion
- Each molecule of hemoglobin can bind to 4 molecules of oxygen (1 oxygen per heme subunit)
- 1 gram of hemoglobin can bind 1.34 mL of Oxygen
Hemoglobin transports oxygen from areas of high oxygen tension to areas of low
oxygen tension. The relationship between oxygen saturation and oxygen tension
can be expressed by the Oxyhemoglobin Dissociation Curve (figure on the right).
In the lungs, where partial pressure due to oxygen is high, the hemoglobin molecule
picks up Oxygen (high oxygen affinity). As the hemoglobin molecule reaches the
capillaries where oxygen tension is low, the hemoglobin molecule releases the
oxygen to the tissues (low oxygen affinity).
Hemoglobin
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Hematology 1
There are some factors that will affect the relationship of hemoglobin affinity to oxygen. A shift to the left (greater affinity
for oxygen is seen in decreased temperature, decreased 2,3-DPG, decreased [H+], increased blood pH, decreased [CO2], and
in the presence of carbon monoxide. Conversely, a shift to the right (reduced affinity for oxygen) is seen in increased
temperatures, increased 2,3-DPG, increased [H+], decreased blood pH, and increased [CO2].
Hemoglobin affinity for oxygen and 2,3-DPG:
When 2,3-DPG is inserted into the hemoglobin molecule, the hemoglobin is in a “tense” or T form, causing decreased affinity
for Oxygen. When the 2,3-DPG is outside the hemoglobin molecule, the hemoglobin is in a “relaxed” or R form, causing
increased affinity for Oxygen
Heme Synthesis: occurs in the mitochondria of the red blood
cell through a series of biochemical reactions culminating in
the insertion of iron molecule into the Protoporphyrrin IX ring
by the action of ferrochelatase (heme synthase).
Hemoglobin
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Hematology 1
Globin Synthesis: Occurs in the ribosomes
- Hemoglobin is composed of 2 pairs of globin polypeptide chains
- Chromosome 16 controls the synthesis of the alpha and zeta globin chains; the alpha and zeta globin chains are
composed of 141 amino acids; zeta globin chain is the embryonic analogue of the alpha globin chain
- Chromosome 11 controls the synthesis of the beta, delta , gamma, and epsilon globin chains; these four globin
chains are composed of 146 amino acids; epsilon globin chain is the embryonic analogue of the beta, delta, and
gamma, globin chains
Normal Hemoglobin variants (throughout human development)
Hemoglobin variant
Globin composition
Proportion in Newborns
Portland
2 zeta, 2 gamma
Gower 1
2 zeta, 2 epsilon
Gower 2
2 alpha, 2 epsilon
HbF (Fetal Hb)
2 alpha, 2 gamma
HbA1
2 alpha, 2 beta
HbA2
2 alpha, 2 delta
*Portland Hb, Gower 1 Hb, and Gower 2 Hb are embryonic hemoglobins
Hemoglobin
0*
0*
0*
80%
20%
< 0.5%
Proportion in children and
adults (> 1y/o)
0*
0*
0*
<1%
97%
2.5%
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Hematology 1
Physiologic Forms of Hemoglobin:
1. Oxyhemoglobin (HbO2) : hemoglobin bound to oxygen
- Found in arterial blood: bright red color
- Conformation of the hemoglobin molecule: R or relaxed state
2. Deoxygenated hemoglobin : hemoglobin not bound to oxygen
- Found in venous blood: dark red
- Conformation of the hemoglobin molecule: T or tense state
Hemoglobin Derivatives (Dyshemoglobins; dysfunctional hemoglobins):
1. Methemoglobin (Hi): aka. Hemiglobin, Ferrihemoglobin
- Hemoglobin with Iron in the oxidized (ferric; Fe3+) state
- Incapable of binding with oxygen
- Color of blood after shaking: Chocolate brown
- Methemoglobinemia may be congenital or acquired by exposure to oxidizing agents
- Methemoglobinemia may be reversed with administration of ascorbic acid (Vit C)
2. Carboxyhemoglobin (HbCO): Hemoglobin bound to carbon monoxide (CO); CO has 200 times greater affinity to
hemoglobin than oxygen
- Incapable of binding with oxygen
- Color of blood after shaking: Cherry red
- Increased in chronic tobacco smokers
- May be reversed by O2 administration
Hemoglobin
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Hematology 1
3. Sulfhemoglobin (SHb): aka. the irreversible hemoglobin
- mixture of oxidized, partially denatured form of hemoglobin
- color of blood after shaking: Mauve lavender
- may be acquired from:
a. prolonged constipation
b. exposure to sulfa drugs (eg. Trimethoprim sulfamethoxazole)
c. chronic infection with Clostridium perfringens
Abnormal hemoglobin variants (hemoglobinopathies): disorders arising from genetic mutations that lead to structural
changes in the hemoglobin molecule
1. HbS: (α2β26→Val); amino acid in the 6th position of the beta chain is replaced by valine
- usually affects Africans or those with African descent.
- May cause Sickle Cell Disease or Sickle Cell trait
2. HbC: (α2β26→Lys)
- usually affects West Africans or those with West African descent.
- Associated with the presence of HbC crystals (inclusion bodies resembling the Washington monument)
3. HbE: (α2β226Glu→Val)
- Usually affects Southeast Asians particularly Thais
4. Hb Bart’s (γ4): 4 gamma globin chains are present
- Cause of hydrops fetalis; stillbirth or premature birth leading to eventual death
- Incompatible with life since blood is not able to oxygenate tissues due to high affinity of Hb Bart’s to oxygen
5. HbH: (β4)
121→Gln
6. HbD (α2β2
)
(detailed discussion of Hemoglobinopathies in Lesson 13)
Hemoglobin
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