Hemoglobin
Introduction
Normal adult Hemoglobin is
type A
or
A
2
Most commmon variant is
fetal hemoglobin
(
HbF
) – major Hb in the fetus which is replaced after birth by
A
.
Another variant is
hemoglobin S
(
HbS
) – crystallizes into long rod when PO
2
ß
and [H
+
]
Ý
:
cells contain more 2,3-DPG therefore curve shifted to the right
Sickle cell trait
= one HbS and one HbA gene, confers malarial resistance
Sickle cell disease
= two HbS genes; red blood cells sickle and obstruct capillary -not compatible with longevity
Sickle cell anemia =
due to shortened red cell life
Most Variants have the hyperbolic dissociation curve of MbO
2
and are useless for O
2
transport. If too
Ý
then lethal
Nitrates and sulfates can oxidize Heme iron from Fe
2+
to Fe
3+
Þ
methemoglobinemia
because oxidized Hb will not bind or trans O
2
Erythropoietin Regulation of RBC Production
Renal cortical interstitial cells produce and secrete
erythropoietin
in response to both
ß
[Hb] or
ß
Pa
O2.
Effect is to stimulate erythropoeisis in bone marrow
Evidence suggests that O
2
sensing mechanisms are in organs where O
2
delivery is
Ý
relative to metabolism.
Erythropoietin production regulated by local [O
2
radicals]
System is so well tuned that [Hb] is very stable
Hypoxic and anemic hypoxia lower the renal cortical Pa
O2
and stimulate erythropoietin production.
Chronic renal failure associated anemia caused by inadequate output of erythropoietin.
why interstitial cells stop production is unknown
treating patients with erythropoietin dramatically improves blood O
2
levels
CO and NO Poisoning
O
2
, CO and NO are specific ligands for Hb because each can donate 2 electrons to coordinate covalent bond
CO has >
250 X
the affinity for Hb than O
2.
produced when Hb is catabolized in the liver, steadily removed in expired air because P
ACO
= 0
circulating HbCO rarely exceeds 1 to 2% of total Hb
cigarette smokers and urban traffic drivers have high levels of HbCO that require several hours to clear
CO binds so tightly to Hb that it disrupts the Heme interactions thus, shifting HbO
2
to the left and
ß
P
VO2
This left shift explains CO toxicity
NO has >
200,000 X
the affinity for Hb than O
2
NO binds irreversibly; at P
NO
0.001 mm Hg, Hb will bind all NO
This can be an issue when NO is prescribed for inhalation to reverse pulmonary hypertension.