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3 - Hemoglobin and the Bohr effect
Oxygen is delivered to cells of the body in exchange
for carbon dioxide -- end-product of enzyme reactions
in the energy producing cycle. This exchange is
accomplished by the hemoglobin molecule, and has
long been taught to students of biochemistry as the
Bohr Effect [1-4].

The Bohr effect provides a prime example of a
protective biochemical feedback mechanism.
Increased metabolic activity leads to greater
production of carbon dioxide, which will force more
oxygen off the hemoglobin molecule. Edsall (1980)
described the decreasing affinity of hemoglobin for
oxygen with increasing carbon dioxide pressure as a
biological adaption of fundamental importance [2].

The dynamic binding or release of oxygen and carbon
dioxide in response to their relative abundance was
discovered by Bohr and his assistants in 1904 [5], and
commemorated 100 years later in a special issue of
the journal Acta Physiologica, Nov 2004, Vol. 182,
Issue 3 [4].

Within the brain, the greater production of carbon
dioxide by the metabolically most active inferior
colliculi insures that this important center for auditory
attention receives oxygen from circulating hemoglobin,
before any other area of the brain, under conditions
of partial hypoxia. This is why the inferior colliculi are
not usually involved in the damage caused by oxygen
insufficiency.

It takes a sudden catastrophic episode of complete
oxygen deficiency (in an event such as suffocation or
cardiac arrest) for the inferior colliculi to be damaged,
but such events most often result in sudden death.
Damage in the inferior colliculi is found only in cases
where survival for at least several days has followed
successful resuscitation.

Myers (1972) discovered that chronic partial hypoxia
is the circumstance that causes damage to the
cerebral cortex in the perinatal period [6]. An
adjustment of circulation (vasodilation) takes place
under conditions of partial hypoxia, to make more
hemoglobin available to structures in the brain that
are producing the most carbon dioxide. Metabolically
active brainstem nuclei like the inferior colliculus are
thus spared, but the distal “watershed” areas of the
cerebral cortex will end up deprived of oxygen. This is
far more likely to be what happens during a traumatic
birth than a brief total cutoff of oxygen, which would
affect only the inferior colliculi and other brainstem
nuclei of high metabolic rate.

A period of total asphyxia would probably not happen
often in the absence of a concomitant period of partial
hypoxia. Therefore, it would be rare for a traumatic
birth to affect only the inferior colliculi without some
involvement of other areas of the brain. If damage to
the inferior colliculi underlies the core syndrome of
autism, it would be rare to find a child without some
other signs of neurological damage, whether that
damage were produced by hypoxia, infection, or
prenatal exposure to toxic substances; and indeed
“soft” neurological signs are noted in most children
with autism.

Hemoglobin is re-oxygenated in the lungs (or in the
placenta for a developing fetus). Oxygen crosses into
the capillaries surrounding the alveoli and combines
with oxygen-depleted hemoglobin. Carbon dioxide,
transported in plasma as bicarbonate, is reconverted
and released into the alveoli, which (if not yet fully
understood) appears to further increase affinity of
hemoglobin for oxygen [4].

The protocol for neonatal resuscitation (at the time of
this writing) relies on bag-and-mask ventilation (from
the outside), apparently with no regard to whether or
not circulation of blood to the capillaries surrounding
the alveoli has been established. The umbilical cord,
clamped within the first half minute or less after birth,
may disconnect the placenta before the first breath in
some cases. Redmond et al. (1965) demonstrated
that transfer of respiratory blood from the placenta to
the lungs takes place with the first breath [7], and
Mercer and Skovgaard have discussed the
importance of the filling of the capillaries around the
alveoli for healthy transition from placental to
pulmonary respiration [8]. An increasing body of
evidence that clamping of the cord should be delayed
a minute or two or three, or four, ought to be heeded
sooner than later, and all the evidence from decades
past be taken into immediate consideration -- no more
randomized controlled trials on human infants should
be done.

Low Apgar scores, even at one minute, are ominous.
Impairment of the auditory system can easily occur,
and impede language development.

White A, Handler P, Smith EL (1968) Principles of Biochemistry, fourth edition. New York:
McGraw-Hill.
Edsall JT (1980) Hemoglobin and the origins of the concept of allosterism. Federation
Proceedings 39:226-35.
Dickerson RE, Geis I (1983) Hemoglobin: structure, function, evolution, and pathology.
Menlo Park, California: Benjamin Cummings.
Jensen FB. Red blood cell pH, the Bohr effect, and other oxygenation-linked phenomena in
blood O2 and CO2 transport. Acta Physiol Scand. 2004 Nov;182(3):215-27.
Bohr C, Hasselbalch K, Krogh A (1904) Ueber einen in biologischer Beziehung wichtigen
Einfluss, den die Kohlensaurespannung des Blutes auf dessen Sauerstoffbindung ubt.
Skandinavishes Archiv fur Physiologie 16:402-412.
Myers RE (1972) Two patterns of perinatal brain damage and their conditions of occurrence.
American Journal of Obstetrics and Gynecology 112:246-276.
Redmond A, Isana S, Ingall D (1965) Relation of onset of respiration to placental
transfusion. Lancet 1 (6 Feb):283-285.
Mercer JS, Skovgaard RL (2002) Neonatal transitional physiology: A new paradigm. Journal
of Perinatal & Neonatal Nursing 15:56-75.