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Lecture 13

BIO120H1 Lecture Notes - Lecture 13: Hemoglobin, Polycythemia, Nfkb1

Course Code
Stephen Reid

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Lecture 13: Blood Gas Transport, Ventilation-Perfusion Matching and the Control of Breathing
1. Oxygen – Haemoglobin Binding
1A. The Oxygen Equilibrium Curve (OEC)
We can quantify the binding of oxygen to haemoglobin using an oxygen equilibrium (or
disassociation) curve, which plots the partial pressure of oxygen in mmHg on the x-axis. The Y-axis can
be the level of oxygen-Hb saturation (as a percentage value) or it can be a measure of oxygen content
(units of oxygen or units of oxygen per units of Hb such as volume %, or molO2/molHb, or gO2/gHb).
The curve is sigmoidal in shape. It is relatively flat at the lowest PO2 levels and then becomes quite steep
before reaching a plateau at higher PO2 levels. The sigmoidal nature of this curve results from positive
cooperativity, in which the binding of one O2 molecule to a Hb subunit facilitates the binding of a
second, and so on. When we have very low partial pressures, the hemoglobin molecule does not a have a
particular high affinity for oxygen - but as one molecule becomes bound, it causes the other heme groups
to increase their affinity for and as these subsequent heme groups bind oxygen, the rate of O2-Hb
saturation increases.
1B. The p50 Value: Quantifying Oxygen – Haemoglobin Binding Affinity
The variable that is used to quantify the affinity of haemoglobin for oxygen is called the p50. It is defined
as the partial pressure of oxygen at which 50% of haemoglobin is bound with oxygen. If we plot
concentration on the y-axis, then the p50 value is defined as the point when the oxygen content of the
blood if 50% of its maximum value.
The OEC curve can shift to the left or to the right depending on regulatory factors such as temperature,
pH, CO2 and the presence of small organic ions (i.e., 2, 3 DPG). If the curve shifts to the left, then there is
a decrease in the p50 value which reflects an increase in the affinity for oxygen of haemoglobin. If the
curve shifts to the right, this leads to an increase in p50 and indicates a decrease in haemoglobin-oxygen
1C. The p50 Value and Oxygen Loading and Unloading
When blood flows through the lungs, with relatively high partial pressures of oxygen, then O2-Hb
saturation will be high. When blood flows to the tissues, then we come to the steep part of the oxygen
equilibrium curve: the low partial pressures will facilitate the removal of oxygen from Hb and therefore
its diffusion out of the blood and into the tissues.
1D. Resting Oxygen Consumption
In the systemic arteries the partial pressure of oxygen is 100 Torr while in the systemic veins it is 40 Torr.
If we look at where these values lie on an oxygen equilibrium curve, we see that at 100mmHg, the
O2*Hb saturation of the arteries is 100% whereas at 40mmH saturation is still quite high, 75%. Thus,
even as the blood travels through the systemic circulation and oxygenates the tissues, it is only giving up
about a quarter of the oxygen that is has bound to it.
When the deoxygenated blood enters the lungs, its partial pressure is low, but the oxygen content of the
blood is still quite high. Why do we have this excess capacity? It is for when our metabolic rate increases,
such as during exercise - essentially, the body has a 'reserve' of saturated oxygen in case it requires more
to maintain metabolic function. When we remember that we only use about a third of our alveolar
capillary length for gas exchange, we can see just how tremendous our capacity is for increasing
metabolic function.
1E. Oxygen-Hb Saturation versus Oxygen Content
Anaemia is a condition where there are a lower number of red cells. Polycythaemia is a condition where
there is an overproduction of red cells. More red cells mean more Hb which means a greater capacity to
carry oxygen. Less red cells mean leas Hb and therefore a reduced capacity to carry oxygen. In all cases
(normal, anaemia and polycythaemia), all of the Hb that is available to bind oxygen can, in theory, bind
oxygen. Therefore in all cases it is possible to achieve 100% oxygen-Hb binding. However, this doesn’t
mean that the oxygen content is the same in all three cases. Oxygen content will be higher in the case of
polycythaemia because there is more Hb available to carry oxygen. Oxygen content will be lowest during
anaemia because there is less Hb available to carry oxygen.
1F. Modification of Oxygen-Hemoglobin (Hb) Binding
Oxygen-haemoglobin binding can be affected by several factors the two most important, from a
physiological-regulation point-of-view are temperature and pH while the partial pressure of CO2 can
also affect it Hb-O2 binding but to a lesser extent. In humans, a byproduct of glycolysis called
2,3-diphospoglycerate can also affect binding as can chloride ions (but, in humans, to a much lesser
degree). These factors alter the oxygen-haemoglobin binding reaction primarily to promote oxygen
uptake by the blood in the lungs and to help deliver oxygen from Hb to the tissues when blood is flowing
through the tissues.
1F-1. Modification of O2-Hb Binding: Temperature
Body temperature is relatively constant in humans; approximately 37 degrees Celsius. However, if we
are breathing air cooler than this, then the lung gas will be cooler than the average body temperature. This
reduced temperature will lower the p50, increasing oxygen-haemoglobin binding affinity and promote
O2 loading onto Hb. In contrast, metabolically active tissues (such as muscles) will have an elevated
temperature as heat is a by-product of metabolism. As blood reaches the tissues, this elevated
temperature will increase the p50, and thereby lower oxygen-haemoglobin binding affinity. This
facilitates oxygen delivery to the tissues.
1F-2. Modification of O2-Hb Binding: pH
The pH of the blood can also influence oxygen-Hb binding to encourage oxygen uptake in the lungs and
oxygen delivery to the tissues. In metabolically active tissues pH is reduced causing an increase in p50
and a decrease in O2-Hb affinity. This enhances the unloading the O2. The opposite occurs in the lungs.
At the lungs CO2 is excreted (exhaled) so blood pH increases slightly. This causes a left-shift in the OEC,
a decrease in pH and an increase in the O2-Hb binding affinity. The Carbamino Effect refers to the CO2
(produced by the tissues) to haemoglobin which causes a reduction in affinity and an increase in p50. It is
a relatively minor effect compared to pH and temperature.
1F-3. Modification of O2-Hb Binding: 2,3-DPG
2, 3-diphospoglycerate (2, 3-DPG) is a potential byproduct of a side-reaction to glycolysis. When
blood-oxygen content is high, the enzymes that produce 2, 3-DPG are inhibited; that is, under normal
conditions (normoxia), 2, 3-DPG is not present. Under hypoxic conditions however, 2, 3-DPG is
produced. It causes a decrease in the O2-Hb binding affinity decreases (an increase in the p50 value)
thereby promoting the unloading of oxygen to the tissues. There is always a trade-off between increasing
and decreasing the O2-Hb affinity. Under conditions of low oxygen we want to simultaneously increase
oxygen affinity in the lungs, so the blood picks up oxygen more efficiently; however, we want a decrease
in oxygen-Hb affinity in the tissues, so the tissues are more readily oxygenated. In this case, it is more
advantageous to have 2, 3-DPG deal with the latter, because even under hypoxic conditions it is still
fairly easy for haemoglobin to pick up oxygen in the lungs.
1G. Carbon Monoxide (CO)
Carbon monoxide is poisonous, and indeed, exposure is often fatal. This is because carbon monoxide
binds to haemoglobin in the same way that oxygen does, however, it has a much greater affinity to
haemoglobin than oxygen. The p50 of CO is far, far lower than the p50 of O2, and as well, it can take
several days for the carbon monoxide molecules to detach from haemoglobin. Thus, O2 molecules cannot
bind to Hb because HB has CO bound to the site where oxygen binds. The results are often fatal.
1H. The Haldane Effect
The Haldane Effect refers to the fact that deoxygenated blood can carry more CO2 than oxygenated
blood (remember, CO2 binds to haemoglobin at the same site as oxygen). There are several reasons for
this; but generally, it is because the binding of O2 to Hb decreases the affinity of Hb for CO2. In addition,
given that the vast majority of CO2 in the blood is not dissolved directly, but instead is in the form of
HCO3- and that oxygenation of Hb leads to a decrease in bicarbonate ions, oxygenation therefore leads to
a decrease in the total [CO2].