SHAPE Curve

RESHAPING: Oxyhemoglobin-Dissociation Curve

The Oxyhemoglobin Dissociation Curve connects multiple aspects of oxygenation and ventilation; which include oxygen binding, carbon dioxide tension, and pH. We will discuss how this physiologic principle can be discussed to explain oxygen binding and carbon dioxide release in the pulmonary capillaries, with the reverse occurring in the tissues.

We will connect what seem to be boring topics and relate them to clinical practice, allowing you to see their relevance and why I LOVE talking about them.

Oxyhemoglobin Dissociation Curve

The relationship is defined between PaO2 (X-Axis and expressed as mm Hg), which range is 60 – 100 mm Hg and SpO2 (Y-Axis and expressed with a percentage) which range is ~ variable ~ but is around 94-100% – their direct correlation allows us to understand that increases in the supplied oxygen (e.g. non or invasively) will provide higher levels of oxygenated hemoglobin, BUT only to a certain point.

Correlation between elevated PaO2 and SpO2

This diagram illustrates two significant points on this curve;

  1. Tissue Level; there is noted to be a PaO2 of 40 mm Hg which correlates to 70% Spo2. Which is seen with O2 OFF-loading and CO2 ON-loading, which can be understood as oxygenation.
  1. Alveolar Level; there is noted to be a PaO2 of 100 mm Hg which correlates to 99% Spo2 Which is seen with O2 ON-loading and CO2 OFF-loading, which can be understood as ventilation,

This upward curve of the chart shows a DIRECT correlation where when oxygen is increased, there will be an increase in SpO2. Although we won’t get into this during this resource material, a scenario should be discussed. 

If a patient is given 100% through their oxygen device and reads an elevated SpO2 (let’s say about >97%), then you draw an ABG there can be a PaO2 of >200 mm Hg or even >300 mm Hg at times. This allows us to understand that there is a significant amount of oxygen that just isn’t being used by the tissues, for example there might not be enough hemoglobin for oxygen binding (4 oxygen molecules per hemoglobin).

In another perspective if there is a patient that is given 100% through their oxygen device and reads a low SpO2 (let’s say about <85%), then you draw an ABG there can be a PaO2 of >200 mm Hg or even >300 mm Hg at times. In this instance this means that there is an issue with the peripheral tissues utilizing that oxygen or decreased hemoglobin or V/Q mismatching.

Left and Right Shift (Acidosis and Alkalosis)

When discussing this concept, most people identify this as understanding the causes for what is known as a left shift which is noted with alkalosis whereas a right shift is seen with acidosis.

Now I’m going to take it another level and discuss affinity, which is one object’s attraction to another. In this scenario we will be discussing affinity towards carbon dioxide and oxygen.

  • Left Shift: Indicates a tighter affinity for oxygen content or a lesser affinity for carbon dioxide
  • Right Shift: Indicates a lesser affinity for oxygen content or a tighter affinity for carbon dioxide

Think Environment

When discussing these topics it can be easier to demonstrate their relationship in terms of environment,

So when thinking about a left shift it is easier to think about the alveoli where oxygen affinity is high and is where hemoglobin picks up oxygen molecules for oxygenation and drops off carbon dioxide for ventilation. 

Whereas when thinking about a right shift think about the tissues where oxygen affinity is low which leads to their release and the on loading of carbon dioxide for transport to the lungs.  

Think Situations

When considering pH, and Carbon Dioxide levels, we can use these to figure out the shift.

  • With a Left Shift, this would be seen with low carbon dioxide levels and high pH levels (more basic).
  • With a Right Shift, this would be seen with high carbon dioxide levels and low pH levels (more acidic).

  Diagram of causes and effects

 

Left-shifted ODC (↓P50

Right-shifted ODC (↑P50

Causes 

↑pH (↓H+

↓pH (↑H+

↓PaCO2 

↑PaCO2 

↓2,3-diphosphoglycerate 

↑2,3-diphosphoglycerate 

↓Temperature 

↑Temperature 

Effect 

Increased haemoglobin oxygen affinity, enhanced oxygen binding 

Decreased haemoglobin oxygen affinity, enhanced release of oxygen in the tissues 

Others 

Fetal haemoglobin 

Adult haemoglobin 

 

Carbon monoxide poisoning 

 

 

Methaemoglobinaemia 

 

 

 A short word on 2,3-Diphosphoglycerate (super nerd moment)

2,3-Diphosphoglycerate (2,3-DPG) is an organic phosphate produced during glycolysis and found in the red blood cell, promoting haemoglobin oxygen release.

  • Increased 2,3-DPG production is seen in anemia, which may minimize tissue hypoxia by right-shifting the ODC and increasing tissue oxygen release.
  • 2,3-DPG undergoes metabolism in banked donor blood causing reduced oxygen unloading capacity after transfusion.
  • Inorganic phosphate is a substrate for the production of 2,3-DPG and thus capillary haemoglobin oxygen release may be impaired if hypophosphataemia is not corrected

 Haldene-Bohr Effect

This sections gets into physiology and when I learned about the oxygen dissociation curve and these physiologic effects, I thought of them as separate concepts. Through time I realized that these are connected and can be used to example changes that we seek clinically, and on a physiologic level.

  • Haldane effect:

Describes how oxygen concentrations determine hemoglobin’s affinity for carbon dioxide. Thus, with lower saturation levels or (deoxygenated blood) can carry INCREASED amounts of carbon dioxide, whereas high saturation levels (oxygenated blood) has a REDUCED carbon dioxide capacity.

In both situations, it is oxygen that causes the change in carbon dioxide levels.

Clinical application: This is represented by a right shift of the oxyhemoglobin dissociation curve and a left shift of the oxyhemoglobin dissociation curve respectively.

  • Bohr’s Effect

Describes how carbon dioxide and H+ affect the affinity of hemoglobin for oxygen. High CO2 and H+ concentrations cause decreases in affinity for oxygen, while low concentrations cause high affinity for oxygen.

Clinical application: In active muscles, carbon dioxide and H+ levels are high. Oxygenated blood that flows past is affected by these conditions, and the affinity of hemoglobin for oxygen is decreased, allowing oxygen to be transferred to the tissues.
 

HALI (heterotropic allosteric ligand interaction) – combining concepts

The Bohr and Haldane effects are allosteric effects caused by binding of different ligands at different spots on Hb – these relationships are either based off oxygen or carbon dioxide and express the affinity for the opposite. When these molecules attach to hemoglobin there is an “Allosteric” effect where there are associated with “shape changes” in molecules. 

This change leads to a shape change of the hemoglobin molecule, resulting in an increase in the affinity of the Hb for O2 at the lung and a decrease in the affinity of Hb for O2 at the tissue.  The shape changes in Hb, therefore, promote O2 uptake at the lung and O2 release at the tissues.  

Pretty cool, wouldn’t you say? 

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