Shifts in the haemoglobin-oxygen dissociation curve: can we manipulate P50 to good effect?

The research article discusses the haemoglobin-oxygen dissociation curve (HODC) and factors that affect its position, especially the P50, the oxygen pressure where haemoglobin is 50% saturated with oxygen. It further delves into how different factors and conditions, such as temperature, pH, and the presence of various substances can alter this curve, and hence affect oxygen binding and release in different species, with specific emphasis on horses.

Decoding the Haemoglobin-Oxygen Dissociation Curve (HODC)

• The HODC represents the relationship between haemoglobin’s ability to bind and release oxygen and the current level of oxygen. This curve can shift under certain conditions, and one key measure of its position is P50 – the partial pressure of oxygen wherein half of the haemoglobin is saturated with oxygen.
• The standard P50 value is determined under specific conditions (pH 7.4; oxygen partial pressure of 40 mm Hg; temperature 37 °C; carboxyhaemoglobin <2%), but it varies in practical situations depending on factors like pH, temperature, and the presence of other substances.

Influencing Factors on P50

• Certain factors can cause a rightward or leftward shift in the HODC, thereby affecting the P50. Rightward shifts (increasing P50) occur due to acidaemia, hypercapnia, pyrexia, and the presence of specific organic and inorganic phosphates and chloride.
• Contrarily, factors like alkalaemia, hypocapnia, hyperoxia, hypothermia, and decreased phosphate and chloride concentration cause a leftward shift (decreasing P50).

Species-Specific Responses

• The influence of different substances on haemoglobin-oxygen affinity varies based on the species. For instance, in humans and dogs which have high 2,3-DPG containing erythrocytes, 2,3-DPG plays a significant role. In comparison, chloride assumes greater importance in ruminants and cats, which have a relatively low intra-erythrocyte 2,3-DPG concentration.
• In the specific case of horses, the study reveals that equine haemoglobin is less reactive to 2,3-DPG compared to human haemoglobin. Yet, alterations in 2,3-DPG concentrations in horses suffering from severe colic seen in the experiment conducted by Cambier’s group raise questions that remain to be answered.

Physiological Effects

• The Bohr and Haldane effects represent how changes in tissue carbon dioxide concentrations and acidification can shift the HODC, thus influencing oxygen release and loading. The prospect of haemoglobin’s role as a nitric oxide carrier and its effect on oxygen release and blood flow adds new dimensions to understanding this complex system.
• In disease conditions, like severe colic in horses, increase in P50 can enhance tissue oxygen extraction, given the arterial oxygen levels are non-critical.
• However, under general anesthesia, arterial hypoxaemia can result from ventilation mismatching and reduced cardiac output, making the right shifted HODC unfavorable for tissue oxygenation.

Implication and Questions for Future Studies

• This research article brings forth the understanding of the complex interaction of different factors that govern the HODC and raises several important queries. The study urges further inquiries into the impacts of interventions like fluid/electrolyte therapy on HODC and P50, possibly leading to optimized patient care.
• The intriguing question remains, can we manipulate P50 for therapeutic benefits?