Question

Given below are three oxygen-dissociation curves of hemoglobin. Considering curve b is the

oxygen dissociation curve of hemoglobin under normal physiological pH and physiological

concentrations of COz and 2,3-BPG, which of the following statements are CORRECT?​

Answer 1

Answer:

Oxygen (O2) competitively and reversibly binds to hemoglobin, with certain changes within the environment altering the affinity in which this relationship occurs. The sigmoidal shape of the oxygen dissociation curve illustrates hemoglobin’s propensity for positive cooperativity, as hemoglobin undergoes conformational changes to increase its affinity for oxygen as molecules progressively bind to each of its four available binding sites. The Bohr effect describes hemoglobin’s lower affinity for oxygen secondary to increases in the partial pressure of carbon dioxide and decreases in blood pH. This lower affinity, in turn, enhances the unloading of oxygen into tissues to meet the oxygen demand of the tissue

Increases in PCO2 and Decreases in pH  

Through the biochemical reactions necessary for cellular respiration, increases in metabolic activity within tissues result in the production of carbon dioxide (CO2) as a metabolic waste product. This increase in tissue PCO2 leads to an increase in hydrogen ion (H+) concentration, represented as a decrease in pH as the environment undergoes the process of acidosis. These effects decrease hemoglobin’s affinity for oxygen, weakening it’s binding capacity and increasing the likelihood of dissociation; this is represented as a rightward shift of the hemoglobin dissociation curve, as hemoglobin unloads oxygen from its binding sites at higher partial pressures of oxygen. Specifically, it is the association of protons (H+ ions) with the amino acids in hemoglobin that cause a conformational change in protein folding, ultimately reducing the affinity of the binding sites for oxygen molecules. This configuration shift of hemoglobin under the influence of protons is classified as the taut (T) form.

Hemoglobin exists in 2 forms, the taut form (T) and the relaxed form (R). This structural change to the taut form leads to low-affinity hemoglobin whereas the relaxed form leads to a high-affinity form of hemoglobin, with respect to oxygen binding. In the lungs, the highly saturated oxygen environment can overcome the lower affinity T-form of hemoglobin, effectively binding despite disadvantageous binding capacity. During this process, initial O2 binding induces an alteration in hemoglobin from the taut to relaxed form, dissociating H+ protons and progressively increasing hemoglobin’s affinity for oxygen at each of the remaining binding sites through positive cooperativity. Under the influence of acidic environments, hemoglobin has a propensity for undergoing the reverse of this conformational change, releasing oxygen in favor of the attachment of H+ protons as hemoglobin shifts from the higher oxygen affinity relaxed form to the lower oxygen affinity taut form.

Overall, this relationship can be quantified by an increase in the P50, as 50% hemoglobin oxygen saturation is achieved at higher-than-normal values of pO2, in comparison to the accepted normal P50 of 27 mmHg. This results in a greater unloading of oxygen in the presence of the acidic environments surrounding body tissues as a result of cellular respiration

Answer 2

Explanation:

Relating oxygen partial pressure, saturation and content: the haemoglobin–oxygen dissociation curve

Julie-Ann Collins, Aram Rudenski, [...], and Ronan O’Driscoll

Additional article information

Abstract

Key Points

In clinical practice, the level of arterial oxygenation can be measured either directly by blood gas sampling to measure partial pressure (PaO2) and percentage saturation (SaO2) or indirectly by pulse oximetry (SpO2).

s and weaknesses of each of these tests and gives advice on their clinical use.

The haemoglobin–oxygen dissociation curve describing the relationship between oxygen partial pressure and saturation can be modelled mathematically and routinely obtained clinical data support the accuracy of a historical equation used to describe this relationship.

Educational Aims

To understand how oxygen is delivered to the tissues.

To understand the relationships between oxygen saturation, partial pressure, content and tissue delivery.

The clinical relevance of the haemoglobin–oxygen dissociation curve will be reviewed and we will show how a mathematical model of the curve, derived in the 1960s from limited laboratory data, accurately describes the relationship between oxygen saturation and partial pressure in a large number of routinely obtained clinical samples.

To understand the role of pulse oximetry in clinical practice.

To understand the differences between arterial, capillary and venous blood gas samples and the role of their measurement in clinical practice.

The delivery of oxygen by arterial blood to the tissues of the body has a number of critical determinants including blood oxygen concentration (content), saturation (SO2) and partial pressure, haemoglobin concentration and cardiac output, including its distribution. The haemoglobin–oxygen dissociation curve, a graphical representation of the relationship between oxygen satur­ation and oxygen partial pressure helps us to understand some of the principles underpinning this process. Historically this curve was derived from very limited data based on blood samples from small numbers of healthy subjects which were manipulated in vitro and ultimately determined by equations such as those described by Severinghaus in 1979. In a study of 3524 clinical specimens, we found that this equation estimated the SO2 in blood from patients with normal pH and SO2 >70% with remarkable accuracy and, to our knowledge, this is the first large-scale validation of this equation using clinical samples. Oxygen saturation by pulse oximetry (SpO2) is nowadays the standard clinical method for assessing arterial oxygen saturation, providing a convenient, pain-free means of continuously assessing oxygenation, provided the interpreting clinician is aware of important limitations. The use of pulse oximetry reduces the need for arterial blood gas analysis (SaO2) as many patients who are not at risk of hypercapnic respiratory failure or metabolic acidosis and have acceptable SpO2 do not necessarily require blood gas analysis. While arterial sampling remains the gold-standard method of assessing ventilation and oxygenation, in those patients in whom blood gas analysis is indicated, arterialised capillary samples also have a valuable role in patient care. The clinical role of venous blood gases however remains less well defined.