OXYGEN DISSOCIATION CURVE

Ascent to high attitude triggers a substantial rise in 2,3-DPG concn in RBC, with a consequent increase in P50 and increase in availability of O2 to tissues (O2 dissociation curve shift to right)
Right shifting of O2, dissociation curve
•    Temperature
•    H+ conc ( pH value)
•    2, 3 – DPG
•    CO2
•    Exercise
•    High altitudes
•    Hypoxia

Ans. is. A. Decreased 2, 3 DPG concentration 
The unique feature of fetal hemoglobin is that it has a higher affinity, for oxygen than adult hemoglobin.
0₂ saturation of the maternal blood in the placenta is so low that the fetus might suffer hypoxic damage if fetal red

cells did not have a greater 0₂ affinity than adult red cells.

• This difference in 0₂ affinities between the two is because fetal hemoglobin binds to 2,3 DPG less effectively than adult hemoglobin.

• Binding of 2-3, DPG to the hemoglobin decreases its affinity for oxygen i.e., it shifts the 0₂ dissociation curve to the right.

• HbF reacts less with 2, 3 -DPG and so is able to bind 0₂ more tenaciously, accounting for the left-shifted 02 dissociation curve at birth.

• The concentration of fetal hemoglobin at birth HbF  70-80 % of total hemoglobin HbA → 30% of total hemoglobin

Ans. is. C. Shift of oxygen dissociation curve to the left 

• The O2-hemoglobin dissociation curve shifts to the right within the capillaries in response to an increase in blood CO2 and Hydrogen ions.
• As the blood flows through the capillaries CO₂ diffuses from the tissue cells into the blood. 
• This increases the blood PCO₂ and hence blood H₂CO₃ and Hydrogen ion concentration.
• Increased hydrogen ions and PCO₂ shift the O₂-hemoglobin dissociation curve rightwards and downwards.
• This enhances the release of O₂ from the blood for the tissues.
  • This is called the Bohr effect.
•  There is a net efflux of fluid as blood passes through the capillaries resulting in increased hematocrit and protein concentration.

Shift of oxygen dissociation curve to the right is caused by factors that decrease the affinity of hemoglobin for oxygen. This is advantageous in the tissues because the blood offloads more oxygen. Conditions which decreases oxygen availability as in anemia and hypoxia the levels of 2,3 DPG increases and shifts the curve to right.

• High Pco2
• Acidic pH
• Rise in temperature
• Rise in red cell DPG concentration

• Low Pco2
• High pH
• Fall in temperature
• Fall in red cell DPG concentration
• Fetal hemoglobin

Three important conditions affect the oxygen–hemoglobin dissociation curve: the pH, the temperature, and the concentration of 2,3-bisphosphoglycerate (BPG; 2,3-BPG). A rise in temperature or a fall in pH shifts the curve to the right. When the curve is shifted in this direction, a higher PO2 is required for hemoglobin to bind a given amount of O2. Conversely, a fall in temperature or a rise in pH shifts the curve to the left, and a lower PO2 is required to bind a given amount of O2. A convenient index for comparison of such shifts is the P50, the PO2 at which hemoglobin is half saturated with O2. The higher the P50, the lower the affinity of hemoglobin for O2.

Ans. A. Oxygen dissociation curve shifts to left.
FACTORS AFFECTING OXYGEN HEMOGLOBIN DISSOCIATION CURVE

• Hb-O₂ dissociation curve shifted to left/right by various factors,

– PO₅₀ mark is baseline for determining curve shift.
– PO₅₀ – PO₂ at which hemoglobin 50% saturated.
– PO₅₀ of normal adult hemoglobin – 26mm Hg (3.47 kpa).

I) CURVE SHIFTING TO RIGHT:

• PO₅₀ higher.

– i.e., 50% hemoglobin saturation happens at higher PO₂

• Indicating decrease in affinity of hemoglobin for oxygen. 

Conditions associated:

• Low pH Hypoxia

• Increase in H⁺ ion concentration (acidosis)

• Reduced PO₂

• High PCO₂

• Increased body temperature

• Increased 2,3-bisphosphoglycerate (2,3 – BPG)/2,3-diphosphoglycerate (DPG)

• Exercise

• Within systemic capillaries.

II) CURVE SHIFTING TO LEFT:

• PO₅₀ lower.

– i.e., 50% hemoglobin saturation happens at lower PO₂

• Indicating increase in affinity of hemoglobin for oxygen. 

Conditions associated:

• High pH.

• Decreased H⁺ ion concentration (alkalosis).

• Reduced PCO₂

• Reduced body temperature.

• Reduced 2,3-bisphosphoglycerate (2,3 -BPG)/2,3-diphosphoglycerate (DPG)

• Fetal hemoglobin.

• CO poisoning.

Ans. B. Blood transfusion
FACTORS AFFECTING OXYGEN HEMOGLOBIN DISSOCIATION CURVE

• Hb-O₂ dissociation curve shifted to left/right by various factors,

– PO₅₀ mark is baseline for determining curve shift.
– PO₅₀ – PO₂ at which hemoglobin 50% saturated.
– PO₅₀ of normal adult hemoglobin – 26mm Hg (3.47 kpa).

I) CURVE SHIFTING TO RIGHT:

• PO₅₀ higher.

– i.e., 50% hemoglobin saturation happens at higher PO₂

• Indicating decrease in affinity of hemoglobin for oxygen. 

Conditions associated:

• Low pH Hypoxia

• Increase in H⁺ ion concentration (acidosis)

• Reduced PO₂

• High PCO₂

• Increased body temperature

• Increased 2,3-bisphosphoglycerate (2,3 – BPG)/2,3-diphosphoglycerate (DPG)

• Exercise

• Within systemic capillaries.

II) CURVE SHIFTING TO LEFT:

• PO₅₀ lower.

– i.e., 50% hemoglobin saturation happens at lower PO₂

• Indicating increase in affinity of hemoglobin for oxygen. 

Conditions associated:

• High pH.

• Decreased H⁺ ion concentration (alkalosis).

• Reduced PCO₂

• Reduced body temperature.

• Reduced 2,3-bisphosphoglycerate (2,3 -BPG)/2,3-diphosphoglycerate (DPG)

• Fetal hemoglobin.

• CO poisoning.

Ans. B. 2,3, DPG
FACTORS AFFECTING OXYGEN HEMOGLOBIN DISSOCIATION CURVE

• Hb-O₂ dissociation curve shifted to left/right by various factors,

– PO₅₀ mark is baseline for determining curve shift.
– PO₅₀ – PO₂ at which hemoglobin 50% saturated.
– PO₅₀ of normal adult hemoglobin – 26mm Hg (3.47 kpa).

I) CURVE SHIFTING TO RIGHT:

• PO₅₀ higher.

– i.e., 50% hemoglobin saturation happens at higher PO₂

• Indicating decrease in affinity of hemoglobin for oxygen. 

Conditions associated:

• Low pH Hypoxia

• Increase in H⁺ ion concentration (acidosis)

• Reduced PO₂

• High PCO₂

• Increased body temperature

• Increased 2,3-bisphosphoglycerate (2,3 – BPG)/2,3-diphosphoglycerate (DPG)

• Exercise

• Within systemic capillaries.

II) CURVE SHIFTING TO LEFT:

• PO₅₀ lower.

– i.e., 50% hemoglobin saturation happens at lower PO₂

• Indicating increase in affinity of hemoglobin for oxygen. 

Conditions associated:

• High pH.

• Decreased H⁺ ion concentration (alkalosis).

• Reduced PCO₂

• Reduced body temperature.

• Reduced 2,3-bisphosphoglycerate (2,3 -BPG)/2,3-diphosphoglycerate (DPG)

• Fetal hemoglobin.

• CO poisoning.

Ans. B. Hypercarbia
FACTORS AFFECTING OXYGEN HEMOGLOBIN DISSOCIATION CURVE

• Hb-O₂ dissociation curve shifted to left/right by various factors,

– PO₅₀ mark is baseline for determining curve shift.
– PO₅₀ – PO₂ at which hemoglobin 50% saturated.
– PO₅₀ of normal adult hemoglobin – 26mm Hg (3.47 kpa).

I) CURVE SHIFTING TO RIGHT:

• PO₅₀ higher.

– i.e., 50% hemoglobin saturation happens at higher PO₂

• Indicating decrease in affinity of hemoglobin for oxygen. 

Conditions associated:

• Low pH Hypoxia

• Increase in H⁺ ion concentration (acidosis)

• Reduced PO₂

• High PCO₂

• Increased body temperature

• Increased 2,3-bisphosphoglycerate (2,3 – BPG)/2,3-diphosphoglycerate (DPG)

• Exercise

• Within systemic capillaries.

II) CURVE SHIFTING TO LEFT:

• PO₅₀ lower.

– i.e., 50% hemoglobin saturation happens at lower PO₂

• Indicating increase in affinity of hemoglobin for oxygen. 

Conditions associated:

• High pH.

• Decreased H⁺ ion concentration (alkalosis).

• Reduced PCO₂

• Reduced body temperature.

• Reduced 2,3-bisphosphoglycerate (2,3 -BPG)/2,3-diphosphoglycerate (DPG)

• Fetal hemoglobin.

• CO poisoning.

Ans. B: Decreased PaCO2
* Hemoglobin is the primary vehicle for transporting oxygen in the blood.

* The oxygen-carrying capacity is determined by the amount of hemoglobin present in the blood. Oxygen is also carried dissolved in the blood’s plasma, but to a much lesser degree.

* A hemoglobin molecule can bind up to four oxygen molecules in a reversible way.

* The oxygen-hemoglobin dissociation curve has a sigmoidal or S-shape.

* The partial pressure of oxygen in the blood at which the hemoglobin is 50% saturated, is known as the P50.

• The P50 is a conventional measure of hemoglobin affinity for oxygen.
• An increased P50 indicates a rightward shift and a decreased affinity of the standard curve, which means that a larger partial pressure is necessary to maintain a 50% oxygen saturation.
• Conversely, a lower P50 indicates a leftward shift and a higher affinity.

* The left shift of the curve is a sign of hemoglobin’s increased affinity for oxygen (e.g. at the lungs). Similarly, the right shift shows decreased affinity, as seen in:

  – An increase in body temperature,
  – An increase in hydrogen ion,
  – An increase in 2, 3-bisphosphoglycerate
  – An increase in carbon dioxide concentration (the Bohr effect)

* With fetal hemoglobin, the shift facilitates diffusion of oxygen across the placenta. The oxygen dissociation curve for myoglobin exists even further to the left.

Ans. is `b’ i.e., Hypoxia
I) CURVE SHIFTING TO RIGHT:

• PO₅₀ higher.

– i.e., 50% hemoglobin saturation happens at higher PO₂

• Indicating decrease in affinity of hemoglobin for oxygen. 

Conditions associated:

• Low pH Hypoxia

• Increase in H⁺ ion concentration (acidosis)

• Reduced PO₂

• High PCO₂

• Increased body temperature

• Increased 2,3-bisphosphoglycerate (2,3 – BPG)/2,3-diphosphoglycerate (DPG)

• Exercise

• Within systemic capillaries.

Ans. is `b’ i.e., Cooperative binding in Hb

• Cooperative binding is responsible for sigmoid shape of the oxygen-hemoglobin dissociation curve.
  
• As myoglobin is monomeric (consists of one polypeptide chain only), it can bind only one molecule of oxygen and for the same reason myoglobin cannot show the phenomenon of cooperative binding. Hence, the oxygen‑myoglobin dissociation curve is hyperbola as compared to sigmoid shape of Hb-O₂ curve.

Hemoglobin – O₂  binding

• Each molecule of hemoglobin can combine with upto four molecules of oxygen. Combination with the first molecule alters the conformation of the hemoglobin molecule in such a way as to facilitate combination with the next oxygen molecule. In light of this, if we look at the curve, as the PO₂ starts rising from 0 mm Hg upwards, initially all hemoglobin molecules in blood starts combining with their first oxygen molecule. This is the most difficult molecule to combine with. Hence saturation rises only slowly with initial rise in PO₂. As PO₂ rises further, hemoglobin molecules combine with their second, third and fourth molecules, which are progressively easier to combine with. Hence saturation rises steeply between PO₂ of 15 mm Hg and 40 mm Hg. When PO₂ rises still further, oxygen finds most of the hemoglobin molecules carrying four molecules of oxygen each. Since no molecules of hemoglobin can carry more than four molecules of oxygen, there is not much scope for more O₂ combining with hemoglobin. Hence the curve becomes almost flat again beyond the PO₂ of 60 mm Hg.
• Thus, the primary reason for the sigmoid shape of the oxygen-hemoglobin dissociation curve is that out of the four molecules of oxygen that can combine with a hemoglobin molecules, the first combines with the greatest difficulty and binding of an oxygen molecules increases affinity to next O₂ molecule. This phenomenon is termed as cooperative binding or cooperativity, i.e., a molecule of O₂ binds to a hemoglobin tetramer more readily if other O₂ molecules are already bound.