Physiology of Oxygen-Hemoglobin Dissociation Curve
Authors: Sravya Kakumanu Kayleigh Yang Victoria Silva
O2
Remaining T-state subunits destabilizeàAll subunits convert to R-state to stabilize HbA (Positive cooperativity)
Normal physiology of hemoglobin:
α α β β
Adult hemoglobin, Hemoglobin A (HbA), is made up of two α- subunits and two β- subunits
When partial pressure of O2 (pO2) is ↓, bonds between subunits are strainedàHbA subunits stabilized in this deoxygenated tense state (T- state)àHas ↓ O2 affinity
O2 O2
As pO2 ↑, O2 binds a T-state subunit àSubunit destabilizesàSubunit changes shapeàBecomes oxygenated relaxed state (R-state)à Has ↑ O2 affinity
O2 O2 O2 O2
O2 rapidly binds to R-state subunits, saturating HbA
Reviewers:
Parker Lieb, Sunawer Aujla, Marissa Zhang, Tara Lohmann* * MD at time of publication
Normal physiology of hemoglobin in the body: In lungs:
In tissues:
↑ O2 consumption due to cellular respiration
↑ pO2 during respiration (~100mmHg)
HbA is in its deoxygenated, T-state
HbA is in its oxygenated, R-state
O2 O2 O2 O2
T-state subunits favor O2 binding
When pO2 > 60, O2 binds to a circulating subunit in the T-state
Subunit destabilizesà Subunit changes shape to R- stateà↑ O2 affinity
Positive cooperativity:
All subunits transition from T- to R-state
O2 quickly binds remaining subunits
↓ pO2 (~40mmHg) R-statesubunitsfavorO2 unloading
O2
O2
O2
O2 O2 O2 O2
In some HbA molecules, O2 remains bound
Reserve oxyhemoglobin is available for higher O2 demand states
Certain disease processes (i.e., Hypoventilation, V/Q mismatch, impaired O2 diffusion) cause pathologically ↓ pO2 states
↑↑ Deoxygenated T-state HbA
Rapid desaturation of remaining oxyhemoglobin due to positive cooperativity
Rapid hypoxia onset at low pO2
When ↓ pO2 in tissues, O2 unloads from a R-state subunit
Subunit destabilizesà Subunit changes shape to T- stateà↓ O2 affinity
Positive cooperativity: All subunits transition from R- to T-state and release O2
O2 unloading in peripheral tissue
O2 O2
O
O2 O2
2
O
O2 O2
O
2
2
Sigmoid-shape oxyhemoglobin ↑↑ O2 loading in dissociation curve pulmonary capillaries
Legend:
Pathophysiology
Mechanism
Final effect
Complications
Published , 2022 on www.thecalgaryguide.com