The exchange of oxygen and carbon dioxide between the lungs, blood, and tissues is a finely tuned process that sustains life. One of the most important physiological principles that helps explain this process is the Bohr effect.
This concept describes how changes in blood chemistry influence the binding and release of oxygen from hemoglobin, ensuring that oxygen is delivered precisely where it is most needed.
For respiratory therapists, understanding the Bohr effect is more than academic—it is directly relevant to patient care and clinical decision-making.
What Is the Bohr Effect?
The Bohr effect is a physiological principle that explains how carbon dioxide (CO₂) levels and blood pH influence hemoglobin’s ability to bind and release oxygen. When CO₂ levels rise or pH decreases (acidosis), hemoglobin’s affinity for oxygen decreases, making it release oxygen more readily to tissues. Conversely, when CO₂ levels are low or pH increases (alkalosis), hemoglobin holds onto oxygen more tightly.
This shifting of the oxyhemoglobin dissociation curve ensures oxygen delivery is matched to tissue demand, promoting oxygen release in metabolically active tissues while enhancing oxygen uptake in the lungs. It is essential for efficient gas exchange and cellular function.
What is the Oxyhemoglobin Dissociation Curve?
The oxyhemoglobin dissociation curve is a graphical representation that shows the relationship between the partial pressure of oxygen (PaO₂) in the blood and the percentage of hemoglobin saturated with oxygen (SaO₂). It illustrates how readily hemoglobin binds to oxygen in the lungs and releases it to the tissues.
The curve has a sigmoid (S-shaped) shape, reflecting hemoglobin’s cooperative binding: once one oxygen molecule binds, hemoglobin’s affinity for additional oxygen increases.
- Left shift: Hemoglobin holds oxygen more tightly (higher affinity), reducing oxygen delivery to tissues.
- Right shift: Hemoglobin releases oxygen more easily (lower affinity), enhancing tissue oxygen delivery.
Note: This curve is central to understanding oxygen transport and the Bohr effect in respiratory care.
Why Does the Bohr Effect Matter?
The Bohr effect ensures that oxygen delivery is matched to tissue demand:
- In active tissues (like exercising muscles), metabolic activity produces more CO₂ and hydrogen ions, lowering pH. This shift makes hemoglobin release more oxygen right where it is needed most.
- In the lungs, where CO₂ is exhaled and the blood is more alkaline, hemoglobin binds oxygen tightly, maximizing oxygen uptake for transport.
Note: In other words, the Bohr effect is the body’s built-in mechanism to optimize oxygen delivery in response to metabolic changes.
Relevance to Respiratory Therapists
For respiratory therapists, the Bohr effect plays a critical role in understanding blood gases, oxygen therapy, and mechanical ventilation:
- Arterial Blood Gas (ABG) Interpretation: ABGs provide key information about a patient’s acid-base balance. A low pH (acidosis) or high CO₂ (hypercapnia) will shift the oxyhemoglobin curve to the right, facilitating oxygen unloading but potentially reducing oxygen saturation. Recognizing this helps therapists understand why hypoxemia may persist even with supplemental oxygen.
- Mechanical Ventilation and Oxygenation: Ventilator settings directly influence CO₂ levels and thus pH. For example, inadequate ventilation may lead to respiratory acidosis, shifting the curve to the right. Conversely, hyperventilation lowers CO₂ and raises pH, shifting the curve to the left, which can impair tissue oxygen delivery despite normal SpO₂ readings.
- Critical Care Situations: In conditions such as sepsis, shock, or diabetic ketoacidosis, metabolic changes affect pH and oxygen binding. Therapists must consider the Bohr effect when interpreting oxygenation and making clinical decisions.
- Exercise and Rehabilitation: During pulmonary rehabilitation or exercise testing, the Bohr effect explains how oxygen is more effectively delivered to working muscles, reinforcing the importance of oxygen delivery dynamics in patient recovery and performance.
Clinical Example
Consider a patient with an acute COPD exacerbation. Their ABG may show elevated PaCO₂ and a low pH. The Bohr effect predicts that hemoglobin will release oxygen more readily to the tissues. However, oxygen saturation may appear low, prompting careful titration of supplemental oxygen to balance oxygen delivery with the risk of CO₂ retention.
Bohr Effect Practice Questions
1. What is the Bohr effect?
An increase in CO₂ or H⁺ concentration (decrease in pH) causes a rightward shift of the oxygen dissociation curve, promoting oxygen release from hemoglobin
2. Which two physiological factors, aside from CO₂ and pH, can shift the oxygen dissociation curve to the right?
Increased temperature and elevated levels of 2,3-diphosphoglycerate (2,3-DPG)
3. In what type of patients is an increase in 2,3-DPG commonly observed?
Patients with chronic lung disease or chronic hypoxemia
4. What does a rightward shift in the oxygen dissociation curve indicate?
At any given PaO₂, hemoglobin binds less oxygen, enhancing oxygen delivery to tissues
5. How does a rightward shift in the oxygen dissociation curve affect oxygen delivery to the tissues?
It increases the amount of oxygen released to tissues due to higher PCO₂ and lower PO₂ in capillary blood
6. On a graph illustrating the Bohr effect, what does the difference between points (a) and (v) represent?
The total amount of oxygen delivered to tissues (Δ2), with a portion enhanced by the Bohr effect (Δ1)
7. How does the Bohr effect function in the alveolar capillary compared to the tissue capillary?
It is reversed; oxygen is loaded into the blood (v → a) rather than unloaded (a → v)
8. What happens to arterial PO₂ and PCO₂ levels during exercise?
They remain relatively unchanged at approximately 100 mmHg and 40 mmHg, respectively
9. What changes occur to venous PO₂ and PCO₂ during exercise?
Venous PO₂ decreases to ~35 mmHg, and PCO₂ increases to ~50 mmHg due to elevated metabolism
10. How does a further increase in PCO₂ during exercise affect the oxygen dissociation curve?
It causes an even greater rightward shift, enhancing oxygen delivery to tissues (Δ3)
11. In which conditions is the Bohr effect more pronounced?
During exercise and in individuals with chronic lung disease
12. What is hemoglobin?
A metalloprotein in red blood cells responsible for transporting oxygen from the lungs to tissues
13. How does the Bohr effect influence hemoglobin’s affinity for oxygen?
It lowers hemoglobin’s affinity for oxygen in the presence of increased CO₂ and decreased pH
14. What happens to hemoglobin’s oxygen-binding affinity at lower pH levels?
Affinity decreases, promoting oxygen release in acidic environments
15. How do hydrogen ions (H⁺) reduce hemoglobin’s affinity for oxygen?
H⁺ binds to hemoglobin, altering its structure and preventing oxygen from binding effectively
16. Why does hemoglobin produce a sigmoidal oxygen dissociation curve?
Because oxygen binding increases hemoglobin’s affinity for additional oxygen until saturation, creating an S-shaped curve
17. What is the physiological importance of the Bohr effect?
It enhances oxygen unloading in metabolically active tissues that produce more CO₂ and H⁺
18. What are skeletal muscles and skin examples of in terms of oxygen transport?
Peripheral tissues where oxygen is delivered and CO₂ is collected
19. What is the primary driving force behind muscular respiration?
The increase in partial pressure of CO₂ within active muscle tissue
20. Why is the Bohr effect essential during physical activity?
It increases oxygen release in active tissues where CO₂ and acidity levels are elevated
21. What gas increases proportionally with enhanced metabolic activity and contributes to the Bohr effect?
Carbon dioxide (CO₂) increases proportionally with metabolic rate, enhancing the Bohr effect
22. The production of what substance during intense exercise can enhance the Bohr effect?
Lactic acid
23. How does the Bohr effect facilitate muscular respiration during activity?
Decreased pH and increased CO₂ in muscle capillaries cause hemoglobin to release more oxygen to active muscles
24. Has skin oxygenation therapy been shown to rejuvenate skin, and why is it less commonly used today?
Yes, but it is less used now due to high cost and potential side effects
25. Why does a carboxytherapy facial promote skin rejuvenation?
It increases local CO₂, which triggers oxygen release in the skin via the Bohr effect
26. What skincare treatment applies the Bohr effect for cosmetic purposes?
Carboxytherapy facial
27. How many participants were involved in the OxyGeneo™ with NeoRevive™ or NeoBright™ clinical trial?
10 participants
28. What pharmaceutical agent uses the Bohr effect as part of its mechanism of action?
Triazole disulfide
29. To which amino acid does triazole disulfide bind on hemoglobin?
Cysteine
30. What conformation of hemoglobin does triazole disulfide stabilize?
R-state (relaxed state), which favors oxygen binding
31. How does triazole disulfide reduce the magnitude of the Bohr effect?
By inhibiting salt bridge formation, which interferes with T-state stabilization
32. What type of hemoglobin is commonly used in blood substitute formulations?
Bovine hemoglobin
33. What chemical is used to cross-link bovine hemoglobin in blood substitutes?
Glutaraldehyde
34. How does glutaraldehyde affect the function of bovine hemoglobin?
It reduces responsiveness to allosteric modulators, including the Bohr effect
35. How does the Bohr effect appear on the oxygen-hemoglobin dissociation curve?
It demonstrates how increased CO₂ shifts the curve to the right, reducing hemoglobin’s affinity for oxygen.
36. Where does the oxygen dissociation curve shift when CO₂ levels in the blood are low?
To the left
37. Where does the oxygen dissociation curve shift when CO₂ levels in the blood are high?
To the right
38. Describe the effect of high CO₂ concentrations on hemoglobin’s affinity for oxygen:
Increased CO₂ forms carbonic acid → H⁺ increases → pH decreases → hemoglobin releases oxygen more readily
39. How does a high CO₂ concentration in respiring tissues affect blood pH?
CO₂ forms carbonic acid, which increases H⁺ concentration and lowers pH
40. Why is the Bohr effect considered a physiological advantage during exercise?
It enhances oxygen delivery to muscles by promoting oxygen unloading in high CO₂, low pH environments
41. What happens to oxygenated hemoglobin as CO₂ levels increase in the blood?
Hemoglobin shifts toward the T-state, decreasing its affinity for oxygen due to lower pH
42. At a tissue oxygen pressure of 40 Torr and a pH of 7.2, what is the expected hemoglobin saturation?
Approximately 50% saturation
43. How does the pH in peripheral tissues compare to that in the lungs?
It is lower due to metabolic CO₂ being converted to bicarbonate, releasing H⁺ ions
44. Why is more oxygen unloaded in actively metabolizing tissues compared to resting tissues?
Active tissues have lower pH due to CO₂ production, which decreases hemoglobin’s oxygen affinity
45. During cardiac arrest, why might sodium bicarbonate be administered to a patient?
To increase blood pH, which may improve hemoglobin’s ability to transport oxygen
46. Why is the statement “bicarbonate prompts hemoglobin to shift to the R state and pick up CO₂” incorrect?
Because H⁺ ions, not CO₂, bind to hemoglobin and influence its state; bicarbonate raises pH by binding to H⁺, not by promoting CO₂ uptake.
47. Hemoglobin acts as a buffer by binding to which molecule to help regulate blood pH?
H⁺ ions
48. How does an increase in H⁺ concentration affect hemoglobin’s oxygen dissociation curve due to the Bohr effect?
It shifts the curve to the right, promoting oxygen release
49. What happens to the pH of the blood when H⁺ ion concentration increases?
The pH decreases
50. What is the indirect role of CO₂ in lowering pH in active tissues?
CO₂ reacts with water to form bicarbonate and H⁺ via carbonic anhydrase, increasing acidity
51. At an oxygen partial pressure of 40 Torr, which pH results in the greatest oxygen delivery to tissues?
pH 7.2
52. What is the approximate hemoglobin saturation at 40 Torr and pH 7.2?
About 50%
53. On an oxygen-hemoglobin dissociation curve, what does a rightward shift indicate?
Decreased oxygen affinity due to low pH or high CO₂, with hemoglobin favoring the T state
54. What happens to oxygenated hemoglobin as H⁺ concentration decreases?
It shifts to the R state and binds more oxygen.
55. Is deoxygenated hemoglobin favored by high or low pH?
Low pH
56. As H⁺ concentration decreases, how does it affect deoxygenated hemoglobin?
It shifts to the R state and increases its affinity for oxygen.
57. Why is the pH in peripheral tissues lower than in the lungs?
Because metabolic CO₂ is converted to bicarbonate and H⁺, increasing acidity in the tissues
58. What happens to deoxygenated hemoglobin as the partial pressure of oxygen (pO₂) increases?
It picks up additional oxygen molecules and shifts to the R state, and it tends to retain bound oxygen.
59. According to the Bohr effect, what happens to hemoglobin at high pH?
Hemoglobin has a high affinity for oxygen and binds it more readily.
60. Which of the following best describes the Bohr effect in relation to pH and oxygen binding?
Hemoglobin binds oxygen at high pH and releases it at low pH.
61. What happens to hemoglobin’s affinity for oxygen at low pH?
It decreases, causing hemoglobin to release oxygen more readily.
62. How does a high concentration of CO₂ and H⁺ affect the hemoglobin-oxygen dissociation curve?
It causes a rightward shift, promoting oxygen release.
63. What does a rightward shift of the hemoglobin dissociation curve indicate?
The T state is favored, and oxygen is more readily released due to low pH.
64. In a hemoglobin dissociation curve showing different pH levels, which curve represents oxygen saturation in the lungs?
The curve at pH 7.6
65. Which of the following best describes hemoglobin’s oxygen-binding affinity in different states?
High in the R state and low in the T state
66. As CO₂ concentration increases in a cell, what happens to H⁺ and pH?
H⁺ increases and pH decreases
67. Does deoxygenated hemoglobin have a high or low affinity for carbon monoxide (CO)?
Low affinity
68. Where does carbon monoxide (CO) bind on the hemoglobin molecule?
To the iron (Fe) atom within the heme group
69. In a hemoglobin dissociation curve, which line would most likely represent fetal hemoglobin compared to adult hemoglobin?
Curve b, due to its higher oxygen affinity
70. How does a change in pH affect the hemoglobin-oxygen binding curve according to the Bohr effect?
Increased H⁺ shifts the curve to the right; decreased H⁺ shifts it to the left
71. Which of the following are expected characteristics of hemoglobin in the lungs?
Hemoglobin is in the R state, the heme group is planar, and the subunits are closer together than in the T state.
72. What factor stabilizes the R state of hemoglobin?
High oxygen concentration
73. At an oxygen tension of 40 Torr and a pH of 7.6, what is the approximate hemoglobin saturation?
About 0.8 (or 80%)
74. What effect does 2,3-BPG have on hemoglobin?
It binds to hemoglobin’s subunits and stabilizes the T state, favoring deoxygenation.
75. Does oxygenated hemoglobin have a high or low affinity for carbon monoxide (CO)?
High affinity
76. If hemoglobin’s affinity for oxygen increases, how will the oxygen dissociation curve shift?
It will shift to the left and upward
77. What happens to oxygenated hemoglobin as O₂ concentration increases?
It tends to retain bound oxygen, and it picks up more oxygen and remains in the R state.
78. How many oxygen molecules can be bound to oxygenated hemoglobin?
Between 1 and 4 oxygen molecules
79. How many oxygen molecules are bound to fully deoxygenated hemoglobin?
0 oxygen molecules
80. Is oxygenated hemoglobin favored by high or low pH?
High pH
81. What happens to oxygenated hemoglobin as CO₂ levels increase?
pH decreases, hemoglobin shifts toward the T state, and oxygen affinity decreases
82. What is the conformational difference between oxygenated and deoxygenated hemoglobin?
Oxygenated hemoglobin is in the R (relaxed) state; deoxygenated hemoglobin is in the T (tense) state.
83. During cardiac arrest, why might sodium bicarbonate be administered?
To increase blood pH, which may improve hemoglobin’s ability to transport oxygen
84. Why is more oxygen unloaded from hemoglobin in an actively metabolizing tissue compared to a resting tissue, even at the same oxygen concentration?
Because the lower pH in active tissues reduces hemoglobin’s affinity for oxygen
85. What happens to the shape of the heme group when oxygen binds to hemoglobin?
It changes from a bent shape to a planar configuration
86. Which of the following are true about oxygen affinity and hemoglobin?
As pH decreases, hemoglobin’s affinity for oxygen decreases. As 2,3-BPG decreases, hemoglobin’s affinity for oxygen increases.
87. At an oxygen concentration of 40 Torr, which pH would result in the lowest hemoglobin saturation?
pH 7.2
88. At what pH is hemoglobin most saturated in the lungs according to the oxygen dissociation curve?
pH 7.6
89. According to the Bohr effect, what is hemoglobin’s behavior at high pH?
It has a higher affinity for oxygen and binds it more readily.
90. What happens to hemoglobin as the partial pressure of oxygen increases?
It picks up additional oxygen and shifts to the R state, and it tends to retain bound oxygen.
91. How does pH differ between the lungs and peripheral tissues, and why?
Peripheral tissues have a lower pH due to CO₂ conversion into bicarbonate and free H⁺ ions.
92. What happens to deoxygenated hemoglobin when H⁺ concentration decreases?
It shifts toward the R state and binds more oxygen if available.
93. Hemoglobin helps buffer the blood and maintain pH by binding to what?
Hydrogen ions (H⁺)
94. Which of the following is true about the oxygen dissociation curve?
A low pH shifts the curve to the right and favors the T state of hemoglobin.
95. At pH 7.2 and 40 Torr of oxygen, what is the approximate hemoglobin saturation?
Approximately 0.5 (or 50%)
96. At 40 Torr of oxygen, which pH would result in greater oxygen unloading to tissues?
pH 7.2
97. What is the effect of 2,3-BPG on hemoglobin’s oxygen-binding ability?
It decreases oxygen affinity by stabilizing the T state.
98. What does a rightward shift in the hemoglobin-oxygen dissociation curve indicate?
Reduced oxygen affinity and enhanced oxygen release in tissues
99. What does a leftward shift in the hemoglobin-oxygen curve indicate?
Increased oxygen affinity and reduced release to tissues
100. How does high CO₂ concentration indirectly lead to more oxygen being unloaded in tissues?
It lowers pH, shifting hemoglobin to the T state and reducing oxygen affinity
Final Thoughts
The Bohr effect is a cornerstone of respiratory physiology and a vital concept for respiratory therapists. By understanding how CO₂ and pH influence oxygen transport, therapists can better interpret ABGs, optimize ventilator settings, and ensure effective oxygen therapy.
In practice, this knowledge empowers clinicians to provide precise, evidence-based care that supports both gas exchange and overall patient outcomes.
Written by:
John Landry is a registered respiratory therapist from Memphis, TN, and has a bachelor's degree in kinesiology. He enjoys using evidence-based research to help others breathe easier and live a healthier life.
References
- Benner A, Patel AK, Singh K, et al. Physiology, Bohr Effect. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025.