Physiology, Bohr Effect


Article Author:
Aakash Patel


Article Editor:
Jeffrey Cooper


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Updated:
10/27/2018 12:31:25 PM

Introduction

Oxygen (O2) tends to combine rapidly and reversibly with hemoglobin, and certain changes within the environment can change the affinity of the oxygen molecules to the hemoglobin. The oxygen dissociation curve has a sigmoidal shape due to oxygen’s property of positive cooperativity. The Bohr effect is a lower affinity of hemoglobin for oxygen due to increases in the partial pressure of carbon dioxide and decreases in blood pH. This lower affinity, in turn, enhances unloading of oxygen into tissues to meet the oxygen demand of the tissue.[1]

Issues of Concern

Increases in PCO2 and Decreases in pH 

Increases in metabolic activity within tissues lead to increases in carbon dioxide (CO2). An increase in tissue PCO2 leads to an increase in hydrogen ion (H+) concentration that leads to a decrease in pH. Together, these effects will lead to a decrease in the affinity of hemoglobin to oxygen and cause the shift of the hemoglobin dissociation curve to the right. Specifically, it is the association of protons (H+ ions) with the amino acids in hemoglobin that tend to reduce the affinity for oxygen. The protons shift the configuration of the amino acids to the T-form, reducing attraction for oxygen.

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. In the high oxygenated environment of the lungs, the O2 can overcome the T-form. During the O2 binding-induced alteration from the T-form to the R form, several amino acid groups will dissociate protons, and the reverse (release of O2 and attachment of protons) will lead to a structural change to the T-form.

This overall leads to an increase in the P50, which means that 50% of saturation is achieved at a higher-than-normal value of PO2. This leads to the greater unloading of oxygen into the tissues.[2]

Cellular

This relationship is mediated by carbonic anhydrase, which is the enzyme that converts the carbon dioxide to carbonic acid and releases hydrogen ion resulting in a lower blood pH. This also results in the production of bicarbonate and a majority of the blood carbon dioxide (CO2) is carried as bicarbonate (70%).[3]

CO2 + H2O <-> H2CO3 <-> H+ + HCO3-

Furthermore, this process usually takes place in peripheral tissues, as the desired effect is to unload oxygen into these tissues and load oxygen in the lungs. Deoxygenation of hemoglobin creates a weaker acid that binds the excess H+ ions to limit the decrease in pH. The increased bicarbonate then diffuses out of the cell down its concentration gradient, moving chlorine ions into the cell to maintain the electrical neutrality. The Haldane effect takes place in the alveoli where oxygenation of hemoglobin leads to dissociation of H+ protons from hemoglobin. This, in turn, leads to an increase in pH, a left shift, and greater attachment of oxygen to hemoglobin.[4]

Related Testing

The measurement of the oxygen and carbon dioxide in the blood can be done with an arterial blood gas (ABG) analysis. An ABG will also measure the body’s acid-base (pH) level and give an approximation of the body’s ventilation and metabolism efforts. Based on the PaCO2 on the blood gas, clinicians can get a sense of the amount of CO2 retention and the effect it may have on the Bohr effect. The normal PaCO2 concentration is around 40 mm Hg, and hypercapnia is defined as a PaCO2 greater than 45. If the PaCO2 is greater than 45 and the PaO2 is less then 60 mm Hg, the patient may be in hypercapnic respiratory failure leading to an increased right shift in the oxygen dissociation curve.

Pathophysiology

Through the Bohr effect, more oxygen is released to those tissues with higher Carbon dioxide concentrations. These effects can be suppressed in chronic diseases, leading to decreased oxygenation of peripheral tissues. Chronic conditions such as asthma, cystic fibrosis, or even diabetes mellitus, can lead to a chronic state of hyperventilation. These states can have ventilation of up to 15 L per minute compared to the normal minute ventilation of 6 L per minute. This hyperventilation can lead to excess exhalation of carbon dioxide resulting in hypocapnia. This would shift the oxygen dissociation curve to the left, leading to impaired oxygen release to peripheral tissues. In this case, the CO2 concentration is low, and oxygen molecules are present, but bound to hemoglobin. This further decreases the required oxygen to our most vital organs, including the brain, liver, kidney, and heart. Thus, the Bohr effect is essential in maintaining equilibrium with carbon dioxide and transport of oxygen.[5]

Carbon Monoxide Effect

While carbon dioxide leads to the greater unloading of oxygen, carbon monoxide has the opposite effect. Carbon monoxide has a 200-times greater affinity for hemoglobin and stabilizes the hemoglobin in the R-form. This facilitates loading of the rest of the molecule with oxygen, but it cannot unload the oxygen into the tissues as it results in a left shift of the oxygen-dissociation curve. With a high enough level of carbon monoxide, hypoxia can be present with a normal pO2 as the hemoglobin molecule will have bound carbon monoxide molecules unable to release oxygen. This condition needs to be treated with hyperbaric oxygen, which facilitates a great enough concentration of oxygen to compete for the carbon monoxide and take back the hemoglobin.[6]

Clinical Significance

The Bohr effect assists the body to adapt to changes in the environment and supply oxygen to tissues with the greatest demand. Increased skeletal muscle activity has a high rate of metabolism and requires a greater amount of oxygen for cellular respiration which also generates carbon dioxide. Exercising muscle will also lead to greater lactic acid release further lowering the blood pH and leading to the greater unloading of oxygen. Other factors that also cause a right shift include increased temperature and increases in 2,3-BPG. Considering the example of exercising a muscle, as heat is produced by the working muscle, the curve shifts to the right providing more oxygen to the active tissue. 2,3-BPG is a byproduct of glycolysis in red blood cells and is increased in hypoxic conditions such as high altitude, chronic lung disease, or congestive heart failure. Hypoxic conditions lead to a greater amount of glycolysis resulting in the increases 2,3-BPG level.[7]


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Physiology, Bohr Effect - Questions

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The Bohr effect describes the relationship between oxygen and which of the following?

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Which factors cause the Bohr effect?



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Which of the following will not decrease hemoglobin affinity for oxygen?



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Physiology, Bohr Effect - References

References

Malte H,Lykkeboe G, The Bohr/Haldane effect: A model based uncovering of the full extent of its impact on O{sub}2{/sub} delivery to and CO{sub}2{/sub} removal from tissues. Journal of applied physiology (Bethesda, Md. : 1985). 2018 May 10     [PubMed]
Kaufman DP,Dhamoon AS, Physiology, Oxyhemoglobin Dissociation Curve null. 2018 Jan     [PubMed]
Mesquida J,Saludes P,Espinal C,Gruartmoner G, In response: Blood CO{sub}2{/sub} exchange monitoring, Haldane effect and other calculations in sepsis and critical illness. Journal of clinical monitoring and computing. 2018 Jun 12     [PubMed]
Du Y,Wang J,Li H,Mao S,Wang D,Xiang Z,Guo R,Chen J, The dual function of the algal treatment: Antibiotic elimination combined with CO{sub}2{/sub} fixation. Chemosphere. 2018 Jul 30     [PubMed]
Kuo SC,Hsu CK,Tsai CT,Chieh MJ, [Hyperbaric Oxygen Therapy and Acute Carbon Monoxide Poisoning]. Hu li za zhi The journal of nursing. 2018 Aug     [PubMed]
Tsuji B,Filingeri D,Honda Y,Eguchi T,Fujii N,Kondo N,Nishiyasu T, Reply to Parkes: Effect of hypocapnia on the sensitivity of hyperthermic hyperventilation and the cerebrovascular response in resting heated humans. Journal of applied physiology (Bethesda, Md. : 1985). 2018 May 1     [PubMed]
Jendroszek A,Malte H,Overgaard CB,Beedholm K,Natarajan C,Weber RE,Storz JF,Fago A, Allosteric mechanisms underlying the adaptive increase in hemoglobin-oxygen affinity of the bar-headed goose. The Journal of experimental biology. 2018 Jul 19     [PubMed]

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