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Bohr Effect: Healthy vs. Sick People

Bohr effect (medical or scientific explanation is below)

“All chronic pain, suffering and diseases are caused
from a lack of oxygen at the cell level."

Prof. A.C. Guyton, MD, The Textbook of Medical Physiology*

* World’s most widely used medical textbook of any kind
* World's best-selling physiology book

The Bohr effect explains cells oxygen release or why red blood cells unload oxygen in tissues, while carbon dioxide (CO2) is the key player in O2 transport due to vasodilation and the Bohr effect (or Bohr law).  The Bohr effect was first described in 1904 by the Danish physiologist Christian Bohr (father of famous physicist Niels Bohr).

What is Bohr effect in simple terms?

Bohr effect in healthy people

The Bohr effect is a normal process in healthy people since healthy people have normal breathing at rest and normal arterial CO2 levels. How does the Bohr effect work? As we know, oxygen is transported in blood by hemoglobin cells. How do these red blood cells know where to release more oxygen and where less? Or why do they unload more oxygen at all? Why is O2 released in tissues? The hemoglobin cells sense higher concentrations of CO2 in tissues and release oxygen in such places.

 Bohr effect explained: How CO2 helps to release O2

Bohr effect summary. More oxygen is released in those tissues that have higher absolute and/or relative CO2 values. Note that this This is true for healthy people who have normal breathing pattern.

Suppressed Bohr effect in people with chronic diseases

Can people with chronic diseases enjoy the normal Bohr effect and normal oxygen delivery to the brain, heart and all other vital organs? Consider these medical studies.

Minute ventilation rates (chronic diseases)

Condition Minute
ventilation
Number of
people
All references or
click below for abstracts
Normal breathing 6 L/min - Medical textbooks
Healthy Subjects 6-7 L/min >400 Results of 14 studies
Heart disease 15 (±4) L/min 22 Dimopoulou et al, 2001
Heart disease 16 (±2) L/min 11 Johnson et al, 2000
Heart disease 12 (±3) L/min 132 Fanfulla et al, 1998
Heart disease 15 (±4) L/min 55 Clark et al, 1997
Heart disease 13 (±4) L/min 15 Banning et al, 1995
Heart disease 15 (±4) L/min 88 Clark et al, 1995
Heart disease  14 (±2) L/min 30 Buller et al, 1990
Heart disease 16 (±6) L/min 20 Elborn et al, 1990
Pulm hypertension 12 (±2) L/min 11 D'Alonzo et al, 1987
Cancer 12 (±2) L/min 40 Travers et al, 2008
Diabetes 12-17 L/min 26 Bottini et al, 2003
Diabetes 15 (±2) L/min 45 Tantucci et al, 2001
Diabetes 12 (±2) L/min 8 Mancini et al, 1999
Diabetes 10-20 L/min 28 Tantucci et al, 1997
Diabetes 13 (±2) L/min 20 Tantucci et al, 1996
Sleep apnea 15 (±3) L/min 20 Radwan et al, 2001
Liver cirrhosis 11-18 L/min 24 Epstein et al, 1998
Hyperthyroidism 15 (±1) L/min 42 Kahaly, 1998
Epilepsy 13 L/min 12 Esquivel et al, 1991
CHV 13 (±2) L/min 134 Han et al, 1997
Panic disorder 12 (±5) L/min 12 Pain et al, 1991
Bipolar disorder 11 (±2) L/min 16 MacKinnon et al, 2007
Dystrophia myotonica 16 (±4) L/min 12 Clague et al, 1994

Overbreathing or hyperventilation in the sick causes hypocapnia or reduced CO2 tension in the lungs and arterial blood (since ventilation-perfusion mismatch is not a common finding in the sick). This leads to hampered oxygen release and reduced cells oxygen tension due to the suppressed Bohr effect (Aarnoudse et al, 1981; Monday & Tétreault, 1980; Gottstein et al, 1976).

Suppressed Bohr effect in the sick due to low CO2Hence, for the suppressed Bohr effect, the absolute CO2 concentration is low (see the picture of the right side), and O2 molecules are stuck with red blood cells. (Scientists call this effect “increased oxygen affinity to hemoglobin”). Hence, CO2 deficiency (hypocapnia) leads to hypoxia or cells oxygen levels (the suppressed Bohr effect). The more we breathe at rest, the less the amount of available oxygen in the cells of vital organs, like brain, heart, liver, kidneys, etc.

Many people believe that breathing more air increases oxygen content in cells. This is not true. Generally, breathing more even reduces oxygen content even in the arterial blood. Indeed, hemoglobin cells in normal blood for very small normal breathing are about 98% saturated with O2. When we hyperventilate this number is about the same (in real life it gets less since most people make a transition to automatic costal or chest breathing that reduces arterial blood O2 levels), but without CO2 and the Bohr effect, this oxygen is tightly bound with red blood cells and cannot get into the tissues in required amounts. Hence, now we know one of the causes why heavy breathing reduces cell oxygen level of all vital organs.

The Bohr effect is crucial for our survival. Why? During each moment of our lives, some organs and tissues work harder and produce more CO2. These additional CO2 concentrations are sensed by the hemoglobin cells and cause them to release more O2 in those places where it is most required. This is a smart self-regulating mechanism for efficient cells oxygen transport.

Bohr effect (medical or scientific explanation)

Bohr effect curvesChristian Bohr stated that at lower pH (more acidic environment, e.g., in tissues), hemoglobin will bind to oxygen with less affinity. Since carbon dioxide is in direct equilibrium with the concentration of protons in the blood, increasing blood carbon dioxide content, according to the Bohr effect, causes a decrease in pH, which leads to a decrease in affinity for oxygen by hemoglobin (and easier oxygen release in capillaries or tissues).

The description of the Bohr effect, which is a physiological law, can be found in nearly all physiological textbooks. Modern studies related to the Bohr effect are devoted to more advanced topics (see the titles of studies for modern research below). It is the central proposition of the Bohr effect that oxygen affinity to hemoglobin depends on absolute CO2 concentrations and reduced CO2 values decrease oxygen delivery to body cells.

Bohr effect and physical exercise

Bohr effect during exerciseFor example, without the Bohr effect, we could not walk or run for even 3-5 minutes. Why? In normal conditions, due to the Bohr effect, more O2 is released in those muscles, which generate more CO2. Hence, these muscles can continue to work with the same high rate.

However, sick people have reduced CO2 blood values. Hence, they are likely to experience symptoms of chronic fatigue, and poor results for physical fitness tests due to tissue hypoxia (low cells oxygen levels).

Professor Henderson about Bohr effect

This is what Professor Henderson from the Yale University wrote about the Bohr effect,

"But even as early as 1885, Miescher (Swiss physiologist) inspired by the insight of genius wrote: "Over the O2 supply of the body, CO2 spreads its protecting wings" Yandell Henderson (1873-1944), in Henderson Y, Carbon dioxide, in Cyclopedia of Medicine, ed. by H.H. Young, Philadelphia, FA Davis, 1940.

Here is YouTube video that considers the Bohr effect and explains the mechanism why overbreathing decreases cells oxygen level.

Another web page related to oxygen transport and cell oxygenation: Vasodilation (expansion of arteries and arterioles due to higher CO2 values) or why breathing less improves perfusion or blood flow to all vital organs.

You can read medical research abstract devoted to the Bohr effect and role of CO2 in cells O2 delivery.

References (abstracts are below)

Aarnoudse JG, Oeseburg B, Kwant G, Zwart A, Zijlstra WG, Huisjes HJ, Influence of variations in pH and PCO2 on scalp tissue oxygen tension and carotid arterial oxygen tension in the fetal lamb, Biol Neonate 1981; 40(5-6): p. 252-263.

Braumann KM, Böning D, Trost F, Bohr effect and slope of the oxygen dissociation curve after physical training, J Appl Physiol. 1982 Jun; 52(6): p. 1524-1529.

Böning D, Schwiegart U, Tibes U, Hemmer B, Influences of exercise and endurance training on the oxygen dissociation curve of blood under in vivo and in vitro conditions, Eur J Appl Physiol Occup Physiol. 1975; 34(1): p. 1-10.

Bucci E, Fronticelli C, Anion Bohr effect of human hemoglobin, Biochemistry. 1985 Jan 15; 24(2): p. 371-376.

Carter AM, Grřnlund J, Contribution of the Bohr effect to the fall in fetal PO2 caused by maternal alkalosis, J Perinat Med. 1985; 13(4): p.185-191.

diBella G, Scandariato G, Suriano O, Rizzo A, Oxygen affinity and Bohr effect responses to 2,3-diphosphoglycerate in equine and human blood, Res Vet Sci. 1996 May; 60(3): p. 272-275.

Dzhagarov BM, Kruk NN, The alkaline Bohr effect: regulation of O2 binding with triliganded hemoglobin Hb(O2)3 [Article in Russian] Biofizika. 1996 May-Jun; 41(3): p. 606-612.

Gersonde K, Sick H, Overkamp M, Smith KM, Parish DW, Bohr effect in monomeric insect haemoglobins controlled by O2 off-rate and modulated by haem-rotational disorder, Eur J Biochem. 1986 Jun 2; 157(2): p. 393-404.

Grant BJ, Influence of Bohr-Haldane effect on steady-state gas exchange, J Appl Physiol. 1982 May; 52(5): p. 1330-1337.

Grubb B, Jones JH, Schmidt-Nielsen K, Avian cerebral blood flow: influence of the Bohr effect on oxygen supply, Am J Physiol. 1979 May; 236(5): p. H744-749.

Gottstein U, Zahn U, Held K, Gabriel FH, Textor T, Berghoff W, Effect of hyperventilation on cerebral blood flow and metabolism in man; continuous monitoring of arterio-cerebral venous glucose differences (author's transl) [Article in German], Klin Wochenschr. 1976 Apr 15; 54(8): p. 373-381.

Hlastala MP, Woodson RD, Bohr effect data for blood gas calculations, J Appl Physiol. 1983 Sep; 55(3): p. 1002-1007.

Jensen FB, Red blood cell pH, the Bohr effect, and other oxygenation-linked phenomena in blood O2 and CO2 transport, Acta Physiol Scand. 2004 Nov; 182(3): p. 215-227.

Kister J, Marden MC, Bohn B, Poyart C, Functional properties of hemoglobin in human red cells: II. Determination of the Bohr effect, Respir Physiol. 1988 Sep; 73(3): p. 363-378.

Kobayashi H, Pelster B, Piiper J, Scheid P, Significance of the Bohr effect for body oxygen level in a model with counter-current blood flow, Respir Physiol. 1989 Jun; 76(3): p. 277-288.

Lapennas GN, The magnitude of the Bohr coefficient: optimal for oxygen delivery, Respir Physiol. 1983 Nov; 54(2): p.161-172.

Matthew JB, Hanania GI, Gurd FR, Electrostatic effects in hemoglobin: Bohr effect and ionic strength dependence of individual groups, Biochemistry. 1979 May 15; 18(10): p.1928-1936.

Meyer M, Holle JP, Scheid P, Bohr effect induced by CO2 and fixed acid at various levels of O2 saturation in duck blood, Pflugers Arch. 1978 Sep 29; 376(3): p. 237-240.

Monday LA, Tétreault L, Hyperventilation and vertigo, Laryngoscope 1980 Jun; 90(6 Pt 1): p.1003-1010.

Tyuma I, The Bohr effect and the Haldane effect in human hemoglobin, Jpn J Physiol. 1984; 34(2): p.205-216.

Winslow RM, Monge C, Winslow NJ, Gibson CG, Whittembury J, Normal whole blood Bohr effect in Peruvian natives of high altitude, Respir Physiol. 1985 Aug; 61(2): p. 197-208.

Back to Effects of carbon dioxide on human health
* Illustrations by Victor Lunn-Rockliffe

Reference Web Pages: Breathing norms, Medical Graphs and Tables about Breathing Rates (Minute Ventilation) and Body Oxygen in Healthy, Normal and Sick People
Breathing norms Parameters, graph, and description of the normal breathing pattern
6 breathing myths 6 myths about breathing and body oxygenation (prevalence: over 90%)
Hyperventilation Definitions of hyperventilation: their advantages and weak points
Hyperventilation Syndrome in the Sick. Table 1. Western scientific evidence about prevalence of CHV (chronic hyperventilation) in patients with various chronic conditions (34 medical studies)
Normal Minute Ventilation in Healthy Subjects: Easy and Light Breathing (14 Studies)
Hyperventilation Prevalence Present in Over 90% of Normal People (24 medical publications)
HV and hypoxia How and why deep breathing reduces oxygenation of cells and tissues of all vital organs
Body oxygen test How to measure your own breathing and body oxygenation (a simple DIY test)
Body oxygen in healthy Table 4. CP (body oxygen level) in healthy people (27 medical studies)
Body oxygen in sick Table 5. CP (body oxygen level) in sick people (14 medical studies)
Buteyko Table of Health Zones with clinical description of most common zones
Morning HV Morning hyperventilation effect or how and why critically ill people are most likely to die during early morning hours

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