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EPISODE #4 | April 11, 2021

Breathing Part 2 - Physiological Adaptations


Episode #4: Breathing Part 2 - Physiological Adaptations

Fun Facts and Health Hacks with Stefan and Zack
● Health hack: Playing or listening to musical instruments for decreased stress, age related cognitive decline, and treatment for stroke, brain injury, dementia and other neurological pathologies. Zack uses music and his instrument the kalimba to promote parasympathetic expression in times of stress of even in between sets of a workout to maximise recovery (1,2,3).

● Fun fact: Piezoelectricity is the generation of an electric charge when a mechanical force is placed upon a crystalline structure such as a microchip, a touch screen, or a quartz crystal watch. Your bones and the way in which they add or remove calcium is determined by piezoelectric effects as well. When a bone is placed under stress it will experience compression in some areas and tension in others causing a relative negative or positive charge respectively. This change in local voltage affects the osteoblasts to build bone or osteoclasts to break down to create the most efficient supportive structure with the least amount of excess weight for the tasks that it is placed under (4,5,6). This change in structure based upon the function of that structure is known as Wolff’s Law (8). This is also present on soft tissues (7).


Breathing and Ventilation (Respiration)
● Essentially your body interacting with the atmosphere around you.● There are two locations where Ventilation takes place.
  1. External Ventilation - The conducting zones or airways including the nasal cavity, trachea and bronchioles move air towards the alveolar sacs. - Oxygen (O2) and carbon dioxide (C02) diffusion across the respiratory membrane, oxygen moving into from the alveolus into the blood and carbon dioxide traveling from the blood to the alveolus. - Partial pressure gradients of O2 and CO2 drive their diffusion. O2 has a much steeper gradient, meaning a creating pressure then that of CO2 but equal because CO2 is 20 times more soluble in plasma (blood). - Equilibrium of the exchange happens in ⅓ of the amount of time red blood cells spend in a pulmonary capillary. This extra time is allotted in case the blood moves faster as in exercise. - There are factors that influence external ventilation: 1. The partial pressures and gas solubilities discussed above. 2. The surface area and thickness of the respiratory membrane. 3. Ventilation-Perfusion coupling: This is a compensation that happens in the arterial and bronchial tissue. → In an area of the alveoli where the partial pressure of oxygen is high, the blood vessels will dilate to pick up more oxygen. If they are low the blood vessels will contract so that oxygen does not travel in the wrong direction, and the blood moves where the oxygen is high. → In areas of the alveoli where the partial pressure of carbon dioxide is high, the bronchioles will dilate so they may expel more out of the blood. In areas where it is low, the bronchioles will constrict as to not allow CO2 to move in the wrong direction, and move that air to somewhere with higher pressure of CO2.
2. Internal Respiration - Involves the capillary gas exchange at the tissues of the body using energy. - Tissue cells use O2 and produce CO2 as a byproduct. - Another pressure gradient is creating, moving oxygen into the tissues and carbon dioxide out (9).


Transportation of Oxygen and Carbon Dioxide
● Most oxygen is transported via hemoglobin(Hb) in Red blood cells (RBCs). Carrying the hemoglobin in the blood decreases its viscosity and the shape of the RBC takes advantage of fluid movement in the center of vessels (concave sail shaped). ● Factors influencing oxygen affinity: - The Partial pressure of oxygen: Once the first O2 molecule binds to iron, the Hb molecule changes shape. As a result, it more readily takes up 2 more O2 molecules and uptake of the fourth is even more facilitated (this works for unloading as well). - Temperature, pH, PCO2 and blood concentrations of BPG (2,3-Bisphosphoglyceric acid). - All these factors influence Hb saturation by modifying its structure, thereby changing affinity of O2.● Most CO2 is transported via bicarbonate ions in plasma and some CO2 (20%) is carried by HB but it does not compete with O2 because it binds to the amino acids of globin. - Most CO2 molecules quickly enter RBCs where the reactions that convert carbon dioxide into bicarbonate ions occurs. - This also happens in blood plasma but is quicker in RBCs because they contain an enzyme, carbonic anhydrase, that reversibly catalyse the conversion of CO2 and water to carbonic acid which then breaks down to bicarbonate and hydrogen ions. - Bicarbonate helps maintain proper blood pH. if the hydrogen ion concentration in blood begins to rise excessively, these ions can be removed by combining them with bicarbonate to form carbonic acid (a weak acid). If the hydrogen ion concentrations blood drops below normal levels, carbonic acid breaks apart, releasing hydrogen ions and lowering pH again (9).


Blood Oxygen Saturations
● Under normal conditions, arterial blood hemoglobin is 98% saturated (Arterial blood 20 % 02 volume). Even during exercise, it maintains above 92% normally, displaying its efficiency. ● As the blood travels through systemic capillaries, it releases oxygen, yielding an Hb saturation of 75% and 02 content of 15 % volume in venous blood (9).


The Bohr and Haldane Effect Relationship 
● Bhor effect: As cells go through cellular metabolism, energy and oxygen are used, CO2 is produced, which increases hydrogen ion levels and the partial pressure of CO2 in capillary blood. Both weaken the Hb-O2 bond, which enhancing unloading of oxygen to the tissue.● Haldane effect: The lower the Partial pressure of O2 and the lower the amount of O2 bound with Hb, the more CO2 that blood can carry. As CO2 is created and enters the blood, it causes more oxygen to unload from Hb (Bohr effect). This dissociation allows more CO2 to combine with Hb. This is the Haldane effect which helps CO2 exchange at both the lungs and tissues. At the lungs, uptake of O2 improves the release of CO2. As Hb binds with O2, the Hydrogen ions released bind with bicarbonate ions making Carbonic acid (then breaks down to CO2 and H2O) which help unload CO2 from the blood in the lungs (9).


Mechanisms Influencing Breathing 
● Breathing has both a voluntary and involuntary controls.● The involuntary component is controlled by respiratory centers in the pons and medulla (brainstem). These are rhythm-generating and integrative centers.● The act on nerves which innervate the respiratory muscles for both inhalation and exhalation. They also receive sensory information from stretch and chemoreceptors so better optimizing breathing rate and depth.● The most powerful stimulant to increase breathing rate and volume is not decreased levels of oxygen but from increasing levels of carbon dioxide and associated rising levels of hydrogen ions (decreasing pH).● There are also higher brain centers including the hypothalamus and cerebral cortex that influence breath, the Hypothalamus (and the rest of the limbic system) create changes in breath related to our emotion, pain and temperature sensation as well as many other stressors. The cortical controls via the cerebral cortex is the mechanism of our conscious control of breath (9).


Breathing Techniques to Influence States of Stress
● Due to the relationship described above between our hypothalamus (and the rest of the limbic system), autonomic nervous system and brain stem breathing centers we can use the conscious controls of breath to work backwards and change states of stress (10).


The Paradox of breathing practices for “pre-workout”
● If we do a hyperventilation esk breathing technique before exercise, we increase sympathetic tone (fight or flight response) and mobilize energy stores for energy. At the same time, hyperventilation means we breath off a lot of our CO2 decreasing its partial pressure. Knowing the Bohr effect, this means an increase in oxygen affinity to hemoglobin and tissues not receiving adequate oxygen.


Concept of Over Breathing
● As described above, chemical regulation of CO2 in the blood is what drives respiration, more CO2 = more breathing.● O2 levels constantly remain above ~95%.● Exhalation will offload relatively too much CO2, if there is a constantly low levels of CO2, the respiratory center in the brainstem will accommodate this as its perception of “normal” leading to increased respiration in the presence of increased CO2.● CO2 is required at certain levels to maintain good blood flow. It stimulates release of Nitric oxide from epithelial cells in the arteries causing vasodilation. Decreased CO2 shown to decrease cerebral blood flow causing symptoms such as headaches or fatigue due to limited O2 delivery to all tissues (11).


Benefits of Nose Breathing
● Nose breathing humidifier, filters and heats the air more efficiently, it decreases volume of air breathed, allows for more abdominal diaphragm breathing increasing NO production (humming amplifies this on exhale) (12,13, 14).● Can be used as an indicator of exercise intensity over Heart Rate.● Nose breathing moistens and warms incoming air, breathing through the mouth can lead to dehydration as considerable moisture is expended. Mouth breathing is ineffective at retaining moisture in exhale so can potentially lead to greater dehydration (9). ● This is especially important during sleep as a lot of recovery and repair is taking place.



Using Breathing Practices During Recovery from Injury
● Breathing practices can still stimulate the tissue from a cardiovascular response to make positive adaptations. Even if you are injured and cannot do your regular workout routine, you can still impact and maintain some levels of fitness with breathing exercises.


Research on the Benefits of Hypoxic States and Breath Holds
● 3 sets of 5 max breath holds increased erythropoietin (EPO) by 24% (15, 16). EPO is a glycoprotein cytokine secreted mainly by the kidney in response to cellular hypoxia; it then stimulates RBC production in the bone marrow (17).● The production of growth factors that lead to the development of new blood vessels (Angiogenesis) (18).● An increase of nitric oxide synthase (in vivo), Nitric oxide synthase is a type of enzyme that catalyzes the production of nitric oxide (NO) from L-arginine. This creates many positive effects on cell tissues and enhances vasodilation (19).● Stem cells can only survive in hypoxic states. These cells are vastly important to all tissue regeneration and survival. Stem cells are abundant within in fetal circulation because the mothers womb is very hypoxic. Once the child is born, the stem cells survive in different areas of the body called niches, one of which being bone marrow. You can see a blood increase of up to 15x of active mesenchymal stem cells (MSC) during hypoxia. Also, when cultured in environments of just 2 percent oxygen, as opposed to the 20 percent oxygen in normal air, stem cells retain their self-renewing abilities. With just a couple of minutes of hypoxia a day, you may stimulate your stem cells to move from bone marrow to the rest of your body (20,21,22,23,24,25,26,27).● Stimulates neuronal stem cell growth as well as increases NO production. This was shown to have benefits in degenerative disease including Parkinsons and Alzheimers (28,29).● Improved mitochondrial efficiency. This study demonstrated in humans that the skeletal muscles of BHD (breath hold divers) have adapted to conserving oxygen within the mitochondria. This was characterized by lower mitochondrial oxygen consumption both during low leak and high (electron transfer system) respiration than matched controls. This may be similar to the adaptations of diving mammals who can maintain oxidative metabolism in hypoxic conditions via improved capacity for oxygen transport and mitochondrial oxidative phosphorylation in skeletal muscle (30). ● Spleen contraction due to breath hold via drop in oxygen pressure. Increased hemoglobin and hematocrit, by releasing RBCs. Study showed that completing 3-5 max breath holds can lead to 2-4% increase in hemoglobin (31,32,33,34). ● Increase Vo2 max (35).● Hypobaric hypoxia Improves body composition (36).



References:
1. Kunikullaya KU, Goturu J, Muradi V, Hukkeri PA, Kunnavil R, Doreswamy V, Prakash VS, Murthy NS. Music versus lifestyle on the autonomic nervous system of prehypertensives and hypertensives--a randomized control trial. Complement Ther Med. 2015 Oct;23(5):733-40. doi: 10.1016/j.ctim.2015.08.003. Epub 2015 Aug 5. PMID: 26365454.

2. Mansky R, Marzel A, Orav EJ, Chocano-Bedoya PO, Grünheid P, Mattle M, Freystätter G, Stähelin HB, Egli A, Bischoff-Ferrari HA. Playing a musical instrument is associated with slower cognitive decline in community-dwelling older adults. Aging Clin Exp Res. 2020 Aug;32(8):1577-1584. doi: 10.1007/s40520-020-01472-9. Epub 2020 Feb 6. PMID: 32144734.

3. Galińska E. Music therapy in neurological rehabilitation settings. Psychiatr Pol. 2015;49(4):835-46. English, Polish. doi: 10.12740/PP/25557. PMID: 26488358.
4.Becker, R. O. (2020). The body electric: Electromagnetism and the foundation of life. New York, NY: William Morrow
5.Williams PA, Saha S. The electrical and dielectric properties of human bone tissue and their relationship with density and bone mineral content. Ann Biomed Eng. 1996 Mar-Apr;24(2):222-33. doi: 10.1007/BF02667351. PMID: 8678354.

6. Pawlikowski, M. (2017). Electric Phenomenon in Bones as a Result of Piezoelectricity of Hydroxyapatite. Archives of Clinical and Biomedical Research, 01(03), 132-139. doi:10.26502/acbr.50170017
7.Jasmina Isakovic, Ian Dobbs-Dixon, Dipesh Chaudhury, Dinko Mitrecic. Modeling of inhomogeneous electromagnetic fields in the nervous system: a novel paradigm in understanding cell interactions, disease etiology and therapy. Science Report. 2018 Aug 27;8(1):12909. doi: 10.1038/s41598-018-31054-9.
8. https://en.wikipedia.org/wiki/Wolff%27s_law
9. Marieb, E. and Hoehn, K., 2010. Human Anatomy & Physiology. 8th ed. San Francisco: Pearson Education, pp.90-112.
10. Brown RP, Gerbarg PL. Yoga breathing, meditation, and longevity. Ann N Y Acad Sci. 2009 Aug;1172:54-62. doi: 10.1111/j.1749-6632.2009.04394.x. PMID: 19735239.
 11. Patrick McKeown, The Oxygen Advantage: The Simple, Scientifically Proven Breathing Technique That Will Revolutionise Your Health and Fitness, London: Piatkus, 2015.
12. J. Lundberg and E. Weitzberg, “Nasal Nitric Oxide in Man,” Thorax 54, no. 10 (October 1999): 947–52, http://dx.doi.org/10.1136/thx.54.10.947.
13. Maniscalco M, Pelaia G, Sofia M. Exhaled nasal nitric oxide during humming: potential clinical tool in sinonasal disease? Biomark Med. 2013 Apr;7(2):261-6. doi: 10.2217/bmm.13.11. PMID: 23547821.
14.Lundberg JO. Nitric oxide and the paranasal sinuses. Anat Rec (Hoboken). 2008 Nov;291(11):1479-84. doi: 10.1002/ar.20782. PMID: 18951492.
15. Kjeld T, Jattu T, Nielsen HB, Goetze JP, Secher NH, Olsen NV. Release of erythropoietin and neuron-specific enolase after breath holding in competing free divers. Scand J Med Sci Sports. 2015 Jun;25(3):e253-7. doi: 10.1111/sms.12309. Epub 2014 Aug 20. PMID: 25142912.
16. de Bruijn R, Richardson M, Schagatay E. Increased erythropoietin concentration after repeated apneas in humans. Eur J Appl Physiol. 2008 Mar;102(5):609-13. doi: 10.1007/s00421-007-0639-9. Epub 2007 Dec 19. PMID: 18097682.
17. An increase in red blood cells: H. Scholz et al., “Role of Erythropoietin in Adaptation to Hypoxia,” Experientia 46, no. 11–12 (December 1990): 1197–1201, https://dx.doi.org/10.1007/bf01936936.
18. Gregg L. Semenza, “Regulation of Hypoxia-Induced Angiogenesis: A Chaperone Escorts VEGF to the Dance,” The Journal of Clinical Investigation 101, no. 1 (July 1, 2001): 39–40, https://doi.org/10.1172/JCI13374.
19. Hypoxic Regulation of Inducible Nitric Oxide Synthase via Hypoxia Inducible Factor-1 in Cardiac Myocytes,” Circulation Research 86, no. 3 (February 2000): 319–25, https://doi.org/10.1161/01.RES.86.3.319
20. Zheng Z Wei et al., “Priming of the Cells: Hypoxic Preconditioning for Stem Cell Therapy,” Chinese Medical Journal 130, no. 19 (October 2017): 2361–2374, https://dx.doi.org/10.4103/0366-6999.215324.
21.“The Role of Hypoxia in Stem Cell Differentiation and Therapeutics,” Journal of Surgical Research 165, no. 1 (January 2011): 112–117, https://dx.doi.org/10.1016/j.jss.2009.09.057;
22. Frédéric Rodesch, Philippe Simon, and Eric Jauniaux, “Oxygen Measurements in Endometrial and Trophoblastic Tissues during Early Pregnancy,” Obstetrics & Gynecology 80, no. 2 (August 1992): 283–5,
23.“Benefits of Hypoxic Culture on Bone Marrow Multipotent Stromal Cells,” American Journal of Blood Research 2, no. 3 (October 2012): 148–159, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484415/.
24.“Multipotential Mesenchymal Stem Cells Are Mobilized into Peripheral Blood by Hypoxia,” Stem Cells 24, no. 10 (October 2006): 2202–2208, https://doi.org/10.1634/stemcells.2006-0164.
25.Cristina Mas-Bargues et al., “Relevance of Oxygen Concentration in Stem Cell Culture for Regenerative Medicine,” International Journal of Molecular Sciences 20, no. 5 (March 2019): 1195, https://dx.doi.org/10.3390/ijms20051195;
26. Se Yun Kwon et al., “Hypoxia Enhances Cell Properties of Human Mesenchymal Stem Cells,” Tissue Engineering & Regenerative Medicine 14, no. 5 (July 2017): 595–604, https://dx.doi.org/10.1007/s13770-017-0068-8.
27.Prakash Chintamani Malshe, “Nisshesha Rechaka Pranayama Offers Benefits through Brief Intermittent Hypoxia,” Ayu 32, no. 4 (October 2011): 451–457, https://dx.d. oi.org/10.4103/0974-8520.96114;
 28. Lidia De Filippis and Domenico Delia, “Hypoxia in the Regulation of Neural Stem Cells,” Cellular and Molecular Life Sciences 68, no. 17 (September 2011): 2831–2844, https://dx.doi.org/10.1007/s00018-011-0723-5; 
29.Eugenia B. Manukhina et al., “Intermittent Hypoxia Training Protects Cerebrovascular Function in Alzheimer's Disease,” Experimental Biology and Medicine 241 no. 12 (June 2016): 1351–1363, https://dx.doi.org/10.1177/1535370216649060.
30. Kjeld, T., Stride, N., Gudiksen, A., Hansen, E. G., Arendrup, H. C., Horstmann, P. F., Zerahn, B., Jensen, L. T., Nordsborg, N., Bejder, J., & Halling, J. F. (2018). Oxygen conserving mitochondrial adaptations in the skeletal muscles of breath hold divers. PloS one, 13(9), e0201401. https://doi.org/10.1371/journal.pone.0201401
31. Lindholm P, Lundgren CE. The physiology and pathophysiology of human breath-hold diving. J Appl Physiol (1985). 2009 Jan;106(1):284-92. doi: 10.1152/japplphysiol.90991.2008. Epub 2008 Oct 30. PMID: 18974367.
32. Baković D, Valic Z, Eterović D, Vukovic I, Obad A, Marinović-Terzić I, Dujić Z. Spleen volume and blood flow response to repeated breath-hold apneas. J Appl Physiol (1985). 2003 Oct;95(4):1460-6. doi: 10.1152/japplphysiol.00221.2003. Epub 2003 Jun 20. PMID: 12819225. 33. Inoue Y, Nakajima A, Mizukami S, Hata H. Effect of Breath Holding on Spleen Volume Measured by Magnetic Resonance Imaging. PLoS One. 2013 Jun 26;8(6):e68670. doi: 10.1371/journal.pone.0068670. PMID: 23840858; PMCID: PMC3694106.  
34. Schagatay E, Andersson JP, Hallén M, Pålsson B. Selected contribution: role of spleen emptying in prolonging apneas in humans. J Appl Physiol (1985). 2001 Apr;90(4):1623-9; discussion 1606. doi: 10.1152/jappl.2001.90.4.1623. PMID: 11247970.
35. Lemaître F, Seifert L, Polin D, Juge J, Tourny-Chollet C, Chollet D. Apnea training effects on swimming coordination. J Strength Cond Res. 2009 Sep;23(6):1909-14. doi: 10.1519/JSC.0b013e3181b073a8. PMID: 19675466.
36. Lippl FJ, Neubauer S, Schipfer S, Lichter N, Tufman A, Otto B, Fischer R. Hypobaric hypoxia causes body weight reduction in obese subjects. Obesity (Silver Spring). 2010 Apr;18(4):675-81. doi: 10.1038/oby.2009.509. Epub 2010 Feb 4. PMID: 20134417.

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