Structure and Function of the Respiratory System

Authors

  • Alcibey Alvarado Internal Medicine and Pneumology. Clínica de Diagnóstico Médico. San José, Costa Rica. Metropolitano Research Institute. San José, Costa Rica

DOI:

https://doi.org/10.14738/aivp.1304.19187

Keywords:

Oxygen, mitochondria, cellular respiration, external respiration, structure, function

Abstract

The atmosphere is a mixture of gases that surround any celestial body that has sufficient gravitational force to prevent the gases from escaping from their environment. At first probably it consisted of volcanic emanations with almost no oxygen. The appearance of oxygen in the atmosphere enabled aerobic life as we know it today. The original gill system of fish was replaced by lungs when oxygen dissolved in seawater was converted into the gaseous state of the atmosphere. The respiratory system developed and evolved over eons to serve its most ancient function: gas exchange. The structure of the respiratory system is designed to serve this function. Other functions subsequently emerged during evolutionary development. Cellular respiration, in the intimacy between the capillary and the cell, and external respiration are discussed to understand the architectural design serving this and other functions of the respiratory system.

References

Herman JR, Newman PA, McPeters R, Krueger AJ, Bhartia PK (1995). Meter 3/total ozone mapping spectrometer observation of the 1993 ozone hole. J Geophys Res. 100:2973-2983.

Maina JN (2002). Fundamental structural aspects and features in the bioengineering of the gas exchangers: comparative perspectives. Adv Anat Embryol Cell Biol. 163: III-XII, 1-108.

Alvarado A, Arce I. (2016). Metabolic functions of the lung, disorders and associated pathologies. J Clin Med Res. 8:689-700. st

Hamilton J. They Made Our World (1 ed). BBC World service and Broadside Books Ltd. 1995: London.

Priestley J. (1776). Experiments and observations on different kinds of air. Vol. II. London: J. Johnson

Wemple ML, Swenson KE, Swenson ER (2023). Oxygen therapy. Part 1-History, Physiology, and Evaluation. NEJM Evid. 2: April.

Wemple ML, Swenson KE, Swenson ER (2023). Oxygen therapy. Part 2- Indications and Toxicity. NEJM Evid. 2. June. th

West JB. Respiratory Physiology: the essentials. (6 Ed). Lippincott Williams & Wilkins. 2000: USA.

Semenza GL, Wang GL (1992). A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at site required for transcriptional activation. Mol Cell Biol.12:5447-

Semenza GL (2007). Life with oxygen. Science. 318:62-64.

Kaelin WG (2007). Von Hippel-Lindau disease. Annu Rev Pathol. 2:145-173.

Coleman ML, Ratcliffe PJ (2009). Signaling cross talk of the HIF system: involvement of the FIH protein. Curr Pharm Des. 15:3904-3907.

Patel SA, Simon MC (2008). Biology of hypoxia-inducible factor-2 alpha in development and disease. Cell Death Differ. 15:628-634.

Semenza GL (2010). Oxygen homeostasis. Wiley Interdiscip Rev Syst Biol Med. 2:336-361.

Taylor CT (2008). Interdependent roles for hypoxia inducible factor and nuclear factor-kβ in hypoxic inflammation. J Physiol. 586:4055-4059.

Eltzschig HK, Carmeliet P (2011). Hypoxia and inflammation. N Engl J Med. 364:656-665.

Alvarado A, Arce I (2016). Immune recognition in lung diseases: basic research and clinical application. Clin Infect Immunol. 1:31-40.

Semenza GL (2003). Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 3:721-732.

De Bock K, De Smet F, Leite de Oliviera, Anthonis K, Carmeliet P (2009). Endothelial oxygen sensors regulate tumor vessels normalization by instructing phalanx endothelial cells. J Mol Med. 87:561-569.

Natarajan V, Parinandi NL. Mitochondrial functions in lung health and disease. New York, USA: Human Press; 2014.

Cloonan SM, Choi AM (2016). Mitochondria in lung disease. J Clin Invest. 126:809-820.

Gray MW, Burger G, Lang BF (1999). Mitochondrial evolution. Science. 283:1476-1481.

Chinnery PF, Zeviani M (2016). Mitochondrial matchmaking. N Engl J Med. 375:1894-1896.

Bialas AJ, Sitarek P, Milkowska-Dymanowska J, Protrowski WJ, Gorski P (2016). The role of mitochondrial and oxidative/ antioxidative imbalance in pathobiology of chronic obstructive pulmonary disease. Oxid Med Cel Longev. 2016:7808576.

Kang MJ, Shadel GS (2016). A mitochondrial perspective of chronic obstructive pulmonary disease pathogenesis. Tuberc Respir Dis (Seoul). 79:207-213. Alvarado, A. (2025). Structure and Function of the Respiratory System. European Journal of Applied Sciences, Vol - 13(04). 180-209.

Seth RB, Sun L, Ea CK, Chen ZJ (2005). Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappa β and IRF 3. Cell. 122:669-682.

Falk MJ, Decherney A, Kahn JP (2016). Mitochondrial replacement techniques - implications for the clinical community. N Engl J Med. 374:1103-1106.

Phimister EG. Mitochondrial donation clearing the final regulatory huddle in the United Kingdom. N Engl J Med. 376:171-173.

Picard M, Wallace DC, Burelle Y (2016). The rise of mitochondria in medicine. Mitochondrion. 30:105-116.

West BJ. Pulmonary Pathophysiology (2nd Ed). Williams & Wilkins. 1982: Baltimore/London.

West JB (2017). Physiology effects of chronic hypoxia. N Engl J Med. 376:1965-1971.

Semenza GL (2011). Oxygen sensing, homeostasis, and disease. N Engl J Med. 365:537-547.

Halliwell B (1996) The Radical View: Free radicals, health and disease. Odyssey 2:10-15.

Bryan CL and Jenkinson SG (1988) Oxygen toxicity. Clin Chest Med 9: 141-152.

Tobin MJ (1986) Update on strategies in mechanical ventilation. Hosp Pract 21: 69-84.

Gerschman R, Gilbert DL, Nye SW, Dwyer P, Fenn Wo (1954) Oxygen poisoning and x-irradiation: a mechanism in common. Science 119: 623-626.

Chapman DJ, Schopf JW (1983) Biological and biochemical effects of the development of an aerobic environment. In: Earths Earliest Biosphere: Its origin and Evolution. Schopf JW (Ed). Princeton Univ. Press pp: 302-320.

Reeves JT, Groves BM, Cymerman A, Sutton Wagner PD, Turkevich DJR, et al. (1990) Operation Everts II: cardiac filling pressure during cycle exercise at sea level. Respir Physiol 80: 147-154.

Ryan US, Ryan JW, Crutchley DJ (1985). The pulmonary endothelial surface. Fed Proc. 44:2306–2309.

Weibel ER. In: Handbook of Physiology, sect 3: The Respiratory System, vol 1: Circulation and nonrespiratory Functions. Fishman AP, Fisher AB, (eds). Bethesda, MD: American Physiological Society; 1985. Lung cell biology; pp. 47–91.

Alvarado A (2023). Ion channels and respiratory channelopathies. Clin Res Trial. 9:1-17.

Powers KA, Dhamoon AS. Physiology, Pulmonary Ventilation and Perfusion. In Stat Pearls. Treasure Island (FL): Stat Pearls Publishing; 2021 Jan-: https://www.ncbi.nlm.nih.gov/books/NBK539907/.

West J B. Pulmonary Physiology. The essentials. Williams and Wilkins Co. Baltimore, USA, 2016.

Dejours P. Principles of Comparative Respiratory Physiology (2nd Ed). Amsterdam, Elsevier North-Holland, 1981.

Levitzky MG. Diffusion of Gases and Interpretation of Pulmonary Function Tests. In Pulmonary Physiology. Mc Graw-Hill Education. (9th Ed). USA 2017, pag 1-11.

Bashir M, Garg N, Muzaffar M, Nyiem M, Jaan I, et al (2024). A comprehensive guide to pulmonary function st tests for 1 -year medical students – Simplifying PFTS and their interpretation. Asian J Med Science. 15:151.

Graham B, Brusasco V, Burgos F, Cooper B, Jensen R, et al (2017). ERS/ATS standards for single-breath carbon monoxide uptake in the lung. Eur Respir J. 49: 16E0016.

Suresh K (2016). Lung Circulation. Compr Physiol. 6:897-943.

Murthy R (2018). Pulmonary vascular pathophysiology. Cardiovasc Diagn Ther 8:208-213.

Bonnet S, Michelakis ED, Porter CJ, Andrade-Navarro MA, Thebaud B, et al (2008). An abnormal mitochondrial-hypoxia inducible factor-1α-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertension. Circulation. 113:2630-2641. 207

Fijalkowska I, Xu W, Comhair SA, Janocha AJ, Mavrakis LA, et al (2010). Hypoxia-inducible factor-1α1 regulates the metabolic shift of pulmonary hypertensive endothelial cells. Am J Pathol. 176;1130-1138.

Archer SL, Marsboom G, Kim GH, Zhan HJ, Thot PT, et al (2010). Epigenetic attenuation of mitochondrial superoxide dismutase 2 in pulmonary arterial hypertension: a basis for excessive cell proliferation and new therapeutic target. Circulation. 121:2661-2671.

Beall CM (2007). Two routes to functional adaptation: Tibetan and Andean high-altitude natives. Proc Natl Acad Sci USA. 104(Supl 1):8655-8660.

Simonson TS, Yang Y, Huff CD, Yun H, Quin G, et al (2010). Genetic evidence for high-altitude adaptation in Tibet. Science. 329:72-75.

Lan SHN, Massam BD, Kulkarni SK, Lang CC (2018). Pulmonary Arterial Hypertension: Pathophysiology and Treatment. Diseases. 6:38.

Barile M (2020). Pulmonary Edema: A Pictorial Review of Imaging Manifestations and Current Understanding of Mechanisms of Disease, Eur J Radiol Open. 7:100274.

Levitsky M. Pulmonary Physiology. McGraw-Hill Education. (9th Ed), USA, 2018.

Kibble J, Halsey CR: The Big Picture, Medical Physiology. McGraw-Hill, USA, 2009.

West, JB (2016). Oxygen conditioning: a new technique for improving living and working at high altitude. Physiology (Bethesda). 31:216-222.

Shimoda, LA, Semenza, GL (2011). HIF and the lung: role of hypoxia-inducible factors in pulmonary development and disease. Am J Respir Crit Care Med. 183:152-156.

Saavedra BM, Escobar AP, Caussade L (2022). Respiratory physiology: transport of oxygen and carbon dioxide in the blood. Neumol Pediatr 2022. 17: 72 – 75.

Altose MD. Pulmonary mechanics. In: Fishman AP (editor). Pulmonary Diseases and Disorders. New York, McGraw-Hill Book (1st Ed). 1980:359-372.

Murray JF. Respiration. In: Smith LH and Their SO (eds). Pathophysiology. The biological principles of disease. Philadelphia, WB Saunders (2nd Ed). 1985: 753-856.

Rahman NM, Wang N-S†. Anatomy of the pleura. In: Light RW, Lee YCG (Eds). Textbook of Pleural Diseases. London, Hooder Arnold (2nd Ed). 2008:13-26.

King RJ, Clements JA. Lipid Synthesis and Surfactant Turnover in the Lungs. Compr Physiol 2011, Supplement 10: Handbook of Physiology, The Respiratory System, Circulation and Nonrespiratory Functions. p. 309-336. First published in print 1985.

Haagsman HP, van Golde LM (1991). Synthesis and assembly of lung surfactants. Annu Rev Physiol. 53:441-

Whitsett JA, Stahlman MT (1998). Impact of advances in physiology, biochemistry, and molecular biology on pulmonary disease in neonates. Am J Respir Crit Care Med.157(4 Pt 2): S67-71.

Clements JA, Avery ME (1998). Lung surfactant and neonatal respiratory distress syndrome. Am J Respir Crit Care Med. 157(4 Pt 2): S59-66.

Mason RJ, Crystal RG (1998). Pulmonary cell biology. Am J Respir Crit Care Med.157(4 Pt 2): S72-81.

He Z, Wang C, Tian, H (2025). Dynamic nature of airway resistance in ARDS: methodological concerns in MPR calculations. Intensive Care Med. 51:450–451.

Chen Y, Yuan Y, Chang Q. (2024). Continuous estimation of respiratory system compliance and airway resistance during pressure-controlled ventilation without end-inspiration occlusion. BMC Pulm Med. 24:1-8.

Hansel TT, Barnes PJ. An atlas of chronic obstructive pulmonary diseases: COPD. A resource for teaching and st lecture (1 ed). Taylor & Francis, 2003, London. Alvarado, A. (2025). Structure and Function of the Respiratory System. European Journal of Applied Sciences, Vol - 13(04). 180-209.

Alvarado A, Arce I (2015). Molecular biology of chronic obstructive pulmonary disease from the bases to the therapeutic decision: a review. Br J Med Medic Res. 10:1-14.

Abara S, Cepeda J (2022). Respiratory physiology: breath control. Neumol Pediatr. 17:117-121.

Aubier M, Murciano D, Milic-Emili J, Toutay E, Daghflus J, et al (1980). Effects of the administration pf O on ventilation and blood gas in patients with chronic obstructive pulmonary disease during acute respiratory failure. Am Rev Respir Dis. 122:747-754.

Button B, Goodell HP, Atieh E, Chen YC, Shenoy SW, et al (2018). Roles of mucus adhesion and cohesion in cough clearance. Proc Antl Acad Sci USA. 115:12501-12506.

Widdicombe JH, Wine JJ (2015). Airway gland structure and function. Physiol Rev. 95:1241-1249.

Fahy JV, Dickey BF (2010). Airway mucus function and dysfunction. N Engl J Med.363:2233-2247.

Downloads

Published

2025-08-03

How to Cite

Alvarado, A. (2025). Structure and Function of the Respiratory System. European Journal of Applied Sciences, 13(04), 180–209. https://doi.org/10.14738/aivp.1304.19187