Editing Gas exchange (section)

== Exchange membrane ==

The membrane across which gas exchange takes place in the alveoli (i.e. the blood-air barrier) is extremely thin (in humans, on average, 2.2&nbsp;μm thick).<ref name="grays" /> It consists of the [[Pneumocytes|alveolar epithelial cells]], their [[basement membrane]]s and the [[Endothelium|endothelial cells]] of the pulmonary capillaries (Fig. 4).<ref name="grays" /><ref name="s-cool">{{Cite web| title= Gas Exchange in humans| url=http://www.s-cool.co.uk/a-level/biology/gas-exchange/revise-it/gas-exchange-in-humans| access-date= 19 March 2013}}</ref> The large surface area of the membrane comes from the folding of the membrane into about 300&nbsp;million alveoli, with diameters of approximately 75–300&nbsp;μm each. This provides an extremely large surface area (approximately 145&nbsp;m<sup>2</sup>) across which gas exchange can occur.<ref name="grays" />

===Alveolar air===
[[File:Alveolar air.png|thumb|right|300 px|'''Fig. 5.''' The changes in the composition of the alveolar air during a normal breathing cycle at rest. The scale on the left, and the blue line, indicate the partial pressures of carbon dioxide in kPa, while that on the right and the red line, indicate the partial pressures of oxygen, also in kPa (to convert kPa into mm Hg, multiply by 7.5).]]

[[File:Alveolus.jpg|thumb|300 px|left|'''Fig. 6.''' A diagrammatic histological cross-section through a portion of lung tissue showing a normally inflated [[Pulmonary alveolus|alveolus]] (at the end of a normal exhalation), and its walls containing the [[Pulmonary circulation|alveolar capillaries]] (shown in cross-section). This illustrates how the alveolar capillary blood is completely surrounded by alveolar air. In a normal human lung all the alveoli together contain about 3 liters of alveolar air. All the alveolar capillaries contain about 100 ml blood.]]

[[Atmosphere of Earth|Air]] is brought to the alveoli in small doses (called the [[tidal volume]]), by [[breathing]] in ([[inhalation]]) and out ([[exhalation]]) through the [[Respiratory tract|respiratory airways]], a set of relatively narrow and moderately long tubes which start at the nose or mouth and end in the alveoli of the lungs in the chest. Air moves in and out through the same set of tubes, in which the flow is in one direction during inhalation, and in the opposite direction during exhalation.

During each inhalation, at rest, approximately 500&nbsp;ml of fresh air flows in through the nose. It is warmed and moistened as it flows through the nose and [[pharynx]]. By the time it reaches the trachea the inhaled air's temperature is 37&nbsp;°C and it is saturated with water vapor. On arrival in the alveoli it is diluted and thoroughly mixed with the approximately  2.5–3.0&nbsp;liters of air that remained in the alveoli after the last exhalation. This relatively large volume of air that is semi-permanently present in the alveoli throughout the breathing cycle is known as the [[functional residual capacity]] (FRC).<ref name=tortora1 />

At the beginning of inhalation the airways are filled with unchanged alveolar air, left over from the last exhalation. This is the [[Dead space (physiology)|dead space]] volume, which is usually about 150&nbsp;ml.<ref>{{cite web|title=Dead space volume - Oxford Reference|url=http://www.oxfordreference.com/view/10.1093/oi/authority.20110803095704195}}</ref> It is the first air to re-enter the alveoli during inhalation. Only after the dead space air has returned to the alveoli does the remainder of the tidal volume (500&nbsp;ml - 150&nbsp;ml = 350&nbsp;ml) enter the alveoli.<ref name=tortora1 /> The entry of such a small volume of fresh air with each inhalation, ensures that the composition of the FRC hardly changes during the breathing cycle (Fig. 5).<ref name=tortora1 /> The alveolar [[Pulmonary gas pressures|partial pressure of oxygen]] remains very close to 13–14&nbsp;[[Pascal (unit)|kPa]] (100&nbsp;mmHg), and the [[Pulmonary gas pressures#Partial pressure of carbon dioxide|partial pressure of carbon dioxide]] varies minimally around 5.3&nbsp;kPa (40&nbsp;mmHg) throughout the breathing cycle (of inhalation and exhalation).<ref name=tortora1 /> The corresponding partial pressures of oxygen and carbon dioxide in the ambient (dry) air at sea level are 21&nbsp;kPa (160&nbsp;mmHg) and 0.04&nbsp;kPa (0.3&nbsp;mmHg) respectively.<ref name=tortora1 />
[[File:Gas exchange.jpg|thumb|right|300 px|'''Fig. 7.''' A highly diagrammatic illustration of the process of gas exchange in the mammalian lungs, emphasizing the differences between the gas compositions of the ambient air, the alveolar air (light blue) with which the alveolar capillary blood equilibrates, and the blood gas tensions in the pulmonary arterial (blue blood entering the lung on the left) and venous blood (red blood leaving the lung on the right). All the gas tensions are in kPa. To convert to mm Hg, multiply by 7.5.]]

This alveolar air, which constitutes the FRC, completely surrounds the blood in the alveolar capillaries (Fig. 6). Gas exchange in mammals occurs between this alveolar air (which differs significantly from fresh air) and the blood in the alveolar capillaries. The gases on either side of the gas exchange membrane equilibrate by simple diffusion. This ensures that the partial pressures of oxygen and carbon dioxide in the blood leaving the alveolar capillaries, and ultimately circulates throughout the body, are the same as those in the FRC.<ref name=tortora1 />

The marked difference between the composition of the alveolar air and that of the ambient air can be maintained because the [[functional residual capacity]] is contained in dead-end sacs connected to the outside air by long, narrow, tubes (the airways: [[nose]], [[pharynx]], [[larynx]], [[trachea]], [[bronchi]] and their branches and sub-branches down to the [[bronchioles]]). This anatomy, and the fact that the lungs are not emptied and re-inflated with each breath, provides mammals with a "portable atmosphere", whose composition differs significantly from the [[Great Oxygenation Event|present-day ambient air]].<ref>{{cite book |last1=Lovelock |first1=James | title=Healing Gaia: Practical medicine for the Planet|url=https://archive.org/details/healinggaiaprac00love |url-access=registration |pages=[https://archive.org/details/healinggaiaprac00love/page/21 21]–34, 73–88|location=New York |publisher=Harmony Books |date=1991|isbn= 978-0-517-57848-3}}</ref>

The composition of the air in the FRC is carefully monitored, by measuring the partial pressures of oxygen and carbon dioxide in the arterial blood. If either gas pressure deviates from normal, reflexes are elicited that change the rate and depth of breathing in such a way that normality is restored within seconds or minutes.<ref name=tortora1 />

===Pulmonary circulation===
{{Main |Pulmonary circulation}}
All the blood returning from the body tissues to the right side of the [[heart]] flows through the [[Pulmonary circulation|alveolar capillaries]] before being pumped around the body again. On its passage through the lungs the blood comes into close contact with the alveolar air, separated from it by a very thin diffusion membrane which is only, on average, about 2&nbsp;μm thick.<ref name=grays /> The gas pressures in the blood will therefore rapidly equilibrate with those in the [[Pulmonary alveolus|alveoli]], ensuring that the arterial blood that circulates to all the tissues throughout the body has an [[Blood gas tension|oxygen tension]] of 13−14&nbsp;kPa (100&nbsp;mmHg), and a [[Blood gas tension|carbon dioxide tension]] of 5.3&nbsp;kPa (40&nbsp;mmHg). These arterial partial pressures of oxygen and carbon dioxide are [[Homeostasis#Levels of blood gases|homeostatically controlled]]. A rise in the arterial <math>P_{{\mathrm{CO}}_2}</math>, and, to a lesser extent, a fall in the arterial <math>P_{{\mathrm{O}}_2}</math>, will reflexly cause deeper and faster breathing until the blood gas tensions return to normal. The converse happens when the carbon dioxide tension falls, or, again to a lesser extent, the oxygen tension rises: the rate and depth of breathing are reduced until blood gas normality is restored.

Since the blood arriving in the alveolar capillaries has a <math>P_{{\mathrm{O}}_2}</math> of, on average, 6&nbsp;kPa (45&nbsp;mmHg), while the pressure in the alveolar air is 13&nbsp;kPa (100&nbsp;mmHg), there will be a net diffusion of oxygen into the capillary blood, changing the composition of the 3&nbsp;liters of alveolar air slightly. Similarly, since the blood arriving in the alveolar capillaries has a <math>P_{{\mathrm{CO}}_2}</math> of also about 6&nbsp;kPa (45&nbsp;mmHg), whereas that of the alveolar air is 5.3&nbsp;kPa (40&nbsp;mmHg), there is a net movement of carbon dioxide out of the capillaries into the alveoli. The changes brought about by these net flows of individual gases into and out of the functional residual capacity necessitate the replacement of about 15% of the alveolar air with ambient air every  5 seconds or so. This is very tightly controlled by the continuous monitoring of the arterial blood gas tensions (which accurately reflect partial pressures  of the respiratory gases in the alveolar air) by the [[Aortic body|aortic bodies]], the [[Carotid body|carotid bodies]], and the [[Central chemoreceptors|blood gas and pH sensor]] on the anterior surface of the [[medulla oblongata]] in the brain. There are also oxygen and carbon dioxide sensors in the lungs, but they primarily determine the diameters of the [[bronchioles]] and [[Pulmonary circulation|pulmonary capillaries]], and are therefore responsible for directing the flow of air and blood to different parts of the lungs.

It is only as a result of accurately maintaining the composition of the 3 liters alveolar air that with each breath some carbon dioxide is discharged into the atmosphere and some oxygen is taken up from the outside air. If more carbon dioxide than usual has been lost by a short period of [[hyperventilation]], respiration will be slowed down or halted until the alveolar <math>P_{{\mathrm{CO}}_2}</math> has returned to 5.3&nbsp;kPa (40&nbsp;mmHg). It is therefore strictly speaking untrue that the primary function of the respiratory system is to rid the body of carbon dioxide "waste". In fact the total concentration of carbon dioxide in arterial blood  is about 26&nbsp;mM (or 58&nbsp;ml per 100 ml),<ref name=ciba>{{cite book |last1=Diem |first1=K. | last2=Lentner |first2=C. | chapter= Blood – Inorganic substances| title= in: Scientific Tables | edition= Seventh |location=Basle, Switzerland |publisher=CIBA-GEIGY Ltd. |date=1970 |page=571}}</ref> compared to the concentration of oxygen in saturated arterial blood of about 9&nbsp;mM (or 20&nbsp;ml per 100 ml blood).<ref name=tortora1 /> This large concentration of carbon dioxide plays a pivotal role in the [[Acid-base homeostasis|determination and maintenance of the pH of the extracellular fluids]]. The carbon dioxide that is breathed out with each breath could probably be more correctly be seen as a byproduct of the body's extracellular fluid [[Homeostasis#Levels of blood gases|carbon dioxide]] and  [[Homeostasis#Blood pH|pH homeostats]]

If these homeostats are compromised, then a [[respiratory acidosis]], or a [[respiratory alkalosis]] will occur. In the long run these can be compensated by renal adjustments to the H<sup>+</sup> and HCO<sub>3</sub><sup>−</sup> concentrations in the plasma; but since this takes time, the [[hyperventilation syndrome]] can, for instance, occur when agitation or anxiety cause a person to breathe fast and deeply<ref>{{cite journal|last=Shu|first=BC |author2=Chang, YY |author3=Lee, FY |author4=Tzeng, DS |author5=Lin, HY |author6=Lung, FW|title=Parental attachment, premorbid personality, and mental health in young males with hyperventilation syndrome.|journal=Psychiatry Research|date=2007-10-31|volume=153|issue=2|pages=163–70|pmid=17659783|doi=10.1016/j.psychres.2006.05.006|s2cid=3931401 }}</ref> thus blowing off too much CO<sub>2</sub> from the blood into the outside air, precipitating a set of distressing symptoms which result from an excessively high pH of the extracellular fluids.<ref name="Edward Newton">{{cite web |url=http://www.emedicine.com/emerg/topic270.htm |title=eMedicine - Hyperventilation Syndrome: Article by Edward Newton, MD |access-date=2007-12-20 }}</ref>

Oxygen has a very low solubility in water, and is therefore carried in the blood loosely combined with [[hemoglobin]]. The oxygen is held on the hemoglobin by four [[Iron(II) oxide|ferrous iron]]-containing [[heme]] groups per hemoglobin molecule. When all the heme groups carry one O<sub>2</sub> molecule each the blood is said to be "saturated" with oxygen, and no further increase in the partial pressure of oxygen will meaningfully increase the oxygen concentration of the blood. Most of the carbon dioxide in the blood is carried as HCO<sub>3</sub><sup>−</sup> ions in the plasma. However the conversion of dissolved CO<sub>2</sub> into HCO<sub>3</sub><sup>−</sup> (through the addition of water) is too slow for the rate at which the blood circulates through the tissues on the one hand, and alveolar capillaries on the other. The reaction is therefore catalyzed by [[carbonic anhydrase]], an [[enzyme]] inside the [[red blood cell]]s.<ref name="Raymond&Swenson2000">{{Cite journal|vauthors=Raymond H, Swenson E | title=The distribution and physiological significance of carbonic anhydrase in vertebrate gas exchange organs| journal=[[Respiration Physiology]]| volume=121| issue=1| year=2000| pages=1–12| doi=10.1016/s0034-5687(00)00110-9| pmid=10854618}}</ref> The reaction can go in either direction depending on the prevailing partial pressure of carbon dioxide. A small amount of carbon dioxide is carried on the protein portion of the hemoglobin molecules as [[carbamino]] groups. The total concentration of carbon dioxide (in the form of bicarbonate ions, dissolved CO<sub>2</sub>, and carbamino groups) in arterial blood (i.e. after it has equilibrated with the alveolar air) is about 26&nbsp;mM (or 58&nbsp;ml/100 ml),<ref name=ciba /> compared to the concentration of oxygen in saturated arterial blood of about 9&nbsp;mM (or 20&nbsp;ml/100 ml blood).<ref name=tortora1 />