Editor-In-Chief: C. Michael Gibson, M.S., M.D. 
Hypoxia is a pathological condition in which the body as a whole (generalised hypoxia) or region of the body (tissue hypoxia) is deprived of adequate oxygen supply. Hypoxia in which there is complete deprivation of oxygen supply, is referred to as anoxia.
Hypoxia is distinguished from apoxemia. Apoxemia is an abnormally low concentration of oxygen in arterial blood . A frequent error is to use the term hypoxemia to mean low oxygen content in arterial blood. It is possible to have a low oxygen content (e.g. due to anemia) but a high PO2 also, and incorrect use can lead to confusion.
Generalised hypoxia occurs in healthy people when they ascend to high altitude, where it causes altitude sickness, and the potentially fatal complications of altitude sickness, high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). Hypoxia also occurs in healthy individuals when breathing mixtures of gases with a low oxygen content, for example while diving underwater, especially with closed-circuit rebreather systems that control the amount of oxygen in the air breathed in. Altitude training uses mild hypoxia to increase the concentration of red blood cells in the body for increased athletic performance.
Symptoms of generalized hypoxia depend on its severity and acceleration of onset. In the case of altitude sickness, where hypoxia develops gradually, the symptoms include headaches, fatigue, shortness of breath, a feeling of euphoria and nausea. In severe hypoxia, or hypoxia of very rapid onset, changes in levels of consciousness, seizures, coma and death occur. Severe hypoxia induces a blue discolouration of the skin, called cyanosis (haemoglobin is a darker red when it is not bound to oxygen (deoxyhaemoglobin), as opposed to the rich red colour that it has when bound to oxygen (oxyhaemoglobin), and when seen through the skin it has an increased tendency to reflect blue light back to the eye). In cases where the oxygen is displaced by another molecule, such as carbon monoxide, the skin may be 'cherry red' instead of cyanotic.
Types of hypoxia
- Hypoxemic hypoxia is a generalized hypoxia, an inadequate supply of oxygen to the body as a whole. The term "hypoxemic hypoxia" refers to the fact that hypoxia occurs as a consequence of low partial pressure of oxygen in arterial blood, in contrast to the other causes of hypoxia that follow, in which the partial pressure of oxygen in arterial blood is normal. Hypoxemic hypoxia may be due to:
- Low partial pressure of atmospheric oxygen such as found at high altitude  or by replacement of oxygen in the breathing mix either accidentally as in the modified atmosphere of a sewer or intentionally as in the recreational use of nitrous oxide.
- Either Sleep apnea or Hypopnea causing a decrease in oxygen saturation of the blood.
- Inadequate pulmonary ventilation (e.g. in chronic obstructive pulmonary disease or respiratory arrest).
- Shunts in the pulmonary circulation or a right-to-left shunt in the heart. Shunts can be caused by collapsed alveoli that are still perfused or a block in ventilation to an area of the lung. Whatever the mechanism, blood meant for the pulmonary system is not ventilated and so no gas exchange occurs (the ventilation/perfusion ratio is zero). Normal anatomical shunt occurs in everyone, because of the Thebesian vessels which empty into the left ventricle and the bronchial circulation which supplies the bronchi with oxygen.
- Anemic hypoxia in which arterial oxygen pressure is normal, but total oxygen content of the blood is reduced.
- Hypemic hypoxia when there is an inability of the blood to deliver oxygen to target tissues.
- Carbon monoxide poisoning which inhibits the ability of haemoglobin to release the oxygen bound to it.
- Methaemoglobinaemia in which an abnormal version of haemoglobin accumulates in the blood
- Histotoxic hypoxia in which quantity of oxygen reaching the cells is normal, but the cells are unable to effectively use the oxygen due to disabled oxidative phosphorylation enzymes.
- Ischemic, or stagnant hypoxia in which there is a local restriction in the flow of otherwise well-oxygenated blood. The oxygen supplied to the region of the body is then insufficient for its needs. Examples are cerebral ischemia, ischemic heart disease and Intrauterine hypoxia, which is an unchallenged cause of perinatal death.
After mixing with water vapour and expired CO2 in the lungs, oxygen diffuses down a pressure gradient to enter arterial blood around where its partial pressure is 100mmHg (13.3kPa). Arterial blood flow delivers oxygen to the peripheral tissues, where it again diffuses down a pressure gradient into the cells and into their mitochondria. These bacteria-like cytoplasmic structures strip hydrogen from fuels (glucose, fats and some amino acids) to burn with oxygen to form water. Released energy (originally from the sun and photosynthesis) is stored as ATP, to be later used for energy requiring metabolism. The fuel's carbon is oxidized to CO2, which diffuses down its partial pressure gradient out of the cells into venous blood to finally be exhaled by the lungs. Experimentally, oxygen diffusion becomes rate limiting (and lethal) when arterial oxygen partial pressure falls to 40mmHg or below.
If oxygen delivery to cells is insufficient for the demand (hypoxia), hydrogen will be shifted to pyruvic acid converting it to lactic acid. This temporary measure (anaerobic metabolism) allows small amounts of energy to be produced. Lactic acid build up in tissues and blood is a sign of inadequate mitochondrial oxygenation, which may be due to hypoxemia, poor blood flow (e.g. shock) or a combination of both. If severe or prolonged it could lead to cell death.
Vasoconstriction and vasodilation
In most tissues of the body, the response to hypoxia is vasodilation. By widening the blood vessels, the tissue allows greater perfusion.
By contrast, in the lungs, the response to hypoxia is vasoconstriction. This is known as "Hypoxic pulmonary vasoconstriction", or "HPV".
To counter the effects of high-altitude diseases, the body must return arterial P02 toward normal. Acclimatization, the means by which the body adapts to higher altitudes, only partially restores P02 to standard levels. Hyperventilation, the body’s most common response to high-altitude conditions, increases alveolar P02 by raising the depth and rate of breathing. However, while P02 does improve with hyperventilation, it does not return to normal. Studies of miners and astronomers working at 3000 meters and above show improved aveolar P02 with full acclimatization, yet the P02 level remains equal to or even below the threshold for continuous oxygen therapy for patients with chronic obstructive pulmonary disease (COPD). In addition, there are complications involved with acclimatization. Polycythemia, in which the body increases the number of red blood cells in circulation, thickens the blood, raising the danger that the heart can’t pump it.
In high-altitude conditions, only oxygen enrichment can counteract the effects of hypoxia. By increasing the concentration of oxygen in the air, the effects of lower barometric pressure are countered and the level of arterial P02 is restored toward normal capacity. A small amount of supplemental oxygen reduces the equivalent altitude in climate-controlled rooms. At 4000 m, raising the oxygen concentration level by 5 percent via an oxygen concentrator and an existing ventilation system provides an altitude of 3000 m, which is much more tolerable for the increasing number of low-landers who work in high altitude. In a study of astronomers working in Chile at 5050 m, oxygen concentrators increased the level of oxygen concentration by 6 percent (that is, from 21 percent to 27 percent). The result was increased worker productivity, less fatigue, and improved sleep.
Oxygen concentrators are uniquely suited for this purpose. They require little maintenance and electricity, provide a constant source of oxygen, and eliminate the expensive, and often dangerous, task of transporting oxygen cylinders to high, remote areas. Offices and housing already have climate-controlled rooms, in which temperature and humidity are at a constant level of comfortableness. Oxygen can be added to this system easily and relatively cheaply.
- Cerebral hypoxia
- Hypoxic tumor
- Time of Useful Consciousness
- Shallow water blackout for special case of hypoxia via self-induced hypocapnia
- Deep water blackout for special case of latent hypoxia
- Altitude training for beneficial use of mild hypoxia
- ↑ West J. "Pulmonary Pathophysiology: The Essentials" 1977 Williams & Wilkins p22
- ↑ 2.0 2.1 Kenneth Baillie and Alistair Simpson. "Altitude oxygen calculator". Apex (Altitude Physiology Expeditions). - Online interactive oxygen delivery calculator
- ↑ Kenneth Baillie and Alistair Simpson. "Oxygen content calculator". Apex (Altitude Physiology Expeditions). - A demonstration of the effect of anaemia on oxygen content
- ↑ Hobler KE, Carey LC (1973). "Effect of acute progressive hypoxemia on cardiac output and plasma excess lactate" (scanned copy). Ann Surg. 177 (2): 199–202. PMID 4572785.
- ↑ West, John B. (2004), "The Physiologic Basis of High-Altitude Diseases", Annals of Internal Medicine 141(10): 791.
- ↑ West, John B. (1995), "Oxygen Enrichment of Room Air to Relieve the Hypoxia of High Altitude", Respiration Physiology 99(2):230.
- ↑ West, "The Physiologic Basis of High-Altitude Diseases", 793.
- Hypoxia - An invisible enemy, Fast, Airbus technical magazine, #38 : presentation for non specialists of hypoxia and related safety procedures in civil airplanes
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