Hypoxia (medical)

Hypoxia is a pathological condition in which the body as a whole (generalized hypoxia) or a region of the body (tissue hypoxia) is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise. A mismatch between oxygen supply and its demand at the cellular level may result in a hypoxic condition. Hypoxia in which there is complete deprivation of oxygen supply is referred to as anoxia.

Hypoxia differs from hypoxemia. In the latter, the oxygen concentration within the arterial blood is abnormally low. ^[1]. It is possible to experience hypoxia and have a low oxygen content (e.g., due to anemia) but maintain high oxygen partial pressure (pO₂). Incorrect use of these terms can lead to confusion, especially as hypoxemia is among the causes of hypoxia (in hypoxemic hypoxia).

Generalized hypoxia occurs in healthy people when they ascend to high altitude, where it causes altitude sickness leading to potentially fatal complications: high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE).^[2] Hypoxia also occurs in healthy individuals when breathing mixtures of gases with a low oxygen content, e.g. while diving underwater especially when using closed-circuit rebreather systems that control the amount of oxygen in the supplied air. A mild and non-damaging intermittent hypoxia is used intentionally during altitude trainings to develop an athletic performance adaptation at both the systemic and cellular level.^[3]

Classification

• Hypoxic hypoxia is a generalized hypoxia, an inadequate supply of oxygen to the body as a whole. The term "hypoxic hypoxia" specifies hypoxia caused by low partial pressure of oxygen in arterial blood. In the other causes of hypoxia that follow, the partial pressure of oxygen in arterial blood is normal. Hypoxic hypoxia may be due to:
  • Low partial pressure of atmospheric oxygen such as found at high altitude ^[4] 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.
  • Low partial pressure of oxygen in the lungs when switching from inhaled anaesthesia to atmospheric air, due to the Fink effect, or diffusion hypoxia.
  • A decrease in oxygen saturation of the blood caused by sleep apnea or hypopnea
  • 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.
• hypemic hypoxia in which arterial oxygen pressure is normal, but total oxygen content of the blood is reduced.^[5]
• Hypoxia when the blood fails to deliver oxygen to target tissues.
  • Carbon monoxide poisoning which inhibits the ability of hemoglobin to release the oxygen bound to it.
  • Methaemoglobinaemia in which an abnormal version of hemoglobin 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. The effect of drinking alcoholic beverages is a common example.
• 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.

Signs and symptoms

The 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, priapism, and death occur. Severe hypoxia induces a blue discolouration of the skin, called cyanosis. Because hemoglobin is a darker red when it is not bound to oxygen (deoxyhemoglobin), as opposed to the rich red colour that it has when bound to oxygen (oxyhemoglobin), 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 appear 'cherry red' instead of cyanotic.

Pathophysiology

After mixing with water vapour and expired CO₂ in the lungs, oxygen diffuses down a pressure gradient to enter arterial blood where its partial pressure is around 100 mmHg (13.3 kPa).^[4] 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. 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 40 mmHg (5.3 kPa) 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.^[6] 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".

Treatment

To counter the effects of high-altitude diseases, the body must return arterial pO₂ toward normal. Acclimatization, the means by which the body adapts to higher altitudes, only partially restores pO₂ to standard levels. Hyperventilation, the body’s most common response to high-altitude conditions, increases alveolar pO₂ by raising the depth and rate of breathing. However, while pO₂ does improve with hyperventilation, it does not return to normal. Studies of miners and astronomers working at 3000 meters and above show improved alveolar pO₂ with full acclimatization, yet the pO₂ level remains equal to or even below the threshold for continuous oxygen therapy for patients with chronic obstructive pulmonary disease (COPD).^[7] 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 pO₂ 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 equivalent of 3000 m, which is much more tolerable for the increasing number of low-landers who work in high altitude.^[8] In a study of astronomers working in Chile at 5050 m, oxygen concentrators increased the level of oxygen concentration by almost 30 percent (that is, from 21 percent to 27 percent). This resulted in increased worker productivity, less fatigue, and improved sleep.^[9]

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 remote areas. Offices and housing already have climate-controlled rooms, in which temperature and humidity are kept at a constant level. Oxygen can be added to this system easily and relatively cheaply.

Narcan can be given.

See also

• Altitude training for beneficial use of mild hypoxia
• Asphyxia
• Cerebral hypoxia
• Deep water blackout for special case of latent hypoxia
• Drowning
• g-LOC cerebral hypoxia induced by excessive g-forces
• Hypoxic tumor
• Hypoxicator a device intended for hypoxia acclimatisation in a controlled manner
• Ischemia
• Hyperoxia
• Sleep apnea
• Shallow water blackout for special case of hypoxia via self-induced hypocapnia
• Time of Useful Consciousness

For aircraft decompression incidents at altitude see:

• 1999 South Dakota Learjet crash (the crash which claimed the life of golfer Payne Stewart)
• 2000 Australia Beechcraft King Air crash
• Helios Flight 522
• Soyuz 11 fatal spacecraft decompression on re-entry

References

Bibliography

• Hypoxia - An invisible enemy, Fast, Airbus technical magazine, #38 : presentation for non specialists of hypoxia and related safety procedures in civil airplanes
• Human Exposure to Vacuum web page, discussing the effects of vacuum on an unprotected human.