Hypoxia (medical)

Hypoxia, or hypoxiation, 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 that, in the latter, the oxygen concentration within the arterial blood is abnormally low. 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). 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.

Hypoxia is also a serious consequence of preterm birth in the neonate. The main cause for this is that the lungs of the human foetus are among the last organs to develop during pregnancy. To assist the lungs to distribute oxygenated blood throughout the body, infants at risk of hypoxia are often placed inside an incubator capable of providing continuous positive airway pressure (also known as a humidicrib).

Classification

 * Hypoxemic hypoxia is a generalized hypoxia, an inadequate supply of oxygen to the body as a whole. The term "hypoxemic 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. Hypoxemic hypoxia may be due to:
 * Hypoventilation. Inadequate pulmonary minute ventilation (e.g., respiratory arrest or by drugs such as opiates)
 * 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 decreased).
 * Normal anatomical shunt occur due to Thebesian veins which empty into the left ventricle and the bronchial circulation which supplies the bronchi with oxygen.
 * Normal physiological shunts occur due to the effect of gravity. The highest concentration of blood in the pulmonary circulation occurs in the bases of the pulmonary tree compared to the highest pressure of gas in the apices of the lungs.
 * V/Q mismatch. When the ventilation does not match the perfusion through the paranchyema of the lung. This can occur for a variety of reasons, the commonest being a Pulmonary embolism
 * Diffusing defects such as pulmonary fibrosis where the Aa gradient has increased.
 * Decreased concentration of oxygen in inspired air. Low partial pressure of atmospheric oxygen such as found at high altitude or by reduced replacement of oxygen in the breathing mix.
 * Low partial pressure of oxygen in the lungs when switching from inhaled anaesthesia to atmospheric air, due to the Fink effect, or diffusion hypoxia.
 * Anaemia in which arterial oxygen pressure is normal, but total oxygen content of the blood is reduced. This is due to a decreased total carrying capacity.
 * 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 use the oxygen effectively, due to disabled oxidative phosphorylation enzymes. Cyanide toxicity is one example.

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). 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 be exhaled finally 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. 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). 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. 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.

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.