# Hypoxia (medical)

{{#invoke:Infobox|infobox}} Hypoxia (also known as Hypoxiation or Anoxemia) is a condition in which the body or a region of the body is deprived of adequate oxygen supply. Hypoxia may be classified as either generalized, affecting the whole body, or local, affecting a region of the body. Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during hypoventilation training[1] or strenuous physical exercise.

Hypoxia differs from hypoxemia in that hypoxia refers to a state in which oxygen supply is insufficient, whereas hypoxemia refers specifically to states that have low arterial oxygen supply.[2] Hypoxia in which there is complete deprivation of oxygen supply is referred to as "anoxia".

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).[3] Hypoxia also occurs in healthy individuals when breathing mixtures of gasses 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.[4]

Hypoxia is also a serious consequence of preterm birth in the neonate. The main cause for this is that the lungs of the human fetus 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). {{ safesubst:#invoke:Unsubst||date=__DATE__ |$B= {{#invoke:Category handler|main}}{{#invoke:Category handler|main}}[citation needed] }} ## Signs and symptoms ### Generalised hypoxia 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 light-headedness / fatigue, numbness / tingling of extremities, nausea and anorexia.[5] In severe hypoxia, or hypoxia of very rapid onset, ataxia, confusion / disorientation / hallucinations / behavioral change, severe headaches / reduced level of consciousness, papilloedema, breathlessness,[6] pallor,[7] tachycardia and pulmonary hypertension eventually leading to the late signs cyanosis, slow heart rate / cor pulmonale and low blood pressure followed by death.[8][9] Because haemoglobin is a darker red when it is not bound to oxygen (deoxyhaemoglobin), as opposed to the rich red color that it has when bound to oxygen (oxyhaemoglobin), when seen through the skin it has an increased tendency to reflect blue light back to the eye.[10] In cases where the oxygen is displaced by another molecule, such as carbon monoxide, the skin may appear 'cherry red' instead of cyanotic.[11] ### Local hypoxia If a tissue is not being perfused properly, it may feel cold and appear pale; if severe, hypoxia can result in cyanosis, a blue discoloration of the skin. If hypoxia is very severe, a tissue may eventually gangrene. Extreme pain may also be felt at or around the site. ## Cause Oxygen passively diffuses in the lung alveoli according to a pressure gradient. Oxygen diffuses from the breathed air, mixed with water vapour, to arterial blood, where its partial pressure is around 100 mmHg (13.3 kPa).[12] In the blood, oxygen is bound to hemoglobin, a protein in red blood cells. The binding capacity of hemoglobin is influenced by the partial pressure of oxygen in the environment, as described in the oxygen–hemoglobin dissociation curve. A smaller amount of oxygen is transported in solution in the blood. {{ safesubst:#invoke:Unsubst||date=__DATE__ |$B= {{#invoke:Category handler|main}}{{#invoke:Category handler|main}}[citation needed] }}

In peripheral tissues, oxygen again diffuses down a pressure gradient into cells and their mitochondria, where it is used to produce energy in conjunction with the breakdown of glucose, fats and some amino acids. {{ safesubst:#invoke:Unsubst||date=__DATE__ |$B= {{#invoke:Category handler|main}}{{#invoke:Category handler|main}}[citation needed] }} Hypoxia can result from a failure at any stage in the delivery of oxygen to cells. This can include decreased partial pressures of oxygen, problems with diffusion of oxygen in the lungs, insufficient available hemoglobin, problems with blood flow to the end tissue, and problems with breathing rhythm. Experimentally, oxygen diffusion becomes rate limiting (and lethal) when arterial oxygen partial pressure falls to 60 mmHg (5.3 kPa) or below. {{ safesubst:#invoke:Unsubst||date=__DATE__ |$B= {{#invoke:Category handler|main}}{{#invoke:Category handler|main}}[citation needed] }}

### Ischemia

#### Other

Hemoglobin's function can also be lost by chemically oxidizing its iron atom to its ferric form. This form of inactive hemoglobin is called methemoglobin and can be made by ingesting sodium nitrite[20] as well as certain drugs and other chemicals.Template:Which

## Physiological compensation

### Acute

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 released. 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.[21] If severe or prolonged it could lead to cell death. {{ safesubst:#invoke:Unsubst||date=__DATE__ |$B= {{#invoke:Category handler|main}}{{#invoke:Category handler|main}}[citation needed] }} In humans, hypoxia is detected by chemoreceptors in the carotid body. This response does not control ventilation rate at normal pTemplate:Chem, but below normal the activity of neurons innervating these receptors increases dramatically, so much so to override the signals from central chemoreceptors in the hypothalamus, increasing pTemplate:Chem despite a falling pTemplate:CO2 In most tissues of the body, the response to hypoxia is vasodilation. By widening the blood vessels, the tissue allows greater perfusion. By contrast, in the lungs, the response to hypoxia is vasoconstriction. This is known as "Hypoxic pulmonary vasoconstriction", or "HPV". {{ safesubst:#invoke:Unsubst||date=__DATE__ |$B= {{#invoke:Category handler|main}}{{#invoke:Category handler|main}}[citation needed] }}

### Chronic

When the pulmonary capillary pressure remains elevated chronically (for at least 2 weeks), the lungs become even more resistant to pulmonary edema because the lymph vessels expand greatly, increasing their capability of carrying fluid away from the interstitial spaces perhaps as much as 10-fold. Therefore, in patients with chronic mitral stenosis, pulmonary capillary pressures of 40 to 45 mm Hg have been measured without the development of lethal pulmonary edema.[Guytun and Hall physiology]

Hypoxia exists when there is a reduced amount of oxygen in the tissues of the body. Hypoxemia refers to a reduction in PO2 below the normal range, regardless of whether gas exchange is impaired in the lung, CaO2 is adequate, or tissue hypoxia exists. There are several potential physiologic mechanisms for hypoxemia, but in patients with COPD the predominant one is V/Q mismatching, with or without alveolar hypoventilation, as indicated by PaCO2. Hypoxemia caused by V/Q mismatching as seen in COPD is relatively easy to correct, so that only comparatively small amounts of supplemental oxygen (less than 3 L/min for the majority of patients) are required for LTOT. Although hypoxemia normally stimulates ventilation and produces dyspnea, these phenomena and the other symptoms and signs of hypoxia are sufficiently variable in patients with COPD as to be of limited value in patient assessment. Chronic alveolar hypoxia is the main factor leading to development of cor pulmonale--right ventricular hypertrophy with or without overt right ventricular failure--in patients with COPD. Pulmonary hypertension adversely affects survival in COPD, to an extent that parallels the degree to which resting mean pulmonary artery pressure is elevated. Although the severity of airflow obstruction as measured by FEV1 is the best correlate with overall prognosis in patients with COPD, chronic hypoxemia increases mortality and morbidity for any severity of disease. Large-scale studies of LTOT in patients with COPD have demonstrated a dose-response relationship between daily hours of oxygen use and survival. There is reason to believe that continuous, 24-hours-per-day oxygen use in appropriately selected patients would produce a survival benefit even greater than that shown in the NOTT and MRC studies.[1]

## Treatment

To counter the effects of high-altitude diseases, the body must return arterial pTemplate:Chem toward normal. Acclimatization, the means by which the body adapts to higher altitudes, only partially restores pTemplate:Chem to standard levels. Hyperventilation, the body’s most common response to high-altitude conditions, increases alveolar pTemplate:Chem by raising the depth and rate of breathing. However, while pTemplate:Chem does improve with hyperventilation, it does not return to normal. Studies of miners and astronomers working at 3000 meters and above show improved alveolar pTemplate:Chem with full acclimatization, yet the pTemplate:Chem level remains equal to or even below the threshold for continuous oxygen therapy for patients with chronic obstructive pulmonary disease (COPD).[22] 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 pTemplate:Chem 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.[23] 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.[22]

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. {{ safesubst:#invoke:Unsubst||date=__DATE__ |\$B= {{#invoke:Category handler|main}}{{#invoke:Category handler|main}}[citation needed] }}

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For aircraft decompression incidents at altitude see:

## References

1. Woorons, Xavier, Hypoventilation training, push your limits! Arpeh, 2014, 164p. (ISBN 978-2-9546040-1-5)
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12. Template:Cite web – Online interactive oxygen delivery calculator.
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18. The formula ${\displaystyle Hb_{CO}(\%)={\frac {CO-2.34}{5.09}}}$ can be used to calculate the amount of carbon monoxide-bound hemoglobin. For example, at carbon monoxide level of 5 ppm, ${\displaystyle ={\frac {5-2.34}{5.09}}=.5\%}$, or a loss of half a percent of their blood's hemoglobin. (Wald et al., 1981)
19. Martin, Lawrence. (1992) All you really need to know to interpret arterial blood gases. 2nd edition ISBN 0-683-30604-9
20. Roueché, Berton (1953) Eleven blue men, and other narratives of medical detection. Boston: Little, Brown.
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