Condition in which tissues are starved of oxygen. The extreme is anoxia (absence of oxygen). There are four types hypoxia: hypoxemic, from low blood oxygen content (e.g., in altitude sickness); anemic, from low blood oxygen-carrying capacity (e.g., in carbon monoxide poisoning); distributive, from low blood flow (e.g., generally in shock or locally in atherosclerosis); and histotoxic, from poisoning (e.g., with cyanide) that keeps cells from using oxygen. If not reversed quickly, hypoxia can lead to necrosis (tissue death), as in heart attack

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.

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.

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).
• 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 effectively use the oxygen due to disabled oxidative phosphorylation enzymes. Cyanide toxicity is one example

 Signs and symptoms

The  symptoms of generalized hypoxia depend on its severity and accelerat

ion 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.Hypoxia means a shortage of oxygen — as compared to anoxia, which means a total lack of it

Hypoxia occurs (i) when there is less than the normal amount of oxygen in the air inhaled; (ii) when breathing is obstructed, is inadequate, or stops; (iii) when oxygen is not transferred normally from the lungs to the blood; (iv) when the blood cannot carry its normal quota of oxygen; (v) when the flow of blood is inadequate, or stops.

The air inhaled may provide insufficient oxygen either because the atmospheric pressure is low (at high altitude) When the supply of fresh air is restricted — with a bag over the head, in a closed cupboard, or in a larger enclosed space crowded with people — oxygen is progressively depleted and exhaled carbon dioxide accumulates. Disturbance of breathing Obstruction to breathing can occur either externally (smothering, strangulation, compression of the chest in a crowd disaster) or internally (choking, allergic swelling of the upper airways, asthmatic attacks). In other less drastic ways breathing can become inadequate to keep the oxygen level up to normal, and carbon dioxide down to normal, in the lungs and blood: when breathing becomes mechanically difficult in some types of lung disease; when there is damage to the brain stem or to the upper spinal cord where the nerves arise which activate the muscles of breathing; or when the muscles themselves are weak. Breathing may be depressed by drugs acting on the control centres in the brain, and it may stop entirely in collapse from various causes (concussion, near-drowning, heart attack, electric shock).

The term suffocation is less precisely defined, but is commonly applied either to obstructed breathing or to lack of fresh air supply.

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In all the types of hypoxia described so far, the haemoglobin in the arterial blood is less than fully saturated with oxygen. The redness of blood depends on this saturation. In hypoxia it becomes more blue, and cyanosis is the outward and visible sign of this when blueness tinges the skin.

The oxygen-carrying capacity of the blood is lowered when red blood cells, and haemoglobin, are in short supply (anaemia): the blood carries less oxygen than normal, although there is sufficient oxygen in the air and in the lungs, and all available haemoglobin is fully saturated. There are also conditions in which the haemoglobin is not all in its normal form. Carbon monoxide poisoning acts by combining with haemoglobin, making it unable to carry oxygen.

Deprivation of blood flow makes organs and tissues hypoxic: the state of ‘ischaemia’. This can occur either as part of whole-body deprivation in heart failure, or locally where blood vessels are obstructed by arterial disease or by clots, or constricted as in the skin in cold exposure.

Defences against hypoxia

The body has ways to defend itself against hypoxia at each stage of the process of oxygen acquisition: by breathing harder, to get more into the lungs; by crowding more red cells into the blood so that it can carry more in every circulating millilitre; by pumping the blood around at a greater rate; and by widening the blood vessels which supply the vital organs. Most of these adjustments   can       be        made   very     rapidly.

When oxygen is low — but tolerably so — in inhaled air, and hence in the blood, the arterial chemoreceptors — minute structures in the neck — sense this and, via the brain, cause a reflex increase           in        breathing.
If hypoxia of a tolerable degree is sustained for weeks, the bone marrow produces extra red blood cells, resulting in polycythaemia. The greater density of red cells brings the oxygen concentration in the blood back towards normal despite their haemoglobin carrying less than it ideally could

The heart compensates for hypoxia by pumping out more blood per minute so that the actual delivery rate of oxygen to the tissues can be kept up despite its lower concentration in the blood.

These automatic attempts at self-preservation operate unless the oxygen lack becomes too profound to sustain brain functions, including that of maintaining breathing itself. At worst, the heart weakens, the blood pressure falls, breathing stops, and cessation of the heartbeat soon follows.

Pathophysiology.

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.

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.