Hypoxia (medical)

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. Low oxygen content in the blood is referred to as hypoxaemia. Hypoxia in which there is complete deprivation of oxygen supply is referred to as anoxia.

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 oedema (HAPE) and high altitude cerebral oedema (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
Symptoms of generalized hypoxia depend on its severity and speed of onset. In the case of altitude sickness, where hypoxia develops gradually, the symptoms include headaches, fatigue, shortness of breath, 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 blue when it is not bound to oxygen (deoxyhaemoglobin), as opposed to the rich red colour that it has when bound to oxygen (oxyhaemoglobin)). In cases where the oxygen is displaced by another molecule, such as carbon monoxide, the skin may be 'cherry red' instead of cyanotic.

Causes of tissue hypoxia

 * Hypoxic hypoxia, when there is an inadequate supply of oxygen. The term "hypoxic 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 listed below, in which the partial pressure of oxygen in arterial blood is normal. Hypoxic hypoxia may be due to:
 * Low partial pressure of atmospheric oxygen (e.g. at high altitude).
 * 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.

Pathophysiology
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 bacterial 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".