hypoxia means a shortage of oxygen — as compared to anoxia, which means a total lack of it. In common with other mammals, humans have evolved with a system of breathing and blood circulation, which allows intake of oxygen from the air and its transport throughout the body. The tissues need to extract oxygen from the blood constantly at a basic rate for their metabolism, along with the extra needed for work and exercise, and also are accustomed to a certain level of oxygen in their immediate environment. The body can compensate to some extent for a decreased level, but life depends on maintainence of the supply of oxygen. Different organs and tissues can survive lack of oxygen for different lengths of time: the brain is the most rapidly and irrevocably damaged. Because the brain regulates breathing and the circulation — the means by which oxygen is supplied to the whole body, including itself — deprivation of the brain prevents restoration of the supply; a potentially lethal vicious circle.

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) or when the supply of fresh air is restricted. At high altitude the air is ‘thinner’ in that every molecule of the gas occupies a larger volume. The blood leaves the lungs carrying less oxygen than normal, therefore the tissues are exposed to a lower oxygen level. If this is not too profound, they can still obtain oxygen at the required rate, at least for resting metabolism, because the rate of flow of blood can increase. The tissues are living at a lower level but are still getting a sufficient oxygen supply.

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. In some circumstances there may be displacement of air by other gases, and the effect of irritant or toxic gases, such as smoke, chlorine, or sulphur dioxide, can complicate the effects of displacement of oxygen.

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).

If obstruction or cessation of breathing is total, the condition is known as asphyxia: it rapidly causes death by depriving the brain of oxygen. A lesser degree of inadequate breathing is called hypoventilation, characterized by a lowered level of oxygen and a raised level of carbon dioxide in the lungs, blood, and tissues; a person suffering from chronic lung disease, for example, can live for many years in a state of moderate hypoxia. The term suffocation is less precisely defined, but is commonly applied either to obstructed breathing or to lack of fresh air supply.

Oxygen transfer from the lungs to the blood

can be impaired in some types of lung disease because the barrier it has to diffuse across is thickened. So despite breathing as much or more than normal, the blood and tissue oxygen level is below normal, although, again, an adequate supply may be maintained by increased blood flow. There are also conditions (including some congenital heart defects) in which the blood is not routed properly through the lungs, so that some blood bypasses the oxygen supply, with the result that arterial blood is hypoxic.

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. This brings the oxygen concentration in the lungs closer to that of the outside air — it remains low, but not as low as it would be if the breathing did not increase. Stimulation of breathing occurs more dramatically when carbon dioxide is accumulating in the blood whilst oxygen is decreasing, such as in the example of breathing in a confined space.

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 down side is that the thicker blood gives extra work to the pumping heart. This defence mechanism cannot of course operate against anaemia, when the fault itself lies in a deficient production of red blood cells.

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.

Sheila Jennett

Hypoxia

Definition

Hypoxia generally refers to a lack of oxygen in any part of the body. In a neurological context, it refers to a reduction of oxygen to the brain despite adequate amounts of blood.

Description

A decrease in oxygen supply to the brain can occur due to choking, strangling, suffocation, head trauma, carbon monoxide poisoning, cardiac arrest, and as a complication of general anesthesia. A failure to deliver oxygen and glucose to the brain causes a cascade of abnormal events. The extent of damage is directly proportional to the severity of the injury. The severity of cerebral ischemia, a low-oxygen state caused by arterial obstruction or lack of blood supply, and the duration of blood-flow loss in the brain determine the extent of brain damage. The neurons can suffer temporary dysfunction, or there may be irreversible damage to nerve cells that are sensitive to minute changes in oxygen levels. Severe damage involving extensive areas can occur (cerebral infarction). Cerebral hypoxia/ischemia can be caused by a broad spectrum of diseases that affect the cardiovascular pumping system or the respiratory system. There are four types of disorders to consider: focal cerebral ischemia, global cerebral ischemia, diffuse cerebral hypoxia, and cerebral infarction.

Focal cerebral ischemia

Focal cerebral ischemia (FCI) is often results from a blood clot in the brain. The blood flow in the affected area is reduced. The reduction could be severe or mild but usually FCI causes irreversible injury to sensitive neurons. The clinical signs and symptoms last approximately 15–30 minutes.

Global cerebral ischemia

Global cerebral ischemia (GCI) is a serious condition caused by ventricular fibrillation or cardiac asystole, which stops all blood flow to the brain. If the GCI lasts more than five to ten minutes, then it is likely the person will have suffered a loss of consciousness that makes recovery doubtful.

Diffuse cerebral hypoxia

Diffuse cerebral hypoxia (DCH) is limited to conditions that cause mild to moderate hypoxemia, or low arterial-oxygen content due to deficient blood oxygenation. Pure cerebral hypoxia causes cerebral dysfunction but not irreversible brain damage. Pure cerebral hypoxia can occur due to pulmonary disease, altitude sickness, or severe anemia.

Cerebral infarction

Cerebral infarction (CI) is a severe condition caused by a focal vascular occlusion in an area of the brain. This causes an area of destruction resulting from a lack of oxygen delivery.

Pathology of cerebral ischemia

Lack of oxygen causes neurons in the brain to die in several ways. Autolysis can occur, which results from the digestion of nerve tissues by enzymes. Cerebral infarction causes the death of neurons; transient cessation of the cerebral circulation for a few minutes causes selective areas of ischemic necrosis. This type of necrosis is especially evident in highly vulnerable neurons that are sensitive to abrupt oxygen deprivation. More prolonged periods of moderate-to-severe hypoxemia or carbon monoxide poisoning can cause a loss of the outer sheath of neurons.

Molecular mechanisms of cerebral hypoxia

In cases of severe ischemia to brain tissue, the tissue loses structural integrity within a few seconds or a few minutes. Soon after there is an abnormal exchange of ions in neurons through a process called depolarization; this is characterized by an influx of sodium and calcium ions inside the neuron, and a simultaneous efflux of potassium ions outside the neuron.

Cerebral edema

Cerebral edema refers to abnormal increases in water content in the brain and occurs with all types of cerebral ischemia and hemorrhagic stroke . Increased water retention in the brain causes an increase in intracranial pressure. This pressure causes the brain to be pushed against the skull, resulting in neurologic deterioration and death due to herniation. Cerebral edema and herniation of the brain is the cause of death for approximately 75% of all fatal stroke victims and 33% of fatalities for all ischemic events to the brain.

Symptoms

Symptoms vary depending on the severity of damage. Symptoms of mild cerebral hypoxia can include poor judgment, memory loss, inattentiveness, and a decrease in motor coordination. In more severe cases, there can be permanent neurologic deficits, coma, seizures , or death.

Treatment

Treatment depends on the cause and availability of equipment. Treatment is urgent and includes basic and advanced life-support measures. It is important to maintain breathing, dispense intravenous fluids and medications, and maintain stability with blood products and medications that control blood pressure and seizures. The outlook depends on the extent of cerebral ischemia.

Resources

BOOKS

Goldman, Lee, et al. Cecil's Textbook of Medicine, 21st ed. Philadelphia: W. B. Saunders Company, 2000.

ORGANIZATIONS

Brain Injury Association. 8201 Greensboro Drive, Suite 611, McLean, VA 22102. (703) 761-0750 or (800) 444-6443; Fax: (703) 761-0755. [email protected]. <http://www.biausa.org>.

National Rehabilitation Information Center (NARIC). 4200 Forbes Boulevard, Suite 202, Lanham, MD 20706-4829. (301) 562-2400 or (800) 346-2742; Fax: (301) 562-2401. [email protected]. <http://www.naric.com>.

Laith Farid Gulli, MD

Robert Ramirez, DO

Hypoxia

Hypoxia is a condition in which cells of the body are deprived of oxygen. Despite the varying reasons for hypoxia, depending on the location within the body, the consequence is the same: tissues cannot survive for long without oxygen. Prolonged oxygen deprivation proves fatal to cells. When the brain is involved, the consequence for a person is coma and death.

Cells acquire energy from oxygen and glucose. Most cells can survive for a short period using an anaerobic (lacking oxygen) metabolic process. But brain cells cannot. The damage to brain cells when hypoxia occurs is immediate. Blood carries a limited amount of reserve oxygen and brain cell death can occur within minutes of falling below normal oxygen levels.

There are several types of hypoxia. One of the more common is hypoxic hypoxia; the reduction of the amount of oxygen passing into the blood because of a reduced oxygen exchange (i.e., reduced lung capacity) or high altitudes. Reduction in lung capacity may be a result of lung damage, disease, or removal of portions of the lungs. Smokers are particularly susceptible to hypoxic hypoxia. People who change altitudes can adjust to the lower oxygen pressure as the blood produces more red blood cells carrying additional hemoglobin (the oxygen-carrying molecule in red blood cells).

Hypemic hypoxia occurs when the number of hemoglobin molecules or red blood cells is reduced. Either condition causes a reduction in the oxygen carrying capacity of the blood. Hypemic hypoxia can result from hemorrhage or anemia. It can also be induced by drugs, chemicals, or an increase in carbon monoxide (a condition experienced by smokers).

Stagnant hypoxia occurs as a result of poor blood circulation. Blood flow is reduced by prolonged sitting in one position, cold temperatures, or being exposed to g-forces (the inertial force produced by acceleration or gravity). People who fly in aircraft frequently, sit in a chair for hours, or are sedentary may experience this type of hypoxia. It is important for the elderly or those whose movement is restricted to be sure they get enough oxygen to avoid this type of hypoxia.

Histotic hypoxia is the inability of the tissues to use oxygen. When organ tissues are involved, they appear blue in color and are called cyanotic. The blue color associated with cyanosis, especially noted around the lips, is due to the build-up of high levels of deoxygenated hemoglobin in capillaries. Drinking alcoholic beverages, poisoning by cyanide or carbon monoxide, and certain narcotics can impair gaseous exchange in the tissues, and lead to hypoxia. Prolonged hypoxia can lead to tissue damage or death.

See also Blood; Hemoglobin; Respiration.

Brock Hall

Hypoxia

Hypoxia is a condition in which cells of the body are deprived of oxygen. Despite the varying reasons for hypoxia, depending on the location within the body, the consequence is the same: tissues cannot survive for long without oxygen. Prolonged oxygen deprivation proves fatal to cells. When the brain is involved, the consequence for a person is coma and death.

Cells acquire energy from oxygen and glucose. Most cells can survive for a short period using an anaerobic (lacking oxygen) metabolic process. But brain cells cannot. The damage to brain cells when hypoxia occurs is immediate. Blood carries a limited amount of reserve oxygen and brain cell death can occur within minutes of falling below normal oxygen levels.

There are several types of hypoxia. One of the more common is hypoxic hypoxia; the reduction of the amount of oxygen passing into the blood because of a reduced oxygen exchange (i.e., reduced lung capacity) or high altitudes. Reduction in lung capacity may be a result of lung damage, disease, or removal of portions of the lungs. Smokers are particularly susceptible to hypoxic hypoxia. People who change altitudes can adjust to the lower oxygen pressure as the blood produces more red blood cells carrying additional hemoglobin (the oxygen-carrying molecule in red blood cells).

Hypemic hypoxia occurs when the number of hemoglobin molecules or red blood cells is reduced. Either condition causes a reduction in the oxygen carrying capacity of the blood. Hypemic hypoxia can result from hemorrhage or anemia. It can also be induced by drugs, chemicals, or an increase in carbon monoxide (a condition experienced by smokers).

Stagnant hypoxia occurs as a result of poor blood circulation. Blood flow is reduced by prolonged sitting in one position, cold temperatures, or being exposed to g forces (the inertial force produced by acceleration or gravity). People who fly in aircraft frequently, sit in a chair for hours, or are sedentary may experience this type of hypoxia. It is important for the elderly or those whose movement is restricted to be sure they get enough oxygen to avoid this type of hypoxia.

Histotic hypoxia is the inability of the tissues to use oxygen. When organ tissues are involved, they appear blue in color and are called cyanotic. The blue color associated with cyanosis, especially noted around the lips, is due to the build-up of high levels of deoxygenated hemoglobin in capillaries. Drinking alcoholic beverages, poisoning by cyanide or carbon monoxide, and certain narcotics can impair gaseous exchange in the tissues, and lead to hypoxia. Prolonged hypoxia can lead to tissue damage or death.

see also Death, cause of; Death, mechanism of.

Hypoxia

Hypoxia is a drastic reduction in the amount of oxygen dissolved in water—a state that can be fatal to fish and other gill-breathing animals. Hypoxia is most often caused by pollution from nitrogen and phosphorus compounds derived from fertilizers, animal waste, sewage, or atmospheric contaminants. The pollutants stimulate an excessive growth of plant material. When these plants—typically algae—die and decay, they support large populations of bacteria, which take oxygen from the water. Pollution with sewage solids has a similar effect. Prevention involves controlling the sources of pollution by improved agricultural practices, treatment of sewage, and, to a lesser extent, reduction of emissions from the burning of fossil fuels.

see also Fish Kills; Wastewater Treatment; Water Pollution.

Kenneth H. Mann