Tissue Hypoxia: Definition, Symptoms, Causes and Treatment

It is a condition in which a region of the body is deprived of an adequate supply of oxygen at the tissue level.

Hypoxia can be classified as generalized, affecting the whole body, or local (tissue), affecting a region of the body.

Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of normal physiology, for example, during hypoventilation training or strenuous physical exercise.

Hypoxia differs from hypoxemia and anoxemia in that hypoxia refers to a state in which oxygen supply is insufficient, while hypoxemia and anoxemia specifically refer to states that have low or no arterial oxygen supply. .

Hypoxia in which there is a complete deprivation of oxygen supply is known as anoxia.

Generalized hypoxia occurs in healthy people when ascending to high altitudes, where it causes altitude sickness that leads to life-threatening complications: high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE). its acronym in English).

Hypoxia also occurs in healthy individuals when breathing gas mixtures with a low oxygen content, such as while submerging underwater, especially when using closed-loop rebreather systems that control the amount of oxygen in the supplied air. .

Mild, non-detrimental intermittent hypoxia is used intentionally during altitude training to develop athletic performance adaptation at both the systemic and cellular level.

Hypoxia is a common complication of premature birth in newborns. Because the lungs develop late in pregnancy, premature babies often have underdeveloped lungs.

To improve lung function, doctors often place babies at risk for hypoxia inside incubators (also known as humidicribs) that provide continuous positive airway pressure.

Local hypoxia or tissue hypoxia

If the tissue is not adequately perfused, you may feel cold and pale; if severe, hypoxia can lead to cyanosis, a blue discoloration of the skin. If the hypoxia is very severe, a tissue can become gangrenous. Extreme pain can also be felt in or around the site.

Tissue hypoxia from low oxygen supply may be due to low hemoglobin concentration (anemic hypoxia), low cardiac output (stagnant hypoxia), or low hemoglobin saturation (hypoxic hypoxia).

The consequence of oxygen deprivation in tissues is a shift to anaerobic metabolism at the cellular level. As such, reduced systemic blood flow can result in increased serum lactate.

Serum lactate levels have been correlated with disease severity and mortality in critically ill adults and ventilated neonates with respiratory distress.

Symptoms of tissue hypoxia

Tissue hypoxia, due to low arterial oxygen tension, inadequate blood flow, or a combination of these two factors, results in a shift to anaerobic metabolism at the cellular level.

Therefore, a reduced systemic blood flow can result in an increase in serum lactate.

Serum lactate levels have been correlated with disease severity and mortality in critically ill adults and ventilated neonates with respiratory distress syndrome.

The normal lactate level in this group of infants is less than 2.5 mmol / L and there is an association with mortality as the serum lactate level rises above this threshold.

This can be a very serious problem. Playing the threat and persistence of blood deprivation, can cause physical inconvenience, pain, and cell death. The blood carries oxygen and nutrients to the cells of the body.

Any decrease in the supply of these substances that sustain the organism produces a depreciation in cellular performance and, if it is very serious, cellular deterioration that the body may or may not compensate for.

If the reduction in blood and oxygen flow is stiff and acute, it is known as ischemia (described later) or shock.

It can occur anywhere on the body as a result of a variety of conditions. It is common in the extremities, such as the hands and feet, the kidneys, the skin, and the heart.

Cognitive decline, attention disorders, depression, emotional instability, uncoordinated motor work, visual, hearing and spatial problems (seeing where your body is in space and placing it in the correct position).

All of this is the consequence of the depreciation of blood flow to certain parts of the brain.

You may experience hypoperfusion without realizing it, and without noticing that your physical and mental abilities are reduced. Even less is possible that you make the link between the pain and your abilities or subtly reduced mood swings.

Lack of care and attention to these signs could lead to an increase in symptoms and possibly a greater danger of serious cell damage from long-term blood flow difficulties.

The most significant symptom you may have is pain in the affected and / or underlying area. Many patients merely choose to live with pain, and accept it as an unfortunate but normal part of life.

Ignoring treatment for this pain could harm you physically and mentally. It could possibly lead to more serious problems in the future if left untreated.

If you have chronic pain, the best thing you can do for yourself is to have an experienced professional spy examine you.


Oxygen diffuses passively into the pulmonary alveoli according to a pressure gradient. Oxygen diffuses from breathed air, mixed with water vapor, into arterial blood, where its partial pressure is around 100 mmHg (13.3 kPa).

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 by the oxygen-hemoglobin dissociation curve. Less oxygen is carried in solution in the blood.

In peripheral tissues, oxygen again diffuses down a pressure gradient into cells and their mitochondria, where it is used for energy along with the breakdown of glucose, fats, and some amino acids.

Hypoxia can be the result of a failure at any stage of oxygen delivery to cells.

This can include decreased partial pressures of oxygen, problems with oxygen diffusion in the lungs, insufficient available hemoglobin, problems with blood flow to the tip tissue, and problems with breathing rate.

Experimentally, oxygen diffusion becomes limiting (and lethal) when arterial oxygen partial pressure drops to 60 mmHg (5.3 kPa) or less.

Almost all oxygen in the blood is bound to hemoglobin, so interfering with this carrier molecule limits oxygen supply to the periphery.

Hemoglobin increases the oxygen transport capacity of the blood approximately 40 times, with the capacity of hemoglobin to transport oxygen influenced by the partial pressure of oxygen in the environment, a relationship described in the oxygen-hemoglobin dissociation curve.

When hemoglobin’s ability to transport oxygen is interfered with, a state of hypoxia can occur.


Ischemia, which means insufficient blood flow to a tissue, can also lead to hypoxia. This is called ‘ischemic hypoxia’.

This can include an embolic event, a heart attack that decreases overall blood flow, or trauma to damaging tissue. An example of insufficient blood flow that causes local hypoxia is gangrene that occurs in diabetes.

Diseases such as peripheral vascular disease can also cause local hypoxia. For this reason, symptoms are worse when a limb is used.

Pain can also be felt as a result of increased hydrogen ions leading to a decrease in blood pH (acidity) created as a result of anaerobic metabolism.

Hypoxemic hypoxia

This specifically refers to hypoxic states where the arterial oxygen content is insufficient. This can be caused by disturbances in the respiratory drive, such as:

Respiratory alkalosis, physiological or pathological bypass of the blood, diseases that interfere with lung function that cause a mismatch between ventilation and perfusion.

Also a pulmonary embolism or alterations in the partial pressure of oxygen in the environment or in the pulmonary alveoli, as can occur at altitude or when diving.

Carbon monoxide poisoning

Carbon monoxide competes with oxygen for binding sites on hemoglobin molecules. Since carbon monoxide binds to hemoglobin hundreds of times more than oxygen, it can prevent oxygen transport.

Carbon monoxide poisoning can occur acutely, as with smoke poisoning, or over a period of time, as with smoking. Due to physiological processes, carbon monoxide is kept at a resting level of 4-6 ppm.

This is increased in urban areas (7-13 ppm) and in smokers (20-40 ppm). A carbon monoxide level of 40 ppm equates to a reduction in hemoglobin levels of 10 g / L.

Carbon monoxide has a second toxic effect, that is, to eliminate the allosteric shift of the oxygen dissociation curve and shift the foot of the curve to the left.

By doing so, hemoglobin is less likely to release its oxygen in peripheral tissues. Certain abnormal variants of hemoglobin also have a higher than normal oxygen affinity, and therefore are also poor at delivering oxygen to the periphery.


Altitude sickness, also known as acute mountain sickness (AMS), is a negative health effect of altitude, caused by acute exposure to low amounts of oxygen at high altitude.

It presents as a collection of nonspecific symptoms, acquired at high altitude or with low air pressure, resembling a case of “flu, carbon monoxide poisoning, or hangover.”

Although minor symptoms such as shortness of breath can occur at altitudes of 1,500 meters (5,000 feet), acute mountain sickness typically occurs above 2,400 meters (8,000 feet). It is difficult to determine who will be affected by altitude sickness.

The diagnosis is supported in those who have a moderate to severe reduction in activities.

Acute mountain sickness can progress to high-altitude pulmonary edema or high-altitude cerebral edema, both life-threatening, and can only be cured by immediate descent to a lower altitude or the administration of oxygen.

The mountain sickness Chronic is a different condition that only occurs after prolonged exposure to high altitude.

Hypoxic respiratory gases

Diving breathing gas can contain insufficient partial pressure of oxygen, particularly in malfunctioning rebreathers. Such situations can lead to unconsciousness without symptoms, as carbon dioxide levels are normal and pure hypoxia is poorly detected by the human body.

A similar problem exists when inhaling certain odorless asphyxiating gases.

Asphyxiating gases reduce / displace the normal oxygen concentration in breathing air, where prolonged exposure to this hypoxic respiratory gas leads to unconsciousness, followed by death from inert gas asphyxiation (suffocation).

When the oxygen level drops below 19.5% v / v (volume / volume), the air is considered oxygen deficient, where oxygen concentrations below 16% volume are considered highly dangerous to humans.

Because asphyxiating gases are relatively inert and odorless, their presence may not be noticed until the body recognizes the effects of elevated blood carbon dioxide ( hypercapnia ).

Inert gas suffocation can be deliberate with the use of a suicide bag. Accidental death has occurred in cases where concentrations of nitrogen in controlled atmospheres, or methane in mines, have not been detected or appreciated.


Hemoglobin function can also be lost by chemically oxidizing its iron atom to its iron form. This inactive form of hemoglobin is called methemoglobin and can be obtained by ingesting sodium nitrite, as well as certain drugs and other chemicals.


Hemoglobin plays an important role in the transport of oxygen throughout the body, and when it is deficient, it can lead to anemia, causing “anemic hypoxia” if tissue perfusion is decreased. Iron deficiency is the most common cause of anemia.

Since iron is used in the synthesis of hemoglobin, less hemoglobin will be synthesized when there is less iron, due to insufficient intake or poor absorption.

Anemia is usually a chronic process that is compensated over time by increased levels of red blood cells through positively regulated erythropoietin. A chronic hypoxic state can be the result of poorly compensated anemia.


Tissue hypoxia (deprivation of oxygen in a tissue) can occur during a bacterial infection as a result of several factors.

The resulting inflammation prevents blood from reaching the site of infection and / or local angiogenesis does not keep pace with oxygen consumption by dividing bacteria and the expanding and infiltrating neutrophil population.

Normal oxygen pressure levels (PO2) are classified as normoxia at 15-21% oxygen, 110-160 mmHg; hypoxia at <12% oxygen, 90 mmHg; and anaerobiosis at <0.01% O2, <5 mmHg.

The partial pressure of oxygen can range from 110 mmHg in the alveoli to 15 mmHg in the liver, and the partial pressure of oxygen depends on the site of the tissue.

Wound sites, representing sites of inflammation and infiltration of myeloid cells, vary between 10 and 20 mmHg, and hypoxia is a characteristic of tissues that experience bacterial infections.

The lack of oxygen at an infection site significantly affects the gene expression of bacterial and host cells, so it is important to study the response to anaerobiosis by S. aureus to develop new therapies and a greater understanding of the organism during the course of an infection.


Tissue hypoxia is the main result of carbon monoxide poisoning. Therefore, according to the chemical and pathophysiological data, oxygen is the “natural antidote.”

To counteract the effects of high altitude illness, the affected area must return the partial arterial pressure of oxygen to normal. Acclimatization, the means by which the affected area adapts to higher altitudes, partially restores the partial pressure of oxygen to standard levels.

Since the clinical signs and symptoms of carbon monoxide toxicity are nonspecific, all suspected victims should be treated with oxygen inhalation immediately after blood is drawn to determine the carboxyhemoglobin content.

Individual responses to similar levels of carbon monoxide exposure vary widely, from death to Parkinson’s syndrome to mild or moderate intellectual shock.

Therefore, immediately after ensuring the airway and adequate ventilation, the administration of normobaric oxygen is the cornerstone of therapy, reducing the half-life of carboxyhemoglobin from a mean of 5 hours (range 2 to 7 hours). about 1 hour.

Hyperbaric oxygen at 2.5 atmospheres reduces it to 20 to 30 minutes and has other benefits, at least in animal models.

For example, in rat brains, it prevents lipid peroxidation and adhesion of leukocytes to the cerebral microvascular endothelium while accelerating the regeneration of inactivated cytochrome oxidase.

Therefore, generally at 2.5 to 3 atmospheres absolute for 90 to 120 minutes, it is considered the treatment of choice for those with syncope, coma, or seizures; a focal neurological deficit; or carboxyhemoglobin greater than 25% (15% in pregnancy).

In theory, normobaric oxygen should be the treatment for less severely poisoned patients, reserving hyperbaric oxygen therapy for severe poisonings. However, there are problems with this policy:

  1. Carboxyhemoglobin levels do not correlate with the clinical severity of carbon monoxide poisoning.
  2. There is no universally accepted scale of severity for carbon monoxide poisoning, although loss of consciousness and neurological deficits generally indicate severe poisoning.
  3. All victims of carbon monoxide poisoning are at risk for delayed neuropsychological sequelae.

Therefore, in general, the following approach is appropriate:

  1. Patients with suspected carbon monoxide poisoning should receive 100% oxygen.
  2. Patients with severe poisoning should receive hyperbaric oxygen regardless of the carboxyhemoglobin level.
  3. Pregnant women should be treated with hyperbaric oxygen regardless of signs and symptoms.
  4. In patients with lesser degrees of intoxication, careful evaluation is recommended before deciding that the appropriate therapy is 100% normobaric oxygen for more than 6 hours.

Administration of more than one cycle of hyperbaric oxygen for those who remain in a coma is controversial.

There are several practical considerations because not all treatment facilities, for example hospital emergency rooms, can measure carboxyhemoglobin or deliver hyperbaric oxygen.

For example, in a recent study, only 44% of acute care hospitals had the ability to measure carboxyhemoglobin.

Hyperbaric oxygen is 100% oxygen at two to three times the atmospheric pressure at sea level. The oxygen tension in the arteries increases to approximately 2000 mm Hg and that of the tissues to almost 400 mm Hg.

Pressure is expressed in multiples of atmospheric pressure, which is 1 at sea level. At sea level, the oxygen concentration in the blood is 0.3 mL / dL. With 100% oxygen at ambient pressure (normobaric), the amount of dissolved oxygen in the blood increases five times to 1.5 ml / dL.

At 3 atmospheres, the dissolved oxygen content reaches 6 ml / dL. Hyperbaric oxygen decreases the formation of bubbles in the blood and replaces inert gases with oxygen, which is rapidly absorbed and used by tissues.

Hyperbaric oxygen can be bactericidal or bacteriostatic, or it can suppress toxin production, increasing the resistance of tissues against infection.

Hyperbaric oxygen is more effective than normobaric oxygen in promoting collagen formation and angiogenesis and therefore may facilitate wound healing.

Hyperbaric oxygen inhibits neutrophil adherence to ischemic vessel walls, decreasing free radical production, vasoconstriction, and tissue destruction.

Hyperbaric oxygen is generally administered in a single-seat chamber or, less frequently, in a multi-occupant chamber. The duration of a single treatment for carbon monoxide poisoning is approximately 45 minutes.

Hyperbaric oxygen with oxygen pressures up to 3 atmospheres for up to 120 minutes is safe.

Adverse effects include reversible myopia, cataracts, tracheobronchial symptoms, self-limited seizures, and barotraumas in the middle ear, cranial sinuses, and, rarely, teeth or lungs.

Claustrophobia can be a problem in single-seat cameras. Despite the contradictory results in the literature on the effect of hyperbaric oxygen versus normobaric oxygen.

Tibbles and Edelsberg determined that patients with severe carbon monoxide poisoning should receive at least one 2.5 to 3.0 atmospheres hyperbaric oxygen treatment because this therapy is the fastest method of treating potentially life-threatening reversible effects.

Treatment of a patient with carbon monoxide poisoning should not be based solely on carboxyhemoglobin levels. The clinical manifestations, carboxyhemoglobin levels and, most importantly, the underlying medical history of the patient must be considered.

In patients with suspected carbon monoxide poisoning, 100% oxygen should be administered immediately with a mask.

The goal is to increase the pressure of arterial oxygen levels, decrease the half-life of carbon monoxide, and facilitate its dissociation from hemoglobin, allowing oxygen to adhere to the released binding sites.

Strict rest should be provided as it decreases oxygen demand and consumption. Patients with respiratory distress and decreased level of consciousness should be intubated and ventilated.

Chest X-rays, blood lactate levels, and arterial gases should be done in the emergency department. Headache improved before hyperbaric oxygen treatment in 72%, resolving completely in 21%.

Of those with residual headache, pain improved with hyperbaric oxygen in 97%, resolving completely in 44%.

Although deaths from carbon monoxide poisoning have decreased in the United States in recent years, the total burden, including fatal and non-fatal cases, has not changed significantly.

Juurlink et al. analyzed available data from six randomized controlled trials that included acutely carbon monoxide poisoned nonpregnant adults.

At 1 month of follow-up after treatment, symptoms possibly related to carbon monoxide poisoning were present in 34.2%, not in those treated with hyperbaric oxygen, compared with 37.2% not treated with hyperbaric oxygen.

They found no evidence that the unselected use of hyperbaric oxygen in the treatment of acute carbon monoxide poisoning reduces the frequency of neurological symptoms within 1 month.

Due to insufficient evidence, they recommend further research to define the role of hyperbaric oxygen in the treatment of carbon monoxide poisoning.

Five years later, the same group examined the evidence for the effectiveness of hyperbaric oxygen for the prevention of neurological sequelae in patients with acute carbon monoxide poisoning.

Four out of six trials found no benefit for hyperbaric oxygen in reducing neurological sequelae, while two others found benefit for hyperbaric oxygen.

The authors conclude that existing randomized trials have not been able to establish the reduction of neurological sequelae with the administration of hyperbaric oxygen to patients with carbon monoxide poisoning.

Close monitoring of serum pH and lactic acid levels is required, since anaerobic metabolism in the presence of tissue hypoxia generates lactic acidosis. Acidosis below 7.15 pH should be treated with baking soda.

Caution should be exercised with the administration of sodium bicarbonate because carbon dioxide, a by-product of its metabolism, could cause respiratory acidosis and must be removed with adequate ventilation.