Juan Carlos Figueroa Casas y Marcelo Figueroa Casas

Hypoxemia and hypoxia: concept and definition

Hypoxemia is defined as the drop in the partial pressure of oxygen in the arterial blood. Although the normal figure may vary from one laboratory to another, it is accepted that hypoxemia exists when the PaO 2 is less than 80 mm Hg breathing air, at sea level ( The normal value of PaO2 falls with age according to the following equation: PaO2 = 103.5 - (0.42 x age)  ). This figure varies if you breathe a gaseous mixture with less oxygen (populations at altitude) or with a higher concentration, as occurs when O2 is supplied for therapeutic purposes. This must be taken into account when measuring PaO2 in each subject.

Hypoxia is defined as oxygen deficit at the tissue level. Its presence is not synonymous with hypoxemia since, while hypoxia implies a low PaO2 within the tissues, hypoxemia implies a drop in PaO2 in the blood that flows to them. In various circumstances, despite having a "good" PaO 2, there is a marked deterioration in tissue oxygenation. It is, therefore, necessary to emphasize that, although PaO 2 is important information, the assessment of peripheral oxygenation should not be based only on that single parameter.

Tissue oxygen supply depends on the interaction of three factors: a) blood oxygen content, determined by PaO 2 and hemoglobin; b / blood flow supplying the tissues, and c) consumption of tissue oxygen, which essentially depends on the level of metabolic activity (exercise, fever, etc.). As can be seen, although hypoxemia may be a cause of hypoxia, it does not necessarily imply its existence and vice versa. There may be, for example, tissue hypoxia due to a drop in blood flow with normal PaO 2 (heart failure, shock) or a hypoxemia of moderate magnitude (PaO 2 <50 mm Hg) with normal blood flow and consumption that is not enough to compromise tissue oxygen level. Also in marked anemia, PaO2 may be normal with decreased O 2 supply to the tissues. It should be interpreted, therefore, that Pa02 accurately indicates the efficiency of lung function but provides only partial information about the oxygen supply to the tissues, which must be complemented with the O 2 content , blood flow and utilization. of 02 for the tissues.


PaO 2


Most frequent causes



FIO2 100%

FIO 2 decrease

  • Altitude


No significant changes

Correction (> 500mm Hg)

Alveolar hypoventilation

  • Depression of the respiratory center
  • Spinal cord injury
  • Enf. neuromuscular 
  • Obstructive lung diseases



Correction (> 500 mm Hg) with risk of PaO 2 increase 

Disruption of diffusion

  • Interstitial diseases
  • Pulmonary edema

Normal or low 

Sharp decrease 

Correction (> 500mm Hg)

Right-left short circuit (shunt) 

  • Anatomical
    • Congenital heart disease
    • Pulmonary AV fistulas
  • Functional
    • Atelectasia
    • Consolidation

Normal or low 

Generally decreases 

Partial improvement (<500 mm Hg) 

Ventilation-perfusion irregularities

  • All kinds of bronchopulmonary disease

Normal or low 

Generally decreases

Correction (> 500mm Hg) 

PvO 2 decrease 

  • Low minute volume
  • Increased tissue consumption
  • Coexistence with lung disease

According to existing lung pathology 


Correction (> 500 mm Hg) according to lung pathology 

Hypoxema: production mechanisms

the mechanisms of hypoxemia production under various clinical conditions and the means of differentiating them are summarized in Table 16-2.

1) Decrease in inspired oxygen pressure. This circumstance commonly occurs at altitude, in atmospheres with excessive combustion of oxygen or during the rebreathing of inspired air (the latter is associated with hypercapnia and can be considered a form of hypoventilation). Its diagnosis does not usually offer problems as long as it is known that a drop in PaO2 occurs with increasing altitude or in other types of atmospheres. Its magnitude also depends on the degree of hyperventilation that occurs. The administration of 02 increases the Pa02 according to the FI02 supplied.

2) Alveolar hypoventilation. Alveolar hypoventilation can be defined as the decrease in the amount of atmospheric air entering the alveoli in the unit of time. It refers to that part of the minute ventilation that participates in an "effective" way in the gas exchange (minute ventilation-physiological dead space). The drop in PaO2 is accompanied in this case by a rise in PaCO 2 proportionally. The O2 gradient remains within normal limits, unless the cause of hypoventilation simultaneously produces ventilation-perfusion imbalances. O 2 administration easily corrects hypoxemia, although there may be a risk of causing increased CO retention if there is no simultaneous increase in ventilation. The most frequent causes of alveolar hypoventilation are listed in Table 16-2.

3) Alterations in diffusion. The diffusion of oxygen from the alveolar gas into the blood can be hampered by diseases that occupy it, the interstitium (pulmonary fibrosis of various etiologies) and / or the alveolus (pulmonary edema / diffuse inflammatory exudate, etc.). CO 2 is usually not altered by this cause since it is 20 times more diffusible than O 2 . This situation rarely leads to significant hypoxemia at rest since the transit time of the red blood cell through the pulmonary capillary (0.75 seconds) provides a margin of safety that allows it to achieve a balance between PAO 2 and PaO 2(normally occurs in 0.15 seconds) at the end of the tour, even taking longer than usual. However, when performing exercise or a stress test and increasing the circulation speed, the capillary transit time is noticeably reduced and then hypoxemia becomes evident or the previously existing hypoxemia is accentuated.

Hypoxemia of diffusion abnormalities is generally associated with normo or hypocapnia, the latter due to hyperventilation secondary to the stimulus caused by hypoxemia. The Aa O 2 gradient is naturally increased. After inhaling 100% oxygen, Pa02 increases markedly as the gradient between alveolar and arterial pressure is restored.

From a practical clinical point of view, it is considered that any interstitial disease sufficiently advanced to cause hypoxemia at rest also produces a ventilation-perfusion irregularity capable of leading to a more significant drop in PaO2 , although that caused by the defect in diffusion. That is why this type of hypoxemia is rarely found in "pure" form.

4) Short circuit from right to left ("shunt") . Short circuits from right to left define vascular communications through which venous blood passes without being exposed to contact with alveolar air and mixes with oxygenated blood. Under physiological conditions, a small amount of venous blood, less than 4% of the minute volume, enters the systemic circulation through the bronchial veins and the Thebesium veins.

In pathological conditions, this abnormality may be due to anatomic causes (heart disease: congenital, pulmonary arteriovenous fistulas) or more commonly, to pulmonary causes that lead to areas of the lung that are perfused but not ventilated (atelectasis, consolidation due to edema or hemorrhage).

Oxygen administration does not correct hypoxemia since short-circuit blood passes without being exposed to alveolar FiO 2 , and then a PaO 2 greater than 50 mm Hg cannot be achieved even with 100% O2 inhalation . The Aa O2 gradient is high. Although theoretically PaCO 2 could rise as a result of the amount contributed by the "shunt" to the systemic circuit, if the lungs are normal and capable of greater ventilation, PaCO 2 will be normal or even low as a consequence of hyperventilation secondary to hypoxemia.

The amount of blood that goes through the "shunt" can be calculated using an equation: Qs / Qt = (CaO2 - CcO2 ) / (CvO 2 - CcO 2 ), where Qs - amount of blood that goes through the "shunt 'Qí - minute volume, and CcU2 = pulmonary capillary O2 content .

5) Irregularities of ventilation-perfusion. This is the most frequent cause of hypoxemia in clinical practice. It originates from the existence of hypoventilated areas of the lung in relation to the perfusion they receive. This occurs as a consequence of incomplete bronchial obstruction due to retention of secretions, bronchospasm, edema, or due to areas with decreased compliance. These areas produce hypoxemia and hypercapnia in the capillaries that flow from them. Since global ventilation is maintained, inspired air that does not enter these areas is diverted to other sectors in which ventilation increases. These areas with increased ventilation give rise to a hypocapnia sufficient to neutralize the increase in PaCO 2which occurs in the hypoventilated sectors, there being then normocapnia or even hypocapnia in the mixed arterial blood. However, given the peculiar sigmoid morphology of the hemoglobin dissociation curve, hyperventilation in areas with a high ventilation-perfusion ratio ("plateau" portion of the curve) does not compensate for the hypoxemia that occurred in areas with a low ratio. ventilation-perfusion ("steep portion of the curve"). As a result, the presence of hypoxemia accompanied by normocapnia is recorded in arterial blood. The Aa O2 gradient is high. Inhalation of oxygen produces the "washing" of N 2 from the hypoventilated alveolar areas, restoring FiO 2 to normal levels and correcting hypoxemia.

6) Decreased O2 content in venous blood. The drop in the O2 content of themixed venous blood can influence the gas exchange and have an effect on the PaO 2 of the blood that leaves the lungs.

The drop in minute volume and the increase in tissue consumption of O 2 produce a decrease in PvO 2 with a decrease in CO2 in the blood that returns from the tissues to the lungs. The effect of CvO 2 reduction on PaO 2it is variable according to the type and degree of pulmonary pathology. In subjects with perfectly homogeneous lungs, this effect is null since in each alveolocapillary unit, PaO 2 is balanced with PAO 2 , while it will be much higher in patients with diseased lungs with severe ventilation-perfusion irregularities. In those units with little or no ventilation in relation to perfusion, the drop in PcO2 will produce a significant reduction in PO2 at the end of the pulmonary capillary.

Patients who present a considerable degree of "shunt" are particularly vulnerable to those factors that alter PO2 . The changes that then occur in the PaOa of subjects with V / Q irregularities may sometimes be due to a decrease in the minute cardiac volume with a secondary fall in PvO 2 , and in such circumstances it is necessary to measure the latter before stating that the lower PaO 2 level indicates an evolutionary worsening of lung injury.

The mechanisms of hypoxemia that have been described are frequently combined with each other and influence to a variable degree the final value of PaO2 .




(See hypoxemia mechanisms)


Hemoglobin drop



Alterations of the oxyhemoglobin curve

CO poisoning

Stored blood transfusions (Decrease of 2-3 DPG)







Arterial obstructions



Cyanide poisoning

Acute respiratory distress syndrome


Hypoxia: production mechanisms

Hypoxia is defined as the insufficient supply of O 2 for the needs of the tissues. The exact number of tissue PO 2 is unknown , although it is believed that as long as figures above a certain minimum level (approximately 4 mm Hg) are maintained, tissue consumption is not affected by the drop in systemic transport.

The causes of hypoxia are classified in Table 16-3. Hypoxemic hypoxia originates from a drop in PaO 2 of sufficient magnitude (below 45-50 mm Hg if there are no other factors involved) to compromise the contribution to cellular mitochondria. Its mechanisms have been previously detailed.

Anemic hypoxia implies a drop in the hemoglobin level or alterations in the dissociation curve. In these cases, the PaO 2 may be normal, but the tissue supply is compromised by a decrease in the content or a deficit in the "delivery".

Circulatory hypoxia is secondary to a reduction in blood flow of general cause (minute volume drop) or local (arterial blockages). Finally, in certain circumstances, cells may be unable to use oxygen adequately even though oxygen arrives in sufficient quantity ("dysxic" hypoxia). This can occur in cyanide poisoning, and inadequate oxygen utilization has also been described in sepsis and in adult acute respiratory distress syndrome.

Clinical signs of hypoxemia and hypoxia. Cyanosis

The clinical signs that indicate the presence of hypoxemia and / or hypoxia can be obvious and dramatic or so insidious and nonspecific that they do not allow us to appreciate the seriousness of the situation.

The patient with obstructive dyspnea and labored breathing certainly attracts the attention of those who assist him immediately. In other circumstances, only neurological or circulatory manifestations are found secondary to decreased oxygen supply, such as headaches, impaired judgment or intellect or level of consciousness, tachycardia, tachypnea, hypertension or arterial hypotension. As can be seen, these manifestations are nonspecific and can be caused by a variety of conditions. They are only repaired if the causal disease is known and its repercussion on the level of blood oxygen is suspected.

Cyanosis has been considered for many years as the classic semiological sign that indicates the decrease in the level of O 2 in the blood and / or tissues. The term cyanosis (from "kyanos" = blue) defines the bluish coloration of the skin and mucosa and is seen earlier in those places where the skin is thinner or where there is an abundant capillary network, such as the tongue, lips, nails, pinnae, cheeks, and nose. Cyanosis responds to the presence of reduced hemoglobin in the blood, the color of which is purple red in contrast to the bright red of oxyhemoglobin.

Cyanosis is evident when the blood flowing through the capillaries contains more than 5 g of reduced Hb per 100 ml (normally there are 0.70 - 0.75 g reduced Hb in 100 ml of arterial blood). However, the presence of cyanosis is not an early sign of hypoxemia or hypoxia. The possibility of appreciating it is influenced by the subjective impression of the observer, as well as by the pigmentation and thickness of the skin, the state of the capillary bed and even by ambient light. The existence of anemia masks its presence (there is not enough Hb to reach 5 g of reduced Hb), while the capillary plethora associated with polycythemia can simulate cyanosis.

Unfortunately, cyanosis can only be clearly recognized when O 2 saturation in arterial blood is less than 75%, that is, a Pa02 of approximately 50 mm Hg, which implies marked hypoxemia. Therefore, it can be affirmed that cyanosis is not an early indicator of the provision of 02 to the tissues and that its detection is a rather late sign of a hypoxemia whose magnitude is severe, with milder degrees previously that go unnoticed. . That is why the absence of cyanosis should not be interpreted in any case as a sign of adequate blood oxygenation.

Cyanosis can be defined as "center 5 or" arterial cause 5 5 when it responds to a fall in PO 2.in arterial blood due to inadequate oxygenation during its transit from the minor circulation to the arterial circuit. Instead, we speak of "peripheral" or "circulatory" cyanosis when it originates from an increase in the consumption of 02 at the capillary level. This can, in turn, be classified as "universal" when general circulatory stasis (heart failure, shock, etc.) originates, or "local" when blood removal and increased O 2 consumption are limited to a single segment. of the organism (thrombophlebitis, obstruction of the superior vena cava, etc.).

Some relatively rare conditions can cause coloration that can be mistaken for cyanosis. Argyria secondary to silver poisoning can produce a grayish discoloration of the skin; but unlike cyanosis the compression of the integuments does not make them pale. Methaemoglobinemia gives a very similar appearance to cyanosis, and should be suspected if normal Pa02 and total hemoglobin with low blood oxygen capacity are found. Blood spectroscopic analysis will allow the diagnosis to be made.