Thus far only 2 of the 3 variables referred to as the arterial blood gases, the arterial
and pH have been discussed. Many abnormal conditions or diseases can cause a low arterial
. They are discussed in the following section about the causes of tissue hypoxia in the section on hypoxic hypoxia.
The causes of tissue hypoxia can be classified (in some cases rather arbitrarily) into 4 or 5 major groups (Table 8–7
). The underlying physiology of most of these types of hypoxia has already been discussed in this or previous chapters.
Hypoxic hypoxia refers to conditions in which the arterial
is abnormally low. Because the amount of oxygen
that will combine with hemoglobin is mainly determined by the
, such conditions may lead to decreased oxygen
delivery to the tissues if reflexes or other responses cannot adequately increase the cardiac output or hemoglobin concentration of the blood.
Conditions causing low alveolar
inevitably lead to low arterial
contents because the alveolar
determines the upper limit of arterial
leads to both alveolar hypoxia and hypercapnia (high CO2
), as discussed in Chapter 3
Hypoventilation can be caused by depression or injury of the respiratory centers in the brain (discussed in Chapter 9); interference with the nerves supplying the respiratory muscles, as in spinal cord injury; neuromuscular junction diseases such as myasthenia gravis; and altered mechanics of the lung or chest wall, as in noncompliant lungs due to sarcoidosis, reduced chest wall mobility because of kyphoscoliosis or obesity, and airway obstruction. Ascent to high altitudes causes alveolar hypoxia because of the reduced total barometric pressure encountered above sea level. Reduced
(fraction of inspired oxygen
) have similar effects. Alveolar carbon dioxide is decreased because of the reflex increase in ventilation caused by hypoxic stimulation, as will be discussed in Chapter 11
. Hypoventilation and ascent to high altitudes lead to decreased venous
content as oxygen
is extracted from the already hypoxic arterial blood. Administration of increased oxygen
concentrations in the inspired gas can alleviate the alveolar and arterial hypoxia in hypoventilation and in ascent to high altitude, but it cannot reverse the hypercapnia of hypoventilation. In fact, administration of elevated
to spontaneously breathing patients hypoventilating because of a depressed central response to carbon dioxide (see Chapter 9
) can further depress ventilation.
Alveolar-capillary diffusion is discussed in greater detail in Chapter 6. Conditions such as interstitial fibrosis and interstitial or alveolar edema can lead to low arterial
and contents with normal or elevated alveolar
that increase the alveolar
to very high levels may raise the arterial
by increasing the partial pressure difference for oxygen
diffusion, as discussed in Chapter 6
True right-to-left shunts, such as anatomic shunts and absolute intrapulmonary shunts, can cause decreased arterial
with normal or even elevated alveolar
. Patients with intrapulmonary shunts have low arterial
, but may not have significantly increased
if they are able to increase their alveolar ventilation or if they are mechanically ventilated. This is a result of the different shapes of the oxyhemoglobin dissociation curve (see Figure 7–1
) and the carbon dioxide dissociation curve (see Figure 7–5
). The carbon dioxide dissociation curve is almost linear in the normal range of arterial
, and arterial
is very tightly regulated by the respiratory control system (see Chapter 9
). Carbon dioxide retained in the shunted blood stimulates increased alveolar ventilation, and because the carbon dioxide dissociation curve is nearly linear, increased ventilation will allow more carbon dioxide to diffuse from the nonshunted blood into well-ventilated alveoli and be exhaled. On the other hand, increasing alveolar ventilation will not get any more oxygen
into the shunted blood and, because of the shape of the oxyhemoglobin dissociation curve, very little more into the unshunted blood. This is because the hemoglobin of well-ventilated and perfused alveoli is nearly saturated with oxygen
, and little more will dissolve in the plasma. Similarly, arterial hypoxemia caused by true shunts is not relieved by high
because the shunted blood does not come into contact with the high levels of oxygen
. The hemoglobin of the unshunted
blood is nearly completely saturated with oxygen
at a normal
of 0.21, and the small additional volume of oxygen
dissolved in the blood at high
cannot make up for the low hemoglobin saturation of the shunted blood.
Alveolar-capillary units with low ventilation-perfusion (
) ratios contribute to arterial hypoxia, as already discussed. Units with high
do not by themselves lead to arterial hypoxia, of course, but large lung areas that are underperfused are usually associated either with overperfusion of other units or with low cardiac outputs (see the section on Hypoperfusion Hypoxia
below). Hypoxic pulmonary vasoconstriction (discussed in Chapter 4
) and local airway responses (discussed in Chapter 2
) normally help minimize
Note that diffusion impairment, shunts, and
mismatch increase the alveolar-arterial
difference (see Table 5–2
Anemic hypoxia is caused by a decrease in the amount of functioning hemoglobin, which can be a result of decreased hemoglobin or erythrocyte production, the production of abnormal hemoglobin or red blood cells, pathologic destruction of erythrocytes, or interference with the chemical combination of oxygen and hemoglobin. Carbon monoxide poisoning, for example, results from the greater affinity of hemoglobin for carbon monoxide than for oxygen. Methemoglobinemia is a condition in which the iron in hemoglobin has been altered from the Fe2+ to the Fe3+ form, which does not combine with oxygen.
Anemic hypoxia results in a decreased oxygen content when both alveolar and arterial
are normal. Standard analysis of arterial blood gases could therefore give normal values unless a co-oximeter
is also used to determine blood oxygen
content are both decreased. Administration of high
is not effective in greatly increasing the arterial oxygen
content (except possibly in carbon monoxide poisoning).
Hypoperfusion hypoxia (sometimes called stagnant hypoxia) results from low blood flow. This can occur either locally, in a particular vascular bed, or systemically, in the case of a low cardiac output. The alveolar
and the arterial
content may be normal, but the reduced oxygen
delivery to the tissues may result in tissue hypoxia. Venous
content are low. Raising the
is of little value in hypoperfusion hypoxia (unless it directly increases the perfusion) because the blood flowing to the tissues is already oxygenated normally.
Histotoxic hypoxia refers to a poisoning of the cellular machinery that uses oxygen to produce energy. Cyanide, for example, binds to cytochrome oxidase in the respiratory chain and effectively blocks oxidative phosphorylation. Alveolar
content may be normal (or even elevated
because low doses of cyanide increase ventilation by stimulating the arterial chemoreceptors). Venous
content are elevated because oxygen
is not utilized.
Tissue edema or fibrosis may result in impaired diffusion of oxygen from the blood to the tissues. It is also conceivable that the delivery of oxygen to a tissue is completely normal, but the tissue’s metabolic demands still exceed the supply and tissue hypoxia could result. This is known as overutilization hypoxia.
Hypoxia can result in reversible tissue injury or even tissue death. The outcome of a hypoxic episode depends on whether the tissue hypoxia is generalized or localized, on how severe the hypoxia is, on the rate of development of the hypoxia (see Chapter 11), and on the duration of the hypoxia. Different cell types have different susceptibilities to hypoxia; unfortunately, brain cells and heart cells are the most susceptible.