Expert Lecture

Hypoxia and Cyanosis

The fundamental purpose of the cardiorespiratory system is:

to deliver O2 (and substrates) to the cells to remove CO2 (and other metabolic products)

from them.

Proper maintenance of this function depends on intact cardiovascular and respiratory systems and a supply of inspired gas containing adequate O2.

An abnormally reduced O2 supply to tissue.

When hypoxia occurs consequent to

respiratory failure, PaO2 declines, PaCO2 usually rises, and the hemoglobin-oxygen (Hb-O2) dissociation

curve is displaced to the right, with greater quantities of O2 released at any level of tissue PO2.

Fig. 1. Oxygen dissociation curves (ODCs) for human hemoglobin (Hb) at 3 different pH levels

Leow, M. K.-S. Advan. Physiol. Edu. 31: 198-201 2007; doi:10.1152/advan.00012.2007

Copyright 2007 American Physiological Society

1. Hypoxic hypoxia : an insufficient O2 supply reaches the blood due, for example, to decreased atmospheric PO2 at high altitudes , reduced alveolar ventilation, or impaired alveolar gas exchange. 2. Anemic hypoxia : reduced O2-carrying capacity of blood, e.g., due to decreased total Hb in iron deficiency anemia. 3. Stagnant or ischemic hypoxia : insufficient O2 reaches the tissue due to reduced blood flow.

4. Hypoxia can also occur when the diffusion distance is increased due to tissue thickening without a corresponding increase in the number of blood capillaries. 5. Histotoxic or cytotoxic hypoxia occurs due to impaired utilization of O2 by the tissues despite a sufficient supply of O2 in the mitochondria, as observed in cyanide poisoning. Cyanide (HCN) blocks oxidative cellular metabolism by inhibiting cytochromoxidase.

Anemic hypoxia Carbon monoxide intoxication Respiratory hypoxia Hypoxia secondary to right-to-left extrapulmonary shunting Circulatory hypoxia Specific organ hypoxia Increased oxygen requirements Improper oxygen utilization

A reduction in the hemoglobin concentration of the blood is attended by a corresponding decline in the O2-carrying capacity of the blood. The PaO2 is normal; but as a consequence of the reduction of the hemoglobin concentration, the absolute quantity of O2 transported per unit volume of blood is diminished.

Hemoglobin that is combined with carbon monoxide (carboxyhemoglobin, COHb) is unavailable for O2 transport. In addition, the presence of COHb shifts the HbO2 dissociation curve to the left so that O2 is unloaded only at lower tensions. By such formation of COHb, a given degree of reduction in O2-carrying power produces a far greater degree of tissue hypoxia than the equivalent reduction in hemoglobin due to simple anemia.

Arterial unsaturation is a common finding in advanced pulmonary disease. The most common cause of respiratory hypoxia :
ventilation-perfusion mismatch, which results from

perfusion of poorly ventilated alveoli. hypoventilation,

elevation of PaCO2 .

shunting of blood across the lung from right to left by

perfusion of nonventilated portions of the lung, as in pulmonary atelectasis or through arteriovenous connections in the lung

As one ascends rapidly to 3000 m (approximately 10,000 ft), the alveolar PO2 declines to about 60 mmHg, and impaired memory and other cerebral symptoms of hypoxia may develop. At higher altitudes, arterial saturation declines rapidly and symptoms become more serious; and at 5000 m (approximately 15,000 ft) unacclimatized individuals usually cease to be able to function normally.

From a physiologic viewpoint, this cause of hypoxia resembles intra-pulmonary right-toleft shunting but is caused by congenital cardiac malformations such as tetralogy of Fallot, transposition of the great arteries, and Eisenmengers syndrome. As in pulmonary right-to-left shunting, the PaO2 cannot be restored to normal with inspiration of 100% O2.

Normal heart

Tetralogy of Fallot

Normal heart

Transposition of the great arteries with Taussig Bing anomaly

As in anemic hypoxia, the PaO2 is usually normal, but venous and tissue PO2 values are reduced as a consequence of reduced tissue perfusion and greater tissue O2 extraction. Generalized circulatory hypoxia occurs in heart failure and in most forms of shock.

Decreased perfusion of any organ resulting in localized circulatory hypoxia may occur secondary to organic arterial obstruction, as in atherosclerosis, or as a consequence of vasoconstriction, as observed in Raynauds phenomenon. Localized hypoxia may also result from venous obstruction and the resultant congestion and reduced arterial inflow.

Edema, which increases the distance through which O2 diffuses before it reaches cells, also can cause localized hypoxia. In an attempt to maintain adequate perfusion to more vital organs, vasoconstriction may reduce perfusion in the limbs and skin, causing hypoxia of these regions in patients with heart failure or hypovolemic shock.

If the O2 consumption of the tissues without a corresponding increase in perfusion, tissue hypoxia ensues and the PO2 in venous blood . Ordinary the 2 clinical picture of patients with hypoxia due to an elevated metabolic rate is quite different from that in other types of hypoxia;
the skin is warm and flushed, owing to increased

cutaneous blood flow that dissipates the excessive heat produced, cyanosis is usually absent.

Exercise is a classic example of increased tissue O2 requirements.

(1) increasing the cardiac output and ventilation and, thus, O2 delivery to the tissues; (2) preferentially directing the blood to the exercising muscles by changing vascular resistances in the circulatory beds of exercising tissues, directly and/or reflexly; (3) increasing O2 extraction from the delivered blood and widening the arteriovenous O2 difference; (4) reducing the pH of the tissues and capillary blood, shifting the Hb-O2 curve to the right and unloading more O2 from hemoglobin.

If the capacity of these mechanisms is exceeded, then hypoxia, especially of the exercising muscles, will result.

Cyanide and several other similarly acting poisons cause cellular hypoxia. The tissues are unable to utilize O2, and as a consequence, the venous blood tends to have a high O2 tension. This condition has been termed histotoxic hypoxia

An important component of the respiratory response to hypoxia originates in special chemosensitive cells in the carotid and aortic bodies and in the respiratory center in the brainstem. The stimulation of these cells by hypoxia increases ventilation, with a loss of CO2, and can lead to respiratory alkalosis.

When combined with the metabolic acidosis resulting from the production of lactic acid, the serum bicarbonate level declines. With the reduction of PaO2, cerebrovascular resistance decreases and cerebral blood flow increases in an attempt to maintain O2 delivery to the brain. However, when the reduction of PaO2 is accompanied by hyperventilation and a reduction of PaCO2, cerebrovascular resistance rises, cerebral blood flow falls, and hypoxia is intensified.

The diffuse, systemic vasodilation that occurs in generalized hypoxia raises the cardiac output. In patients with underlying heart disease, the requirements of peripheral tissues for an increase of cardiac output with hypoxia may precipitate congestive heart failure. In patients with ischemic heart disease, a reduced PaO2 may intensify myocardial ischemia and further impair left ventricular function.

One of the important mechanisms of compensation for chronic hypoxia is an increase in the hemoglobin concentration and in the number of red blood cells in the circulating blood, i.e., the development of polycythemia secondary to erythropoietin production.

Definition: chronic hypoxemia secondary to prolonged residence at a high altitude (>13,000 ft, 4200 m) It is characterized by :

a blunted respiratory drive, reduced ventilation, erythrocytosis, cyanosis, weakness, right ventricular enlargement secondary to pulmonary hypertension stupor.

Cyanosis is a bluish discoloration of the skin,lips, nails, etc. due to excessive arterial deoxyhemoglobin ( > 50 g/L). Reduced hemoglobin =

saturation X [Hemoglobin] 100

Cyanosis is a sign of hypoxia in individuals with normal or only moderately reduced total Hb levels. When total Hb is extremely low, O2 deficiencies (anemic hypoxia) can be lifethreatening, even in the absence of cyanosis. Cyanosis can occur in absence of significant hypoxia when the Hb level is elevated.

Cyanosis refers to a bluish color of the skin and mucous membranes resulting from an increased quantity of reduced hemoglobin, or of hemoglobin derivatives, in the small blood vessels of those areas. It is usually most marked in the lips, nail beds, ears, and malar eminences.

Cyanosis, especially if developed recently, is more commonly detected by a family member than the patient. The florid skin characteristic of polycythemia vera must be distinguished from the true cyanosis discussed here. A cherry-colored flush, rather than cyanosis, is caused by COHb.

Cyanosis becomes apparent when the concentration of reduced hemoglobin in capillary blood exceeds 40 g/L (4 g/dL). It is the absolute, rather than the relative, quantity of reduced hemoglobin that is important in producing cyanosis. Cyanosis is also observed when nonfunctional hemoglobin, such as methemoglobin or sulfhemoglobin , is present in blood.

Central type, the SaO2 is reduced or an abnormal hemoglobin derivative is present, and the mucous membranes and skin are both affected. Peripheral cyanosis is due to a slowing of blood flow and abnormally great extraction of O2 from normally saturated arterial blood. It results from vasoconstriction and diminished peripheral blood flow, such as occurs in cold exposure, shock, congestive failure, and peripheral vascular disease.

1. The time of onset of cyanosis. Cyanosis present since birth or infancy is usually due to congenital heart disease. 2. Central and peripheral cyanosis must be differentiated. Evidence of disorders of the respiratory or cardiovascular systems are helpful. Massage or gentle warming of a cyanotic extremity will increase peripheral blood flow and abolish peripheral, but not central, cyanosis.

3. The presence or absence of clubbing of the digits should be ascertained. 4. PaO2 and SaO2 should be determined, and in patients with cyanosis in whom the mechanism is obscure, spectroscopic examination of the blood performed to look for abnormal types of hemoglobin (critical in the differential diagnosis of cyanosis).