Cyanosis

Jeanne Lofstedt • W. David Wilson • Jeffrey Lakritz

■ Definition Cyanosis is the bluish discoloration of skin, conjunctivae, and visible mucous membranes that results from an increase in the absolute amount of reduced hemoglobin in the blood.⁷⁶

■ Pathophysiology Oxygen is carried in blood in two forms, dissolved and in combination with hemoglobin (Hb).

The Bohr effect describes the ability of hemoglobin to bind to a number of different ligands (CO₂, H⁺, and 2,3- diphosphoglycerate [2,3-DPG]), which results in modification of hemoglobin’s affinity for oxygen. When tissue pH decreases, hemoglobin acts as a buffer and binds excess H⁺, which decreases its affinity for oxygen. When the CO₂ concentration increases, some CO₂ is converted to bicarbonate and the remainder is bound to hemoglobin to form carbaminohemoglobin; this also decreases the affinity of hemoglobin for oxygen. Therefore the net effect of a decreased blood pH and increased blood CO₂ concentration is unloading of oxygen to the tissues. Conversely, as the CO₂ concentration in the pulmonary capillaries decreases and blood pH rises, the affinity of hemoglobin for oxygen increases; thus the net effect of elevated blood pH in pulmonary capillaries is increased uptake of oxygen by hemoglobin.

The affinity of hemoglobin for oxygen is also influenced by the concentration of 2,3-DPG, a metabolic intermediate of the Rapoport-Luebering shunt involved in erythrocyte glycolysis. An increase in the 2,3-DPG concentration may occur in association with chronic hypoxemia (high altitude, chronic lung disease), anemia, chronic alkalosis, phosphate retention, and red cell pyruvate kinase deficiency. When the 2,3-DPG concentration is increased, the affinity of hemoglobin for oxygen is decreased, resulting in improved unloading of oxygen to peripheral tissues. Conversely, a decreased 2,3-DPG level results in an increased affinity of hemoglobin for oxygen. A decrease in the 2,3-DPG concentration may occur in stored blood, in association with chronic acidosis, and with hypophosphatemia.

Cyanosis develops when the oxygen saturation of hemoglobin is below 80%. With a normal oxygen-hemoglobin dissociation curve, the PaO₂ is usually below 40 mm Hg before cyanosis is noted in the patient.⁷⁷ The hemoglobin concentration of blood must be near normal for cyanosis to be clinically evident⁷⁸; therefore patients with severe anemia and concomitant marked arterial oxygen desaturation may not show cyanosis. In contrast, patients with marked polycythemia may be cyanotic at higher arterial oxygen saturation than patients with normal hematocrit values.

Classification

Cyanosis can be classified as either peripheral or central.

PERIPHERAL CYANOSIS. Peripheral cyanosis is caused by slowing of blood flow to an area, resulting in abnormally increased extraction of oxygen from normally saturated arterial blood. Decreased blood flow through the peripheral capillary bed may be caused by vasoconstriction of superficial vessels,

■ TABLE 5.1

Pathophysiologic Classification of Central Cyanosis and Examples of Associated Conditions

obstruction of arteries or veins, or low cardiac output.

CENTRAL CYANOSIS. Central cyanosis results from either inadequate oxygenation of arterial blood or the presence of an abnormal hemoglobin derivative and is characterized by cyanosis of mucous membranes (Table 5.1). Causes of inad­equate oxygenation of arterial blood are respiratory disease or congenital cardiac anomalies causing right-to-left shunting (Boxes 5.16 and 5.17). Acquired abnormalities of hemoglobin function can be induced by a number of chemicals. Exposure to these chemicals results in the formation of methemoglobin or sulfhemoglobin, neither of which is capable of binding oxygen. Nitrites and nitrates are powerful reducing agents that produce methemoglobinemia by directly oxidizing hemoglobin to methemoglobin. Nitrate poisoning is most commonly associated with the incorporation of nitrate-accumulating plants (e.g., pigweed [Amaranthus retroflexus], lamb’s quarters [Chenopodium album], and mintweed [Salvia reflexa]) in livestock forage. Nitrate intoxication is usually seen only in ruminants because rumen microorganisms reduce nitrate to the more toxic nitrite ion. Congenital defects in hemoglobin function have been reported in humans and may occur in large domestic animals. Examples of such defects are nicotinamide adenine dinucleotide methemoglobin reductase deficiency and familial methemoglobinemia.