What is cyanosis?

Causes and Symptoms

Cyanosis, a dark blue discoloration of the skin
and nail beds, is a sign of a disorder, not a disease in itself, and it may have several causes. It is also not a symptom sensed by a patient but a physical finding. To appear, cyanosis requires a concentration in arterial blood of 4 to 5 grams per deciliter of reduced hemoglobin. Anemic patients may not show cyanosis even though their hemoglobin saturations are low. Its presence indicates one or more of the following: inadequate oxygenation of arterial blood (a decrease of oxygen saturation to 85 percent or less), the presence of a normal constituent (methemoglobin) in increased concentration, or the presence of an abnormal constituent (sulfhemoglobin).

Inadequate oxygenation of normally circulating blood. The obstruction of large airways (the tracheobronchial system) can occur from external compression or the aspiration of solid or semisolid materials (foodstuffs, particularly ground meat). Laryngospasm may be a factor. The aspiration of aqueous fluids, as in drowning in freshwater, can fill the alveoli and decrease or prevent the contact of inspired air with the blood in the pulmonary capillaries. Freshwater can pass rapidly into the blood and eventually free the alveoli for gas exchanges. Drowning in seawater is usually accompanied by marked laryngospasm. If the hypertonic seawater reaches the alveoli, then water will cross from the blood into the alveoli and produce even more fluid and froth in the lungs (pulmonary
edema).

The inhalation of certain toxic agents, available industrially or used in warfare, can damage the alveoli and the pulmonary capillaries and produce pulmonary edema. Typical agents are chlorine and phosgene. Smoke inhalation is another possible cause of lung damage. Pulmonary edema from cardiac failure can occur as a result of increased pressure in the alveolar capillaries. Respiratory distress syndrome, or noncardiogenic pulmonary edema, occurs probably as the end result of a variety of initiators (shock, sepsis) culminating in the production of damaging free radicals.

Pharmacologically active agents such as heroin and morphine injected intravenously, as by drug abusers, can produce fulminating pulmonary edema extremely rapidly, possibly as the result of alpha-adrenergic discharge. Substances such as ethchlorvynol can also produce this condition if injected intravenously, although they may be innocuous if taken orally.

Pulmonary infections such as pneumococcal pneumonia can cause edema through the perfusion of alveoli that are filled with fluid, that is, nonventilated. This condition is essentially venous admixture, and it can occur when three or more lobes of the lungs are involved. Chronic obstructive pulmonary disease (COPD) can produce cyanosis because of destruction of lung tissue (emphysema) and because of obstruction to air movement. Oxygenation is incomplete, and cyanosis is a common feature of advanced disease.

Low oxygen concentration in ambient atmosphere occurs with ascent to high altitudes. In certain caves, oxygen may be displaced by carbon dioxide. Incorrect gas mixtures may be administered to patients under anesthesia or on artificial respiration. The oxygen of the ambient atmosphere may be decreased in closed environments such as submarines. Polycythemia (increased numbers of red blood cells per unit volume of blood) may occur as a result of chronic exposure to high altitudes or as a spontaneous problem (polycythemia vera). The oxygen content of the blood may be normal or high, but the unoxygenated portion may be increased so that a ruddy cyanosis may be present.

Admixture of venous and arterial blood flows.
Patent ductus arteriosus
is a heart defect that produces blue baby syndrome. It offers a classic example of the direct entry of venous blood into the arterial system, as the lungs are partially bypassed. Other cardiopulmonary abnormalities, such as right-to-left shunts, can also produce cyanosis.

Localized circulatory problems. Frostbite and Raynaud’s phenomenon are examples of localized occurrence of cyanosis. In these conditions, vascular changes limit blood flow, leading to congestion and unsaturation.

Increased concentrations of methemoglobin or sulfhemoglobin. Naturally occurring methemoglobin is present at about the 1 percent level in blood. From 0.5 to 3 percent of the total hemoglobin is oxidized each day and returned to deoxyhemoglobin through enzymatic reductase activity. In congenital forms of methemoglobinemia, cyanosis appears when the concentration of methemoglobin approaches 10 percent of the total (about l.4 grams per deciliter).

Acquired increased concentration can be caused by a variety of agents (such as sodium perchorate, Paraquat, nitroglycerine, and inhaled butyl and isobutyl nitrites) by oxidizing hemoglobin to methemoglobin through the formation of free radicals. Nitrates, absorbed by mouth, are transformed into nitrites in the gut and also produce methemoglobin. Sulfhemoglobin can also be formed and produces cyanosis at concentrations of 0.5 gram per deciliter.

Treatment and Therapy

Treatment is directed not to the cyanosis itself but to the underlying problem. Oxygen administration is crucial in many but not all cases.

For airway obstruction, the Heimlich maneuver may be lifesaving, as may an emergency tracheostomy. Drowning requires artificial respiration, positioning of the body so that drainage of fluid from the lungs is facilitated, and administration of oxygen, if available. Full cardiopulmonary resuscitation (CPR) may be needed. Pulmonary edema from cardiac failure or respiratory distress syndrome calls into use a variety of approaches, but oxygen is almost always provided. Artificial respiration and oxygen are usually required in heroin, morphine, and ethchlorvynol pulmonary edema. COPD and emphysema are chronic, progressive disorders in which oxygen, bronchodilators, antibiotics, steroids, and surgical interventions (lung volume reduction) may be used. In methemoglobinemia, the congenital forms may not require any treatment. If the cyanosis is the result of exposure to nitrites and other potential oxidants, then methylene blue is usually effective.

Perspective and Prospects

Cyanosis has been recognized for centuries as a sign or indicator of an underlying problem. The focus of investigations has been on identifying these problems. The properties of the hemoglobins have been investigated by physiologists and hematologists, leading to an understanding of their structures and functions. Surgical correction of the vascular abnormalities of so-called blue babies by Alfred Blalock and Helen Taussig led to the development of the field of cardiovascular
surgery. Molecular biology has provided knowledge of the enzymatic and genetic factors involved in the development of methemoglobinemia.

Bibliography

A.D.A.M. Medical Encyclopedia. "Cyanotic Heart Disease." MedlinePlus, November 21, 2011.

A.D.A.M. Medical Encyclopedia. "Skin Discoloration—Bluish." MedlinePlus, May 25, 2011.

Dickerson, Richard E., and Irving Geis. Hemoglobin: Structure, Function, Evolution, and Pathology. Menlo Park, Calif.: Benjamin/Cummings, 1983.

Heart Information Center. "Cyanosis." Texas Heart Institute, August 2012.

Icon Health. Cyanosis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004.

Nagel, Ronald L., ed. Hemoglobin Disorders: Molecular Methods and Protocols. Totowa, N.J.: Humana Press, 2003.

Weibel, Ewald R. The Pathway for Oxygen: Structure and Function in the Mammalian Respiratory System. Cambridge, Mass.: Harvard University Press, 1984.