Cyanosis is a bluish discoloration of the nails, skin and/or mucosa due to the increased amount of reduced hemoglobin (Hb). An amount of more than 5 gm% in capillary blood is required for these symptoms to manifest.
Unreduced hemoglobin is the form of hemoglobin in red blood cells after the oxygen of oxyhemoglobin is released in the tissues. It is also called unoxygenated hemoglobin.
High levels of deoxygenated hemoglobin within the superficial vessels [dermal capillaries and subpapillary venous plexus] cause this bluish appearance.
The dermal thickness, skin pigmentation, and state of the cutaneous capillaries determine if the bluishness is visible or not.
Therefore, cyanosis is best seen where the overlying epidermis is thin and the area has a rich network of the vessel blood vessel. Lips, the tip of nose, cheeks, ears, and oral mucous membranes are the areas where cyanosis would be better appreciated.
The term is derived from the Greek word kuaneos meaning dark blue.
Because, approximately 5 g/dL of unoxygenated hemoglobin in the capillaries is required before the bluishness could be appreciated clinically, the patients who suffer from anemia may be hypoxemic without showing any cyanosis.
Mechanism of Generation of Cyanosis
In an adult, on an average, there is 15 gm % of hemoglobin, 95% of which is saturated with oxygen and only 5% i.e. 0.75 gm % is reduced. Hence, in capillaries, a mean of the two i.e. only 2-3 gm% is reduced hemoglobin and the color of the skin and mucous membranes is pink.
When the amount of reduced hemoglobin exceeds 5 gm% in the capillaries, the blood appears dark, giving the tissues a bluish hue.
This requirement of 5 g/dL of reduced or deoxygenated hemoglobin in the capillaries translates into a reduced hemoglobin content of 3.4 g/dL in arterial blood.
Therefore, patients with higher hemoglobin levels manifest cyanosis earlier [at higher oxygen saturation] than those with lower hemoglobin or anemic.
Oxygen saturation (SaO2) is a measurement of the percentage of how much hemoglobin is saturated with oxygen.
Let us understand this by example.
A patient with Hb 15 g/dL would not generate 5 g/dL of reduced Hb in the capillaries until the SaO2 level reached about 79% .
But when Hb is 9 g/dl, the threshold SaO2 level for manifesting cyanosis is lowered to about 65%. At this level of hypoxemia, other manifestations of hypoxemia like respiratory symptoms and mental status changes are usually seen apart from cyanosis.
And at further lower levels of Hb, the patient may die of hypoxemia before cyanosis became evident.
Therefore, an anemic person would be in danger of developing hypoxemia symptoms without developing cyanosis.
Types of Cyanosis
- Cyanosis due to abnormal pigment
Central cyanosis refers to generalized cyanosis apparent at the lips, tongue, and sublingual tissues in addition to hands and feet. In fact, it would be visible in lips, tongue etc. areas earlier. There is a systemic cause causing hypoxemia [low levels of oxygen] for central cyanosis to occur. This is more dangerous type than peripheral.
Peripheral cyanosis causes bluish discoloration of the hands and feet and occurs with vasoconstriction and diminished peripheral blood flow.
Mixed cyanosis is said to occur when there are both central and peripheral causes.
Cyanosis due to abnormal pigmentation occurs when the abnormal pigment in the blood due to drug intake or other reason imparts the abnormal color. Technically, these would be a type of central cyanosis.
Causes of Cyanosis
Reduced arterial oxygen saturation
- High altitude
- Impaired lung function due to various diseases leading to alveolar hypoventilation, ventilation-perfusion mismatch and/or impaired oxygen diffusion
- Severe pneumonia
- Pulmonary embolism
- Chronic obstructive lung disease
- Anatomical shunts causing venous blood being mixed with arterial
- Cyanotic Congenital heart disease like Fallot’s tetrad
- Pulmonary arteriovenous malformations
- Multiple small intrapulmonary shunts
- Hemoglobin with low oxygen affinity
- Carboxyhemoglobinemia (chocolate cyanosis)
All conditions that cause central cyanosis are also the causes of peripheral cyanosis.
Other causes are
- Reduced cardiac output
- Heart failure
- Exposure to cold
- Hypovolemia leading to the redistribution of blood flow from extremities
- Arterial or venous obstruction
- Acute left ventricular failure
- Mitral stenosis (left atrial failure and peripheral vasoconstriction)
Cyanosis Due to Abnormal Pigments
Normal hemoglobin has iron in ferrous form. In methemoglobinemia, iron is in the ferric form. Methemoglobin is designated as MHb.
Substances like nitrates (well water ingestion), sulfonamide or aniline dyes oxidize Hb to MHb, but this is immediately reduced back to Hb by methemoglobin reductase I or diaphorase I.
If there is a deficiency of diaphorase I MHb circulates in the blood causing cyanosis.
Sulfhemoglobin (SHb) is an abnormal sulfur-containing a substance which is not normally present in the blood but is formed by the toxic action of drugs and chemicals like sulphonamides, phenacetin, and acetanilide.
SHb forms an irreversible change in the Hb pigment that has no capacity to carry oxygen.
It is the term used for conditions where the cyanosis is present in certain parts and absent in others.
- Only of lower limbs- Patent ductus arteriosus (PDA) with reversal of shunt.
- Only of upper limbs- PDA with reversal of shunt in transposition of great vessels.
- Cyanosis of left upper and both lower limbs- PDA with reversal of shunt and pre-ductal coarctation of the aorta.
Pseudocyanosis is the term used when there is a bluish tinge to the skin and/or mucous membranes but there is no hypoxemia or peripheral vasoconstriction.
It should be considered when there is no heart or lung disease and the skin does not blanch under pressure.
Metals like silver, lead or drugs like phenothiazines, amiodarone, chloroquine hydrochloride are usually responsible for this condition.
Conditions Where Cyanosis Does Not Occur
- In severe anemia where hemoglobin is less than 5 gm%, even if all the hemoglobin is reduced in the capillaries, it will be less than the critical level of 5 gm% and cyanosis does not occur.
- In carbon monoxide poisoning, carboxy-hemoglobin prevents reduction of oxyhemoglobin and the former has a cherry red color. Hence there is no cyanosis.
Diagnosis of Cyanosis
Clinical assessment of hypoxemia is not reliable. Therefore a patient with cyanosis should be thoroughly investigated.
- Arterial Blood Gases
- Complete Blood Count – Hemoglobin level is increased with chronic cyanosis. White cell count is increased in pneumonia and pulmonary embolism.
- ECG to rule out cardiac abnormalities.
- Chest X-ray to rule out pneumonia, pulmonary infarction, cardiac failure.
- Ventilation-perfusion scan or pulmonary angiography to rule out pulmonary causes
- Echocardiography to look for cardiac defects.
- Hemoglobin spectroscopy to look for methaemoglobinaemia, sulfhaemoglobinaemia.
- Digital subtraction angiography to rule out acute arterial occlusion.
- Duplex Doppler or venography to find acute venous occlusion.
Cyanosis is a sign or manifestation of an underlying cause. So the underlying cause should be treated. Oxygen for patients in hypoxia is indicated.
- Martin L, Khalil H. How much reduced hemoglobin is necessary to generate central cyanosis?. Chest. 1990 Jan. 97(1):182-5.
- Bradberry SM. Occupational methaemoglobinaemia. Mechanisms of production, features, diagnosis and management including the use of methylene blue. Toxicol Rev. 2003. 22(1):13-27.