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Cyanosis is the change of body tissue color to a bluish-purple hue as a result of having decreased amounts of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Body tissues that show cyanosis are usually in locations where the skin is thinner, including the mucous membranes, lips, nail beds, and ear lobes. Some medications containing amiodarone or silver, Mongolian spots, large birth marks, and the consumption of food products with blue or purple dyes can also result in the bluish skin tissue discoloration and may be mistaken for cyanosis. Cyanosis is further classified into central cyanosis vs. peripheral cyanosis.


Pathophysiology

The mechanism behind cyanosis is different depending on whether it is central or peripheral.


Central cyanosis

Central cyanosis is caused by a decrease in arterial oxygen saturation (SaO2) and begins to show once the concentration of deoxyhemoglobin in the blood reaches a concentration of ≥ 5.0 g/dL (≥ 3.1 mmol/L or oxygen saturation of ≤ 85 %). Causes of central cyanosis are discussed
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.


Peripheral cyanosis

Peripheral cyanosis happens when there is increased concentration of deoxyhemoglobin on the venous side of the peripheral circulation. In other words, cyanosis is dependent on the concentration of deoxyhemoglobin. Patients with severe
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
may appear normal despite higher than normal concentrations of deoxyhemoglobin. On the other hand, patients with increased amounts of red blood cells (e.g. polycythemia vera) can appear cyanotic even with lower concentrations of deoxyhemoglobin.


Causes


Central cyanosis

Central cyanosis is often due to a circulatory or ventilatory problem that leads to poor blood oxygenation in the lungs. It develops when arterial oxygen saturation drops below 85% or 75%. Acute cyanosis can be a result of asphyxiation or choking and is one of the definite signs that ventilation is being blocked. Central cyanosis may be due to the following causes: #
Central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
(impairing normal ventilation): #*
Intracranial hemorrhage Intracranial hemorrhage (ICH), also known as intracranial bleed, is bleeding within the skull. Subtypes are intracerebral bleeds (intraventricular bleeds and intraparenchymal bleeds), subarachnoid bleeds, epidural bleeds, and subdural blee ...
#*
Drug overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.
(e.g. heroin) #* Generalized tonic–clonic seizure (GTCS) #
Respiratory system The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies g ...
: #*
Pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severit ...
#* Bronchiolitis #* Bronchospasm (e.g.
asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
) #* Pulmonary hypertension #* Pulmonary embolism #* Hypoventilation #*
Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...
, or COPD ( emphysema) #
Cardiovascular system The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
: #* Congenital heart disease (e.g. Tetralogy of Fallot, right to left shunts in heart or great vessels) #*
Heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
#* Valvular heart disease #*
Myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...
#
Hemoglobinopathies Hemoglobinopathy is the medical term for a group of inherited blood disorders and diseases that primarily affect red blood cells. They are single-gene disorders and, in most cases, they are inherited as autosomal co-dominant traits. There are two ...
: #*
Methemoglobinemia Methemoglobinemia, or methaemoglobinaemia, is a condition of elevated methemoglobin in the blood. Symptoms may include headache, dizziness, shortness of breath, nausea, poor muscle coordination, and blue-colored skin (cyanosis). Complications ...
#* Sulfhemoglobinemia #*
Polycythemia Polycythemia (also known as polycythaemia) is a laboratory finding in which the hematocrit (the volume percentage of red blood cells in the blood) and/or hemoglobin concentration are increased in the blood. Polycythemia is sometimes called e ...
#* Congenital cyanosis (HbM Boston) arises from a
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...
in the α-codon which results in a change of
primary sequence Biomolecular structure is the intricate folded, three-dimensional shape that is formed by a molecule of protein, DNA, or RNA, and that is important to its function. The structure of these molecules may be considered at any of several length ...
, H → Y.
Tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...
stabilises the Fe(III) form ( oxyhaemoglobin) creating a permanent T-state of Hb. # Others: #* High
altitude Altitude or height (also sometimes known as depth) is a distance measurement, usually in the vertical or "up" direction, between a reference datum and a point or object. The exact definition and reference datum varies according to the context ...
, cyanosis may develop in ascents to altitudes >2400 m. #*
Hypothermia Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe ...
#*
Frostbite Frostbite is a skin injury that occurs when exposed to extreme low temperatures, causing the freezing of the skin or other tissues, commonly affecting the fingers, toes, nose, ears, cheeks and chin areas. Most often, frostbite occurs in t ...
#* Obstructive sleep apnea


Peripheral cyanosis

Peripheral cyanosis is the blue tint in fingers or extremities, due to an inadequate or obstructed circulation. The blood reaching the extremities is not oxygen-rich and when viewed through the skin a combination of factors can lead to the appearance of a blue color. All factors contributing to central cyanosis can also cause peripheral symptoms to appear but peripheral cyanosis can be observed in the absence of heart or lung failures. Small blood vessels may be restricted and can be treated by increasing the normal oxygenation level of the blood. Peripheral cyanosis may be due to the following causes: * All common causes of central cyanosis * Reduced cardiac output (e.g.
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
or hypovolemia) * Cold exposure * Chronic obstructive pulmonary disease (COPD) *Arterial obstruction (e.g. peripheral vascular disease,
Raynaud phenomenon Raynaud syndrome, also known as Raynaud's phenomenon, eponymously named after the physician Auguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862, is a medical condition in which the spasm of small arteries cau ...
) * Venous obstruction (e.g. deep vein thrombosis)


Differential cyanosis

Differential cyanosis is the bluish coloration of the lower but not the upper extremity and the head. This is seen in patients with a
patent ductus arteriosus ''Patent ductus arteriosus'' (PDA) is a medical condition in which the ''ductus arteriosus'' fails to close after birth: this allows a portion of oxygenated blood from the left heart to flow back to the lungs by flowing from the aorta, which has ...
. Patients with a large ductus develop progressive pulmonary vascular disease, and
pressure overload Pressure overload refers to the pathological state of cardiac muscle in which it has to contract while experiencing an excessive afterload. Pressure overload may affect any of the four chambers of the heart, though the term is most commonly appli ...
of the right ventricle occurs. As soon as pulmonary pressure exceeds aortic pressure, shunt reversal (right-to-left shunt) occurs. The upper extremity remains pink because deoxygenated blood flows through the patent duct and directly into the descending aorta while sparing the
brachiocephalic trunk The brachiocephalic artery (or brachiocephalic trunk or innominate artery) is an artery of the mediastinum that supplies blood to the right arm and the head and neck. It is the first branch of the aortic arch. Soon after it emerges, the brachi ...
,
left common carotid In anatomy, the left and right common carotid arteries (carotids) (Entry "carotid"
in
left subclavian arteries.


Evaluation

A detailed history and physical examination (particularly focusing on the cardiopulmonary system) can guide further management and help determine the choice of testing to be performed. Tests that can be performed include pulse oximetry, arterial blood gas, complete blood count, methemoglobin level, electrocardiogram, echocardiogram, X-Ray, CT scan, cardiac catheterization, and hemoglobin electrophoresis. In newborns, peripheral cyanosis typically presents in the distal extremities, circumoral, and periorbital areas. Of note, mucous membranes remain pink in peripheral cyanosis as compared to central cyanosis where the mucous membranes are cyanotic. It is important to note that skin pigmentation and hemoglobin concentration can affect the evaluation of cyanosis. Cyanosis may be more difficult to detect on people with darker skin pigmentation. However, cyanosis can still be diagnosed with careful examination of the typical body areas such as nail beds, tongue, and mucous membranes where the skin is thinner and more vascular. As mentioned above, patients with severe anemia may appear normal despite higher than normal concentrations of deoxyhemoglobin. Signs of severe anemia may include pale mucosa (lips, eyelids, and gums), fatigue, lightheadedness, and irregular heartbeats.


Management

Cyanosis is a symptom rather than a disease itself, so management should be focused on treating the underlying cause. If it is an emergency, management should always begin with securing the airway, breathing, and circulation. In patients with significant respiratory distress, supplemental oxygen (in the form of nasal canula or continuous positive airway pressure depending on severity) should be given immediately. If the methemoglobin levels are positive for methemoglobinemia, first-line treatment is to administer methylene blue.


History

The name ''cyanosis'' literally means ''the blue disease'' or ''the blue condition''. It is derived from the color cyan, which comes from ''cyanós (κυανός)'', the Greek word for ''blue''. It is postulated by Dr. Christen Lundsgaard that cyanosis was first described in 1749 by
Jean-Baptiste de Sénac Jean-Baptiste de Sénac (1693–1770) was a French physician was born in the district of Lombez in Gascony, France. Early life and education Details of his early life are sketchy, however, it is generally thought that he studied medicine at the ...
, a French physician who served King
Louis XV Louis XV (15 February 1710 – 10 May 1774), known as Louis the Beloved (french: le Bien-Aimé), was King of France from 1 September 1715 until his death in 1774. He succeeded his great-grandfather Louis XIV at the age of five. Until he reache ...
. De Sénac concluded from an autopsy that cyanosis was caused by a heart defect that led to the mixture of arterial and venous blood circulation. But it was not until 1919, when Dr. Lundsgaard was able to derive the concentration of deoxyhemoglobin (''8 volumes per cent'') that could cause cyanosis.


See also

* Acrocyanosis * Blue baby syndrome * Raynaud's phenomenon *
Blue Fugates The Fugates, a family living in the hills of Kentucky starting in the 19th century, were commonly known as the "Blue Fugates" or the "Blue People of Kentucky". They are known for being carriers of a genetic trait that led to the blood disorder m ...


References


External links

{{Respiratory system symptoms and signs Medical signs Symptoms and signs: Skin and subcutaneous tissue