View source for Cyanosis

{{Short description|Decreased oxygen in the blood}}
{{Redirect|Cyanotic|the band|Cyanotic (band)}}
{{Infobox medical condition (new)
| name = Cyanosis
| synonyms = 
| image = Cynosis.JPG
| caption = Cyanosis of the hand of a patient with [[Hypoxia (medical)|low oxygen saturations]]
| pronounce = 
| field = [[Pulmonology]], [[cardiology]]
| symptoms = [[Hypothermia]], numbness in the area where the cyanosis is, coughing, wheezing, difficulty breathing
| complications = 
| onset = 
| duration = 
| types = Circumoral, central, peripheral
| causes = Airway problems, lung problems, heart problems, exposure to extreme cold
| risks = 
| diagnosis = 
| differential = [[Circumoral cyanosis]], [[peripheral cyanosis]], [[central cyanosis]]
| prevention = Avoid exposure to freezing cold temperatures, limit smoking or [[caffeine]], avoid touching [[cyanide]]
| treatment = 
| medication = [[Antidepressants]], anti-hypertension medication, or if caused by other reasons, [[naloxone hydrochloride]]
| prognosis = 
| frequency = 
| deaths = 
}}
'''Cyanosis''' is the change of  [[Tissue (biology)|tissue]] color to a bluish-purple hue, as a result of decrease in the amount of oxygen bound to the [[hemoglobin]] in the [[red blood cell]]s of the [[capillary bed]].<ref name=":0">{{Citation|last1=Adeyinka|first1=Adebayo|title=Cyanosis|date=2021|url=https://www.ncbi.nlm.nih.gov/books/NBK482247/|work=StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=29489181|access-date=2021-10-28|last2=Kondamudi|first2=Noah P.}}</ref> Cyanosis is apparent usually in the  [[Tissue (biology)|body tissues]] covered with thin [[skin]], including the [[mucous membrane]]s, lips, [[nail beds]], and ear lobes.<ref name=":0"/> Some medications may cause discoloration such as medications containing [[amiodarone]] or [[silver]]. Furthermore, [[mongolian spot]]s, large birthmarks, 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.<ref>{{Cite journal|last=Dereure|first=Olivier|date=2001|title=Drug-Induced Skin Pigmentation: Epidemiology, Diagnosis and Treatment|url=http://link.springer.com/10.2165/00128071-200102040-00006|journal=American Journal of Clinical Dermatology|language=en|volume=2|issue=4|pages=253–262|doi=10.2165/00128071-200102040-00006|pmid=11705252|s2cid=22892985|issn=1175-0561|url-access=subscription}}</ref><ref>{{Cite journal|last1=Conlon|first1=Joseph D|last2=Drolet|first2=Beth A|date=2004|title=Skin lesions in the neonate|url=https://linkinghub.elsevier.com/retrieve/pii/S0031395504000483|journal=Pediatric Clinics of North America|language=en|volume=51|issue=4|pages=863–888|doi=10.1016/j.pcl.2004.03.015|pmid=15275979|url-access=subscription}}</ref>  Appropriate [[physical examination]] and history taking is a crucial part to diagnose cyanosis. Management of cyanosis involves treating the main cause, as cyanosis is not a disease, but rather a [[symptom]].<ref name=":0" />

Cyanosis is further classified into '''central cyanosis''' and '''peripheral cyanosis'''.

== Pathophysiology ==
[[File:Cynosis Illustration.jpg|thumb|upright=1.3|Presentation of cyanosis varies depending on the color of the skin]]
The mechanism behind cyanosis is different depending on whether it is central or peripheral.

=== Central cyanosis ===
Central cyanosis occurs due to decrease in [[arterial oxygen saturation]] (SaO2), and begins to show once the concentration of [[Hemoglobin#Deoxygenated hemoglobin|deoxyhemoglobin]] in the blood reaches a concentration of ≥ 5.0 g/dL (≥ 3.1&nbsp;mmol/L or oxygen saturation of ≤ 85%).<ref>{{cite book|title=Mini Oxford Handbook of Clinical Medicine|edition=7th|page=56}}</ref> This indicates a cardiopulmonary condition.<ref name=":0"/>

Causes of central cyanosis are discussed [[#Central cyanosis 2|below]].

=== 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]] may appear normal despite higher-than-normal concentrations of deoxyhemoglobin. While patients with increased amounts of red blood cells (e.g., [[polycythemia vera]]) can appear cyanotic even with lower concentrations of deoxyhemoglobin.<ref name=":1" /><ref name=":2">{{Cite journal|last1=McMullen|first1=Sarah M.|last2=Patrick|first2=Ward|date=2013-03-01|title=Cyanosis|url=https://www.amjmed.com/article/S0002-9343(12)00904-7/abstract|journal=The American Journal of Medicine|language=English|volume=126|issue=3|pages=210–212|doi=10.1016/j.amjmed.2012.11.004|pmid=23410559|s2cid=244083635 |issn=0002-9343|url-access=subscription}}</ref> [[File:Cyanotic neonate.jpg|thumb|A baby with a heart condition. Note purple nailbeds.]]

== Causes ==

=== Central cyanosis ===
Central cyanosis is often due to a circulatory or [[Respiratory system|ventilatory]] problem that leads to poor blood [[Oxygenation (medical)|oxygenation]] in the [[lung]]s. It develops when arterial oxygen saturation drops below 85% or 75%.<ref name=":1" />

Acute cyanosis can be a result of [[asphyxiation]] or [[choking]] and is one of the definite [[Signs and symptoms|signs]] that ventilation is being blocked.
[[File:Child with measles modified by cyanosis Wellcome L0061496.jpg|thumb|Child with congenital heart disease with central cyanosis that is worsened by [[measles]]. Note the bluish-purple discoloration of the fingernails, lips, eyelids, and nose, along with prominent [[nail clubbing]].]]

Central cyanosis may be due to the following causes:

# [[Central nervous system]] (impairing normal ventilation):<ref name=":1" />
#* [[Intracranial hemorrhage]]
#* [[Drug overdose]] (e.g., [[heroin]])
#* [[Generalized tonic–clonic seizure]] (GTCS)
# [[Respiratory system]]:<ref name=":0"/><ref name=":1" />
#* [[Pneumonia]]
#* [[Bronchiolitis]]
#* [[Bronchospasm]] (e.g., [[asthma]])
#* [[Pulmonary Hypertension|Pulmonary hypertension]]
#* [[Pulmonary embolism]]
#* [[Hypoventilation]]
#* [[Chronic obstructive pulmonary disease]], or COPD ([[emphysema]])<ref name=":1" />
# [[Cardiovascular disease|Cardiovascular system]]:<ref name=":0"/><ref name=":1" /> 
#* [[Congenital heart disease]] (e.g., [[Tetralogy of Fallot]], [[Right-to-left shunt|right to left shunts in heart or great vessels]])
#* [[Heart failure]]
#* [[Valvular heart disease]]
#* [[Myocardial infarction]]
# [[Hemoglobinopathy|Hemoglobinopathies]]:<ref name=":1" />
#* [[Methemoglobinemia]]{{efn|Note this causes "spurious" cyanosis, in that, since [[methemoglobin]] appears blue, the patient can appear cyanosed even in the presence of a normal arterial oxygen level.}}
#* [[Sulfhemoglobinemia]]{{efn|Note a rare condition in which there is excess sulfhemoglobin (SulfHb) in the blood. The pigment is a greenish derivative of hemoglobin which cannot be converted back to normal, functional hemoglobin. It causes cyanosis even at low blood levels.}}
#* [[Polycythemia]]
#* [[Congenital]] cyanosis (HbM Boston) arises from a [[mutation]] in the α-codon which results in a change of [[primary sequence]], H → Y. [[Tyrosine]] stabilizes the [[Fe(III)]] form ([[oxyhaemoglobin]]) creating a permanent T-state of Hb.[[File:Peripheral Cyanosis due to Ischemia.jpg|thumb|Peripheral cyanosis in an individual with [[Peripheral artery disease|peripheral vascular disease]].]]
# Others:
#* High [[altitude]], cyanosis may develop in ascents to altitudes >2400 m.<ref name=":0"/><ref name=":1" />
#* [[Hypothermia]]<ref name=":1" />
#* [[Frostbite]]<ref>{{Cite book|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK536914/|title=StatPearls|chapter=Frostbite|year=2021|publisher=StatPearls|pmid=30725599 |last1=Basit |first1=H. |last2=Wallen |first2=T. J. |last3=Dudley |first3=C. }}</ref>
#* [[Obstructive sleep apnea]]<ref name=":1" />
{{notelist}}

=== Peripheral cyanosis ===

Peripheral cyanosis is the blue tint in fingers or extremities, due to an inadequate or obstructed circulation.<ref name=":1">{{cite web| vauthors = Pahal P, Goyal A | title = Central and Peripheral Cyanosis | publisher = StatPearls | date=July 2020 | url = https://www.ncbi.nlm.nih.gov/books/NBK559167/ | pmid = 32644593}}</ref> 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 [[Blood#Color|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.<ref name=":1" /> Small blood vessels may be restricted and can be treated by increasing the normal oxygenation level of the blood.<ref name=":1" />
[[File:Blausen 0707 PatentDuctusArteriosus.png|thumb|Initial direction of blood flow in patients with [[patent ductus arteriosus]]. Once the pressure of the pulmonary arteries increases more than the aorta due to [[Right ventricular hypertrophy|right heart hypertrophy]], the direction of blood flow reverses, sending deoxygenated blood through the patent duct directly into the descending aorta while sparing the [[brachiocephalic trunk]], [[Common carotid artery|left common carotid]], and [[Subclavian artery|left subclavian artery]], therefore causing the differential cyanosis.]]
Peripheral cyanosis may be due to the following causes:<ref name=":1" />
* All common causes of central cyanosis
* Reduced [[cardiac output]] (e.g., [[heart failure]] or [[hypovolemia]])
* Cold exposure
* [[Chronic obstructive pulmonary disease]] (COPD)
*Arterial obstruction (e.g., [[peripheral vascular disease]], [[Raynaud phenomenon]])
* Venous obstruction (e.g., [[deep vein thrombosis]])

=== Differential cyanosis ===
[[File:Local hypxia.jpg|thumb|This illustration depicts a self-induced local (tissue) hypoxia on the right hand (right side of the picture) versus a normal left hand (left side of the picture). The cyanosis was achieved by inflating and tightening the blood pressure cuff on the right arm.]]Differential cyanosis is the bluish coloration of the lower but not the [[upper extremity]] and the head.<ref name=":1" /> This is seen in patients with a [[patent ductus arteriosus]].<ref name=":1" /> Patients with a large ductus develop progressive [[Pulmonary vascular system|pulmonary vascular]] disease, and [[pressure overload]] of the [[right ventricle]] occurs.<ref name=":5">{{Citation|last1=Gillam-Krakauer|first1=Maria|title=Patent Ductus Arteriosus|date=2021|url=https://www.ncbi.nlm.nih.gov/books/NBK430758/|work=StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=28613509|access-date=2021-11-19|last2=Mahajan|first2=Kunal}}</ref> As soon as pulmonary pressure exceeds [[aortic pressure]], shunt reversal (right-to-left shunt) occurs.<ref name=":5"/> The upper extremity remains pink because [[deoxygenated blood]] flows through the patent duct and directly into the [[descending aorta]] while sparing the [[brachiocephalic trunk]], [[Common carotid artery|left common carotid]], and [[Subclavian artery|left subclavian arteries]].

== Evaluation ==
A detailed history and [[physical examination]] (particularly focusing on the [[Cardiopulmonary|cardiopulmonary system]]) can guide further management and help determine the medical tests to be performed.<ref name=":0"/> Tests that can be performed include [[pulse oximetry]], [[Arterial blood gas test|arterial blood gas]], [[complete blood count]], [[methemoglobin]] level, [[Electrocardiography|electrocardiogram]], [[Echocardiography|echocardiogram]], [[X-ray|X-Ray]], [[CT scan]], [[cardiac catheterization]], and [[hemoglobin electrophoresis]].

In [[newborns]], peripheral cyanosis typically presents in the [[Distal extremity|distal extremities]], circumoral, and periorbital areas.<ref name=":4">{{Cite journal|last=Lees|first=Martin H.|date=1970|title=Cyanosis of the newborn infant|url=https://linkinghub.elsevier.com/retrieve/pii/S0022347670800245|journal=The Journal of Pediatrics|language=en|volume=77|issue=3|pages=484–498|doi=10.1016/S0022-3476(70)80024-5|pmid=5502102|url-access=subscription}}</ref> Of note, [[mucous membrane]]s remain pink in peripheral cyanosis as compared to central cyanosis where the mucous membranes are cyanotic.<ref name=":4"/>
[[File:CongenitalHeartCase-133.jpg|thumb|An example of cyanosis in an individual with darker skin pigmentation. Note the pale purple (instead of the typical bluish-purple hue) nail beds. This patient also had prominent digital clubbing due to a congenital heart disease with right-to-left shunting (this patient had [[Tetralogy of Fallot]]).]]

[[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 [[Blood vessel|vascular]].<ref name=":0"/> As mentioned [[#Pathophysiology|above]], patients with severe [[anemia]] may appear normal despite higher than normal concentrations of deoxyhemoglobin.<ref name=":1" /><ref name=":2"/> Signs of severe [[anemia]] may include pale [[Mucous membrane|mucosa]] (lips, eyelids, and gums), [[fatigue]], [[lightheadedness]], and [[irregular heartbeats]].
[[File:Cyanoza .jpg|thumb|An example of cyanosis in an elderly individual with darker skin pigmentation. Note the dark purple hue of the lips.]]

== Management ==
Cyanosis is a [[symptom]], not 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 cannula|nasal canula]] or [[continuous positive airway pressure]] depending on severity) should be given immediately.<ref>{{Citation|last=Ramji|first=Siddarth|title=Neonatal Resuscitation|date=2013|url=http://dx.doi.org/10.5005/jp/books/11894_109|work=IAP Textbook of Pediatrics|pages=28|publisher=Jaypee Brothers Medical Publishers (P) Ltd.|doi=10.5005/jp/books/11894_109|isbn=9789350259450|access-date=2021-11-05|url-access=subscription}}</ref><ref>{{Cite journal|last=Sasidharan|first=Ponthenkandath|date=2004|title=An approach to diagnosis and management of cyanosis and tachypnea in term infants|url=http://dx.doi.org/10.1016/j.pcl.2004.03.010|journal=Pediatric Clinics of North America|volume=51|issue=4|pages=999–1021|doi=10.1016/j.pcl.2004.03.010|pmid=15275985|issn=0031-3955|url-access=subscription}}</ref>

If the [[methemoglobin]] levels are positive for [[methemoglobinemia]], first-line treatment is to administer [[methylene blue]].<ref name=":0"/>

== 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''.<ref>{{cite book|title=[[Mosby's Medical, Nursing & Allied Health Dictionary]]|year=1994|edition=4th|series=Mosby-Year Book|page=425}}</ref>

It is postulated by Dr. Christen Lundsgaard that cyanosis was first described in 1749 by [[Jean-Baptiste de Sénac]], a French physician who served King [[Louis XV]].<ref name=":3">{{Cite journal|last=Lundsgaard|first=C.|title=Studies on Cyanosis|date=1919-09-01|journal=The Journal of Experimental Medicine|volume=30|issue=3|pages=259–269|doi=10.1084/jem.30.3.259|issn=0022-1007|pmc=2126682|pmid=19868357}}</ref> De Sénac concluded from an [[autopsy]] that cyanosis was caused by a heart defect that led to the mixture of [[Artery|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.<ref name=":3"/>

==See also==
* [[Acrocyanosis]]
* [[Blue baby syndrome]]
* [[Raynaud's phenomenon]]
* [[Blue Fugates]]

==References==
{{Reflist}}

== External links ==
{{Medical resources
|  ICD10          = {{ICD10|R|23|0|r|20}}
|  ICD9           = {{ICD9|782.5}}
|  ICDO           = 
|  DiseasesDB     = 17332
|  OMIM           = 
|  MedlinePlus    =
|  eMedicineSubj  = med
|  eMedicineTopic = 3002
|  eMedicine_mult = 
|  MeshID         = D003490
}}

{{Skin and subcutaneous tissue symptoms and signs}}
{{Respiratory system symptoms and signs}}
{{Authority control}}

[[Category:Medical signs]]
[[Category:Symptoms and signs: Skin and subcutaneous tissue]]
[[Category:Human skin color]]