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 to ≤85% or ≤75%.

Acute cyanosis can be as a result of asphyxiation or choking, and is one of the definite signs that respiration is being blocked.

Central cyanosis may be due to the following causes:

1. Central nervous system (impairing normal ventilation):

- Intracranial hemorrhage

- Drug overdose (e.g. heroin)

- Tonic–clonic seizure (e.g. grand mal seizure)

2. Respiratory system:

- Pneumonia

- Bronchiolitis

- Bronchospasm (e.g. asthma)

- Pulmonary hypertension

- Pulmonary embolism

- Hypoventilation

- Chronic obstructive pulmonary disease, or COPD (emphysema)

3. Cardiovascular diseases:

- Congenital heart disease (e.g. Tetralogy of Fallot, right to left shunts in heart or great vessels)

- Heart failure

- Valvular heart disease

- Myocardial infarction

4. Blood:

- Methemoglobinemia * 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.

- Polycythaemia

- Congenital cyanosis (HbM Boston) arises from a mutation in the α-codon which results in a change of primary sequence, H → Y. Tyrosine stabilises the Fe(III) form (oxyhaemoglobin) creating a permanent T-state of Hb.

5. Others:

- High altitude, cyanosis may develop in ascents to altitudes >2400 m.

- Hypothermia

- Obstructive sleep apnea

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 or hypovolaemia)

- Cold exposure

- Chronic obstructive pulmonary disease (COPD)

- Arterial obstruction (e.g. peripheral vascular disease, Raynaud phenomenon)

- Venous obstruction (e.g. deep vein thrombosis)

This refers specifically to hypoxic states where the arterial content of oxygen is insufficient. This can be caused by alterations in respiratory drive, such as in respiratory alkalosis, physiological or pathological shunting of blood, diseases interfering in lung function resulting in a ventilation-perfusion mismatch, such as a pulmonary embolus, or alterations in the partial pressure of oxygen in the environment or lung alveoli, such as may occur at altitude or when diving.

Carbon monoxide competes with oxygen for binding sites on hemoglobin molecules. As carbon monoxide binds with hemoglobin hundreds of times tighter than oxygen, it can prevent the carriage of oxygen.

Carbon monoxide poisoning can occur acutely, as with smoke intoxication, or over a period of time, as with cigarette smoking. Due to physiological processes, carbon monoxide is maintained at a resting level of 4–6 ppm. This is increased in urban areas (7–13 ppm) and in smokers (20–40 ppm). A carbon monoxide level of 40 ppm is equivalent to a reduction in hemoglobin levels of 10 g/L.

CO has a second toxic effect, namely removing the allosteric shift of the oxygen dissociation curve and shifting the foot of the curve to the left. In so doing, the hemoglobin is less likely to release its oxygens at the peripheral tissues. Certain abnormal hemoglobin variants also have higher than normal affinity for oxygen, and so are also poor at delivering oxygen to the periphery.

The mortality rate of meconium-stained infants is considerably higher than that of non-stained infants; meconium aspiration used to account for a significant proportion of neonatal deaths. Residual lung problems are rare but include symptomatic cough, wheezing, and persistent hyperinflation for up to five to ten years. The ultimate prognosis depends on the extent of CNS injury from asphyxia and the presence of associated problems such as pulmonary hypertension. Fifty percent of newborns affected by meconium aspiration would die fifteen years ago; however, today the percent has dropped to about twenty.

In a study conducted between 1995 and 2002, MAS occurred in 1,061 of 2,490,862 live births, reflecting an incidence of 0.43 of 1,000. MAS requiring intubation occurs at higher rates in pregnancies beyond 40 weeks. 34% of all MAS cases born after 40 weeks required intubation compared to 16% prior to 40 weeks.

Although there is no definitive reporting on its incidence, acrocyanosis shows prevalence in children and young adults than in patients thirty years of age or older. Epidemiological data suggests that cold climate, outdoor occupation, and low body mass index are significant risk factors for developing acrocyanosis. As expected, acrocyanosis would be more prevalent in women than in men due to differences in BMI. However, the incidence rate of acrocyanosis often decreases with increasing age, regardless of regional climate. It completely resolves in many women after menopause implying significant hormonal influences.

Individual susceptibility to HAPE is difficult to predict. The most reliable risk factor is previous susceptibility to HAPE, and there is likely to be a genetic basis to this condition, perhaps involving the gene for angiotensin converting enzyme (ACE). Recently, scientists have found the similarities between low amounts of 2,3-BPG (also known as 2,3-DPG) with the occurrence of HAPE at high altitudes. Persons with sleep apnea are susceptible due to irregular breathing patterns while sleeping at high altitudes.

Acrocyanosis is common initially after delivery in the preterm and full term newborn Intervention normally is not required, although hospitals opt to provide supplemental oxygen for precautionary measures.

The incidence of clinical HAPE in unacclimatized travelers exposed to high altitude (~) appears to be less than 1%. The U.S. Army Pike's Peak Research Laboratory has exposed sea-level-resident volunteers rapidly and directly to high altitude; during 30 years of research involving about 300 volunteers (and over 100 staff members), only three have been evacuated with suspected HAPE.

A 2008 bulletin from the World Health Organization estimates that 900,000 total infants die each year from birth asphyxia, making it a leading cause of death for newborns.

In the United States, intrauterine hypoxia and birth asphyxia was listed as the tenth leading cause of neonatal death.

The risk may be reduced by administering a non-particulate antacid (e.g. Sodium Citrate) or an H-antagonist like Ranitidine.

Perinatal asphyxia, neonatal asphyxia or birth asphyxia is the medical condition resulting from deprivation of oxygen to a newborn infant that lasts long enough during the birth process to cause physical harm, usually to the brain. Hypoxic damage can occur to most of the infant's organs (heart, lungs, liver, gut, kidneys), but brain damage is of most concern and perhaps the least likely to quickly or completely heal. In more pronounced cases, an infant will survive, but with damage to the brain manifested as either mental, such as developmental delay or intellectual disability, or physical, such as spasticity.

It results most commonly from a drop in maternal blood pressure or some other substantial interference with blood flow to the infant's brain during delivery. This can occur due to inadequate circulation or perfusion, impaired respiratory effort, or inadequate ventilation. Perinatal asphyxia happens in 2 to 10 per 1000 newborns that are born at term, and more for those that are born prematurely. WHO estimates that 4 million neonatal deaths occur yearly due to birth asphyxia, representing 38% of deaths of children under 5 years of age.

Perinatal asphyxia can be the cause of hypoxic ischemic encephalopathy or intraventricular hemorrhage, especially in preterm births. An infant suffering severe perinatal asphyxia usually has poor color (cyanosis), perfusion, responsiveness, muscle tone, and respiratory effort, as reflected in a low 5 minute Apgar score. Extreme degrees of asphyxia can cause cardiac arrest and death. If resuscitation is successful, the infant is usually transferred to a neonatal intensive care unit.

There has long been a scientific debate over whether newborn infants with asphyxia should be resuscitated with 100% oxygen or normal air. It has been demonstrated that high concentrations of oxygen lead to generation of oxygen free radicals, which have a role in reperfusion injury after asphyxia. Research by Ola Didrik Saugstad and others led to new international guidelines on newborn resuscitation in 2010, recommending the use of normal air instead of 100% oxygen.

There is considerable controversy over the diagnosis of birth asphyxia due to medicolegal reasons. Because of its lack of precision, the term is eschewed in modern obstetrics.

People generally require tracheostomy and lifetime mechanical ventilation on a ventilator in order to survive. However, it has now been shown that biphasic cuirass ventilation can effectively be used without the need for a tracheotomy. Other potential treatments for Ondine's curse include oxygen therapy and medicine for stimulating the respiratory system. Currently, problems arise with the extended use of ventilators, including fatal infections and pneumonia.

Most people with CCHS (unless they have the Late Onset form) do not survive infancy, unless they receive ventilatory assistance during sleep. An alternative to a mechanical ventilator is diaphragm pacing.

Central hypoventilation syndrome (CHS) is a respiratory disorder that results in respiratory arrest during sleep. CHS can either be congenital (CCHS) or acquired (ACHS) later in life. It is fatal if untreated. It is also known as Ondine's curse.

ACHS can develop as a result of severe injury or trauma to the brain or brainstem. Congenital cases are very rare and involve a failure of autonomic control of breathing. In 2006, there were only about 200 known cases worldwide. As of 2008, only 1000 total cases were known. The diagnosis may be delayed because of variations in the severity of the manifestations or lack of awareness in the medical community, particularly in milder cases. However, as there have been cases where asymptomatic family members also were found to have CCHS, it may be that these figures only reflect those found to require mechanical ventilation. In all cases, episodes of apnea occur in sleep, but in a few patients, at the most severe end of the spectrum, apnea also occurs while awake.

Although rare, cases of long-term untreated CCHS have been reported and are termed late onset CCHS (LO-CCHS). Cases that go undiagnosed until later life and middle age, although the symptoms are usually obvious in retrospect. There have, however, even been cases of LO-CCHS where family members found to have it have been asymptomatic. Again, lack of awareness in the medical community may cause such a delay. CCHS susceptibility is not known to be affected by gender.

The most common cause is post-surgical atelectasis, characterized by splinting, i.e. restricted breathing after abdominal surgery.

Another common cause is pulmonary tuberculosis. Smokers and the elderly are also at an increased risk. Outside of this context, atelectasis implies some blockage of a bronchiole or bronchus, which can be within the airway (foreign body, mucus plug), from the wall (tumor, usually squamous cell carcinoma) or compressing from the outside (tumor, lymph node, tubercle). Another cause is poor surfactant spreading during inspiration, causing the surface tension to be at its highest which tends to collapse smaller alveoli. Atelectasis may also occur during suction, as along with sputum, air is withdrawn from the lungs. There are several types of atelectasis according to their underlying mechanisms or the distribution of alveolar collapse; resorption, compression, microatelectasis and contraction atelectasis.

Historically it is said that a patient is at risk if they have:

- Residual gastric volume of greater than 25ml, with

- pH of less than 2.5

However these are indirect measurements and are not factors that directly influence aspiration risk.

Patients with a high risk should have a rapid sequence induction. High risk is defined as these factors:

1. Non-elective surgical procedure

2. Light anaesthesia/unexpected response to stimulation

3. Acute or chronic, upper or lower GI pathology

4. Obesity

5. Opioid medication

6. Neurological disease, impaired conscious level, or sedation

7. Lithotomy position

8. Difficult intubation/airway

9. Gastrointestinal reflux

10. Hiatal hernia

The atmosphere is composed of 78% nitrogen and 21% oxygen. Since oxygen is exchanged at the alveoli-capillary membrane, nitrogen is a major component for the alveoli's state of inflation. If a large volume of nitrogen in the lungs is replaced with oxygen, the oxygen may subsequently be absorbed into the blood, reducing the volume of the alveoli, resulting in a form of alveolar collapse known as absorption atelectasis.

Status asthmaticus is slightly more common in males and is more common among people of African and Hispanic origin. The gene locus glutathione dependent S-nitrosoglutathione (GSNOR) has been suggested as one possible correlation to development of status asthmaticus.

Methemoglobinemia may be acquired. Classical drug causes of methemoglobinaemia include antibiotics (trimethoprim, sulfonamides, and dapsone), local anesthetics (especially articaine, benzocaine, and prilocaine), and aniline dyes, metoclopramide, rasburicase, chlorates, and bromates. Ingestion of compounds containing nitrates (such as the patina chemical bismuth nitrate) can also cause methemoglobinemia.

In otherwise healthy individuals, the protective enzyme systems normally present in red blood cells rapidly reduce the methemoglobin back to hemoglobin and hence maintain methemoglobin levels at less than one percent of the total hemoglobin concentration. Exposure to exogenous oxidizing drugs and their metabolites (such as benzocaine, dapsone, and nitrates) may lead to an increase of up to a thousandfold of the methemoglobin formation rate, overwhelming the protective enzyme systems and acutely increasing methemoglobin levels.

Infants under 6 months of age have lower levels of a key methemoglobin reduction enzyme (NADH-cytochrome b5 reductase) in their red blood cells. This results in a major risk of methemoglobinemia caused by nitrates ingested in drinking water, dehydration (usually caused by gastroenteritis with diarrhea), sepsis, or topical anesthetics containing benzocaine or prilocaine. Nitrates used in agricultural fertilizers may leak into the ground and may contaminate well water. The current EPA standard of 10 ppm nitrate-nitrogen for drinking water is specifically set to protect infants. Benzocaine applied to the gums or throat (as commonly used in baby teething gels, or sore throat lozenges) can cause methemoglobinemia.

Arterial blood with elevated methemoglobin levels has a characteristic chocolate-brown color as compared to normal bright red oxygen-containing arterial blood. If methemoglobinemia is suspected, an arterial blood gas and co-oximetry panel should be obtained.

For individuals who survive the initial crush injury, survival rates are high for traumatic asphyxia.

Although this data may be underestimated as a result of misdiagnosis and failure to report illnesses in fatal cases, the current estimates are fairly representative of neonates with hyperammonemia. The United States has an estimated frequency of UCED of 1 per 25,000 live births. The international prevalence is between an estimated 1:8,000-1:44,000, varying widely by location. In order for THAN to be diagnosed, urea cycle deficiencies must be excluded, and the diagnosis must be made within 24–36 hours of birth. In 1996, one study said that there were only a confirmed 33 cases of THAN worldwide in literature. This study also admitted that at first they did not consider the possibility that the infant did not have a urea cycle deficiency. The hospital that this case occurred in did not have equipment to measure urea cycle enzymes, so they confirmed the diagnosis post mortem with an autopsy. Therefore, it is important to consider that many infants diagnosed with regular hyperammonemia, may have actually had THAN, but the urea cycle deficiency was not excluded and therefore did not meet the criteria for diagnosis.

"Fire-eater's lung" is an important variant of hydrocarbon pneumonitis, which typically involves adolescents or young adults who are exposed through mishap during flame-blowing performances using a variety of different flammable materials. The substances used overlap with some of the pediatric exposures (kerosene, gasoline) but can also include other hydrocarbons such as jet fuel and, in France, an aromatic hydrocarbon enriched petroleum-distillate called "kerdan". There has also been a case of citronella oil aspiration in a fire-eater. As with hydrocarbon pneumonitis in children, fire-eater's lung can also be complicated by pneumatocele. Although the term "acute lipoid pneumonia" has been used to refer to the "fire-eater's lung" syndrome, this is a misnomer.

This can be caused by taking medications that contain sulfonamides under certain conditions (i.e., overdosing of sumatriptan).

Sulfhemoglobinemia is usually drug induced. Drugs associated with sulfhemoglobinemia include sulphonamides and sulfasalazine. Another possible cause is occupational exposure to sulfur compounds.

It can be caused by phenazopyridine.