If the alveolar ventilation is insufficient, there will not be enough oxygen delivered to the alveoli for the body's use. This can cause hypoxemia even if the lungs are normal, as the cause is in the brainstem's control of ventilation or in the body's inability to breathe effectively.

In conditions where the proportion of oxygen in the air is low, or when the partial pressure of oxygen has decreased, less oxygen is present in the alveoli of the lungs. The alveolar oxygen is transferred to hemoglobin, a carrier protein inside red blood cells, with an efficiency that decreases with the partial pressure of oxygen in the air.

- Altitude. The external partial pressure of oxygen decreases with altitude, for example in areas of high altitude or when flying. This decrease results in decreased carriage of oxygen by haemoglobin. This is particularly seen as a cause of cerebral hypoxia and mountain sickness in climbers of Mount Everest and other peaks of extreme altitude. For example, at the peak of Mount Everest, the partial pressure of oxygen is just 43 mmHg, whereas at sea level the partial pressure is 150 mmHg. For this reason, cabin pressure in aircraft is maintained at 5,000 to 6,000 feet (1500 to 1800 m).

- Diving. Hypoxia in diving can result from sudden surfacing. The partial pressures of gases increases when diving, increases by one ATM every ten metres. This means that a partial pressure of oxygen sufficient to maintain good carriage by haemoglobin is possible at depth, even if it is insufficient at the surface. A diver that remains underwater will slowly consume their oxygen, and when surfacing, the partial pressure of oxygen may be insufficient (shallow water blackout). This may manifest at depth as deep water blackout.

- Suffocation. Decreased concentration of oxygen in inspired air caused by reduced replacement of oxygen in the breathing mix.

- Anaesthetics. Low partial pressure of oxygen in the lungs when switching from inhaled anesthesia to atmospheric air, due to the Fink effect, or diffusion hypoxia.

- Air depleted of oxygen has also proven fatal. In the past, anesthesia machines have malfunctioned, delivering low-oxygen gas mixtures to patients. Additionally, oxygen in a confined space can be consumed if carbon dioxide scrubbers are used without sufficient attention to supplementing the oxygen which has been consumed.

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.

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

Treatment of infants suffering birth asphyxia by lowering the core body temperature is now known to be an effective therapy to reduce mortality and improve neurological outcome in survivors, and hypothermia therapy for neonatal encephalopathy begun within 6 hours of birth significantly increases the chance of normal survival in affected infants.

There has long been a debate over whether newborn infants with birth 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.

Transient tachypnea of the newborn occurs in approximately 1 in 100 preterm infants and 3.6-5.7 per 1000 term infants. It is most common in infants born by Cesarian section without a trial of labor after 35 weeks' gestation. Male infants and infants with an umbilical cord prolapse or perinatal asphyxia are at higher risk. Parental risk factors include use of pain control or anesthesia during labor, asthma, and diabetes.

Type 1 respiratory failure is defined as a low level of oxygen in the blood (hypoxemia) without an increased level of carbon dioxide in the blood (hypercapnia), and indeed the PCO may be normal or low. It is typically caused by a ventilation/perfusion (V/Q) mismatch; the volume of air flowing in and out of the lungs is not matched with the flow of blood to the lungs. The basic defect in type 1 respiratory failure is failure of oxygenation characterized by:

This type of respiratory failure is caused by conditions that affect oxygenation such as:

- Low ambient oxygen (e.g. at high altitude)

- Ventilation-perfusion mismatch (parts of the lung receive oxygen but not enough blood to absorb it, e.g. pulmonary embolism)

- Alveolar hypoventilation (decreased minute volume due to reduced respiratory muscle activity, e.g. in acute neuromuscular disease); this form can also cause type 2 respiratory failure if severe

- Diffusion problem (oxygen cannot enter the capillaries due to parenchymal disease, e.g. in pneumonia or ARDS)

- Shunt (oxygenated blood mixes with non-oxygenated blood from the venous system, e.g. right to left shunt)

Hypoxemia (PaO2 6.0kPa).

The basic defect in type 2 respiratory failure is characterized by:

Type 2 respiratory failure is caused by inadequate alveolar ventilation; both oxygen and carbon dioxide are affected. Defined as the buildup of carbon dioxide levels (PCO) that has been generated by the body but cannot be eliminated. The underlying causes include:

- Increased airways resistance (chronic obstructive pulmonary disease, asthma, suffocation)

- Reduced breathing effort (drug effects, brain stem lesion, extreme obesity)

- A decrease in the area of the lung available for gas exchange (such as in chronic bronchitis)

- Neuromuscular problems (Guillain–Barré syndrome, motor neuron disease)

- Deformed (kyphoscoliosis), rigid (ankylosing spondylitis), or flail chest.

The rate of BPD varies among institutions, which may reflect neonatal risk factors, care practices (e.g., target levels for acceptable oxygen saturation), and differences in the clinical definitions of BPD.

Giving the mother glucocorticoids speeds the production of surfactant. For very premature deliveries, a glucocorticoid is given without testing the fetal lung maturity. The American College of Obstetricians and Gynecologists (ACOG), Royal College of Medicine, and other major organizations have recommended antenatal glucocorticoid treatment for women at risk for preterm delivery prior to 34 weeks of gestation. Multiple courses of glucocorticoid administration, compared with a single course, does not seem to increase or decrease the risk of death or neurodevelopmental disorders of the child.

In pregnancies of greater than 30 weeks, the fetal lung maturity may be tested by sampling the amount of surfactant in the amniotic fluid by amniocentesis, wherein a needle is inserted through the mother's abdomen and uterus. Several tests are available that correlate with the production of surfactant. These include the lecithin-sphingomyelin ratio ("L/S ratio"), the presence of phosphatidylglycerol (PG), and more recently, the surfactant/albumin (S/A) ratio. For the L/S ratio, if the result is less than 2:1, the fetal lungs may be surfactant deficient. The presence of PG usually indicates fetal lung maturity. For the S/A ratio, the result is given as mg of surfactant per gm of protein. An S/A ratio 55 indicates mature surfactant production(correlates with an L/S ratio of 2.2 or greater).

Acute respiratory distress syndrome (ARDS) has some similarities to IRDS. Transient tachypnea of the newborn presents with respiratory distress syndrome in the preterm newborn.

Due to the higher incidence of TTN in newborns delivered by caesarean section, it has been postulated that TTN could result from a delayed absorption of fetal lung fluid from the pulmonary lymphatic system. The increased fluid in the lungs leads to increased airway resistance and reduced lung compliance. It is thought this could be from lower levels of circulating catecholamines after a caesarean section, which are believed to be necessary to alter the function of the ENaC channel to absorb excess fluid from the lungs. Pulmonary immaturity has also been proposed as a causative factor. Levels of phosphatidylglycerol (an indicator of lung maturity) were found to be negative in certain newborns

Mild surfactant deficiency has also been suggested as a causative factor.

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.

Prolonged high oxygen delivery in premature infants causes necrotizing bronchiolitis and alveolar septal injury, with inflammation and scarring. This results in hypoxemia. Today, with the advent of surfactant therapy and high frequency ventilation and oxygen supplementation, infants with BPD experience much milder injury without necrotizing bronchiolitis or alveolar septal fibrosis. Instead, there are usually uniformly dilated acini with thin alveolar septa and little or no interstitial fibrosis. It develops most commonly in the first 4 weeks after birth.

It may result in death, and it is one of the most common causes of death for people with sickle cell anemia.

Let us consider some scenarios where there is a defect in ventilation and/ or perfusion of the lungs.

In condition such as pulmonary embolism, the pulmonary blood flow is affected, thus the ventilation of the lung is adequate, however there is a perfusion defect with defect in blood flow. Gas exchange thus becomes highly inefficient leading to hypoxemia as measured by arterial oxygenation. A ventilation perfusion scan or lung scintigraphy shows some areas of lungs being ventilated but not adequately perfused. This also leads to a high A-a gradient which is not responsive to oxygen

In conditions with right to left shunts, there is again a ventilation perfusion defect with high A-a gradient. However, the A-a gradient is responsive to oxygen therapy. In cases of right to left shunts more of deoxygenated blood mixes with oxygenated blood from the lungs and thus to a small extent the condition might neutralize the high A-a gradient with pure oxygen therapy.

Patient with parenchymal lung diseases will have an increased A-a gradient with moderate response to oxygen therapy.

A patient with hypoventilation will have complete response to 100% oxygen therapy

This has a poor prognosis, as it is a fixed abnormality. Causes include post-term pregnancy, placental insufficiency, and NSAID use by the mother.

This has a good prognosis if it is reversible. Causes include polycythemia and hyperfibrinogenemia.

Ventilation Perfusion mismatch or "V/Q defects" are defects in total lung ventilation perfusion ratio. It is a condition in which one or more areas of the lung receive oxygen but no blood flow, or they receive blood flow but no oxygen due to some diseases and disorders.

The V/Q ratio of a healthy lung is approximately equal to 0.8, as normal lungs are not perfectly matched., which means the rate of alveolar ventilation to the rate of pulmonary blood flow is roughly equal.

The ventilation perfusion ratio can be measured by measuring the A-a gradient i.e. the alveolar-arterial gradient.

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.

Hydroxyurea is a medication that can help to prevent acute chest syndrome. It may cause a low white blood cell count, which can predispose the person to some types of infection.

According to the theory of thrifty phenotype, placental insufficiency triggers epigenetic responses in the fetus that are otherwise activated in times of chronic food shortage. If the offspring actually develops in an environment rich in food it may be more prone to metabolic disorders, such as obesity and type II diabetes.

With liver transplantation, the 5 year survival rate is 74%, which is comparable to patients who undergo liver transplants who do not suffer from hepatopulmonary syndrome.

Placental insufficiency or utero-placental insufficiency is the failure of the placenta to deliver sufficient nutrients to the fetus during pregnancy, and is often a result of insufficient blood flow to the placenta. The term is also sometimes used to designate late decelerations of fetal heart rate as measured by electronic monitoring, even if there is no other evidence of reduced blood flow to the placenta, normal uterine blood flow rate being 600mL/min.