Introduction

Hypoxia is when you have a low level of oxygen in your body tissues. It is a condition in which a sufficient amount of oxygen does not reach the tissues to the point where it affects the functioning of the body. This occurs due to low blood supply or low oxygen content in the blood (hypoxemia). Hypoxia can vary from mild to severe. Hypoxia can present in acute or chronic forms. Some tissues can tolerate hypoxia for a longer duration, however,  other tissues are severely damaged by low oxygen levels in them.¹

Respiratory system

Overview of the respiratory system

The respiratory system enables the exchange of gases where oxygen (O₂) is inspired and carbon dioxide (CO₂) is expired. Lungs are the main organs of the respiratory system and they are situated on each side of the heart. The right lung has three sections whilst the left lung has two sections. The respiratory system starts at the nose and mouth, continues through air passages (airways) and reaches the main respiratory organs, the lungs.²

• The air we breathe enters through our nose or mouth and then moves down the trachea (windpipe)
• The trachea then divides into left and right bronchi which further branch into bronchioles. Bronchioles are small and narrow airways. This system as a whole is often called the bronchial tree
• The bronchioles end in many tiny air sacs called alveoli in the lungs
• Each alveol is made up of tiny blood vessels called capillaries. The capillaries connect to a network of veins and arteries that take blood into various parts of the body
• The pulmonary artery and its branches deliver deoxygenated blood (low in oxygen) to the capillaries that surround the alveoli. The capillaries and alveoli have thin walls. These are one cell thick which allows easy exchange of oxygen and carbon dioxide

Organ systems involved in gaseous exchange

Cardiovascular system³

• Pulmonary circulation
• Alveolar capillaries

Respiratory system

• Alveoli
• Alveolar sacs
• Alveolar ducts
• Respiratory bronchioles

Transfer of oxygen from outside air into lungs

• Ventilation (airflow to the alveoli): Ventilation is the process by which air moves inside and outside of the alveoli³
• Diffusion (gas exchange through the interstitial tissue): It is the passive movement of gases from an area of high to low concentration, down a concentration gradient. Gas exchange via diffusion occurs between the alveoli and the capillaries in the lungs
• Perfusion (blood flow to the lungs): The flow of blood to alveolar capillaries occurs by this process.
• V/Q ratio: This ratio evaluates ventilation (V) to perfusion (Q). Collective changes in ventilation and perfusion in the lungs are measured using this ratio. The V/Q ratio shows regional variation³

Causes of hypoxia

Reduced oxygen tension: for example in high altitudes¹

Hypoventilation which is due to:

• Airway obstruction - foreign body inhalation or laryngeal oedema
• Chronic obstructive pulmonary disease (COPD)
• Bronchial asthma 
• Impaired respiratory drive: deep sedation or coma
• Restricted movement of the chest wall: obesity, hypoventilation syndrome, circumferential burns, massive ascites, or ankylosing spondylitis
• Neuromuscular diseases, such as myasthenia gravis, muscular dystrophy, amyotrophic lateral sclerosis (ALS), or phrenic nerve injury

Ventilation-perfusion mismatch (V/Q mismatch)

• Decreased V/Q Ratio (impaired ventilation or high perfusion): chronic bronchitis, obstructive airway disease, mucus plugs, pulmonary oedema
• Increased V/Q Ratio (impaired perfusion): pulmonary embolism, emphysema

Right-to-left shunt

• In right to left shunt case, blood crosses from the right to the left side of the heart without oxygenation
• Anatomic Shunts: intracardiac shunts (ASD, VSD, PDA), pulmonary arteriovenous malformations, fistulas, and hepatopulmonary syndrome
• Physiologic Shunting: pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS)

Impaired diffusion of oxygen

• Interstitial oedema, interstitial inflammation, or fibrosis, pulmonary oedema and interstitial lung disease

Signs and symptoms of hypoxia

• Hypoxia can be acute or chronic and the severity of hypoxia determines the severity of the symptom
• Acute hypoxia may present with dyspnea and tachypnea
• Severe hypoxia can cause tachycardia since the heart tries to pump enough oxygen into tissues
• In cases of upper airway obstruction, stridor can be heard on physical examination
• In severe hypoxia, the skin can be cyanotic
• Severe decline in oxygen delivery can cause deterioration of organ function
• Neurologic manifestations: restlessness, headache and confusion
• In severe cases, comas can occur and if not cured, this may lead to death
• In chronic hypoxia, dyspnea on exertion can be seen
• Fever can be present in case of infection causing hypoxia¹

Types of hypoxia

• Hypoxemic Hypoxia: is a condition where you have low oxygen in the blood. Causes include hypoventilation, pulmonary shunting, and impaired alveolar diffusion
• Circulatory Hypoxia: circulatory hypoxia is caused by the inability of the heart to pump enough blood. There will be plenty of oxygen but the heart is unable to pump hence enough blood does not reach the tissues
• Anaemic Hypoxia: the low haemoglobin in the blood leads to a decrease in oxygen-carrying capacity leading to inadequate oxygen delivery
• Histotoxic Hypoxia: in histotoxic hypoxia, the cells are unable to utilise oxygen effectively. Histotoxic hypoxia is seen during cyanide poisoning¹

Evaluation of acute hypoxia

1. Pulse oximetry: It helps to evaluate arterial oxygen saturation (SaO₂) i.e. the amount of oxygen bound to haemoglobin in arterial blood
2. Arterial blood gas (ABG): Arterial blood gas helps to evaluate hypoxemia. Arterial oxygen tension (PaO₂) is the amount of oxygen dissolved in the plasma. The partial pressure of CO₂ is related to minute ventilation and is an indirect measure of the exchange of CO₂ with the air via the alveoli¹
3. Imaging
   • Imaging studies of the chest help to identify the cause of hypoxia. Chest X-ray and CT scan can evaluate pneumonia, hyperinflated lungs in COPD, pulmonary oedema and other conditions. CT scans can give images that outline the exact cause of hypoxia and help in detecting pulmonary embolism
   • VQ scan can detect the ventilation-perfusion mismatch. This helps in the diagnosis of acute or chronic pulmonary embolism¹

Evaluation of chronic hypoxia

1. Pulmonary Function Test (PFT): PFT helps in the diagnosis of lung disorders. This test provides a direct measure of the lung volumes, bronchodilator response and diffusion capacity. This test can also differentiate between obstructive lung diseases (upper airway obstruction, bronchial asthma, COPD) and restrictive lung diseases (chest wall abnormalities, interstitial lung diseases)¹
2. Nocturnal (overnight) Trend Oximetry: Nocturnal (overnight) Trend Oximetry gives information about oxyhaemoglobin saturation over a specific period. This test is primarily used to assess the need for oxygen supplementation at night
3. Six-Minute Walk Test: This test provides information on oxyhemoglobin saturation response to exercise
4. Haemoglobin levels: Secondary polycythemia can indicate chronic hypoxia¹

Treatment and management of hypoxia

Management of hypoxia includes maintaining patent airways, increasing the oxygen content of the inspired air and improving the diffusion capacity.¹

1. Maintaining patent airways
   • Ensure unobstructed upper airways with good suctioning
   • Placement of an endotracheal tube or tracheostomy if necessary
   • Bronchodilators can be used to maintain unobstructed lower airways
   • Increase the fraction of inspired O₂ (FiO₂)
2. Low-flow devices
   • Nasal cannula
   • Simple face mask
   • Reservoir cannula (Oxymizer)
   • Partial-rebreather mask
   • Non-rebreather mask
   • Double trunk mask
3. High-flow devices: high-flow devices require a humidifier, heated tubing and an oxygen blender
   • Venturi mask
   • High-flow nasal cannula
   • Air/oxygen Blender
4. Positive pressure ventilation: It allows for accurate delivery of FiO2
   • Non-invasive ventilation - is the last resort to avoid intubation
   • Continuous positive airway pressure mask (CPAP)
   • Bilevel-positive airway pressure (BiPAP)
   • Invasive ventilation
5. Improve the diffusion of oxygen through the alveolar interstitial tissue: the overall idea is to treat the underlying cause of respiratory failure
   • In pulmonary oedema cases, diuretics can be used
   • In interstitial lung disease, steroids can be used
   • As an ultimate method of increasing oxygenation, extracorporeal membrane oxygenation (ECMO) can be utilised¹

FAQs

What are the 4 types of hypoxia?

There are four types of hypoxia: hypoxemic hypoxia, anaemic hypoxia, circulatory hypoxia, and histotoxic hypoxia

What is hypoxemia vs hypoxia?

• Hypoxemia is when you have low oxygen levels in your blood
• Hypoxia is when you have low oxygen levels in your tissues

Summary

Hypoxia is a lack of oxygen in the tissues of your body. Cells in the body require oxygen to function properly. There are four types of hypoxia: hypoxemic, circulatory, anaemic and histotoxic hypoxia. Hypoxia can be caused by obstruction of airways, anaemia, asthma, bronchitis, emphysema, pneumonia, pulmonary oedema, chronic obstructive pulmonary disease, pulmonary oedema and pulmonary embolism. Signs and symptoms include restlessness, headache, rapid heart rate and shortness of breath. Hypoxia can be treated by diuretics, steroids, oxygen delivery devices and continuous positive airway masks.