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Hypoxia-Induced Pulmonary Hypertension

Posted on February 14, 2022
Medically reviewed by
Steven C. Pugliese, M.D.
Article written by
Ashley Knox

Hypoxia occurs when there is a low amount of oxygen in the body. People commonly encounter low-oxygen conditions when they travel to high altitudes and experience “thin air,” where the lower air pressure results in less oxygen available to breathe.

Some diseases can also restrict the amount of oxygen that enters the lungs, such as chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (scarring in the lungs), sleep apnea, pneumonia, and more. These diseases can make it difficult to breathe, and they can also trigger changes in the blood vessels of the lungs, leading to pulmonary hypertension (PH).

What Is Hypoxia-Induced Pulmonary Hypertension?

“Pulmonary” is a term referring to the lungs, while “hypertension” means high blood pressure. “Pulmonary hypertension,” therefore, refers to high blood pressure in the blood vessel connecting the heart to the lungs. This special blood vessel runs from the heart, connects to tiny air sacs in the lungs, and passes back into the heart again. This is how oxygen gets from the air into our bloodstream. A common measurement of blood pressure is around 120 over 80 mmHg in healthy people. This measurement reflects the blood’s pressure circulating in the body.

Pulmonary artery blood pressure measures the blood pressure in the pulmonary artery, which carries blood from the heart to the lungs. Since blood does not have to travel far from the heart to the lungs, normal pressure in the pulmonary artery is relatively low — less than 20 mmHg. Pulmonary artery pressure above 25 mmHg is associated with PH. High pulmonary vascular resistance, or the resistance against blood flow through the pulmonary blood vessels, is another sign of PH.

Hypoxia-induced PH in humans was first reported in 1947, when scientists found that people who were temporarily exposed to low levels of oxygen showed rapid increases in their pulmonary artery blood pressure. This response is beneficial in the short term, because it gets more blood into the lungs — and enough oxygen in the bloodstream. However, long-term exposure to low oxygen (chronic hypoxia) can have severe adverse effects.

People who travel to high-altitude areas — places in the mountains, for example — can experience symptoms like cough, headaches, dizziness, and shortness of breath. High-altitude traveling is also associated with a higher pulmonary artery blood pressure. These symptoms go away when people return to lower altitudes or when they are given oxygen.

Hypoxia-induced PH is the second most common cause of PH after heart disease. The World Health Organization classifies PH into five groups, with hypoxia-induced PH being Group III.

How Hypoxia Causes Pulmonary Hypertension

Scientists are still learning exactly how hypoxia leads to PH. Generally, research shows that over time, hypoxic conditions cause the pulmonary arteries to narrow. As the vessels narrow, less blood can flow through. This restricts blood flow to the lungs and causes the heart to pump harder.

Pulmonary arteries are lined with specialized cells called pulmonary arterial smooth muscle cells. These cells can relax to increase blood flow or contract to decrease blood flow through the arteries. When oxygen levels are low in a particular area of the lungs, smooth muscle cells in that area contract to reduce blood flow to that area. This helps divert blood to healthy areas of the lungs that are richer in oxygen.

These changes can occur rapidly, and blood pressure improves when the damaged area of the lung receives proper oxygen again. During prolonged exposures to low oxygen, however, the pulmonary arteries permanently narrow, which makes it more difficult for blood to flow to the lungs — and makes the heart pump harder to compensate.

The heart has four chambers that pump blood to different parts of the heart, lungs, and the rest of the body. Blood is sent to the lungs via the pulmonary artery, which exits through the right ventricle of the heart. As the blood pressure increases in the pulmonary artery, the right ventricle works harder to pump. Over time, the right ventricle becomes enlarged (right ventricular hypertrophy). Eventually, the overworked right ventricle cannot pump blood well, leading to right heart failure and death.

Hypoxia-inducible factors (HIFs) play a major role in the changes in pulmonary blood vessels in low-oxygen conditions. HIFs are transcription factors, which means that they are responsible for turning on certain genes in our body. In normal oxygen conditions, HIFs are not active. Low-oxygen conditions signal HIFs to activate and alter different gene expressions. Though some HIFs usually help control immune responses, studies of mice show that other HIFs contribute to changes in the pulmonary blood vessels that lead to PH in hypoxic conditions.

Other processes that can contribute to hypoxia-induced PH include:

  • Oxidative stress — This occurs when unstable molecules damage DNA and proteins in cells in response to low-oxygen conditions.
  • Inflammation — This is the body’s way of responding to infections or damage. Inflammation can also be triggered by oxidative stress. It can lead to further restriction of blood flow and stress on the heart and lungs, making PH worse.
  • Fibrosis of the heart — Fibroblasts make collagen to build structures in the body and heal wounds. Heart injury activates myofibroblasts, a special type of fibroblast. A study in rats showed that hypoxia caused fibrosis in the heart, which leads to heart dysfunction and failure.

High-Altitude Communities and Pulmonary Hypertension

Not everyone who lives at a high altitude experiences hypoxia-induced PH. Some populations that have lived at high altitudes for thousands of years show genetic adaptations to their environments that help them avoid hypoxia-induced PH. For example, Tibetan people have genetic changes in how HIFs function that might make them less likely to experience PH.

One systematic review compared pulmonary artery pressure measurements for people living at high altitudes to those living at low altitudes. Though high-altitude populations had higher pulmonary artery pressures, researchers suggested that less than 1 percent of this population experiences severe PH.

Symptoms and Diagnosis of Hypoxia-Induced Pulmonary Hypertension

The symptoms of hypoxia-induced PH are similar to other types of PH. They include:

  • Shortness of breath or difficulty breathing (dyspnea)
  • Lowered capacity to exercise
  • Chest pain (angina)
  • Fatigue
  • Swelling in the legs, abdomen, or around the eyes (edema)
  • Changes in skin color or temperature
  • Cognitive changes referred to as “brain fog”

Diagnosing hypoxia-induced PH depends on your symptoms, medical history, pulmonary artery pressure measurement, heart function, lung function, and exposure to low-oxygen conditions. Many of these require specialized tests, such as lung scans, echocardiography, and lung function tests.

Treatment for Hypoxia-Induced Pulmonary Hypertension

There are no specific treatments for hypoxia-induced PH. Treatments will depend on the underlying cause, so talking with your health care team is important in finding the right treatment for you.

Hypoxia-induced PH caused by traveling to high altitudes can often be reversed by returning to lower elevations. For most people with hypoxia-induced PH (especially due to COPD), long-term oxygen treatment can help relieve symptoms and prevent the underlying disease from getting worse.

Unfortunately, there are not a lot of studies on medications that can benefit people with hypoxia-induced PH. Although not routinely recommended by current guidelines, some medications to manage pulmonary arterial hypertension may also be used in some cases to treat hypoxia-induced PH. These medications include:

  • Prostaglandins — These drugs are vasodilators, meaning they help dilate (relax and open up) blood vessels in the lungs to increase blood flow. Inhaled or intravenous versions of these medications may be useful for those with hypoxia-induced PH due to interstitial lung disease. The U.S. Food and Drug Administration (FDA) recently approved an inhaled version of treprostinil for treatment of PH due to interstitial lung disease, making it the first FDA-approved treatment for Group III PH.
  • Calcium channel antagonists — Procardia (nifedipine) has been shown to reduce pulmonary blood pressures in people with PH living at high altitudes. Some studies suggest that these medications may improve PH for people with COPD, but not for those with interstitial lung disease.
  • Phosphodiesterase 5 inhibitors — Revatio (sildenafil) has been studied in people with PH due to interstitial lung disease. It may show some small improvements in quality of life, but more studies are needed.
  • Endothelin receptor antagonists — Studies show that endothelin-1 is increased in people experiencing hypoxia at high altitudes. Endothelin-1 is a vasoconstrictor (a substance made by the body that narrows blood vessels). Endothelin receptor antagonists block endothelins, which can help blood vessels widen and improve blood flow.

Treating underlying conditions such as lung disease or sleep apnea can improve hypoxia-induced PH. Quitting smoking is essential in preventing lung disease or keeping existing lung disease from getting worse.

Medications to manage lung disease can also improve your ability to breathe and get enough oxygen. Inhaled bronchodilators (inhalers) and steroid pills are common treatments for COPD. Sleep apnea can be treated with a device to help you breathe at night, like a continuous positive airway pressure (CPAP) machine or supplemental oxygen.

Preconditioning or training for short periods in hypoxic conditions can help improve resistance to hypoxia. One study of rats showed that a nanocurcumin supplement coupled with physical training helped protect against hypoxia at high altitudes.

Exercise can also be helpful for people with hypoxia-induced PH due to other diseases. Pulmonary rehabilitation programs focus on teaching you how to increase your fitness to improve symptoms and breathe more efficiently.

Talk to People Who Understand

On myPHteam, the social network for people with pulmonary hypertension and their loved ones, more than 41,800 members come together to ask questions, give advice, and share their stories with others who understand life with pulmonary hypertension.

Have you experienced hypoxia-induced pulmonary hypertension? Share your experience in the comments below, or share your story on myPHteam.

References
  1. Altitude — National Geographic
  2. Hypoxemia — Mayo Clinic
  3. Thin Air, Thick Vessels: Historical and Current Perspectives on Hypoxic Pulmonary Hypertension — Frontiers in Medicine
  4. The Influence of Short Periods of Induced Acute Anoxia Upon Pulmonary Artery Pressures in Man — American Journal of Physiology
  5. Sleep Apnea: Symptoms and Causes — Mayo Clinic
  6. Oxidative Stress, Kinase Activity, and Inflammatory Implications in Right Ventricular Hypertrophy and Heart Failure Under Hypobaric Hypoxia — International Journal of Molecular Sciences
  7. How the Heart Works — MyHealth.Alberta.ca
  8. Regulation of Hypoxia-Induced Pulmonary Hypertension by Vascular Smooth Muscle Hypoxia-Inducible Factor-1α — American Journal of Respiratory and Critical Care Medicine
  9. Tsantan Sumtang Attenuated Chronic Hypoxia-Induced Right Ventricular Structure Remodeling and Fibrosis by Equilibrating Local ACE-AngII-AT1R/ACE2-Ang1-7-Mas Axis in Rat — Journal of Ethnopharmacology
  10. Pulmonary Artery Pressure and Arterial Oxygen Saturation in People Living at High or Low Altitude: Systematic Review and Meta-Analysis — Journal of Applied Physiology
  11. Treatment of Pulmonary Hypertension Related to Disorders of Hypoxia — Advances in Pulmonary Hypertension
  12. Endothelin-1 in Pulmonary Hypertension Associated With High-Altitude Exposure — Circulation
  13. FDA Approves First Drug for Group 3 PH — Pulmonary Hypertension Association
  14. The Use of Sildenafil To Treat Pulmonary Hypertension Associated With Interstitial Lung Disease — Respirology
  15. Reversal of Hypoxic Pulmonary Hypertension by Hypoxia-Inducible Overexpression of Angiotensin-(1-7) in Pulmonary Endothelial Cells — Molecular Therapy: Methods and Clinical Development
  16. COPD: Diagnosis and Treatment — Mayo Clinic
  17. Rhodiola crenulata Extract Counteracts the Effect of Hypobaric Hypoxia in Rat Heart via Redirection of the Nitric Oxide and Arginase 1 Pathway — BMC Complementary and Alternative Medicine
  18. Cardioprotection by Intermittent Hypoxia Conditioning: Evidence, Mechanisms, and Therapeutic Potential — American Journal of Physiology-Heart and Circulatory Physiology
  19. Combinatorial Therapy of Exercise-Preconditioning and Nanocurcumin Formulation Supplementation Improves Cardiac Adaptation Under Hypobaric Hypoxia — Journal of Basic and Clinical Physiology and Pharmacology
  20. How Pulmonary Rehab Helps You Breathe — American Lung Association
  21. 2015 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension — European Respiratory Journal
  22. The Trouble With Group 3 Pulmonary Hypertension in Interstitial Lung Disease: Dilemmas in Diagnosis and the Conundrum of Treatment — Chest
All updates must be accompanied by text or a picture.
Steven C. Pugliese, M.D. is affiliated with the Hospital of the University of Pennsylvania in Philadelphia, serving as the director of the pulmonary embolism response team, co-director of the comprehensive pulmonary embolism program, and an assistant professor of clinical medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Ashley Knox is a doctoral candidate at the University of Colorado, where she studies the noncoding RNAs involved in gammaherpesvirus pathogenesis. Learn more about her here.

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