Hypoxic pulmonary vasoconstriction

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Hypoxic pulmonary vasoconstriction (HPV), also known as the Euler-Liljestrand mechanism, is a physiological phenomenon in which small pulmonary arteries constrict in the presence of alveolar hypoxia (low oxygen levels). By redirecting blood flow from poorly-ventilated lung regions to well-ventilated lung regions, HPV is thought to be the primary mechanism underlying ventilation/perfusion matching. [1] [2]

Contents

The process might initially seem counterintuitive, as low oxygen levels might theoretically stimulate increased blood flow to the lungs to increase gas exchange. However, the purpose of HPV is to distribute bloodflow regionally to increase the overall efficiency of gas exchange between air and blood. While the maintenance of ventilation/perfusion ratio during regional obstruction of airflow is beneficial, HPV can be detrimental during global alveolar hypoxia which occurs with exposure to high altitude, where HPV causes a significant increase in total pulmonary vascular resistance, and pulmonary arterial pressure, potentially leading to pulmonary hypertension and pulmonary edema.

Several factors inhibit HPV including increased cardiac output, hypocapnia, hypothermia, acidosis/alkalosis, increased pulmonary vascular resistance, inhaled anesthetics, calcium channel blockers, positive end-expiratory pressure (PEEP), high-frequency ventilation (HFV), isoproterenol, nitric oxide, and vasodilators.

Molecular mechanism

The classical explanation of HPV involves inhibition of hypoxia-sensitive voltage-gated potassium channels in pulmonary artery smooth muscle cells leading to depolarization. [3] [4] This depolarization activates voltage-dependent calcium channels, which increases intracellular calcium and activates smooth muscle contractile machinery which in turn causes vasoconstriction. However, later studies have reported additional ion channels and mechanisms that contribute to HPV, such as transient receptor potential canonical 6 (TRPC6) channels, and transient receptor potential vanilloid 4 (TRPV4) channels. [5] [6] Recently it was proposed that hypoxia is sensed at the alveolar/capillary level, generating an electrical signal that is transduced to pulmonary arterioles through gap junctions in the pulmonary endothelium to cause HPV. [7] This contrasts with the classical explanation of HPV which presumes that hypoxia is sensed at the pulmonary artery smooth muscle cell itself. Specialized epithelial cells (neuroepithelial bodies) that release serotonin have been suggested to contribute to hypoxic pulmonary venoconstriction. [8]

High altitude pulmonary edema

High-altitude mountaineering can induce pulmonary hypoxia due to decreased atmospheric pressure. This hypoxia causes vasoconstriction that ultimately leads to high altitude pulmonary edema (HAPE). For this reason, some climbers carry supplemental oxygen to prevent hypoxia, edema, and HAPE. The standard drug treatment of dexamethasone does not alter the hypoxia or the consequent vasoconstriction, but stimulates fluid reabsorption in the lungs to reverse the edema. Additionally, several studies on native populations remaining at high altitudes have demonstrated to varying degrees the blunting of the HPV response. [9]

Related Research Articles

<span class="mw-page-title-main">Hypoxia (medicine)</span> Medical condition of lack of oxygen in the tissues

Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level. Hypoxia may be classified as either generalized, affecting the whole body, or local, affecting a region of the body. Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise.

<span class="mw-page-title-main">Meconium aspiration syndrome</span> Medical condition affecting newborn infants

Meconium aspiration syndrome (MAS) also known as neonatal aspiration of meconium is a medical condition affecting newborn infants. It describes the spectrum of disorders and pathophysiology of newborns born in meconium-stained amniotic fluid (MSAF) and have meconium within their lungs. Therefore, MAS has a wide range of severity depending on what conditions and complications develop after parturition. Furthermore, the pathophysiology of MAS is multifactorial and extremely complex which is why it is the leading cause of morbidity and mortality in term infants.

<span class="mw-page-title-main">Respiratory system</span> Biological system in animals and plants for gas exchange

The respiratory system is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies greatly, depending on the size of the organism, the environment in which it lives and its evolutionary history. In land animals, the respiratory surface is internalized as linings of the lungs. Gas exchange in the lungs occurs in millions of small air sacs; in mammals and reptiles, these are called alveoli, and in birds, they are known as atria. These microscopic air sacs have a very rich blood supply, thus bringing the air into close contact with the blood. These air sacs communicate with the external environment via a system of airways, or hollow tubes, of which the largest is the trachea, which branches in the middle of the chest into the two main bronchi. These enter the lungs where they branch into progressively narrower secondary and tertiary bronchi that branch into numerous smaller tubes, the bronchioles. In birds, the bronchioles are termed parabronchi. It is the bronchioles, or parabronchi that generally open into the microscopic alveoli in mammals and atria in birds. Air has to be pumped from the environment into the alveoli or atria by the process of breathing which involves the muscles of respiration.

<span class="mw-page-title-main">Altitude sickness</span> Medical condition due to rapid exposure to low oxygen at high altitude

Altitude sickness, the mildest form being acute mountain sickness (AMS), is a harmful effect of high altitude, caused by rapid exposure to low amounts of oxygen at high elevation. People can respond to high altitude in different ways. Symptoms may include headaches, vomiting, tiredness, confusion, trouble sleeping, and dizziness. Acute mountain sickness can progress to high-altitude pulmonary edema (HAPE) with associated shortness of breath or high-altitude cerebral edema (HACE) with associated confusion. Chronic mountain sickness may occur after long-term exposure to high altitude.

Dead space is the volume of air that is inhaled that does not take part in the gas exchange, because it either remains in the conducting airways or reaches alveoli that are not perfused or poorly perfused. It means that not all the air in each breath is available for the exchange of oxygen and carbon dioxide. Mammals breathe in and out of their lungs, wasting that part of the inhalation which remains in the conducting airways where no gas exchange can occur.

<span class="mw-page-title-main">Pulmonary edema</span> Fluid accumulation in the tissue and air spaces of the lungs

Pulmonary edema, also known as pulmonary congestion, is excessive fluid accumulation in the tissue or air spaces of the lungs. This leads to impaired gas exchange, most often leading to shortness of breath (dyspnea) which can progress to hypoxemia and respiratory failure. Pulmonary edema has multiple causes and is traditionally classified as cardiogenic or noncardiogenic.

<span class="mw-page-title-main">Diving reflex</span> The physiological responses to immersion of air-breathing vertebrates

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Vascular resistance is the resistance that must be overcome for blood to flow through the circulatory system. The resistance offered by the systemic circulation is known as the systemic vascular resistance (SVR) or may sometimes be called by the older term total peripheral resistance (TPR), while the resistance offered by the pulmonary circulation is known as the pulmonary vascular resistance (PVR). Systemic vascular resistance is used in calculations of blood pressure, blood flow, and cardiac function. Vasoconstriction increases SVR, whereas vasodilation decreases SVR.

<span class="mw-page-title-main">Pulmonary hypertension</span> Increased blood pressure in lung arteries

Pulmonary hypertension is a condition of increased blood pressure in the arteries of the lungs. Symptoms include shortness of breath, fainting, tiredness, chest pain, swelling of the legs, and a fast heartbeat. The condition may make it difficult to exercise. Onset is typically gradual. According to the definition at the 6th World Symposium of Pulmonary Hypertension in 2018, a patient is deemed to have pulmonary hypertension if the pulmonary mean arterial pressure is greater than 20mmHg at rest, revised down from a purely arbitrary 25mmHg, and pulmonary vascular resistance (PVR) greater than 3 Wood units.

<span class="mw-page-title-main">Generalized hypoxia</span> Medical condition of oxygen deprivation

Generalized hypoxia is a medical condition in which the tissues of the body are deprived of the necessary levels of oxygen due to an insufficient supply of oxygen, which may be due to the composition or pressure of the breathing gas, decreased lung ventilation, or respiratory disease, any of which may cause a lower than normal oxygen content in the arterial blood, and consequently a reduced supply of oxygen to all tissues perfused by the arterial blood. This usage is in contradistinction to localized hypoxia, in which only an associated group of tissues, usually with a common blood supply, are affected, usually due to an insufficient or reduced blood supply to those tissues. Generalized hypoxia is also used as a synonym for hypoxic hypoxia This is not to be confused with hypoxemia, which refers to low levels of oxygen in the blood, although the two conditions often occur simultaneously, since a decrease in blood oxygen typically corresponds to a decrease in oxygen in the surrounding tissue. However, hypoxia may be present without hypoxemia, and vice versa, as in the case of infarction. Several other classes of medical hypoxia exist.

<span class="mw-page-title-main">High-altitude pulmonary edema</span> Human disease

High-altitude pulmonary edema (HAPE) is a life-threatening form of non-cardiogenic pulmonary edema that occurs in otherwise healthy people at altitudes typically above 2,500 meters (8,200 ft). However, cases have also been reported between 1,500–2,500 metres or 4,900–8,200 feet in more vulnerable subjects.

Hyperoxia occurs when cells, tissues and organs are exposed to an excess supply of oxygen (O2) or higher than normal partial pressure of oxygen.

<span class="mw-page-title-main">Hypoxemia</span> Abnormally low level of oxygen in the blood

Hypoxemia is an abnormally low level of oxygen in the blood. More specifically, it is oxygen deficiency in arterial blood. Hypoxemia has many causes, and often causes hypoxia as the blood is not supplying enough oxygen to the tissues of the body.

Aerospace physiology is the study of the effects of high altitudes on the body, such as different pressures and levels of oxygen. At different altitudes the body may react in different ways, provoking more cardiac output, and producing more erythrocytes. These changes cause more energy waste in the body, causing muscle fatigue, but this varies depending on the level of the altitude.

A pulmonary shunt is the passage of deoxygenated blood from the right side of the heart to the left without participation in gas exchange in the pulmonary capillaries. It is a pathological condition that results when the alveoli of parts of the lungs are perfused with blood as normal, but ventilation fails to supply the perfused region. In other words, the ventilation/perfusion ratio of those areas is zero.

<span class="mw-page-title-main">Effects of high altitude on humans</span> Environmental effects on physiology and mental health

The effects of high altitude on humans are mostly the consequences of reduced partial pressure of oxygen in the atmosphere. The medical problems that are direct consequence of high altitude are caused by the low inspired partial pressure of oxygen, which is caused by the reduced atmospheric pressure, and the constant gas fraction of oxygen in atmospheric air over the range in which humans can survive. The other major effect of altitude is due to lower ambient temperature.

<span class="mw-page-title-main">TRPC6</span> Protein and coding gene in humans

Transient receptor potential cation channel, subfamily C, member 6 or Transient receptor potential canonical 6, also known as TRPC6, is a human gene encoding a protein of the same name. TRPC6 is a transient receptor potential channel of the classical TRPC subfamily.

Juxtacapillary receptors, J-receptors, or pulmonary C-fiber receptors are sensory nerve endings located within the alveolar walls in juxtaposition to the pulmonary capillaries of the lung, and are innervated by fibers of the vagus nerve. Although their functional role is unclear, J-receptors respond to events such as pulmonary edema, pulmonary emboli, pneumonia, congestive heart failure and barotrauma, which cause a decrease in oxygenation and thus lead to an increase in respiration. They may be also stimulated by hyperinflation of the lung as well as intravenous or intracardiac administration of chemicals such as capsaicin. The stimulation of the J-receptors causes a reflex increase in breathing rate, and is also thought to be involved in the sensation of dyspnea, the subjective sensation of difficulty breathing. The reflex response that is produced is apnea followed by rapid breathing, bradycardia, and hypotension. The physiologic role of this reflex is uncertain, but it probably occurs in pathologic states such as pulmonary congestion or embolization. These receptors were discovered by Autar Paintal.

Hypoxic ventilatory response (HVR) is the increase in ventilation induced by hypoxia that allows the body to take in and transport lower concentrations of oxygen at higher rates. It is initially elevated in lowlanders who travel to high altitude, but reduces significantly over time as people acclimatize. In biological anthropology, HVR also refers to human adaptation to environmental stresses resulting from high altitude.

Swimming induced pulmonary edema (SIPE), also known as immersion pulmonary edema, is a life threatening condition that occurs when fluids from the blood leak abnormally from the small vessels of the lung (pulmonary capillaries) into the airspaces (alveoli).

References

  1. ↑ Silverthorn, D.U. (2016). "Chapter 14-15". Human physiology (7th ed.). New York: Pearson Education. p. 544.
  2. ↑ Sylvester, J. T.; Shimoda, Larissa A.; Aaronson, Philip I.; Ward, Jeremy P. T. (2012-01-01). "Hypoxic pulmonary vasoconstriction". Physiological Reviews. 92 (1): 367–520. doi:10.1152/physrev.00041.2010. ISSN   1522-1210. PMC   9469196 . PMID   22298659. S2CID   78887723.
  3. ↑ Post, J. M.; Hume, J. R.; Archer, S. L.; Weir, E. K. (1992-04-01). "Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction". The American Journal of Physiology. 262 (4 Pt 1): C882–890. doi:10.1152/ajpcell.1992.262.4.C882. ISSN   0002-9513. PMID   1566816.
  4. ↑ Yuan, X. J.; Goldman, W. F.; Tod, M. L.; Rubin, L. J.; Blaustein, M. P. (1993-02-01). "Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes". The American Journal of Physiology. 264 (2 Pt 1): L116–123. doi:10.1152/ajplung.1993.264.2.L116. ISSN   0002-9513. PMID   8447425. S2CID   31223667.
  5. ↑ Weissmann, Norbert; Dietrich, Alexander; Fuchs, Beate; Kalwa, Hermann; Ay, Mahmut; Dumitrascu, Rio; Olschewski, Andrea; Storch, Ursula; Mederos y Schnitzler, Michael (2006-12-12). "Classical transient receptor potential channel 6 (TRPC6) is essential for hypoxic pulmonary vasoconstriction and alveolar gas exchange". Proceedings of the National Academy of Sciences of the United States of America. 103 (50): 19093–19098. Bibcode:2006PNAS..10319093W. doi: 10.1073/pnas.0606728103 . ISSN   0027-8424. PMC   1748182 . PMID   17142322.
  6. ↑ Goldenberg, Neil M.; Wang, Liming; Ranke, Hannes; Liedtke, Wolfgang; Tabuchi, Arata; Kuebler, Wolfgang M. (2015-06-01). "TRPV4 Is Required for Hypoxic Pulmonary Vasoconstriction". Anesthesiology. 122 (6): 1338–1348. doi:10.1097/ALN.0000000000000647. ISSN   1528-1175. PMID   25815455. S2CID   24364626.
  7. ↑ Wang, Liming; Yin, Jun; Nickles, Hannah T.; Ranke, Hannes; Tabuchi, Arata; Hoffmann, Julia; Tabeling, Christoph; Barbosa-Sicard, Eduardo; Chanson, Marc; Kwak, Brenda R.; Shin, Heesup S.; Wu, Songwei; Isakson, Brant E.; Witzenrath, Martin; de Wit, Cor; Fleming, Ingrid; Kuppe, Hermann; Kuebler, Wolfgang M. (2012-11-01). "Hypoxic pulmonary vasoconstriction requires connexin 40-mediated endothelial signal conduction". The Journal of Clinical Investigation. 122 (11): 4218–4230. doi:10.1172/JCI59176. ISSN   1558-8238. PMC   3484430 . PMID   23093775.
  8. ↑ Lauweryns, Joseph M.; Cokelaere, Marnix; Theunynck, Paul (1973). "Serotonin Producing Neuroepithelial Bodies in Rabbit Respiratory Mucosa". Science. 180 (4084): 410–413. doi:10.1126/science.180.4084.410. ISSN   0036-8075.
  9. ↑ Swenson, Erik R. (24 Jun 2013). "Hypoxic Pulmonary Vasoconstriction". High Altitude Medicine & Biology. 14 (2): 101–110. doi:10.1089/ham.2013.1010. PMID   23795729.
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