Hypoxic pulmonary vasoconstriction (HPV), also known as the Euler-Liljestrand mechanism, is a

physiological Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...

phenomenon in which small pulmonary arteries constrict in the presence of alveolar

hypoxia Hypoxia means a lower than normal level of oxygen, and may refer to: Reduced or insufficient oxygen * Hypoxia (environmental), abnormally low oxygen content of the specific environment * Hypoxia (medical), abnormally low level of oxygen in the tis ...

(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. 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 Altitude or height (also sometimes known as depth) is a distance measurement, usually in the vertical or "up" direction, between a reference datum and a point or object. The exact definition and reference datum varies according to the context ...

, where HPV causes a significant increase in total

pulmonary vascular resistance Vascular resistance is the resistance that must be overcome to push blood through the circulatory system and create flow. The resistance offered by the systemic circulation is known as the systemic vascular resistance (SVR) or may sometimes be ca ...

, and pulmonary arterial pressure, potentially leading to pulmonary hypertension and

pulmonary edema Pulmonary edema, also known as pulmonary congestion, is excessive edema, liquid accumulation in the parenchyma, tissue and pulmonary alveolus, air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia an ...

. Several factors inhibit HPV including increased

cardiac output In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: t ...

, hypocapnia,

hypothermia Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe h ...

acidosis Acidosis is a process causing increased acidity in the blood and other body tissues (i.e., an increase in hydrogen ion concentration). If not further qualified, it usually refers to acidity of the blood plasma. The term ''acidemia'' describes t ...

alkalosis Alkalosis is the result of a process reducing hydrogen ion concentration of arterial blood plasma (alkalemia). In contrast to acidemia (serum pH 7.35 or lower), alkalemia occurs when the serum pH is higher than normal (7.45 or higher). Alkalosis i ...

, increased pulmonary vascular resistance, inhaled anesthetics, calcium channel blockers,

positive end-expiratory pressure Positive end-expiratory pressure (PEEP) is the pressure in the lungs (alveolar pressure) above atmospheric pressure (the pressure outside of the body) that exists at the end of expiration. The two types of PEEP are extrinsic PEEP (PEEP applied by ...

(PEEP),

high-frequency ventilation High-frequency ventilation is a type of mechanical ventilation which utilizes a respiratory rate greater than four times the normal value. (>150 (Vf) breaths per minute) and very small tidal volumes. High frequency ventilation is thought to reduce ...

(HFV), isoproterenol,

nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...

, and vasodilators.

Molecular mechanism

The classical explanation of HPV involves inhibition of hypoxia-sensitive

voltage-gated potassium channel Voltage-gated potassium channels (VGKCs) are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized ce ...

s in pulmonary artery smooth muscle cells leading to depolarization. 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. 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 junction Gap junctions are specialized intercellular connections between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regulate ...

s in the pulmonary

endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...

to cause HPV. This contrasts with the classical explanation of HPV which presumes that hypoxia is sensed at the pulmonary artery smooth muscle cell itself.

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 Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena cav ...

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.

References

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External links

American Thoracic SocietyAmerican Journal of Physiology, Lung Cellular and Molecular Physiology
{{Respiratory physiology Respiratory physiology