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

physiological Physiology (; ) is the science, scientific study of function (biology), functions and mechanism (biology), mechanisms in a life, living system. As a branches of science, subdiscipline of biology, physiology focuses on how organisms, organ syst ...

phenomenon in which small

pulmonary The lungs are the primary organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the backbone on either side of the heart. Their function in the respiratory syste ...

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. 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 In respiratory physiology, the ventilation/perfusion ratio (V/Q ratio) is a ratio used to assess the efficiency and adequacy of the ventilation-perfusion coupling and thus the matching of two variables: * V – Ventilation (physiology), ventilatio ...

during ''regional'' obstruction of airflow is beneficial, HPV can be detrimental during ''global'' alveolar hypoxia which occurs with exposure to

high altitude Altitude 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 (e.g., aviation, geometry, geographical s ...

, where HPV causes a significant increase in total

pulmonary vascular resistance 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 or may sometimes be called by another ter ...

, and pulmonary arterial pressure, potentially leading to

pulmonary hypertension Pulmonary hypertension (PH or PHTN) is a condition of increased blood pressure in the pulmonary artery, arteries of the lungs. Symptoms include dypsnea, shortness of breath, Syncope (medicine), fainting, tiredness, chest pain, pedal edema, swell ...

and

pulmonary edema Pulmonary edema (British English: oedema), also known as pulmonary congestion, is excessive fluid accumulation in the tissue or air spaces (usually alveoli) of the lungs. This leads to impaired gas exchange, most often leading to shortness ...

. 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: tha ...

hypocapnia Hypocapnia (from the Greek words meaning ''below normal'' and ''kapnós'' meaning ''smoke''), also known as hypocarbia, sometimes incorrectly called acapnia, is a state of reduced carbon dioxide in the blood. Hypocapnia usually results from deep ...

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 ...

acidosis Acidosis is a biological process producing hydrogen ions and increasing their concentration in blood or body fluids. pH is the negative log of hydrogen ion concentration and so it is decreased by a process of acidosis. Acidemia The term ac ...

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 ...

, increased pulmonary vascular resistance, inhaled

anesthetics An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into tw ...

, 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 (HFV) 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 ...

(HFV),

isoproterenol Isoprenaline, also known as isoproterenol and sold under the brand name Isuprel among others, is a sympathomimetic medication which is used in the treatment of acute bradycardia (slow heart rate), heart block, and rarely for asthma, among other ...

nitric oxide Nitric oxide (nitrogen oxide, nitrogen monooxide, 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 den ...

, and

vasodilators Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wal ...

Molecular mechanism

The classical explanation of HPV involves inhibition of hypoxia-sensitive

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

s in pulmonary artery smooth muscle cells leading to depolarization. This depolarization activates

voltage-dependent calcium channel Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'' muscle, glial cells, neurons) with a permeability t ...

s, 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 membrane channels between adjacent cells that allow the direct exchange of cytoplasmic substances, such small molecules, substrates, and metabolites. Gap junctions were first described as ''close appositions'' alongside tight ...

s in the pulmonary

endothelium The endothelium (: endothelia) 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 r ...

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. Specialized

epithelial cells Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

(neuroepithelial bodies) that release serotonin have been suggested to contribute to hypoxic pulmonary venoconstriction.

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 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 . HAPE is a severe presentation of altitude sickness. Cases have also been re ...

(HAPE). For this reason, some climbers carry supplemental oxygen to prevent hypoxia, edema, and HAPE. The standard drug treatment of

dexamethasone Dexamethasone is a fluorinated glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive pulmonary disease (COPD), croup, brain swelling, eye pain following eye su ...

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