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 chemica ...
phenomenon in which small
pulmonary
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of ...
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 matching of two variables:
* V – ventilation – the air that reaches the alveoli
* Q – perfusion – the blo ...
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
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 c ...
, and pulmonary arterial pressure, potentially leading to
pulmonary hypertension and
pulmonary edema
Pulmonary edema, also known as pulmonary congestion, is excessive liquid accumulation in the tissue and air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia and respiratory failure. It is due ...
.
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: th ...
,
hypocapnia
Hypocapnia (from the Greek words υπό meaning ''below normal'' and καπνός ''kapnós'' meaning ''smoke''), also known as hypocarbia, sometimes incorrectly called acapnia, is a state of reduced carbon dioxide in the blood. Hypocapnia usually ...
,
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 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'' describe ...
/
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). Alkalosi ...
, 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 two ...
, 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 ...
(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
Isoprenaline, or isoproterenol (brand name: Isoprenaline Macure), is a medication used for the treatment of bradycardia (slow heart rate), heart block, and rarely for asthma. It is a non-selective β adrenoceptor agonist that is the isopropyla ...
,
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 ...
, and
vasodilators
Vasodilation 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. The process is the opposite of vasoconstriction ...
.
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 c ...
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, etc.) with a permea ...
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 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 regula ...
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 ve ...
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
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 . However, cases have also been reported between in more vulnerable subjects.
...
(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 ...
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