Hypoxic pulmonary vasoconstriction and cor pulmonale
Low oxygen constricts the small pulmonary arteries. In one poorly ventilated patch this protects gas exchange; across the whole lung, it strains the right ventricle.
Explain hypoxic pulmonary vasoconstriction, its role in V/Q matching and how chronic hypoxia leads to pulmonary hypertension and cor pulmonale.
The short version
- Hypoxic pulmonary vasoconstriction diverts blood from poorly ventilated lung to well-ventilated lung and keeps V/Q matched.
- Low oxygen inhibits Kv channels, the smooth muscle depolarises, L-type calcium channels open and the vessel constricts.
- When the whole lung is hypoxic, as in COPD, constriction plus remodelling of the small arteries raises pulmonary vascular resistance.
- Pulmonary hypertension is a mean pulmonary artery pressure above 20 mmHg at rest; lung disease causes the pre-capillary type, with a normal wedge pressure.
- Right ventricular hypertrophy caused by pulmonary hypertension from lung disease is cor pulmonale.
The pulmonary circuit: low pressure, low resistance
Hypoxic pulmonary vasoconstriction is one reflex with two very different outcomes. Starve one patch of lung of oxygen and blood flow to that patch falls. Starve the whole lung for years and the right side of the heart can fail.
The pulmonary circulation is a low-pressure, low-resistance circuit.[2] The normal mean pulmonary artery pressure is about 14 mmHg, and pulmonary hypertension is a mean above 20 mmHg at rest.[5]
Lung disease causes pre-capillary pulmonary hypertension: the problem is in the lung vessels, not the left heart. The wedge pressure, which reflects the left atrium, is normal at 15 mmHg or below, and pulmonary vascular resistance is raised (3 Wood units or more in the 2019 definition).[5]
Hypoxic pulmonary vasoconstriction: the mechanism
When oxygen is low, the small pulmonary arteries constrict. This is hypoxic pulmonary vasoconstriction (HPV), and it is unique to the pulmonary circulation.[1][4] The mechanism is in four steps.[1][3]
- Low oxygen inhibits Kv channelsVoltage-gated potassium channels in the pulmonary artery smooth muscle are inhibited, so less potassium leaves the cell.
- The cell depolarisesWith less positive charge leaving, the smooth muscle cell depolarises.
- Calcium channels openDepolarisation opens L-type calcium channels and calcium flows in.
- The vessel constrictsCalcium entry makes the small pulmonary artery constrict.
Why HPV helps: V/Q matching and the shunt fraction
The reflex reduces blood flow to poorly ventilated regions and diverts it to well-ventilated ones. That keeps ventilation and perfusion matched.[1][2][7]
- Cardiac output = 5 L/min; pneumonia fills one lobe.
- Suppose 1 L/min still flows through the unventilated lobe. That blood picks up no oxygen and stays venous.
- Shunt fraction = 1 / 5 = 20%.
- HPV cuts the lobe's flow to 0.5 L/min: 0.5 / 5 = 10%.
- The shunt fraction has halved, and arterial PaO₂ is better for it.
This is the helpful, local version of the reflex.
The harmful version: chronic hypoxia and pulmonary hypertension
The harmful version appears when the whole lung is hypoxic. In COPD, in other chronic lung disease and at high altitude, the entire pulmonary bed is under low oxygen and constricts, so pulmonary vascular resistance rises.[4]
Chronic hypoxia also remodels the vessels: the small arteries thicken and muscularise, becoming stiffer and more resistant.[2][4]
The result is pulmonary hypertension, which in COPD is usually mild to moderate, with a mean pressure below about 35 mmHg.[2]
| Situation | Hypoxia is | Effect of constriction |
|---|---|---|
| Pneumonia in one lobe | Local | Flow diverted to ventilated lung; shunt fraction falls; V/Q better matched |
| COPD, chronic lung disease, high altitude | Whole lung | Vascular resistance rises; small arteries remodel; pulmonary hypertension |
Cor pulmonale: when the right ventricle fails
The right ventricle is built for low pressure and now pumps against a high one. It hypertrophies, dilates and eventually fails.
Cor pulmonale is right ventricular hypertrophy caused by lung disease, through pulmonary hypertension. COPD is its most common cause.[2][6][8]
Treatment links back to the mechanism: in COPD with severe resting hypoxaemia, long-term oxygen therapy improves survival and slows progression of pulmonary hypertension.[2]
Practice question
Original · USMLE styleA 67-year-old woman with a 45 pack-year smoking history and long-standing COPD has progressive dyspnoea and ankle swelling. Examination shows raised jugular venous pressure, bilateral pitting oedema and a loud pulmonic component of the second heart sound. On room air, arterial PaO₂ is 54 mmHg. Echocardiography shows right ventricular hypertrophy with normal left ventricular systolic function. Right heart catheterisation shows a mean pulmonary artery pressure of 32 mmHg and a pulmonary artery wedge pressure of 9 mmHg.
Common questions
What is hypoxic pulmonary vasoconstriction?
It is the constriction of the small pulmonary arteries when oxygen is low, and it is unique to the pulmonary circulation. It diverts blood from poorly ventilated lung to well-ventilated lung.
How does hypoxia cause pulmonary vasoconstriction?
Low oxygen inhibits voltage-gated potassium channels in the pulmonary artery smooth muscle. Less potassium leaves the cell, so it depolarises, L-type calcium channels open and calcium entry constricts the vessel.
Why does chronic hypoxia cause pulmonary hypertension?
When the whole lung is hypoxic, the entire pulmonary bed constricts and the small arteries thicken and muscularise. Both changes raise pulmonary vascular resistance.
What is cor pulmonale?
It is right ventricular hypertrophy caused by pulmonary hypertension from lung disease, and COPD is its most common cause. Right heart failure from left heart disease is not cor pulmonale.
What is the pulmonary artery wedge pressure in pulmonary hypertension from lung disease?
Lung disease gives pre-capillary pulmonary hypertension, so the wedge pressure, which reflects the left atrium, is normal at 15 mmHg or below.
Transcript
Read the full narration, by chapter682 words
0:00The hook and today's objective
Starve one patch of lung of oxygen, and blood flow to that patch falls. Starve the whole lung for years, and the right side of the heart can fail. The same reflex, two very different outcomes. How? Today: explain hypoxic pulmonary vasoconstriction, and how chronic hypoxia leads to pulmonary hypertension and cor pulmonale.
0:23The pulmonary circuit: low pressure, low resistance
The pulmonary circulation is a low-pressure, low-resistance circuit. The normal mean pulmonary artery pressure is about 14 mm Hg, and pulmonary hypertension is a mean above 20 at rest. Lung disease causes pre-capillary pulmonary hypertension, meaning the problem is in the lung vessels, not the left heart: the wedge pressure, which reflects the left atrium, is normal, 15 or below.
0:50Hypoxic vasoconstriction: small arteries constrict
When oxygen is low, the small pulmonary arteries constrict. This is hypoxic pulmonary vasoconstriction, and it is unique to the pulmonary circulation.
1:02The mechanism: Kv channels, depolarisation, calcium
Low oxygen inhibits voltage-gated potassium channels in the smooth muscle of the pulmonary arteries, so potassium builds up inside and the cell depolarises. Depolarisation opens L-type calcium channels, calcium flows in, and the vessel constricts.
1:19Why it helps: V/Q matching
This reflex reduces blood flow to poorly ventilated regions and diverts it to well-ventilated ones. That keeps ventilation and perfusion matched.
1:30Worked example: pneumonia and the shunt fraction
A worked example. Cardiac output is five litres a minute, and pneumonia fills one lobe. Suppose one litre a minute still flows through that unventilated lobe. That blood picks up no oxygen and stays venous, so the shunt fraction is one over five, 20%. Vasoconstriction cuts the lobe's flow to half a litre a minute. Half over five is 10%. The shunt fraction has halved, and the arterial PaO2 is better for it. That is the helpful, local version.
2:05The harmful version: the whole lung is hypoxic
The harmful version is when the whole lung is hypoxic. In COPD, in other chronic lung disease, and at high altitude, the entire pulmonary bed is under low oxygen and constricts, so pulmonary vascular resistance rises. Chronic hypoxia also remodels the vessels:
2:22Remodelling and pulmonary hypertension
the small arteries thicken and muscularise, and become stiffer and more resistant. The result is pulmonary hypertension, usually mild to moderate in COPD, with a mean pressure below about 35.
2:38The right ventricle and cor pulmonale
The right ventricle is built for low pressure, and now pumps against a high one. It hypertrophies, dilates, and eventually fails. Right ventricular hypertrophy caused by lung disease, through pulmonary hypertension, is cor pulmonale. Two points. Right heart failure from left heart disease is not cor pulmonale. And cor pulmonale is not simply right heart failure, which can have other causes. COPD is its most common cause. The treatment links back: in COPD with severe resting hypoxaemia, long-term oxygen therapy improves survival and slows progression of pulmonary hypertension. Your turn.
3:22Your turn: practice question
A 67-year-old woman has a 45 pack-year smoking history and chronic COPD. She has ankle oedema, a raised jugular venous pressure and a loud pulmonic second sound. On room air her arterial PaO2 is 54. Right heart catheterisation gives a mean pulmonary artery pressure of 32 and a wedge pressure of nine. Echocardiography shows right ventricular hypertrophy with normal left ventricular systolic function. Which best explains her pulmonary hypertension?
3:57The options, one at a time
A, elevated left atrial pressure from mitral stenosis. B, a ventricular septal defect with left-to-right shunting. C, loss of hypoxic pulmonary vasoconstriction in the diseased lung. D, sustained hypoxic vasoconstriction and arterial remodelling. E, hypoxia-induced pulmonary arteriolar vasodilation. Pause here and decide. A is out: mitral stenosis raises the wedge pressure, and hers is nine. B is out: a septal defect with left-to-right shunting would add flow, with no link to her hypoxia or lung disease. C is out: it is the opposite. Hypoxic vasoconstriction is preserved, and it is the problem. E is out: hypoxia constricts pulmonary vessels. It does not dilate them.
4:56The answer
So the answer is D. Chronic hypoxia constricts and remodels the small pulmonary arteries, raising resistance and strain on the right ventricle, which is cor pulmonale.
5:09High-yield recap
Three things to keep. One: hypoxic vasoconstriction diverts blood to well-ventilated regions and keeps V over Q matched. Two: chronic whole-lung hypoxia constricts and remodels small arteries, raising resistance. Three: right ventricular hypertrophy caused by pulmonary hypertension from lung disease is cor pulmonale.
5:33Next lesson
Next lesson: carbon monoxide, cyanide and methaemoglobin poisoning.
Sources
Numbers in the text, e.g. [1], point here- Mechanisms of hypoxemia. Lung India 2017. pmc.ncbi.nlm.nih.gov/articles/PMC5234199/
- Shujaat A, et al. Pulmonary hypertension and chronic cor pulmonale in COPD. 2007. pmc.ncbi.nlm.nih.gov/articles/PMC2695205/
- Lai N, et al. Ca2+ and ion channels in hypoxia-mediated pulmonary hypertension. 2015. pmc.ncbi.nlm.nih.gov/articles/PMC4396234/
- Hypoxic pulmonary hypertension: the paradigm is changing. pmc.ncbi.nlm.nih.gov/articles/PMC4204154/
- Simonneau G, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension (6th World Symposium). 2019. pmc.ncbi.nlm.nih.gov/articles/PMC6351336/
- StatPearls. Cor Pulmonale. ncbi.nlm.nih.gov/books/NBK430739/
- OpenStax Anatomy and Physiology 2e, 22.4 Gas Exchange. openstax.org/books/anatomy-and-physiology-2e/pages/22-4-gas-exchange
- Further per-claim sources in the ledger: PMC13214134, PMC8859503, PMC13609463, PMC13706757; PMC12789187 (Wang X, et al. Cor pulmonale in COPD in mice. Physiol Rep 2026; its introduction states COPD is the most common cause of cor pulmonale). pmc.ncbi.nlm.nih.gov/articles/PMC12789187/
The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.
Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted (recoloured, outlined, labelled): "Pulmonary circulation", "Lungs", "Systolic heart failure" (heart plate, with a schematic right-ventricle overlay). Alveoli and vessels: "Intrapulmonary airway, vein, artery" by Servier via Bioicons, CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/), adapted. Original diagrams: the smooth-muscle cell, the pressure number line, the shunt-fraction bar and the vessel cross-sections. No AI-generated teaching images.
Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-RESP-009.
For exam study only, not medical advice. Read the medical disclaimer.
In this series
Playlist on YouTube- EP 01Lung volumes and capacities, explained5:26
- EP 02Obstructive vs restrictive lung disease: FEV1/FVC and loops5:23
- EP 03Lung compliance, Laplace and surfactant: why alveoli stay open5:23
- EP 04V/Q mismatch: shunt, dead space and the oxygen test5:18
- EP 05A-a gradient: the alveolar gas equation and the causes of hypoxaemia5:39
- EP 06Oxygen-hemoglobin dissociation curve: P50, shifts and content5:19
- EP 07CO₂ transport: bicarbonate, the chloride shift, Bohr vs Haldane5:29
- EP 08Central vs peripheral chemoreceptors and oxygen-induced hypercapnia5:27
- EP 09Hypoxic pulmonary vasoconstriction and cor pulmonale5:41
- EP 10CO, cyanide and methaemoglobin: why SpO₂ and PaO₂ fool you5:34