Pulmonary Circulation & Diffusion
A low-pressure bed that recruits, redirects blood, and trades gas by diffusion
Two circulations and a low-pressure bed
Pulmonary versus bronchial. The pulmonary arteries carry the entire right-ventricular output to the alveolar capillaries for gas exchange. The bronchial arteries, branches of the aorta and intercostal arteries, carry only about 1–2% of cardiac output and nourish the airway walls down to the terminal bronchioles. Part of the bronchial venous return drains into the pulmonary veins, and thebesian veins empty some coronary venous blood directly into the left heart. This deoxygenated admixture is a normal physiologic shunt, one reason PaO2 is slightly lower than alveolar PO2 even in healthy lungs.
Low pressure by design. Pulmonary artery pressure is about 25/8 mmHg with a mean near 15 mmHg, compared with a mean aortic pressure near 95 mmHg. PVR, calculated as (mean PAP − left atrial pressure) / cardiac output, is roughly one-tenth of SVR, and the thin-walled vessels contain little smooth muscle. A resting mean PAP above 20 mmHg defines pulmonary hypertension (older definitions used ≥25).
Recruitment and distension. The bed is highly compliant. When cardiac output rises, as in exercise, capillaries that were closed — mostly at the apex — open (recruitment) and those already open widen (distension). PVR therefore falls, pulmonary artery pressure rises only slightly, and the larger capillary surface increases diffusing capacity.
Lung volume and PVR. Two vessel populations respond oppositely to inflation. Extra-alveolar vessels are held open by radial traction from surrounding lung, so they narrow at low lung volumes. Alveolar capillaries in the alveolar walls are stretched and compressed as alveoli enlarge, so they narrow at high volumes. Total PVR traces a U-shaped curve with its minimum near functional residual capacity.
Non-respiratory functions. The pulmonary endothelium converts angiotensin I to angiotensin II via ACE, inactivates bradykinin, serotonin and some prostaglandins, filters small emboli, and holds a blood reservoir for the left ventricle.
Hypoxic pulmonary vasoconstriction
Mechanism. A fall in alveolar PO2 inhibits O2-sensitive K+ channels in pulmonary arteriolar smooth muscle. The cell depolarizes, voltage-gated Ca2+ channels open, and the arteriole constricts. Acidosis and hypercapnia augment the response. Nitric oxide and prostacyclin dilate pulmonary vessels, whereas endothelin-1 and thromboxane A2 constrict them.
Purpose. Constriction in poorly ventilated regions diverts blood toward well-ventilated alveoli, preserving V/Q matching. Systemic arterioles behave in the opposite way, dilating when tissue is hypoxic so that flow matches metabolic demand. Drugs that blunt the reflex, such as nitroprusside or calcium channel blockers, can worsen hypoxemia in pneumonia or COPD.
Fetal and neonatal circulation. The fetal lung is fluid-filled and hypoxic, so PVR is high and most right-sided output bypasses the lungs through the foramen ovale and ductus arteriosus. With the first breaths, alveolar PO2 rises, NO is released and PVR falls steeply.
Chronic global hypoxia. When the whole lung is hypoxic — COPD, obstructive sleep apnea, residence at high altitude — vasoconstriction becomes diffuse and sustained, and vascular remodeling follows. The result is pulmonary hypertension, right-ventricular hypertrophy and eventually cor pulmonale. Long-term oxygen for hypoxemic COPD relieves the vasoconstriction and is one of the few therapies that prolongs survival. Uneven vasoconstriction at altitude overperfuses unconstricted vessels and contributes to high-altitude pulmonary edema.
Gravity and the West zones
Principle. In the upright lung, gravity raises arterial (Pa) and venous (Pv) pressures toward the base while alveolar pressure (PA) is nearly uniform, so perfusion increases from apex to base and the ranking of the three pressures sets regional flow.
| Zone | Pressure relationship | Flow | When it matters |
|---|---|---|---|
| Zone 1 (apex) | PA > Pa > Pv | None; ventilated but unperfused alveoli (dead space) | Absent normally; appears with hemorrhage or hypovolemia (↓Pa) or positive-pressure ventilation and high PEEP (↑PA) |
| Zone 2 (middle) | Pa > PA > Pv | Driven by Pa − PA (waterfall effect) | Upper and middle lung when upright |
| Zone 3 (base) | Pa > Pv > PA | Continuous; driven by Pa − Pv | Lung bases; where a pulmonary artery catheter must wedge for PCWP to reflect left atrial pressure |
Diffusion across the alveolar–capillary barrier
Fick's law. Gas transfer = (A/T) × D × (P1 − P2), where A is surface area (roughly 50–100 m²), T is barrier thickness (normally well under 1 μm), P1 − P2 is the partial-pressure gradient, and the diffusion constant D is proportional to solubility divided by the square root of molecular weight. Emphysema destroys area, fibrosis thickens the barrier, and high altitude shrinks the alveolar PO2 gradient. DLCO measures the lung's overall diffusing capacity using carbon monoxide.
CO2 versus O2. CO2 is far more soluble than O2, which outweighs its slightly larger molecular weight, so CO2 diffuses about 20 times more readily. CO2 exchange is almost never diffusion-limited, and diffusion defects cause hypoxemia long before hypercapnia; hypercapnia points instead to hypoventilation or severe V/Q mismatch.
Perfusion versus diffusion limitation. Red cells spend about 0.75 s in a pulmonary capillary at rest. For a perfusion-limited gas, plasma partial pressure reaches the alveolar value within the first third of that time (about 0.25 s), so the only way to take up more is to bring more blood. For a diffusion-limited gas, the gradient persists to the end of the capillary, so uptake depends on the membrane.
| Feature | Perfusion-limited | Diffusion-limited |
|---|---|---|
| Examples | N2O, CO2, O2 under normal conditions | CO; O2 with fibrosis or emphysema, or strenuous exercise at altitude |
| Capillary partial pressure | Equilibrates with alveolar gas early | Never equilibrates; gradient persists |
| To increase uptake | Increase blood flow | Increase area or gradient, thin the barrier |
Why CO is special. Hemoglobin binds CO so avidly that plasma PCO stays near zero along the capillary, making CO transfer membrane-limited and ideal for measuring diffusing capacity. O2 becomes diffusion-limited with a diseased barrier, or when low alveolar PO2 at altitude meets the short transit time of heavy exercise.
Pulmonary edema and Starling forces
The Starling equation. Net filtration = Kf[(Pc − Pi) − σ(πc − πi)], where Pc and Pi are capillary and interstitial hydrostatic pressures, πc and πi the corresponding oncotic pressures, Kf the filtration coefficient and σ the reflection coefficient for protein.
Hydrostatic (cardiogenic) edema. Raised capillary pressure from LV failure, mitral stenosis or volume overload pushes fluid out; it typically appears when PCWP exceeds about 18 mmHg, and the fluid is protein-poor.
Permeability edema. In ARDS, sepsis, transfusion-related acute lung injury and aspiration, the barrier leaks (Kf rises, σ falls), so protein-rich fluid floods alveoli at a normal PCWP (≤18 mmHg).
Safety factors. Lymph flow can rise several-fold to remove extra filtrate, so edema appears only once lymphatic capacity is overwhelmed. Fluid first collects in the interstitium (Kerley B lines, peribronchial cuffing) and then floods alveoli. Chronically high left atrial pressure, as in mitral stenosis, enlarges lymphatics and raises the pressure the lungs tolerate.