Pulmonary Vascular Tone

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  • Pulmonary vascular resistance = (Pulmonary driving pressure / Cardiac output) = (Mean PA pressure - Left atrial pressure) / Cardiac output
  • Pulmonary vascular resistance (PVR) is about 1/8 to 1/10 of the systemic vascular resistance
Mean pulmonary blood pressure = 15
Left atrium blood pressure = 5
Pulmonary blood flow = 5~6
PVR = Pressure difference / blood flow
= (15-5)/5 or (15-5)/6
= about 1.7~2.0 mmHg/L/min
  • about 100 dyne.sec.cm-5
  • Flow is laminar therefore pulmonary vascular resistance is also given by:
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  • n = viscosity : ↑Hct → ↑Resistance
  • l = length → constant
  • r = radius
  • Pulmonary Vascular Resistance determined by viscosity and radius of the vessel

Effect of Pulmonary Blood Flow

  • As cardiac output increases, increased flow to pulmonary circulation causes:
  • Distension of already opened capillaries (the more important adaptation to increased flow)
  • Recruitment of closed capillaries (although most capillaries never completely collapse, even those in zone 1 have a small amount of plasma passing through them)

Effect of Lung Inflation

  • High/Low lung volumes result in increased pulmonary vascular resistance, at FRC resistance is minimal
  • Alveolar vessels are exposed to alveolar pressure and are compressed if this increases
  • Corner capillaries lie within the junction of 3 or more alveoli and are generally unaffected by alveolar filling, however may expand at high lung volumes and constrict at small lung volumes
  • Extra-alveolar vessels are exposed to less pressure and are pulled open by radial traction from the surrounding lung, decreasing their pressure with inspiration

Active control of Pulmonary Vascular Resistance[edit]

  • Smooth muscle tone affects pulmonary vessel calibre.

Neural Control

  • Adrenergic - via noradrenaline, adrenaline, dopamine - from the first five thoracic nerves, travel to the pulmonary vessels via the cervical ganglia and a plexus around the trachea
  • α and β receptors supply smooth muscle of arteries and veins, mainly those > 30μm, but with far less effect than in systemic circulation
  • α1 receptors mediate vasoconstriction mainly in response to noradrenaline release
  • β2 receptors produce vasodilatation mainly in response to circulating adrenaline
  • α1 effects predominate and sympathetic stimulation increases pulmonary vascular resistance overall
  • Cholinergic - via the vagus nerve, cause pulmonary vasodilatation by release of ACh and M3 muscarinic receptor stimulation

Cellular Mechanisms Controlling Pulmonary Vascular Tone

  • Many different receptor types are present on vascular endothelial and smooth muscle cells
  • Endothelial cells produce NO which is required for many of the vasodilatory pathways
  • NO activates cGMP production which activates a protein kinase enzyme, reducing myosin phosphorylation and intracellular calcium levels
  • Pulmonary vasodilators acting directly on smooth muscle mostly activate adenyl cyclase to produce cAMP as a second messenger:
  • cAMP activates protein kinase enzymes with an array of effects, importantly reducing myosin phosphorylation and intracellular calcium levels to cause relaxation of the muscle cell
  • Pulmonary vasoconstrictors usually act via G-protein coupled receptors, activating myosin phosphorylation and releasing calcium from intracellular stores

Humoral Control

  • Catecholamines - circulating adrenaline following sympathetic stimulation acts on α and β receptors, producing predominant vasoconstriction
  • Eicosandoids - PGF, thomboxane A2 etc. vasoconstriction, PGI2 (prostacyclin) vasodilates
  • Amines - Histamine - H1, serotonin, angiotensin II - normally constrict resting smooth muscle, but relaxes it if adrenaline present
  • Peptides - substance P and neurokinin A etc

Drug Effects

  • Nitric oxide - causes vasodilatation. Rapidly inactivated by Hb, therefore works mainly in well ventilated regions of lung, diverting blood flow away from poorly ventilated areas
  • Prostacyclin - intravenous PGI2 - used for treatment of pulmonary hypertension and to reduce PA pressure
  • Also causes systemic circulation problems, therefore usually delivered by inhalation which reduces systemic symptoms (somewhat)
  • ACE inhibitors - reduce PVR only with long term treatment
  • Phosphodiesterase inhibitors eg. sildenafil- inhibit cAMP/cGMP breakdown which enhance activity of pathways ending in NO
  • Calcium antagonists - inhibit L-type calcium channels, but can worsen hypoxia and lead to heart failure due to negative ionotropic effects
  • Isoproterenol, aminophylline, ganglion blockers - cause vasodilatation

Hypoxic Pulmonary Vasoconstriction

  • Vasoconstriction is also mediated by alveolar hypoxia (with a small contribution from mixed venous PO2), in a non-linear fashion - resembling the shape of the HbO2 curve, with a P50 of 30mmHg, mediated by metalloporphyrin
  • Diverts pulmonary blood flow away from regions in which the oxygen tension is low and is important in maintaining V/Q match
  • Starts within ~5 minutes, then reaches maximal response at ~2-4 hours
  • This is important in cor pulmonale and sleep apnoea syndrome
  • Elevated PCO2 has a slight pressor effect, acidosis augments the HPV response
Pulmonary blood flow measurement:[edit]
  • Fick Principle: Rate of appearance/disappearance of any substance in any organ is given by the A-V concentration difference multiplied by blood flow
  • O2 consumed = A-V[O2] difference x bloodflow
  • V = Q(CaO2 - CvO2) or Q = VO2 / (CaO2-CvO2)
(using CvO2 taken from PA blood, O2 volume utilised determined by tracing slope of a Benedict-Roth spirometer with a soda-lime absorber)
  • CO2 excretion can also be used
  • Dilution Methods
  • Indicator dilution - indocyanine green dye injected into venous circulation and serial arterial concentrations are recorded.
  • The conservation of mass principal is then used to derive the flow
  • Thermodilution - cold saline is injected into the RA and serial temperature measurements made
  • Has the advantages of having no recirculation, and allows for repeated measurements.
  • Requires many correction factors
  • Body Plethysmograph
  • Measures N2O uptake in pulmonary blood flow
  • N2O uptake is flow limited, allowing flow to be calculated
  • This method only measures pulmonary capillary flow, wheres the other methods measure pulmonary blood flow
  • Radioactive perfusion scan
  • Using 133Xe and a scintillation gamma camera to determine regional differences