2002A04 Outline the physiological factors that influence pulmonary vascular resistance.

· Intro

· Physical

· Metabolic

· Autonomic

· Local

Definition

· Resistance to flow by all pulmonary vascular beds combined

Pulmonary circulation

· Low pressure (1/8 of systemic – 25/8mmHg)

o Minimal transudation

o Preserved gas exchange

· Low resistance (1/8 of systemic – 0.25-2 Wood units)

o Distributed across the circuit, not only at arterioles

· Many factors cause ↓SVR but ↑PVR

o e.g. ↑temp, ↓pO₂, ↑pCO₂, ↓pH, histamine

Equations

· RV output = (mPAP – LVEDP) / PVR

· Resistance = (8 x length x viscosity) / (π x radius⁴)

o Factors increasing SVR:

§ ↓Radius (power 4, hence most important factor)

§ ↑Viscosity (↑Hct, ↑temp, ↓flow rate)

§ ↑Length (rarely important)

Physical:
-Blood pressure	· ↑PAP or ↑PVP -> ↑radius o Recruitment of collapsed vessels (West zone 1 o Distension of patent vessels (West zones 2, 3)
-Alveolar pressure	· IPPV, PEEP -> ↑alveolar pressure -> vessel collapse o ↑West Zone 1: where PA > Pa > Pv o ↓Total vascular surface area
-Relative lung volume	· ↓Volume -> ↓radial traction -> compress extra-alveolar vessels · ↑Volume -> alveolar distension -> compress alveolar vessels · PVR lowest at FRC
Metabolic:
-O₂	· i.e. hypoxic pulmonary vasoconstriction (HPV) · Vasoconstriction∝ 1 / (PAO20.6 x PvO20.4) · Phase 1: onset immediate, max 5 mins o ?Inhibit K⁺ channel ?↓mitochondrial ROS ?↓ATP:ADP · Phase 2: onset 40 mins, max 2 hours o ?↑↓COX/LOX activity ?↑↓gene transcription · Local HPV: improves V/Q matching e.g. in pneumonia · Global HPV: ↑↑PVR (e.g. high altitude)
-CO₂	· ↑CO₂ -> ↓r
-pH	· ↓pH ->↓r
-Temp	· ↓T -> ↓r
Autonomic:
-SNS	· Neural NAd -> α₁ -> ↓r · Hormonal Ad -> β₂-> ↑r
-PSNS	· ACh -> ↑NO release -> ↑r
Local:
-Dilators	· NO: ↑cGMP -> activate MLCP, ↓Ca²⁺ influx, ↑K⁺ efflux · PGI₂
-Constrictors	· Endothelin -> ↑ICF [Ca²⁺] · TXA₂ -> ↑ICF [Ca²⁺] · Serotonin · Histamine · Bradykinin