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

 

List:

·         Intro

·         Physical

·         Chemical

·         Rheologic

·         Disease states

·         (Drugs)

 

Intro:

Pulmonary cf. systemic

·   Low pressure (1/8 of systemic) -> minimal transudation, preserved gas exchange

·   Low resistance (1/8 of systemic); more accurately low impedance since pulsatile flow

·   Resistance distributed across the circuit, not only at arterioles

·   Many factors ↓SVR but ↑PVR (e.g. ↓pO2, ↑pCO2, ↓pH, histamine)

Equations

·   RV output = (mPAP – LVEDP) / PVR

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

·   Hence factors ↑PVR: ↓radius (note power 4), ↑viscosity, ↑length (not under control)

Normal values

·   SPBP 25mmHg

·   DPBP 8

·   mPAP 15

·   LVEDP 6

·   PVR 0.25-2mmHg/L/min

West zones and blood flow

·   Z1: alveolar (PA) > arterial (Pa) > venous (Pv); no flow

·   Z2: Pa > PA > Pv: flow in systole

·   Z3: Pa > Pv > PA; flow throughout

 

·   Increased PVR if: ↑size Z1,2 and ↓size Z3 -> ↓total vascular surface area

 

Physical determinants (major):

Blood pressure

·   ↑PAP or ↑PVP -> ↓PVR

o Recruitment: ↑ pressure -> re-open collapsed vessels (West zone 1

o Distension: ↑pressure -> ↑ radius of open vessels (West zones 2, 3)

(Unlike systemic circulation)

Relative lung volume

·   ↓volume -> ↓radial traction -> compress extra-alveolar vessels (e.g. supine)

·   ↑volume -> alveolar distension -> compress alveolar vessels

·   PVR minimal at FRC

Alveolar pressure

·   IPPV, PEEP -> ↑PA -> ↑size Z1

 

Chemical:

O2 (major)

·   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

·   ↑pCO2 -> vasoconstriction (VC)

pH

·   ↓pH -> VC

Neural

·   SNS: noradrenaline -> α1 adrenoceptor -> ↑ICF [Ca2+] -> VC

·   PSNS: vasodilatation (VD)

·   NANC: nitric oxide -> ↑cGMP -> activate MLCP, ↓Ca2+ influx, ↑K+ efflux -> vasodilation

·   Neural controls less important in pulmonary circulation

Hormonal

·   Adrenaline:

o α1-> VC

o β1 -> VD

Local

·   Dilators:

o Nitric oxide -> VD (as above)

o PGI2 -> ↑cAMP -> VD

·   Constrictors:

o Endothelin -> ↑ICF [Ca2+]

o TXA2 -> ↑ICF [Ca2+]

o Serotonin

o Histamine

o Bradykinin

 

Rheologic:

Hyperviscosity

·   Hypothermia

·   Polycythaemia: e.g. secondary to severe COPD

 

Disease states:

Left heart disease

·   e.g. LV failure, mitral regurgitation

·   Early: due to simple increase in hydrostatic pressure

·   Later: exacerbated by remodelling

Lung disease

·   e.g. COPD

Pulmonary embolism

·   ↓Total vascular surface area

Autoimmune disease

·   e.g. associated with scleroderma

Primary pulmonary hypertension

·   Rare

 

(Drugs)

Dilators

·   SNS amines: dobutamine

·   PDE inhibitor: milrinone

·   CCB: e.g. nifedipine

·   ETRA: bosentan

·   Prostacyclin analogues: iloprost

·   ACE inhibitors

·   Vasopressin

·   Nitrodilators: GTN, NTP, inhaled nitric oxide

·   General anaesthetics: sevoflurane, propofol

Constrictors

·   Ketamine

·   N2O

 

Feedback welcome at ketaminenightmares@gmail.com