The Pulmonary Circulation

Importance

Separate pulmonary and systemic circulations are optimal for facilitating gas exchange The anatomy and physiology of the pulmonary circulation are markedly different from the systemic circulation Abnormalities in pulmonary blood flow affect the oxygenating function of the lung Anaesthesia and surgery may have important effects on the pulmonary circulation, especially in disease states The pulmonary circulation may be altered therapeutically to improve V/Q ratios

Overview

Functional anatomy Determinants of:

Pulmonary blood flow Pulmonary blood volume Pulmonary haemodynamics pressures vascular resistance

Measurement of pulmonary blood flow

Pulmonary Vascular Anatomy

Arteries

Pulmonary blood flow ~ systemic PVR only 1 / 6 SVR Media thickness ~ 1/2 systemic Lie close to corresponding air passages Transition at 100 (ID) Virtually no muscular tissue* Thin media of elastic tissue Structurally similar to venules

Arterioles

pulmonary vascular anatomy

Pulmonary endothelial cells

Exposed to entire cardiac output Link pulmonary and systemic circulations Regulate vascular smooth muscle tone Dense network over alveolar walls More than one alveolus per capillary network Cross- sectional area influenced by alveolar inflation Venules ~ arterioles (gas exchange possible with reverse flow) Veins do not accompany arteries (via intersegmental septae)

Capillaries

Venules and veins

The Bronchial Circulation

Arises from arch of aorta 1% of cardiac output Nutrient down to terminal bronchioles Humidifies / warms inspired air Some flow returns to systemic circulation (azygos to SVC) ~ normal systemic flow Some flow returns to pulmonary veins = venous admixture

Pulmonary Blood Flow

Slightly less than systemic flow

Bronchial and thebesian venous admixture

From 5 l/m at rest to 25 l/m with exercise Increased PBF minimally affects PVR

Limited ability to control flow distribution PBF is markedly affected by gravity:

dependent perfusion > nondependent

Maldistribution of pulmonary flow affects gas exchange

Pulmonary Blood Volume

Influenced by:

Posture

Falls by 27% on standing from lying (due to systemic pooling) Due to greater vasomotor activity of systemic circulation Increased by vasopressors / MAST suit Decreased by vasodilators / lumbar sympathectomy

Drugs

Left heart failure

Pulmonary Vascular Pressures

Small pressure drop cf. systemic circulation

PAP = 25/10mmHg

Concept of driving pressure rather than simple intravascular pressure (cf atmospheric) is useful.. Pulmonary driving pressure = mPAP - mLAP

Driving pressure is unaffected by IPPV as PAP and PVP are both increased PBF = driving pressure / PVR

Effect of gravity on alveolar and vascular pressures

No flow Flow Flow Pa - pA Pa - pV

ZONE 1 pA > pa >pV ZONE 2 Pa > pA > pV ZONE 3 Pa > pV > pA

pulmonary vascular pressure

Transmural pressure = pressure gradient from inside to outside of vessel For larger vessels, extravascular pressure = intrathoracic pressure Transmural pressure gradients are highest in dependent parts of lung
Site of pulmonary oedema

Effect of changes in intra-alveolar pressure on intrathoracic and pulmonary vascular pressures

Intrathoracic P = alveolar P - alveolar transmural P

Alveolar transmural pressure depends on lung volume IPPV: Intrathoracic pressure increases by less than 1/2 the inflating pressure

Less if poor lung compliance

Increased intra-alveolar pressure directly increases SAP (early valsalva) and PAP

spont.vent.produces higher PAP with expiration

Pulmonary Vascular Resistance

PVR = Pulmonary driving pressure Cardiac output

But: Assumes laminar blood flow PVR falls as flow increases due to low vasomotor tone Blood is a non - Newtonian fluid (viscosity varies with linear velocity) Units: usually 50-150 dyne.s.cm
-5

Factors Affecting PVR -passive

Cardiac output Increased CO produces minimal impact on PAP due to dilation / recruitment of collapsed vessels Recruitment mainly in non-dependent lung

Usually all of lung is perfused during spont.vent Especially with pneumonectomy / ASD / VSD

Distension occurs in all pulmonary vessels

Lung inflation Minimum at FRC...

Relationship Between PVR and Lung Volume

RV FRC TLC

Pulmonary vascular resistance

compression of alveolar vessels

compression of corner vessels* / HPV of collapsed lung units Lung Volume *lie at junctions between 3 or more alveoli

Active Control of Pulmonary Vascular Resistance

Usual state = active vasodilatation Many receptors / agonists implicated in vitro, relative importance in humans is unknown Many of the basic control mechanisms probably act directly on smooth muscle Endothelium acts to modulate the smooth muscle response

...active control of pulmonary vascular resistance

Endothelial / smooth muscle receptors... Many types Agonists:

from nerve endings (eg. Noradrenaline / Ach) Produced locally (eicosanoids) Via blood (peptides)

Some similar / identical agonists may produce opposite effects at different receptors

Eg. Noradrenaline at 1 and 2 receptors

Role of the endothelium and NO

Many pulmonary vasodilators (eg. Ach / vasopressin) are endothelium-dependent Common pathway mainly via NO Basal production of NO helps maintain a low PVR

Activation and Action of NO in the Pulmonary Vasculature

Receptor activation

Vascular endothelium

Ca++ NO synthase L-arginine L-citrulline

NO
GTP Guanylate cyclase

Vascular muscle

Cyclic GMP

G Kinase Ca++ RELAXATION

Respiratory effects on PVR

Hypoxia Induces HPV

Unique to pulmonary vasculature Mediated by both mixed venous (20%) and alveolar hypoxaemia (80%) Overall response is nonlinear Optimises V/Q Diverts blood from foetal lungs If chronic: produces pulmonary hypertension

HPV diverts blood from poorly perfused areas

Mechanism of HPV

Mediated via small arterioles (30-30m)

Distal to lobar arteries, proximal to capillaries Non-neural (occurs in transplanted lung)

Biphasic response
Initial phase: Seconds - maximal at 5-10 minutes Returns almost to baseline Second phase: Slow, sustained vasoconstriction, plateau at ~ 40 min.

Mechanism

Inhibition of O2 sensitive K+ channels Inhibits K+ efflux, producing depolarisation and Ca++ entry through voltage -dependent Ca++ channels

The Effect of Changes in Mixed Venous and Alveolar PO2 on Pulmonary Vasoconstriction

100 80 Pressor response (% max.) 60 40 20 0 0 20 40 Alveolar PO2 60 80

Mixed venous PO2 10mmHg 20mmHg 30mmHg 40mmHg 60mmHg

Effect of pCO2 and pH on HPV

Hypercapnia and acidosis

Both respiratory and metabolic acidosis augment HPV Slight vasoconstriction

Hypocapnia and alkalosis

Metabolic and respiratory alkalosis both inhibit / abolish HPV Vasodilation

Anaesthesia and PVR

Intravenous

Minimal effect on HPV, vascualar tone or oxygenation Except ketamine (increases PVR) Minimal effect on PVR, decrease PAP PAP effect: sevoflurane > isoflurane Effect on PBF due to negative inotropy Halothane reduces PBF, no effect on PVR Isoflurane No effect on HPV at 1-1.2 MAC

Volatile anaesthetics

N20

increases PVR / attenuates HPV Reduced / no effect if chronically elevated PVR

Neural Control of Pulmonary Blood Flow

1. Adrenergic

Thoracic sympathetic fibers Smooth muscle of pulmonary arteries / arterioles Both constrictor ( 1-norad.) and dilator (2-circulating adren.) 2- vasodilatation Presynaptic: inhibition of NA release Postsynaptic: increase NO production in endothelium

Dominant effect is 1: sympathetic stimulation

PVR

neural control of pulmonary blood flow

2. Cholinergic

Vagal stimulation produces vasodilatation ACh release stimulates M3 receptors Endothelium and NO dependent ACh is constrictor if no endothelium ? Significance of cholinergic control in humans

3. Non- adrenergic / non- cholinergic (NANC)

Anatomically related to ANS Different neurotransmitters Mostly inhibitory in lung, vasodilatation via NO release ? Functional significance

Humoral Control of Pulmonary Blood Flow

*Probably minimal role in control of normal PBF

Involved in pulmonary vascular diseases Adrenaline / dopamine: and effects Mainly vasoconstrictor Pulmonary vessels metabolise arachadonic acid to PGs/TXA2 Mainly constrictor except PGI2 May be involved in pulmonary hypertension in sepsis / CHD / reperfusion injury

Catecholamines

Eicosonoids

humoral control of pulmonary blood flow

Amines

Histamine: variable, constricts resting smooth muscle 5-HT (serotonin): released from activated platelets Constrictor May aggravate pulmonary hypertension due to PE Diverse responses Mainly vasodilatation via endothelial receptors Mainly vasoconstriction via direct smooth muscle action Variable responses Adenosine is a vasodilator

Peptides

Purine nucleosides

Receptors and agonists involved in active control of pulmonary vascular tone Receptor Group Adrenergic 2 Cholinergic Amines
2

Subtypes

Principle agonists noradrenaline

Responses

Endothelium dependent? No

constriction

Purines

Eicosanoids Peptides

adrenaline M3 H1 H2 5-HT1 P2x P2y A1 A2 TP ? NK1 NK2 AT ANP B2 ETA, ETB V1

noradrenaline constriction Yes dilatation Yes acetylcholine dilatation histamine variable histamine dilatation 5-HT variable ATP constriction ATP dilatation adenosine constriction adenosine dilatation thromboxane A2 constriction No Prostacyclin (PGI2) dilatation Substance P dilatation Neurokinin A constriction angiotensinogen constriction ANP dilatation bradykinin dilatation endothelin const.A, dil.B vasopressin dilatation

Yes Yes No variable No Yes No No ? Yes No No No Yes NoA, YesB Yes

Measurement of the pulmonary circulation

Pulmonary blood volume

Dye - dilution: PA to PV or LA Usually 10-20% of blood volume PAP: Swan - Ganz catheter / echocardiography PVP: PCWP / LA catheter Fick principle Dye / thermal dilution 2-D ultrasound of PA + Doppler flow velocity

Pulmonary vascular pressure

Pulmonary blood flow...

pulmonary blood flow

Fick principle O2 extraction = amount added to blood flowing though lungs

VO2 = Q (Ca O2 - Cv O2)

Q= Ca O2 - Cv O2
Limitations:

VO2

Does not include extrapulmonary shunt flow Does not include oxygen consumption by the lung May be large if lungs are infected

Modified Fick Method

Soluble, inert tracer gas (15% N2O,freon / argon) Short sampling period (single breath)

Mixed venous concentration ~ 0

tracer gas uptake Q = art. tracer gas concentration* * ~ PET. ALV tracer gas X blood solubility coefficient Noninvasive Limited if large alveolar dead space or shunt

Thermodilution Measurement of Cardiac Output

SVC
injectate at known T

temp PA
thermistor

time

Higher blood flow

lower temperature rise in PA

Echocardiographic Measurement of Pulmonary Blood Flow

Diameter of PA measured

PA cross -sectional area calculated Velocity. time integral (VTI)

VTI = area under curve

Mean flow in PA measured / beat

Vel. DPa

Stroke volume = PA area X VTI Cardiac output = SV X HR

time

Summary

The pulmonary circulation differs markedly in anatomy and function to the systemic circulation Large changes in cardiac output produce little change in PAP due to distension and recruitment Pulmonary arteries are low pressure and less influenced by neural control than are systemic The pulmonary circulation has limited ability to control blood flow distribution through the lung

summary

Pulmonary vascular resistance is influenced passively by factors such as cardiac output, posture and lung volume Pulmonary vascular resistance is actively influenced by cellular, respiratory, neural and humeral factors