CS 2015

Pulmonary Circulation and Its Determinants

Christian StrickerAssociate Professor for Systems Physiology

ANUMS/JCSMR - ANU

Christian.Stricker@anu.edu.auhttp://stricker.jcsmr.anu.edu.au/Perfusion.pptx

THE AUSTRALIAN NATIONAL UNIVERSITY

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Aims

At the end of this lecture students should be able to

• outline factors involved in gas diffusion;

• determine alveolar pressure gradients for CO2 and O2;

• explain why CO2 diffuses much better than O2;

• identify factors determining perfusion;

• illustrate how gases and chemicals modulate perfusion;

• recognise implications of ventilation-perfusion relationship;

and

• locate anatomical and physiological shunts.

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Contents

• Specializations maximising pulmonary gas exchange

• Factors determining gas exchange

• Considerations for O2 and CO2 diffusion

• Pressure gradients for CO2 and O2

• Perfusion of lung tissue

• Gases and chemicals that modulate perfusion

• Ventilation-perfusion relationship and its implications

• Inhomogeneities in ventilation-perfusion relationship

• Anatomical and physiological shunts

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Alveolar Vascular Sheet

• Capillary bed is very tight (frog).– Top: small artery

– Bottom: vein

• Individual capillary segments are so short

that blood forms an almost continuous

sheet (“sheet of flowing blood”): Very close

proximity of gas and blood.

• Gas exchange via “pulmonary membrane”:– Surface area: 70 m2

– Blood content (cap.): 60 - 140 mL

– Blood content/m2: 1 - 2 mL ≈ 1 µm

thickness (fast gas exchange).

– Capillary diameter: 5 µm (RBC 7 µm):

hardly any plasma space between RBC

membrane and endothelium.

Guy

ton

& H

all,

2001

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• Human lung tissue sample at EM level

• Short diffusion distances: 0.5 - 4 µm (around a nucleus).

• Factors affecting gas diffusion:

1. Thickness of membrane

2. Diffusion coefficient

3. Total surface area of respiratory membrane

4. Pressure gradients

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Alveolar Respiratory Membrane

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1. Membrane Thickness

• Average distance of diffusion: 0.3 - 0.7 µm

• A significant decrease in diffusion is only

evident if membrane thickens > 2 - 3 x.

• Thickening due to pathological processes– Lung oedema (interstitial and alveolar fluid)

– Lung fibrosis (interstitial) due to inflammation

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2. Diffusion Coefficient

• Gas diffusion rate same as that in water.

• Depends on gas solubility in membrane.

• Diffusion rate of CO2 23 x better than that of O2,

which is about 2 x that of N2.

• There are hardly ever diffusion problems for CO2.

• O2 diffusion can easily become limited.

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• Some loss of area (70 m2) throughout life.

• When loss reaches about ¼ - ⅓ of original total,

gas exchange is severely restricted even under

resting conditions (reserve, “surgical volume”…).

• Changes due to pathological processes:– Emphysema (loss of alveolar surface area): smoker,

α1-antitrypsin deficiency, etc.

– Lung resections (surgical removal).

3. Total Membrane Surface Area

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4. Pressure Gradients (ΔP)

• Driving force for diffusion is the difference in partial

pressures in capillary and alveolus (pressures in figure).

• Rate of gas exchange dependent on ventilation,

perfusion (CO) and haemoglobin concentration.

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• tContact: 0.3 - 0.8 s

• Diffusion time: 0.3 s

• Pressure gradient for

- O2 is 2.5 x, and for

- CO2 is 1.15 x

initial value.

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Lung Perfusion ( )• Overall, corresponds to CO.

• Low pressure in lung vessels:– Systolic: 25 torr; diastolic: 10 torr (low resistance)

– In capillaries: ~10 torr; left atrium ~7 torr

– Capillary pressure (10 torr) < colloid-osmotic

pressure (plasma, 26 torr): normally lung is dry.

– Intrathoracic vessels as capacitive elements:

700 - 900 mL “stored” in vessels and exposed to

intrathoracic pressure differences (~10 beats).

• Pulsatile flow even in capillaries (different to

systemic circulation).

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Vascular Resistance (RL)• Low resistance in lung vessels: RL = 10 x

smaller than that of systemic circulation.– 40% of RL is determined in capillaries (different to

systemic circulation).

– Not all capillaries are used under resting conditions:

recruitment during high demand with little drop in RL.

– Vessel compliance low (C = ΔV / ΔP): volume

increase matched with big pressure increase.

• Lung volume determines RL (in capillaries):

– RL↑ at beginning of expiration (because PA↑).

– RL↓ at beginning of inspiration (because PA↓).

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Hydrostatic Considerations

• Human lung: about 30 cm from base to apex;

ΔPorthostatic ~ 30 cm H2O = 22 torr.

– within range of capillary pressure.

• Countering PCap (~10 torr) are ΔPorthostatic and PA: PCap at apex

can be ≤ 0 → collapsed capillaries → no/minimal perfusion.

• Perfusion is best at base and worst at apex.

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Modulation of Pulmonary Flow• Vasoconstrictors

– Low

– α-adrenergic action

– Thromboxane A2

– Angiotensin

– Leukotrienes

– Neuropeptides

– Serotonin

– Endothelin

– Histamine

– Prostaglandins

• Vasodilators– High

– β-adrenergic action

– Nitric oxide

– Prostacyclin

– Acetylcholine

– Bradykinin

– Dopamine

– Adenosine

• Pulmonary blood flow is NOT much dependent on .

• Global hypoxia increases RL (mountain climber; people in Andes with right

ventricular hypertrophy).

• Hypoxic vasoconstriction is local (shutting down/shifting blood flow to

other areas): only massive pneumonia impacts on gas exchange globally.

• >20% of vessels need to be hypoxic before increase in RL is measured.

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Ventilation - Perfusion Relationship

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THE PAS-DE-DEUX IS

DETERMINED BY

ALVEOLAR GASES:

and

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Relationship• For optimal function, ventilation and perfusion need to be

matched; if mismatched, O2 and CO2 exchange are impaired.

• can be defined at the level of– total lung ( )

– group of alveoli

– single alveolus ( )

• For normal resting individuals with ≈ 4 L/min and

CO ≈ 5.0 L/min, .

• If ventilation > perfusion: (relative hyperventilation)

• If ventilation < perfusion: (relative hypoventilation)

• In patients with cardiopulmonary disease, mismatching of

ventilation and perfusion is the most frequent cause of

systemic arterial hypoxaemia ( ↓).– Typically improves under exercise (see previous lecture).

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and Gas Partial Pressures

• If not ventilated, alveolar partial pressures reach those in blood (hypoventilated):– Vessels: vasoconstriction (“shut problem area off”…)

– Bronchi dilate → improves ventilation.

• If not perfused, alveolar partial pressures reach those in trachea (hyperventilated):– Vessels: vasodilation (“open area up”…).

– Bronchi constrict → limits ventilation.

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and Homeostasis

• Poorly ventilated lung areas are poorly perfused:

↑, ↓ → RL↑

Alveolo-vascular effect

• Poorly perfused lung areas are poorly ventilated:

↑, ↓ → RAW↑

Alveolo-bronchiolar effect

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Ventilation – Perfusion Summary

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Local Relationships • Ventilation increases from apex to

base of lung.

• Perfusion increases also, but more

than ventilation.

• If , then

• From apex to base, ↓ (read

horizontally):– at apex relative hyperventilation

( ): RL↓; RAW↑

– at base relative hypoventilation

( ): RL↑; RAW↓

• Homeostatic principle to keep

within limits.

Modified after Despopoulos & Silbernagl 2003

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Impairment of Gas Exchange

• Anatomical shunt (extra-alveolar shunt): 2 - 3% of CO.– Bronchial/mediastinal veins, thebesian vessels in left myocardium

(drainage directly into ventricle); biggest shunt occurs in the heart.

– O2 therapy does not help here, because shunted blood never “sees” O2.

• Physiological shunt = venous admixture: atelectasis caused by mucus

plugs in airways, airway oedema, foreign bodies and tumours.

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Take-Home Messages

• Unique property of lung with dual circulation and ability to

accommodate large volume of blood.

• Hypoxia causes pulmonary vessels constriction

(“paradoxical”).

• Bronchi constrict due to hypocapnia limiting .

• Diffusion of CO2 is much better than that of O2.

• CO and haemoglobin concentration are non-ventilatory factors

affecting gas exchange.

• Upright, and ↑ from apex to base.

• Apex is relatively hyper-, base hypoventilated.

• Hypoxaemia can result from: anatomical shunt, physiological

shunt ( mismatching, hypoventilation), and change in gas

mixture.

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MCQWhich of the following statements best describes the relative

differences in blood flow among the upper, middle and lower

portions of the lung during resting conditions (standing) and

during exercise in a running person?

Standing & resting Running

A Upper < middle < lower Upper < middle < lower

B Upper < middle < lower Upper = middle = lower

C Upper < middle < lower Upper > middle > lower

D Upper = middle = lower Upper > middle > lower

E Upper > middle > lower Upper < middle < lower

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That’s it folks…

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MCQWhich of the following statements best describes the relative

differences in blood flow among the upper, middle and lower

portions of the lung during resting conditions (standing) and

during exercise in a running person?

Standing & resting Running

A Upper < middle < lower Upper < middle < lower

B Upper < middle < lower Upper = middle = lower

C Upper < middle < lower Upper > middle > lower

D Upper = middle = lower Upper > middle > lower

E Upper > middle > lower Upper < middle < lower