Pulmonary Circulation

Dr. Judith C.W. Mak

Department of Pharmacology & Pharmacy

(PHAR6200/MMPH6172, Lecture #2)

 Learning Outcomes
At the end of the lecture, students should be able to
• Discuss the two main types of circulation
• Differentiate between pulmonary and systemic (or
bronchial) circulation
• Describe regional differences in pulmonary blood flow in
an upright person
• Define zones I, II, and III in the lung, with respect to
pulmonary vascular pressure and alveolar pressure
• Describe the mechanisms for pulmonary edema
Apply Your Knowledge

Do humans have an open or closed

circulatory system?
 Human Circulatory Systems
There are 3 major components:

• Heart (= pump) – made of cardiac muscle

• Vessels (arteries, veins, capillaries) (= tubing or

pipe)

• Blood (= transport medium) - fluid

 Vascular System

The human vascular system

consists of approximately 70,000
miles of blood vessels; this could
reach from New York to San
Francisco about 24 times!!

Blood vessels, along with the heart, are

responsible for the circulation of blood
throughout the body.
Functions of Circulatory System
• Carry O2 to cells and CO2 away from
cells
• Deliver nutrients through body (after
absorption in small intestine)
• Carry liquid wastes away from cells
(H2O, salt, urea)
• Help in fighting infections
• Temperature regulation
• pH regulation
 Types of Circulation
Two circulations
– Systemic : blood vessels that transport
blood to and from all the body tissues
high pressure, low flow

– Pulmonary : blood vessels that carry

blood to and from the lungs
low pressure, high flow
The Double Pump
Pulmonary and Systemic Circulation
Exchange of oxygen and
carbon dioxide in the
lungs’ capillaries

O2 and CO2 exchange between

capillary beds and body tissues.
 capillary beds of head

Systemic
and upper extremities

(to pulmonary aorta

circuit)

Circulation
(from
pulmonary
circuit)

heart
Longer loop
carries blood to capillary beds of other
organs in thoracic cavity

and from body

capillary bed of liver
tissues

capillary beds of intestines

 Pulmonary Circulation
Right pulmonary artery Left pulmonary artery

This loop capillary

bed of
capillary bed
of left lung

oxygenates right
lung
pulmonary
trunk (to systemic circuit)

blood

(from
systemic
circuit)
pulmonary
veins

heart
lungs
Flow Chart
 Pulmonary Circulation
• heart to lungs and back again

• driven by the right side of heart

• pumping oxygen-poor blood through the lungs

• releasing carbon dioxide from blood to the lungs

• picking up oxygen from the lungs to the blood

 Systemic Circulation
• driven by the left side of heart

• pumping oxygen-rich blood through the body

• delivering oxygen to the body cells

• removing carbon dioxide from the body cells

 Differences between Pulmonary
and Systemic Circulation
• Blood in the pulmonary circulation is not pumped so
far as in the systemic circulation and the pulmonary
arteries have a larger diameter, thinner walls, and
less elastic tissue. As a result, resistance to blood
flow is very low meaning that less pressure is needed
to move blood through the lungs.

• Because resistance in the pulmonary circulation is

low, normal pulmonary capillary hydrostatic pressure
is lower than systemic capillary hydrostatic pressure
which tends to prevent pulmonary edema.
 Function of Lung

• To match ventilation with perfusion

Ventilation – air flow

Perfusion – blood flow

Pulmonary Gas Exchange

3 processes:
- ventilation
- diffusion
- perfusion

Diffusion – driven by the alveolar-arterial O2 difference

Two Circulations in the Lung
• Pulmonary Circulation
– Arises from Right Ventricle
– Receives 100% of blood flow

• Bronchial Circulation
– Arises from the aorta
– Part of systemic circulation
– Receives about 2% of left ventricular
output
 Pulmonary Circulation (I)
• Pulmonary arteries carry partially de-
oxygenated blood.

• Pulmonary veins carry oxygenated blood.

• Pulmonary arteries “travel” with the airways.

• Pulmonary capillaries lie in the alveolar septa.

• Pulmonary veins drain into the left atrium.

Pulmonary Circulation (II)
• In series with the systemic circulation

• Receives 100% of cardiac output

(3.5L/min/m2)

• RBC travels through lung in 4-5 seconds

• 280 billion capillaries, supplying 300 million

alveoli
– Surface area for gas exchange = 50 – 100 m2
 Functional Anatomy of the
Pulmonary Circulation
• Thin walled vessels at all levels
• Pulmonary arteries have far less smooth
muscle in the wall than systemic arteries

• Consequences of this anatomy - the vessels are:

– Distensible
– Compressible
 Bronchial Circulation
• Bronchial arteries carry oxygenated blood.

• Bronchial veins carry partially de-oxygenated

blood.

• The bronchial arteries come off of the

systemic circulation (~2% of the total cardiac
output).

• The bronchial veins drain into the

pulmonary veins and thence into the left
atrium.
 Bronchial Circulation
• ~2% of total cardiac output
• Provides oxygen to supporting tissues of the lung
– Connective supporting tissue
– Septa
– Large and small bronchioles – down through the terminal
bronchioles
– Large blood vessels
• Systemic circulation with systemic blood pressure
• Drains into the left atrium and the right atrium
• Blood in the left atrium is a venous admixture (2%
deoxygenated blood and 98% oxygenated blood)
Schematic Representation of the
Bronchopulmonary Anastomoses

The McGraw-Hill Companies Inc. 2006

Local Blood Pressure in the Pulmonary and
Systemic circulation
 Differences in Blood Pressure of
Pulmonary and Systemic Circulations (1)

• Gravity and Distance:

– Distance above or below the heart adds to, or
subtracts from, both arterial and venous pressure
– Distance between Apex and Base (about 23 cm)
Systemic Pulmonary
Aorta 100 mmHg Main PA 15 mmHg

Head 50 mmHg Apex 2 mmHg

Feet 180 mmHg Base 25 mmHg

 Differences in Blood Pressure of
Pulmonary and Systemic Circulations (2)

• Control of regional perfusion in the systemic circulation:

– Large pressure head allows alterations in local vascular resistance to
redirect blood flow to areas of increased demand (e.g. to muscles
during exercise)
– Pulmonary circulation is all performing the same job, no need to
redirect flow (exception occurs during hypoxemia)

• Consequences of pressure differences:

– Left ventricle work load is much greater than right ventricle
– Differences in wall thickness indicates differences in work load
Apply Your Knowledge

What is the purpose of pulmonary

circulation?
 Functions of Pulmonary Circulation (1)
• Gas exchange (respiratory)
– Add oxygen and remove carbon dioxide from mixed venous blood

Non-respiratory
• Filter – clots that form in systemic veins in response to injury must go
through the lungs before reaching the left heart. The small pulmonary
vessels filter out these clots. They are the broken down and absorbed.

• Blood reservoir – supply blood to fill the left ventricle

• Supply nutrients to lung itself
– Pulmonary circulation supplies nutrients for the alveolar ducts and
alveoli
– Bronchial vessels from the systemic circulation supply nutrition to the
rest of the lung
– Deoxygenated bronchial venous blood mixes with oxygenated
pulmonary venous blood in pulmonary veins (anastomosis shunt)
Functions of Pulmonary Circulation (2)
• Fluid exchange – removal of alveolar fluid

• Metabolic functions of the lung

– The type II alveolar cells make pulmonary surfactant, which is
essential for normal compliance of the lung
– In the lung, angiotensin converting enzyme (ACE) converts
inactive angiotensin I to active angiotensin II
– The lung makes immunoglobulin A, which provides a defense
mechanism against pulmonary infection
– Synthesis and/or release of endothelin
serotonin
prostaglandin E2 (PGE2)
nitric oxide (NO)
Influences on Pulmonary Vascular
Resistance (1)
• Pulmonary vessels have:
- Little vascular smooth muscle.
- Low intravascular pressure.
- High distensibility and compressibility.

• Vessel diameter influenced by extravascular forces:

- Gravity
- Body position
- Lung volume
- Alveolar pressures/intrapleural pressures
- Intravascular pressures
Influences of Pulmonary Vascular
Resistance (2)
• Transmural pressure = Pressure inside (Pi) –
Pressure outside (Poutside)
– Increased transmural pressure - increases vessel diameter.
– Decreased transmural pressure - decreased vessel
diameter (increase in PVR).
– Negative transmural pressure - vessel collapse.

Poutside
Pi

• Different effects of lung volume on alveolar and

extraalveolar vessels.
 Effect of Transmural Pressure on
Pulmonary Vessels During Inspiration

Resistance  Length and Resistance  1/(Radius)4

Three Zone Model of Distribution of Blood Flow
Gravity and Blood Flow
Zones of the Lung

PA = alveolar pressure
Pa = pulmonary arterial pressure
Pv = pulmonary venous pressure
Effects of Increased Pressure on
Vascular Resistance
Pressures in the Lung
Cardiac Output
Recruitment and Distension
of Capillaries
Effects of Lung Volume on
Resistance
 RV = residual volume
FRC = functional residual capacity
TLC = total lung capacity

Source: Pulmonary Physiology, The McGraw-Hill Companies, Inc., 2007

 Pulmonary Vascular Resistance
During Exercise
• During exercise cardiac output increases (e.g. 5-fold), but
with little change in mean pulmonary artery pressure
– How is this possible?
input pressure - output pressure
Vascular Resistance =
blood flow

• Pressure = Flow x Resistance

• If pressure does not change, then PVR must decrease with
increased blood flow
• Passive effect
– Recruitment: Opening of previously collapsed capillaries
– Distensibility: Increase in diameter of open capillaries
Control of Pulmonary Vascular Resistance (1)
• Passive Influences on PVR:
Influence Effect on PVR Mechanism

 Lung Volume (above Lengthening and

Increase
FRC) Compression
 Lung Volume (below Compression of Extra-
Increase
FRC) alveolar Vessels
Recruitment and
 Flow, Pressure Decrease
Distension
Decrease in Dependent Recruitment and
Gravity
Regions Distension
 Interstitial Pressure Increase Compression
Positive Pressure Compression and
Increase
Ventilation Derecruitment
Control of Pulmonary Vascular Resistance (2)
• Active Influences on PVR:
Increase Decrease
Parasympathetic
Sympathetic Innervation
Innervation
-Adrenergic agonists Acetylcholine
Thromboxane/PGE2 -Adrenergic Agents
Endothelins Prostacycline
Angiotensin II Nitric oxide
Histamine Bradykinin
Alveolar Hypoxemia
Vasoactive Substances in the Lung

Vasocontrictors Vasodilators

Catecholamines PGE2
Angiotensin II PGI2
Histamine EDRF or NO
Endothelin
Serotonin
Gravity, Alveolar Pressure and Blood Flow

• NO zone 1 in normal
healthy person

Zone 2 (intermittent flow) at

the apices

Zone 3 (continuous flow) in all

the lower areas

• In normal lungs, zone 2

begins 10 cm above the
mid-level of the heart to the
top of the lungs
Regional Pulmonary Blood Flow Depends
Upon Position Relative to the Heart

Main PA 15 mmHg
Apex 2 mmHg
Base 25 mmHg
Effects of reducing the Alveolar PO2
Lung Ventilation/Perfusion Ratios

• Ventilation and perfusion are normally matched in the

lungs.
i.e. gas exchange (ventilation = V) nearly matches
pulmonary arterial blood flow (perfusion = Q)
The ratio of V/Q in lung at rest 0.8 (4.2 L/min
ventilation divided by 5.5 L/min blood flow)
• If mismatched, impairment of O2 and CO2 transfer
results.
• Ventilation is greater at the bottom of the lung.
• Perfusion – blood flow in the lungs is lowest at the
apex and highest at the base.
Effects of Altering the V/Q Ratio
on the PO2 and PCO2
The Pattern of V/Q Ratio
The high V/Q at the apex
Summary
 Causes of Non-uniform V/Q
• Non-uniform ventilation (V) due to uneven airway resistance
– emphysema
– bronchitis
– tumors, edema
– bronchoconstriction

• Non-uniform ventilation (V) due to uneven lung compliance

– fibrosis
– COPD
– tumors, edema

• Non-uniform perfusion (Q)

– embolus, thrombosis
– tumors, edema
– Compression due to increased alveolar pressure
– gravity
 Good –
Hypoxia matches
V and Q
Decreases
Shunt effect
Opposite to systemic circulation
where hypoxia  vasodilation

Mechanism: hypoxia inhibits

voltage-gated K+ channels,
Good for fetus
depolarizes, open Ca++ channels,
Bad after birth –
muscle contracts. Causes
pulmonary
hypertension
Hypoxic Pulmonary Vasoconstriction (1)

• Lower airway or alveolar PO2

(Alveolar hypoxia)

• Redirection of blood flow away

from poorly oxygenated alveoli
towards alveoli with higher PO2

• Optimization or improvement of
gas exchange

• Mechanism – unknown, but may

involve a hypoxia sensitive K+ channel
Hypoxic Pulmonary Vasoconstriction (2)
• Alveolar hypoxia causes active vasoconstriction at level of pre-
capillary arteriole.

• Mechanism is NOT completely understood:

– Response occurs locally and does not require innervation.
– Mediators have not been identified.
– Graded response between pO2 levels of 100 down to 20 mmHg.

• Functions to reduce the mismatching of ventilation and perfusion

(i.e. V/Q ratio).

• Not a strong response due to limited muscle in pulmonary

vasculature.

• General hypoxemia (high altitude or hypoventilation) can cause

extensive pulmonary artery vasoconstriction.
 Normal Values of Pressures in the
Pulmonary Circulation

• Right atrial pressure. Mean value near 0 mmHg

• Right ventricle. Systolic pressure = 25 mmHg

Diastolic pressure = 0 mmHg

• Pulmonary artery. Systolic pressure: 20-30 mmHg

Diastolic pressure: 6-12 mmHg
Mean value: 10-15 mmHg

• Left atrial pressure. Mean value about 5 mmHg

Blood Flow through Different Parts of the
Circulation must be Balanced
 Venous Return
• Mechanisms that “pump” blood from lower body
to heart

– muscular pump: during contractions of skeletal muscle

surrounding the veins, it forces the blood to move in only
one direction when valves close to prevent backflow

– respiratory pump: during inspiration the diaphragm

moves downward increasing pressure in abdominal
cavity and decreasing pressure in thoracic cavity
(i.e. blood flows toward the heart)
 Pulmonary Edema
• The lungs are normally ‘dry.’
• There is a very thin layer of liquid lining
the interior of the airspaces (i.e. pleural
cavity).
• Any increase in the amount of liquid in
the lungs increases the diffusion
distance for O2 and CO2.
Possible causes of pulmonary edema

• Damage to the capillary membrane (sepsis, O2 toxicity,

inhaled toxins)
• Increase in capillary hydrostatic pressure (left heart
failure or mitral valve disease)
• Decrease in plasma protein (starvation, liver disease)
• Insufficient pulmonary lymphatic draining
• Unknown etiology
– High altitude (generalized hypoxic vasoconstriction)
– Drowning
– Head injury
– drug (heroin) overdose
 Barrier Function of Alveolar Wall

• Capillary endothelial cells:

– permeable to water, small molecules, ions
– barrier to proteins

• Alveolar epithelial cells:

– more effective barrier than the endothelial cells
– found to pump both salt and water from the
alveolar space
 Hydrostatic Gradient
Counteracts Osmotic Gradient
• Hydrostatic pressure in the pulmonary
capillary bed > hydrostatic pressure in the
interstitium
– hydrostatic pressure drives fluid from the capillaries
into the pulmonary interstitium

• Osmotic pressure in the plasma > osmotic

pressure in the interstitium
– osmotic pressure normally would draw fluid from the
interstitial space into the capillaries
Fluid Movement
 Pulmonary Hypertension
Definition

> Normal Values for Hemodynamic Parameters

Pulmonary Artery Systolic Pressure (PAS): 20-30 mm Hg

Pulmonary Artery Diastolic Pressure (PAD): 6-12 mm Hg

Pulmonary Artery Mean Pressure (PAM): 10-15 mm Hg

Definition of Pulmonary Hypertension

• High blood pressure occurs in the arteries of the

lungs

• A mean pulmonary artery pressure of >25 mm Hg

at rest or >30 mm Hg during exercise

• At rest
- sustained vasoconstriction/remodelling

• During exercise
- reduced distensibility/recruitment of vessels
 Pulmonary Hypertension
• Primary - rare, no known cause (20-40 yr), die within 5 yrs

• Secondary - as a result of cardiac complications due to

lung disorders
 COPD
 Interstitial lung disease
 Obstructive sleep apnea (OSA)
 Sarcoidosis - a chronic inflammation of the lung tissue
that limits lung volume and makes the lungs “stiff”

These lung diseases can prevent the transfer of adequate O2

from the lungs to the blood. As the blood vessels are
deprived of O2, they begin to constrict.
What happens in pulmonary arterial hypertension?

3
2

1 = narrowing of blood vessels due to vasoconstriction

2 = changes in thickness of the blood vessel walls ( amount of muscle)
3 = the formation of small blood clots within the blood vessels
Structure and Function of
Blood Vessels
 The Blood Vessels
• Arteries (and arterioles) – carry blood away 
from the heart
• Capillaries – where nutrient and gas exchange 
occur
• Veins (and venules) – carry blood toward the 
heart.
Blood Vessels
Types of Blood Vessels
Capillary Types
 Arteries
• Two main types
– elastic (conducting) arteries: largest diameter,
function as a pressure reservoir
– muscular arteries: medium-sized diameter,
distribute blood to various parts of the body

• Carry blood away from the heart to the tissues

• Innervated by sympathetic fibres of ANS

 Arterioles
• muscular arteries divide into smaller arteries

• small arteries divided into arterioles

• arterioles feed capillaries

• a key role in regulating blood flow from arteries

to capillaries and in altering arterial blood
pressure
– vasoconstriction and vasodilation
 Capillaries
• microscopic vessels that connect arterioles and
venules
• penetrate most body tissues with dense
interweaving networks called capillary beds
• function in exchange of gases, nutrients and
wastes between blood and body cells via
diffusion
• number varies with metabolic activity of tissue
they serve
Capillary Bed
 Veins
• Venules drain blood from capillaries, then join
to form veins that take blood to the heart.
• Veins have much less smooth muscle and
connective tissue than arteries.
• Veins often have valves that prevent the
backward flow of blood when closed.
• Veins carry about 70% of the body’s blood and
act as a reservoir during hemorrhage.
 Pulmonary Vessels
• Vessels branch like the tracheobronchial tree
– Arteries
• Thin walls – less muscle and elastin
• Arteries are short but have a large diameter
• Arteries are very distensible
– Veins: structurally like veins in the systemic circulation
– Capillaries: most extensive capillary network of any organ
• Capillaries occupy 70 – 80% of the alveolar surface
• Capillary surface area – 40x body surface area
• Flow described as “sheet action”
• Systemic capillaries – surrounded by interstitial fluid
• Pulmonary capillaries – surrounded by very small area of
interstitial fluid and primarily by air filled alveoli
• Diameter of capillaries and capillary blood flow is determined by
the relationship between blood pressure and alveolar pressure
Pulmonary Capillary Beds
 Circulation of Blood
Aorta

Arteries

Arterioles

Capillaries

Venules
Arteries carry blood away from the heart and veins carry
Veins blood toward the heart. The capillaries are exchange
vessels located between the arterial and venous systems.
Vena Cava
Apply Your Knowledge

Which type of vessel is the smallest,

forming the link between arterioles
and venules?
 References
• Hall, JE. Guyton and Hall Textbook of Medical
Physiology (13th Ed.) Elsevier, 2015; Unit VII,
Chapter 38

• West, JB. Respiratory Physiology: The

Essentials (9th Ed.) Lippincott Williams &
Wilkins, 2012
E-mail: [email protected]