Gas exchange in the
lungs. Ventilation to
perfusion ratio
Dariusz Nowak
Respiration
• Provides O
2
to the tissues and removes CO
2
• Precisely regulated to maintain pAO
2
85-100 mmHg and
pACO
2
35-45 mmHg
Under these conditions
97 % (and more) of Hb is saturated with O
2
100 ml of blood contains about 21 ml of O
2
(0.3 ml dissolved)
pH of blood is 7.35-7.45
• Can be divided into four steps:
- pulmonary ventilation
- Diffusion of O
2
and CO
2
between the alveoli and the blood
- Transport of O
2
and CO
2
in the blood and body fluids
- Regulation of ventilation
Respiration
• Inspiration –active , requires contraction of inspiratory
muscles – increase in chest cage volume
• Diaphragm – most important inspiratory muscle , but
does not increase the chest cage volume
• External intercostals
• Additional inspiratory muscles: sternocleidomastoid ,
anterior serati, scaleni
Quiet expiration – passive due to elastic recoil of lungs
and chest wall
Deep expiration – active
Abdominal recti, internal intercostals
Respiration
Flow = ∆P/R
∆P = increase in pressure , R = airways resistance
Pleural cavity, pleural fluid – lubricant
• Pleural pressure – pressure of the fluid in the space
between lung pleura and the chest wall pleura
• Expressed in cm of water against atmospheric pressure
(difference)
• 1 atmosphere = 10000 cm of water
• Alveolar pressure – pressure of the air inside the alveoli
Open glottis and no airflow – alv. pressure is equal to atm.
pressure
Respiration
Normal breathing
Inspiration 0.5 l of air in 2s
Expiration 0.5 l of air in 2-3s
Transpulmonary pressure (recoil pr.) = alveolar
pressure –
-
intrapleural pressure
•
measure of elastic forces in the lungs that tend to
collapse the lungs
•
intrapleural pressure = pressure in the oesophagus
Compliance of the lungs
Compliance = ∆ V / ∆ P (V – air spaces volume, P –
pressure)
• Increases with age
• Increased in pulmonary emphysema
• Decreased in pulmonary fibrosis
What influences lung compliance ?
• Elastic forces of the lung tissue, elastin fibers, collagen
fibers
• Surface tension of the alveolar-lining fluid and
epithelial-lining fluid in other air spaces
Surface tension
P = 2xα /R
R – radius of the alveolus , α – surface tension
Surfactant
• Produced by type II pneumocytes
• Degraded by alveolar macrophages
• Components: phospholipid dipalmitoylphosphatidylcholine
Surfactant apoproteins, Ca
2+
• Reduces the surface tension
• Antibacterial activity
• Lack of surfactant –premature babies –infant respiratory
distress syndrome (atelectasis and lower airways infections)
• Excess of surfactant – no degradation by alveolar
macrophages – pulmonary proteinosis
Why alveoli do not collapse at the
end of expiration ?
• Presence of surfactant
• Tension of alveolar capillaries
• Closing of small airways at the end
of forced expiration
Work of breathing
Work of inspiration (3 fractions)
1- required to expand lungs against the lung and
chest elastic forces – elastic work (compliance
work)
2- required to overcome the viscosity of lungs
and other chest wall structures – tissue
resistance work
3- required to overcome the airways resistance
during the movement of air into the lungs –
airway resistance work
Pulmonary fibrosis
Bronchial asthma
Energy required for respiration
Normal quiet respiration
3-5% of the total energy consumed by the body
Intensive exercise
Increases as much as 50-times
Severe chronic obstructive pulmonary disease
(COPD)
Work of breathing is very high and causes
cachexia
Pulonary volumes and capacities
Tidal volume = 500 ml (quiet respiration)
All pulmonary volumes and capacities depend on
sex , age and height
How to express results of spirometric tests and
how to compare results obtained for various
subjects
% of predicted value
Ventilation
Minute respiratory volume – amount of new air
moved into the airways each minute
Quiet respiration:
Respiratory rate = 12/min
TV = 500 ml
12x0,5 l = 6 l/min
Maximal voluntary ventilation = 200 l/min
Scotoma, dizzines, hyperventilation tetany
Why ?
Decrease in blood CO
2
and Ca
2+
level
Ventilation
Dead space – the space in the respiratory passages where
no gas exchange takes place.
Is about 150 ml
Increases slightly with age
Anatomic dead space
Alveolar dead space – volume of alveoli with no or very
poor blood flow in adjacent capillaries
Physiologic dead space = anatomic + alveolar
• Minute alveolar ventilation= respiratory rate x (TV-V
D
)
TV – tidal volume
V
D
– physiologic dead space
airways
Factors causing constriction:
Parasympathetic nerves
Acetylocholine
Histamine
Cold air
SO
2
, smoke , dust
Inflammatory mediators : e.g PAF (platelet activating factor),
leukotrienes
Factors causing relaxation:
Sympathetic nerves
Adrenaline
Atropine (and derivatives)
Beta-2- agonists
Functions of the respiratory
passageways
• Warming
• Humidification
• Cleaning (filtration, precipitation)
Mucocilliary clearance
Alveolar macrophages
Pulmonary circulation
• Pulmonary vessels : pulmonary artery, right
and left main branches, arteries, arterioles,
capillaries, veins
Supply blood to lungs for gas exchange
• Bronchial vessels: arteries , capillaries, veins –
supply blood to supporting tissues of lung
• Lymphatic vessels – prevent pulmonary edema
Pulmonary circulation
• High flow = cardiac output = flow in systemic
circulation
• Low pressure
• Low resistance
Mean pulmonary arterial pressure = 15 mmHg
(systolic =25 , diastolic= 8 mmHg)
Blood volume in the lungs – about 450 ml
70 ml in pulmonary capillaries
Blood stays in pulmonary capillaries for 0.8 s
During exercise – 0.3 s
Control of pulmonary blood flow
distribution
• PO
2
in alveoli decreases below 73 mmHg –
alveolar hypoxia – adjacent blood vessels (small
arteries) constrict
• Blood flow decreases in hypoventilated areas of
the lung
• Large areas are hypoventilated – increase in
resistance of pulmonary circulation – increased
work of right ventricle- hypertrophy and
insufficiency of right ventricle.
• Body position
Gas exchange
•
CO
2
is 20-times more soluble than O
2
•
CO
2
diffuses 20-times faster through alveolar-blood
barrier thanO
2
•
Gas concentration gradient
Consequences for laboratory findings during development
of respiratory insufficiency
1.
Hypoxemia during exercise, CO
2
normal or decreased
due to compensatory hyperventilation
2.
Hypoxemia at rest
3.
Hypoxemia and hypercapnia at rest
Alveolar-blood barrier (respiratory
membrane)
1- alveolar lining fluid
2- alveolar epithelium
3- epithelial basement membrane
4- thin interstitial space
5- capillary basement membrane
6- capillary endothelium
What affects the rate of CO
2
and O
2
diffusion ?
1- thicknes of the membrane
2- surface area of the membrane
3- diffusion coefficient of the gas in the
substance of the membrane
4 – gas concentration gradient
5 – blood flow in capillaries
Lung diffusing capacity
For O
2
, CO
2
, CO , NO
For CO – important , used in clinical practice
Why ?
CO has 250-times higher affinity to hemoglobin than O
2
.
Its pressure in capillary blood is O mmHg
Gas mixture for determination of carbon monoxide lung
diffusing capacity (DL
CO
)
CO- 0.3%, helium or CH
4
, and N
2
at balance
Age ,sex, height, cigarette smoking , blood hemoglobine
level,
Correction for Hb and alveolar volume
< 80% of predicted – clinical significance
Ventilation-perfusion ratio
Va –alveolar ventilation
Q – blood flow
Va/Q = normal
Va/Q = O - shunt
Va/Q = ∞ - physiologic dead space
Physiologic shunt
Shunted blood – normally 2% of the cardiac
output
Ventilation-perfusion ratio
Normal person , upright position
Top of the lung Va/Q > 2.5 times than ideal value
(physiologic dead space)
Middle of the lung
Bottom of the lung Va/Q < 0.6 times than ideal value
(physiologic shunt)
Chronic obstrucive pulmonary disease (COPD)
Cigarette smoking
• Obstruction of small airways and destruction of alveolar
walls with capillaries
• Some lung areas exhibit seriuos shunt or serious dead
space
Transport of O
2
and CO
2
in the blood
Arterial blood :hemoglobin saturation with O
2
= 97% , PO
2
=95
mmHg
In venous blood: Hb saturation with O
2
= 75% , PO
2
= 40 mmHg
Normal subject
Hb level = 15 g/dl
1 g Hb binds about 1.34 ml O
2
15x 1.34 = 20.1 ml
0.3 ml O
2
dissolved in blood
Total amount of O
2
is 20.4 ml in 100 ml blood
Venous blood contains 14,4 ml O
2
/dl
20.1 – 14.4 = 5.7
About 5 to 6 ml of O
2
is transported to tissues by 100 ml of blood
Factors influencing binding of O
2
to
hemoglobin
• H
+
concentration (pH)
• Increased CO
2
concentration
• Increased temperature
• Increased 2,3-diphosphoglycerate (2,3-
DPG) concentraton in erythrocytes
• CO has 250-times higher affinity to Hb
than O
2
Transport of CO
2
in the blood
Resting conditions
4 ml CO
2
are transported from tissues to the lungs
in 100 ml of venous blood
1- dissolved - 7% of total
2- bicarbonate ions (enzyme carbonic anhydrase) –
70 %
3- combination with –NH
2
groups of Hb and plasma
proteins,
Carbaminohemoglobin - 23 %