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Gas exchange
Pulmonary gas exchange
CO2
O2
CO2
O2
Pulmonary capillary
Tissue gas exchange
Tissue cells
CO2
O2
CO2
O2
Tissue capillaries
Physical principles of gas
exchange

Diffusion: continuous
random motion of gas
molecules.

Partial pressure: the
individual pressure of
each gas, eg. PO2
Boyle’s law states that the pressure of a fixed
number of gas molecules is inversely
proportional to the volume of the container.
Laws governing gas diffusion

Henry’s law:
The amount of dissolved
gas is directly
proportional to the partial
pressure of the gas
Laws governing gas diffusion

Graham's Law
When gases are dissolved in liquids, the relative rate of
diffusion of a given gas is proportional to its solubility in
the liquid and inversely proportional to the square root of
its molecular mass
Laws governing gas diffusion

Fick’s law
The net diffusion rate of a gas across a fluid
membrane is proportional to the difference in
partial pressure, proportional to the area of the
membrane and inversely proportional to the
thickness of the membrane
Factors affecting gas exchange
P  S  T  A
D
d  MW

D:
Rate of gas diffusion






P:
S:
T:
A:
d:
MW:
Difference of partial pressure
Solubility of the gas
Absolute temperature
Area of diffusion
Distance of diffusion
Molecular weight
Gas partial pressure (mmHg)
Atmosphere
Alveoli
Arterial
Venous
Tissue
Po2 159
104
100
40
30
Pco2 0.3
40
40
46
50
In the lungs, the concentration gradients favor the diffusion of
oxygen toward the blood and the diffusion of carbon dioxide
toward the alveolar air; owing to the metabolic activities of cells,
these gradients are reversed at the interface of the blood and the
active cells.
Factors that affect the velocity of
pulmonary gas exchange

Thickness of respiratory membrane呼吸膜

Surface area of respiratory membrane

The diffusion coefficient 扩散系数of the gas

The pressure difference of the gas between the
two sides of the membrane
Respiratory membrane

Is the structure through which oxygen diffuse from the
alveolus into the blood, and carbon dioxide in the
opposite direction.
alveolus
capillary
endothelial cell
surfactant
CO2
epithelial
cell
O2
red blood cell
interstitial space
Ventilation-perfusion ratio 通气/血流比值

Alveolar ventilation (V) = 4.2 L
 Pulmonary blood flow (Q) = 5 L
 V/Q = 0.84 (optimal ratio of air supply and blood
supply)
Ventilation-perfusion ratio
Effect of gravity on V/Q
Physiologic dead space
VA/QC
Physiologic shunt
Normal
Mismatching of the air supply and blood supply in individual alveoli.
The main effect of ventilation-perfusion inequality is to decrease the
Po2 of systemic arterial blood.
Gas transport in the blood

Respiratory gases are transported in the blood
in two forms:
– Physical dissolution
– Chemical combination
Alveoli
O2
Blood
Tissue
→dissolve→combine→dissolve→ O2
CO2 ←dissolve←combine←dissolve← CO2
Transport of oxygen

Forms of oxygen transported
– Chemical combination: 98.5%
– Physical dissolution: 1.5%

Hemoglobin (血红蛋白，Hb) is essential for the
transport of O2 by blood

Normal adult hemoglobin is composed of
four subunits linked together, with each
subunit containing a single heme -- the
ring-like structure with a central iron atom
that binds to an oxygen atom.
Hemoglobin is the gas-transport molecule inside erythrocytes.
Oxygen binds to the iron atom. Heme attaches to a polypeptide chain
by a nitrogen atom to form one subunit of hemoglobin. Four of these
subunits bind to each other to make a single hemoglobin molecule.
Two forms of Hb

Deoxygenated state (deoxyhemoglobin) -when it has no oxygen

Oxygenated form (oxyhemoglobin) -carrying a full load of four oxygen
High PO2
Hb + O2
HbO2
Low PO2
Cooperativity of Hb

Deoxy-hemoglobin is relatively
uninterested in oxygen, but when one
oxygen attaches, the second binds more
easily, and the third and fourth easier yet.

The same process works in reverse: once
fully loaded hemoglobin lets go of one
oxygen, it lets go of the next more easily,
and so forth.

Oxygen capacity 氧容量
– The maximal capacity of Hb to bind O2 in a
blood sample

Oxygen content 氧含量
– The actual binding amount of O2 with Hb

Oxygen saturation 氧饱和度
– Is expressed as O2 bound to Hb devided by
the maximal capacity of Hb to bind O2
– (O2 content / O2 capacity) x 100%
Hb>50g/L ---Cyanosis紫绀

Cyanosis is a physical sign causing bluish
discoloration of the skin and mucous
membranes.
 Cyanosis is caused by a lack of oxygen in the
blood.
 Cyanosis is associated with cold temperatures,
heart failure, lung diseases, and smothering. It is
seen in infants at birth as a result of heart
defects, respiratory distress syndrome, or lung
and breathing problems.
Cyanosis

Hb>50g/L
Carbon monoxide poisoning

CO competes for the O2 sides in Hb

CO has extremely high affinity for Hb

Carboxyhemoglobin---20%-40%, lethal.

A bright or cherry red coloration to the skin
Oxygen-hemoglobin dissociation
curve

The relationship between O2 saturation of Hb
and PO2

Cooperativity
As the concentration of oxygen increases, the percentage of
hemoglobin saturated with bound oxygen increases until all
of the oxygen-binding sites are occupied (100% saturation).
Note that venous blood is typically 75% saturated with oxygen.
Factors that shift oxygen
dissociation curve

PCO2 and [H+]

Temperature

2,3-diphosphoglycerate (2,3-二磷酸甘油酸，
DPG)
Chemical and thermal factors that
alter hemoglobin’s affinity to bind
oxygen alter the ease of “loading”
and “unloading” this gas in the
lungs and near the active cells.
Chemical and thermal factors that
alter hemoglobin’s affinity to bind
oxygen alter the ease of “loading”
and “unloading” this gas in the
lungs and near the active cells.
High acidity and low acidity can be caused by high PCO2 and low
PCO2, respectively.
CO2+H2O  H2CO3  H++HCO3-
Transport of carbon dioxide

Forms of carbon dioxide transported
– Chemical combination: 93%
 Bicarbonate ion (HCO3-) : 70%
 Carbamino hemoglobin(氨基甲酸血红蛋白 ): 23%
– Physical dissolve: 7%
Total blood carbon dioxide
Sum of

Dissolved carbon dioxide

Bicarbonate

carbon dioxide in carbamino hemoglobin
CO2 transport in tissue
capillaries
tissues
CO2
CO2
tissue capillaries
CO2 + Hb
HbCO2
CO2 + H2O carbonic anhydrase H2CO3
HCO3-
H+ +HCO3Cl
-
plasma
tissue capillaries
CO2 transport in pulmonary capillaries
alveoli
CO2
pulmonary capillaries
CO2
CO2 + Hb
HbCO2
CO2 + H2O carbonic anhydrase H2CO3
HCO3H+ +HCO3plasma
Clpulmonary capillaries
Cl-
Cell Respiration

Cellular respiration is the process by which the chemical
energy of "food" molecules is released and partially
captured in the form of ATP. Carbohydrates, fats, and
proteins can all be used as fuels in cellular respiration,
but glucose is most commonly used as an example to
examine the reactions and pathways involved.
Cell Respiration
• Oxidation
• Glycolysis
Regulation of respiration

Breathing is controlled by the central
neuronal network to meet the metabolic
demands of the body
– Neural regulation
– Chemical regulation
Respiratory center

Definition:
– A collection of functionally similar neurons that
help to regulate the respiratory movement
Respiratory center

Medulla

Pons

Higher respiratory center: cerebral cortex,
Basic respiratory center: produce
and control the respiratory
rhythm
hypothalamus & limbic system

Spinal cord: respiratory motor neurons
Neural regulation of respiration

Voluntary breathing center
– Cerebral cortex

Automatic (involuntary) breathing center
– Medulla
– Pons
Neural generation of rhythmical
breathing
The discharge of
medullary inspiratory
neurons provides rhythmic
input to the motor neurons
innervating the inspiratory
muscles. Then the action
potential cease, the
inspiratory muscles relax,
and expiration occurs as
the elastic lungs recoil.

Inspiratory
neurons 吸气
神经元

Expiratory
neurons 呼气
神经元
Respiratory center

Dorsal respiratory group (medulla) – mainly
causes inspiration

Ventral respiratory group (medulla) – causes
either expiration or inspiration

Pneumotaxic center (upper pons) – inhibits
apneustic center & inhibits inspiration,helps
control the rate and pattern of breathing

Apneustic center (lower pons) – to promote
inspiration
Hering-Breuer inflation reflex
(Pulmonary stretch reflex肺牵张反射 )

The reflex is originated in the lungs and
mediated by the fibers of the vagus nerve:
– Pulmonary inflation reflex肺扩张反射:
 inflation of the lungs, eliciting expiration.
– Pulmonary deflation reflex肺缩小反射:
 deflation, stimulating inspiration.
Pulmonary inflation reflex
 Inflation
of the lungs  +pulmonary
stretch receptor +vagus nerve  -
medually inspiratory neurons 
+eliciting expiration
Summary:
Chemical control of respiration

Chemoreceptors
– Central chemoreceptors中枢化学感受器: medulla
 Stimulated by [H+] in the CSF
– Peripheral chemoreceptors外周化学感受器:
 Carotid body
– Stimulated by arterial PO2 or [H+]
 Aortic body
Central chemoreceptors
Peripheral chemoreceptors
Chemosensory neurons
that respond to changes
in blood pH and gas
content are located in
the aorta and in the
carotid sinuses; these
sensory afferent
neurons alter CNS
regulation of
the rate of ventilation.
Effect of carbon dioxide on
pulmonary ventilation
Small changes in the
carbon dioxide content
of the blood quickly
trigger changes in
ventilation rate.
CO2    respiratory activity
Central and peripheral
chemosensory neurons
that respond to increased
carbon dioxide levels in
the blood are also
stimulated by the acidity
from carbonic acid, so
they “inform” the
ventilation control center
in the medulla to increase
the rate of ventilation.
CO2+H2O  H2CO3  H++HCO3-
Effect of hydrogen ion on
pulmonary ventilation
[H+]    respiratory activity
Regardless
of the source,
increases in
the acidity of
the blood cause
hyperventilation.
Regardless of the source,
increases in the acidity of
the blood cause
hyperventilation, even if
carbon dioxide levels are
driven to abnormally low
levels.
Effect of low arterial PO2 on
pulmonary ventilation
PO2    respiratory activity
A severe reduction in the arterial concentration of
oxygen in the blood can stimulate hyperventilation.
Chemosensory neurons
that respond to decreased
oxygen levels in the blood
“inform” the ventilation
control center in the
medulla to increase the rate
of ventilation.
In summary:
The levels of
oxygen, carbon
dioxide, and
hydrogen ions
in blood and CSF
provide information
that alters the
rate of ventilation.
Regulation of respiration
Questions
1. Why is increased depth of breathing far more effective
in evaluating alveolar ventilation than is an equivalent
increase in breathing rate?
Questions

2. Describes the effects of PCO2, [H+] and
PO2 on alveolar ventilation and their
mechanisms.
–
–
–
CO2 -  respiratory activity; Peripheral mechanism
and central mechanism, the latter is the main one.
[H+]  -  respiratory activity; Peripheral mechanism
and central mechanism, the former is the main one.
PO2  -  respiratory activity; Peripheral
mechanism is excitatory.
Questions

3. What is the major result of the ventilationperfusion inequalities throughout the lungs?

4. Describe the factors that influence gas
exchange in the lungs.

5. If an experimental rabbit’s vagi were
onstructed to prevent them from sending
action potential, what will happen to respiration?