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Respiration
2
Xia Qiang, PhD
Department of Physiology
Zhejiang University School of Medicine
Email: [email protected]
Gas exchange
Pulmonary gas exchange
O2
CO2
Tissue gas exchange
CO
2
O2
CO2
O2
Pulmonary capillary
Tissue cells
CO2
O2
CO2
O2
Tissue capillaries
Physical principles of gas
exchange
Laws governing gas diffusion
• Henry’s law
The amount of dissolved
gas is directly
proportional to the partial
pressure of the gas
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
• 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:
T:
A:
S:
Rate of gas diffusion
Absolute temperature
Area of diffusion
Solubility of the gas
•
•
•
P:
d:
MW:
Difference of partial pressure
Distance of diffusion
Molecular weight
Changes in the concentration of dissolved gases are indicated as the blood
circulates in the body. Oxygen is converted to water in cells; cells release
carbon dioxide as a byproduct of fuel catabolism.
In lungs
Oxygen diffusion along
the length of the
pulmonary capillaries
quickly achieves
diffusional equilibrium,
unless disease processes
in the lungs reduce the rate
of diffusion.
In tissue
Factors that affect pulmonary gas
exchange
• Thickness of respiratory membrane
• Surface area of respiratory membrane
• Ventilation-perfusion ratio (V/Q)
Respiratory membrane
alveolus
capillary
endothelial cell
surfactant
CO2
epithelial
cell
O2
red blood cell
interstitial space
Ventilation-perfusion ratio
• Alveolar ventilation (V) = 4.2 L
• Pulmonary blood flow (Q) = 5 L
• V/Q = 0.84 (optimal ratio)
Ventilation-perfusion ratio
Effect of gravity on V/Q
VA/QC
Gas transport in the blood
• Forms of gas transported
• Physical dissolve
• Chemical combination
Alveoli
O2
Blood
Tissue
→dissolve→combine→dissolve→ O2
CO2 ←dissolve←combine←dissolve← CO2
Transport of oxygen
• Forms of oxygen transported
• Physical dissolve: 1.5%
• Chemical combination: 98.5%
• Hemoglobin (Hb) is essential for the transport of
O2 by blood
Adding hemoglobin to compartment B substantially increases
the total amount of oxygen in that compartment, since the
bound oxygen is no longer part of the diffusional equilibrium.
High PO2
Hb + O2
HbO2
Low PO2
• Oxygen capacity
The maximal amount of O2 that can
combine with Hb at high PO2
• Oxygen content
The amount of O2 that combines with Hb
• Oxygen saturation
(O2 content / O2 capacity) x 100%
Cyanosis
• Hb>50g/L
Carbon monoxide poisoning
• CO competes for the O2 sides in Hb
• CO has extremely high affinity for Hb
O2
O
CO 2
COCO O2
Oxygen-hemoglobin dissociation
curve
• The relationship between O2 saturation of Hb
and PO2
Factors that shift oxygen
dissociation curve
• PCO2 and [H+]
• Temperature
• 2,3-diphosphoglycerate (DPG)
Bohr Effect
• Increased delivery of oxygen to the tissue when
carbon dioxide and hydrogen ions shift the
oxygen dissociation curve
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.
Transport of carbon dioxide
• Forms of carbon dioxide transported
• Physical dissolve: 7%
• Chemical combination: 93%
• Bicarbonate ion: 70%
• Carbaminohemoglobin: 23%
CO2 transport in tissue capillaries
tissues
CO2
CO2
CO2+H2O
tissue capillaries
H2CO3
H+
CO2 +
+ HCO 3
R-NH2
R-NHCOO+
H+
CO2 + Hb
HbCO2
CO2 + H2O carbonic anhydrase H2CO3
HCO3-
H+ +HCO3Cl
-
plasma
tissues capillaries
CO2 transport in pulmonary capillaries
alveoli
CO2
pulmonary capillaries
CO2
CO2 + Hb
HbCO2
CO2 + H2O carbonic anhydrase H2CO3
HCO3H+ +HCO3plasma
Clpulmonary capillaries
Cl-
Carbon Dioxide Dissociation Curve
Haldane Effect
• When oxygen binds with hemoglobin,
carbon dioxide is released
PO2=40 mmHg
PO2=100 mmHg
Bohr effect and Haldane effect
tissue capillaries
H2CO3
Bohr effect
HbO2
HbO2
H+ +HCO3-
HbH
Hb + O2
Hb + O2
Haldane effect
CO2
HbCO2
Regulation of respiration
• Breathing is autonomically controlled by
the central neuronal network to meet the
metabolic demands of the body
• Breathing can be voluntarily changed,
within certain limits, independently of body
metabolism
Respiratory center
• A collection of functionally similar neurons
that help to regulate the respiratory
movement
• Respiratory center
• Medulla
Basic respiratory center
• Pons
• Higher respiratory center: cerebral cortex,
hypothalamus & limbic system
Respiratory center
• Dorsal respiratory group (medulla) –
mainly causes inspiration
• Ventral respiratory group (medulla) –
causes either expiration or inspiration
• Pneumotaxic center (pons) – helps control
the rate and pattern of breathing
Pulmonary mechanoreceptors
A:Slowly Adapting
Receptor (SAR)
B: Rapidly Adapting
Receptor (RAR)
C: J-receptors (C-fibers)
Location
Fibers
Stimulus
Effect
SAR
trachea-terminal
large
bronchioles
myelinated
(smooth muscle)
Stretch
(lung volume)
termination of
inspiration
RAR
trachearespiratory
bronchioles
(epithelium)
lung volume,
noxious gases,
cigarette smoke,
histamine, lung
deflation
bronchocontriction,
(rapid & shallow
breathing)
Cfibers
alveolar
capillary
membrane
volume of
interstitial fluid
Apnea followed by
a rapid & shallow
breathing
HR&BP
small
myelinated
nonmyelinated
Hering-Breuer inflation reflex
(Pulmonary stretch reflex)
• The reflex reactions originating in the
lungs and mediated by the fibers of the
vagus nerve: inflation of the lungs, eliciting
expiration, and deflation, stimulating
inspiration
Hering-Breuer reflex
End of inspiration
FRC
FRC
Chemical control of respiration
• Chemoreceptors
• Central chemoreceptors
• Peripheral chemoreceptors
• Carotid body
• Aortic body
Central 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.
Carotid body
Effect of carbon dioxide on
pulmonary ventilation
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 oblongata to
increase the rate of
ventilation.
Effect of hydrogen ion on
pulmonary ventilation
[H+]    respiratory activity
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
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.
The levels of
oxygen, carbon
dioxide, and
hydrogen ions
in blood and CSF
provide information
that alters the
rate of ventilation.
An integrated perspective recognizes the
variety and diversity of factors that alter
the rate of ventilation.
End.