respiration 2 xia qiang, phd department of physiology zhejiang university school of medicine email:...
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Respiration
2Xia Qiang, PhDDepartment of PhysiologyZhejiang University School of MedicineEmail: [email protected]
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Gas exchange
Tissue capillaries
Tissue cellsCO2
CO2O2
O2
Pulmonary capillary
CO2O2
CO2
CO2
O2
O2
Pulmonary gas exchange Tissue gas exchange
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Physical principles of gas exchange
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Laws governing gas diffusion
• Henry’s law
The amount of dissolved gas is directly proportional to the partial pressure of the gas
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Boyle’s law states that the pressure of a fixed number of gas molecules is inversely proportional to the volume of the container.
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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
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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
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• D: Rate of gas diffusion • T: Absolute temperature• A: Area of diffusion• S: Solubility of the gas
P: Difference of partial pressure• d: Distance of diffusion• MW: Molecular weight
MWd
ATSPD
Factors affecting gas exchange
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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.
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In lungs
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Oxygen diffusion along the length of the pulmonary capillaries quickly achieves diffusional equilibrium, unless disease processesin the lungs reduce the rate of diffusion.
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In tissue
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Factors that affect pulmonary gas exchange
• Thickness of respiratory membrane
• Surface area of respiratory membrane
• Ventilation-perfusion ratio (V/Q)
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Respiratory membrane
surfactant
epithelial cell
interstitial space
alveolus capillary
red blood cell
endothelial cell
OO22
COCO22
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Ventilation-perfusion ratio
• Alveolar ventilation (V) = 4.2 L • Pulmonary blood flow (Q) = 5 L • V/Q = 0.84 (optimal ratio)
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Ventilation-perfusion ratio
VA/QC
Effect of gravity on V/Q
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Gas transport in the blood
• Forms of gas transported• Physical dissolve• Chemical combination
Alveoli Blood Tissue
O2 →dissolve→combine→dissolve→ O2
CO2 ←dissolve←combine←dissolve← CO2
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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
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Adding hemoglobin to compartment B substantially increasesthe total amount of oxygen in that compartment, since thebound oxygen is no longer part of the diffusional equilibrium.
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Hb + O2 HbO2
High PO2
Low PO2
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• 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%
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Cyanosis
• Hb>50g/L
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Carbon monoxide poisoning
• CO competes for the O2 sides in Hb
• CO has extremely high affinity for Hb
OO22
OO22 OO22COCO
COCOCOCO
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Oxygen-hemoglobin dissociation curve• The relationship between O2 saturation of Hb
and PO2
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Factors that shift oxygen dissociation curve
• PCO2 and [H+]
• Temperature
• 2,3-diphosphoglycerate (DPG)
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Bohr Effect
• Increased delivery of oxygen to the tissue when carbon dioxide and hydrogen ions shift the oxygen dissociation curve
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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.
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Transport of carbon dioxide
• Forms of carbon dioxide transported
• Physical dissolve: 7%
• Chemical combination: 93%
• Bicarbonate ion: 70%
• Carbaminohemoglobin: 23%
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tissue capillaries
tissues
CO2 transport in tissue capillaries
CO2 + Hb HbCO2
CO2
plasmaplasmatissues capillaries
CO2 + H2O H2CO3
H+ +HCO3-
HCOHCO33--
COCO22+H+H22OO HH22COCO33
carbonic anhydrase
CO2
ClCl--
COCO22
++R-NHR-NH22
R-NHCOOR-NHCOO--
++HH++
HH++
++HCOHCO33
--
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pulmonary capillaries
CO2 + Hb HbCO2
H+ +HCO3-
HCOHCO33--
H2CO3carbonic anhydraseCO2 + H2O
plasmaplasma
alveoli
Cl-
pulmonary capillaries
CO2 transport in pulmonary capillaries
COCO22
CO2
Cl-Cl-
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Carbon Dioxide Dissociation Curve
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Haldane Effect
• When oxygen binds with hemoglobin,
carbon dioxide is released
PO2=40 mmHg
PO2=100 mmHg
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Bohr effect and Haldane effect
H2CO3 H+ +HCO3-
HbO2 Hb + O2
CO2
HbCO2
HbH
Bohr effect
Haldane effectHbO2 Hb + O2
tissue capillaries
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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
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Respiratory center
• A collection of functionally similar neurons that help to regulate the respiratory movement
• Respiratory center• Medulla• Pons• Higher respiratory center: cerebral cortex,
hypothalamus & limbic system
Basic respiratory center
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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
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Pulmonary mechanoreceptors
A:Slowly Adapting Receptor (SAR)
B: Rapidly Adapting Receptor (RAR)
C: J-receptors (C-fibers)
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Location Fibers Stimulus Effect
SARtrachea-terminal bronchioles
(smooth muscle)
large myelinated
Stretch
(lung volume)termination of inspiration
RAR
trachea-respiratory
bronchioles
(epithelium)
small myelinated
lung volume,
noxious gases, cigarette smoke, histamine, lung deflation
bronchocontriction,
(rapid & shallow breathing)
C-fibers
alveolar capillary membrane
non-myelinated
volume of interstitial fluid
Apnea followed by a rapid & shallow breathing HR&BP
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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
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Hering-Breuer reflex
End of inspiration
FRC
FRC
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Chemical control of respiration
• Chemoreceptors
• Central chemoreceptors
• Peripheral chemoreceptors
• Carotid body
• Aortic body
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Central chemoreceptors
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Chemosensory neuronsthat respond to changesin blood pH and gas content are located in the aorta and in thecarotid sinuses; thesesensory afferentneurons alter CNSregulation of the rate of ventilation.
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Carotid body
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Effect of carbon dioxide on pulmonary ventilation
CO2 respiratory activity
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Central and peripheralchemosensory 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.
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Effect of hydrogen ion on pulmonary ventilation
[H+] respiratory activity
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Regardless of the source, increases in the acidity of the blood cause hyperventilation, even if carbon dioxide levels are driven to abnormally low levels.
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Effect of low arterial PO2 on pulmonary ventilation
PO2 respiratory activity
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Chemosensory neuronsthat respond to decreasedoxygen levels in the blood“inform” the ventilation control center in themedulla to increase the rate of ventilation.
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The levels ofoxygen, carbondioxide, and hydrogen ionsin blood and CSFprovide informationthat alters therate of ventilation.
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An integrated perspective recognizes the variety and diversity of factors that alter the rate of ventilation.
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End.