Transcript CO2

Respiratory Physiology
（呼吸生理学）
赖蒽茵
浙江大学医学院生理系 求是特聘教授
浙江省“千人计划”人才，博导
[email protected]
May 26 and 27, 8:00 – 9:35 am, 基础医学各论 I
紫金港校区西2-303, 2012级五年制临床, 共162人
Respiratory
Exchange of oxygen (O2)
and carbon dioxide (CO2)
with environment
Pulmonary ventilation
气体经呼吸道进出肺的过程
The process of moving air into and out of the lungs
Pulmonary ventilation
呼吸过程中肺内压的变化
吸气时，肺内压为
尽力吸气时
-2 to -1mmHg
(-100 to -30mmHg）
呼气时，肺内压为 1 to 2 mmHg
尽力呼气时 （60 to 140mmHg）
Thorax
The thorax is a closed compartment that is bounded at the
neck by muscles and connective tissue and completely
separated from the abdomen by the diaphragm.
Mechanics of pulmonary ventilation
Muscles that cause lung expansion and contraction
吸气肌：diaphragm (膈肌)
external intercostals (肋间外肌)
呼气肌：abdominal muscles (腹肌)
internal intercostals (肋间内肌)
Structures of pulmonary ventilation
Breathing is an active process
To inhale
• Contraction of external intercostal muscles
→elevation of ribs & sternum →increased front-toback dimension of thoracic cavity →lowers air
pressure in lungs →air moves into lungs
• Contraction of diaphragm →diaphragm moves
downward →increases vertical dimension of
thoracic cavity →lowers air pressure in lungs →air
moves into lungs
•To exhale
Relaxation of external intercostal muscles &
diaphragm →return of diaphragm, ribs, &
sternum (胸骨) to resting position →restores
thoracic cavity to pre-inspiratory volume
→increases pressure in lungs →air is exhaled
Pattern of respiration
•Abdominal breathing 腹式呼吸
•Thoracic breathing 胸式呼吸
•Eupnea平静呼吸
•Forced breathing 用力呼吸
Principles of pulmonary ventilation
• Direct force of breathing
– Pressure gradient between atmosphere and lung
• Original force of breathing
– Respiratory movement
Respiration
A processes involved in exchange of oxygen (O2) and
carbon dioxide (CO2) between an organism and the
environment
•Consist of
– Inspiration: the inhalation of air into the lung
– Expiration: breathing out
Respiratory system
Upper airway
Lower airway
The relaxation/contraction
of circular smooth muscle
lining these “airways’”
determines how easily
airflow can occur.
Most gas exchange
occurs in the
alveolar sacs.
Four major steps of respiration
• 1.Pulmonary ventilation
• 2.Gas exchange
– Lung
– Tissue
• 3.Gas transport in blood
• 4.Cellular respiration
Respiratory process
｝外呼吸External
respiration
气体在血液中的运输
Gas transport in the
blood
｝内呼吸Internal
respiration
Process of
respiration:
Fig. 13.06
Gas exchange
Pulmonary gas exchange
CO2
Tissue gas exchange
Tissue cells
CO
O2
2
O2
CO2
O2
Pulmonary capillary
O2
CO2
Tissue capillaries
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
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
Po2
Arterial
Venous Tissue
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.
In the interface of the blood and the active cells, these gradients are
reversed due to the metabolic activities of cells.
Pulmonary gas exchange factors
• Thickness of respiratory membrane (呼吸膜)
• Surface area of respiratory membrane
• The diffusion coefficient of gas (扩散系数)
• The pressure difference of gas between the two sides of membrane
Alveoli
Each of the clustered
alveoli includes an
abundance of pulmonary
capillaries, thereby
assuring that the
ventilated air is brought
into close proximity to
the “pulmonary” blood,
allowing efficient and
thorough gas exchange
between the air and the
blood.
Extensive branching
of alveoli produces
lots of surface area
for exchange between
air and blood.
Alveolar and
capillary
walls are thin,
permitting rapid
diffusion of gases.
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
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. (porphyrin molecules,卟啉分子)
• 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.
High PO2
Hb + O2
HbO2
Low PO2
• 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
• is a physical sign causing bluish discoloration of the
skin and mucous membranes.
• is caused by a lack of oxygen in the blood.
• is associated with cold temperatures, heart failure, lung
diseases. It is seen in infants at birth as a result of heart
defects, respiratory distress syndrome, or lung and
breathing problems.
Hb + O2
HbO2
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 (致命的).
• A bright or cherry red coloration to the skin
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
tissues
CO2
CO2 transport in tissue capillaries
tissue capillaries
CO2
CO2 + Hb
HbCO2
CO2 + H2Ocarbonic anhydrase H2CO3
H+
HCO3-
+HCO3Cl -
plasma
tissue capillaries
CO2 transport in pulmonary capillaries
alveoli
CO2
pulmonary capillaries
CO2
CO2 + Hb
HbCO2
carbonic anhydrase H2CO3
CO2 + H2O
HCO3H+ +HCO3plasma
Clpulmonary capillaries
Cl-
Airflow (F) is a function of the pressure differences
between the alveoli (Palv) and the atmosphere (Patm)
divided by airflow resistance (R).
Air enters the lungs when Palv < Patm
Air exits the lungs when Palv > Patm
Intrapleural pressure （胸内压）
Intrapleural pressure is the pressure within pleural cavity (胸膜腔)
Intrapleural pressure
• Pleural cavity
– Pleural cavity is the closed space between parietal
pleura & lungs covered with visceral pleura
Intrapleural pressure
the pressure within pleural cavity
Direct measurement of intrapleural pressure
Indirect measurement of intrapleural pressure
Measurement of the
pressure inside the
esophagus
Formation of intrapleural pressure
•Fetus lung
Air in lungs after delivery
Formation of intrapleural pressure
• Air in lungs after delivery
• Because the elastic recoil (弹性回缩) causes the lungs to
try to collapse, a negative force is always needed to the
outside of the lungs to keep the lungs expanded. This
force is provided by negative pressure in the normal
pleural space.
Intrapleural pressure
• Intrapleural pressure = Intrapulmonary pressure –
the recoil pressure of the lung
• Intrapleural pressure = – the recoil pressure of the
lung
Pressures involved - intrapulmonary pressure =
atmospheric pressure (760 mmHg) - collapsing
force of lung (肺回缩力) - intrapleural pressure
Physiological significance of intrapleural
negative pressure (胸膜腔负压)
•Allow expansion of the lungs (利于肺的扩张)
• Facilitate the venous & lymphatic return
(促进静脉血和淋巴液的回流)
Pneumothorax (气胸)
Air escapes from the lungs or leaks through the chest
wall and enters the pleural cavity
Lateral 单侧
Bilateral双侧
Compliance of the lungs (肺的顺应性)
•The extent to which the lungs expand for each unit
increase in pressure C=ΔV/ΔP (L/cmH2O)
•Determined by the elastic forces of the lungs (R, 肺弹
性阻力) C=1/R
Compliance of the lungs
• Compliance (顺应性): the expand ability of elastic
tissues when acted on by foreign forces or the extent
to which the lungs expand for each unit increase in
pressure.
• C=ΔV/ΔP (L/cmH2O)
• Elastic Resistance (R)
C=1/R
Compliance （顺应性）varies within the lung
according to the degree of inflation. Poor compliance is
seen at low volumes (because of difficulty with initial
lung inflation) and at high volumes (because of the limit
of chest wall expansion), with best compliance in the
mid-expansion range.
Resistances to Ventilation
• Elastic resistance: The ability of an elastic structure to
resist stretching or distortion. 70%
• Non-elastic resistance: 30%
气道阻力
咽喉 + 直径 > 2mm气道 的气道阻力 = 80%
直径 < 2mm气道 的气道阻力 = 20%
Lung compliance is a
measure of the
lung’s “stretchability.”
When compliance is
abnormally high, the
lungs might fail to
hold themselves open,
and are prone to collapse.
When compliance is
abnormally low, the
work of breathing is
increased.
肺气肿
肺纤维化
Elastic forces of the lungs
• 1/3 Elastic forces of the lung tissue itself （肺组织本身
的弹性回缩力）
• 2/3 Elastic forces caused by surface tension (表面张力)
of the fluid that lines the inside walls of the alveoli
Surface tension
• Elastic-like force existing in the surface of a
liquid, tending to minimize the area of surface
• Caused by asymmetries (不对称) in the intermolecular
forces between surface molecules
Surface tension
• The surface tension at the
air-water interfaces within
the alveoli.
• At an air-water interface, the
attractive forces between the
water molecules (surface
tension) make the alveoli
like stretched balloons that
constantly try to shrink and
resist further stretching.
Pierre Simon Laplace
(1749 -1827)
Laplace’s law: P=2T/r
P=肺泡內压力, T=表面张力, r=肺泡半径
Laplace’s law: P=2T/r
In the absence of surfactant,
the attraction between water
molecules can cause alveolar
collapse.
Alveolar surfactant (表面活性物质)
• Secreted by type II alveolar epithelial cells
• Surfactant is a complex mixture of
– Several phospholipids (二软脂酰卵磷脂
dipalmitoyl phosphatidyl choline, DPPC)
– Surfactant-associated proteins
– Ions (calcium)
Type II alveolar epithelial cells
Physiological effect of Alveolar surfactant
• Reduces surface tension, eases expansion of lung
• Maintains the stability of alveoli in different size
• Keeps the dryness of alveoli
Neonatal respiratory distress syndrome (NRDS)
(新生儿呼吸窘迫综合征) lack of surfactant
retraction of soft tissue on inspiration
By reducing the surface tension of water,
surfactant helps prevent alveolar collapse.
Laplace’s law: P=2T/r
Ta=Tb
Ta>Tb
ra>rb
ra>rb
Pa<Pb
Pa=Pb
Pulmonary surfactant
• Pulmonary surfactant is a mixture of phospholipids and
protein.
• It is secreted by type II alveolar cells.
• It lowers the surface tension of the water layer at the
alveolar surface, which increases lung compliance, makes
the lungs easier to expand.
• Its surface tension is lower in smaller alveoli thus
stabilizing alveoli.
• A deep breath increases its secretion by stretching the type
II cells. Its concentration decreases when breaths are small.
• Production in the fetal lung occurs in late gestation (妊娠).
Non-elastic resistance (非弹性阻力)
• Airway resistance气道阻力: 80~90%
– caused by gas molecules and the inner wall of
airway
– R1/r4
• Inertial resistance惯性阻力
• Viscous resistance粘滞阻力: The effect of surface
friction between a particle and a liquid.
• Regulation of the respiratory smooth muscle by
autonomic nervous system:
– Vagus nerve: Ach  M receptor  Contraction
– Sympathetic nerve: NE  2-receptor 
Relaxation
• Regulation of the respiratory smooth muscle by
endocrine or paracrine factors:
– Histamine, Bradykinin  Contraction
– NE, E, Isoproterenol  Relaxation
Timed vital capacity (时间肺活量)
Pulmonary volumes and capacities
• Spirometer (肺活量计)
a spirometer---a device used to measure lung health.
Blowing forcefully into the tube provides a quick, easy measure of
FEV (Forced expiratory volume, 用力呼气量 = timed vital capacity,
TVC 时间肺活量）.
To learn your FEV, you will be asked to hold the tube of a spirometer
in your mouth, inhale as much air as possible, then exhale forcefully
into the spirometer.
Pulmonary volumes
• Tidal volume (潮气量TV)
Volume of air inspired or expired with each normal
breath
Normal value: 400~500 ml
• Inspiratory reserve volume (补吸气量IRV)
Amount of air that can be inspired above and
beyond TV
Normal value: 1500~2000 ml
• Expiratory reserve volume (补呼气量ERV)
Amount of air that can be expired after a tidal
expiration
Normal value: 900~1200 ml
• Residual volume (残气量RV)
The volume of air remaining in the lungs at the end
of a maximal exhalation
Normal value: M 1500 ml, F 1000 ml
The tidal volume is the amount of air moved in/out of the airways
in a single breathing cycle. Inspiratory and expiratory reserve
volumes are the additional volume that can inspired or expired;
all three quantities sum to the lung’s vital capacity. The residual
volume is the amount of air that must remain in the lungs to
prevent alveolar collapse.
Pulmonary capacities
• Inspiratory capacity 深吸气 = IRV+TV
• Functional residual capacity 功能残气量
The volume of air that still remains in the lungs after
expiration of a resting tidal volume.
FRC = ERV+RV
• Vital volume (肺活量 Vital capacity, VC)
The maximal of air that a person can expire after a
maximal inspiration
VC = TV+IRV+ERV
Normal value: M 3500 ml, F 2500 ml
Pulmonary capacities
• Total lung capacity 肺总量 = VC+RV
The maximal volume of air the lungs can accommodate
Pulmonary capacities
• Forced expiratory volume (用力肺活量，timed vital volume时间
肺活量)
The maximal volume of air that can be exhaled as fast as possible
from the lungs following a maximal inspiration
Normal value:
1st sec. (FEV1) -- 83％
2nd sec. (FEV2) -- 96％
3rd sec. (FEV3) -- 99％
Pulmonary ventilation
• Pulmonary ventilation (每分通气量VE)
The total amount of air inspired/expired during one minute
VE = TV x breaths/min = 500 X12 = 6000 ml
Pulmonary ventilation
• Alveolar ventilation (肺泡通气量VA)
The amount of inspired air that is available for gas exchange
each minute
VA = (TV - dead space无效腔) x breaths/min
= (500-150) X12 = 4200 ml
Dead space
Dead space
• Anatomical dead space
Volume in respiratory passageways which can not be
exchanged
~ 150ml
• Alveolar dead space
Alveoli which have little or no blood supply and
cease to function in gas exchange
Normally ~ 0
Because of the anatomic dead space, “Fresh” inspired air is diluted
by the left over air remaining in the lungs from the previous
breathing cycle.
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
低位脑干--脑桥和延髓
• Medulla
• Pontine (脑桥)
Basic respiratory center: produce and control
the respiratory rhythm
• Higher respiratory center: cerebral cortex,
hypothalamus & limbic system (下丘脑和边缘系统)
• Spinal cord: respiratory motor neurons
低位脑干--脑桥和延髓
Basic respiratory center: produce and control the respiratory rhythm
Respiratory center
• Dorsal respiratory group (medulla) – mainly causes
inspiration
• Ventral respiratory group (medulla) – causes either
expiration or inspiration
• Pneumotaxic center (upper pons 脑桥上部) – inhibits
apneustic center & inhibits inspiration,helps control the
rate and pattern of breathing
• Apneustic center (lower pons) – to promote inspiration
Neural regulation of respiration
• Voluntary breathing center
– Cerebral cortex
• Automatic (involuntary) breathing center
– Medulla
髓
– Pontine
脑桥
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.
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.
舌咽神经
迷走神经
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 (迷走神经):
– 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  -
medualar inspiratory neurons 
+eliciting expiration
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.
Summary
Questions
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
•
What is the major result of the ventilationperfusion inequalities throughout the lungs?
•
Describe the factors that influence gas exchange
in the lungs.
•
If an experimental rabbit’s vagi were obstructed
to prevent them from sending action potential,
what will happen to respiration?