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Gas exchangeGas exchange
Tissue capillaries
Tissue cellsCO2
CO2O2
O2
Pulmonary capillaryCO2
CO2
O2
O2
Pulmonary gas exchange Tissue gas exchange
Physical principles of gas exchangePhysical principles of gas exchange
Diffusion:Diffusion: continuous continuous random motion of gas random motion of gas molecules.molecules.
Partial pressure:Partial pressure: the i the individual pressure of ndividual pressure of each gas, eg. each gas, eg. POPO22
Boyle’s law states that the pressure of a fixednumber of gas molecules is inversely proportional to the volume of the container.
Laws governing gas diffusionLaws governing gas diffusion
Henry’s law:Henry’s law:
The amount of dissolved The amount of dissolved gas is directly gas is directly proportional to the partial proportional to the partial pressure of the gaspressure of the gas
Laws governing gas diffusionLaws governing gas diffusion
Graham's LawGraham's Law
When gases are dissolved in liquids, the relative rate of When gases are dissolved in liquids, the relative rate of
diffusion of a given gas is proportional to its diffusion of a given gas is proportional to its solubilitysolubility in t in t
he liquid and inversely proportional to the he liquid and inversely proportional to the square root of square root of
its molecular massits molecular mass
Laws governing gas diffusionLaws governing gas diffusion
Fick’s lawFick’s law
The net diffusion rate of a gas across a fluid mThe net diffusion rate of a gas across a fluid m
embrane is proportional to the difference in embrane is proportional to the difference in parpar
tial pressuretial pressure, proportional to the , proportional to the area area of the meof the me
mbrane and inversely proportional to the mbrane and inversely proportional to the thicknthickn
essess of the membrane of the membrane
D: D: Rate of gas diffusion Rate of gas diffusion
P: P: Difference of partial pressureDifference of partial pressure S: S: Solubility of the gas Solubility of the gas T: T: Absolute temperatureAbsolute temperature A: A: Area of diffusionArea of diffusion d: d: Distance of diffusionDistance of diffusion MW: MW: Molecular weightMolecular weight
MWd
ATSPD
Factors affecting gas exchangeFactors affecting gas exchange
Gas partial pressure (mmHg)Gas partial pressure (mmHg)
AtmosphereAtmosphere Alveoli Arterial VenousAlveoli Arterial Venous Tissue Tissue
PoPo22 159159 104 104 100100 4040 30 30
PcoPco22 0.3 0.3 40 40 40 4640 46 50 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 Factors that affect the velocity of pulmonary gas exchangepulmonary 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 t
wo sides of the membrane
Respiratory membraneRespiratory membrane
surfactant
epithelial cell
interstitial space
alveolus capillary
red blood cell
endothelial cell
OO22
COCO22
Is the structure through which oxygen diffuse from the Is the structure through which oxygen diffuse from the alveolus into the blood, and carbon dioxide in the alveolus into the blood, and carbon dioxide in the opposite direction.opposite direction.
Ventilation-perfusion ratio Ventilation-perfusion ratio 通气通气 //血流比值血流比值
Alveolar ventilation (V) = 4.2 L Alveolar ventilation (V) = 4.2 L Pulmonary blood flow (Q) = 5 L Pulmonary blood flow (Q) = 5 L V/Q = 0.84 (optimal ratio of air supply and blood V/Q = 0.84 (optimal ratio of air supply and blood
supply)supply)
Ventilation-perfusion ratio Ventilation-perfusion ratio
VA/QC
Effect of gravity on V/Q
Physiologic dead space
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 PoPo22 of systemic arterial blood.
Gas transport in the bloodGas transport in the blood Respiratory gases are transported in the blood in Respiratory gases are transported in the blood in
two forms:two forms:– Physical dissolutionPhysical dissolution– Chemical combinationChemical combination
AlveoliAlveoli BloodBlood TissueTissue
OO22 →dissolve→combine→dissolve→ O →dissolve→combine→dissolve→ O22
COCO22 ←dissolve←combine←dissolve← CO ←dissolve←combine←dissolve← CO22
Transport of oxygenTransport of oxygen
Forms of oxygen transportedForms of oxygen transported
– Chemical combination: 98.5%Chemical combination: 98.5%
– Physical dissolution: 1.5%Physical dissolution: 1.5%
Hemoglobin (Hemoglobin ( 血红蛋白,血红蛋白, Hb) is essential for the Hb) is essential for the
transport of Otransport of O22 by blood by blood
Normal adult hemoglobin is composed of fNormal adult hemoglobin is composed of four subunits linked together, with each subour subunits linked together, with each subunit containing a single heme -- the ring-likunit containing a single heme -- the ring-like structure with a central iron atom that bine structure with a central iron atom that binds to an oxygen atom.ds 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 HbTwo forms of Hb
Deoxygenated state (deoxyhemoglobin)Deoxygenated state (deoxyhemoglobin) -- --
when it has no oxygenwhen it has no oxygen
Oxygenated form (oxyhemoglobin)Oxygenated form (oxyhemoglobin) -- carry -- carry
ing a full load of four oxygening a full load of four oxygen
Hb + O2 HbO2
High PO2
Low PO2
Cooperativity of HbCooperativity of Hb
Deoxy-hemoglobin is relatively uninteresteDeoxy-hemoglobin is relatively uninterested in oxygen, but when one oxygen attached in oxygen, but when one oxygen attaches, the second binds more easily, and the ts, the second binds more easily, and the third and fourth easier yet.hird and fourth easier yet.
The same process works in reverse: once The same process works in reverse: once fully loaded hemoglobin lets go of one oxyfully loaded hemoglobin lets go of one oxygen, it lets go of the next more easily, and gen, it lets go of the next more easily, and so forth. so forth.
Oxygen capacity Oxygen capacity 氧容量氧容量– The maximal capacity of Hb to bind OThe maximal capacity of Hb to bind O2 2 in a blood in a blood
samplesample
Oxygen content Oxygen content 氧含量氧含量– The actual binding amount of OThe actual binding amount of O22 with Hb with Hb
Oxygen saturation Oxygen saturation 氧饱和度氧饱和度– Is expressed as OIs expressed as O2 2 bound to Hb devided by the mbound to Hb devided by the m
aximal capacity of Hb to bindaximal capacity of Hb to bind OO22
– (O(O22 content / O content / O22 capacity) x 100% capacity) x 100%
Hb>50g/L ---Hb>50g/L ---CyanosisCyanosis 紫绀紫绀 CyanosisCyanosis is a physical sign causing bluish is a physical sign causing bluish
discoloration of the skin and mucous discoloration of the skin and mucous membranes. membranes.
CyanosisCyanosis is caused by a lack of oxygen in the is caused by a lack of oxygen in the blood. blood.
CyanosisCyanosis is associated with cold temperatures, is associated with cold temperatures, heart failure, lung diseases, and smothering. It is heart failure, lung diseases, and smothering. It is seen in infants at birth as a result of heart seen in infants at birth as a result of heart defects, respiratory distress syndrome, or lung defects, respiratory distress syndrome, or lung and breathing problems.and breathing problems.
CyanosisCyanosis
Hb>50g/LHb>50g/L
Carbon monoxide poisoning Carbon monoxide poisoning
CO competes for the OCO competes for the O22 sides in Hb sides in Hb
CO has extremely high affinity for HbCO has extremely high affinity for Hb Carboxyhemoglobin---20%-40%, lethal. Carboxyhemoglobin---20%-40%, lethal. A bright or cherry red coloration to the skinA bright or cherry red coloration to the skin
Oxygen-hemoglobin dissociation Oxygen-hemoglobin dissociation curvecurve
The relationship between OThe relationship between O22 saturation of Hb a saturation of Hb a
nd POnd PO22
CooperativityCooperativity
As the concentration of oxygen increases, the percentage ofhemoglobin saturated with bound oxygen increases until allof the oxygen-binding sites are occupied (100% saturation).
Note that venous blood is typically 75% saturated with oxygen.
Factors that shift oxygen Factors that shift oxygen dissociation curvedissociation curve
PCOPCO22 and [H and [H++]]
TemperatureTemperature
2,3-diphosphoglycerate (2,3-diphosphoglycerate (2,3- 二磷酸甘油
酸, DPG)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 PCOPCO22 and lo and low PCOw PCO22, respectively., respectively.COCO22+H+H22OO HH22COCO33 HH+++HCO+HCO33
--
Transport of carbon dioxideTransport of carbon dioxide
Forms of carbon dioxide transportedForms of carbon dioxide transported
– Chemical combination:Chemical combination: 93% 93%
Bicarbonate ion (Bicarbonate ion (HCOHCO33--)) : 70% : 70%
Carbamino hemoglobin(Carbamino hemoglobin( 氨基甲酸血红蛋白 氨基甲酸血红蛋白 ): 23%): 23%
– Physical dissolve:Physical dissolve: 7% 7%
Total blood carbon dioxideTotal blood carbon dioxide
Sum ofSum of
Dissolved carbon dioxide Dissolved carbon dioxide
BicarbonateBicarbonate
carbon dioxide in carbamino hemoglobincarbon dioxide in carbamino hemoglobin
tissue capillaries
tissuesCO2 transport in tissue
capillaries
CO2 + Hb HbCO2
CO2
plasmaplasmatissue capillaries
CO2 + H2O H2CO3
H+ +HCO3-
HCOHCO33--
carbonic anhydrase
CO2
ClCl--
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-
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.
• Oxidation • Glycolysis
Cell Respiration
Regulation of respirationRegulation of respiration
Breathing is controlled by the central Breathing is controlled by the central
neuronal network to meet the metabolic neuronal network to meet the metabolic
demands of the bodydemands of the body
– Neural regulation Neural regulation
– Chemical regulationChemical regulation
Respiratory centerRespiratory center
Definition: Definition:
– A collection of functionally similar neurons A collection of functionally similar neurons
that help to regulate the respiratory movementthat help to regulate the respiratory movement
Respiratory centerRespiratory center
MedullaMedulla
PonsPons
Higher respiratory center:Higher respiratory center: cerebral cortex, cerebral cortex,
hypothalamus & limbic systemhypothalamus & limbic system
Spinal cord: respiratory motor neurons Spinal cord: respiratory motor neurons
Basic respiratory center: produce and control the respiratory rhythm
Voluntary breathing centerVoluntary breathing center
– Cerebral cortexCerebral cortex
Automatic (involuntary) breathing centerAutomatic (involuntary) breathing center
– MedullaMedulla
– PonsPons
Neural regulation of respirationNeural regulation of respiration
Neural generation of rhythmical Neural generation of rhythmical breathingbreathing
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 neInspiratory ne
urons urons 吸气神经元
Expiratory neExpiratory ne
urons urons 呼气神经元
Respiratory centerRespiratory center
Dorsal respiratory groupDorsal respiratory group (medulla) – mainly causes i (medulla) – mainly causes i
nspirationnspiration
Ventral respiratory groupVentral respiratory group (medulla) – causes either e (medulla) – causes either e
xpiration or inspirationxpiration or inspiration
Pneumotaxic centerPneumotaxic center (upper pons) – inhibits apneusti(upper pons) – inhibits apneusti
c center & inhibits inspiration,helps control the rate ac center & inhibits inspiration,helps control the rate a
nd pattern of breathingnd pattern of breathing
Apneustic centerApneustic center (lower pons) – to promote inspirati (lower pons) – to promote inspirati
on on
Hering-Breuer inflation reflex(Pulmonary stretch reflex 肺牵张反射 )
The reflex is originated in the lungs and m
ediated 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 st
retch receptor +vagus nerve -me
dually inspiratory neurons +eliciting
expiration
Summary:Summary:
Chemical control of respirationChemical control of respiration
ChemoreceptorsChemoreceptors
– Central Central chemoreceptorschemoreceptors 中枢化学感受器 :: medulla medulla
Stimulated by [HStimulated by [H++]] in the CSF in the CSF
– Peripheral Peripheral chemoreceptorschemoreceptors 外周化学感受器 :
Carotid bodyCarotid body
– Stimulated by arterial Stimulated by arterial POPO22 or or [H[H++]]
Aortic bodyAortic body
Central chemoreceptors
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.
Peripheral chemoreceptorsPeripheral chemoreceptors
Small changes in thecarbon dioxide contentof the blood quickly trigger changes in ventilation rate.
Effect of carbon dioxide on Effect of carbon dioxide on pulmonary ventilationpulmonary ventilation
CO2 respiratory activity
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 to increase the rate of ventilation.
COCO22+H+H22OO HH22COCO33 HH+++HCO+HCO3-3-
Regardlessof the source,increases in the acidity ofthe blood cause hyperventilation.
Effect of hydrogen ion on Effect of hydrogen ion on pulmonary ventilationpulmonary 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.
A severe reduction in the arterial concentration of oxygen in the blood can stimulate hyperventilation.
Effect of low arterial POEffect of low arterial PO22 on on pulmonary ventilationpulmonary ventilation
PO2 respiratory activity
Chemosensory neuronsthat respond to decreasedoxygen levels in the blood“inform” the ventilation control center in themedulla to increase the rate of ventilation.
The levels ofoxygen, carbondioxide, and hydrogen ionsin blood and CSFprovide informationthat alters therate of ventilation.
In summary:
Regulation of respirationRegulation of respiration
1. Why is increased depth of breathing far more effective
in evaluating alveolar ventilation than is an equivalent
increase in breathing rate?
QuestionsQuestions
QuestionsQuestions
2. Describes the effects of PCO2, [H+] and 2. Describes the effects of PCO2, [H+] and PO2 on alveolar ventilation and their PO2 on alveolar ventilation and their mechanisms.mechanisms.
– CO2CO2 - - respiratory activity; Peripheral mechanism respiratory activity; Peripheral mechanism and central mechanism, the latter is the main one.and central mechanism, the latter is the main one.
– [H+] [H+] - - respiratory activity; Peripheral mechanism respiratory activity; Peripheral mechanism and central mechanism, the former is the main one.and central mechanism, the former is the main one.
– PO2 PO2 - - respiratory activity; Peripheral mechanism respiratory activity; Peripheral mechanism is excitatory.is excitatory.
QuestionsQuestions
3. What is the major result of the ventilation-pe3. What is the major result of the ventilation-pe
rfusion inequalities throughout the lungs?rfusion inequalities throughout the lungs?
4. Describe the factors that influence gas exch4. Describe the factors that influence gas exch
ange in the lungs.ange in the lungs.
5. If an experimental rabbit’s vagi were onstruc5. If an experimental rabbit’s vagi were onstruc
ted to prevent them from sending action potentted to prevent them from sending action potent
ial, what will happen to respiration?ial, what will happen to respiration?