Gas exchange Tissue capillaries Tissue cells CO 2 O2O2 O2O2 Pulmonary capillary CO 2 O2O2 O2O2 Pulmonary gas exchangeTissue gas exchange.

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?