Respiration

2Xia Qiang, PhDDepartment of PhysiologyZhejiang University School of MedicineEmail: xiaqiang@zju.edu.cn

Gas exchange

Tissue capillaries

Tissue cellsCO2

CO2O2

O2

Pulmonary capillary

CO2O2

CO2

CO2

O2

O2

Pulmonary gas exchange Tissue gas exchange

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

• 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

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 processesin 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

surfactant

epithelial cell

interstitial space

alveolus capillary

red blood cell

endothelial cell

OO22

COCO22

Ventilation-perfusion ratio

• Alveolar ventilation (V) = 4.2 L • Pulmonary blood flow (Q) = 5 L • V/Q = 0.84 (optimal ratio)

Ventilation-perfusion ratio

VA/QC

Effect of gravity on V/Q

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

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 increasesthe total amount of oxygen in that compartment, since thebound oxygen is no longer part of the diffusional equilibrium.

Hb + O2 HbO2

High PO2

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

OO22

OO22 OO22COCO

COCOCOCO

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%

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

--

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-

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

H2CO3 H+ +HCO3-

HbO2 Hb + O2

CO2

HbCO2

HbH

Bohr effect

Haldane effectHbO2 Hb + O2

tissue capillaries

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• Pons• Higher respiratory center: cerebral cortex,

hypothalamus & limbic system

Basic respiratory center

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

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

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 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.

Carotid body

Effect of carbon dioxide on pulmonary 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 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 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.

An integrated perspective recognizes the variety and diversity of factors that alter the rate of ventilation.

End.