Respiration 2 Xia Qiang, PhD Department of Physiology Zhejiang University School of Medicine

Gas exchange Tissue capillaries Tissue cells CO 2 O2O2 O2O2 Pulmonary capillary CO 2 O2O2 O2O2 O2O2 Pulmonary gas exchangeTissue 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 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 processes in 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 alveoluscapillary red blood cell endothelial cell O2O2O2O2 CO 2

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

Ventilation-perfusion ratio V A /Q C  Effect of gravity on V/Q

Gas transport in the blood Forms of gas transported Physical dissolve Chemical combination AlveoliBloodTissue O 2 →dissolve→combine→dissolve→ O 2 CO 2 ←dissolve←combine←dissolve← CO 2

Transport of oxygen Forms of oxygen transported Physical dissolve: 1.5% Chemical combination: 98.5% Hemoglobin (Hb) is essential for the transport of O 2 by blood

Adding hemoglobin to compartment B substantially increases the total amount of oxygen in that compartment, since the bound oxygen is no longer part of the diffusional equilibrium.

Hb + O 2 HbO 2 High PO 2 Low PO 2

Oxygen capacity The maximal amount of O 2 that can combine with Hb at high PO 2 Oxygen content The amount of O 2 that combines with Hb Oxygen saturation (O 2 content / O 2 capacity) x 100%

Cyanosis Hb>50g/L

Carbon monoxide poisoning CO competes for the O 2 sides in Hb CO has extremely high affinity for Hb O2O2O2O2 O2O2O2O2 O2O2O2O2 CO CO CO

Oxygen-hemoglobin dissociation curve The relationship between O 2 saturation of Hb and PO 2

Factors that shift oxygen dissociation curve PCO 2 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 CO 2 transport in tissue capillaries CO 2 + HbHbCO 2 CO 2 plasma tissues capillaries CO 2 + H 2 O H 2 CO 3 H + +HCO 3 - HCO 3 - CO 2 +H 2 O H 2 CO 3 carbonic anhydrase CO 2 Cl - CO 2 + R-NH 2 R-NHCOO - + H + + HCO 3 -

pulmonary capillaries CO 2 + HbHbCO 2 H + +HCO 3 - HCO 3 - H 2 CO 3 carbonic anhydrase CO 2 + H 2 O plasma alveoli Cl- pulmonary capillaries CO 2 transport in pulmonary capillaries CO 2 Cl-

Carbon Dioxide Dissociation Curve

Haldane Effect When oxygen binds with hemoglobin, carbon dioxide is released PO 2 =40 mmHg PO 2 =100 mmHg

Bohr effect and Haldane effect H 2 CO 3 H + +HCO 3 - HbO 2 Hb + O 2 CO 2 HbCO 2 HbH Bohr effect Haldane effect HbO 2 Hb + O 2 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)

LocationFibers Stimulus Effect SAR trachea-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

Chemical control of respiration Chemoreceptors Central chemoreceptors Peripheral chemoreceptors Carotid body Aortic body

Central 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.

Carotid body

Effect of carbon dioxide on pulmonary ventilation CO 2    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 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 PO 2 on pulmonary ventilation PO 2    respiratory activity

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.

The levels of oxygen, carbon dioxide, and hydrogen ions in blood and CSF provide information that alters the rate of ventilation.

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

End.