Breathing and Exercise

Ventilation (1) Gas Exchange (2) Gas Transport (3) Gas Exchange (4) Cell Respiration (5) Respiration Requires the Interaction of Physiological Systems Respiration Requires the Interaction of Physiological Systems

Conducting Zone: Structure-Function Nasal Cavity is rich in blood supply which warms inspired air. Moist lining humidifies. Upper airways are mainly cartilaginous plates that are ‘stiff’ and conduct air efficiently. Lower airways contain more smooth muscle which can regulate airflow by relaxing and expanding. Mucociliary ‘elevator’ filters.

Respiratory Zone - Structure- Function Type 1 epithelial cells are thin (0.1 to 0.5 µm) making gas exchange with blood efficient. Type 2 epithelial cells make surfactant which keep alveoli ‘open’. Alveolar macrophages remove bacteria and other contaminants. Highly branched allows for great surface area for gas exchange.

(P atm - P alv ) Airway Resistance Flow = End-Expiration

(P atm - P alv ) Airway Resistance Flow = Inspiration

(P atm - P alv ) Airway Resistance Flow = Expiration

Inspiration

Inspiratory Muscle Action

Expiration

Volume (liters) Time

Lung Volumes and Capacities in Healthy Subjects Males Females Measures (20-30 yrs) (20-30 yrs) VC RV FRC TLC RV/TLC x % 24% Measurements are in ml except where indicated.

Lung Volumes and Capacities in Healthy Subjects Males Females Males Measures (20-30 yrs) (20-30 yrs) (50 to 60 yrs) VC RV FRC TLC RV/TLC x % 24% 40% Measurements are in ml except where indicated.

Dead Space Anatomical Dead Space (ADS) is the volume of air needed to fill the conducting zone. Physiological Dead Space (PDS) is ADS + nonfunctional alveoli. Healthy people: ADS = PDS Some pulmonary diseases: ADS < PDS

Ventilation of Dead Space and Alveoli V T is volume required to fill dead space (V D ) + alveoli (V A ). In healthy subjects: V T = ~500 ml V D = ~150 ml V A = ~350 ml

Ventilatory Adjustments and Respiratory Efficiency Increase tidal volume –alveolar ventilation increases –dead space ventilation is unchanged Increase respiratory frequency –alveolar ventilation increases –dead space ventilation increases Increasing tidal volume more efficient!!!

What Determines the Work of Breathing? Lung and Chest Wall Compliance Tissue and Airway Resistance

Elastic Properties of the Lung are a Determinant of Compliance Elastic Properties of the Lung are a Determinant of Compliance Lung Volume Transpulmonary Pressure Compliance = y/x

Lung Volume is a Determinant of Compliance Lung Volume (% Total Lung Capacity) Transpulmonary Pressure (cm H 2 O) Total Lung Capacity (elastic elements are stretched) Functional Residual Capacity Residual Volume (airways are compressed)

Resistance Tissue resistance (~20% of total resistance) Airway resistance (~80% of total resistance) –Airway dimensions –Smooth muscle contraction –Intrapleural pressure

Regulation of Airway Smooth Muscle Airways constricted by: Parasympathetic stimulation Acetylcholine Histamine Leukotrienes Thromboxane A2 Serotonin  -adrenergic agonists Decreased PCO 2 Airways dilated by: Sympathetic stimulation (  2 receptors) Circulating  2 agonists Nitric oxide Increased PCO2 in small airways Decreased PO2 in small airways

Lung Volume is Invesrsely related to Airway Resistance Lung Volume Airway Resistance High Intrapleural Pressures Compress Airways Low Intrapleural Pressures Distend Airways

Airway Compression and Intrapleural Pressure

Ventilation (1) Gas Exchange (2) Gas Transport (3) Gas Exchange (4) Cell Respiration (5) Respiration Requires the Interaction of Physiological Systems Respiration Requires the Interaction of Physiological Systems

Regulation of Pulmonary Vascular Blood Flow Pulmonary artery pressure Extravascular events Chemical regulation of pulmonary vascular smooth muscle Gravity

Pulmonary Vascular Resistance Mean Pulmonary Artery Pressure (mmHg) Increased Pressure decreases Vascular Resistance in the Pulmonary Circulation

Recruitment Distension

Ventilation-Perfusion Matching Regional Ventilation –Increased by high CO 2 Regional Circulation –Decreased by low O 2 Ensures regions of the lung that are well ventilated are also well perfused

Ventilation (1) Gas Exchange (2) Gas Transport (3) Gas Exchange (4) Cell Respiration (5) Respiration Requires the Interaction of Physiological Systems

Diffusion of Gases O2O2 CO 2 T P1P1 P2P2 A ()V AD T PP gas    12

Surface Area for Pulmonary Gas Exchange is Influenced by: Body position Body size Exercise Some pulmonary diseases

Atmospheric Air (mmHg) Humidified Air (mmHg) Alveolar Air (mmHg) Expired Air (mmHg) N2N (78.6%)563.4 (74.1%)569.0 (74.9%)566.0 (74.5%) O2O (20.8%)149.3 (19.7%)104.0 (13.6%)120.0 (15.7%) CO (0.04%) 40.0 (5.3%)27.0 (3.6%) H2OH2O 3.7 (0.5%)47.0 (6.2%) Total 760 (100.0%) Partial Pressures of Respiratory Gases as they Enter and Leave the Lungs at Sea Level Partial Pressures of Respiratory Gases as they Enter and Leave the Lungs at Sea Level

Gas Pressure Gradients in the Lung Values are PO 2 and PCO 2 in mmHg Pulmonary Capillary Alveoli Environment Tissue Metabolism Air-Blood Barrier Artery Vein O2O2 CO

Gas Pressure Gradients in the Lung: Light to Moderate Exercise Gas Pressure Gradients in the Lung: Light to Moderate Exercise Values are PO 2 and PCO 2 in mmHg Pulmonary Capillary Alveoli Environment Tissue Metabolism Air-Blood Barrier Artery Vein O2O2 CO

l5 O 2 molecules are dissolved in solution on both sides of the semi-permeable membrane (no net movement). Dissolved O 2 = 5 Dissolved O 2 = 5 Hemoglobin as an O 2 Carrier

lHemoglobin now binds 4 O 2 molecules, leaving only one in solution. There is now a 5:1 dissolved O 2 ratio (O 2 now moves from left to right). Hb Dissolved O 2 = 5 Dissolved O 2 = 1 Hemoglobin as an O 2 Carrier

l5 O 2 molecules are dissolved in solution on both sides of the semi-permeable membrane (no net movement). Dissolved O 2 = 5 Dissolved O 2 = 5 Hemoglobin as an O 2 Carrier

RBC transit in pulmonary capillary at rest is 1.0 sec RBC transit in pulmonary capillary during exercise is as little as 0.5 sec

RBC transit in pulmonary capillary at rest is 1.0 sec RBC transit in pulmonary capillary during exercise is as little as 0.5 sec

Diffusion - Limited Transfer in the Lung Presence of an end capillary to alveolus partial pressure difference

Perfusion-Limited Transfer in the Lung Absence of an end capillary partial pressure difference An increase in blood flow increases gas exchange with air by sending more blood through pulmonary capillaries.

Diffusion of O 2 to Tissues Diffusion-Limited

Diffusion of CO 2 from Tissues Perfusion-Limited

Transport of O 2 in the Blood

O 2 Carrying Capacity of Blood

Capacity of Blood to Transport O 2 is determined by Characteristics of the Hb-O 2 Dissociation Cure Capacity of Blood to Transport O 2 is determined by Characteristics of the Hb-O 2 Dissociation Cure

‘S’ Shape of Hb-O 2 Dissociation Curve Caused by interaction of 4 Hb subunits as they bind O 2. Hb subunits associate with O 2 sequentially with each successive binding facilitating the next. Flat upper portion insures consistent and adequate O 2 delivery over a broad range of alveolar and arterial PO 2. Steep portion permits rapid unloading of O 2 from Hb during times of need, when PO 2 is low.

Hb-O 2 Binding Affinity is Influenced by Many Factors Hb-O 2 Binding Affinity is Influenced by Many Factors

Venous Blood has a Decreased O 2 Carrying Capacity Venous Blood has a Decreased O 2 Carrying Capacity

Bohr Effect Tissues: High CO 2 or reduced pH decrease Hb affinity for O 2 and facilitates O 2 unloading from blood. Lungs: Reduced CO 2 or increased pH increase Hb affinity for O 2 and facilitate O 2 uptake by the blood.

Transport of CO 2 in the Blood

Blood CO 2 Transport CO 2 ~ 7% HbCO 2 ~ 23% HCO 3 - ~ 70%

Haldane Effect describes the Reduced Capacity of Arterial Blood to Transport CO 2 Haldane Effect describes the Reduced Capacity of Arterial Blood to Transport CO 2 Blood CO 2 (ml/dl) Blood PCO 2 (mmHg)

Haldane Effect Tissues: Deoxygenated Hb affinity for CO 2 is higher than Hb-O 2 affinity for CO 2. This results in an increased capacity of blood to carry CO 2. Lungs: Hb-O 2 has decreased affinity for CO 2 and is more acidic than deoxygenated Hb. This facilitates CO 2 removal from the pulmonary capillaries.

Control of Breathing Requires Three Elements: One that Senses the 'Internal Climate', One that Integrates Sensory Info and Central Commands, One that Carries Out the Order Central Controller pons, medulla, other parts of brain Sensors Effectors Negative Feedback chemical, mechanical, and other receptors inspiratory and expiratory muscles InputOutput

Medullary Respiratory Centers Figure 22.25

Depth and Rate of Breathing: P CO2

Peripheral and Central Chemoreceptors have different Response Characteristics Breathing is stimulated by: Peripheral -  PCO 2,  pH,  PO 2 Central -  pH,  PCO 2 (indirect) Central response to arterial PCO 2 is of greater magnitude. Peripheral response to arterial PCO 2 is faster.

Ventilation (liters/min) Time (sec) Sole Source of Ventilatory Drive to Hypoxia Comes from Peripheral Chemoreceptors Sole Source of Ventilatory Drive to Hypoxia Comes from Peripheral Chemoreceptors Hypoxia Peripheral Chemoreceptor afferent nerves intact or denervated

Respiratory adjustments are geared to both the intensity and duration of exercise During vigorous exercise: –Ventilation can increase 20 fold –Breathing becomes deeper and more vigorous, but respiratory rate may not be significantly changed (hyperpnea) Exercise-enhanced breathing is not prompted by an increase in P CO2 or a decrease in P O2 or pH –These levels remain surprisingly constant during exercise Respiratory Adjustments: Exercise

As exercise begins: –Ventilation increases abruptly, rises slowly, and reaches a steady state When exercise stops: –Ventilation declines suddenly, then gradually decreases to normal Respiratory Adjustments: Exercise

Pulmonary Response to Constant Load Exercise

Exercise-Induced Lactic Acidosis H C0 2 H 2 C0 3 H + + HC0 3 - CA

Incremental Exercise Test

Acclimatization – respiratory and hematopoietic adjustments to altitude include: –Increased ventilation – 2-3 L/min higher than at sea level –Chemoreceptors become more responsive to P CO2 –Substantial decline in P O2 stimulates peripheral chemoreceptors Respiratory Adjustments: High Altitude