P PP P P PP PP Exam I Exam II Exams handed back at end of class... Chapters 23: Respiratory System Respiratory System: A. Functional Anatomy B. Mechanisms of Breathing C. Gas Exchange D. Gas Transport E. Control of Respiration Today: A. Gas Exchange B. Gas Transport C. Control of Respiration Mariners Twins 2 0 Supplies the body with oxygen and disposes of carbon dioxide Chapters 23: Respiratory System Gas Exchange: Physical Properties of Gases: Chapters 23: Respiratory System Gas Exchange: Physical Properties of Gases: 1) Dalton’s Law of Partial Pressures: 0.21 mm Hg Carbon Dioxide • The total pressure of a gas is equal to the sum of the pressures of its constituents 0.04% Carbon Dioxide 159 mm Hg Oxygen PAtmosphere = 760 mm Hg 20.94% Oxygen PO2 = 0.21 x 760 mm Hg = 159 mm Hg Partial Pressure of Dry Room Air 601 mm Hg Nitrogen PN2 = 0.79 x 760 mm Hg = 601 mm Hg 79% Nitrogen PCO2 = 0.0004 x 760 mm Hg = 0.30 mm Hg % Composition of Air Chapters 23: Respiratory System Chapters 23: Respiratory System Gas Exchange: Physical Properties of Gases: Gas Exchange: 2) Henry’s Law: • Gases in a mixture dissolve in a liquid in proportion to their partial pressures Lung air modified by gas exchange: Why is alveolar gas high in CO2 and water vapor? 1) O2 into blood; CO2 out of blood 2) Humidification of air (conducting pathways) 3) Mixture of fresh and residual air / breath • Gases diffuse down pressure gradients Additional factors affecting gas/liquid interchange: • Solubility of gas in water • Carbon Dioxide >> Oxygen >> Nitrogen Ø “The Bends” (pg 872) • Temperature • Solubility inversely related to temperature 0.04% Carbon Dioxide 20.94% Oxygen H2O = 6.2% N2 = 74.5% 79% Nitrogen % Composition of Air O2 = 13% CO2 = 6% % Composition of Lung Air Chapters 23: Respiratory System Chapters 23: Respiratory System Gas Exchange: External / Internal Respiration: 1) External Respiration (O2 / CO2 exchange between blood and lungs) • Pulmonary gas exchange driven by gas partial pressures • PO2 in alveoli = ~100 mmHg Net movement into blood • PO2 in blood = ~40 mmHg • PCO2 in alveoli = ~40 mmHg Net movement into alveoli • PCO2 in blood = ~45 mmHg Gas Exchange: External / Internal Respiration: 1) External Respiration (O2 / CO2 exchange between blood and lungs) • Pulmonary gas exchange driven by gas partial pressures • PO2 in alveoli = ~100 mmHg Net movement into blood • PO2 in blood = ~40 mmHg • PCO2 in alveoli = ~40 mmHg Net movement into alveoli • PCO2 in blood = ~45 mmHg • Thin, extensive exchange area maximizes exchange rates • Thickness < 1.0 µm; exchange area ~ 50-70 m2 • Ventilation-perfusion Coupling Chapters 23: Respiratory System Chapters 23: Respiratory System Gas Exchange: Ventilation-perfusion Coupling: • Mechanism for matching flow of blood with volume of gas in alveoli (Autoregulatory homeostasis) Gas Exchange: Ventilation-perfusion Coupling: When PO2 is low and PCO2 is high in alveoli: 1) Ventilation = amount of gas reaching alveoli 2) Perfusion = blood flow in pulmonary capillaries Bronchioles Bronchioles Alveoli Alveoli ↓ PO2 ↑ PCO2 Pulmonary venules Pulmonary arterioles Pulmonary venules Pulmonary arterioles Pulmonary capillaries Pulmonary capillaries Chapters 23: Respiratory System Chapters 23: Respiratory System Gas Exchange: Ventilation-perfusion Coupling: Gas Exchange: Ventilation-perfusion Coupling: When PO2 is low and PCO2 is high in alveoli: 1) Bronchioles dilate (↑ ventilation) When PO2 is low and PCO2 is high in alveoli: 1) Bronchioles dilate (↑ ventilation) 2) Pulmonary arterioles constrict (↓ blood flow) Bronchioles Bronchioles Alveoli ↓ PO2 ↑ PCO2 Pulmonary venules Pulmonary arterioles Pulmonary capillaries Alveoli ↓ PO2 ↑ PCO2 Pulmonary venules Pulmonary arterioles Pulmonary capillaries Chapters 23: Respiratory System Chapters 23: Respiratory System Gas Exchange: Ventilation-perfusion Coupling: Gas Exchange: Ventilation-perfusion Coupling: When PO2 is high and PCO2 is low in alveoli: When PO2 is high and PCO2 is low in alveoli: 1) Bronchioles constrict (↓ ventilation) Bronchioles Bronchioles Alveoli Alveoli ↑ PO2 ↓ PCO2 ↑ PO2 ↓ PCO2 Pulmonary venules Pulmonary arterioles Pulmonary venules Pulmonary arterioles Pulmonary capillaries Pulmonary capillaries Chapters 23: Respiratory System Chapters 23: Respiratory System Gas Exchange: Ventilation-perfusion Coupling: Gas Exchange: External / Internal Respiration: When PO2 is high and PCO2 is low in alveoli: 1) Bronchioles constrict (↓ ventilation) 2) Pulmonary arterioles dilate (↑ blood flow) Bronchioles Alveoli ↑ PO2 ↓ PCO2 2) Internal Respiration (O2 / CO2 exchange between blood and tissues) • Driven by gas partial pressures • PO2 in blood = ~104 mmHg • PO2 in tissue = ~40 mmHg Net movement into tissue • PCO2 in blood = ~40 mmHg • PCO2 in tissue = ~45 mmHg Net movement into blood Pulmonary venules Pulmonary arterioles Pulmonary capillaries Gas movements in body: Chapters 23: Respiratory System Respiratory System: A. Functional Anatomy B. Mechanisms of Breathing C. Gas Exchange D. Gas Transport E. Control of Respiration Supplies the body with oxygen and disposes of carbon dioxide (Figure 23.17) Chapters 23: Respiratory System Gas Transport: Oxygen Transport: • Most O2 in blood bound to hemoglobin (Hb) (> 98.5%) • O2 solubility low in plasma (~ 1.5%) • Hb can bind up to 4 O2 molecules (saturated) • HHb = deoxyhemoglobin (reduced) • HbO2 = oxyhemoglobin (oxidized) HHb Blood PO2 PO2 100 mm Hg 40 mm Hg HbO2 tissues O2 O2 H+ + O2 Exchange: Lung → Blood O2 O2 O2 Red Blood Cell O2 O2 Tissue Blood Chapters 23: Respiratory System PO2 PO2 40 mm Hg 100 mm Hg O2 Exchange: Blood → Tissue O2 HbO2 + H+ HHb + O2 O2 lungs + O2 Chapters 23: Respiratory System Alveoli Chapters 23: Respiratory System O2 Gas Transport: Oxygen Transport: • O2 association / dissociation with Hb depends on number of O2 molecules present • Cooperative binding (lungs) HHb + O2 O2 HbO2 + • As each Hb subunit binds 1 O2, the affinity of the Hb for binding O2 increases. H+ • Reversible binding (tissues) • As each Hb subunit releases 1 O2, the affinity of the Hb for binding O2 decreases. Red Blood Cell O2 O2 O2 Chapters 23: Respiratory System Chapters 23: Respiratory System Gas Transport: Oxygen Transport: • % O2 saturation of Hb depends on PO2 Gas Transport: Oxygen Transport: • % O2 saturation of Hb depends on PO2 Oxygen-Hb Dissociation Curve 15 60 10 40 5 20 0 20 40 60 80 100 PO2 • PO2 ~ 100 mm Hg (Alveoli PO2) • Hb 98% saturated with O2 • 20 ml O2 / 100 ml blood Oxygen Content = 20 vol % Oxygen-Hb Dissociation Curve 100 20 80 15 60 10 40 5 20 0 20 40 PO2 Lungs Tissues 60 80 100 Sigmoid curve ml O2 / 100 ml blood 80 Sigmoid curve % O2 saturation of hemoglobin 20 ml O2 / 100 ml blood % O2 saturation of hemoglobin 100 • PO2 ~ 40 mm Hg (Tissue PO2) • Hb 75% saturated with O2 • 15 ml O2 / 100 ml blood Oxygen Content = 15 vol % Chapters 23: Respiratory System Chapters 23: Respiratory System Gas Transport: Oxygen Transport: Gas Transport: Oxygen Transport: • % O2 saturation of Hb depends on PO2 Volume of O2 unloaded to tissues 20 80 15 60 10 40 5 20 Sigmoid curve • Hb saturated at 70 mm Hg ml O2 / 100 ml blood % O2 saturation of hemoglobin 100 Oxygen-Hb Dissociation Curve • Adapted for varying PO2 • Only 25% O2 unloaded from systemic circuit • Venous reserve Factors influencing O2 affinity of Hb (modify structure): 1) Temperature • ↑ temperature = ↓ O2 affinity (Figure 23.21) 2) pH (Bohr effect) • ↓ pH = ↓ O2 affinity 3) PCO2 • ↑ PCO2 = ↓ O2 affinity 4) BPG (2,3-biphosphoglycerate) • Intermediate of anaerobic metabolism 0 20 40 60 80 • ↑ BPG = ↓ O2 affinity 100 PO2 Chapters 23: Respiratory System Gas Transport: Oxygen Transport: “Adaptive Complex”: • During extreme physical activity: 1) Temperature 2) pH 3) PCO2 All facilitate unloading of O2 at tissues... Chapters 23: Respiratory System Gas Transport: Oxygen Transport Impairment: Hypoxia: Inadequate delivery of O2 to tissues 1) Anemic hypoxia (RBC deficiency) 2) Ischemic hypoxia (circulation deficiency) 3) Histotoxic hypoxia (tissue uptake; cyanide) 4) Hypoxemic hypoxia (reduced arterial PO2) Ø Carbon monoxide poisoning 4) BPG Chapters 23: Respiratory System Gas Transport: Carbon Dioxide Transport: • CO2 = waste product of aerobic metabolism • Produced in tissues / expelled in lungs • CO2 carried in blood 3 ways: 1) Dissolved directly in plasma (7 - 10%) 2) Bound to amino acids of Hb (20 - 30%) • Carbaminohemoglobin 3) Converted to bicarbonate ion (HCO3-) (60 - 70%) Chapters 23: Respiratory System Gas Transport: Carbon Dioxide Transport: Hb Plasma CA CO2 + H20 H2CO3 H+ + HCO3- • Carbon dioxide (CO2) combines with water (H2O) to form carbonic acid (H2CO3) in RBCs • Reaction catalyzed by carbonic anhydrase (CA) • H2CO3 dissociates into hydrogen ion (H+) and bicarbonate ion (HCO3- ) • HCO3- released into plasma • H+ binds to Hb (Bohr effect - lowers O2 affinity) Chapters 23: Respiratory System Gas Transport: Carbon Dioxide Transport: • CO2 transport allows for blood buffering • HCO3- acts as a proton acceptor (H+) in plasma • If blood [H+] rises, H+combines with HCO3• If blood [H+] drops, H+ dissociates from H2CO3 Tissue Blood Chapters 23: Respiratory System PCO2 PCO2 45 mm Hg 40 mm Hg CO2 Exchange: Tissue → Blood slow CO2 + H2O Cl- CO2 CA CO2 + H2O CO2 PCO2 40 mm Hg 45 mm Hg HbCO2 Red Blood Cell CO2 Blood H+ + HCO3- H2CO3 Hb + CO2 CO2 PCO2 H+ + HCO3Chloride Shift Cl- CO2 • Mechanism maintains stable blood pH ~ 7.4 Alveoli H2CO3 HCO3- CO2 Chapters 23: Respiratory System Tissue Blood Chapters 23: Respiratory System CO2 Exchange: Blood → Lung PO2 PO2 100 mm Hg O2 / CO2 Exchange Interactions 40 mm Hg slow CO2 + H2O H2CO3 H+ + HCO3- CO2 PCO2 PCO2 45 mm Hg 40 mm Hg ClClCA CO2 CO2 + H2O CO2 H+ + HCO3- H2CO3 Hb + CO2 HbCO2 Red Blood Cell CO2 Lung PO2 100 mm Hg CA CO2 CO2 + H2O O2 HHb + O2 (Bohr Effect) CO2 Chapters 23: Respiratory System PO2 40 mm Hg O2 / CO2 Exchange Interactions PCO2 PCO2 40 mm Hg 45 mm Hg Chapters 23: Respiratory System Respiratory System: A. Functional Anatomy B. Mechanisms of Breathing C. Gas Exchange D. Gas Transport E. Control of Respiration CO2 O2 CA CO2 + H2O H+ + HCO3- H2CO3 HHb + O2 HbO2 + H+ Red Blood Cell HbO2 + H+ Red Blood Cell HCO3- Blood H+ + HCO3- H2CO3 Supplies the body with oxygen and disposes of carbon dioxide Chapters 23: Respiratory System Control of Respiration: Neural Mechanisms: 1) Medullary Respiratory Centers (reticular formation): • Dorsal Respiratory Group (DRG) • Inspiratory center (“pacesetter”: 12-15 breaths/min) • Excites diaphragm (phrenic nerve) • Excites ext. intercostals (intercostal nerves) • Ventral Respiratory Group (VRG) Chapters 23: Respiratory System Control of Respiration: Factors Influencing Rate / Depth of Breathing: 1) Pulmonary Irritant Reflexes • Irritants (mucus/ inhaled debris) stimulate coughing/sneezing • Triggered by receptors in lungs 2) Inflation (Hering-Breuer) Reflex • Lung stretch inhibits inspiratory center • Triggered by stretch receptors in lungs • Mixed innervation (inspiration/expiration) • Role in forced expiration? 2) Pons Respiratory Centers • Modulate respiratory rhythm Chapters 23: Respiratory System Control of Respiration: Higher Brain Center Influences: 1) Hypothalamic Control • Emotion / pain can modulate respiratory rate • Acts through limbic system 2) Cortical Control • Voluntary control (bypasses medullary centers) Chapters 23: Respiratory System Control of Respiration: Chemical Factors Influencing Breathing: 1) [PCO2] • Most powerful respiratory stimulant • Mediated through medullary chemoreceptors • ↑ CO2 = ↑ H+ in cerebrospinal fluid = ↑ ventilation rate • ↑ CO2 = hypercapnia; ↓ CO2 = hypocapnia 2) [PO2] • Minor respiratory stimulant • Mediated through peripheral chemoreceptors (e.g. aorta) • Stimulated by [PO2] < 60 mm Hg • ↓ O2 = ↑ respiratory rate Chapters 23: Respiratory System Control of Respiration: Chemical Factors Influencing Breathing: 1) Arterial pH • Mediated through peripheral chemoreceptors Chapters 23: Respiratory System Influences on respiratory center: • ↓ pH = ↑ respiratory rate (Figure 23.25) Chapters 23: Respiratory System Homeostatic Imbalances of Respiratory System: 1) Chronic Obstructive Pulmonary Disease • Obstructive disorders of the airways 2) Asthma • Acute Inflammation/constriction of airways 3) Tuberculosis • Bacterial infection invades lungs 4) Lung Cancer • Aggressive cancer - metastasizes rapidly • Strongly associated with smoking Chapters 23: Respiratory System