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Respiratory System For the body to survive, there must be a constant supply of O2 and a constant disposal of CO2 Respiratory System Respiratory System - Overview: Assists in the detection of odorants Protects system (debris / pathogens / dessication) 5 3 4 Produces sound (vocalization) Provides surface area for gas exchange (between air / blood) 1 2 Moves air to / from gas exchange surface Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Table 19.1 1 Respiratory System Functional Anatomy: Epiglottis • Conduction of air Upper Respiratory System • Gas exchange Lower Respiratory System • Filters / warms / humidifies incoming air 1) External nares 2) Nasal cavity • Resonance chamber 3) Uvula 5) Larynx 4) Pharynx • Nasopharynx • Oropharynx • Laryngopharynx 6) Trachea 7) Bronchial tree 8) Alveoli • Provide open airway • channel air / food • voice production (link) Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.1 Respiratory System Functional Anatomy: Trachea Primary Bronchus Naming of pathways: • > 1 mm diameter = bronchus • < 1 mm diameter = bronchiole • < 0.5 mm diameter = terminal bronchiole Bronchi bifurcation (23 orders) Green = Conducting zone Purple = Respiratory zone Bronchiole Terminal Bronchiole Respiratory Bronchiole Alveolus Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9 2 Respiratory System Functional Anatomy: Respiratory Mucosa / Submucosa: Near trachea Near alveoli Epithelium: Mucosa: Mucous membrane (epithelium / areolar tissue) Pseudostratified columnar Simple cuboidal Cilia No cilia Lamina Propria (areolar tissue layer): smooth muscle smooth muscle Mucous glands No mucous glands Cartilage: Plates / none Rings Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9 Respiratory System Functional Anatomy: How are inhaled debris / pathogens cleared from respiratory tract? Nasal Cavity: Particles > 10 µm Conducting Zone: Particles 5 – 10 µm Mucus Escalator Respiratory Zone: Particles 1 – 5 µm Macrophages Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.2 3 Respiratory System Functional Anatomy: Pseudostratified ciliated columnar epithelium Trachea Goblet cells: Unicellular mucous secreting glands Esophagus Tough, flexible tube 15 – 20 tracheal cartilages (~ 1” diameter) • Protect airway (C-shaped) • Allow for food passage Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9 Respiratory System Functional Anatomy: Right primary bronchus wider, shorter & steeper ( blockage hazard) Bronchus (> 1 mm diameter) • 1º = Extrapulmonary bronchi • 2º = Intrapulmonary bronchi Bronchitis: Inflammation of airways Pseudostratified ciliated columnar epithelium Smooth muscle Cartilage plate Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9 4 Respiratory System Mucous glands rare – Why? Functional Anatomy: Pseudostratified ciliated columnar epithelium Cartilage plates? Thick smooth muscle Allergic attack = Histamine = Bronchoconstriction Sympathetic stimulation (NE; 2 receptors) • Leads to bronchodilation Synthetic drugs (e.g., albuterol) trigger response Bronchiole E (medulla) triggers response (< 1 mm diameter) Alveoli Parasympathetic stimulation (ACh; muscarinic receptors) • Leads to bronchoconstriction (300 million / lung) Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9 Respiratory System Functional Anatomy: Surrounded by fine elastic fibers Respiratory bronchiole Terminal bronchiole Alveolar sac Type I Pneumocytes: • Simple squamous; forms wall of alveoli • Alveolar pores (1 – 6 / alveoli) Total surface area: 75 - 90 m2 (~1/2 tennis court) 200 m Type II Pneumocytes: • Cuboidal / round; secrete surfactant • Reduces surface tension (stops alveoli collapse) Alveolar macrophages: • Clear debris on alveolar surface Alveolar pores Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.8 5 Respiratory System Pneumonia: Thickening of respiratory membrane Functional Anatomy: Gas exchange occurs readily in the alveoli of the lung via simple diffusion across the respiratory membrane 0.1 – 0.5 m thick Respiratory Membrane: 1) Type I pneumocytes 2) Endothelial cells of capillaries 3) Fused basement membranes Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.9 Respiratory System Respiratory Physiology: Respiration includes: 1 1) Pulmonary ventilation (pumping air in / out of lungs) 2) External respiration (gas exchange @ blood-gas barrier) 2 3) Transport of respiratory gases (blood) 4) Internal respiration (gas exchange @ tissues) 3 4 Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.19 6 Respiratory System Pulmonary Ventilation: Simplified Model: Trachea Trachea Visceral pleura Lung Parietal pleura Pleural cavity Thoracic wall Lung Pleural cavity Thoracic wall Diaphragm Diaphragm Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.12 Respiratory System Pulmonary Ventilation: Atmospheric pressure = ~ 760 mm Hg (Consider Patmospheric = 0 mm Hg) Pressure relationships in the thoracic cavity: Intrapulmonary pressure (Ppul = 0 mm Hg) 1) Intrapulmonary Pressure (w/in the alveoli): • Static conditions = 0 mm Hg • Inhalation (inspiration) = Ppul slightly negative • Exhalation (expiration) = Ppul slightly positive 2) Intrapleural pressure (w/in pleural cavity): • Always relatively negative (~ - 4 mm Hg) • Prevents lungs from collapsing Diaphragm Intrapleural pressure (Pip = - 4 mm Hg) atmospheric pressure = Patm = 0 mm Hg 7 Respiratory System Pulmonary Ventilation: Why is the intrapleural pressure negative? Answer: Interaction of opposing forces Forces equilibrate at Pip = - 4 mm Hg Forces acting to collapse lung: 1) Elasticity of lungs 2) Alveolar surface tension Force resisting lung collapse: 1) Elasticity of chest wall Surface tension of serous fluids keep lungs “stuck” to chest wall Pneumothorax: (“sucking chest wound”) Puncture of chest wall; results in inability to generate negative pressure and expand the lungs Costanzo (Physiology, 4th ed.) – Figure 5.9 Respiratory System Pulmonary Ventilation: Pulmonary ventilation is a mechanical process that depends on thoracic cavity volume changes Boyle’s Law: P1V1 = P2V2 P = pressure of gas (mm Hg) V = volume of gas (mm3) P1 = initial pressure; V1 = initial volume P2 = resulting pressure; V2 = resulting volume Example: 4 mm Hg (2 mm3) = P2 (4 mm3) P2 = 2 mm Hg CHANGING THE VOLUME RESULTS IN INVERSE CHANGE OF PRESSURE Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.13 8 Respiratory System Pulmonary Ventilation: Pulmonary ventilation is a mechanical process that depends on thoracic cavity volume changes 0 mm Hg Inspiration: Muscular expansion of thoracic cavity - 4 mm Hg A) Contraction of diaphragm • Lengthens thorax (pushes liver down) B) Contraction of external intercostal muscles • Widens thorax 0 mm Hg Diaphragm Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.13 Respiratory System Pulmonary Ventilation: Pulmonary ventilation is a mechanical process that depends on thoracic cavity volume changes 0 mm Hg Inspiration: Muscular expansion of thoracic cavity - 6 mm Hg A) Contraction of diaphragm • Lengthens thorax (pushes liver down) B) Contraction of external intercostal muscles • Widens thorax Results in: • Reduced intrapleural pressure (Pip) • Reduced intrapulmonary pressure (Ppul) - 1 mm Hg Results in decreased pressure in thoracic cavity and air enters Diaphragm 9 Respiratory System Internal pressure can reach +100 mm Hg Pulmonary Ventilation: (e.g., why you should exhale when lifting weights) Pulmonary ventilation is a mechanical process that depends on thoracic cavity volume changes Expiration: Retraction of thoracic cavity Results in increased pressure in thoracic cavity; air exits 0 mm Hg - 4 mm Hg A) Passive Expiration • Diaphragm / external intercostals relax • Elastic rebound (lungs rebound) B) Active (“Forced”) Expiration • Abdominal muscles contract • Internal intercostals contract Eupnea: Quiet breathing (active inspiration; (passive expiration) +1 0 mm Hg Hyperpnea: Forced breathing (active inspiration; (active expiration) Diaphragm Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.13 Respiratory System Pulmonary Ventilation: Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.14 10 Respiratory System Pulmonary Ventilation: Several physical factors exist influence pulmonary ventilation A) Airway resistance Q = Airflow (L / min) P = Pressure gradient (mm Hg) R = Airway resistance (mm Hg / L / sec) Q = P / R Airflow is directly proportional to pressure difference between outside air and alveoli and inversely proportional to resistance of the airway Resistance determined by Poiseuille’s Law: 8Lη Reminder: r4 Parasympathetic system produces bronchial constriction R = Resistance η = Viscosity of inspired air Resistance R = Why don’t the smallest airways provide the highest resistance? Medium-sized bronchi Terminal bronchioles ( diameter = resistance) Sympathetic system produces bronchial dilation L = Length of airway r = Radius of airway ( diameter = resistance) Bifurcation stage Respiratory System Respiratory Distress Syndrome (e.g., pre-mature babies) Pulmonary Ventilation: Several physical factors exist influence pulmonary ventilation B) Surface tension in alveoli Surface tension generated as neighboring liquid molecules on the surface of alveoli are drawn together by attractive forces Pressure required to keep alveolus open Law of Laplace: 2T P = r P = Collapsing pressure on alveolus (dynes / cm2) T = Surface tension (dynes / cm) r = Radius of alveolus (cm) Surfactant Problem? Dipalmitoyl phosphatidylchorine (DPPC) Costanzo (Physiology, 4th ed.) – Figure 5.12 11 Respiratory System Pulmonary Ventilation: Several physical factors exist influence pulmonary ventilation C) Lung compliance Measure of change in lung volume that occurs with a given transpulmonary pressure CL = VL CL = Lung compliance (cm3 / mm Hg) VL = Lung volume (cm3) (Ppul – Pip) Ppul = Intrapulmonary pressure (mm Hg) Ppi = Intrapleural pressure (mm Hg) (Transmural pressure) The higher the lung compliance, the easier it is to expand the lungs at a given pressure Determined by: 1) Elasticity of lung Barrel Chest Emphysema: Increased lung compliance due to loss of elastic fibers Fibrosis: Decreased lung compliance due to scar tissue build-up 2) Surface tension Respiratory System Tidal Volume: Amount of air moved into / out of lung during single respiratory cycle Pulmonary Ventilation: Respiratory Volumes / Capacities: (spirometric reading) Inspiratory reserve Volume (IRV) (~ 3100 ml) Inspiratory capacity (~ 3600 ml) Increases with: • Body size • Gender • Conditioning Vital capacity (~ 4800 ml) Decreases with: • Age Resting Tidal Volume (~ 500 ml) Expiratory reserve volume (~ 1200 ml) Functional residual capacity Residual volume (~ 1200 ml) (~ 2400 ml) Total lung capacity (~ 6000 ml) (Male) (Female ~ 4200 ml) Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.16 12 Cardiovascular System – Vessels Pathophysiology: Forced vital capacity (FVC) is the total volume of air that can be forcibly expired after maximal inspiration; this is a useful measure of lung disease FEV = Forcefully expired volume FEV1 FVC < 0.8 > 0.8 0.8 • Both FEV1 and FVC low but FEV1 decreased more than FVC • Both FEV1 and FVC low but FVC decreased more than FEV1 Costanzo (Physiology, 4th ed.) – Figure 5.6 Respiratory System Pulmonary Ventilation: Physiologic Dead Space: Anatomic dead space plus any ventilated alveoli that might not participate in gas exchange Not all inhaled air participates in gas exchange; this volume is referred to as dead space Anatomic Dead Space: Volume of air found in the conducting airways, including the nose bronchioles Rule of Thumb: Anatomical dead space in a healthy young adult is equal to 1 ml / pound of ideal body weight Costanzo (Physiology, 4th ed.) – Figure 5.3 13 Respiratory System Pulmonary Ventilation: Ventilation rate is the volume of air moved into an out of the lungs per unit time Minute Volume: VM = f (breaths / minute) x VT (tidal volume) = 12 breaths / minute x 500 mL = 6000 mL / minute = 6.0 liters / minute Alveolar Ventilation: (or physiologic dead space) VA = f (breaths / minute) x (VT (tidal volume) - VD (anatomic dead space)) = 12 breaths / minute x (500 mL - 150 mL) = 4200 mL / minute Available for gas transfer… = 4.2 liters / minute Respiratory System Respiratory Physiology: Respiration includes: 1 1) Pulmonary ventilation (pumping air in / out of lungs) 2) External respiration (gas exchange @ blood-gas barrier) 2 3) Transport of respiratory gases (blood) 4) Internal respiration (gas exchange @ tissues) 3 4 Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.19 14 Respiratory System Pulmonary Ventilation: Gas exchange in the respiratory system refers to diffusion of O2 and CO2 in the lung and in the peripheral tissues Basic Properties of Gases: A) Dalton’s Law of Partial Pressures: The total pressure of a gas is equal to the sum of the pressure of its constituents For dry gases: Patmosphere: 760 mm Hg 21% O2 PX = PB x F PX = Partial pressure of gas (mm Hg) PB = Barometric pressure (mm Hg) F = Fractional concentration of gas 79% N2 PO2 = 760 x 0.21 PO2 = 160 mm Hg % Composition of Atmospheric Air Respiratory System Gas Exchange: Gas exchange in the respiratory system refers to diffusion of O2 and CO2 in the lung and in the peripheral tissues Basic Properties of Gases: A) Dalton’s Law of Partial Pressures: The total pressure of a gas is equal to the sum of the pressure of its constituents 21% O2 79% N2 % Composition of Atmospheric Air Patmosphere: 760 mm Hg For humidified gases: PX = (PB – PH2O) x F PX = PB = PH2O F = Partial pressure of gas (mm Hg) Barometric pressure (mm Hg) = Water vapor pressure at 37C (47 mm Hg) Fractional concentration of gas PO2 = (760 – 47) x 0.21 PO2 = 150 mm Hg 15 Note: At equilibrium, the partial pressure of a gas in the liquid phase equals the partial pressure in the gas phase Respiratory System Gas Exchange: (the “bends”) Gas exchange in the respiratory system refers to diffusion of O2 and CO2 in the lung and in the peripheral tissues CO2 >> O2 >> N2 Basic Properties of Gases: Solubility: How much of a gas will dissolve in a liquid at a given partial pressure B) Henry’s Law: Gases in a mixture dissolve in a liquid in proportion to their partial pressures CX = PX x Solubility CX = Concentration of dissolved gas (mL X / 100 mL blood) PX = Partial pressure of gas (mm Hg) Solubility = Solubility of gas in blood (mL X / 100 mL / mm Hg) [O2] = PO2 x Solubility [O2] = 150 x 0.003 [O2] = 0.45 mL / 100 mL blood Respiratory System Gas Exchange: Gas exchange in the respiratory system refers to diffusion of O2 and CO2 in the lung and in the peripheral tissues Respiratory membrane Basic Properties of Gases: C) Fick’s Law: The transfer of a gas across a cell membrane depends on the driving force, gas solubility, and the surface area available for transport VX = VX = D = A = P = X = DAP x directly proportional inversely proportional Volume of gas transferred per unit time Diffusion coefficient of the gas (includes solubility) Surface area Partial pressure difference of the gas Thickness of the membrane The driving force for diffusion of a gas is the partial pressure difference of the gas, not the concentration difference 60 PO2 in lung 100 40 PO2 in blood 16 Respiratory System In solution, only dissolved gases contribute to partial pressures Gas Exchange: Unlike alveolar air, where there is only one form of gas, blood is able to carry gases in addition forms PX Bound gas Dissolved gas Gases bind directly to plasma proteins or to hemoglobin The higher the solubility of a gas, the higher the concentration of the gas in solution Chemically modified gas Gases react with blood components to form new products Total gas concentration = Dissolved gas + Bound gas + Chemically modified gas Respiratory System Gas Exchange: Gas transport in the lungs: Costanzo (Physiology, 4th ed.) – Figure 5.16 17 Costanzo (Physiology, 4th ed.) – Figure 5.17 Respiratory System Gas Exchange: VX = Systemic tissues undergo reversal of pattern observed at lung Patmosphere: 760 mm Hg Gas transport in the lungs: DAP x PX = PB x F Diffusional coefficient 20x greater for CO2 than for O2 O2 = 21% CO2 = 0% O2 = 21% CO2 = 0% Lung air modified by gas exchange: PX = (PB – PH2O) x F 1) O2 into blood; CO2 out of blood 2) Mixture of fresh and residual air O2 = 14% CO2 = 6% PO2 = 60 PX = (PB – PH2O) x F PCO2 = 6 The amount of O2 / CO2 transferred corresponds to the needs of the body Composition reflects metabolic activity of body 1:1 exchange rate Due to rapid diffusion of gases, equilibrium reached ? Costanzo (Physiology, 4th ed.) – Figure 5.18 Respiratory System Gas Exchange: Gas exchange across the alveolar / pulmonary capillary barrier is described as either diffusion-limited or perfusion-limited Diffusion-limited: The total amount of gas transported across the alveolar / capillary barrier is limited by the diffusional process Partial pressure gradient maintained across entire length of capillary (gas does not equilibrate) Example: Carbon monoxide Perfusion-limited: The total amount of gas transported across the alveolar / capillary barrier is limited by blood flow Example: Nitrous oxide Partial pressure gradient not maintained across length of capillary (gas equilibrates) gas transport = diffusion rate gas transport = blood flow 18 Respiratory System Gas Exchange: Under normal conditions, O2 transport into pulmonary capillaries is a perfusion-limited process PO2 (mm Hg) Exercise Rest “wiggle room” PO2 does not equilibrate until hemoglobin saturated Remember: PO2 only measures free O2 concentration Time in pulmonary capillary (s) Start of capillary End of capillary Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.18 Respiratory System Pathophysiology: In certain pathologic conditions, O2 transport becomes diffusion limited Lung fibrosis PO2 equilibrium never reached Alveolar wall thickens; slows down diffusion rate Outcome: Decreased PO2 in systemic arterial blood, especially during physical activity VX = DAP x Costanzo (Physiology, 4th ed.) – Figure 5.19 19 Respiratory System A man climbs to the top of a tall mountain where the barometric pressure is measured at 50 mm Hg. What are the implications to oxygen transport into pulmonary capillaries for A) PaO2, B) rate, and C) exercise Exercise Rest “shortness of breath” Driving force: 50 – 25 = 25 mm Hg VX = DAP x Costanzo (Physiology, 4th ed.) – Figure 5.19 Respiratory System Respiratory Physiology: Respiration includes: 1 1) Pulmonary ventilation (pumping air in / out of lungs) 2) External respiration (gas exchange @ blood-gas barrier) 2 3) Transport of respiratory gases (blood) 4) Internal respiration (gas exchange @ tissues) 3 4 Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.19 20 Respiratory System Oxygen Transport in Blood: O2 is carried in two forms in blood: dissolved and bound to hemoglobin A) Dissolved O2: Accounts for 2% of total O2 content of blood Henry’s Law: Recall: The concentration of dissolved O2 is proportional to the partial pressure of O2 CX = PX x Solubility CX = Concentration of dissolved gas (mL X / 100 mL blood) PX = Partial pressure of gas (mm Hg) Solubility = Solubility of gas in blood (mL X / 100 mL / mm Hg) Grossly insufficient to meet the demands of the tissues [O2] = PO2 x Solubility [O2] = 100 x 0.003 At rest, tissues require 250 mL O2 / min [O2] = 0.30 mL / 100 mL blood O2 delivery = CO x [dissolved O2] O2 delivery = 5.0 L / min x 0.3 mL O2 / 100 mL O2 delivery = 15 mL O2 / min Respiratory System Oxygen Transport in Blood: O2 is carried in two forms in blood: dissolved and bound to hemoglobin B) O2 bound to hemoglobin: Accounts for remaining 98% of total O2 content of blood Globular protein: 2 & 2 subunits each containing a heme moiety • 4 O2 / hemoglobin Iron (ferrous state – Fe2+) bound to nitrogens Oxyhemoglobin = O2 bound to hemoglobin Shouldn’t O2 oxidize iron (ferric state – Fe3+ )? Deoxyhemoglobin = No O2 present No – nitrogen bonds prevent this… Methemoglobin = Iron in ferric • Does not bind O2 (Fe3+) state BUT – if it does happen: Methemoglobin reductase – reduces Fe3+ to Fe2+ 21 Respiratory System Oxygen Transport in Blood: O2 is carried in two forms in blood: dissolved and bound to hemoglobin B) O2 bound to hemoglobin: Hemoglobin structure demonstrates a developmental shift Fetal hemoglobin Adult hemoglobin (hemoglobin F - HbF) (hemoglobin A - HbA) 22 2 2 Hemoglobin F has a higher affinity for O2 than hemoglobin A, facilitating O2 transfer across the placenta Respiratory System Oxygen Transport in Blood: O2 is carried in two forms in blood: dissolved and bound to hemoglobin B) O2 bound to hemoglobin: Amount of O2 bound to hemoglobin determined by the hemoglobin concentration and by the O2-binding capacity of that hemoglobin O2-binding Capacity: PUTTING IT ALL TOGETHER: The maximum amount of O2 that can be bound to hemoglobin per volume of blood O2 Content: The actual amount of O2 per unit volume of blood (Assumes hemoglobin 100% saturated) Under normal conditions: • 1.0 g of hemoglobin can bind 1.34 mL 02 • [hemoglobin A] = 15 g / 100 mL THUS O2-binding capacity = 15 g / 100 mL x 1.34 mL O2 / g HbA O2-binding capacity = 20.1 mL O2 / 100 mL blood O2 content = (O2-binding capacity x % saturation) + dissolved O2 O2 Delivery to tissues: The actual amount of O2 delivered to the tissues O2 = Cardiac output x O2 content of blood delivery 22 Respiratory System Oxygen Transport in Blood: Reminder: Each hemoglobin as the capacity to bind 4 O2 molecules O2 is carried in two forms in blood: dissolved and bound to hemoglobin B) O2 bound to hemoglobin: The % saturation of hemoglobin is a function of the PO2 of blood O2-hemoglobin Dissociation Curve: Describe relationship between percent saturation of Hb and partial pressure of oxygen Sigmoid curve P50 Point at which 50% of Hb saturated THE PERCENT SATURATION OF HEME SITES DOES NOT INCREASE LINEARLY AS PO2 INCREASES Change in value is an indicator for a change in affinity of Hb for O2 Sub-unit Cooperativity: Oxygenation of first heme group facilitates oxygenation of other heme groups ( P50 = affinity) Costanzo (Physiology, 4th ed.) – Figure 5.20 Respiratory System Oxygen Transport in Blood: O2 is carried in two forms in blood: dissolved and bound to hemoglobin B) O2 bound to hemoglobin: Under normal, resting conditions, arterial blood hemoglobin is 98% saturated and only ~ 25% of O2 is unloaded at tissues Small drop in PO2 equates to large increase in O2 unloading “wiggle room” O2 unloaded to resting tissues Additional O2 unloaded to exercising tissues ~ complete saturation Points to Ponder: 1) Hemoglobin is almost completely saturated at a PO2 of 70 mm Hg ADAPTIVE SIGNIFICANCE? 2) The unloading of O2 occurs on the steep portion of the dissociation curve ADAPTIVE SIGNIFICANCE? Tissues Tissues (exercising) (at rest) Lungs Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.20 23 Respiratory System 2,3-DPG = 2,3-diphosphoglycerate • Byproduct of RBC glycolysis • Binds to chains of hemoglobin Oxygen Transport in Blood: O2 is carried in two forms in blood: dissolved and bound to hemoglobin B) O2 bound to hemoglobin: The O2-hemoglobin dissociation curve can shift to the right or the left depending on local conditions in the blood Right shift = Decreased Hb affinity for O2 • Facilitates unloading of O2 A) PCO2 B) pH Increased P50 Bohr effect C) temperature D) 2,3-DPG ‘Adaptive Complex’ Influence Hb saturation by modifying hemoglobin’s three-dimensional structure Costanzo (Physiology, 4th ed.) – Figure 5.22 Respiratory System 2,3-DPG = 2,3-diphosphoglycerate • Byproduct of RBC glycolysis • Binds to chains of hemoglobin Oxygen Transport in Blood: O2 is carried in two forms in blood: dissolved and bound to hemoglobin B) O2 bound to hemoglobin: The O2-hemoglobin dissociation curve can shift to the right or the left depending on local conditions in the blood Left shift = Increased Hb affinity for O2 • Hinders unloading of O2 Decreased P50 A) B) C) D) ? PCO2 pH temperature 2,3-DPG Increased affinity of hemoglobin F (fetus) due to 2,3-DPG binding ? Costanzo (Physiology, 4th ed.) – Figure 5.22 24 Respiratory System Pathophysiology: Carbon monoxide poisoning is catastrophic for O2 delivery to tissues 1) CO decreases O2 bound to Hb Example: • CO binds to Hb with an affinity that is 250x greater than that of O2 (forms carboxyhemoglobin) Left shift “cherry red” 2) CO causes left shift of dissociation curve • Heme groups not bound to CO have an increased affinity for O2 Costanzo (Physiology, 4th ed.) – Figure 5.22 Respiratory System Carbon Dioxide Transport in Blood: CO2 is carried in three forms in blood: dissolved, bound to hemoglobin, and as bicarbonate (HCO3-) A) Dissolved CO2: Accounts for 5% of total CO2 content of blood Henry’s Law: CX = PX x Solubility CX = Concentration of dissolved gas (mL X / 100 mL blood) PX = Partial pressure of gas (mm Hg) Solubility = Solubility of gas in blood (mL X / 100 mL / mm Hg) [CO2] = PCO2 x Solubility [CO2] = 40 x 0.07 (Arterial blood) [CO2] = 2.80 mL / 100 mL blood 25 Respiratory System Carbon Dioxide Transport in Blood: CO2 is carried in three forms in blood: dissolved, bound to hemoglobin, and as bicarbonate (HCO3-) B) CO2 bound to hemoglobin: Accounts for 3% of total CO2 content of blood • CO2 binds to the terminal amino groups on globins Reminder: The binding of CO2 to hemoglobin causes a conformational change reducing the affinity of Hb for O2 (right shift) IN TURN Carbaminohemoglobin = CO2 bound to hemoglobin When less O2 is bound to Hb, the affinity of Hb for CO2 increases (the Haldane effect) Respiratory System Carbon Dioxide Transport in Blood: CO2 is carried in three forms in blood: dissolved, bound to hemoglobin, and as bicarbonate (HCO3-) C) CO2 converted to HCO3- : Accounts for remaining 92% of total CO2 content of blood Diffuses into RBCs CA CO2 + REVERSABLE H20 H2CO3 Plasma (contributes to the Bohr effect) H+ + HCO3- 1) Carbon dioxide (CO2) combines with water (H2O) to form carbonic acid (H2CO3) • Reaction catalyzed by carbonic anhydrase (CA) 2) H2CO3 dissociates into hydrogen ion (H+) and bicarbonate ion (HCO3- ) • HCO3- released into plasma • H+ buffered in RBC by deoxyhemaglobin 26 Respiratory System Carbon Dioxide Transport in Blood: CO2 is carried in three forms in blood: dissolved, bound to hemoglobin, and as bicarbonate (HCO3-) C) CO2 converted to HCO3- : Accounts for remaining 92% of total CO2 content of blood Chloride shift: To maintain charge balance in RBCs, a Cl- is exchanged with a HCO3- as the HCO3- leaves the cell • Band three protein functions as passive transporter Costanzo (Physiology, 4th ed.) – Figure 5.24 Respiratory System Gas Transport - Review: Tissue – Blood Interface: Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.10 27 Respiratory System Note: Carbonic anhydrase also embedded in respiratory membrane Gas Transport: Lung – Blood Interface: Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.10 Respiratory System Ventilation / Perfusion Relationships: Recall: The pulmonary circulation carries blood from the right ventricle and returns blood to the left atrium Pulmonary blood flow is regulated primarily by altering the resistance of the arterioles Mechanisms of Regulation: A) Partial pressure of alveolar O2 Hypoxic vasoconstriction PAO2 B) Vasoactive Chemicals Reduces pulmonary flow to poorly ventilated alveoli Vasoconstrict vessel Mechanism of Action: • If PAO2 falls below 70 mm Hg, voltage-gated Ca2+ gates open in vascular smooth muscle, leading to contraction Thromboxane A2 Source: Endothelium Action: Vasoconstriction Prostacyclin Source: Endothelium Action: Vasodilator Can act locally (blocked alveolus) or globally (high altitude) 28 Respiratory System Ventilation / Perfusion Relationships: The distribution of pulmonary blood flow with the lung is uneven due to the effects of gravity Zone 1: Apex of lung Low blood flow Gravitational Effect Palveoli > Parterial > Pvein Lower vessel pressures • Pulmonary capillaries compressed by surrounding alveoli Zone 2: Middle of lung Parterial > Palveoli > Pvein Medium blood flow • Minimal compression; blood flow driven by Partial vs. Palveoli difference Zone 3: Base of lung Parterial > Pvein > Palveoli High blood flow • The greatest number of capillaries open; high arterial and venous pressures Higher vessel pressures Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.26 Respiratory System Control of Breathing: Breathing is regulated so the lungs can maintain the PaO2 and PaCO2 within a normal range Medullary Respiratory Centers: Amphetamines / Caffeine: respiratory center activity 1) Ventral Respiratory Group • Inspiratory center PRCs Oscillating rhythm of neuronal firing / quiescence • ‘Pacesetter’ (12 – 15 breaths / min) 2) Dorsal Respiratory Group • Expiratory center • Active during forced exhalation VRG Barbiturates / Opiates / Alcohol: respiratory center activity DRG Pontine Respiratory Centers: 1) Apneustic Center • Triggers prolonged inspiratory gasps Intercostal nerves Phrenic nerve 2) Pneumotaxic Center • Turns off inspiration • Limits size of tidal volume Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.23 29 Respiratory System Control of Breathing: Depth and rate of breathing can be modified in response to changing demands on the body Most important factors regulating ventilation are chemical Peripheral chemoreceptors • Carotid body (IX) • Aortic arch (X) (+) (CSF) Central chemoreceptors (+) Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24 Respiratory System Control of Breathing: Chemical Factors: Hypercapnia: Increased PCO2 in arterial blood Hypocapnia: Decreased PCO2 in arterial blood A) PCO2 • Most potent respiratory stimulant (maintained @ 3 mm Hg) • Mediated via central / peripheral chemoreceptors Can cross blood-brain barrier Can not cross blood-brain barrier CO2 = ventilation CO2 = ventilation Ultimately leads to change in pH of cerebral spinal fluid Costanzo (Physiology, 4th ed.) – Figure 5.32 30 Respiratory System Control of Breathing: Chemical Factors: A) PCO2 • Most potent respiratory stimulant (maintained @ 3 mm Hg) • Mediated via central / peripheral chemoreceptors B) PO2 • Minor respiratory stimulant ( O2 = respiratory rate) • Mediated via peripheral chemoreceptors • Stimulated by PO2 < 60 mm Hg in arterial blood C) Arterial pH • Independent of changes in arterial PCO2 • Compensatory mechanism for metabolic acidosis • Mediated by peripheral chemoreceptors (carotid body only) Issue for individuals with COPD: Continual high levels of PCO2 in system results in PO2 taking over regulation IF RESPIRATORY DISTRESS OCCURS Respiratory System Control of Breathing: Depth and rate of breathing can be modified in response to changing demands on the body Addition factors contribute to ventilation regulation Hering-Breuer Reflex: When lung / airways stretched, inspiratory center inhibited Lung stretch receptors Peripheral chemoreceptors • Carotid body (IX) • Aortic arch (X) Function in anticipatory response to exercise (+) (CSF) Central chemoreceptors (+) (-) Vagus (X) nerve (+) Joint / muscle stretch receptors Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24 31 Respiratory System Control of Breathing: Laryngeal spasm (e.g., sarin gas) Depth and rate of breathing can be modified in response to changing demands on the body Addition factors contribute to ventilation regulation Lung stretch receptors (+) (CSF) Central chemoreceptors (+) Nasal cavity = Sneeze Lower conduction system = Cough Apnea (-) Vagus (X) nerve (cessation of breathing) (-) (+) Irritant receptors Joint / muscle stretch receptors Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24 Epiglottis closes; thoracic cavity shrinks Epiglottis opens; air forcefully released (~ 100 mph) Respiratory System Control of Breathing: Depth and rate of breathing can be modified in response to changing demands on the body Higher control centers; Voluntary control over breathing Addition factors contribute to ventilation regulation Hypoventilation: Decrease breathing rate / depth Pain / emotional stimuli acting through hypothalamus (+ / -) Hyperventilation: Increase breathing rate / depth (+ / -) Lung stretch receptors Rate / depth of respiration exceeds demands for O2 delivery / CO2 removal (+) (CSF) Central chemoreceptors (+) (-) Vagus (X) nerve (-) (+) Joint / muscle stretch receptors Irritant receptors Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24 32 Respiratory System formaldehyde benzene vinyl chloride arsenic ammonia hydrogen cyanide ~ 3,400 deaths / year contributed to secondhand smoke… Increase in lung cancer rates correlated with rise in smoking among adult men and women 1900 1956 1978 2004 = Rare… = 29,000 deaths = 105,000 deaths = 160,440 deaths 33