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