Respiration During Exercise I The Respiratory System z Provides a means of gas exchange between the environment and the body – Alternatative to pulmonary ventilation? – Pulmonary vs. cellular respiration – Diffusion is the primary mechanism of gas exchange z Plays a role in the regulation of acid-base balance during exercise Anatomy of the Respiratory System 1 Position of the Lungs, Diaphragm and Pleura Conducting and Respiratory Zones Conducting zone Respiratory zone z Conducts air to respiratory z Where gas exchange zone by bulk flow occurs z Humidifies, warms, and z Airway generations 17filters air 23 – Respiratory bronchioles = z Airway generations 0-16 – Trachea = generation 0 – L & R main bronchi = gen. 1 through – Terminal bronchiole = gen. 16 gen. 17-19 – Alveolar ducts = gen. 20- 22 – Alveolar sac = gen. 23 Lung Cross-Sectional Area z Total cross-sectional area increases slowly from generation 1-15 (conducting zone) z Total cross-sectional area increases exponentially from about generation 15 through 23 z Total surface area is around 50 to 100 square meters (tennis court) z There are ~300,000,000 alveoli 2 Blood Gas Barrier z z The BGB separates the alveolar air from the blood in the pulmonary capillaries It consists of: – Alveolar endothelium – Basement membrane (type IV collagen) – Capillary endothelium (endothelial cell membrane) z Total thickness is 0.2 to 0.4 micrometers, thinner than a red blood cell Pathway of Air to Alveoli Conducting Zone Respiratory Zone Muscles of Respiration Inspiration Expiration 3 Mechanics of Breathing z Ventilation z Inspiration - Active – Movement of air into and out of the lungs via bulk flow – Diaphragm contracts, pushing down on the abdomen – External intercostals contract, push ribs and sternum up and out – Movements increases volume, lower thoracic pressure – Pressure gradient creates flow z Expiration – Passive (at rest) – Diaphragm & ext. intercostals relax, thoracic pressure returns to atmospheric pressure – During exercise, expiration can become active with involvement of internal intercostals et al. The Mechanics of Inspiration and Expiration Mechanics of Breathing: Resistance to flow z z z Flow = potential/resistance (like I = V/R) Airflow = delta Pressure/resistance Primary determinant of resistance is airway diameter (bronchodilation/bronchoconstriction – beta2 recept) – Majority of airway resistance comes from resp. generations ~2-9 (upper conducting zone) – Physical obstruction (choking) = resistance to inspiration and expiration – Asthma – bronchospasm – resistance to inflow and outflow – Emphasema/COPD – resistance primarily to expiration, dynamic compression of conducting airways, diagnosis 4 Law of Laplace and the role of Surfactant z LaPlace: in a sphere, P = 4T/r – P = pressure, T=surface (wall) tension, r=radius – As r increases P decreases and vice versa z In a system of alveoli of different radii – Pressure in small alveoli will exceed that in large alveoli – A pressure gradient stimulates FLOW – Small alveoli will collapse, larger alveoli will expand z Surfactant (a detergent) reduces the wall tension and helps keep the alveoli inflated – Surfactant is not produced until late gestation (type II cells) – No surfactant at birth = acute infant distress syndrome – Artificial surfactant Mechanics: Elasticity, FRC, and Pleural Pressure z z z z z Both the chest wall (ribs etc.) and the lung have elastic properties Lung recoil would tend to collapse the lung The chest wall recoil would tend to expand the chest The lung and chest wall forces reach equilibrium at the functional residual capacity (FRC) at the lung. This is the volume of the lung at the end of a normal, passive expiration. The balance of the inward pull of the lungs and the outward pull of the chest creates the intrapleural pressure of about –5 mmH2O A key to some symbols zA = alveolar z a = arterial z c= capillary z v = venous z I = inspired z E = expired 5 Pulmonary or Minute Ventilation (V) z The amount of air moved in or out of the lungs per minute (Liters/min) – Product of tidal volume (VT) and breathing frequency (f) V = VT x f z terms: – VT – f – VA – VD Tidal volume – amount of air breathed in and out in a single, normal breath (ml or L) Respiratory rate – breaths/min Alveolar ventilation – L/min Deadspace ventilation – L/min Alveolar vs. Dead Space Ventilation Dead Space – airway space where gas exchange cannot take place – nose/mouth through end of the conducting zone - VD is the portion of the VE that ventilates the dead space - VA is the portion of the VE that ventilates the respiratory zone VE = VA + VD Panting is primarily dead space ventilation Pulmonary Volumes and Capacities z z Measured by spirometry Tidal Volume (VT) z Functional Residual Volume (FRC) z Vital capacity (VC) – Volume of air inspired and expired in a a normal breath – Volume of air remaining in the lungs after a normal expiration – Maximum amount of air that can be expired following a maximum inspiration z Residual volume (RV) – Volume of air remaining in the lungs after a maximum expiration – Impossible to expire the RV – Difficult to directly measure the RV 6 A Spirogram Showing Pulmonary Volumes and Capacities Diffusion – Fick Principle z Gases diffuse from high → low partial pressure (as ions diffuse from high to low concentration) – Between lung and blood – Between blood and tissue z Fick’s V gas = law of diffusion A T x D x (P1-P2) V gas = rate of diffusion A = tissue area T = tissue thickness D = diffusion coefficient of gas P1-P2 = difference in partial pressure Diffusion - Fick Principle V gas = A T x D x (P1-P2) V gas = rate of diffusion A = tissue area T = tissue thickness D = diffusion coefficient of gas P1-P2 = difference in p pressure A = dependent on alveolar surface area T = thickness of the blood gas barrier – can be thickened by disease or edema D is proportional to solubility over the squ root of molecular wt In general, bigger molecules have lower diffusion coefficients CO2 is about 20X more soluble than O2 – much higher D P1-P2 is affected by the PAO2 (P1) and the mixed capillary PO2 (P2) *or CO2 or other gas* 7 Partial Pressure of Gases – Computing the PIO2 z z z Each gas in a mixture exerts a portion of the total pressure of the gas (Dalton’s Law) The partial pressure of oxygen (PO ) 2 – Air is 20.93% oxygen – Total pressure of air at sea level = 760 mmHg – PO2 = 760*0.2093 = 159 mmHg Water vapor: 100% saturation at body temp = 47 mmHg PIO = 0.2093 x (760-47) = 150 mmHg 2 Got PIO2, Now computing the PAO2 z In healthy mammals, Alveolar PO2 – Atmospheric Pressure (sets PIO2) – PACO2 – very similar to PaCO2 - RER depends on: “alveolar gas equation” PAO2 = PIO2 – PaCO2/RER Example: PAO2 = 150 – 40/.8 = 150 – 50 = 100 mmHg Computing PaCO2 (~PACO2) z In healthy mammals, PaCO2 depends on: – Metabolic rate – VCO2 – Alveolar ventilation rate – VAO2 PACO2 = VCO2/VA * K (K = constant) So, PaCO2 is proportional to the metabolic rate divided by the alveolar ventilation - hyperventilation - high altitude - hypoventilation 8 Partial Pressure and Gas Exchange Why is PaO2 slightly less than PAO2? z PAO2 is always greater than PaO2 normal conditions in a healthy mammal, this difference is < or = ~10 mmHg z Contributors: z Under – Shunt – thebian circulation from lungs – Incomplete equilibrium (diffusion limitation) – Mismatch of ventilation and perfusion (more later) EXAMPLE: Flagstaff What is the atmospheric pressure in Flagstaff (~7,000 ft)? 9 O2 Transport in the Blood z z O2 is not very soluble in water at body temp (CO2 is ~20X more soluble) O2 is bound to hemoglobin (Hb) for transport in the blood – Oxyhemoglobin: O2 bound to Hb – Deoxyhemoglobin: O2 not bound to Hb z Carrying capacity: – – – – 4 O2 per Hb = 100% saturated (3/Hb = 75% etc.) 1.39 ml O2/g Hb Human males have about 15 g Hb/100ml blood Human females tend to have lower [Hb] Oxyhemoglobin Dissociation Curve Flagstaff? O2-Hb Dissociation Curve: Effect of pH z Blood pH declines during heavy exercise in humans (not necessarily in dogs etc.) z Muscle pH may decline more (source of the acid) z Results in a “rightward” shift of the curve – “Bohr effect” – Favors “offloading” of O2 to the tissues – Of course, increased pH leads to left shift 10 O2-Hb Dissociation Curve: Effect of pH -Exercise humans, dogs -High altitude short term, llamas -High altitude long term O2-Hb Dissociation Curve: Effect of Temperature z Increased blood temperature results in a weaker Hb-O2 bond z Decreased temperature leads to left shift z Increased temperature leads to right shift of curve – Easier “offloading” of O2 at tissues O2-Hb Dissociation Curve: Effect of Tº Tº 11 O2 Transport in Muscle z Myoglobin (Mb) shuttles O2 from the cell membrane to the mitochondria z Higher affinity for O2 than hemoglobin – Even at low PO2 – Allows Mb to store O2 Dissociation Curves for Myoglobin and Hemoglobin CO2 Transport in Blood z Dissolved in plasma (5-10%) – Solubility in H2O at body temperature is 0.067 ml CO2/100ml H20/mmHg – about 3 ml/100ml blood if PaCO2 is 40 mmHg z Bound to Hb (5-20%) z Bicarbonate (70-80%) – “carbaminohemoglobin” – CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3– Enzyme: carbonic anhydrase – found in RBC’s, not free in plasma – Also important for buffering H+ 12 CO2 Transport in Blood Release of CO2 From Blood Ventilation and AcidAcid-Base Balance z z Blood pH is regulated in part by ventilation H+ + HCO3- --- CO2 + H2O A decrease in ventilation causes a build up of CO2 – Hypoventilation if less than VCO2 – Increases blood PaCO2 – Raises H+ concentration – respiratory acidosis z An increase in ventilation causes exhalation of additional CO2 – Hyperventilation if exceeds VCO2 – Reduces blood PaCO2 – Lowers H+ concentration – respiratory alkalosis 13
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