Ventilation and Diffusion PDF

Ventilation and Diffusion Dr John P Winpenny Senior Lecturer in Physiology School of Medicine University of St Andrews ([email protected]) Footer: Ventilation and Diffusion 1 Learning Outcomes • • • • • • • • • Define the term "partial pressure“ and know how to calculate a gas partial pr...

Ventilation and Diffusion Dr John P Winpenny Senior Lecturer in Physiology School of Medicine University of St Andrews ([email protected]) Footer: Ventilation and Diffusion 1 Learning Outcomes • • • • • • • • • Define the term "partial pressure“ and know how to calculate a gas partial pressure Explain what factors determine how much gas dissolves in a liquid Explain what factors affect the diffusion of gases across the air-blood barrier, and the consequences of such factors on arterial blood gases State the normal partial pressures of nitrogen, oxygen, carbon dioxide and water vapour in atmospheric air and alveolar air (in mmHg and kPa) Describe the processes involved in an oxygen molecule moving from alveolar air to the blood Describe the processes involved in a carbon dioxide molecule moving from blood to the alveolar air State how different disease states can affect the diffusion of O2 and CO2 across the alveolar barrier Describe how altitude affects PO2 Describe the effects of high pressure on blood gases Overview • • • • Gas Laws Gas exchange between air and blood Gas movements at the tissues Extremes of Physiology: altitude and diving 3 The Conducting Airways • The conducting airways – Cartilage, few smooth muscles – Collapse rare • Respiratory bronchioles & alveolar ducts – No cartilage, lots of smooth muscle – Susceptible to collapse during expiration • Anatomical Dead Space – 150mls – Up to generation 17 • Humans have ~ 300 million alveoli and cross sectional area increases from 2.5cm2 at trachea to around 100m2 Cross Sectional Area and Air Velocity Primary Functions Of The Respiratory and Cardiovascular Systems • One of the primary functions of the cardiovascular systems is to transport O2 from the lungs to all tissues in the body • And CO2 from the tissues to the lungs • The lungs expire this CO2 to the atmosphere • Both gases move by diffusion down their concentration gradients Figure from Review of Medical Physiology by Ganong Dalton’s Law of Partial Pressures • “Total pressure (PTotal) of a mixture of gases is the sum of their individual partial pressures (Px)” • Atmospheric Pressure (PB) at sea level is 760mmHg or 101.325 kPa • • • • Nitrogen (PN2): Oxygen (PO2): Carbon dioxide (PCO2): Argon (PAr): 78.09% x 760 mmHg = 593.48 mmHg 20.95% x 760 mmHg = 159.22 mmHg 0.030% x 760 mmHg = 0.23 mmHg 0.930% x 760 mmHg = 7.07 mmHg • If atmospheric pressure changes then partial pressure changes • If proportion of gas changes its partial pressure changes 100mmHg  13.3 kPa 40mmHg  5.33 kPa 7.5mmHg = 1kPa 7 Henry’s Law • States that the concentration of O2 dissolved in water ([O2]dis) is proportional to the Partial pressure (PO2) in the gas phase [O2]dis = s x PO2 where s = solubility of O2 in water For blood plasma s = 0.0013 mM/mmHg at 37oC, so [O2]dis = 0.0013 x 100 mmHg = 0.13 mM (arterial blood) [O2]dis = 0.0013 x 40 mmHg = 0.05 mM (mixed venous blood) • CO2 is the most soluble, O2 is about 1/20th as soluble and N2 is barely soluble at atmospheric pressure 8 Alveolar Gas Composition • Alveolar air is warmed and humidified • • • • Nitrogen (PN2): Oxygen (PO2): Carbon dioxide (PCO2): Argon (PAr): 78.09% x (760 – 47) mmHg = 556.78 mmHg 20.95% x (760 – 47) mmHg = 149.37 mmHg 0.030% x (760 – 47) mmHg = 0.21 mmHg 0.930% x (760 – 47) mmHg = 6.63 mmHg • O2 in lungs is actually lower (104 mmHg), CO2 is higher (40 mmHg) and water vapour is higher (as a consequence of this N2 is lower) • Why? – alveolar air is made up of ‘fresh air’ plus the air that remains in the lungs after the last breath 9 Gas exchange between alveolar and blood • O2 has to: – dissolve in an aqueous layer – diffuse across the membranes – enter the blood Flow = (∆P x A x D) / T O2 • Rate of diffusion is proportional to – – – – – Partial pressure difference (∆P) Surface area (A) Solubility (D, diffusion coefficient) molecular mass (D, diffusion coefficient) Inversely proportional to tissue thickness (T) O2 10 Gas exchange between alveolar and blood • • • • Surface area of lungs is large 50 -100 m2 Large number of alveoli (~500 million) Thickness is small (0.2 – 0.5 µm) Concentration gradient is large – PO2 alveolar air is 100 mmHg – PO2 of venous blood is 40 mmHg, so diffusion rapid • Molecular mass insignificant, but solubility very important, with CO2 diffusing 20 x more rapidly than O2 • At rest, takes about 0.75 - 1 second for blood to pass through pulmonary capillaries O2 equilibrium only takes about 0.25 s (so not normally diffusion-limited) • • In exercise, capillary transit time can be reduced to as little as 0.3 s (so now diffusion-limited) 11 Gas exchange between alveolar and blood • CO2 moves in the other direction, from blood capillary into alveoli • Smaller concentration gradient – alveolar PCO2 is 40 mmHg – venous PCO2 is 45 mmHg • However, greater solubility, so CO2 diffusing 20 x more rapidly than O2 • Same amount of gas moves Low CO2 High CO2 12 Diffusion Limitations of Gas Exchange • Flow = (∆P x A x D) / T • In oedema, T (thickness of barrier) increases • Transit time through capillary may not be sufficient to complete full gas exchange – gas exchange reduced – More marked effect on O2 than CO2, due to greater solubility of CO2 • In emphysema, A reduced (breakdown of tissue and alveolar sacs) – Gas exchange reduced • In pulmonary fibrosis, T increased (deposition of fibrotic tissue) – Gas exchange reduced • Mucus, inflammation of airway, tumours, reduce gas entry – Gas exchange reduced 13 Altitude • At altitude, atmospheric pressure is reduced • Hence, PO2 is reduced • Denver, Colorado, 1620m (5300 ft) above sea level – PB is 632 mmHg (down from 760 mmHg) – Inspired PO2 – 125 mmHg (down from 149 mmHg) – Alveolar PO2 – 84 mmHg (down from 104 mmHg) – Alveolar PCO2 – 34 mmHg (down from 40 mmHg) 14 Physiological Adaptations to Altitude • Acute – Hypoxia sensed by peripheral chemoreceptors – Ventilatory drive increases initially but blunted by central chemoreceptors that respond to decreased PaCO2 due to increased ventilation – CO increases due to suppression of cardioinhibitory centre • Adaptive – Central chemoreceptors adapt so ventilation rate continues to increase – PaCO2 drops leading to respiratory alkalosis, kidneys compensate by reducing acid excretion blood pH normalises – Alkalosis stimulates 2,3 DPG production – leads to rightward shift of O2 dissociation curve 15 Physiological Adaptations to Altitude • Acclimation – Blood – Erythropoietin release stimulated – Hb conc. increases to 200 g/L from 150 g/L – Vasculature – Hypoxia stimulates angiogenesis – Capillary density increases throughout body – Cardiopulmonary system – Vascular and ventricular remodelling – Smooth muscle growth increase vascular wall thickness – Right ventricle hypertrophies 16 Diving • Atmospheric pressure increases by 760 mmHg (1 atmosphere) every 10 m depth • Effects of Depth – Increase in partial pressure, N2 and O2 dissolve into blood at lethal excess – Volume decrease • Gas toxicity – N2 narcosis – partial pressure of N2 (40m and below) rises and starts to dissolve in body tissues – O2 poisoning – again tightly regulated at sea level and system essentially saturated – At high pressure O2 dissolves in blood in excess of the buffering capacity of Hb – Heliox – N2 replaced by helium and percentage of O2 tailored to reduce harm – He less readily dissolves in body tissues and less narcotic. 17 Summary • O2 and CO2 exchange occurs by diffusion , driven by partial pressures gradients for both gases • O2 has limited water solubility • CO2 is 20 x more soluble than O2 in blood • Atmospheric pressure decreases with altitude above sea level • PO2 also decreases causing hypoxia • Diving increases partial pressure of inspired gases • O2 and N2 become potentially toxic as dissolve into tissues at depth 18 References • Boron, WF & Boulpaep, EL (2017) Medical Physiology (3rd Edition) – Chapter 30 Gas Exchange in the Lungs p660-674 – Chapter 61 Environmental Physiology p1223-1234 • Guyton & Hall (2016) Textbook of Medical Physiology (13th Edition) – • Chapter 40 Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide Through the Respiratory Membrane pp517-526 Preston RR & Wilson TE (2013) Lippincott’s Illustrated Reviews: Physiology (1st Edition) – Chapter 23 Gas Exchange p280-297 • Naish, J & Syndercombe Court, D. (2019). 3rd Edition. Medical Sciences – Chapter 13 The Respiratory System p603-642