Lungs

• Basic concept of air:

  • flow of air is caused by pressure differential
  • flow will originate from area of high pressure
• Pulmonary structures:

  • alveoli = terminal end of bronchioles
  • connection between external and internal environment
  • highly perfused (fed by pulmonary arteriole)
• Mechanics of ventilation:

  inspiration:

  • diaphragm goes down; contracts
  • lungs expand, reducing pressure
  • pressure differential causes air to flow in

  expiration:

  • sternum and ribs swing down; diaphragm goes up
  • lungs compress, increasing pressure
  • pressure differential causes air to go out
• Pressure changes:

  • positive pressure = air out
  • negative pressure = air in
  • intrapleural pressure = less than intrapulmonary pressure to allow lungs to stay popped open
• Flow and pressure vs volume:

  • elastic recoil on expiration
  • volume and flow increase with exercise, but at max exercise, we are not encroaching on max capacity
  • lungs are well-suited to take in air and increase ventilation to demands of exercise
  • must generate greater pressures to increase volume and flow as exercise increases relative to max expiratory and inspiratory pressures we can create
• Ventilation (VE):

  • movement of air in and out of lungs
  • minute ventilation = total volume of expired gas per minute
  • VE = RR x VT
  • normal resting ventilation = 6 L/min
• VE does what with metabolic demand?

  VE rises with metabolic demand as exercise intensity increases
• VE and incremental exercise:

  • as we start exercising, we first alter our ventilation by increasing VT
  • as intensity increases, we rely on RR rather than VT
• VA (alveolar ventilation):

  • = volume of gas per minute that participates in gas exchange; represents large fraction of VE
  • dead space ventilation (VD) = fraction of VE that does not participate in gas exchange; respiratory passages and non-perfused alveoli
  • increase VD = increase VE to maintain VA
  • VA = VE - VD
  • VA = RR (VT - VD)
• Distribution of VT:

  • physiological dead space = alveoli that receive air but are not perfused
  • anatomical dead space = air just doesn’t get to these alveoli
• Effects of RR and VT on VE and VA:

  • less air/breath is comprised of VD because our physiological dead space changes
  • increase exercise = change in cardiac output = increase perfusion)
  • VA is always less than VE
  • VD still contributes, but not as much once intensity increases
• Changes in breathing:

  • we operate with out lungs half full
  • as intensity increases, volume and respiratory frequency increase
  • reduce where volumes are at end of expiration so we can generate bigger inspiration
• Changes in breathing:

  with moderate to heavy exercise…

  • increased VE achieved by increased VT and RR
  • increase VT by encroaching on inspiratory and expiratory reserve volumes
  • reduced end-expiratory lung volume (EELV) is maintain at max exercise in fit people (lungs with higher volume have hard time inspiring; therefore reduce EELV so we can increase VT)
• Gas exchange:

  • why do we breathe = to take up O2 and remove CO2
  • where does exchange occur = alveolar-pulmonary capillary interface
  • how does it occur = pulmonary diffusion
  • how do we know gases exchange properly = by partial pressure of O2 and CO2 in arterial blood (blood leaving heart)
  • what determines proper gas exchange = VA / Q matching and diffusion capacity
• Concepts of diffusion:

  Dalton’s Law of partial pressure:

  • individual gases in a mixture exert pressure proportional to their abundance
  • more molecules in given space = greater partial pressure
  • sum of partial pressures = total pressure
• Concepts of diffusion:

  Henry’s Law of diffusion between gases and liquids:

  • amount of gas dissolved depends on: 1) pressure differential between gas above fluid and in fluid; 2) solubility of gas in fluid
  • without gradient, gases are in equilibrium = no diffusion
• Gas concentration and pressures:

  • concentration = amount of gas in given volume; determined by gas partial pressure and solubility
  • pressure = force exerted by gas against surfaces
  • partial pressure = percentage concentration (F) x total pressure of gas mixture (P)
• Gas concentration and pressure:

  percentage:

  • O2 = 14.5
  • CO2 = 5.5

  partial pressure:

  • O2 = 103 mmHg
  • CO2 = 39 mmHg
• Alveolar-capillary interface:

  • site of pulmonary diffusion = alveolar wall + capillary wall + basement membrane
  • are inflow = bronchial tree —> alveoli
  • blood inflow = right ventricle —> pulmonary arteries —> pulmonary capillaries (deoxygenated blood)
  • 2 functions = replenish blood O2; remove CO2
• O2 exchange in alveoli:

  • atmosphere PO2 = 150 mmHg
  • alveolar PO2 = 100 mmHg
  • pulmonary artery PO2 = 40 mmHg
  • diffusion of gas occurs quickly
• Fick’s Law of diffusion:

  rate of diffusion through respiratory membrane is…

  • directly proportional to: 1) surface area; 2) partial pressure; 3) diffusion constant (gas solubility and molecular weight)
  • inversely proportional to: 1) thickness of tissue (ex. edema)
• Ventilation-perfusion relationship:

  • usually air flow to alveoli ~ blood flow to alveoli
  • well ventilated but poorly perfused = wasted ventilation
  • well perfused but poorly ventilated = wasted perfusion
  • having a ventilation/perfusion mismatch will mean you need to increase VE to satisfy gas exchange requirements
• Ventilation-perfusion relationship:

  • both VA and Q contribute to dead space
• Gas exchange:

  • differences in partial pressure cause exchange of O2 and CO2 between:
  • alveoli and pulmonary capillaries (alveolar-arterial interface)
  • tissues and tissue capillaries (arterial-myocyte interface)
• Gas exchange:

  • O2 = 159, 149, 100, 100, 100, 40, 40, 40 (O2 in)
  • CO2 = 0.3, 0.3, 40, 40, 40, 46, 46, 46 (CO2 out)
• External gas exchange:

  • O2 into capillaries
  • CO2 into alveoli
  • diffusion at venous ends of pulmonary capillaries, PO2 in blood = PO2 in alveoli, and PCO2 in blood = PCO2 in alveoli
  • PO2 in pulmonary veins is less than pulmonary capillaries due to VA-Q mismatch
• Internal gas exchange:

  • O2 diffuses out of arterial ends of tissue capillaries
  • CO2 diffuses out of tissue
  • PO2 in blood = PO2 in tissues
  • PCO2 in blood = PCO2 in tissues
• O2 transport cascade:

  PO2 is important because:

  • its gradient drives diffusion
  • it impacts how O2 and CO2 are transported and delivered
  • drop from 159-103 due to humidified air (water vapour contributes to partial pressure; p.p. drops)
  • PO2 = 100 comes from alveolar average
• O2 transportation in blood:

  red blood cells:

  • no nucleus; unable to reproduce; replaced via hematopoiesis
  • produced and destroyed at equal rates
  • contain hemoglobin

  hemoglobin:

  • O2 transporting protein
  • 4 O2 per hemoglobin
  • heme and globin
  • O2 binding increases affinity for more O2 to bind
• Blood components:

  • 55% plasma
  • 45% formed elements (RBC & WBC)
• O2 transport in blood:

  2 ways:

  • dissolved in fluid portion of blood (establishes PO2; 2%)
  • combined with hemoglobin (98%)
• Arterial O2 content (CaO2):

  • CaO2 expressed in mL O2 per 100 mL of blood
  • equal to sum of…
  • O2 bound to hemoglobin
  • dissolved O2
• Fun facts:

  • arterial O2 content will not change with increased activity
  • BUT venous O2 content falls with increased activity
• a-vO2difference vs exercise intensity:

  • from high to low intensity, venous O2 content decreases
  • a-vO2difference increases as we increase intensity because we extract more O2 arriving at tissue level
• Oxyhemoglobin dissociation curve:

  • dissolved O2 controls O2 release from hemoglobin
  • percent of O2 bound to hemoglobin depends on PO2
  • as PO2 dissolves, percent of O2 bound to hemoglobin decreases
  • the farther the PO2 falls, the more O2 we release from hemoglobin
• Oxyhemoglobin:

  • 100 mmHg —> all O2 bound to hemoglobin
  • as blood gets to tissue, PO2 falls (40 mmHg)
• Dissociation curve shifting:

  left shift:

  • decrease O2 unloading
  • increase affinity
  • increase pH
  • decrease PCO2
  • decrease temperature

  right shift:

  • increase O2 unloading
  • decrease affinity
  • decrease pH
  • increase PCO2
  • increase temperature
  • relevant with exercise (increase heat and acidity in active tissues = increase O2 release)
• Bohr shift:

  • severe intensity
  • where CO2 or H are high, O2 is less tightly bound to hemoglobin and O2 is released more readily
  • to counteract acidity
• CO2 transport in blood:

  3 ways:

  • dissolved in fluid (establishes PCO2; 10%)
  • combined with hemoglobin (20%)
  • combined with water as bicarbonate (70%)
• Haldane effect:

  • when O2 binds with hemoglobin, CO2 is released
  • when O2 offloads from hemoglobin, CO2 binds to increase CO2 transport
  • bodies tolerate O2 partial pressures
  • bodies cannot tolerate CO2 partial pressures
  • as PCO2 falls, we release more CO2 from hemoglobin
  • curve up = carry away CO2
  • curve down = carry less CO2