PGY 206 Final

• Respiration term used in 2 ways: Mitochondrial O2 utilization (aerobic metabolism) and Ventilation (breathing, gases move via bulk flow, conducting airways are essential)
• The Thorax


  • Chest wall: diaphragm (skeletal muscle sheet), thorax (rib cage, spinal column, trunk muscles)
  • Thoracic cavity: contains lungs, trachea, heart, large vessels, esophagus, thymus
  • Pleural cavity: Space between visceral and parietal pleurae

  
• Conducting Zone


  • Conducts air flow (bulk flow) to respiratory zone
  • Warms and humidifies inspired air
  • Cleans air: Secretes mucus, Cilia move mucus, Emphysema (smoking) decreases cilia mobility, Cystic Fibrosis decreases cilia mobility

  
• Conducting vs. Respiratory Zone (contain alveoli)

  
• Respiratory Zone (contain alveoli)


  • In some of the alveolar walls, pores permit the flow of air between alveoli
  • Most air-facing surfaces of the alveoli wall are lined by a thin layer of water (continuous layer type I alveolar cells)
  • Type II alveolar cells produce a detergent-like substance called surfactant (lowers surface tension of water)
  • Alveolar macrophages

  
• Alveoli


  • Primary site of gas exchange
  • Approx. 300 million in adult lung, 60–80 m2 surface area (tennis court)
  • Barrier to diffusion is 2 cells across (2 micrometers)
  • Type I: epithelial cells with structural function (80-90% of cells), thin, interconnected by pores
  • Type II: secrete surfactant
  • Macrophages – clean debris
• Air moves between in the respiratory zone (alveoli) via diffusion
• Intrapulmonary or Alveolar pressure (PA)

  Equals atmospheric pressure at 'rest', altered by changes in lung volume

  
• Intrapleural pressure (Ppl)


  Subatmospheric (negative) at rest, determined by lungs and chest wall

  
• Transpulmonary pressure


  Pressure difference across lung (PA - Ppl), determines lung volume

  
• Pleural Pressure (Ppl) is intrapleural pressure, is always more negative than PA, and is affected by forces of gravity
• Understanding Pressure change in lung using Boyle's Law

  1. Ideal Gas Law: PV = nRT (a constant if temperature and number of molecules is unchanged, a "closed container")

  2. Changes in lung volume alter intrapulmonary pressure (PA)

  3. With lung expansion, PA falls below atmospheric pressure (PATM or PM), air flows in

  4. With lung compression, PA increases above PATM, air flows out

  
• Inspiration


  1. Active process: Diaphragm contracts, increasing thoracic volume, Parasternal/external intercostals contract (accessory muscles), pulling the ribs up and out

  2. Intrapleural pressure (PPl) becomes more negative, Lung 'pulled' open, increasing lung volume, Intrapulmonary pressure (PA) becomes more negative (subatmospheric), Air flows into lungs
• Expiration


  1. Passive (sleep, quiet breathing): Inspiratory muscles relax, Intrapleural pressure becomes less negative, Lung volume decreases, Intrapulmonary pressure becomes positive, Air flows out of lung

  2. Active (exercise, speech, cough, panting, etc.): Internal intercostal and abdominal muscles contract, Expiratory pressures increased, Air flow faster, more variable

  
• Pressure Changes in Quiet Breathing

  • Inspiration: Intrapulmonary pressure (PA) is less than atmospheric pressure, Approximately (-3 mm Hg)
  • Expiration: PA is greater than atmospheric pressure, Approximately +3 mm Hg

  
• Pneumothorax


  • Air enters the pleural space causing the lung to collapse
  • Open pneumothorax – Air enters via open wound to chest wall
  • Closed pneumothorax – Air enters via lung injury, chest wall remains intact

  
• Airway resistance


  • Lung Resistance = ease with which air flows through airways, Primarily determined by airway diameter: smooth muscle tone (asthma), support by surrounding tissue (emphysema)
  • Flow = (pressure change)/resistance
  • Conducting airways have cartilage and muscle, Respiratory zone – held open by surrounding tissue (tethering, pulled open)
• Compliance


  The ability to stretch, Change in lung volume per change in transpulmonary pressure (PA - Ppl), C = (change is volume)/(change in pressure)

  Lungs 100x more compliant than toy balloon, Determined by lung structure and surface tension

  Pulmonary fibrosis - stiff fibrous tissue that restricts ling inflation
• Compliance and Surface Tension

  • Alveoli lined by thin liquid layer, H2O molecules in liquid attract one another, generating tension at the air-liquid surface, Water tension within alveoli acts like a pressure pulling alveoli closed, Resists lung expansion
• Compliance and Surfactant


  • Phospholipid mixture, Alveolar type II cells produce it, Lowers surface tension of water, More effective as alveolar radius decreases
  • Clinical relevance: RDS – Respiratory Distress Syndrome (infants); ARDS (acute), Premature babies lack surfactant, Artificial surfactant available
• Elastic recoil


  Result of elastin fibers in the lung tissue, Allows the lung to recoil back to its original shape, Different than compliance,

  Analogy: Elastic recoild of elestaic band of new vs old socks

  Emphysema destroys elastin fibers decreasing elastic recoil (blwon up balloon vs plastic bag)
• Gas Exchange in the Lungs

  • Gases move between air and blood by diffusion due to concentration gradient: O2 diffuses from air to blood, CO2 diffuses from blood to air, Process rapid due to large surface area, short diffusion distance, Each gas moved down its concentration or partial pressure gradient
• Dalton's Law


  Pressure of a gas mixture = sum of pressures each gas exerts independently, PATM = PN2 + P02 + PC02 + PH20= 760 mm Hg
• Partial pressure


  Pressure exerted by one gas in a mixture, Dry air is 21% O2, PO2 = 0.21 x 760 = 150 mm Hg
• Gas partial pressures equilibrate between air and blood via Henry's Law


  gas dissolved in liquid exerts a pressure, In liquid equilibrated with a gas mixture, partial pressures are equal in the two phases, the amount of each gas dissolved in liquid is determined by: temperature of the fluid, partial pressure of the gas, solubility of the gas
• O2 transport in blood

  • O2 is not very soluble in plasma, RBC have hemoglobin which increases oxygen concentration in blood, RBC are flattened biconcave discs with a large surface area to promote diffusion of gases, Hemoglobin contains iron to transport O2 from lungs to tissues, Iron group of the heme helps transport O2 from the lungs to the tissues
• Oxyhemoglobin Dissociation Curve

  1. S-Shape, binding cooperativity,
  2. Upper plateau: O2 loading in lungs,
  3. Steep slope: unloading in tissues
• Changes in O2 Binding Affinity

  • Left shift (more affinity): pH rise / H+ drop, PCO2 drop, Temperature drop, 2,3-DPG drop
  • Right shift (less affinity): Opposite of left shift
• Red blood cells (RBCs)

  • Flattened biconcave discs with a large surface area to promote diffusion of gases
  • Each RBC contains hundreds of millions of hemoglobin molecules that contain iron
  • The iron group of the heme helps to transport O2 from the lungs to the tissues

  
• O2 is not very soluble in plasma
• RBCs have hemoglobin which increases oxygen concentration in blood
• Oxyhemoglobin Dissociation Curve

  • S-Shape: binding cooperativity
  • Upper plateau: O2 loading in lungs
  • Steep slope: unloading in tissues
• As PO2 increases


  The percentage of hemoglobin saturated with bound oxygen increases until all of the oxygen-binding sites are occupied (100% saturation)
• Systemic venous blood is typically 75% saturated with oxygen
• Changes in O2 Binding Affinity

  • Left shift (more affinity): pH rise / H+ drop, PCO2 drop, Temperature drop, 2,3-DPG drop
  • Right shift (less affinity): pH drop / H+ rise, PCO2 rise, Temperature rise, 2,3-DPG rise
• CO2 transport in the blood

  1. HCO3- (70%), Carbonic anhydrase (ca)

  2. Dissolved CO2 (10%)

  3. Carbaminohemoglobin (20%)
• In the lungs, the concentration gradient of oxygen

  Favors its movement from the alveolar air into the pulmonary blood
• At active cells, the "disappearance" of oxygen (its incorporation into water molecules by mitochondria)


  Sets up the gradient that moves it from the systemic blood into the active cells
• The low concentration of carbon dioxide in the alveolar air


  Sets up the gradient that moves it from the pulmonary blood into the alveolar air
• At active cells, the production of carbon dioxide during fuel catabolism


  Sets up the gradient to move it from the cells into the systemic blood