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1. 22 The Respiratory System: Part B

2. Breathing or pulmonary ventilation • A mechanical process that depends on volume changes in the thoracic cavity • Volume changes lead to pressure changes, which lead to the flow of gases to equalize pressure • Consists of two phases • Inspiration – air flows into the lungs • Expiration – gases exit the lungs

3. Pressure Relationships in the Thoracic Cavity • Respiratory pressure is always described relative to atmospheric pressure • Atmospheric pressure (Patm) • Pressure exerted by the air surrounding the body • Negative respiratory pressure is less than Patm • Positive respiratory pressure is greater than Patm • Intrapleural pressure (Pip) – pressure within the pleural cavity • always less than intrapulmonary pressure and atmospheric pressure • Intrapulmonary pressure (Ppul) – pressure within the alveoli • eventually equalizes itself with atmospheric pressure

4. Intrapleural Pressure and Pressure Relationships • Negative Pip is caused by opposing forces • Two inward forces promote lung collapse • Elastic recoil of lungs decreases lung size • Surface tension of alveolar fluid reduces alveolar size • One outward force tends to enlarge the lungs • Elasticity of the chest wall pulls the thorax outward • If Pip = Ppul the lungs collapse • (Ppul – Pip) = transpulmonary pressure • Keeps the airways open

5. Intrapleural pressure • As a result of the relationship between the lungs and the pleurae (lungs pull the visceral pleura in), the intrapleural pressure is below atmospheric pressure – average of -4 mmHg • This pressure (or the fluid bond between the pleurae) prevents the collapsing of the lungs due to there elasticity

6. Pulmonary ventilation – inspiration and expiration • Pulmonary ventilation depends on volume changes in the thoracic cavity • Volume changes lead to pressure changes • Pressure changes lead to flow of gases • Boyle’s Law- The volume of a fixed amount of gas is inversely proportional to the total amount of pressure applied. • If the pressure doubles, the volume shrinks to half. • In the lungs – if lungs volume increase the pressure decreases (intrapulmonary pressure)

7. Modes of breathing • Quiet breathing – eupnea • Inhalation is active and exhalation is passive (relaxation of muscles) • Forced breathing – hyperpnea • Both inhalation and exhalation involve muscle contraction – both active • Inhalation involve muscles like the pec. minor, sternocleidomastoid and more • Exhalation involves the internal intercostals and abdominal muscles among others

8. Physical Factors Influencing Ventilation • 3 factors influence pulmonary ventilation • Airway Resistance • Alveolar Surface Tension • Lung Compliance

9. Airway Resistance • As airway resistance rises, breathing movements become more difficult • Resistance is usually insignificant because of • Large airway diameters in the first part of the conducting zone • Progressive branching of airways as they get smaller, increasing the total cross-sectional area • Severely constricted or obstructed bronchioles: • Can prevent life-sustaining ventilation • Can occur during acute asthma attacks which stops ventilation • Epinephrine release via the sympathetic nervous system dilates bronchioles and reduces air resistance

10. Alveolar Surface Tension • Surface tension – the attraction of liquid molecules to one another at a liquid-gas interface • The liquid coating the alveolar surface is always acting to reduce the alveoli to the smallest possible size • Surfactant, a detergent-like complex, reduces surface tension and helps keep the alveoli from collapsing • Normally, surfactant synthesis starts at about the 25th week of fetal development and production reaches optimal levels at 34th week • Premature babies with insufficient surfactant can be treat with aerosol administration with artificial surfactant until lungs mature

11. Lung Compliance • Compliance is the indication of the lungs expandability • The ease with which lungs can be expanded • Factors that diminish lung compliance • Scar tissue or fibrosis that reduces the natural elasticity of the lungs • Blockage of the smaller respiratory passages with mucus or fluid • Reduced production of surfactant • The mobility of the thoracic cage – changes cause to the articulations of the ribs or to the muscles involved.

12. Respiratory Volumes • Used to assess a person’s respiratory status • Tidal volume (TV) • Inspiratory reserve volume (IRV) • Expiratory reserve volume (ERV) • Residual volume (RV)

13. Respiratory Capacities • Inspiratory capacity (IC) equals TV plus IRV • Maximum amount of air (about 3.5 liters) a person can breath in • Functional residual capacity (FRC) equals the ERV plus RV • Amount of air remains in the lungs at the end of normal expiration • Vital capacity (VC) equals IRV+ERV+TV • Maximum amount of air a person can expel from the lungs after filling with inspiratory capacity • Total lung capacity (TLC) equals VC+RV • Maximum volume to which the lungs can be expanded

14. Dead Space • Some of the inspired air does not contribute to the gas exchange in the alveoli • Anatomical dead space – volume of the conducting respiratory passages (150 ml) • Alveolar dead space – alveoli that cease to act in gas exchange due to collapse or obstruction • Total dead space – sum of alveolar and anatomical dead spaces • On expiration, the air in the anatomical dead space is expired first

15. Pulmonary Function Tests • Spirometer – an instrument used to evaluate respiratory function • Spirometry can distinguish between: • Obstructive pulmonary disease – increased airway resistance by narrowing or blocking airways (ex. Asthma) • Restrictive disorders – reduction of pulmonary compliance thus limiting inflation of lungs. • Caused by any disease that produces pulmonary fibrosis

16. Nonrespiratory Air Movements • Most result from reflex action • Examples include: coughing, sneezing, crying, laughing, hiccupping, and yawning

17. Gas exchange and transport

18. Respiratory physiology is a series of integrated processes • External respiration • Exchange of gases between interstitial fluid and the external environment • Internal respiration • Exchange of gases between interstitial fluid and cells • Transport of oxygen and carbon dioxide • To understand the above processes, first consider • Physical properties of gases • Composition of alveolar gas

19. Basic properties of gases • Dalton’s Law of Partial Pressures • Total pressure exerted by a mixture of gases is the sum of the pressures exerted independently by each gas in the mixture (as if no other gases were present) • The separate contribution of each gas in a mixture is called partial pressure (symbolized with P) • The partial pressure of each gas is directly proportional to its percentage in the mixture

20. Composition of air in alveoli • The composition of air we breath is not the composition in the alveoli: • The air is humidified by the contact with the mucus membrane – so PH2O is >10 times higher than the inhaled air • Freshly inspired air is mixed with residual air left from previous breathing cycle • That causes the oxygen to be diluted and CO2 to be higher • Alveolar gas exchanges O2 and CO2 with blood • As a result, PO2 of alveolar air is about 65% of that of the inhaled air and PCO2 is >130 higher

21. Alveolar gas exchange Diffusion between liquid and gases (Henry’s law) • When a mixture of gases is in contact with a liquid, each gas will dissolve in the liquid in proportion to its partial pressure • The greater the concentration of a particular gas, the more and the faster that it will go into a solution • The amount of gas that will dissolve in a liquid also depends upon its solubility: • Carbon dioxide is the most soluble • Oxygen is 1/20th as soluble as carbon dioxide • Nitrogen is practically insoluble in plasma

22. External Respiration: Pulmonary Gas Exchange • Factors influencing the movement of oxygen and carbon dioxide across the respiratory membrane (what is the respiratory membrane?) • Partial pressure gradients and gas solubility • Matching of alveolar ventilation and pulmonary blood perfusion • Structural characteristics of the respiratory membrane

23. Partial Pressure Gradients and Gas Solubility • The partial pressure oxygen (PO2) of venous blood is 40 mm Hg; the partial pressure in the alveoli is 104 mm Hg • This steep gradient allows oxygen partial pressures to rapidly reach equilibrium (in 0.25 seconds) • this is one third of the time a RBC is in the pulmonary capillary (0.75 seconds) • Although carbon dioxide has a lower partial pressure gradient (45 mm Hg in the blood and 40 mm Hg in the alveoli; a gradient of 5 mm Hg): • It diffuses in equal amounts with oxygen because it is 20 times more soluble in plasma than oxygen

24. Surface Area and Thickness of the Respiratory Membrane • The amount of gas that moves across a tissue is • proportional to the area of the sheet • inversely proportional to its thickness • Respiratory membranes: • Are only 0.5 to 1 m thick, allowing for efficient gas exchange • Have a total surface area of about 60 m2 (40 times that of one’s skin)

25. Internal Respiration • The factors promoting gas exchange between systemic capillaries and tissue cells are the same as those acting in the lungs • The partial pressures and diffusion gradients are reversed • PO2 in tissue is always lower than in systemic arterial blood • PO2 of venous blood draining tissues is 40 mm Hg and PCO2 is 45 mm Hg

26. Oxygen Transport: Role of Hemoglobin • Molecular oxygen is carried in the blood: • Bound to hemoglobin (Hb) within red blood cells • Dissolved in plasma (O2 has low solubility in water and only 1.5% is dissolved in plasma) • Each Hb molecule binds four oxygen atoms in a rapid and reversible process • The hemoglobin-oxygen combination is called oxyhemoglobin (HbO2) • Hemoglobin that has released oxygen is called reduced hemoglobin/deoxyhemoglobin (HHb) • Saturated hemoglobin – when all four hemes of the molecule are bound to oxygen • Partially saturated hemoglobin – when one to three hemes are bound to oxygen

27. The Oxygen-Hemoglobin Saturation Curve • PO2 of 40 mm Hg – (average in the tissues) Hb is 75% saturated • only 25% of the O2 is unload from Hb in resting conditions • PO2 of 60-70 mm Hg – Hb is 90% saturated • PO2 of 20 mm Hg – Hb is only 30% saturated • Ex. – active muscle; relatively high percentage of O2 released with small decrease in Po2

28. Factors That Increase Release of Oxygen by Hemoglobin • As cells metabolize glucose, carbon dioxide is released into the blood causing: • Increases in PCO2 and H+ concentration in capillary blood • Declining pH (acidosis), which weakens the hemoglobin-oxygen bond (Bohr effect) • Metabolizing cells have heat as a byproduct and the rise in temperature increases BPG synthesis • All these factors ensure oxygen unloading in the vicinity of working tissue cells

29. Carbon Dioxide Transport • Carbon dioxide is transported in the blood in three forms • Dissolved in plasma – 7 to 10% • Chemically bound to hemoglobin – 20% is carried in RBCs as carbaminohemoglobin • Bicarbonate ion in plasma – 70% is transported as bicarbonate (HCO3–)

30. Carbon Dioxide Transport • In areas with high PCO2, carbon dioxide leaves the cell, diffuses through the interstitial fluid and enters a capillary. • Most of it enters an erythrocyte that contains an enzyme, carbonic anhydrase which catalyses the following reaction: • CO2  + H20  -----> H2CO3 -----> H+  + HCO3-- . • The bicarbonate ion leaves the red blood cell (against concentration gradient) and travels to the lungs in the plasma of the blood. • In exchange, Cl- moves from plasma into RBCs to maintain the electrical balance between plasma and RBC (chloride shift) • It often combines with Na+ present in the plasma to form sodium bicarbonate which plays a role in maintaining the homeostasis of blood pH.

31. Haldane Effect • The amount of CO2 that can be transported in the blood is influenced by Hb saturation with O2. • The lower the amount of Hb-O2 the higher the CO2 carrying capacity (Haldane effect): • Deoxyhemoglobin has higher affinity to CO2 • Deoxyhemoglobin buffers more H+ thus promoting conversion of CO2 to HCO3- • At the tissues, as more carbon dioxide enters the blood: • More oxygen dissociates from hemoglobin (acidosis - Bohr effect) • More carbon dioxide combines with hemoglobin, and more bicarbonate ions are formed • This situation is reversed in pulmonary circulation