Dr. Zainab H.H Dept. of Physiology Lec.3,4 RESPIRATION Dr. Zainab H.H Dept. of Physiology Lec.3,4

objectives Define physical laws of gases List types of dead spaces and their effect on the alveolar ventilation Describe physical properties of the lung List the functions of the surfactant Describe the work of breathing

Physical Laws of Gases Dalton’s Law: Total pressure exerted by a mixture of gases = sum of the pressures exerted by the individual gases. Partial pressure: The pressure that an particular gas exerts independently. Partial pressures = % of that gas x total pressure.

Partial Pressure of Gases PATM = PN2 + PO2 + PCO2 + PH2O = 760 mm Hg. In atmosphere: N2 = 79%, 760 mmHg x 0.79 = 600mmHg PN2 O2 = 21%, 760 mmHg x 0.21 = 159 mmHg PO2 CO2 = 0.04%, 760 mmHg x 0.0004 = 0.3 mm Hg PCO2

Partial Pressure of Gases PH2O contributes to partial pressure (47 mmHg). Water vapor also has a Partial pressure in humidified air as in the respiratory passages. Atmospheric PO2 decreases on a mountain and increases as one dives into the ocean. The partial pressure of CO2 is negligible at 0.03 mm Hg

Effect of Water Vapor As fresh air enters the nose and mouth it is immediately mixed with water vapor Since the total pressure remains constant, the water vapor lowers the partial pressure of all other gases For this reason, the PO2 is lowered to about 149 mmHg

Dead Space the volume of inspired air that is not involved in gas exchange. Types of dead space volume are: Anatomic dead space (VANA ): formed by the gas conduction parts of the airway that are not involved in gas exchange, such as the mouth, nasal cavity, pharynx, trachea and upper bronchial airways. Usually estimated ~ 2.2 ml per kg body weight ~154 ml in 70 kg man)

Dead Space Alveolar dead space: composed of those alveoli that are being ventilated but not perfused. They are therefore, in effect, not contributing to gas exchange Physiologic dead space: this is the sum of the two volumes above. further lowers the PO2 to about 100 mmHg

Factors affecting VANA Size of subject: VANA ↑ with ↑ in body size Age: from early adulthood, VANA ↑ ~ 1 ml/year VANA ↑ slightly in inspiration: airway diameter larger Tracheostomy →  VANA Breathing through snorkel: additional tubes →↑ dead space

Alveolar Air Inspired air is humidified (water vapor) Fresh inspired air mixes with the large volume of old air and the dead space At the end of each inspiration, less than 15% of the air in the alveoli is fresh air.

Alveolar Air Atmospheric CO2 mixes with high CO2 levels from residual volume in the alveoli increasing PCO2 to 40 mmHg Atmospheric O2 mixes with “old” air already in alveolus to arrive at PO2 of 105 mmHg

Partial Pressures of Gases in Inspired Air & Alveolar Air

Alveolar Ventilation VA Volume of fresh air entering alveoli per minute VA = (TV – VANA) X f, where TV = tidal volume VANA = anatomical dead space f = respiratory rate

Alveolar Ventilation VA TV = 500ml body weight = 70 kg Respiratory rate = 10/min = (500 - 154) X 10 = 3.46 L/min VA Normal VA ~ 4L/min (adult male) Normal pulmonary ventilation ~ 5-6L/min

Alveolar Ventilation VA Affected by: Total Flow in and out Anatomic Dead Space Functional Dead Space Gas Mixing

Atmospheric Air ≠ Alveolar Air. Why? Alveolar air is only partially replaced by atmospheric air. O2 is constantly being absorbed into the pulmonary blood from the alveolar air CO2 is constantly diffusing from the pulmonary blood into the alveoli Dry atmospheric air that enters the respiratory passages is humiliated before it reaches the alveoli

Disorders Caused by High Partial Pressures of Gases Nitrogen narcosis: At sea level nitrogen is physiologically inert. Under hyperbaric conditions: Nitrogen dissolves slowly. Can have deleterious effects. Resembles alcohol intoxication. Decompression sickness: Amount of nitrogen dissolved in blood as a diver ascends decreases due to a decrease in PN2. If occurs rapidly, bubbles of nitrogen gas can form in tissues and enter the blood. Block small blood vessels producing the “bends.”

Physical Properties of the Lungs Ventilation occurs as a result of pressure differences induced by changes in lung volume. Physical properties that affect lung function: Compliance. Elasticity. Surface tension.

Compliance (Stretchability) Ease with which the lungs can expand. DV/DP = 200ml/cmH2O Under normal physiological situations Variations in the respiratory cycle: compliance is greater after expiration. Position: Compliance is less in lying down due to less FRC(functional residual capacity) The lung 100 x more distensible than a balloon. Compliance is reduced by factors that produce resistance to distension.

Factors that Determine Compliance: 1. Elastic forces of the lung tissue itself (elastin and collagen fibers intermingle among the lung parenchyma 2. Elastic forces caused by surface tension of the fluid that lines the inside walls of the alveoli and other lung spaces Surface Tension accounts for 2/3 of total elastic forces in normal lung

Elasticity This is 1/compliance. Thus, it is a measure of the elastic recoil of the lung (tendency to return to initial size after distension). What generates this force? The elastic properties of the elastin and collagen network of the lung Surface tension at the alveolus Elastic tension increases during inspiration and is reduced by recoil during expiration.

Surface Tension Force exerted by fluid in alveoli to resist distension. Lungs secrete and absorb fluid, leaving a very thin film of fluid. This film of fluid causes surface tension. Fluid absorption is driven (osmosis) by Na+ active transport. Fluid secretion is driven by the active transport of Cl- out of the alveolar epithelial cells. H2O molecules at the surface are attracted to other H2O molecules by attractive forces. Force is directed inward, raising pressure in alveoli.

Surface Tension (continued) Law of Laplace: Pressure is directly proportional to surface tension; and inversely proportional to radius. Pressure in smaller alveolus would be greater than in larger alveolus, if surface tension were the same in both.

Surface Tension (continued) In a model with two bubbles of different radii in communication with each other absence of surfactant: the pressure p of the small bubble is higher than p of the large bubble airflow is generated from the smaller into the larger bubble. small alveoli collapsing and larger alveoli expanding.

Surface Tension (continued) It is thus important that the surface tension (T) changes in proportion with the radius of curvature (r) of the surface on which tension exerts. The surface-active material (pulmonary surfactant), lining the alveoli, helps to stabilize alveolar surface forces. The surfactant lowers T of the less inflated alveolus, such that its recoil pressure is not higher than that of the bigger one.

Surfactant Surface active agent secreted by type II alveolar epithelial cells Complex mixture of phospholipids monolayer lining the alveoli Dipalmitoylphosphatidylcholine 62% Phosphatidylglycerol 5% Other phospholipids 10% Neutral lipids 13% Proteins 8% Carbohydrate 2% Begin to be secreted between the 6th and 7th month of gestation

Surfactant Spreads over the surface of a fluid The polar heads point at the alveolar wall, the lipophilic side chains point at the lumen Reduces attractive forces of hydrogen bonding by becoming interspersed between H20 molecules). Surface tension in alveoli is reduced. As alveoli radius decreases, surfactant’s ability to lower surface tension increases.

Importance of Surfactant Lowers surface tension Stabilizes the size of the alveoli Prevents the accumulation of fluid Keep airways and alveoli open during end expiration Cause even distribution of air during late inspiration.

An infant born prematurely in gestational week 25 has neonatal respiratory distress syndrome. Which of the following would be expected in this infant? (A) Arterial PO2 of 100 mm Hg (B) Collapse of the small alveoli (C) Increased lung compliance (D) Normal breathing rate (E) Lecithin:sphingomyelin ratio of greater than 2:1 in amniotic fluid

Surface Tension of Different watery fluids 72 dynes/cm – pure water 50 dynes/cm – normal fluids lining the alveoli but without surfactant 5 to 30 dynes/cm – fluids lining the alveoli with surfactant included.

Airway Resistance lung volume determine the airway resistance: The greater the lung volume, the less the overall airway resistance due to the effects of radial traction. Radial traction is due to the elastin and collagen in the airways. The larger the lung volume, the greater the elastic recoil forces across the airways  pulls the others around it open  increasing their caliber  reducing their resistance by the Poiseuille equation.

Airway Resistance The physiologic factors that influence the diameter of the airways, and hence airways resistance are: Lung volumes Respiratory secretions Activity of airway smooth muscle cells determined by the ANS and chemical mediators

Airway Resistance At lower lung volumes, the effect of radial traction is diminished  reducing the caliber of the airways. Notes: only airways that are unsupported by mural cartilage are subject to the effects of radial traction. radial traction is lost in emphysema. This leads to air trapping and increased lung volumes.

Work of Breathing 1. Compliance work or Elastic work – that required to expand the lungs against the lung and chest elastic forces 2. Tissue resistance work – required to overcome the viscosity of the lung and chest wall structures 3. Airway resistance work – required to overcome airway resistance to movement of air into the lungs

Work of Breathing Compliance and Tissue resistance work – increased by diseases that cause fibrosis of the lungs as in tuberculosis Airway resistance work – increased by diseases that obstruct the airways as in asthma

Work of Breathing Airway resistance requires actual work to be done to overcome it. Airway resistance to flow is present during both inspiration and expiration. The energy required to overcome it, which represents the actual work of breathing, is dissipated as heat.

Work of Breathing The work of breathing is best displayed on a pressure-volume curve of one respiratory cycle. Shows the different pathways for inspiration and expiration, known as hysteresis

Energy Expenditure is Increased When: Pulmonary compliance is decreased Airway resistance is increased Elastic recoil is decreased There is need for increased ventilation