HMP 210: MEDICAL PHYSIOLOGY III. Dr Lee Ngugi Kigera

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1 HMP 210: MEDICAL PHYSIOLOGY III Dr Lee Ngugi Kigera

2 HMP 200: RESPIRATORY PHYSIOLOGY AND MECHANICS OF RESPIRATION HMP 201: TRANSPORT OF GASES AND RESPIRATORY CONTROL

3 Reference books Review of Medical Physiology William Ganong Textbook of Medical Physiology Guyton and Hall Textbook of medical physiology by Walter boron, emile boulpaep Bernie and Levy physiology 6th ed E-resources e,g

4 HMP 200: RESPIRATORY PHYSIOLOGY AND MECHANICS OF RESPIRATION Objectives Describe the structures and functions of the conducting and respiratory zones of the lungs Describe mechanics of respiration Describe gas exchange in the lungs Describe the pulmonary circulation Describe other functions of the respiratory sys

5 Respiration includes 2 process 1. external respiration-ventilation and gaseous exchange 2. internal respiration- oxygen utilization

6 Respiratory sys components -lungs -pump -brain areas that control resp Tracts, nerves that connect brain to muscles

7 Anatomy The respiratory system is divided into a respiratory zone, which is the site of gas exchange between air and blood, and a conducting zone-transport gas into and out of respsys --nose & mouth to and including terminal bronchioles

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12 Nasal passages humidify and warm air Trachea-alveolar sacs airway divides 23 times 1 st 16 are in conducting zone Next 7 in respiratory zone respiratory bronchioles, alveolar ducts and alveoli Increase cross sectional area 2.5cm 2 at trachea-18,000 cm 2 at alveoli-low velocity

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15 The alveoli are surrounded by pulmonary capillaries air and blood are separated only by the alveolar epithelium and the capillary endothelium, so they are about 0.5 µm apart

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18 Humans have 300 million alveoli, total area of the alveolar walls in contact with capillaries in both lungs is about 70 m2. Alveoli lined by 2 types of epithelial cells -Type I cells-primary lining cells -type II cells- secrete surfactant????? Other types of cells present in the lungs

19 Functions of the conducting zone -warming air -humidifying - filtering particles- mucous - cleaning- macrophages

20 Bronchiiand their innervation The trachea and bronchi have cartilage in their walls but relatively little smooth muscle. lined by a ciliated epithelium that contains mucous and serous glands. bronchioles and terminal bronchioles, and their walls do not contain cartilage----contain more smooth muscle,

21 walls of the bronchi and bronchioles are innervated by the autonomic nervous system. Muscarinicreceptors --cholinergic discharge causes bronchoconstriction. The bronchial epithelium and smooth muscle contain β2-adrenergic receptors--mediate bronchodilation.

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23 Lungs are enveloped by two layers of wet epithelial membrane collectively called the pleural membranes. Pleural space

24 parietal pleura, lines the inside of the thoracic wall. visceral pleura, covers the surface of the lungs thin layer of fluid between interpleural space

25 can become a real space if the visceral and parietal pleurae separate when a lung collapses The lungs slide easily on the chest wall, but resist being pulled away from each other Lungs and chest wall are elastic Interpleuralis subatmospheric the lungs have tendency to recoil from chest wall and chest wall has tendency to recoil in opposite direction

26 if chest wall is opened, lungs collapse If lungs lose elasticity, chest expands to become barrel shaped

27 Mechanics of respiration Boyle's Lawdescribes the relationship between the pressure (P) and the volume (V) of a gas. The law states that if the volume increases, then the pressure must decrease (or vice versa) PV= constant

28 Mechanics of respiration The movement of air into and out of the lungs occurs as a result of pressure differences induced by changes in lung volumes. Normal, quiet inspiration results from muscle contraction (active process), normal expiration from muscle relaxation and elastic recoil (passive process)

29 Inspiration Inhalation Contraction of inspiratorymuscles increases intrathoracic volume Contraction of the diaphragmcauses an increase in the size of the thoracic cavity, while contraction of the external intercostal muscles elevates the ribs and sternum.

30 Lungs pulled into more expanded position Interpleuraland intrapulmonary pressure falls from -2.5 mm Hg to -6 (relative to atmospheric pressure) Pressure in airway becomes negative gases move from regions of high pressure to low pressure, air rushes into the lungs.

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33 Expiration Exhalation At the end of inspiration, the inspiratory muscles relax the lungs recoil begins to pull the chest back to expiratory position. Intrathoracic volume decreases Pressure in the airway becomes positive to atmospheric pressure---gases move from regions of high pressure to low pressure, air rushes out of the lungs.

34 Passive process- quiet breathing

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38 Respiratory muscles Inspiratory muscles Movement of the diaphragm--75% of the change in intrathoracicvolume during quiet inspiration---vertical direction Phrenic nerve Also used in eructation, vomiting External intercostal muscles Elevate lower limbs-increase antero-posterior, lateral volume

39 scalene and sternocleidomastoidmuscles in the neck --accessory inspiratorymuscles that help to elevate the thoracic cage during deep labored respiration

40 Expiratory muscles Contraction of these result in decrease in intrathoracic volume and forced expiration Internal intercostals pull rib cage downward Anterior abdominal wall muscles-pull rib cage downward, increase abdominal pressure which pushes diaphragm upwards

41 Lung volumes

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43 The fraction of the vital capacity expired during the first second of a forced expiration is referred to as FEV1

44 The amount of air inspired per minute (pulmonary ventilation, respiratory minute volume) is normally about 6 L (500 ml/ breath x 12 breaths/min). The space in the conducting zone of the airways occupied by gas that does not exchange with blood in the pulmonary vessels anatomical dead space.

45 ???? spirometry????? Lung volume changes in obstructive and restrictive airway disease

46 Bronchial muscle tone Bronchial dilation produced by - inspiration - sympathetic discharge -VIP bronchial constriction produced by - expiration - parasympathetic discharge -cold air - irritants and chemicals - Cytokines and inflammatory mediators

47 Physiological properties of lungs for inspiration to occur, the lungs must be able to expand when stretched; they must have high compliance For expiration to occur, the lungs must get smaller when this tension is released: they must have elasticity

48 The tendency to get smaller is also aided by surface tension forces within the alveoli. Compliance the ease with which the lungs can expand under pressure change in lung volume per change in airway pressure, expressed as Δ V /Δ P. Stretchability/ distensability Fibrosis reduces compliance

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50 Elasticity tendency of a structure to return to its initial size after being distended. high content of elastinproteins, the lungs are very elastic and resist distension

51 Surface tension The forces that act to resist distension include: -elastic resistance -surface tension that is exerted by fluid in the alveoli. surface tension acts to collapse the alveolus and in the process increases the pressure of the air within the alveolus

52 Surface tension occurs at fluid gas interface Water molecules pull together---water lines alveoli hence will tend to collapse alveoli This surface tension acts to collapse the alveolus, and in the process increases the pressure of the air within the alveolus. The law of Laplace, the pressure thus created is directly proportional to the surface tension and inversely proportional to the radius of the alveolus

53 According to this law, the pressure in a smaller alveolus would be greater than in a larger alveolus if the surface tension were the same in both. The greater pressure of the smaller alveolus would then cause it to empty its air into the larger one

54 Surfactant Alveolar fluid contains a substance that reduces surface tension---surfactant Lipid surface tension lowering substance Secreted by type II alveolar cells If the surface tension is not kept low when the alveoli become smaller during expiration, they collapse in accordance with the law of Laplace

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58 Surfactant also helps prevent pulmonary edema---unopposed surface tension would cause transudation of fluid from blood to alveoli Surfactant begins to be produced in late fetal life. premature babies are sometimes born with lungs that lack sufficient surfactant and their alveoli are collapsed --respiratory distress syndrome (RDS) or hyaline membrane disease

59 Collapsed alveoli atelectasis mothers can be given exogenous corticosteroids to accelerate the maturation of their fetus s lungs

60 Clinical application, the first breath of life is difficult because the newborn must overcome great surface tension forces in order to inflate its partially collapsed alveoli. Thetranspulmonarypressure required for the first breath is 15 to 20 times that required for subsequent breaths, and an infant with respiratory distress syndrome must duplicate this effort with every breath. Fortunately, many babies with this condition can be saved by mechanical ventilators and by exogenous surfactant delivered to the baby s lungs

61 Work of breathing Work is performed by the respiratory muscles --in stretching the elastic tissues of the chest wall and lungs (elastic work; approximately 65% ) ----moving inelastic tissues (viscous resistance; 7% of total), ----moving air through the respiratory passages (airway resistance; 28% of total

62 pressure times volume (g/cm2 x cm3 = g x cm) has the same dimensions as work (force x distance), The amount of elastic work required to inflate the whole respiratory system is less than the amount required to inflate the lungs alone because part of the work comes from elastic energy stored in the thorax.

63 Quiet breathing-laminar flow-less work done to overcome airway resistance-less energy used During rapid respiration air flow is turbulentmore work done to overcome airway resistance more energy used During normal quiet respiration,---3 to 5 % of the total energy expended by the body is required for pulmonary ventilation

64 Work of breathing increased in conditions associated with dyspnea -asthma -emphysema - heart failure Respiratory muscle can get fatigued pump failure Aminophyllineincreases force of contraction of the diaphragm

65 Differences in ventilation & blood flow in different parts of the lung

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67 In the upright position, ventilation per unit lung volume is greater at the base of the lung than at the apex Because of the stiffness of the lung, the increase in lung volume per unit increase in pressure is smaller when the lung is initially more expanded, and ventilation is consequently greater at the base

68 Blood flow is also greater at the base than the apex The relative change in blood flow from the apex to the base is greater than the relative change in ventilation, so the ventilation/perfusion ratio is low at the base and high at the apex Due to gravity not present in supine position Persist in weightlessness of space???

69 DEAD SPACE & UNEVEN VENTILATION gas that occupies the conducting zones is not available for gas exchange with pulmonary capillary blood---anatomic dead space In normal health, anatomic dead space approximate to body weight in pounds

70 Man weighing 150 lb (68 kg) -in inspiration, only 1 st 350 ml of 500 ml (tidal volume) mixes with air in alveoli -150 ml will be in the conducting zone -expiration, 1 st 150 ml is from conducting zones, last 350 ml from alveoli Alveolar ventilation amount of air reaching alveoli per minute

71 Rapid shallow breathing produces less alveolar ventilation

72 anatomic dead space (respiratory system volume exclusive of alveoli) total (physiologic) dead space (volume of gas not equilibrating with blood; ie, wasted ventilation). In health, they are identical

73 in disease states, no exchange may take place between the gas in some of the alveoli and the blood, some of the alveoli may be overventilated volume of gas in nonperfusedalveoli and any volume of air in the alveoli in excess of that necessary to arterialize the blood in the alveolar capillaries is part of the dead space (nonequilibrating) gas volume Single breath N 2 curve or Xenon

74 Total dead space can be calculated from Bohr s equation??? Bohr s equation

75 Properties of gases Partial pressures Unlike liquids, gases expand to fill the volume available to them, volume occupied by a given number of gas molecules at a given temperature and pressure is the same regardless of the composition of the gas

76 Thus, the pressure exerted by any one gas in a mixture of gases (its partial pressure) is equal to the total pressure times the fraction of the total amount of gas it represents. composition of dry air is 20.98% O2, 0.04% CO2, 78.06% N2, and 0.92% other inert constituents barometric pressure (PB) at sea level is 760 mm Hg (1 atmosphere).

77 partial pressure (indicated by the symbol P) of O2 in dry air is therefore 0.21 x 760, or 160 mm Hg at sea level water vapor in the air in most climates reduces these percentages, and therefore the partial pressures inspired air is saturated by the time it reaches the lungs

78 The Ph2 O at body temperature (37 C) is 47 mm Hg the partial pressures at sea level of the other gases in the air reaching the lungs are PO2, 149 mm Hg; PCO2, 0.3 mm Hg; and PN2 (including the other inert gases), 564 mm Hg.

79 Gas diffuses from areas of high pressure to areas of low pressure, rate of diffusion depending on the concentration gradient and the nature of the barrier between the two areas When a mixture of gases is in contact with and permitted to equilibrate with a liquid, each gas in the mixture dissolves in the liquid to an extent determined by its partial pressure and its solubility in the fluid

80 Pressures of Gases Dissolved in Water and Tissues Gases dissolved in water or in body tissues also exert pressure when the gas dissolved in fluid encounters a surface, it exerts its own partial pressure in the same way that a gas in the gas phase does.

81 partial pressures of the separate dissolved gases are designated the same as the partial pressures in the gas state, that is, Po2, Pco2, Pn2, The partial pressure of a gas in a liquid is the pressure that, in the gaseous phase in equilibrium with the liquid, would produce the concentration of gas molecules found in the liquid.

82 Gas exchange in the lungs Composition of alveolar air Not the same composition as atmospheric air --alveolar air is only partially replaced by atmospheric air with each breath (mixing) ---oxygen is constantly being absorbed into the pulmonary blood --carbon dioxide is constantly diffusing from the pulmonary blood into the alveoli

83 --dry atmospheric air that enters the respiratory passages is humidified before it reaches the alveoli

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86 Volume of gas in alveoli at end of quiet expiration is about 2000ml ( functional residual capacity, FRC) Each 350 ml increment of inspired and expired air has relatively little effect on PO2 and PCO2.

87 Diffusion across alveolocapillary membrane gas exchange occurs through the membranes of all the terminal portions of the lungs, not merely in the alveoli themselves micrometer,--very thin 70 sq m Total blood in pulm capillaries ml rapidity of the respiratory exchange of oxygen and carbon dioxide.

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89 Diffusion through the membrane determined by (1) the thickness of the membrane, --edema ---fibrosis (2) the surface area of the membrane, -- pneumonectomy -- emphysema

90 (3) the diffusion coefficient of the gas in the substance of the membrane, --solubility --CO2 diffuses 20x more rapidly than O2 (4) the partial pressure difference of the gas between the two sides of the membrane.

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