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Physiology of Respiratory system General physiology By Assist. Prof.Dr. Majida Alqayim Departement of physiology and pharmacology College of veterinary medicine University of baghdad Respiration Exchange of gases between the air and the cells of the body, in the followings steps: • Pulmonary ventilation :The physical movement of air into and out of the lungs. • External Respiration: Movement of respiratory gases from the lung into the blood. Involves diffusion across a respiratory membrane. • Internal respiration: The use of oxygen by the mitochondria to produce ATP by oxidative phosphorylation with production of carbon dioxide as a waste product. Introduction:Respiratory System The respiratory system is made up of a gas-exchanging organ (the lungs) and a "pump" that ventilates the lungs. The pump consists of the chest wall; the respiratory muscles, which increase and decrease the size of the thoracic cavity; the areas in the brain that control the muscles; and the tracts and nerves that connect the brain to the muscles. At rest, a normal human breathes 12 to 15 times a minute. About 500 mL of air per breath, or 6 to 8 L/min, is inspired and expired. This air mixes with the gas in the alveoli, and, by simple diffusion, O2 enters the blood in the pulmonary capillaries while CO2 enters the alveoli. In this manner, 250 mL of O2 enters the body per minute and 200 mL of CO2 is excreted. Traces of other gases, such as methane from the intestines, are also found in expired air. Alcohol and acetone are expired when present in appreciable quantities in the body. Lungs are cone-shaped organs situated in the thoracic cavity. The left lung is divided by an oblique fissure into superior and inferior lobes. The right lung is divided by oblique and horizontal fissures into superior, middle and inferior lobes. Each lobe receives a secondary (lobar) bronchus from the primary bronchi. Inside the lungs, the secondary bronchi give rise to smaller bronchi called 'tertiary (segmental) bronchi', which in turn divide into smaller tubes called 'bronchioles'. Bronchioles branch repeatedly to form the terminal bronchioles that divide into respiratory bronchioles. GROSS AND MICROSCOPIC STRUCTURE OF THE LUNGS Between the trachea and the alveolar sacs, the airways divide 23 times. The first 16 generations of passages form the conducting zone of the airways that transports gas from and to the exterior. They are made up of bronchi, bronchioles, and terminal bronchioles. The remaining seven generations form the respiratory zones where gas exchange occurs; they are made up of respiratory bronchioles, alveolar ducts, and alveoli. These multiple divisions greatly increase the total cross-sectional area of the airways, from 2.5 cm2 in the trachea to 11,800 cm2 in the alveoli . Consequently, the velocity of air flow in the small airways declines to very low values. Blood gas barrier • • • • 1. A layer of fluid lining the alveolus and containing surfactant that reduces the surface tension of the alveolar fluid 2. The alveolar epithelium composed of thin epithelial cells 3. An epithelial basement membrane 4. A thin interstitial space between the alveolar epithelium and the capillary membrane 5. A capillary basement membrane that in many places fuses with the alveolar epithelial basement membrane 6. The capillary endothelial membrane Alveolar wall • The alveoli are lined by two types of epithelial cells. Type I cells are flat cells with large cytoplasmic extensions and are the primary lining cells of the alveoli, covering approximately 95% of the alveolar epithelial surface area. Type II cells (granular pneumocytes) are thicker and contain numerous lamellar inclusion bodies. A primary function of these cells is to secrete surfactant; however, they are also important in alveolar repair as well as other cellular physiology. Although these cells make up approximately 5% of the surface area, they represent approximately 60% of the epithelial cells in the alveoli. The alveoli also contain other specialized cells, including pulmonary alveolar macrophages (PAMs, or AMs), lymphocytes, plasma cells, neuroendocrine cells, and mast cells. The mast cells contain heparin, various lipids, histamine, and various proteases that participate in allergic reactions Cells within airway Airway wall Pulmonary and bronchial circulation Pulmonary and bronchial circulation Pulmonary and bronchial circulation Air ways divisions Volume of conducting zone is about 150 ml volume of respiratory zone is 3 litters Dead space • • • • • Definition - It is the volume of the respiratory tract that does not participate in gas exchange. It is approximately 300 ml in normal lungs. It is important to distinguish between the anatomic dead space (respiratory system volume exclusive of alveoli) and the total (physiologic) dead space (volume of gas not equilibrating with blood; ie, wasted ventilation). Physiological dead space= Anatomical dead space + Alveolar dead space Normally, the volume (in mL) of this anatomic dead space is approximately equal to the body weight in pounds. As an example, in a man who weighs 150 lb (68 kg), only the first 350 mL of the 500 mL inspired with each breath at rest mixes with the air in the alveoli. Air that reaches the alveoli, but for one reason or other does not take part in gas exchange, is not considered as Alveolar dead space (for example, air that goes to an unperfused alveolus). influencing alveolar dead space:Low cardiac output can increase alveolar dead space (increasing West's zone 1) Pulmonary embolism. Alveolar ventilation (VA) is the volume of air reached the alveoli in per minute that (1) reaches the alveoli and (2) takes part in gas exchange. • Rapid shallow breathing produces much less alveolar ventilation than slow deep breathing at the same respiratory minute volume (Table ). Regions lacking gas exchange constitute alveolar dead space. 10/min 30/min Respiratory rate 600 mL 200 mL Tidal volume 6L 6L Minute volume (600 – 150) x 10 = 4500 mL (200 – 150) x 30 = 1500 mL Alveolar ventilation Mechanics of ventilation (breathing) Pulmonary ventilation:-The physical movement of air into and out of the lungs. A mechanical process that depends on volume changes in the thoracic cavity, lead to pressure changes( Boyle's law ), which lead to the flow of gases in and out of the thoracic cavity to equalize pressure. Ventilation results from bulk flow of air as the result of pressure gradients which created between alveoli and atmospheric pressure as a result of volume changes. Boyle's law :-This law states that the pressure of gas in any container is inversely related to the volume of the container. In other words, when volume increases, pressure decreases and when volume decreases, pressure increases. P1V1 = P2V2 P = pressure of a gas in mm Hg V = volume of a gas in cubic millimeters Mechanics of Breathing As the external intercostals & diaphragm contract, the lungs expand. The expansion of the lungs causes the pressure in the lungs (and alveoli) to become slightly negative relative to atmospheric pressure. As a result, air moves from an area of higher pressure (the air) to an area of lower pressure (our lungs & alveoli). During expiration, the respiration muscles relax & lung volume descreases. This causes pressure in the lungs (and alveoli) to become slight positive relative to atmospheric pressure. As a result, air leaves the lungs. Pulmonary ventilation The factors limiting the pulmonary ventilation :• 1- - ve Intraplueral pressure • 2--Elastic recoil ( elastine proteins , collagen fiber, intraplueral fluid) • 3- lung surface tension During inspiration, alveolar volume increases and intra-alveolar pressure falls causing air molecules to enter down the pressure gradient created by the inspiration. The air flow stops when pressure is equal to atmospheric pressure (0 mm Hg). During expiration, alveolar volume decreases and intra-alveolar pressure increases causing air molecules to leave down a pressure gradient in the reverse direction until the pressure returns to 0 mm Hg. The movement of air into and out of the alveoli is due to the changes in the volume of the thoracic cavity produced by the muscles of ventilation. . • Alveolar ventilation Alveolar ventilation (VA) is the volume of air reached the alveoli in per minute that (1) reaches the alveoli and (2) takes part in gas exchange • Pulmonary ventilation Different regions of ventilation There is regional differences of ventilation in the lower regions are better ventilated from upper This differences in the intrapleural -ve pressure between upper and lower due to the gravity and the lung mass. . Regional blood flow in the Lung The uneven distribution of blood flow can be explained by the hydrostatic pressure differences within the blood vessels. Causes of Un even Blood flow 1- Gravity. 2- mass of the lung 3-Non gravitational resistance Ventilation- perfusion ratio Ventilation – the amount of gas reaching the alveoli Perfusion – the blood flow reaching the alveoli Ventilation and perfusion must be tightly regulated for efficient gas exchange Changes in PCO2 in the alveoli cause changes in the diameters of the pulmonary arterioles Alveolar CO2 is high/O2 low: vasoconstriction Alveolar CO2 is low/O2 high: vasodilation Gas exchange is dependent on local matching of regional ventilation-to-perfusion ratio ( ˙ VA/ ˙Q), where Well ventilated regions ideally have high capillary blood flows. Poorly ventilated regions ideally have little capillary blood flow. Three regions or 3 zones in standing position and 2 zones in laying and animals Effect of Ventilation-Perfusion Inequality on Overall Gas Exchange ventilation-perfusion inequality. When ventilation and blood flow are mismatched in various regions of the lung, impairment of both O2 and CO2 transfer results. Different regions for gas exchange This diagram explain the causes of regional distribution for different microbial infections in the lung Gases diffusion and transportation • Diffusion of any gas is judged by the Fick’s law of diffusion , in which transfer of any gas ( v• )through a sheet of tissue is proportional to tissue surface area (A) and the difference in gas partial pressure (P1- P2) between the two sides of the tissue , and inversely to thickness of the tissue(T ) • Lung is big A( 50-100 m2 ) and Low T( microne) • D :- diffusion coaffeciant of any gas it depends on :-a. property of tissue • b. molecular of gas • c. solubility of gas Gas Exchange in the Lungs O2 transport in the blood Oxygen–hemoglobin dissociation curve. Oxygen transported in two forms: 1. Dissolved in the solution (> 2%) – oxygen is not very soluble. 2. Bound to hemoglobin (< 98%) – much more important. Factors Affecting the Affinity of Hemoglobin for Oxygen Three important conditions affect the oxygen– hemoglobin dissociation curve: the pH, the temperature, and the concentration of 2,3biphosphoglycerate (BPG; 2,3-BPG). A rise in temperature or a fall in pH shifts the curve to the right (Figure 36–3). When the curve is shifted in this direction, a higher PO2 is required for hemoglobin to bind a given amount of O2. Conversely, a fall in temperature or a rise in pH shifts the curve to the left, and a lower PO2 is required to bind a given amount of O2. A convenient index for comparison of such shifts is the P50, the PO2 at which hemoglobin is half saturated with O2. The higher the P50, the lower the affinity of hemoglobin for O2. Factors affect on Hb-O2 association curve Carbon Dioxide transporting:- Fate of CO2 in Blood. In plasma 1. Dissolved 2. Formation of carbamino compounds with plasma protein 3. Hydration, H+ buffered, HCO3– in plasma In red blood cells 1. Dissolved 2. Formation of carbamino-Hb 3. Hydration, H+ buffered, 70% of HCO3– enters the plasma 4. Cl– shifts into cells; mOsm in cells increases