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SUMMARY: RESPIRATION Functions of the respiratory system: - Function off the respiratory zone: gas exchange: o In the lungs, we add oxygen to the blood and release carbon dioxide in the environment. o In working cells, oxygen diffuses from blood to ISF to cells, while metabolic waste products such as carbon dioxide move in the opposite direction. o Therefore, both respiratory system and CVS work in collaboration to allow appropriate gas exchange. - Functions of the conducting airways: 1. Defence against bacterial infection and foreign particles: The epithelial cells possess cilia and secrete mucous Foreign particles stick to the mucous and the cilia constantly sweeps the mucous up into the pharynx. Tobacco smoking paralyzes the cilia, thus inhibiting this defence mechanism. 2. Warm and moisten inhaled air 3. Produce sound and speech with the vocal cords 4. Regulation of air flow: smooth muscle around the airways may contract or relax to alter resistance to air flow. Anatomy of the respiratory system: - The respiratory tract: o Air can enter either by the mouth or the nose o If it enters by the nose, it passes through the nasal septum and the nasal turbinates, which clean the air of big dust particles. o Air then passes into the pharynx (common to air and food), the larynx, and the trachea. o The trachea divides into two bronchi, each of which divides into lobar and segmental bronchi. o Right main bronchus = 3 lobar bronchi o Left main bronchus = 2 lobar bronchi o The segmental bronchi divides further into smaller branches o The smallest airways without alveoli are the terminal bronchioles o Surface of the lungs = visceral pleura - Subdivisions of the conducting airways and terminal respiratory units: o The airways consist of a series of tubes that branch and become narrower, shorter and more numerous as they penetrate into the lungs. - Conducting and respiratory zones: o Conducting zone: Airways from the mouth and nose 1 openings, all the way down to the terminal bronchioles. They conduct air from environment to the respiratory zone. Since they do not participate in gas exchange, they are said to form the anatomical dead space. o Respiratory zone: Characterized by the presence of alveoli in the walls of the airways. Begins where the terminal bronchioles divide into the respiratory bronchioles. Site for gas exchange Makes most of the lungs Smallest physiological unit of lungs = acinus (1 respiratory bronchiole) Blood supply: o Pulmonary circulation: Brings mixed venous blood to the lungs, allowing for the blood to get oxygenated, and then back to the heart, where it enters the systemic circulation. Branches from the pulmonary artery run with the airways. When the alveoli are reached, arterioles divide into a capillary bed. o Bronchial (systemic) circulation: Supplies oxygenated blood to the tracheobronchial tree Bronchial arteries from the aorta supply the airway walls. Alveolar cell types: o Epithelial cells: Type I: Little is known about their specific metabolic activity Type II: Produce pulmonary surfactant, a substance that decreases the surface tension of the alveoli o Endothelial cells: Constitute the walls of the pulmonary capillaries May be as thin as 0,1 micron o Alveolar macrophages: Remove foreign particles that may have escaped the mucocilliary defence system of the airways. - - 2 - Respiratory muscles: o Inspiratory muscles: Principal: External intercostals: elevate ribs Parasternal intercartilaginous: elevate ribs Diaphragm: dome descend, increasing longitudinal dimension of chest and elevating lower ribs Accessory: Sternocleidomastoid: elevates sternum Scalenus: elevate and fix upper ribs: o Anterior o Middle o Posterior o Expiratory muscles: Quiet breathing: Expiration results from passive recoil of lungs Active breathing: Internal intercostals, except parasternal intercartilaginous muscles: depress ribs Abdominal muscles : depress lower ribs, compress abdominal contents o Rectus abdominus o External oblique o Internal oblique o Transversus abdominus Summary of events during respiration: - Inspiration: o Diaphragm and intercostal muscles contract 3 - o Thoracic cage expands o Intrapleural pressure becomes more subatmospheric o Transpulmonary pressure increase o Lungs expand o Alveolar pressure becomes subtamospheric o Air flows into alveoli Expiration: o Diaphragm and intercostal muscles stop contracting o Chest wall moves inwards o Intrapleural pressure goes back towards preinspiratory value o Transpulmonary pressure goes back towards preinspiratpry value o Lung recoil towards preinspiratory volume o Air in lungs is compressed o Alveolar pressure becomes greater than atmospheric pressure o Air flows out of the lungs Spirometry: measuring lung volumes A spirometer is a machine that measures amounts of inhaled or exhaled air. It can directly measure tidal volume, vital capacity, inspiratory capacity, expiratory reserve volume and expiratory reserve volume, but not residual volume, functional residual capacity or total lung capacity. Ventilation: - Minute ventilation versus alveolar ventilation: o Ventilation = amount of air inspired into the lungs over some period of time. o It is usually meausured for 1 minute: this is why we call it minute ventilation. 4 - - o Not all air inspired reaches the respiratory zone. Some stays in the conducting airways, forming the anatomical dead space. o Thus, we can define alveolar respiration as the amount of air that reaches the respiratory zone per minute and available for gas exchange. Physiological dead space: o In some pathological conditions, an amount of inspired air that reaches the respiratory zone does not take place in gas exchange. This represents the alveolar dead space. o Physiological dead space is the sum of anatomical and alveolar dead space. Types of alveolar ventilation: o Normal alveolar ventilation: alveolar ventilation matches carbon dioxide production and keeps its partial pressure at a constant level. o Alveolar hyperventilation: more oxygen is supplied and more carbon dioxide is removed than metabolic rates needs. o Alveolar hypoventilation: alveolar ventilation is below that required by the metabolic activity of the body. Gas diffusion: - Diffusion rate: o Passage of oxygen across the alveolar-capillary membrane occurs by passive diffusion and is governed by Fick’s law. o Diffusion rate is proportional to : Surface area Partial pressure gradient 1/thickness of the alveolar capillary membrane. o Diffusion of oxygen and carbon dioxide always occurs from higher to lower partial pressure. o In order for a gas to diffuse through a liquid, the gas must be soluble in the liquid. o Since carbon dioxide is considerably more soluble than oxygen, it diffuses about 20x more rapidly. o However, the time required for equilibrium between alveolar and capillary blood is about the same for the two gases, since the difference of pressure between alveolus and capillary is 10x higher for oxygen than for carbon dioxide, thus compensating for the solubility difference. - Transit time: o Although the transit time of blood through the pulmonary capillaries is only 0,75 seconds at rest, diffusion is so rapid than the partial pressure of oxygen of the air and that of the blood reach equilibrium before the blood has passed even half way along the pulmonary capillary. o In a normal long, diffusion of both oxygen and carbon dioxide is accomplished within 1/3 of the transit time. Pulmonary blood flow: - Pulmonary circulation and blood pressure: o Differences between systemic and pulmonary circulation: Blood pressure is lower in the pulmonary circulation The walls of the pulmonary capillaries are thinner than those of the systemic circulation. The mean pulmonary artery pressure is about 15mmHg while the left atrial pressure is about 5mmHg. 5 - - - - - Vascular resistance: o Remember that flow = pressure/resistance o The pulmonary resistance is 1/10 that of the systemic circulation. o The low vascular resistance in the pulmonary circulation relies on the thin walls of the vascular system o Pulmonary circulation = low vascular resistance and high compliance. This allows the lungs to accept the whole cardiac output at all times. o Because of the high compliance, the vessels are affected by pressure at all time. o When the alveolar pressure increases above the pressure in the capillaries, they collapse. o On the other hand, arterioles and veins are pulled open when lungs expand because they are subjected to intrapleural pressure. Accommodation of pulmonary blood vessels: o 2 methods of accommodation are used to decrease vascular resistance in the lungs: Distension: already perfused blood vessels increase their diameter. Recruitment: previously closed vessels may open as the cardiac output rises. o Drugs: Drugs such as serotonin, histamine, NE, which cause the contraction of smooth muscle increase pulmonary resistance in the larger pulmonary arteries Drugs such as acetylcholine and isoproteranol, which can relax smooth muscle, may decrease pulmonary vascular resistance. Effects of gravity on pulmonary blood flow: o In upright position, blood flow increases almost linearly from top to bottom, because gravity distends blood vessels at the bottom of the lungs, while the capillaries at the top may be completely compressed if pressure is greater in alveoli than in capillaries. Effects of gravity on ventilation: o Ventilation occurs preferentially at the bottom than at the top of the lungs because the alveoli are more opened at the bottom than at the top of the lungs (think of the slinky demonstration). Distribution of ventilation perfusion ration in the lungs in normal gravity: o Ventilation increases from top to bottom of the lung, but blood flow increases more rapidly. o Therefore, the ventilation-perfusion ratio is abnormally high at the top and much lower at the bottom. Transport of oxygen and carbon dioxide: - Oxygen physically dissolved in plasma: o Henry’s law: the number of gas molecules dissolved in a liquid is proportional to the partial pressure of the gas above the liquid. o Because oxygen is relatively insoluble in water, the amount of oxygen dissolved in blood is small and proportional to the partial pressure of oxygen (0,3ml O2 / 100ml plasma). o However, the metabolic need for oxygen is much greater than the amount dissolved in blood so there must be another way of transporting oxygen in blood. 6 - - - - Oxygen bound to hemoglobin: o Found in red blood cells o Increases the amount of oxygen transported by 65x at partial pressure of oxygen of 100mmHg o Each molecule of hemoglobin consists of a heme (iron porphyrin) joined to a globin (protein) o Consists of 4 polypeptide chains, each containing a Fe++ that can bind 1 molecule of oxygen. o It is essential for the transport of oxygen because it combines rapidly and reversibly with it. o Note that oxygen that is bound to Hb does not contribute to the partial pressure of oxygen in blood. However, the partial pressure of oxygen in plasma determines the amount of oxygen that combines with Hb. The oxygen dissociation curve: o The HbO2 dissociation curve determines the amount of oxygen by hemoglobin for a given partial pressure of oxygen. o The curve is flat at high pressures of oxygen (in alveoli) and steep at low pressures of oxygen (in peripheral tissues) o Thus, at small values of PO2, as seen in peripheral tissues, a small drop in PO2 unloads the oxygen from hemoglobin to the tissue. o This provides an automatic mechanism that matches tissue oxygen supply to tissue oxygen need. o In the muscle cell, a similar substance to hemoglobin has been found: myoglobin. Its major function is to act as an intracellular carrier which facilitates the diffusion of oxygen throughout the muscle cell. o The total amount of oxygen in the blood depends mostly on the concentration of hemoglobin. The Bohr effect: o Bohr effect: shift of the HbO2 dissociation curve to the right when blood carbon dioxide or temperature increases, or blood pH decreases. o The curve shifting to the right means that for a given drop in oxygen pressure, an additional amount of oxygen is released from hemoglobin to the working tissues. o This has almost no effect on the total amount of oxygen combined with hemoglobin above 80mmHg. Transport of CO2: o Physically dissolved in blood (10%) o Combined to Hb to form HbCO2 (11%): it combines with the globin portion of Hb, not with the heme portion, as oxygen does. Therefore there is no competition for binding site. o As bicarbonate (79%): carbon dioxide combines with water to form carbonic acid. This reaction is enhanced by carbonic anhydrase. 7 - - - The Haldane effect: o In the tissue capillaries, Hb free of oxygen may act as a buffer and combine with H+. This occurs because reduced Hb is less acidic than HbO2. o Therefore, the presence of reduced Hb in the tissue capillaries helps with the blood loading of capillaries by pushing equations 1 and 2 to the right. o Result: for a given partial pressure of carbon dioxide, more CO2 is carried in deoxygenated blood than in oxygenated blood. Respiratory failure: o Occurs when the respiratory system is unable to do its job properly, due to failure of: The gas exchanging capabilities of the lungs The neural control of ventilation The neuromuscular breathing apparatus (respiratory muscles and their innervation) Arterial hypoxia (hypoxemia): o Deficient blood oxygenation o There are 5 general causes of hypoxia: Inhalation of low PO2 Hypoventilation Ventilation/perfusion imbalance in the lungs. Shunts of blood across the lungs. Oxygen diffusion impairment. Important equations: - Measurement of FRC: o FRC can be measured by helium dilution. o You put a given volume of helium, whit a known concentration, in a spirometer and you ask the patient to breath in and out from the spirometer until equilibrium is reached. FRC = (C1 x V1/C2) – V1 o Where: o C1 is the concentration of helium in the spirometer at the beginning o V1 is the volume of helium in the spirometer o C2 is the concentration of helium in the spirometer after equilibration. - Minute ventilation: VE = VT x f o Where VT is the tidal volume and f is the number of breaths per minute o Note that there should be a dot over VE to indicate that it is a change with respect to time. - Alveolar ventilation VA = VE –VD o Where VD is the volume f the anatomical dead space o Note that there should be a dot over each of the values in the equation o Anatomical dead space is around 150mL in the average adult. A good estimation is the subject’s weight in pounds. 8