Respiratory Physiology (Lecture Note) PDF

RESPIRATORY PHYSIOLOGY (LECTURE NOTE) Yusuf B. For CCUK  Course objectives At the end of the course, students should be able to – Describe structure and functions of the respiratory system – List the passages through which air passes from the exterior to the al...

RESPIRATORY PHYSIOLOGY (LECTURE NOTE) Yusuf B. For CCUK  Course objectives At the end of the course, students should be able to – Describe structure and functions of the respiratory system – List the passages through which air passes from the exterior to the alveoli. – List the major muscles involved in respiration, and state the role of each. – Explain the mechanism of breathing – Explain pulmonary blood flow and circulation – Describe pulmonary ventilation and lung compliance, and role of surfactants – State and explain lung volumes and capacities and the pulmonary function test – Describe composition of inspired air, expired air and alveolar air, and physiologic and anatomic dead space – Explain the transport of respiratory gases – Describe control of respiration and respiratory changes in various conditions (i.e. exercise, high altitude and deep sea)  INTRODUCTION Respiration is process of exchange of gases between the living organism and external environment through breathing. The goal of respiration is to provide oxygen to the tissues and to remove carbon dioxide. The respiratory system provides for gas exchange—intake of O2 and elimination of CO2 Respiratory system does not participate in all stages of respiration, instead, respiratory system work together with cardiovascular system (cardiopulmonary system)  PHYSIOLOGIC ANATOMY Respiratory system is composed of the nose, pharynx, larynx, trachea, bronchi, bronchioles and lungs. Structurally, the respiratory system consists of: – The upper respiratory system: the nose, nasal cavity, pharynx, and associated structures and – The lower respiratory system: the larynx, trachea, bronchi and lungs. Functionally, the nasal cavity, pharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles constitute the conducting zone, a series of interconnecting cavities and tubes which function to filter, warm, and moisten air and conduct it into the lungs. The respiratory zone is part of the respiratory system where gas exchange occurs. These include the respiratory bronchioles, alveolar ducts, alveolar sacs and alveoli. They are the main sites of gas exchange between air and blood.  THE LUNGS The lungs are paired cone shaped organs that are separated by the mediastinum Each lung is enclosed and protected by a double-layered serous membrane called the pleural membrane The outer parietal pleura lines the wall of the thoracic cavity, while the inner visceral pleura covers the lungs themselves The parietal and visceral pleurae are separated by pleural cavity containing pleural fluid, a lubricating fluid secreted by the membranes. The pleural fluid reduces friction between the membranes, allowing them to slide easily over one another during breathing and also produce surface tension. The lung is divided by fissures into lobes, and each lobe receive its own lobar bronchi  The structural and functional unit of lungs is called the respiratory unit. Exchange of gases occur only through the respiratory unit The respiratory unit is made of the respiratory bronchioles, alveolar ducts, alveolar sacs and the alveoli.  Alveolus The alveolus is a pouch like structure with a diameter of about 0.2 to 0.5 mm, lined by epithelial cells (pneumocytes). There are 2 types of alveolar pneumocytes; type I and type II Type I alveolar cells are the squamous epithelial cells that form about 95% of the total number of cells. They form the site of gaseous exchange between the alveolus and blood. Type II alveolar cells are cuboidal in nature and form about 5% of alveolar cells. These cells are also called granular pneumocytes and they secrete alveolar fluid and surfactant.  Surfactant Surfactant is a surface active agent in water. It greatly reduces the surface tension of water. Surfactant is a complex mixture of several phospholipids, proteins, and ions (mostly calcium). The most important components are the phospholipid (dipalmitoylphosphatidylcholine), surfactant apoproteins, and calcium ions. The phospholipid is responsible for reducing the surface tension. It lowers the surface tension of alveolar fluid, which reduces the tendency of alveoli to collapse and thus maintains their patency It is secreted by type II alveolar cells (type II pneumocytes), which contain microvilli on their alveolar surface and constitute about 10 per cent of the alveoli. Functions of surfactant Surfactant reduces the surface tension in the alveoli of lungs and prevents collapsing tendency of lungs. It plays an important role in the inflation of lungs after birth. It play a role in defense within the lungs against infection and inflammation. Deficiency of surfactant causes respiratory distress syndrome. Factors that influence formation of the lung surfactants The formation of lung surfactant is stimulated by: – thyroid hormones and glucocorticoids, surfactant proteins (SP-B, SP-C) which are produced by degradation of lung surfactant. Another surfactant protein (SP-A) regulates the uptake of (SP-C) by type II pneumocytes. Formation of surfactant is inhibited by: – insulin, smoking, long term inhalation of pure oxygen, and cessation of the pulmonary circulation for a long time (as in open heart surgery when the patient is put on pump oxygenator). Respiratory distress syndrome (RDS) Respiratory distress syndrome is a breathing disorder of premature newborns in which the alveoli do not remain open due to a lack of surfactant. The more premature the newborn, the greater the chance that RDS will develop. RDS is more common in infants whose mothers have diabetes and in males Symptoms include labored and irregular breathing, flaring of the nostrils during inhalation, grunting during exhalation, and cyanosis (blue skin colour). It can be managed by delivering oxygen to the baby  PULMONARY BLOOD FLOW AND CIRCULATION From the right ventricle of the heart, deoxygeneted blood is carried by the pulmonary artery to the lungs for oxygenation. Oxygenated blood return to the left atrium via the pulmonary vein The lung tissue is supplied with oxygen and nutrients thru the bronchial artery, a branch of descending thoracic aorta. Venous drainage is by bronchial vein. Right bronchial vein drain into azygos vein, while the left bronchial veins drain into acessory hemiazygos or left superior intercostal veins. Some deoxygenated blood from bronchial circulation empties into pulmonary veins and pass to the left atrium, forming a physiologic shunt.  Blood flow to pulmonary circulation = cardiac output (5L/min) Pulmonary blood vessels are more distensible than systemic blood vessels, thus, the blood pressure is less in pulmonary blood vessels. The pulmonary vascular system is a low pressure bed. – Pulmonary Arterial Pressure: Systolic pressure : 25 mm Hg Diastolic pressure : 10 mm Hg Mean arterial pressure : 15 mm Hg. Pulmonary capillary pressure is about 7 mm Hg. This pressure is sufficient for exchange of gases between alveoli and blood. Factors that regulate pulmonary blood flow include: – Cardiac output – Vascular resistance – Nervous factors – Chemical factors – Gravity and hydrostatic pressure.  Other functions of the respiratory system include – regulating blood pH, – contains receptors for the sense of smell, – Filters inspired air, – Defense against infection. In the alveolar cavity, there are large phagocytic cells called the pulmonary alveolar macrophages (PAMs). – Regulate body temperature by removing water and heat in exhaled air – Secrete angiotensin converting enzyme – Secrete heparin from mast cells – Synthesize hormones, e.g. prostaglandins , acetylcholine, serotonin – produces sounds, and – Serves as blood reservoir.  PULMONARY VENTILATION Air flows between the atmosphere and the alveoli of the lungs because of alternating pressure differences created by contraction and relaxation of respiratory muscles. The rate of airflow and the amount of effort needed for breathing are also influenced by alveolar surface tension, compliance of the lungs, and airway resistance Respiration occurs in two phases; inspiration and expiration. Air moves into the lungs when the air pressure inside the lungs is less than the air pressure in the atmosphere. Air moves out of the lungs when the air pressure inside the lungs is greater than the air pressure in the atmosphere.  Pulmonary ventilation is defined as the volume of air that moves in and out of respiratory tract in a given unit of time during quiet breathing. It is also called minute ventilation or respiratory minute volume (RMV). Pulmonary ventilation is a cyclic process, by which fresh air enters the lungs and an equal volume of air leaves the lungs. Normal value of pulmonary ventilation is 6,000 mL (6 L)/minute. It is the product of tidal volume (TV) and respiratory rate (RR). – Tidal volume × Respiratory rate – 500 mL × 12 breaths/minute =6,000 mL/minute.  Breathing is the act of inspiration and expiration, which occurs in a regular cyclical manner. During rest a breathing cycle consists of 3 phases: inspiration, expiration, followed by a short expiratory pause. Breathing occurs regularly at a rate of 12- 15 breaths per minute in adults Eupnea = Easy breathing during rest. Tachypnea = Increase in frequency without increase in depth of breathing. Hyperpnea = Increase in frequency and depth of breathing. qAQaMuscles of breathing Primary inspiratory muscles are the external intercostal muscles, supplied by intercostal nerves (T1 to T11), and the diaphragm, which is supplied by phrenic nerve (C3 to C5). Accessory inspiratory muscles; sternocleidomastoid, scalene, serratus anterior, levator scapulae and pectoral muscles. Primary expiratory muscles are the internal intercostal muscles, which are innervated by intercostal nerves. Accessory expiratory muscles; serratus superior, inferior, rectus abdominis. Respiratory pressures Two types of pressures are exerted in the thoracic cavity and lungs during process of respiration: Intra-pleural pressure or intra-thoracic pressure: pressure existing in pleural cavity, between the visceral and parietal layers of pleura. It is exerted by the suction of the fluid that lines the pleural cavity. It is always negative to (less than) atmospheric pressure. The normal pleural pressure at rest is about –5 mmHg. This is the amount of pressure required to hold the lungs open to their resting level. During normal inspiration, expansion of the chest cage pulls outward on the lungs with greater force and creates more negative pressure, to an average of about –7.5 mmHg.  Intra-alveolar pressure or intra-pulmonary pressure: pressure of air existing in the lung alveoli. At rest (between breaths), it is equal to atmospheric pressure. It becomes negative during inspiration and positive during expiration During normal inspiration, alveolar pressure decreases to about –3 mmHg This slight negative pressure is enough to pull 0.5 liter of air into the lungs during normal quiet inspiration. During expiration, the alveolar pressure rises to about +3 mmHg, and this forces the 0.5 liter of inspired air out of the lungs. The difference between the alveolar pressure and the pleural pressure gives the transpulmonary pressure. It is the pressure difference between that in the alveoli and that on the outer surfaces of the lungs. It is a measure of the elastic forces in the lungs that tend to collapse the lungs (recoil pressure). Mechanism of breathing Boyle’s law: pressure α 1/volume When volume ↓se, pressure ↑se At rest, the intra-pulmonary (intra-alveolar) pressure is equal to atmospheric pressure. During inspiration, contraction of external intercostal muscles move the ribs upward and outward, causing an increase in the anteroposterior and lateral diameters of the thorax The dome-shaped diaphragm also contract and move downward, towards the abdomen, causing increase in vertical diameter of the thorax The above two phenomenon cause increase in volume of the thoracic cavity. The intra-pulmonary pressure now decreases, becoming lower than atmospheric pressure. Air moves into the lungs NB: Contraction of the external intercostals is responsible for about 25% of the air that enters the lungs during normal quiet breathing.  Normal expiration during quiet breathing is a passive process because no muscular contractions are involved. Expiration results from elastic recoil of the lungs and chest wall, both of which have a natural tendency to recoil after they have been stretched. As the diaphragm relaxes, its dome moves superiorly owing to its elasticity. As the external intercostals relax, the ribs are depressed. These movements decrease the vertical, lateral, and anteroposterior diameters of the thoracic cavity, which decreases lung volume. In turn, the alveolar pressure increases above atmospheric pressure Air then flows from the area of higher pressure in the alveoli to the area of lower pressure in the atmosphere  The respiratory membrane Exchange of O2 and CO2 between the air in the lungs and the blood takes place by diffusion across the alveolar and capillary walls, which together form the respiratory membrane It is formed by the alveolar membrane and capillary membrane, and separates air in the alveoli from the blood in capillary. The respiratory membrane consists of four layers: A layer of type I and type II alveolar cells and associated alveolar macrophages that constitutes the alveolar wall An epithelial basement membrane underlying the alveolar wall A capillary basement membrane that is often fused to the epithelial basement membrane The capillary endothelium  LUNG COMPLIANCE Compliance is defined as change in volume per unit change in pressure It is the ability of the lungs and thorax to expand, i.e. it is the expansibility of lungs and thorax. Compliance is a measure of stiffness of lungs. The stiffer the lungs, the less is the compliance Compliance refers to how much effort is required to stretch the lungs and chest wall. High compliance means that the lungs and chest wall expand easily; low compliance means that they resist expansion. Lung compliance is related to elasticity and surface tension. The lungs normally have high compliance and expand easily because elastic fibers in lung tissue are easily stretched and surfactant in alveolar fluid reduces surface tension.  Factors that increase lung compliance include old age, Emphysema (due to destruction of elastic fibers in alveolar walls). Factors that decrease lung compliance include: – Lung compliance decreases in conditions such as tuberculosis, pulmonary edema, deficiency of surfactant (respiratory distress syndrome), paralysis of the intercostal muscles, – Fibrotic pleurisy (inflammation of pleura resulting in fibrosis) – Paralysis of respiratory muscles – Pleural effusion (accumulation of large amount of fluid in pleural cavity) – Pneumothorax (presence of air), hydrothorax (presence of water), hemothorax (blood in thorax) and pyothorax (accumulation of pus in pleural cavity). – Lung compliance is lower in lungs with smaller size(e.g. a patient with one lung has approximately half the compliance of a normal person) – It is lower during inspiration than during expiration. Work of breathing Work of breathing is the work done by respiratory muscles during breathing to overcome the resistance in thorax and respiratory tract During normal quiet breathing, all respiratory muscle contraction occurs during inspiration, while expiration is almost entirely a passive process caused by elastic recoil of the lungs and chest cage. Thus, under resting conditions, the respiratory muscles perform “work” to cause inspiration but not to cause expiration. During the work of breathing, the energy is utilized to overcome three types of resistance: – Elastic resistance of lungs and thorax (compliance) – Nonelastic viscous resistance (tissue resistance). – Airway resistance Thus, the work of inspiration can be divided into three fractions: – (1) that required to expand the lungs against the lung and chest elastic forces, called compliance work or elastic work; – (2) that required to overcome the viscosity of the lung and chest wall structures, called tissue resistance work; and – (3) that required to overcome airway resistance to movement of air into the lungs, called airway resistance work. LUNG VOLUMES AND CAPACITIES AND LUNG FUNCTION TEST The lung volumes are the volumes of air associated with different phases of the respiratory cycle They are directly measured while lung capacities are inferred from the lung volumes They are correlated with body size, gender, age etc There are four lung volumes: Vt, IRV, ERV and RV  Tidal volume: Amount of air breathed in or out of the lungs during normal quiet breathing. About 500mL Inspiratory reserve volume: Extra amount of air that can be inspired forcefully after normal inspiration. About 3300mL Expiratory reserve volume: Amount of air that can be expired forcefully after normal expiration. About 1000mL Residual volume: minimum amount of air that remains in the lungs after maximal expiratory effort. About 1200mL. It helps to decrease the surface tension whereby allowing the alveoli to be inflated easily.  LUNG CAPACITIES Lung capacities are the combinations of two or more lung volumes added together. We have: Vital capacity: TV + IRV + ERV Inspiratory capacity: TV + IRV Expiratory capacity: TV + ERV Functional residual capacity: ERV + RV Total lung capacity: TV + IRV + ERV + RV  The lung volumes and capacities are measured using a spirometer Graphical record of lung volumes using spirometer is a Spirogram Spirometer cannot be used to measure residual volume, instead, RV is measured by helium dilution technique among others  Effects of Aging on Lung Volumes Lung elasticity decreases Hence, Residual volumes increase Therefore, VC decreases, however TLC do not decreases significantly. Pathological Conditions Affecting The Lung Volumes and Capacities Diseases that decrease Vital Capacity Poliomyelitis: due to damage to phrenic N Myopathies Pulmonary fibrosis Infections E.g: when there is excessive fluid in the pleural cavity Timed Vital Capacity/Force Expiratory Volume (FEV) FEV is the volume of air, which can be expired forcefully in a given unit of time (after a deep inspiration). It is a dynamic lung volume. – FEV1 = Volume of air expired forcefully in 1 second – FEV2 = Volume of air expired forcefully in 2 seconds – FEV3 = Volume of air expired forcefully in 3 seconds Normal FEV1 is about 80% of the vital capacity.  FEV1 is a test for the airway resistance. In obstructive lung diseases (e.g. bronchial asthma) vital capacity is reduced and FEV1 is markedly reduced. FEV is highly reduced in obstructive diseases (like asthma and emphysema), and is slightly reduced in some restrictive respiratory diseases like fibrosis of lungs Peak Expiratory Flow Rate (PEFR) Is the maximum rate at which the air can be expired after a deep inspiration It is normally about 400 litres/min. It is the measure of the power of muscles of expiration and the respiratory airway resistance. It is measured by using Wright peak flow meter  It is reduced in conditions that weakens the expiratory muscles or increase the airway resistance. PEFR is useful for assessing respiratory diseases PEFR is reduced in all type of respiratory disease. However, reduction is more significant in the obstructive diseases than in the restrictive diseases. Thus, in restrictive diseases, the PEFR is 200 L/minute and in obstructive diseases, it is only 100 L/minute  ABNORMALITIES OF BREATHING Apnea: Apnea is defined as the temporary arrest of breathing (absence of breathing). Apnea can be produced voluntarily, which is called breath holding or voluntary apnea Apnea occurs voluntarily, after hyperventilation or during swallowing (deglutition apnea) Clinically, apnea is classified into: Obstructive Apnea Occurs because of airway obstruction mainly due to excess tissue growth like tonsils and adenoids.  Common obstructive apnea occurs in sleep (Sleep apnea) Sleep apnea is the temporary stoppage of breathing that occurs repeatedly during sleep. It commonly affects overweight people. Major cause for sleep apnea is obstruction of upper respiratory tract by excess tissue growth in airway, like enlarged tonsils and large tongue. It is characterized by loud snoring. Central Apnea Central apnea occurs due to brain disorders, especially when the respiratory centers are affected. It is seen in premature babies and is characterized by a short pause in between breathing. Hyperventilation Hyperventilation means increased pulmonary ventilation due to forced breathing. In hyperventilation, both rate and force of breathing are increased and a large amount of air moves in and out of lungs. Thus, pulmonary ventilation is increased to a great extent. Very often, hyperventilation leads to dizziness, discomfort and chest pain Hyperventilation may be produced voluntarily or during exercise Hypoventilation Hypoventilation is the decrease in pulmonary ventilation caused by decrease in rate or force of breathing. The amount of air moving in and out of lungs is reduced. „Hypoventilation occurs when respiratory centers are suppressed or by administration of some drugs. It occurs during partial paralysis of respiratory muscles Dyspnea Dyspnea means difficulty in breathing. Physiologically, dyspnea can occur during severe muscular exercise It can also occur due to respiratory disorder (e.g. pneumonia, pulmonary oedema), cardiac disorder (left ventricular failure, mitral stenosis), or metabolic disorder (like diabetic acidosis, uremia). Emphysema Emphysema is a disorder characterized by destruction of the walls of the alveoli, producing abnormally large air spaces that remain filled with air during exhalation. It causes less surface area for gas exchange, and O2 diffusion across the damaged respiratory membrane is reduced. Blood O2 level is decreased, and any mild exercise that raises the O2 requirements of the cells leaves the patient breathless. It is generally caused by a long-term irritation; cigarette smoke, air pollution, and occupational exposure to industrial dust.  GASEOUS EXCHANGE The ultimate purpose of breathing is to: Provide a continual supply of fresh oxygen and Remove C02 unloaded from the blood The blood serve as a transport medum for 02 and C02 between the lungs and the tissues Gas exchange occurs down partial pressure gradients by simple passive diffusion  At the pulmonary, alveolar P02 is relatively high while the PC02 is relatively low In contrast, the systemic venous blood entering the lungs is relatively low in 02 and high in C02 having given up 02 and picked up C02 at the systemic capillary level  Gases diffuse along their pressure gradient Partial pressure of oxygen in the atmospheric air is 159 mm Hg and in the alveoli, it is 104 mm Hg. Because of the pressure gradient of 55 mm Hg, oxygen easily enters from atmospheric air into the alveoli Partial pressure of oxygen in the pulmonary capillary is 40 mm Hg and in the alveoli, it is 104 mm Hg. Pressure gradient of 64 mm Hg facilitates the diffusion of oxygen from alveoli into the blood Partial pressure of carbon dioxide in alveoli is 40 mm Hg whereas in the blood it is 46 mm Hg. Pressure gradient of 6 mm Hg is responsible for the diffusion of carbon dioxide from blood into the alveoli  In atmospheric air, partial pressure of carbon dioxide is only about 0.3 mm Hg whereas, in the alveoli, it is 40 mm Hg. So, carbon dioxide passes to atmosphere from alveoli easily due to very high pressure gradient At the tissue level, Oxygen enters the cells of tissues from blood and carbon dioxide is expelled from cells into the blood also along pressure gradient. Partial pressure of oxygen in the arterial end of systemic capillary is only 95 mm Hg. Average oxygen tension in the tissues is 40 mmHg. Thus, a pressure gradient of about 55 mm Hg exists between capillary blood and the tissues so that oxygen can easily diffuse into the tissues Partial pressure of carbon dioxide is high in the cells and is about 46 mm Hg. Partial pressure of carbon dioxide in arterial blood is 40 mm Hg. Pressure gradient of 6 mm Hg is responsible for the diffusion of carbon dioxide from tissues to the blood  During strenuous exercise or other conditions that greatly increase pulmonary blood flow and alveolar ventilation, the diffusing capacity for oxygen increases to about 65 ml/min/mm Hg, This increase is caused by opening up of many previously dormant pulmonary capillaries or extra dilation of already open capillaries, thereby increasing the surface area of the blood into which the oxygen can diffuse, and also due to a increase in ventilation-perfusion ratio  ALVEOLAR VENTILATION The ultimate importance of pulmonary ventilation is to continually renew the air in the gas exchange areas of the lungs, where air is in proximity to the pulmonary blood. These areas include the alveoli, alveolar sacs, alveolar ducts, and respiratory bronchioles. The rate at which new air reaches these gas exchange areas is called alveolar ventilation. Alveolar ventilation is thus the amount of air utilized for gaseous exchange every minute Dead space air is excluded in alveolar ventilation Alveolar ventilation = (Tidal volume – Dead space) x RR – (500 – 150) mL × 12/minute = 4,200 mL (4.2 L)/minute.  Dead space Dead space is the part of the respiratory tract, where gaseous exchange does not take place. Air present in the dead space is called dead space air Dead space can be anatomical dead space or physiological dead space Anatomical dead space includes nose, pharynx, trachea, bronchi and branches of bronchi up to terminal bronchioles. These structures serve only as the passage for air movement, as gaseous exchange does not take place in these structures Physiological dead space includes anatomical dead space and also air in the alveoli which do not receive adequate blood flow, and in the alveoli which are non- functioning. In some respiratory diseases, alveoli do not function because of dysfunction or destruction of alveolar membrane. Dead space air is measured using Nitrogen washout method Normally, the anatomic and physiologic dead spaces are nearly equal because all alveoli are functional in the normal lung Normal volume of dead space air is 150 mL  Ventilation-perfusion ratio Ventilation-perfusion ratio is the ratio of alveolar ventilation and the amount of blood that perfuse the alveoli. Ventilation-perfusion ratio = VA/Q. – VA = alveolar ventilation (4,200mL/minute) – Q = pulmonary blood flow (5000mL/minute). Normal value = 0.84 Ventilation-perfusion ratio signifies the gaseous exchange. It is affected by change in alveolar ventilation or in blood flow. – Ventilation without perfusion = dead space – Perfusion without ventilation = shunt  TRANSPORT OF RESPIRATORY GASES Exchange of respiratory gases takes place at the lungs and tissue levels by bulk flow diffusion. At the lungs, O2 diffuse from alveoli into the blood, and CO2 from blood to alveoli At tissue level, the opposite takes place. Oxygen transport consist of four steps: – Movt from air into alveoli (inspiration) – Diffusion from alveoli into blood – Transport to tissue and – Diffusion from systemic capillary into tissue  Diffusing capacity for oxygen is 21 mL/minute/1 mmHg. Diffusing capacity for carbon dioxide is 400 mL/minute/1 mmHg. Thus, the diffusing capacity for carbon dioxide is about 20 times more than that of oxygen Diffusing capacity is defined as the volume of gas that diffuses through the respiratory membrane each minute for a pressure gradient of 1 mmHg.  Factors Affecting Diffusing Capacity Diffusion capacity is directly proportional to: – Pressure gradient – Solubility of gas – Surface area of respiratory membrane It is inversely proportional to: – Molecular mass of gas – Thickness of respiratory membrane  Transport of oxygen Once oxygen has diffused from the alveoli into the pulmonary blood, it is transported to the peripheral tissues Oxygen is transported in two forms in the blood, i.e. dissolved in plasma (only 0.3mL/100mL) or in combination with haemoglobin (about 97%) Because of poor solubility of oxygen in water, only about 3% of O2 is transported by the plasma. Oxygen molecule combines loosely and reversibly with the heme portion of  When PO2 is high, as in the pulmonary capillaries, oxygen binds with the hemoglobin, but when PO2 is low, as in the tissue capillaries, oxygen is released from the haemoglobin Combination of oxygen with haemoglobin is only as a physical combination, i.e. it is only oxygenation and not oxidation, so that it can easily be released at the tissue. Haemoglobin combines with oxygen readily whenever the partial pressure of oxygen in the blood is more, while it releases it whenever the partial pressure of oxygen in the blood is less  At the lungs, oxygen diffuse from alveoli into pulmonary capillary and dissolve in plasma until PO2 rises to about 100mmHg. At equilibrium, plasma contain only 0.3mL of dissolved O2 per 100mL of total plasma O2 Due to this high oxygen tension in the plasma, it diffuses into the red blood cells and combine with haemoglobin Oxygen combines with the iron in heme part of haemoglobin.  Each molecule of haemoglobin contains 4 atoms of iron and each atom of iron combines with one molecule of oxygen. Thus, each molecule of Hb carries 4 molecules of oxygen Iron of the haemoglobin is present in ferrous form and after combination with oxygen, iron remains in ferrous form only. One gram of Hb transport 1.34mL of oxygen. Thus, oxygen carrying capacity of Hb is 1.34mL/g  Oxygen carrying capacity of blood refers to the amount of oxygen transported by blood. Blood contain about 15 g/dL of Hb. Since oxygen carrying capacity of hemoglobin is 1.34 mL/g, blood with 15 g/dL of Hb should carry 20.1 mL/dL of oxygen (i.e. 20.1 mL of oxygen in 100 mL of blood). But oxygen carrying capacity of blood is only 19 mL/dL because the haemoglobin is not fully saturated with oxygen. It is only 95% saturated.  Oxygen-haemoglobin dissociation curve The most important factor that determines how much O2 binds to hemoglobin is the PO2; the higher the PO2, the more O2 combines with Hb If a graph of the percentage saturation of Hb is plotted against partial pressures of O2, it gives a sigmoid shaped curve known as the oxygen-haemoglobin dissociation curve The curve shows the degree of saturation of haemoglobin at different partial pressures of oxygen. It demonstrates the relationship between partial pressure of oxygen and the percentage saturation of hemoglobin with oxygen. It explains hemoglobin’s affinity for oxygen. It demonstrates a progressive increase in the percentage of haemoglobin bound with oxygen as blood PO2 increases (per cent saturation of hemoglobin). Lower part of the curve indicates dissociation of oxygen from hemoglobin. Upper part of the curve indicates the uptake of oxygen by hemoglobin depending upon partial pressure of oxygen Because the blood leaving the lungs and entering the systemic arteries usually has a PO2 of about 95 mm Hg, the usual oxygen saturation of systemic arterial blood is about 97 percent. In normal venous blood returning from the peripheral tissues, the PO2 is about 40 mm Hg, and the saturation of hemoglobin is about 75 percent.  P50 is the partial pressure of oxygen at which hemoglobin is 50% saturated with oxygen. It is about 25 to 27 mm Hg At PO2 of 40 mm Hg, percentage saturation of Hb is 75%. It becomes 95% when the partial pressure of oxygen is 100 mm Hg.  Factors Affecting Oxygen- hemoglobin Dissociation Curve Oxygen-hemoglobin dissociation curve is shifted to left or right by various factors A shift to right indicates dissociation of oxygen from haemoglobin A shift to left indicates acceptance (association) of oxygen by haemoglobin Three important factors affect the oxygen– hemoglobin dissociation curve: – pH – Temperature – Concentration of 2,3-biphosphoglycerate (2,3-BPG), also called 2,3-diphosphoglycerate (2,3-DPG)  Factors that cause shift to the right: – Decrease in pH – Increased body temperature – Decrease in partial pressure of oxygen – Increase in partial pressure of carbon dioxide (Bohr effect) – Excess of 2,3-BPG in RBC. 2,3-BPG is a byproduct in Embden-Meyerhof pathway of carbohydrate metabolism. It combines with β-chains of hemoglobin. It increases in conditions like muscular exercise and in high attitude, so, the oxygen- haemoglobin dissociation curve shifts to right to release more O2.  Factors that cause shift to the left: – Increase in pH – Decreased body temperature – Increase in partial pressure of oxygen – Decrease in partial pressure of carbon dioxide – Presence of foetal haemoglobin. In foetal blood, because foetal hemoglobin has more affinity for oxygen than the adult haemoglobin  Bohr Effect Bohr effect is the effect by which presence of carbon dioxide decreases the affinity of haemoglobin for oxygen. In the tissues, due to continuous metabolic activities, the partial pressure of carbon dioxide is very high and carbon dioxide enters the blood Presence of carbon dioxide decreases the affinity of haemoglobin for oxygen, and enhance further release of oxygen to the tissues Shift of the oxygen-haemoglobin dissociation curve to the right in response to increases in blood carbon dioxide and hydrogen ions enhances the release of oxygen from the blood in the tissues and oxygenation of the blood Bohr effectin the was lungs. by Christian Bohr in 1904. postulated  As blood pass through the tissues, carbon dioxide diffuses from the tissue into the blood, thus, increasing the blood PCO2, which in turn raises the blood H2CO3 and the hydrogen ion concentration. These effects shift the oxygen-haemoglobin dissociation curve to the right and downward, forcing oxygen away from haemoglobin, and therefore delivering increased amounts of oxygen to the tissues.  In the lungs, the opposite effect occurs, where carbon dioxide diffuses from the blood into the alveoli, there by reducing the blood PCO2 and decreasing the hydrogen ion concentration, shifting the oxygen- haemoglobin dissociation curve to the left and upward, causing more oxygen to bind with Hb.  Transport of CO2 CO2 is transported in four ways: – 1. As dissolved form: dissolved in plasma as solution. Only 3mL/100mL (7%) is transported in this form – 2. As bicarbonate (63%): From plasma, CO2 enters the RBCs and combine with water to form carbonic acid (in the presence of carbonic anhydrase). Almost all carbonic acid (99.9%) then dissociates into bicarbonate and hydrogen ions. The bicarbonate ions diffuse through the cell membrane into plasma in exchange for chloride (chloride shift/ Hamburger phenomenon). Reverse chloride shift occurs in the lungd. The hydrogen ions dissociated from carbonic acid are buffered by hemoglobin inside the cell. – 3. As carbamino compounds (30%). In combination with Hb and Hamburger plasma proteins phenomenon was discovered by Hartog Jakob Hamburger in 1892 CO2 dissociation curve The amount of carbon dioxide combining with blood depends upon the partial pressure of carbon dioxide. Carbon dioxide dissociation curve is the curve that demonstrates the relationship between the partial pressure of carbon dioxide and the quantity of carbon dioxide that combines with blood.  Haldane Effect Haldane effect is the effect by which combination of oxygen with hemoglobin displaces carbon dioxide from hemoglobin. Excess of oxygen content in blood causes shift of the carbon dioxide dissociation curve to right. Due to the combination with oxygen, hemoglobin becomes strongly acidic. It causes displacement of carbon dioxide from haemoglobin because highly acidic hemoglobin has low tendency to combine with carbon dioxide, so carbon dioxide is displaced from blood. Haldane effect was first described by John Scott Haldane in 1860.  Also, because of the acidity, hydrogen ions are released in excess. Hydrogen ions bind with bicarbonate ions to form carbonic acid. Carbonic acid in turn dissociates into water and carbon dioxide and the carbon dioxide is released from blood into alveoli. Haldane effect is essential for release of carbon dioxide from blood into the alveoli of lungs and also for uptake of A B Exchange of O2 and CO2 in (A) pulmonary capillaries (external respiration) and (B) systemic capillaries (internal respiration)  CONTROL OF RESPIRATION Respiration is a reflex process, but it can be controlled voluntarily for a short period of time Respiration is controlled by two major mechanisms, i.e. nervous and chemical mechanisms  Nervous control of respiration The respiratory center is composed of several groups of neurons located bilaterally in the medulla oblongata and pons of the brain stem It is divided into three major collections – (1) a dorsal respiratory group (inspiratory center), located in the dorsal portion of the medulla, which mainly causes inspiration – (2) a ventral respiratory group (expiratory center), located in the ventrolateral part of the medulla, which mainly causes expiration and – (3) the pneumotaxic center (also called pontine respiratory group), located dorsally in the superior portion of the pons, which mainly controls rate and depth of breathing. The dorsal respiratory group of neurons plays the most fundamental role in the control of respiration  Dorsal respiratory group Dorsal respiratory group of neurons are inspiratory neurons situated in the nucleus of tractus solitarius present in the upper part of the medulla oblongata Nucleus of tractus solitarius is the sensory termination of both the vagal and the glossopharyngeal nerves, which transmit sensory signals into the respiratory center from peripheral chemoreceptors, baroreceptors and several types of receptors in the lungs. The basic rhythm of respiration is generated mainly in the dorsal respiratory group  During normal quiet breathing, neurons of the DRG send impulses to the diaphragm via the phrenic nerves and the external intercostal muscles via the intercostal nerves The diaphragm and external intercostals contract and inspiration occurs. When the DRG becomes inactive after two seconds, the diaphragm and external intercostals relax for about three seconds, allowing the passive recoil of the lungs and thoracic wall. Then, the cycle repeats itself.  The ventral respiratory group The ventral respiratory group of neurons are situated in nucleus ambiguous and nucleus retroambiguous in the medulla oblongata, anterior and lateral to the nucleus of tractus solitarius. It has both inspiratory neurons in the central area of the group, and expiratory neurons in the caudal and rostral areas of the group. Normally, ventral respiratory group is inactive during quiet breathing, but become active during forced breathing like during exercise, when playing a wind instrument, or at high altitudes.  They stimulate accessory inspiratory and expiratory muscles During forceful inhalation, nerve impulses from the DRG activate neurons of the VRG involved in forceful inhalation to send impulses to the accessory muscles of inhalation to contract, which result in forceful inhalation. During forceful exhalation, neurons of the VRG involved in forceful exhalation send impulses to the accessory muscles of exhalation to contract, resulting in forceful exhalation.  The pre-Botzinger complex is a cluster of neurons located in the VRG above the nucleus ambiguous and is believed to be important in the generation of the rhythm of breathing It receives sensory inputs form the nucleus of tractus solitarius and projects excitatory signals to the inspiratory neurons of the DRG and VRG and inhibitory signals to the expiratory neurons of the VRG. It is composed of pacemaker cells that set the basic rhythm of breathing The pacemaker cells send input to the DRG, driving the rate at which DRG neurons fire action potentials  Pneumotaxic center A pneumotaxic center is located in the nucleus parabrachialis and subparabrachial nuclei (also called ventral parabrachial or Kolliker-Fuse nucleus) located in the dorsolateral part of reticular formation in upper pons. It control the DRG by acting through apneustic center. It inhibits the apneustic center so that the dorsal group neurons are inhibited, thus, stopping inspiration and starting expiration The pneumotaxic center, therefore, influences the switching between inspiration and expiration. It increases respiratory rate by reducing the duration of inspiration  A strong pneumotaxic signal can increase the rate of breathing to 30 to 40 breaths per minute, whereas a weak pneumotaxic signal may reduce the rate to only 3 to 5 breaths per minute. The Apneustic center Apneustic center is situated in the reticular formation of lower pons. It increases depth of inspiration by acting directly on dorsal group neurons It has an inherent tonic activity which stimulated the inspiratory neurons of the DRG  Control of respiration from higher centers (cerebral cortex) Though breathing is an involuntary action, it can be controlled voluntarily, at least for some a short time due to voluntary impulses from cerebral cortex, e.g. taking a deep breath, or holding the breath under water or due to bad odour Higher centers alter respiration by sending impulses directly to dorsal group of neurons. Impulses from anterior cingulate gyrus, genu of corpus callosum, olfactory tubercle and posterior orbital gyrus of cerebral cortex inhibit respiration.  Impulses from motor area of cerebral cortex cause forced breathing When breath is held for some time, CO2 and H+ build up in the body. When PCO2 and H concentrations increase to a certain level, the DRG are strongly stimulated, and nerve impulses are sent along the phrenic and intercostal nerves to inspiratory muscles, and breathing resumes, whether the person likes it to or not Nerve impulses from the hypothalamus and limbic system also stimulate the respiratory center, allowing emotional stimuli to alter breathing as, for example, in laughing and crying  Ondine’s curse Is a pathological condition in which the nervous automatic breathing control is paralyzed, while the voluntary control system is retained. Person can stay alive only by staying awake and remembering to breathe, or maintained on mechanical respirator during sleep. This condition may develop in cases of bulbar poliomyelitis (poliomyelitis of the medulla oblongata) or due to compression of the medulla.  Hering-Breuer Reflex Stretch receptors (baroreceptors) are located in the walls of bronchi and bronchioles. When these receptors become stretched during overinflation of the lungs, nerve impulses are sent along the vagus nerves to the dorsal respiratory group (DRG) The DRG is inhibited and the diaphragm and external intercostals relax. As a result, further inhalation is stopped and exhalation begins.  As air leaves the lungs during exhalation, the lungs deflate and the stretch receptors are no longer stimulated. Thus, the DRG is no longer inhibited, and a new inhalation begins. This inflation-deflation reflex is referred to as the Hering–Breuer reflex It is a protective mechanism that prevents excessive inflation of the lungs, for example, during severe exercise,  Proprioceptor Stimulation of Breathing At the beginning of exercising, the rate and depth of breathing increase, even before changes in PO2, PCO2, or H level occur. The main stimulus for these quick changes in respiratory effort is input from proprioceptors, which monitor movement of joints and muscles. Nerve impulses from the proprioceptors stimulate the DRG. Axon collaterals (branches) of upper motor neurons that originate in the primary motor cortex (precentral gyrus) also feed excitatory impulses into the DRG NB: respiratory centers are also affected by impulses from baroreceptors, juxtacapillary (J) receptors in the wall of alveoli,  Chemical control of respiration Chemical mechanism of regulation of respiration is operated through the chemoreceptors. Chemoreceptors are sensitive to hypoxia (decreased O2 conc), hypercapnea (increased CO2 conc) and acidosis (increased H+ conc/decrease pH) Chemoreceptors can be central chemoreceptors (in brain) or peripheral chemoreceptors. Central chemoreceptors are situated in deeper part of medulla oblongata, in close proximity and connected to the DRG.  They are in close contact with blood and cerebrospinal fluid and are responsible for 70% to 80% of increased ventilation through chemical regulatory mechanism. Main stimulant for central chemoreceptors is the increased hydrogen ion concentration. Blood H+ cannot cross blood brain barrier and blood-cerebrospinal fluid barrier. If carbon dioxide increases in the blood, it can easily cross the blood brain barrier and blood cerebrospinal fluid barrier and enter the interstitial fluid of brain or the cerebrospinal fluid.  There, the carbon dioxide combines with water to form carbonic acid, which dissociates into hydrogen ion and bicarbonate ion Hydrogen ions stimulate the central chemoreceptors. From chemoreceptors, the excitatory impulses are sent to DRG, resulting in increased ventilation, and the excess carbon dioxide is washed out and respiration is brought back to normal Peripheral chemoreceptors are the chemoreceptors present in carotid and aortic bodies and are stimulated mainly by hypoxia. Aortic bodies are supplied by the vagus nerves, while the carotid bodies are supplied by the glossopharyngeal nerves.  Hypoxia cause stimulation of aortic and Hering nerves which excite the DRG, resulting in increased ventilation. This provides enough oxygen and rectifies the hypoxia In addition to hypoxia, peripheral chemoreceptors are also mildly stimulated by hypercapnea and increased hydrogen ion concentration.  HYPOXIA Hypoxia = abnormal decreased oxygen in tissue Decreased blood supply to tissue = ischaemia Hypoxia can be – hypoxic hypoxia – anaemic hypoxia – stagnant hypoxia or – histotoxic hypoxia Hypoxic hypoxia is due to reduction in PO2 in arterial blood. It may caused by inspiring low O2 air (e.g. in high altitude), decrease pulmonary ventilation (e.g. in pneumothorax, paralysis of respiratory muscles, etc), insufficient lung perfusion.  In anaemic hypoxia, the oxygen carrying capacity of blood is decreased as a result of anaemia, cyanide or CO poisoning Stagnant hypoxia is as a result of sluggish blood flow to tissue (e.g. due to shock, haemorrhage, embolism/thrombosis or congestive heart failure) In histotoxic hypoxia, there is anability of the body cells to utilize O2 supplied to them due to cyanide or sulfide poisoning. These poisonous substances destroy the cellular oxidative enzymes and there is a complete paralysis of cytochrome oxidase system. So, even if oxygen is supplied, the tissues are not in a position to utilize it.  HYPERCAPNEA Hypercapnea is the increased carbon dioxide content of blood. „ Hypercapnea occurs in conditions, which leads to blockage of respiratory pathway, as in case of asphyxia. It also occurs while breathing the air containing excess carbon dioxide. During hypercapnea, the respiratory centers are stimulated excessively. It leads to dyspnea. The pH of blood reduces and blood becomes acidic. Hypercapnea is associated with tachycardia and increas ed blood pressure. There is flushing of skin due to peripheral vasodilatation. The nervous system is also affected, resulting in headache, depression and laziness. Muscular rigidity, fine tremors and generalized convulsions. Finally, giddiness and loss of consciousness occur.  HYPOCAPNEA Hypocapnea is the decreased carbon dioxide content in blood. „Hypocapnea occurs in conditions associated with hypoventilation. It also occurs after prolonged hyperventilation, because of washing out of excess carbon dioxide It cause depression of respiratory centers, leading to decreased rate and force of respiration. The pH of blood increases, leading to respiratory alkalosis. Calcium concentration decreases. It causes tetany (neuromuscular hyperexcitability and carpopedal spasm). Dizziness, mental confusion, muscular twitching and loss of consciousness also occur RESPIRATORY CHANGES IN EXERCISE ASSIGNMENT  RESPITRATORY CHANGES IN HIGH ALTITUDE High altitude is the region of earth located at an altitude of above 8,000 feet above sea level. When ascending to high altitude, atmospheric pressure falls and the amount of air in the environment decreases. PO and PN also fall proportionately 2 2 Barometric pressure decreases to about 523mmHg at altitude of 10,000 feet above sea level At 50,000 feet, it decreases further to 87 mm Hg. As the barometric pressure decreases, the atmospheric oxygen partial pressure decreases proportionately  PO2 at sea level is 159 mm Hg, but at 50,000 feet, it decreases to only 18 mm Hg Though amount of oxygen in the atmosphere is same as that of sea level, PO 2 decreases proportionately due to decrease in barometric pressure This leads to hypoxia. When a person ascends to high altitude, especially by rapid ascent, the various systems in the body cannot cope with lowered oxygen tension and effects of hypoxia start. In order to be able to survive at such an altitude, the body has to acclimatize to the environment Acclimatization help the body to cope with adverse effects of hypoxia at high altitude  Acclimatization to high altitude include – Increased pulmonary ventilation: Increase in pulmonary ventilation is due to the stimulation of chemoreceptors – Increased O2 Diffusing Capacity of The Lung: Due to increased pulmonary blood flow and increased ventilation, diffusing capacity of gases increases in alveoli. It enables more diffusion of oxygen in blood – Stimulation of Erythropoiesis: RBC count increases and packed cell volume increases to about 59%. Hemoglobin concentration rises to 20g/dL – Circulatory/Cardiovascular Adjustments: vasodilatation, increase in rate and force of contraction of the heart and increased cardiac output. Increased cardiac output increases the pulmonary blood flow and pressure, leading to pulmonary hypertension that may be associated with right ventricular hypertrophy Cellular Acclimatization: there is increase in number of mitochondria and oxidation enzymes involved in metabolic reaction, and also increase in vascularity in tissues (angiogenesis) – There is increase in 2,3 – DPG level which increase oxygen delivery to tissues  Mountain sickness It is a condition characterized by adverse effects of hypoxia at high altitude, usually in first timers. It occurs within a day in these persons, before they get acclimatized to the altitude Symptoms include: – Loss of appetite, nausea and vomiting – Increase heart rate and force of contraction – Increased pulmonary blood pressure results in pulmonary edema, which causes breathlessness. – Because of cerebral oedema, there is headache, depression, disorientation, irritability, lack of sleep, weakness and fatigue. Sudden exposure to hypoxia in high altitude causes vasodilatation in brain, which leads to increased capillary pressure and leakage of fluid from capillaries into the brain tissues Symptoms of mountain sickness disappear by breathing oxygen.  Occasionally, a person who remains at high altitude too long develops chronic mountain sickness The red cell mass and haematocrit become exceptionally high Pulmonary arterial pressure becomes too much elevated more than that which occurs during acclimatization, Right side of the heart becomes greatly enlarged Peripheral arterial pressure begins to fall Congestive heart failure ensues and death often follows unless the person is removed to a lower altitude.  DEEP SEA DIVING Exposure to hyperbaric conditions (high ambient pressure) occurs when one descends under water as in diving or with descent in a caisson for underwater construction work. In deep sea or mines, the barometric pressure increases significantly. Increased pressure leads to compression on the body and internal organs, and decrease in volume of gases. For every 10m of depth under the sea, pressure increases by 1 atm In order to prevent collapse of the lungs, the air breathed by the diver must be supplied under high pressure (hyperbaric air) Hyperbaric air contain oxygen, nitrogen and CO2  Nitrogen narcosis Narcosis = unconsciousness or stupor (lethargy with suppression of sensations and feelings/sleepy state). Nitrogen narcosis is the narcotic effect produced by nitrogen at high pressure. Under hyperbaric conditions, respiratory gases (O2, N2, CO2) become toxic, particularly to the nervous system. Nitrogen is soluble in fat. During compression by high barometric pressure in deep sea, nitrogen escapes from blood vessels and gets dissolved in the fat present in various parts of the body, especially the neuronal membranes. Dissolved nitrogen acts like an anesthetic agent, suppressing the neuronal excitability  It is common in deep sea divers, who breathe compressed air (air under high pressure). Breathing compressed air is essential for a deep sea diver or an underwater tunnel worker, in order to equalize the surrounding high pressure that is threatening to collapse the lungs. Nitrogen narcosis is characterized by an altered mental state, similar to alcoholic intoxication When a diver remains beneath the sea for an hour or more and is breathing compressed air, at about 120 ft, the first symptom of mild nitrogen narcosis appears  The diver becomes very jovial (marked euphoria), careless and does not understand the seriousness of the conditions. At 150 to 200 feet, the diver becomes drowsy. At 200 to 250 feet, he becomes extremely fatigued and weak. There is loss of concentration and judgment. Ability to perform skilled work or movements (manual dexterity) is also lost. Beyond the depth of 250 ft (8.5 atmospheres pressure), the person becomes unconscious. Features of nitrogen narcosis are similar to those of alcoholic intoxication, hence, it is often called “ruptures of the depths” There is loss of memory and impaired intellectual functions. At greater depths manual dexterity is lost, there is clumsiness, drowsiness and narcosis (sleepy state).  Oxygen toxicity Oxygen toxicity is the increased oxygen content in tissues, beyond certain critical level. It occurs because of breathing pure oxygen with a high pressure of 2 to 3 atmosphere (hyperbaric oxygen). The extremely high tissue PO2 that occurs when oxygen is breathed at very high alveolar oxygen pressure can be detrimental to many of the body’s tissues.  If pure oxygen is breathed under pressure higher than 3 atm, oxygen free radicals are formed in the tissues which include superoxide free radical ‘O2- and hydrogen peroxide H2O2 which are highly oxidizing agents. The agents oxidize the polyunsaturated fatty acids of the cell membrane and the cellular enzymes systems causing severe damage to the cells. Breathing oxygen at 4 atmospheres pressure of oxygen (PO2 = 3040 mm Hg) will cause brain seizures followed by coma within 30 to 60 minutes. The seizures often occur without warning and are likely to be lethal to divers submerged beneath the sea.  Other symptoms of acute O2 toxicity includes nausea, muscle twitches, dizziness, visual disturbances, irritability, disorientation, convulsion and coma At a pressure of 4 atm (30m depth) convulsions and coma occur in about 30 minutes. The dangerous aspect of these symptoms is that they have rapid onset In this condition, an excess amount of oxygen is transported in plasma as dissolved form because oxygen carrying capacity of hemoglobin is limited to 1.34 mL/g.  Effects include Tracheobronchial irritation and pulmonary edema Metabolic rate increases in all the body tissues and the tissues are burnt out by excess heat. Heat also destroys cytochrome system, leading to damage of tissues. When brain is affected, first hyperirritability occurs. Later, it is followed by increased muscular twitching, ringing in ears and dizziness. Finally, the toxicity results in convulsions, coma and death.  Decompression sickness (Caisson diseases) Decompression sickness (a.k.a. dysbarism, compressed air sickness, caisson disease, bends or diver’s palsy )is the disorder that occurs when a person returns rapidly to normal surroundings (sea level) from the area of high atmospheric pressure like deep sea. High barometric pressure at deep sea leads to compression of gases in the body, which reduces the volume of the gases  If one dives in water while breathing air, he is exposed to high PN2. If he stays down for some time, large volumes of N2 dissolve in body fluids (one litre of nitrogen for each atmosphere). When nitrogen is compressed by high atmospheric pressure in deep sea, it escapes from blood vessels, enters the organs and gets dissolved in the fat of the tissues and tissue fluids (especially the brain tissues). On slow ascent up to the surface, N2 leaves the body fluids to the blood, then to the lungs where it is expired out in air. If the ascent was rapid “Decompression sickness” occurs.  Rapid ascent make N2 to leave the body fluids rapidly and make nitrogen bubbles in the tissue fluids and blood. The bubbles travel through blood vessels and ducts, obstructing blood flow and produce air embolism, leading to decompression sickness. As long as the person remains in deep sea, nitrogen remains in solution and does not cause any problem. Decompression sickness also occurs in a person who ascends up rapidly from sea level in an airplane without any precaution  Decompression sickness is characterized by: – severe pain in tissues, particularly the joints (bends) – Sensation of numbness, tingling or pricking (paresthesia) and itching – Temporary paralysis – Muscle cramps associated with severe pain – Coronary artery occlusion and coronary ischemia, caused by bubbles in the blood – Occlusion of blood vessels in brain and spinal cord – Damage of tissues of brain and spinal cord because of obstruction of blood vessels by the bubbles – Dizziness, paralysis of muscle, shortness of breath and choking – Fatigue, unconsciousness and death Decompression sickness is prevented by very slow ascent to sea level, with short stay at regular intervals. Stepwise ascent allows nitrogen to come back to the blood, without forming bubbles. If it occurs, it can be treated by hyperbaric oxygen therapy  Decompression sickness can also be prevented by using helium in the gas mixture instead of nitrogen Helium has only about one fifth the narcotic effect of nitrogen, and only about one half as much volume of helium dissolves in the body tissues as nitrogen, and the volume that does dissolve diffuses out of the tissues during decompression several times as rapidly as does nitrogen, thus reducing the problem of decompression sickness The low density of helium (one seventh the density of nitrogen) keeps the airway resistance at a minimum. Nitrogen is highly dense that airway resistance can increase extremely, thus, increasing the work of breathing even beyond endurance. SCUBA devise also minimize decompression sickness SCUBA (self-contained underwater breathing apparatus) SCUBA is a devise used by deep sea divers and the underwater tunnel workers, to prevent the ill effects of increased barometric pressure in deep sea or tunnels. This instrument can be easily carried and it contains air cylinders, valve system and a mask. The SCUBA devise make it is possible to breathe air or gas mixture without high pressure. Also, because of the valve system, only the amount of air necessary during inspiration enters the mask and the expired air is expelled out of the mask. Disadvantage of this instrument is that the person using this can remain in the sea or tunnel only for a short period. Especially, beyond the depth of 150 feet, the person can stay only for few minutes  PRACTICE Which structures are part of the conducting zone of the respiratory system? What functions do the respiratory and cardiovascular systems have in common? How many lobes and secondary bronchi are present in each lung? How many lobes and secondary bronchi are present in each lung? Describe the location, structure, and function of the trachea. Describe the structure of the bronchial tree. Why are the right and left lungs slightly different in size and shape? State the types of cells that make up the wall of an alveolus and their functions Exchange of respiratory gases occurs by diffusion across the respiratory membrane, discuss Define and state the contents of bronchopulmonary segment? Describe the mechanism of breathing and muscles involved in breathing State and describe the following laws in relation to respiration – Boyle’s law – Dalton’s law – Fick’s law – Henry’s law  Which of the following is NOT a function of the lungs? A. Metabolism B. Serves as a reservoir of blood C. immunity D. control of arterial blood pressure E. none of the above How does the intra-pleural and intra-alveolar pressures change during a normal, quiet breathing? Describe how alveolar surface tension, compliance, and airway resistance affect breathing If you breathe in as deeply as possible and then exhale as much air as you can, which lung capacity have you Demonstrated? Define FEV1 State the factors that make oxygen to enter pulmonary capillaries from alveoli and to enter tissue cells from systemic capillaries? Describe how the blood transports oxygen and carbon dioxide What is the most important factor that determines how much O2 binds to hemoglobin? As pH decreases or PCO2 increases, the affinity of haemoglobin for O2 declines. Discuss  Explain how exercise affects the oxygen-haemoglobin dissociation curve and its benefit to the exercising person Is O2 more available or less available to tissue cells when you have a fever? Why? How do temperature, H, PCO2, and 2,3-BPG influence the affinity of Hb for O2? Which nerve convey impulses from the respiratory center to the diaphragm? Describe the role of the following centers in breathing – Dorsal respiratory group – Ventral respiratory group – Pontine respiratory group The peripheral chemoreceptors are most sensitive to – A hypoxia – B acidosis – C hypercapnia An increase in arterial blood PCO2 stimulates – A. the dorsal respiratory group – B. the ventral respiratory group – C. apneustic centre  How do the cerebral cortex, levels of CO2 and O2, proprioceptors, inflation reflex, temperature changes, pain, and irritation of the airways modify breathing? On the summit of Mount Everest, where the barometric pressure is about 250 mm Hg, the partial pressure of O2 is about – A) 0.1 mm Hg. – B) 0.5 mm Hg. – C) 5 mm Hg. – D) 50 mm Hg. The vital capacity is – A) the amount of air that normally moves into (or out of) the lung with each respiration. – B) the amount of air that enters the lung but does not participate in gas exchange. – C) the largest amount of air maximally expired after forced inspiration. – D) the largest amount of gas that can be moved into and out of the lungs in 1 min. The tidal volume is – A) the amount of air that moves into (or out of) the lung with each respiration. – B) the amount of air that enters the lung but does not participate in gas exchange. – C) the largest amount of air expired after maximal expiratory effort. – D) the largest amount of gas that can be moved into and out of the lungs in 1 min.  Which of the following is responsible for the movement of O2 from the alveoli into the blood in the pulmonary capillaries? – A) active transport – B) filtration – C) secondary active transport – D) facilitated diffusion – E) passive diffusion Airway resistance – A) is increased if the lungs are removed and inflated with saline. – B) does not affect the work of breathing. – C) is increased in paraplegic patients. – D) is increased in asthma. – E) makes up 80% of the work of breathing. Surfactant lining the alveoli – A) helps prevent alveolar collapse. – B) is produced by alveolar type I cells and secreted into the alveolus. – C) is increased in the lungs of heavy smokers. – D) is a glycolipid complex.  Most of the CO2 transported in the blood is – A) dissolved in plasma. – B) in carbamino compounds formed from plasma proteins. – C) in carbamino compounds formed from hemoglobin. – D) as HCO3 Which of the following has the greatest effect on the ability of blood to transport oxygen? – A) hemoglobin concentration in the blood – B) pH of plasma – C) CO2 content of red blood cells – D) temperature of the blood The main respiratory control center – A) send out regular bursts of impulses to expiratory muscles during quiet respiration. – B) is unaffected by stimulation of pain receptors. – C) is located in the pons. – D) send out regular bursts of impulses to inspiratory muscles during quiet respiration. – E) is unaffected by impulses from the cerebral cortex. Intravenous lactic acid increases ventilation. The receptors responsible for this effect are located in the – A) medulla oblongata. – B) carotid bodies. – C) lung parenchyma. – D) aortic baroreceptors. – E) trachea and large bronchi Spontaneous respiration ceases after – A) transection of the brain stem above the pons. – B) transection of the brain stem at the caudal end of the medulla. – C) bilateral vagotomy. – D) bilateral vagotomy combined with transection of the brain stem at the superior border of the pons.  The following physiologic events that occur in vivo are listed in random order: – (1) decreased CSF pH; – (2) increased arterial PCO2; – (3) increased CSF PCO2; – (4) stimulation of medullary chemoreceptors; – (5) increased alveolar PCO2. What is the usual sequence in which they occur when they affect respiration? – A) 1, 2, 3, 4, 5 – B) 4, 1, 3, 2, 5 – C) 3, 4, 5, 1, 2 – D) 5, 2, 3, 1, 4 Which of the following is the first branching of the bronchial tree that has gas exchanging capabilities? – A. Terminal bronchioles. – B. Respiratory bronchioles. – C. Alveoli – D. segmental bronchi Which of the following is in the correct path of CO2 from the tissue to the atmosphere? – A). Reaction with H2O to make H2CO3, dissociation to H+ and HCO3-, H+ combines with imidazole side chain of hemoglobin, carried back to lungs as HHb+ and HCO3-, reverse reaction forms CO2. – B). O2 is metabolized to CO2, reaction with H2O to make H2CO3, H2CO3 combines with imidazole side chain of hemoglobin, H2CO3Hb+ is carried back to the lungs, reverse reaction forms CO2. – C). Reaction with H2O to make H2CO3, dissociation to H+ and HCO3-, HCO3- combines with imidazole side chain of hemoglobin, carried back to the lungs as HCO3-Hb+ and H+, reverse reaction forms CO2. – D). O2 is metabolized to CO2, reaction with H2O to make H2CO3, dissociation to H+ and HCO3-, carried back to lungs in this form, reverse reaction forms CO2.  Which of the following is TRUE at rest? – A. TLC>VC>TV>FRC – B. TLC>FRC>VC>TV – C. TLC>VC>FRC>TV – D. TLC>FRC>TV>VC Which of the following does NOT happen during inspiration? – A. The ribs move upward. – B. The diaphragm lifts up. – C. The antero-posterior dimensions of the chest are increased. – D. The tranverse dimensions of the thorax are increased. During inspiration, how does alveolar pressure compare to atmospheric pressure? – A. Alveolar pressure is greater than atmospheric. – B. Alveolar pressure is less than atmospheric. – C. Alveolar pressure is the same as atmospheric. Which of the following represents the pressure difference that acts to distend the lungs? – A. Alveolar pressure – B. Airway opening pressure – C. Transthoracic pressure – D. Transpulmonary pressure  If a patient had a progressive lung disease that required an ever increasing pressure to fill the same volume of lung, how would the lung's compliance be affected? – A. It would increase it. – B. It would stay the same. – C. It would decrease it.