2024 MEDSCI 142 Respiratory System PDF

Illustration from Fig. 23.08, Tortora & Grabowski “Principles of Anatomy and Physiology” 10th edition. John Wiley & Sons, New York. ISBN 978-0471415015 b...

Illustration from Fig. 23.08, Tortora & Grabowski “Principles of Anatomy and Physiology” 10th edition. John Wiley & Sons, New York. ISBN 978-0471415015 b A/Prof. Sue McGlashan 127 system Respiratory 5 Topic Prof. Julian Paton 4pm MEDSCI 142 COURSE GUIDE © 2024 4pm 128 MEDSCI 142 COURSE GUIDE © 2024  129 4pm Lectures 1 & 2 of 6 The lung Dr Sue McGlashan Introduction The lungs are internal pockets of the body surface in which atmospheric air is brought close to pulmonary capillaries so that gas exchange can take place. Two things are essential for efficient exchange: the diffusion distance between air and blood must be small, and the surface area over which exchange takes place must be large. These are achieved in human lungs. The diffusion distance is about 0.5 micrometres, which is one fifteenth of the diameter of a red blood cell, a very small distance indeed. The internal surface area of the lungs is about 100m2, which is half the size of a tennis court. These first two lectures explain the structure of the lungs and associated airways, in preparation for an account of respiratory physiology which follows in lectures 3 - 6. Topics 1. Three kinds of respiration 2. Following the airway from nose to alveoli 3. Lungs: their shape, subdivisions and pleurae 4. Muscles of ventilation Intended learning outcomes (ILOs) After thoughtfully reviewing these two sessions, you should be able to: 1. Distinguish between external, internal and cellular respiration. 2. Describe or label a diagram of the nasal cavities, and comment on their function. 3. Distinguish three regions of the pharynx and explain how food is kept out of the airway during swallowing. 4. List, in descending order of size, the passages which make up the conducting and respiratory airways. 5. Describe the main features of the trachea. 6. Label a diagram of the bronchial or bronchiolar wall. 7. Describe, label or draw the cells that are present in the alveolar wall. 8. Identify what constitutes the diffusion barrier. 9. List or label the lobes of the lungs. 10. Define what is meant by a lung segment, and explain its clinical significance. 11. Name the pleurae and describe their relations to the lung, body wall and diaphragm. 12. Briefly explain how movements of the rib cage and diaphragm cause ventilation of the lungs, and name the muscles chiefly responsible. Resources These two lectures are well covered in Tortora & Derrickson. AP 3rd ed. pp. 1091-1112 AP 2nd ed. pp. 1246-1269 14th ed. pp. 841-858 13th ed. pp. 919-937 NOTE: Omit the sections on the larynx and voice production. MEDSCI 142 COURSE GUIDE © 2024 4pm 130 1 Respiration and ventilation External respiration is the process in the lungs by which oxygen is absorbed from the atmosphere into blood within the pulmonary capillaries, and carbon dioxide is excreted. Internal (or tissue) respiration describes the exchange of gases between blood in systemic capillaries and the tissue fluid and cells which surround them. It is not the subject of this lecture. Cellular respiration is the process within individual cells through which they gain energy by breaking down molecules such as glucose. It occurs in mitochondria, consumes oxygen and generates carbon dioxide. It is not the subject of this lecture. Pulmonary ventilation (breathing) describes the bulk movement of air into and out of the lungs. The ventilatory pump comprises the rib cage with its associated muscles, and the diaphragm. The conducting part of the respiratory system is a series of cavities and thick-walled tubes which conduct air between the nose and the deepest recesses of the lungs, and in doing so warm, humidify and clean it. The conducting airways are the nasal cavities, pharynx, larynx, trachea, bronchi and bronchioles. The respiratory part of the system comprises the tiny, thin-walled airways where gases are exchanged between air and blood. The airways are respiratory bronchioles, alveolar ducts and sacs, and the alveoli themselves. Cellular respiration Right within cells cardiac pump (blood) O2 Ventilatory pump CO2 (air) Left cardiac pump External (blood) Internal respiration respiration air - blood - blood tissues C. Quilter, University of Auckland a MEDSCI 142 COURSE GUIDE © 2024  131 4pm 2 Entering the cavern of the nasal cavity Tortora & Derrickson Fig 23.2b Properties of the nasal cavity - preparing air for gas exchange the nasal cavity is a tall, narrow chamber lined with mucous membrane. The wet membrane humidifies and warms inspired air. the medial surface is flat, the lateral surface carries three sloping shelves (conchae) which increase the surface area of the mucous membrane. air-filled (paranasal) sinuses open into the cavity. They lighten the face and add resonance to the voice. the roof of the cavity carries the olfactory epithelium. Turbulence caused by sniffing carries air up to the epithelium. Axons of olfactory receptor cells lead towards the brain through perforations in the overlying bone, the cribriform plate. MEDSCI 142 COURSE GUIDE © 2024 4pm 132 C. Quilter, University of Auckland a 3 Three parts of the pharynx 4 Swallowing The pharynx is a vertical passage with three parts, each having an anterior opening. The pharynx is an airway but also a foodway. In terms of its structure it is primarily part of the gastrointestinal system. 5 Pattern of branching of the airways Structure Generation Trachea 0 Main stem bronchi 1 Lobar bronchi 2 CONDUCTING Segmental bronchi 3 ZONE Smaller bronchi 4-9 Bronchioles 10-15 Terminal bronchioles 16-19 Respiratory bronchioles 20-23 RESPIRATORY Alveolar ducts 24-27 ZONE Alveolar sacs 28 See also: Tortora & Derrickson Fig 23.7 6 Trachea The windpipe: a tube about 12 cm long and as thick as your thumb. Supported by incomplete “C-shaped” rings of cartilage. Free ends of the cartilage are connected by trachealis muscle (smooth); contraction narrows the diameter of the trachea, but whether or not this has any functional significance is debated. Lined with a ciliated epithelium (pseudostratified columnar). Cilia transport a mucous sheet upwards to the nasopharynx (the “mucociliary escalator”). Esophagus sits immediately posterior to the trachea, lying in the shallow groove formed by the trachealis muscle. MEDSCI 142 COURSE GUIDE © 2024  C. Quilter, University of Auckland a 7 The wall of a bronchus 8 The wall of a bronchiole 133 4pm MEDSCI 142 COURSE GUIDE © 2024 4pm 134 C. Quilter, University of Auckland a 9 Terminal and respiratory bronchioles 10 Alveoli Capillaries wrapped around a single alveolus. 11 Cells in the alveolar wall Note: in this schematic diagram the volume of the alveolar air space is greatly reduced, and the thickness of the squamous pneumocytes and the capillary endothelial cells is exaggerated. MEDSCI 142 COURSE GUIDE © 2024  135 4pm 12 The diffusion barrier 13 Summary: variations along the length of the airway Epithelial Smooth Mucous Cartilage DO NOT MEMORISE THIS lining muscle glands DIAGRAM C-shaped Trachea Pseudo- rings stratified columnar Relatively Irregular Bronchus ciliated less plates Bronchiole Columnar ciliated Terminal bronchiole Respiratory Cuboidal Relatively bronchiole ciliated more Alveolar duct Squamous Alveolar pneumocytes sac and surfactant Alveolus cells Main points: Cartilage supports the large airways during inspiration, but does not continue beyond the smallest bronchi. Mucous glands stop there too. Thickness of the epithelium decreases as airway diameter decreases. The epithelium of the conducting airways contains secretory cells. Goblet cells secrete mucus in the large airways, Club cells release a serous (watery) secretion in bronchioles. Small airways have more smooth muscle (in spiral orientation) in relation to their size than large ones, but the muscle coat does not continue beyond the smallest bronchioles. MEDSCI 142 COURSE GUIDE © 2024 4pm 136 C. Quilter, University of Auckland a 14 Subdivisions of the lung Primary bronchi (2) are right and left main stem bronchi supplying each lung. Secondary bronchi are lobar bronchi supplying lobes (2 on the left, 3 on the right). Tertiary bronchi are segmental bronchi supplying segments of the lung (8 on the left, 10 on the right). Each segment has its own air and blood supply. Thus when a localised tumour occurs in the lung, a surgeon who knows the approximate boundaries can remove one or more segments containing the tumour without excessive leakage of air or blood from neighbouring segments. 15 Lung segments The right lung is shown, in lateral (left) and medial (right) views. The lung is divided into ten bronchopulmonary segments, each segment being supplied by a segmental (= tertiary) bronchus (numbered 1 - 10 in the central drawing). 16 Pleurae A smooth membrane (pleura) covers each lung; and also lines the thoracic cavity in which the lung sits. The two membranes (pleurae) are continuous at the root of the lung (hilum). A thin film of fluid separates the pleurae. The fluid allows the pleurae to slide past each other without friction. Although the fluid allows sliding movement between the pleurae, it also prevents them from being separated. When the thoracic wall moves inwards or outwards, the lungs must follow. Similarly when the diaphragm moves upwards or downwards, the lungs must follow. Fist surrounded Lung surrounded by soft balloon. by soft balloon. The balloon is reflected (turned The balloon through 180 degrees) at the contains air, not hilum where the main stem fist. bronchus enters the lung. MEDSCI 142 COURSE GUIDE © 2024  137 4pm C. Quilter, University of Auckland a 17 Ventilation: movement of the ribs Quiet breathing: Movement of the ribcage is responsible for about 25% of air movement into and out of the lungs. Inspiration is active. It requires contraction of the external intercostal muscles which run obliquely between ribs. Expiration is passive. The ribcage returns to its resting position without requiring muscular action. Breathing during exercise: Both sets of intercostal muscles are now active; externals for inspiration, internals for expiration. The ribs pivot around their joints with the When the ribs lift they The internal intercostal muscles vertebral column. The orientation of the swing upwards and run at right angles to the externals. external intercostal muscles means that outwards, in the same way When they contract they drag the contraction has the effect of lifting the ribs, that the handle of a bucket ribs downwards. Active contraction (rotating them around their pivot points). does. This movement only occurs during forceful In this diagram the relative proportions of the ribs and vertebral exhalation. increases the volume of bodies have been distorted to clarify the muscle action. the thorax. 18 Ventilation: movement of the diaphragm The diaphragm is a dome-shaped platform which forms the floor of the thorax and the roof of the abdomen. Its central part is a thin sheet of connective tissue, (technically an aponeurosis) called the central tendon. The lateral margins are muscular. The muscle is fast-acting skeletal muscle, innervated by the phrenic nerve. Thorax Contraction of the diaphragmatic muscle flattens the diaphragm, pulling its central dome downwards. This increases the volume of the thorax and causes inspiration. Passive relaxation of the muscle allows the diaphragm to lift back towards the thorax, reducing thoracic volume, (expiration). Movement of the diaphragm is responsible for 75% of bulk flow of air during quiet Abdomen breathing, a smaller proportion during exercise. The relative proportions of the parts in this diagram have been distorted to clarify the muscle action. MEDSCI 142 COURSE GUIDE © 2024 4pm 138 Lecture 3 of 6 The respiratory cycle & mechanics of breathing Professor Julian Paton Intended learning outcomes (ILOs) After thoughtfully reviewing this session, you should be able to: 1. Define respiration 2. List the main muscles associated with breathing and their innervation 3. Describe the respiratory cycle with reference to changes in intra-pulmonary and intra- pleural pressure 4. Explain how different lung volumes are measured 5. List the name of some clinical tests aimed at assessing respiratory function Resources These lectures are well covered in Tortora & Derrickson, chapter 23. Other suggested references (optional) W.F. Boron & E.L. Boulpaep J.B. West Medical Physiology 4th Edition Respiratory Physiology – the essentials Elsevier Williams & Wilkins ISBN 0-683-08937-4 J. Widdicombe & A. Davies Respiratory Physiology 2nd Edition Edward Arnold ISBN 0-683-08940-4 Summary Definition of Respiration The function of respiration is to extract oxygen from the air for aerobic metabolism and remove carbon dioxide from respiring tissues and exhaust into atmosphere. This is achieved by rhythmic contraction of the respiratory muscles to allow for inspiration (active process at rest) and expiration (passive at rest and active during exercise). MEDSCI 142 COURSE GUIDE © 2024  139 4pm Respiratory Muscles and their nervous innervation The main respiratory muscles include the diaphragm and external intercostal muscles (used for inspiration) and internal intercostals and abdominal muscles (for active expiration during exercise but also for cough and vocalization). At rest, inspiration is an active process requiring muscle contraction whereas expiration is passive relying on the recoil forces of the chest wall & lungs. Spinal Origins of Respiratory Motor Outflows (i) Phrenic: cervical (C) segments C3-C5 innervates diaphragm (inspiratory) (ii) Intercostals: T1-L1 external (inspiratory) and internal intercostal muscles (expiratory) (iii) Abdominal: T7-L1 (expiratory) Structural Considerations of the Thoracic Cage The lungs are separated from the chest wall by the pleural space. Measurements of pressure within the pleural space (intrapleural pressure; Ppl) indicate a pressure gradient such that the intrapleural pressure is negative (-2 to -10 cm water) relative to the alveolar or pulmonary pressure (intrapulmonary pressure; Ppul). This negative Ppl helps keep the lungs from collapsing and “adheres” them to the chest wall. MEDSCI 142 COURSE GUIDE © 2024 4pm 140 Mechanics of Ventilation During an inspiration chest volume increases (i.e. diaphragm contracts downwards and ribs upwards and outwards - “bucket handle” analogy). The net effect is a more negative pleural pressure (pressure between lungs and chest wall - Ppl) which causes the lungs to expand (i.e. inflate) with the chest. The result of the lungs inflating is a decrease in pulmonary pressure (pressure within air spaces in lungs; Ppul) relative to atmospheric pressure. Since air moves from areas of high to low pressure, air rushes into lungs. Pneumothorax MEDSCI 142 COURSE GUIDE © 2024  141 4pm Lung Volumes The volume of air moving into the lungs at rest is the tidal volume (VT) which is 0.5 L for an average adult human. This can be measured on a spirometer. The volume of air from a maximal expiration to maximal inspiration = vital capacity. Residual volume cannot be measured with a spirometer but assessed by a dilution method involving breathing helium gas (which is inert). This techniques allows total lung capacity (TLC) to be measured. From this, residual volume = TLC - vital capacity. Fig 23.15 T&D The average values for a healthy adult male and female are indicated, with the values for a female in parentheses. Volumes = measured; capacities = calculated; Capacities = sum of two or more volumes Respiratory Volumes Measured Tidal breath (VT) Respiratory frequency (f) Minute ventilation VE = (VT x f) Inspiratory reserve volume Expiratory reserve volume MEDSCI 142 COURSE GUIDE © 2024 4pm 142 Calculating Minute & Alveolar Ventilation Dots above the Vs indicate a time derivative.. VE = Minute ventilation = frequency of breathing x VT = 12 breaths/min x 0.5 L = 6 L/min at rest. > 6 L/min = Hyperventilation vs < 6 L/min = Hypoventilation. VA = Alveolar ventilation accounts for the anatomical dead space in the airway VD = Dead space = 2.2 ml/kg = 150 ml. VD = Dead space ventilation = 150 ml x 12 = 1.8 L/min. VA = ( VT - VD ) x f = (0.5 - 0.15) x 12 = 4.2 L/min... VE = VA + VD = 4.2 + 1.8 = 6 L/min MEDSCI 142 COURSE GUIDE © 2024  143 4pm Lecture 4 of 6 The dynamics of ventilation & control of the airways Professor Julian Paton Intended learning outcomes (ILOs) After thoughtfully reviewing this session, you should be able to: 1. Define compliance of the lung and importance of surfactant to reduce surface tension 2. Explain the consequences of chronic obstructive pulmonary disease (COPD) & fibrosis to ventilation on lung compliance 3. Describe the respiratory airway tree, the ‘funnel effect’, dead space and its impact on ventilation 4. Describe a reflex involved in controlling airflow 5. Give examples of diseases affecting airway resistance Resources These lectures are well covered in Tortora & Derrickson, chapter 23. Summary At rest, inspiration is an active process requiring muscle contraction. At rest, expiration is a passive process relying on radial traction which depends on physical properties of the lungs (elasticity and surface tension). Note: in respiratory physiology the term compliance is used (i.e. reciprocal of elasticity). Recoil Force Elasticity Surface tension of the lungs in the lungs 1 Compliance = Elasticity Elasticity Compliance change in volume Compliance = change in pressure MEDSCI 142 COURSE GUIDE © 2024 4pm 144 Surface tension within the lung Surface tension plays a major role in the elastic recoil force of the lung and is important for deflating the lung. Surface tension within the lung exists at the liquid-gas interface in the alveoli. Surface tension is caused by the cohesive forces between the molecules in a liquid. Within the alveoli, the force created by surface tension is measured as a pressure that attempts to collapse the alveoli. La Place’s law To measure the surface tension induced pressure within the alveoli (PA) we 2T use La Place’s law where PA = 2 x surface tension divided by the alveolar P= R radius. This means the smaller the radius the greater the deflating pressure. Lung compliance Lung compliance = change in volume of lung divided by change in pressure and tends to collapse lungs at functional residual capacity (FRC). Pulmonary disease states typically affect compliance of the lung and/or chest wall: e.g. chronic obstructive pulmonary disease or COPD (increased lung compliance caused by smoking) and fibrosis (“stiff lung” caused by air contaminants). Anatomical considerations of the respiratory airway tree The upper airway tree comprises cartilaginous tubes (trachea, main stem bronchi; lobar bronchi) which are in the form of rings initially. Cartilage is essential for keeping airways patent. The upper tree (first 16 generations) are non-respiratory in function and form the conducting zone – which makes up anatomical dead space. Dead space causes contamination of freshly inhaled air diluting the oxygen content. It is approximately 2.2 ml per kg. The respiratory zone (or unit) comprises the respiratory bronchioles, alveolar duct and alveolar sac. These latter structures are free of cartilage and are kept open by the lung parenchyma. MEDSCI 142 COURSE GUIDE © 2024  145 4pm Cross sectional area and air flow down the airway The cross sectional area increases from the trachea to the alveoli x500 - so called “funnel effect”. This is a result of over 300 million alveoli. The flow of air in the conducting zone is rapid and highly turbulent but becomes slow and laminar in the respiratory zone due to large surface area. Control of airflow Airway resistance is dependent on airway diameter. The highest is in the upper airway and lowest in the bronchioles. Airway resistance is dependent on lung volume a inflating the lung pulls airways open via radial traction. The airways contain smooth muscle and are innervated by parasympathetic (PS) and sympathetic nerves. The PS nerves cause bronchoconstriction and the sympathetic nerves bronchodilatation. The bronchal smooth muscle also has numerous receptors sensitive to humoral and hormonal influences. The bronchiole smooth muscle contains beta2- adrenoceptors, which are targeted using agonists in people with asthma, for example. Reflex control of the airways The bronchioles are innervated with sensory stretch receptors that generate action potentials during lung inflation that are sent to the brainstem. This triggers a reflex bronchodilatation mediated via the sympathetic nervous system to reduce airway resistance and facilitates air flow into the alveoli. MEDSCI 142 COURSE GUIDE © 2024 4pm 146 Lecture 5 of 6 Perfusion of the lung & the alveolar gas-blood interface Professor Julian Paton Intended learning outcomes (ILOs) After thoughtfully reviewing this session, you should be able to: 1. Explain why the pulmonary circulation is a low pressure system 2. Explain the significance of the terms: sheet flow, vessel distension/recruitment 3. Explain the reasons for regional differences in blood flow in the upright lung 4. Explain why the ideal ventilation-perfusion ratio (V:Q) value is one but in reality it is < 1 5. Describe the implications of pulmonary hypertension and consequences for ventilation 6. Explain the factors controlling diffusion of gas from the alveoli into the blood stream 7. Explain what is meant by gas diffusion vs. blood perfusion limitation of gas uptake from the lungs Resources These lectures are well covered in Tortora & Derrickson, chapter 23. Summary Arterial shunts in the pulmonary circulation Blood to the pulmonary vascular bed originates from the right ventricle. The pulmonary vein carries oxygenated blood but is contaminated by blood from the tracheobronchial circulation that by-passes the lungs (“anatomical shunt”). Typically, pulmonary pressure = 28/10mmHg which means blood can only be pumped to a height of 35cm at systole and 13cms during diastole. If the lung is positioned >13cm above heart blood flow at the top of the lung may be highly pulsatile occurring at systole only. This will depend on posture (e.g. upright vs supine). MEDSCI 142 COURSE GUIDE © 2024  147 4pm Factors controlling blood flow in the lungs (i) Physical: Since blood vessels are attached to the lung parenchyma physical or passive mechanisms related to lung volume alter size of vessel diameter as they do with the small airways and alveoli. As pulmonary artery pressure increases pulmonary vascular resistance decreases due to distension and recruitment of vessels. (ii) Hypoxia: A decreased oxygen level (hypoxemia) causes vasoconstriction via a direct effect and limits blood flow to poorly ventilated alveoli. Hypercapnia also does this. Regional variations in pulmonary blood flow Blood flowing through poorly ventilated alveoli, as found in the top of the lung, forms a physiological shunt reducing PaO2 levels in the pulmonary vein. There is better perfusion at the base of the lung. This regional variation in blood flow is a consequence of gravity, which restricts the height blood can be pumped (i.e. hydrostatic pressure). Factors causing regional variations in perfusion of the lung Three pressures must be considered: (i) hydrostatic pressure (HP) or pulmonary blood pressure Pa; (ii) arterial venous difference Pv (this is the driving force for blood flow) and (iii), alveolar pressure PA. For convenience the lung is divided into 3 zones. Zone 1: Top of the lung where the HP is lowest (ie poorly perfused) PA>Pa>Pv. Zone 2: The HP in the middle of the lung is greater than PA but PA is still larger than Pv so Pa>PA>Pv. Zone 3: The base of the lung has the greatest HP and is best perfused and both Pa and Pv are found to be greater than PA (ie: Pa>Pv>PA). In real life no strict zonal boundaries; zones 1-3 form a continuum. MEDSCI 142 COURSE GUIDE © 2024 4pm 148 Ventilation-Perfusion Ratio or VA/Q Ideally VA/Q = 1; ie Alveolar Ventilation (freq x tidal vol less dead space) divided by cardiac output. A VA/Q ratio of 1 is ideal and perfectly matches perfusion with ventilation. In reality, this ratio is 0.8. Factors controlling diffusion across alveolar membrane Area x Diffusion Constant* x (Partial Pressure difference) Gas diffused = Thickness of separating tissues * Diffusion constant = Solubility of Gas / Molecular Weight For O2 and CO2 the solubility is more important than their molecular weights. CO2 is 25x more soluble than O2 and diffuses 0.86x faster than O2. However, lung equilibrium for exchange of CO2 & O2 are similar since: (i) chemical reaction that releases CO2 is relatively slow, (ii), driving force of CO2 from blood to alveolus (45-40mmHg) is approx. 10x less than that driving force of O2 from alveolus to blood (100-40mmHg). MEDSCI 142 COURSE GUIDE © 2024  149 4pm Lecture 6 of 6 Transport of oxygen and carbon dioxide in blood Professor Julian Paton Intended learning outcomes (ILOs) After thoughtfully reviewing this session, you should be able to: 1. Explain how oxygen and carbon dioxide are transported in blood 2. Explain the physiological significance of the oxygen dissociation curve for heamoglobin 3. Describe the difference between saturation and content of oxygen in blood 4. Explain why foetal haemoglobin and myoglobin have left shifted oxygen dissociation curves 5. Describe the Bohr shift, chloride shift and the Haldane effect 6. Explain how blood gas levels themselves control the rate and depth of breathing Resources These lectures are well covered in Tortora & Derrickson, chapter 23. Summary Two methods for carrying O2 in blood (i) Binding with Hb - 1L blood (i.e. 150g Hb) carries 200mls of O2 by: (ii) Dissolving in plasma - ONLY - 0.2ml/L at PO2 of 80mmHg. Relationship between O2 and Hb Hb (MWt. 64,500) contains polypeptide chain (globin) and 4 ferrous iron groups (haem). Each heam group binds with one O2 molecule using a salt bridge in a co-operative fashion: Hb + O2 = HbO2 or Hb4 + 4O2 = Hb4O8 (i) Blood O2 saturation (%) The oxygen dissociation curve is the % Saturation of O2 vs Partial pressure of O2 (mmHg) and indicates the proportion of Hb bound with O2. Co-operative binding explains the sigmoidal relationship. I = partial pressure of O2 when blood is 50% saturated. Note: the % saturation of O2 is independent of the amount of Hb present. MEDSCI 142 COURSE GUIDE © 2024 4pm 150 (i) Blood O2 content (ml/litre blood) It is also essential to determine blood O2 content. e.g. In an anemic condition, blood O2 saturation may be 100% but blood O2 content will be lower. Blood O2 levels depend on both PO2 & Hb content. Physiological advantages of O2 dissociation curve The steep lower part means that at the tissues (where PaO2 is low) Hb releases large amounts of O2 for only a small drop in capillary PO2. Factors affecting O2 dissociation curve At tissues the following occurs: 1. pH decreases (by 0.2 units). The increase in [H+] shifts curve to right - so called Bohr Shift. Thus, for any given PO2 more O2 is released i.e. HbO2 + H+ = HHb + O2. Note: HHb has a lower affinity to bind with O2 than Hb 2. CO2 is high which increases [H+] and shifts curve to right. Note: CO2 also reacts with Hb to displace O2. 3. Temperature increases and shifts curve to right 4. 2,3-Diphosphoglycerate (DPG) levels are high & shifts curve to right. Note: At lungs 1-4 all decrease and Hb has a higher affinity for uptake of O2. For clarity: 1. [H+] decreases at the lungs (i.e. an increase in pH). MEDSCI 142 COURSE GUIDE © 2024  151 4pm CO2 is transported in 3 ways In plasma (a) Dissolved in solution - 20 times more soluble than O2 CO2 + H2O = H2CO3 = H+ + HCO3- (b) Combines with proteins to form carbamino compounds R-NH2 + CO2 = R-NHCOO + H+ (H+ are buffered by proteins) In red blood cells (RBC) (c) Carried in HCO3 form: CO2 + H20 = H2CO3 = H+ + HCO3 Note: (i) presence of carbonic anhydrase speeds up reaction in RBCs; (ii) ­­H+ are buffered by Hb to form HHb - encourages equation to the right (mass equilibrium theory). Cl- shift In RBCs equation c (see above), HCO3- moves out of cell down its concentration gradient so allowing more HCO3- to form via mass equilibrium theory. The entrance of Cl- ions (i.e. Cl- shift) maintains the cellular electroneutrality. CO2 dissociation curve Two curves since HbO2 has less affinity for CO2 than Hb (deoxyHb). This means that HbO2 or arterial blood has a curve displaced to the right - this is called the Haldane Shift. Actual curve is steeper than expected since arterial and venous points are joined. Note: The CO2 dissociation curve cannot be saturated reflecting its dependence upon PCO2, high CO2 solubility & methods of transport. MEDSCI 142 COURSE GUIDE © 2024 4pm 152 Chemical Control of Respiration Control of ventilation is by sensors that "taste" the blood. These are known as chemoreceptors. Two types are: (a) peripheral and (b) central chemoreceptors. a. Peripheral Chemoreceptors Location: Aortic arch (aortic bodies) and at carotid artery bifurcation (carotid bodies). Connected to brainstem via vagal and glossopharyngeal nerves (cranial X & IX) respectively. Stimulants: Highly sensitive to hypoxia, also protons and carbon dioxide. Reflex Response: When activated increase both the rate and depth of breathing (i.e. minute volume increases) by acting on brainstem respiratory network. b. Central Chemoreceptors - major chemical control of ventilation via CO2 Location: Neurons and/or astrocytes