Case 2 Notes.docx

PEAK PERFORMANCE Pulmonary Volumes and Capacities Volumes Tidal volume: is the volume of air displaced between normal inspiration and expiration (≈500ml). Inspiratory reserve volume: is the extra volume of air that can be inspired over and above the normal tidal volume when the person inspires with...

PEAK PERFORMANCE Pulmonary Volumes and Capacities Volumes Tidal volume: is the volume of air displaced between normal inspiration and expiration (≈500ml). Inspiratory reserve volume: is the extra volume of air that can be inspired over and above the normal tidal volume when the person inspires with full force (≈3000ml). Expiratory reserve volume: is the maximum extra volume of air that can be expired by forceful expiration after the end of a normal tidal expiration (≈1100ml). Residual volume: is the volume of air remaining in the lungs after the most forceful expiration; (≈1200ml). $$\begin{matrix} \mathbf{\text{Tidal\ }} \\ \mathbf{\text{Volume}} \\ \end{matrix}\mathbf{+ \ }\begin{matrix} \mathbf{\text{Inspiratory}} \\ \mathbf{\text{Reserve\ }} \\ \mathbf{\text{Volume\ }} \\ \end{matrix}\mathbf{+ \ }\begin{matrix} \mathbf{\text{Expiratory}} \\ \mathbf{\text{Reserve\ }} \\ \mathbf{\text{Volume}} \\ \end{matrix}\mathbf{+ \ }\begin{matrix} \mathbf{\text{Residual}} \\ \mathbf{\text{Volume}} \\ \end{matrix}\mathbf{= Maximum\ Volume}$$ Capacities In describing events in the pulmonary cycle, it is sometimes desirable to consider two or more of the volumes together. Such combinations are called pulmonary capacities: Inspiratory capacity: = tidal volume + inspiratory reserve volume (≈3500ml). This is the amount of air a person can breathe in, beginning at the normal expiratory level and distending the lungs to the maximum amount. Functional residual capacity: = expiratory reserve volume + residual volume (≈2300ml). This is the amount of air that remains in the lungs at the end of normal expiration. Vital capacity: = inspiratory reserve volume + tidal volume + expiratory reserve volume (≈4600ml). This is the maximum amount of air a person can expel from the lungs after first filling the lungs to their maximum extent and then expiring to the maximum extent. Total lung capacity: = inspiratory reserve volume + tidal volume + expiratory reserve volume + residual volume (≈5800ml). The maximum volume to which the lungs can be expanded with the greatest possible effort. All pulmonary volumes and capacities are about 20-25 % less in women than in men, and they are greater in large and athletic people than in small and asthenic people. Methods of Studying Respiratory Abnormalities Arterial Blood Gases This is a blood test that measures: The arterial oxygen tension (arterial partial pressure of O2) = PaO2 Normal Range: 12.0-13.3 kPa (80-100 mmHg) Decreased PaO2 is known as hypoxaemia. (note: hypoxia is the failure of oxygenation at the tissue level) (note: hypoxaemia is where the PaO2 is below the normal range) The arterial carbon dioxide tension (arterial partial pressure of CO2) = PaCO2 Normal Range: 4.8-6.1 kPa (35-45 mmHg) Increased in PaCO2 (hypercapnia) usually results in a decreased pH (more acidic) of the blood due to its conversion into carbonic acid which then dissociates into H+ ions and bicarbonate ions (HCO3-). This will cause increased respiratory rate to get more blood to the lungs for gas exchange (of CO2 out of the body). The acidity of the arterial blood = pH. Normal Range: 7.35-7.45 Pulse Oximetry Pulse oximeters with finger or ear probes all non-invasive continuous assessment of oxygen saturation in patients. This helps to assess hypoxaemia and its response to therapy. They measure the difference in absorbance of light by oxygenated and deoxygenated blood to calculate its oxygen saturation (SaO2). Peak Expiratory Flow Rate (PEFR) This is the maximum rate at which a person can forcibly expel air form their lungs at any time. Expressed usually in litres per minute (L/min). The maximum expiratory flow is much greater when the lungs are filled with a large volume of air then when they are almost empty. Normal values are dependent on height: 1.5m = 350 L/min; 1.6m = 400 L/min; 1.7m = 450 L/min; 1.8m = 500 L/min A low value can help diagnose asthma in the correct clinical context. Procedure: Subjects are asked to take a full inspiration to total lung capacity and then blow out forcefully into the peak flow meter. Spirometry Procedure: person inspires maximally to the total lung capacity and then exhales into the spirometer with the maximum expiratory effect as rapidly and as completely as possible. The spirometer measures the forced expiratory vital capacity (FVC) and the forced expiratory volume at the end of the first second (FEV1). FEV1 is expressed as a percentage of the FVC, i.e. how much of the FVC is exhaled by the end of the first second. The image compares the FVC of a normal person to a person with airway obstruction. Healthy person: Larger lung volume. Larger FEV1 (80%). Airway obstruction: Lower lung volume. Lower FEV1 (47%). In serious airway obstruction, as often occurs in acute asthma, the FEV1 can decrease to less than 20%. Types of Respiratory Failure Type I: hypoxia WITHOUT hypercapnia. Type II: hypoxia WITH hypercapnia. Gas Exchange After alveolar ventilation, the next step is the diffusion of oxygen from the alveoli into the pulmonary blood and the diffusion of carbon dioxide from the pulmonary blood into the alveoli. The process of diffusion is the random movement of molecules in all directions through the respiratory membrane and adjacent fluids. We should know about mechanism of diffusion as well as the rate of diffusion. Molecular Basis of Gas Diffusion A source of energy is needed for diffusion to occur. This is provided by the kinetic motion of the gas molecules: Free molecules (not physically attached to one another) have linear movement at high velocity until they strike other molecules. They are deflected in a new direction and subsequent collisions occur. This gives rise to the rapid and random movement of the gas molecules. Net diffusion of a gas is always in one direction: Gas molecules will always diffuse from an area of high concentration to an area of low concentration, along the concentration gradient. This is because: There are more gas molecules in the area of high concentration and less gas molecules in the area of low concentration. The rate of diffusion from the high concentration area to the low concentration is greater than the rate of diffusion from the low concentration area to the high concentration area. Therefore, the net diffusion is from the high concentration area to the low concentration area. Partial Pressures Gas Pressures in a Mixture of Gases Pressure is caused by multiple impacts of moving molecules against a surface. Therefore, the pressure of a gas acting on the surfaces of the respiratory passages and alveoli is proportional to the summated force of impact of all the molecules of that gas striking the surface at any given instant. This means that the pressure is directly proportional to the concentration of the gas molecules. The rate of diffusion of a gas is directly proportional to the pressure caused by that gas alone, which is called the partial pressure of that gas. Example of partial pressures: Composition of air: 79% nitrogen 21% oxygen The total pressure of this mixture at sea level is 760 mmHg. Each gas contributes to the total pressure in direct proportion to its concentration. Therefore: 79% of 760 mmHg is caused by nitrogen (600 mmHg). 21% of 760 mmHg is caused by oxygen (160 mmHg). The partial pressure of nitrogen is 600 mmHg in this mixture. The partial pressure of oxygen is 160 mmHg in this mixture. Pressures of Gases Dissolved in Water and Tissues Gases dissolved in water or in body tissues also exert pressure because the dissolved gas molecules are moving randomly and have kinetic energy. When the dissolved gas molecule encounters a surface, such as the membrane of a cell, it exerts its own partial pressure in the same way that a gas in the gas phase does. Factors that determine the partial pressure of a gas dissolved in a fluid: The partial pressure of a gas in a solution is determined by: Its concentration The solubility coefficient of the gas Solubility Coefficient: Some types of molecules, especially carbon dioxide, are physically or chemically attracted to water molecules, and so are more soluble, whereas others are repelled, and so are less soluble. Attraction to water molecules means more dissolved gas molecules without a change in the partial pressure within the solution. Repulsion to water molecules develops high partial pressure with fewer dissolved gas molecules. The higher the solubility coefficient, the lower the partial pressure. These relations are expressed by the following formula, which is Henry’s Law: $$\mathbf{Partial\ Pressure = \ }\frac{\mathbf{\text{Concentration\ of\ Dissolved\ Gas}}}{\mathbf{\text{Solubility\ Coefficient}}}$$ At atmospheric pressure (=760 mmHg), carbon dioxide is 20 times as soluble as oxygen (it has a solubility coefficient which is 20 times greater than that of oxygen). Therefore, the partial pressure of carbon dioxide is one-twentieth that exerted by oxygen. As solubility coefficient increases, the partial pressure decreases. Diffusion of Gases between the Gas Phase in the Alveoli and the Dissolved Phase in the Pulmonary Blood The partial pressure of each gas in the alveolar respiratory gas mixture tends to force molecules of that gas into solution in the blood of the alveolar capillaries. Conversely, the molecules of the same gas that are already dissolved in the blood are bouncing randomly in the fluid of the blood, and some of these bouncing molecules escape back into the alveoli. The rate at which they escape is directly proportional to their partial pressure in the blood. If the partial pressure is greater in the gas phase in the alveoli, as is normally true for oxygen, then more molecules will diffuse into the blood than in the other direction. Alternatively, if the partial pressure of the gas is greater in the dissolved state in the blood, which is normally true for carbon dioxide, then net diffusion will occur toward the gas phase in the alveoli. Vapour Pressure of Water When non-humidified air is inspired into the respiratory passageways, water immediately evaporates from the surfaces of these passages and humidifies the air. The partial pressure that the water molecules exert to escape through the surface is called the vapour pressure of the water. At normal body temperature (37oC), this vapour pressure is 47 mm Hg. Therefore, once the gas mixture has become fully humidified—that is, once it is in “equilibrium” with the water—the partial pressure of the water vapour (PH2O) in the gas mixture is 47 mm Hg. The vapour pressure of water is dependent entirely on the temperature of the water. The greater the temperature, greater the kinetic energy of molecules, and so the greater the vapour pressure. Therefore, there is a greater likelihood that the water molecules will escape from the surface of the water into the gas phase. Diffusion of Gases through Fluids If the partial pressure of a gas is greater in one area than in another area, there will be net diffusion from the high-pressure area to the low-pressure area. In addition to the pressure difference, several other factors affect the rate of gas diffusion in a fluid. They are; The solubility of the gas in the fluid The greater the solubility of the gas, the greater the number of molecules available to diffuse for any given partial pressure difference. The cross-sectional area of the fluid The greater the cross-sectional area of the diffusion pathway, the greater the total number of molecules that diffuse. The distance through which the gas must diffuse The shorter the distance the molecules must diffuse, the lesser the time it will take for the molecules to diffuse the entire distance. The molecular weight of the gas The lesser the molecular weight of the molecule, the greater its velocity. The temperature of the fluid The greater the temperature, the greater the kinetic activity of the molecules. Composition of Alveolar Air Compositions of alveolar air and atmospheric air are different. Alveolar air doesn’t have the same concentration of gases as atmospheric air. This is because: Alveolar air is only partially replaced by atmospheric air with each breath. Oxygen is constantly being absorbed into the pulmonary blood from the alveolar air. Carbon dioxide is constantly diffusing from the pulmonary blood into the alveoli. Dry atmospheric air that enters the respiratory passages is humidified even before it reaches the alveoli. As soon as the atmospheric air enters the respiratory passages it is exposed to the fluids that cover the respiratory surfaces. Alveolar Air has more CO2 and less O2 than inhaled air. During exhalation, this alveolar air mixes with air in the dead space of the lungs producing exhaled air. The partial pressure of water vapour at a normal body temperature of 37°C is 47 mmHg, which is therefore the partial pressure of water vapour in the alveolar air. Because the total pressure in the alveoli cannot rise to more than the atmospheric pressure (760 mm Hg at sea level), this water vapour simply dilutes all the other gases in the inspired air. Rate at Which Alveolar Air Is Renewed by Atmospheric Air The average male functional residual capacity of the lungs measures about 2300ml. Yet only 350ml of new air is brought into the alveoli with each normal inspiration, and this same amount of old alveolar air is expired. Therefore, the volume of alveolar air replaced by the new atmospheric air with each breath is only a fraction of the total, so multiple breaths are required to exchange most of the alveolar air. Slow replacement of alveolar air: Important in preventing sudden changes in gas concentrations in the blood. This makes the respiratory control mechanism much more stable. It helps prevent excessive increases and decreases in… Tissue oxygenation Tissue carbon dioxide concentration Tissue pH …when respiration is temporarily interrupted. Oxygen Concentration and Partial Pressure in the Alveoli Oxygen is continually being absorbed from the alveoli into the pulmonary blood, and new oxygen is continually being inspired into the alveoli form the atmosphere. Oxygen concentration in the alveoli and its partial pressure is controlled by: The rate of absorption of oxygen into the blood (Decreases alveoli oxygen concentration). The rate of entry of new oxygen into the lungs by ventilation (Increases alveoli oxygen concentration). Carbon Dioxide Concentration and Partial Pressure in the Alveoli Carbon dioxide is continually being formed in the body and then carried in the blood to the alveoli; it is continually being removed from the alveoli by ventilation. The alveolar PCO2 increases directly in proportion to the rate of carbon dioxide excretion. The alveolar PCO2 decreases in inverse proportion to alveolar ventilation. Expired Air Expired air is a combination of dead space air and alveolar air; its overall composition is therefore determined by: The amount of the expired air that is dead space air. The amount that is alveolar air. The diagram shows the progressive changes in oxygen and carbon dioxide partial pressures in the expired air during the course of expiration. The first portion of this air, the dead space air (mostly oxygen) from the respiratory passageways, is typical humidified air. Then, progressively more and more alveolar air becomes mixed with the dead space air until all the dead space air has finally been washed out and nothing but alveolar air is expired at the end of expiration. The less the air that is expired, the greater the concentration of oxygen in the expired air. This is because most of the air expired in this case will be dead space air (mostly oxygen). With a larger expired volume of expired air, the concentration of carbon dioxide in the expired air increases. Therefore, the method of collecting alveolar air for a study is simply to collect a sample of the last portion of the expired air after forceful expiration has removed all the dead space air. Diffusion of Gases through the Respiratory Membrane The respiratory unit is composed of a respiratory bronchiole, alveolar ducts, and alveoli. There are about 300 million alveoli in the two lungs. The different layers of the respiratory membrane are; A layer of fluid lining the alveolus and containing surfactant (reduces the surface tension of the alveolar fluid). The alveolar epithelium composed of thin epithelial cells (simple squamous cells). An epithelial basement membrane. A thin interstitial space between the alveolar epithelium and the capillary membrane. A capillary basement membrane that in many places fuses with the alveolar epithelial basement membrane. The capillary endothelial membrane. Factors affecting the Rate of Gas Diffusion through the Respiratory Membrane The factors that determine the rate of diffusion through the membrane are: The thickness of the membrane. E.g. can increase as a result of oedema fluid. The surface area of the membrane. E.g. can decrease as a result of emphysema. The diffusion coefficient of the gas in the substance of the membrane. Dependent on the gas’s solubility in the membrane and, inversely, on the square root of the gas’s molecular weight. $D \propto \ \frac{\mathrm{\Delta}P\ \times A\ \times S}{d\ \times \ \sqrt{}MW}$ $\begin{matrix} \text{Diffusion\ } \\ \text{Rate} \\ \end{matrix} = \ \frac{\begin{matrix} \text{Partial} \\ \text{Pressure} \\ \text{Difference} \\ \end{matrix}\ \times \ \begin{matrix} Cross - sectional \\ \text{Area} \\ \end{matrix}\ \times Solubility}{distance\ \times \ \sqrt{\text{Molecular\ Weight}}\ }$ The partial pressure difference of the gas between the two sides of the membrane. The greater the partial pressure, the greater the rate of diffusion through the membrane. Diffusing Capacity of the Respiratory Membrane Diffusing Capacity: “volume of a gas that will diffuse through the membrane each minute for a partial pressure difference of 1 mmHg”. Factors affecting the rate of diffusion affect the diffusing capacity as well. Diffusing Capacity for Oxygen In the average young man, the diffusing capacity for oxygen, under resting conditions averages 21 ml/min/mmHg. The mean oxygen pressure difference across the respiratory membrane during normal, quiet breathing is about 11 mmHg. 21 ml/min/mmHg x 11 mmHg = 230 ml/min. This means that, normally, 230 ml of oxygen diffuse through the respiratory membrane each minute; this is equal to the rate at which the body uses oxygen. Change in Oxygen Diffusing Capacity during Exercise The diffusing capacity for oxygen increases up to 3 times. This increase is caused by several factors: 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. A better match between the ventilation of the alveoli and the perfusion of the alveolar capillaries with blood, called the ventilation/perfusion ratio. Ventilation/Perfusion Ratio Ventilation: aeration of the lungs. Perfusion: blood flow to the lungs. Normally to some extent, and especially in many lung diseases, some areas of the lungs are well ventilated but have almost no blood flow, whereas other areas may have excellent blood flow but little or no ventilation. This leads to impaired gas exchange. The person may suffer severe respiratory distress despite both normal total ventilation and normal total pulmonary blood flow, but with the ventilation and blood flow going to different parts of the lungs. In quantitative terms, the ventilation-perfusion ratio is expressed as Va/Q. When Va (alveolar ventilation) is normal for a given alveolus and Q (blood flow) is also normal for the same alveolus, the ventilation-perfusion ratio (Va/Q) is also said to be normal. When the ventilation (Va) is zero, yet there is still perfusion (Q) of the alveolus, the Va/Q is zero. When there is adequate ventilation (Va) but zero perfusion (Q), the ratio Va/Q is infinity. At a ratio of either zero or infinity, there is no gas exchange through the respiratory membrane of the affected alveoli. Va/Q is equal to zero (without any alveolar ventilation): The air in the alveolus comes to equilibrium with the blood oxygen and carbon dioxide. Venous blood perfuses the pulmonary vessels The gases in this venous blood equilibrate with the alveolar gases. Normal venous blood (v): has a PO2 of 40 mmHg and a PCO2 of 45 mmHg. When Va/Q = 0, PO2 = 40 mmHg and PCO2 = 45 mmHg are the normal partial pressures of these two gases in alveoli that have blood flow but no ventilation. Va/Q equals infinity (no capillary blood flow to carry oxygen away or to bring carbon dioxide to the alveoli): Alveolar air comes to equilibrium with the humidified inspired air. The inspired air loses no oxygen to the blood and gains no carbon dioxide from the blood. Normal inspired and humidified air: has a PO2 of 149 mmHg and a PCO2 of 0 mmHg. When Va/Q = infinity, PO2 = 149 mmHg and PCO2 = 0 mmHg are the normal partial pressures of these two gases in alveoli that have ventilation but no blood flow. Gas Exchange and Alveolar Partial Pressures When Va/Q Is Normal When there is normal alveolar ventilation and normal alveolar perfusion, gas exchange through the respiratory membrane is optimal. Alveolar PO2 is normally 104 mmHg, which lies between that of the inspired air (149 mm Hg) and that of venous blood (40 mm Hg). Alveolar PCO2 is normally 40 mmHg, which lies between that in venous blood (45 mmHg) and that in inspired air (0 mmHg). Physiologic Shunt Whenever Va/Q is below normal, there is inadequate ventilation (reduced Va) to provide the oxygen needed to fully oxygenate the blood flowing through the alveolar capillaries. A certain fraction of the venous blood passing through the pulmonary capillaries does not become oxygenated. This fraction is called shunted blood. The total quantitative amount of shunted blood per minute is called the physiologic shunt. Physiologic Dead Space Whenever Va/Q is above normal, the alveolar perfusion is low (reduced Q), there is far more available oxygen in the alveoli than can be transported away from the alveoli by the flowing blood. The ventilation of these alveoli is said to be wasted. The ventilation of the anatomical dead space areas of the respiratory passageways is also wasted. The sum of these two types of wasted ventilation is called the physiologic dead space. Abnormal VA/Q in the Upper and Lower Normal Lung Upper Lung: Normally, in the upright position, both alveolar perfusion and alveolar ventilation are less in the upper part of the lung than in the lower part. Alveolar perfusion is decreased more than ventilation is. Therefore, at the top of the lung, Va/Q is too high causing moderate degree of physiologic dead space in this area of the lung. Lower Lung: In the bottom of the lung, there is slightly too little ventilation in relation to blood flow, with Va/Q being too low. In this area, a small fraction of the blood fails to become normally oxygenated, and this represents a physiologic shunt. Transport of Oxygen and Carbon Dioxide in Blood and Tissue Fluids Oxygen: After diffusion of oxygen into pulmonary blood, it is transported to the peripheral tissue capillaries almost entirely in combination with haemoglobin. The presence of haemoglobin in the red blood cells allows the blood to transport considerably more oxygen than could be transported in the form of dissolved oxygen in the water of the blood. In the body’s tissue cells, oxygen is metabolised into carbon dioxide. This carbon dioxide enters the tissue capillaries and is transported back to the lungs. Carbon dioxide, like oxygen, also combines with chemical substances in the blood that increase carbon dioxide transport. Transport of Oxygen from the Lungs to the Body Tissues Diffusion of Oxygen from the Alveoli to the Pulmonary Capillary Blood: Qualitative: Oxygen diffuses from the alveoli into the pulmonary blood as a result of the partial pressure difference. There is a higher PO2 in the capillary blood now so oxygen will diffuse out of the capillaries in tissues and into the surrounding tissue cells. Conversely, when oxygen is metabolized in the cells to form carbon dioxide, the intracellular PCO2 rises, causing carbon dioxide to diffuse out of the cells and into the tissue capillaries. There is a higher PCO2 in the capillary blood now so carbon dioxide will diffuse out of the pulmonary capillaries and into the alveoli. Quantitative: PO2 of alveolar air averages 104 mmHg. PO2 of venous blood averages 40mmHg. Initial pressure difference: 104 – 40 = 64 mmHg. The curve shows the rapid increase in pulmonary blood PO2 as the blood passes through the capillary. The PO2 rises almost to that of the alveolar air by the time the blood has moved a third of the distance trough the pulmonary capillary, becoming almost 104 mmHg. The blood normally stays in the capillaries three times as long as needed to cause full oxygenation (saturation). Uptake of Oxygen by the Pulmonary Blood during Exercise: During strenuous exercise, a person’s body requires more oxygen. Due to the increased cardiac output, the time that blood remains in the pulmonary capillary may be reduced to less than half the normal amount. Yet, due to the speed of saturation the blood still becomes almost saturated with oxygen. This is because: Normally, the pulmonary blood is nearly fully saturated by the time the blood has moved a third of the distance trough the capillary. Therefore, during exercise, even with a shortened time of exposure in the capillaries the blood can still become nearly fully oxygenated. The diffusing capacity increases almost threefold during exercise due to: Increased surface area of capillaries participating in the diffusion (vasodilation). A more nearly ideal ventilation/perfusion ratio in the upper lung (reduced physiologic shunt). There is also increased ventilation at the start of exercise to reach aerobic conditions is as less time as possible. The ventilation is constantly regulated during exercise by peripheral chemoreceptors. The chemoreceptors sense increase in CO2 more than a decrease in O2. Vasodilation At the start of exercise, the sympathetic nervous system causes vasoconstriction, thus the conditions are anaerobic at the start. With sufficient oxygen levels, the conditions become aerobic. Both types of respiration cause vasodilation. Transport of Oxygen in the Arterial Blood About 98% of blood that enters the left atrium from the lungs is saturated to a PO2 of 104 mmHg. A small amount of blood, the bronchial circulation, which supplies the lungs with blood isn’t exposed to air. This is called “Shunt flow”, as this blood is shunted past the gas exchange areas. The PO2 of shunt flow is the same as normal venous blood of 40 mmHg. The shunt flow blood combines with oxygenated blood from pulmonary veins. This is called venous admixture. This venous admixture of blood causes the PO2 of blood entering the left heart to fall to 95 mmHg. Diffusion of Oxygen from the Peripheral Capillaries into the Tissue Fluid: The PO2 in the capillaries or peripheral tissues is 95 mmHg. The PO2 of the interstitial fluid surrounding the tissue cells is 40 mmHg. This means there is a partial pressure difference. Oxygen diffuses out of the capillaries and into the tissue fluid. The capillary PO2 falls to 40 mmHg. This is the PO2 of the blood entering the systemic veins. If the blood flow through a particular tissue is increased, the tissue PO2 becomes correspondingly higher. However, the upper limit to which the PO2 can rise, even with maximal blood flow, is 95 mm Hg, because this is the oxygen pressure in the arterial blood (equilibrium). If the cells use more oxygen for metabolism, this reduces the interstitial fluid PO2. In summary, tissue PO2 is determined by a balance between: the rate of oxygen transport to the tissues in the blood. the rate at which the oxygen is used by the tissues. Oxygen is always being used by the cells. Therefore, the intracellular PO2 in the peripheral tissue cells remains lower than the PO2 in the peripheral capillaries. Carbon Dioxide: Diffusion of Carbon Dioxide from the Peripheral Tissue Cells into the Capillaries and from the Pulmonary Capillaries into the Alveoli In tissue cells, oxygen is metabolized and carbon dioxide is formed. Carbon dioxide diffuses in the direction exactly opposite to the diffusion of oxygen. There is one major difference between diffusion of carbon dioxide and of oxygen: Carbon dioxide can diffuse about 20 times as rapidly as oxygen. Therefore, the pressure differences required to cause carbon dioxide diffusion are, in each instance, far less than the pressure differences required to cause oxygen diffusion. The PCO2 are approximately the following: Intracellular PCO2 = 46 mm Hg Interstitial PCO2 = 45 mm Hg Arterial blood PCO2 = 40 mm Hg (entering tissues) Venous blood PCO2 = 45 mm Hg (leaving tissues) Pulmonary capillaries PCO2 at arterial end = 45 mm Hg Pco2 of the alveolar air = 40 mm Hg. Thus, only a 5 mmHg pressure difference causes all the required carbon dioxide diffusion out of the pulmonary capillaries into the alveoli. This diffusion occurs in the time the pulmonary blood has travelled one third the distance through the capillaries. Effect of Rate of Tissue Metabolism and Tissue Blood Flow on Interstitial PCO2 A decrease in blood flow increases peripheral tissue PCO2. An increase in blood flow decreases the interstitial PCO2. An increase in tissue metabolic rate greatly increases the interstitial PCO2. Haemoglobin Role of Haemoglobin in Oxygen Transport About 97% of oxygen in arterial blood is carried in chemical combination with hemoglobin. The remaining 3% is transported in the dissolved state in the water of the plasma and blood cells. Oxygen combines loosely and reversibly with the heme portion of haemoglobin: When PO2 is high, oxygen binds with haemoglobin. When PO2 is low, oxygen is released from the haemoglobin. Oxygen-Hemoglobin Dissociation Curve The usual oxygen saturation of systemic arterial blood averages 97%. The usual oxygen saturation of systemic venous blood averages 75%. There is about 15 grams of hemoglobin in each 100 milliliters of blood. Each gram of hemoglobin can bind with a maximum of 1.34 milliliters of oxygen. On average, the 15 grams of haemoglobin/100 milliliters of blood = 20 milliliters of oxygen (if the hemoglobin is 100 per cent saturated). This is usually expressed as 20 volumes percent. Amount of Oxygen Released Normal arterial blood is 97% saturated; this is about 19.4 milliliters of oxygen per 100 milliliters of blood. After the tissue capillaries, this amount is reduced to 14.4 milliliters (Po2 of 40 mm Hg, 75% saturated hemoglobin), 5 milliliters of oxygen delivered by each 100 milliliters of blood. Haemoglobin still retains three-quarters of its oxygen. Venous blood has a relatively large oxygen reserve, which can be mobilized if tissue oxygen demands increase. During exercise: The muscles use oxygen at a rapid rate lowering muscle interstitial PO2 (40 mmHg to 15 mm Hg). At this low pressure, only 4.4 milliliters of oxygen remain bound with the haemoglobin in each 100 milliliters of blood. 15 milliliters of oxygen is delivered to the tissues by each 100 milliliters of blood flow during exercise (5ml normally). The percentage of the blood that gives up its oxygen as it passes through the tissue capillaries is called the utilization coefficient. The normal value for this is about 25%- that is, 25% of the oxygenated hemoglobin gives its oxygen to the tissues. During strenuous exercise, the utilization coefficient can increase to 75%-85%. Effect of Hemoglobin to “Buffer” the Tissue PO2 Under normal conditions, tissues require about 5 milliliters of oxygen from each 100 milliliters of blood passing through the tissue capillaries. It can see that for the normal 5 milliliters of oxygen to be released per 100 milliliters of blood flow, the PO2 must fall from 95 mmHg to about 40 mmHg. Therefore, the tissue PO2 normally cannot rise above this 40 mm Hg level, because if it did, the amount of oxygen needed by the tissues would not be released from the hemoglobin. In this way, the hemoglobin normally sets an upper limit on the oxygen pressure in the tissues at about 40 mm Hg. During exercise, extra amounts of oxygen must be delivered from the hemoglobin to the tissues. But this can be achieved with little further decrease in tissue Po2 because of; The steep slope of the dissociation curve The increase in tissue blood flow caused by the decreased Po2 A very small fall in Po2 causes large amounts of extra oxygen to be released from the haemoglobin. Factors That Shift the Oxygen-Hemoglobin Dissociation Curve A number of factors can displace the dissociation curve in one direction or the other in the manner shown: Bohr Effect - When the blood becomes slightly acidic (increased CO2), with the pH decreasing from the normal value of 7.4 to 7.2, the oxygen-hemoglobin dissociation curve shifts to the right and downwards. Therefore, the quantity of oxygen that binds with the hemoglobin at any given alveolar Po2 becomes considerably increased, thus allowing greater oxygen transport to the tissues. The normal BPG in the blood keeps the oxygen-hemoglobin dissociation curve shifted slightly to the right all the time. During exercise, several factors shift the dissociation curve to the right, thus delivering the extra oxygen to the active muscles: The muscles release large amounts of carbon dioxide, increasing the blood H+ concentration. In addition the temperature of the muscles rises, increasing the oxygen delivery. These factors shift the curve to the right. This right-hand shift of the curve forces oxygen to be released from the blood haemoglobin to the muscle at Po2 levels as great as 40 mm Hg, even when 70% of the oxygen has already been removed from the haemoglobin. In the lungs, the shift occurs in the opposite direction, allowing the pickup of extra amounts of oxygen from the alveoli. Transport of Carbon Dioxide in the Blood Carbon dioxide diffuses out of the tissue cells. Most carbon dioxide is transported as carbonic acid. Some carbon dioxide binds to regions of haemoglobin to form carbamino compounds. A small portion of the carbon dioxide is transported in the dissolved state to the lungs. Reaction of Carbon Dioxide with Water in the Red Blood Cells: CO2 + water = carbonic acid (influence of carbonic anhydrase). Carbonic acid dissociates into hydrogen ions (H+) and bicarbonate ions (HCO3-). H+ + haemoglobin (Hb) = HHb Haemoglobin acts as an acid-base buffer. HCO3- diffuse out of the red cells into the plasma, while chloride ions diffuse into the red cells to take their place, a phenomenon called the chloride shift. This maintains the pH of red blood cell. In addition to reacting with water, carbon dioxide reacts directly with amine radicals of the haemoglobin molecule to form the compound carbaminohaemoglobin (CO2Hb). This is a reversible reaction that occurs with a loose bond, so that the carbon dioxide is easily released into the alveoli. The Haldane Effect Bohr Effect: an increase in carbon dioxide in the blood causes oxygen to be displaced from the hemoglobin. Haldane Effect: binding of oxygen with hemoglobin tends to displace carbon dioxide from the blood. This is the opposite of Bohr effect. The Haldane effect results from the simple fact that the combination of oxygen with hemoglobin in the lungs causes the hemoglobin to become a stronger acid. This displaces carbon dioxide from the blood and into the alveoli in two ways: The more highly acidic haemoglobin has less tendency to combine with carbon dioxide to form carbaminohemoglobin, thus displacing much of the carbon dioxide. The increased acidity of the haemoglobin also causes it to release an excess of hydrogen ions: The H+ + HCO3- = carbonic acid Carbonic acid dissociates into water and carbon dioxide. The carbon dioxide is released from the blood into the alveoli and into the air. Hypercapnia Hypercapnia means excess carbon dioxide in the body fluids. If hypercapnia does begin to occur, this immediately stimulates pulmonary ventilation, which corrects the hypercapnia. The transport capacity of the blood for carbon dioxide is more than three times that for oxygen, so that the resulting tissue hypercapnia is much less than the tissue hypoxia. At very high levels of PCO2, the excess carbon dioxide now begins to depress respiration rather than stimulate it. This culminates rapidly in a respiratory death. Acid-Base Disturbances Normal pH range (7.37 – 7.45). A pH below the normal range is called acidosis. A pH above the normal range is called alkalosis. These imbalances have potentially fatal effects. Cause Compensation Acidosis Respiratory Increased PCO2 Increased HCO3- (to react with the excess H+) Metabolic Decreased HCO3- (build-up of H+ as it can’t bind to this) Decreased PCO2 Alkalosis Respiratory Decreased PCO2 Decreased HCO3- Metabolic Increased HCO3- Metabolic imbalances: There is a change in pH, without necessarily a change in gas partial pressures. If the Base Excess (normally: -2 to +2), is out of the normal range, the condition is metabolic instead of respiratory. Base Excess: Increase in base excess (alkalosis) is due to: Increased excretion of acid in the kidneys. Increased retention of bicarbonate ions in the kidneys. Decrease in base excess (acidosis) is due to: Overproduction of acid. Increased loss of bicarbonate ions in the kidneys. Classifications of Respiratory Failure: Type I: Hypoxia (low PO2) Normal (or low) PCO2 Disturbance of ventilation/perfusion ratio Type II: Hypoxia (low PO2) Raised PCO2 Alveolar ventilation reduced Mixed: Type I and Type II present together. Asthma WHO definition 2013: Asthma attacks all age groups but often starts in childhood. It is a disease characterised by recurrent attacks of breathlessness and wheezing, which vary in severity and frequency from person to person. In an individual they may occur from hour to hour and day to day. This condition is due to inflammation of the air passages in the lungs and affects the sensitivity of the nerve endings in the airways so they become easily irritated. In an attack, the lining of the passages swell causing the airways to narrow and reducing the flow of air in and out of the lungs. Symptoms: Dyspnea (breathlessness) Coughing Wheezing Tightness of chest Status Asthmaticus: a state of unremitting attacks. Most frequent form has onset in childhood between ages 3-5 years and may worsen or improve during adolescence. Three characteristics: Airflow limitation - reversible spontaneously or with treatment Bronchial hyper-responsiveness – this is “easily triggered bronchospasm” as a result of a wide range of stimuli Inflammation of the bronchi - T lymphocytes, mast cells, eosinophils (plasma exudation), oedema, smooth muscle hypertrophy, matrix disposition, mucus plugging and epithelial damage. Chronic Asthma: inflammation accompanied by irreversible airflow limitation as a result of airway wall remodelling. Asthma may be categorized into: Atopic (extrinsic) – implying a definite external cause: Type I IgE-mediated hypersensitivity reaction. The disease usually begins in childhood and is triggered by environmental allergens. A positive family history of asthma is common, and a skin test with the offending antigen in these patients results in an immediate wheal-and-flare reaction. Atopic asthma may also be diagnosed based on evidence of allergen sensitisation by serum radioallergosorbent tests (called RAST), which identify the presence of IgE specific for a panel of allergens. Often seen in patients with family history of allergic rhinitis (eczema). Non-atopic (intrinsic) – when no causative agent can be identified: These individuals with asthma do not have evidence of allergen sensitisation. Skin test results are usually negative. A positive family history of asthma is less common in these patients. Respiratory infections due to viruses are common triggers in non-atopic asthma. In these patients hyper irritability of the bronchial tree probably underlies their asthma. Drug-induced Asthma: Several pharmacologic agents provoke asthma. Aspirin-sensitive asthma occurs in individuals with recurrent rhinitis and nasal polyps. These individuals are sensitive to aspirin as well as NSAIDS, and they experience not only asthmatic attacks but also urticaria. It is probable that aspirin triggers asthma in these patients by inhibiting the cyclooxygenase pathway of arachidonic acid metabolism without affecting the lipoxygenase route, thus tipping the balance toward elaboration of the bronchoconstrictor leukotrienes. Propranolol: This is a sympatholytic non-selective beta blocker (antagonist). Sympatholytic: inhibits postganglionic functioning of sympathetic nervous system. In this case, this is achieved through blocking beta adrenergic receptors. Used to treat hypertension, anxiety and panic. These can trigger an asthma attack. Occupational Asthma: This form of asthma is stimulated by fumes, organic and chemical dusts, gases, and other chemicals. Minute quantities of chemicals are required to induce the attack, which usually occurs after repeated exposure. The underlying mechanisms vary according to stimulus and include type I hypersensitivity reactions, direct release of bronchoconstrictor substances, and hypersensitivity responses of unknown origin. Aetiology and Pathogenesis Atopy - described as a group of disorders that appear to run in families, have characteristic sealing skin reactions to common allergens in the environment and to have circulating allergen-specific IgE. Genetic and environmental factors affect serum IgE levels: Genetic: genes controlling production of cytokines IL-3,4,5,9,13 and GM-CSF - in turn affect mast and eosinophil development and longevity as well as IgE production. Clean hypothesis: The hygiene hypothesis proposes that childhood exposure to germs and certain infections helps the immune system develop. This teaches the body to differentiate harmless substances from the harmful substances that trigger asthma. In theory, exposure to certain germs teaches the immune system not to overreact. Cold air and exercise : Cold air is less humid than warm air. The inhalation of cold, dry air will also precipitate an attack, due to the cooling and drying of epithelial cells. Typically, the attack does not occur while exercising but afterwards. Allergen-induced asthma (Atopic Asthma) Inhalation of allergen by atopic asthmatic individuals leads to the development of different types of reactions: Immediate asthma (early reaction): Airflow limitation begins within minutes of contact with the allergen, reaches its maximum in 15-20 minutes and subsides by 1 hour. Dual and late phase reactions: This follows an immediate reaction. Many asthmatics develop a more prolonged and sustained attack of airflow limitation which responds less well to inhalation of bronchodilators such as salbutamol. Isolated late phase reactions: Occurs with no preceding immediate response. After inhalation of some occupational sensitisers such as isocyanates. Pathogenesis of Asthma Early Phase Reaction In the airways, the scene for the reaction is set by initial sensitisation to inhaled allergens, which stimulate induction of Th2 cells. Th2 cells secrete cytokines that promote allergic inflammation and stimulate B cells to produce IgE and other antibodies. These include: IL-4, which stimulates the production of IgE by B cells. IL-5, which is a eosinophil chemotactic agent. IL-13, which stimulate mucus secretion from bronchial submucosal glands and also promote IgE production by B cells. SENSITISATION: The Fc part of IgE binds to FcεR on mast cells/ basophils, exposing its variable region. This IgE loading takes 10-15 days. This is the SENSITISATION PHASE as the mast cells/ basophils are ready to work the next time the pollen appears. When the antigen reappears, they will come into contact with sensitised (IgE-loaded) mast cells and stimulate it and cause an initial phase reaction and a secondary reaction. INNITIAL PHASE REACTION Upon stimulation, the mast cells undergo degranulation, secreting preformed products (primary mediators). These include histamine, proteases, neutrophil chemotactic factor and eosinophil chemotactic factor. The proteases will do two things: Further tissue damage, causing the release of more inflammation mediators. Convert C3 and C5 into C3a and C5a which will bind to the receptors on the mast cells, thus simulating the mast cells further. The histamine has the following effects: Vasodilation Increased vascular permeability leading to partial edema in the area. Spasmatogenic: histamine receptors are found on the smooth muscle lining of the various tracts. Histamine causes them to contract. Increasing glandular secretions, causing luminal obstruction. Overall, histamine causes narrowing of the lumen of the tract. SECONDARY REACTION This phase largely consists of inflammation with recruitment of leukocytes. Upon stimulation, the nucleus of the mast cell is activated, leading to protein synthesis of cytokines. These small, soluble proteins (cytokines) are released by the mast cell (and epithelial cells) and they act as signaling molecules. The cytokines are termed secondary mediators as they are not preformed. Two important cytokines are secreted by mast cells and epithelial cells: IL-3 and IL-5, which are chemotactic agents for eosinophils. IL-5 and IL-3 are also produced by Th2. The second wave of mediators stimulates the late reaction. Eotaxin - produced by airway epithelial cells, potent chemoattractant and activator of eosinophils. Major basic protein (MBP) of eosinophils causes epithelial damage and more airway constriction. Also, the mast cell secretes leukotrienes, which attract neutrophils. Eosinophils secrete their granular contents: histaminases (reducing inflammation) and enzymes that destroy leukotrienes (reducing attraction of neutrophils). Many mediators have been implicated in the asthmatic response: Leukotrienes C4, D4, and E4: extremely potent mediators that cause prolonged bronchoconstriction as well as increased vascular permeability and increased mucus secretion. Acetylcholine: released from intrapulmonary motor nerves, which can cause airway smooth muscle constriction by directly stimulating muscarinic receptors. Over time “airway remodelling” occurs, these changes include: Hypertrophy and hyperplasia of bronchial smooth muscle: Hyperplasia of the helical bands of airway smooth muscle. Smooth muscle also alters in function to contract more easily and stay contracted because of a change in actin-myosin cross-link cycling. These changes allow asthmatic airways to contract too much and too easily. (Muscular Bronchoconstriction/Bronchospasm) Epithelial injury: In the conducting airways there is loss of ciliated columnar cells into the lumen. Metaplasia occurs with a resultant increase in number and activity of mucus-secreting goblet cells. Increased airway vascularity. Increased subepithelial mucus gland hypertrophy/hyperplasia. Overall thickening of airway wall. Basement membrane is thickened due to subepithelial fibrosis with deposition of types III and V collagen below the true basement membrane. Mast cells are present in the perivascular tissue (connective tissue around vessels) and under the mucosal lining of the skin, respiratory tract, GI tract and urogenital tract. They are well distributed around the body, increasing the chance of a free antigen binding to a loaded mast cell. Mast cells are very sensitive and can be stimulated by many factors, some of which include: Cross-linking of loaded IgE by multivalent antigens. C3a, C4a, C5a (mast cells have receptors for these). Drugs: codine and morphine. Venoms such as that from a bee sting. Morphology In patients dying of status asthmaticus the lungs are overdistended because of overinflation, with small areas of atelectasis (partial or complete collapse of lung). The most striking macroscopic finding is occlusion of bronchi and bronchioles by thick, tenacious mucus plugs. Curschmann Spirals: histologically, we see spiral shaped mucus plugs. The mucus plugs contain whorls of shed epithelium. These result either from: Mucus plugging in subepithelial mucous gland ducts which later become extruded (forced out). Plugs in bronchioles. Numerous eosinophils and Charcot-Leyden crystals are present. These are collections of crystalloid made up of a eosinophil lysophospholipase binding protein called galectin-10. Clinical Course of Asthma The classic acute asthmatic attack lasts up to several hours. In some patients these symptoms of chest tightness, dyspnea, wheezing, and cough with or without sputum production, persist at a low level constantly. In its most severe form, status asthmaticus, the severe acute paroxysm (sudden attack of an activity/emotion) persists for days and even weeks. Under these circumstances airflow obstruction might be so extreme as to cause severe cyanosis and even death. The clinical diagnosis is aided by the demonstration of: An increase in airflow obstruction Difficulty with exhalation (prolonged expiration, wheeze) Elevated eosinophil count in the peripheral blood and the finding of eosinophils Curschmann spirals Charcot-Leyden crystals in the sputum (atopic asthma) Up to 50% of childhood asthma remits in adolescence only to return in adulthood in a significant number of patients. In other cases there is a variable decline in baseline lung function. Investigations Diagnosis: Compatible clinical history plus either/or: FEV1 ≥ 15% (and 200 ml) increase following administration of a bronchodilator/trial of corticosteroids. 20% diurnal (daily) variation on ≥ 3 days in a week for 2 weeks on PEF diary. FEV1 ≥ 15% decrease after 6 mins of exercise. Treatment There are two categories of antiasthma drugs; Bronchodilators - reverse the bronchospasm of the immediate phase Anti-inflammatory agents. Bronchodilators; anti-inflammatory agents inhibit or prevent the inflammatory components of both phases Bronchodilators β2 –adrenergic receptor agonists – Salbutamol/ Salmetrol Their primary effect in asthma is to dilate the bronchi by direct action on the β2-adrenergic receptors of smooth muscle. They also inhibit mediator release from mast cells and TNF-α release from monocytes They increase mucus clearance by an action on cilia. Two categories of β2-adrenergic receptor agonists are used in asthma. Short-acting agents: Salbutamol Given by inhalation The maximum effect occurs within 30 minutes and the duration of action is 3-5 hours. They are usually used on an 'as needed' basis to control symptoms. Longer-acting agents: Salmetrol These are given by inhalation. The duration of action is 8-12 hours. They are not used 'as needed' but are given regularly, twice daily, as adjunctive therapy in patients whose asthma is inadequately controlled by glucocorticoids. Side Effects: Tremor Tachycardia Cardiac dysrhythmia Xanthine drugs – Theophylline Acts as an inhibitor of phosphodiesterase, with resultant increase in cAMP – Causing muscle relaxation. They are more likely to cause side effects and have a less favourable risk: benefit ratio. Unwanted effects: CNS: stimulant (tremor, sleep disturbance) Cardiovascular (stimulate heart, vasodilation) GI tract (anorexia, nausea, vomiting) Muscarinic receptor antagonists – ipratropium Blocks actions of acetylcholine at receptor in parasympathetic nervous system. Low levels of acetylcholine released from cholinergic nerves in airways. Few muscarinic receptors activated. Inhibit elevated mucus secretion in asthma and cause bronchodilation. Well tolerated. Cysteinyl leukotriene receptor antagonists - Montelucast Prevent exercise-induced asthma and decrease both early and late responses to inhaled allergen. Their action is additive with β2-adrenoceptor agonists. They also reduce sputum eosinophilia. Act at cysteinyl-leukotriene receptors - on bronchiole smooth muscle cells – blocking C4, D4. Prevent actions of bronchial spasmogens. Stimulate mucus secretion. Side Effects: Headache Gastrointestinal disturbances Anti-inflammatory Agents Usually given by inhalation. Full effect usually takes a day or two. Glucocorticoids - Beclometasone They are not bronchodilators. They prevent the progression of chronic asthma. They are used as prophylactic treatment for asthma. They are effective in acute severe asthma. They decrease formation of cytokines in particular the Th2 cytokines that recruit and activate eosinophils (IL-5) They are responsible for promoting the production of IgE and the expression of IgE receptors. Glucocorticoids also inhibit the generation of some (PGE2 and PGI2) vasodilators. Corticosteroids inhibit the allergen-induced influx of eosinophils into the lung. Glucocorticoids: Reduce production of: Cytokines Spasmogens (LTC4, LTD4) Leucocyte chemotaxins (LTB4, PAF) Therefore reduce: Bronchospasm Recruitment and activation of inflammatory cells Mechanism of glucocorticoid action: Enter cells Bind to intracellular receptors in cytoplasm GRα GRβ Receptor complex move to nucleus Binds to DNA in nucleus Alters gene transcription E.g. induction of lipocortin E.g. repression of IL-3 Reduced synthesis of IL-3 (the cytokine that regulates mast cell production) may explain why long-term steroid treatment eventually reduces the number of mast cells in the respiratory mucosa, and hence suppresses the early-phase response to allergens and exercise. Side Effects: Oral Candidas Sore throat Croaky voice Patient adherence Adherence means following the advice of health-care professionals. – this includes taking preventive action, keeping medical appointments, following self-care advice, and taking medication as advised Non-adherence is usually defined as a failure to follow advice, which will lead to a harmful effect on health Patients’ own reports, pill counts and analysis of blood or urine samples can be used to measure adherence – patients consistently overestimate their own adherence It is estimated that 40-50% of all patients are non-adherent It has been suggested that 10-25% of hospital admissions are due to non-adherence Patients are non-adherent for a variety of reasons, patients may forget to take medication or find it difficult, and others may disagree with the diagnosis or the medication regime Key questions in the patients mind influence adherence – i.e. do I really need this medication? Adherence is most likely when patients understand what they are being asked to do and why Patients must also remember what they are being asked to do if they are to act on it later Satisfaction with the doctor and the consultation makes adherence more likely Patients are more likely to feel satisfied and to understand advice when doctors find out what they think is wrong and discuss this. The doctor should seek to reach an agreement with the patient with the patient about what is wrong and what should be done about it. The importance of such co-operation has been underlined by the proposal that, instead of encouraging adherence, doctors should seek to establish “concordance” in their consultations. If doctors can facilitate joint, negotiated decision-making, or concordance, about treatment then patients are more likely to adhere. Promoting patient satisfaction – Adherence is more likely when doctors consider and discuss the patient’s perspective, understanding and motivation. Increasing patient understanding – Doctors can increase understanding by simplifying information and by discussion of patients health beliefs. Helping patients remember – Doctors can increase patient’s recall by using explicit information, stressing and repeating instruction and giving specific written advice. Adherence tends to be better when patients experience symptoms of illness. This has a clear implication for medical conditions such as hypertension Adherence falls as the complexity or burden of dosing regimens increases. It is generally easier for patients to adhere to single daily doses than multiple daily doses and their associated timing schedules. Adherence rates are lower when patients experience unpleasant medication Side effects. Adherence is not strongly influenced by demographic factors such as age, sex, or socioeconomic status. Better adherence is found when; Patients believe their condition is serious They perceive more benefits from adherence There are fewer barriers to adherence Patients are more motivated Adherence tends to be poorer in patients who are depressed or have low levels of social support Adherence tends to be better if patients have longer consultations and a trusting relationship with a doctor who expresses a genuine interest in their health. Better doctor-patient relationships lead to better adherence Systemic Biases in Risk Perception (LEARN THIS!!! HINT): Compression: overestimate low risks, underestimate high ones. Miscalibration: overestimate accuracy of own knowledge. Availability: overestimate notorious risks. Optimism: underestimate personal susceptibility. Health behaviours Our health is affected by a range of behaviours, which can be categorised as Health protective behaviours – Includes screening behaviours Health risk behaviours - Includes things such as smoking, substance misuse and unsafe sex Behaviour is determined by many factors, including individual differences, social surroundings and influences, and cultural aspects. In order to devise effective health promotion programmes we need to know the main causes of specific behaviours in different groups of people. For example, young people might be more motivated to eat a low-fat diet and regularly brush their teeth to improve their appearance rather to improve their health Theory of planned behaviour (TPB) The theory of planned behaviour represents a progression from the theory of reasoned action. This theory states that the strongest predictor of behaviour will be a person’s intentions. This is affected by 3 factors; Attitude towards a behaviour, which is composed of either a positive or negative evaluation of a particular behaviour and beliefs about the outcome of the behaviour. Subjective norm, which is composed of the perception of social norms and pressures to perform a behaviour and an evaluation of whether the individual is motivated to comply with this pressure. Perceived behavioural control, which is composed of a belief that the individual can carry out a particular behaviour based upon a consideration of internal control factors and external control factors, both of which relate to past behaviour. According to the TPB, these three factors predict behavioural intentions, which are then linked to behaviour. The TPB also states that perceived behavioural control can have a direct effect on behaviour without the mediating effect of behavioural intentions. Self-efficacy theory Self-efficacy is the belief in one's effectiveness in performing specific tasks.