بسم هللا الرحمن الرحيم

بسم هللا الرحمن الرحيم Yesterday we spoke of the increased airway resistance and its two examples: 1) emphysema, where we have destruction of the alveolar wall and thus reducing the area available for diffusion and increasing the capillary bed (increasing pulmonary-vascular resistance) leading to cardiac problems like heartdilatation -- corpulmonale. 2)chronic bronchitis, is due to cigarette smoking: the same applies for emphysema where we have hyperplasia of goblet cells in chronic bronchitis, excessive secretion of mucous, forming a good medium of bacterial growth and thus bronchitis; productive cough for 3 months, continuously for 3 months continuously in the winter time for 2 years is enough to diagnose it. All patients with chronic bronchitis have some sort of emphysema and the opposite is true; overlap between the two diseases. Patients with bronchial asthma given a bronchodilator, β2 agonist (albuterol, salbuterol) which are specific β2-agonist, and if FEV1 is improved by 200 ml like for example: measure FEV for first second, give medicine and then measure it again... if improved by 200 ml or 12% this means reversibility (the condition is reversible): diagnostic for asthma,but chronic bronchitis or emphysema is unlikely to be reversible. One test we didn't mention is peak expiratory flow, maximum flow, and maximum velocity. 600L/min or 10L/s peak expiratory flow is when you ask the patient to exhale from TLC as forcefully as possible and you measure the maximum flow, which can be measured when lungs are fully inflated... so at TLC, the flow equals around 10 L/ s or 600 L/ min, if you start the test at lower volumes you get less flow so when you reach the residual volumethere is no flow at the residual volume (expiratory flow). TLC 50% RV TLC = Maximum flow Inspiratory flow: you ask the patient to inspire in the machine either followed by expiratory or expiration then forced inspiration and you measure the flow, then you get a loop as seen in the figure. The patient with emphysema has destruction not only in the alveolar wall but also the elastic fibers are destroyed, therefore his compliance is more than normal and the penalty is that he cannot deflate the lung easily he has to put effort, easy to inhale, difficult to exhale: more than normal TLC. In this patient we will see that a normal person: the tendency of lung to collapse is balanced by thorax's tendency to expand and FRC equals 2.2 L but this patient has destruction of the elastic fibers, the tendency for the lung to collapse is decreased. In most of pulmonary pathology, the thorax is not considered. 1

So in this person, he tries to increase his FRC hoping to do two things: to decrease the tendency of thorax to expand and to increase the lung tendency to collapse so he reaches a new equilibrium point... so his FRC is more than a normal person. FRC in normal person: tendency thorax to expand = tendency for lung to collapse. The patient, the FRC is more because he wants to decrease the tendency of thorax to expand and increase lung tendency to collapse and when you perform a PFT (pulmonary function test), his TLC is higher, 6.7 L instead of 5.7; his FRC ismore, he cannot exhale the vital capacity as a normal person and therefore his RV is higher too. New FRC FRC = 2.2L This figure below gives us a different diagram in the flow vs. volume loop, the peak flow is still less because he has increased airway resistance. The line in the middle: above is expiratory and below is inspiratory. This person has TLC more but the peak flow is less because he has increase airway resistance (on the left). A person with restrictive lung disease (on the right) can exhale easily but cannot inhale so he cannot reach the TLC and tendency to collapse is huge (opposite to emphysema) for some reason (surface tension, elastic fibers or whatever reason) so he has reduced the FRC to TLC` TLC RV reduce the tendency to collapse and to increase the tendency of the thorax to expand (figure) therefore causing the FRC to fall below normal and his TLC is also below normal as well as his RV. He will exhale easily and inhale with difficulty. TLC decreased but he has no airway resistance, he will show a different curve. TLC is less (seen in spirometer). The peak flow is less than normal but is more than normal person at the same volume, so the curve is shifted to the right where the RV is less, TLC is lessand the FEV1 is also less than normal. FVC is less than normal, however the FEV1/ FVC ratio = 80%. Respiratory membrane 2

Is composed of 5 layers which are the total layers where the oxygen must cross to enter the RBC's in order to bind to Hb. These 5 layers are: alveolar epithelium, basement membrane, interstitium, capillary basement membrane, capillary endothelium : These 5 layers altogether form the respiratory membrane, so oxygen or CO 2 must cross all these 5 layers. The thickness of these layers is 0.2 micrometers maybe 0.5-0.6mm. Now we will test the respiratory membrane: is it normal or abnormal Under normal conditions, you think of two things: 1) do you have sufficient area. The area available for diffusion is between 50-100 meters square (respiratory membrane). The thickness we have here is it 0.1 micrometer or 0.2, because diffusion of gas is directly proportional to area and inversely proportional to thickness. Letscompare the gases in the alveolar: Until now, we consider it the same as arterial regarding same composition of oxygen and CO 2, if you measurealveolar; it is nearly equal to arterial although there is some difference. Ventilation: is equal to 6L/ min this is divided to alveolar ventilation 4.2 L/ min and ADS 1.8 L/min. We care about the 4.2 L/ min because this is the new fresh air. Perfusion is 5 L at rest(the cardiac output). Therefore V/Q = 4.2 / 5 = 0.84 Last time, we considered regional differences between V and Q in the base and the apex : soif we were to draw the lung and considered PCO 2 alveoli and PO 2 in the alveoli as well, a normal person is it PO 2 of 100 and PCO 2 of 40. If we have ventilation but not perfusion = ventilation perfusion ration infinity pulmonary embolism, no blood flow... the PO 2 in the alveoli would be 150 and the PCO 2 in the alveoli is 0. V/Q = 0, no ventilation but with perfusion, PO 2 alveoli = 40 like that of the venous and PCO 2 = 45. The lung's base lies where we have less than 100 PO 2 and the apex where we have more than 100 PO 2. V/Q = 0 like a shunt unit, as in R-L shunt unitwhen the blood for example from the right heart to the left heart without getting a chance for oxygenation is called R-L shunt... so at this point, it is a shunt unit. 3

V/Q=0 Ventilation with not perfusion: dead-space unit. PCO 2 45 40 Apex Base 40 100 150 PO 2 a Lung disease can also be classified in terms of pathophysiology as shunt-producing diseases (V/Q=0) or dead-space producing diseases (V/Q= ). The composition of alveolar air in terms of PO 2 and PCO 2 depends on two things: adequate ventilation and adequate perfusion. Assuming perfusion is constant but you are changing the ventilation, how will this increase or decrease is going to affect the alveolar gas composition: if you increase ventilation: PO 2 alveoli depends on two things the entry of oxygen and its uptake. If the uptake is constant, you are not going to exercise, but you are going to hyper-ventilate at rest, what changes might be expected inthe alveolar gas? if you hyper-ventilateyou expect the alveolar air to be closer in terms of composition to the outside air... therefore PO 2 is increased and PCO 2 is decreased hyperventilation: decreased arterial CO 2. The production of CO 2 is the same and utilization of oxygen remains the same so alveolar ventilation and its relationship with alveolar PO 2 is a linear line and then a plateau: the last thing you can reach is to reach oxygen composition of outside air, reaching 150 mmhg no more than that (not 150 O 2 160). The same applies for CO 2, more ventilation the less the alveolar CO 2. so in the end, what is important inthe RS? we care about the ABG's, arterial blood gases: alveolar blood gases are their "cousins". If you hyperventilate you increase oxygen partial pressure in the blood BUT NOT ITS CONTENT and decrease that of CO 2 partial pressure and content. So the PCO 2 alveoli what increases and decreases it? If you produce more CO 2 in your body it will increase. so you have VCO 2 = production, high metabolism, exercise for example. if you increase ventilation you will decrease it. PCO 2 = (VCO2)/ (VA) * K K= 0.863 4 PO 2, CO 2 VA CO 2

CO 2 production at rest = 200 ml/ min alveolar ventilation per min = 4.2L/min So PCO 2 = 200/4.2 * K = 40 mm Hg So if you increase CO 2 production it will increase and decrease alveolar ventilation will increase, hypoventilation increases alveolar CO 2 and thus increasesarterial CO 2 as well. Alveolar O 2 : Normally we consume 250 ml oxygen at rest. In CVS, we learned to measure CO we needed to know oxygen consumption. CO 2 production over O 2 production = 200/ 250 = 0.8 this is called respiratory quotient or respiratory exchange ration. This is normal. If you eat carbs and nothing else, for each oxygen you consume you will produce one CO 2, causing the respiratory exchange ration = 1but because you are consuming fat whose RQ is equal to 0.7; proteins 0.8; carbs 1 and mixed food is equal to 0.8. The goal of the respiratory system: to maintain normal ABG's, what are the factors of theseabgs : 1) availability of oxygen in outside air 2) patent airways 3) inflatable balloons 4) ventilation: how does this affect these two gases? PO2 alveoli aredirectly proportional to alveolar ventilation and indirectly to oxygen consumption. So here alveolar ventilation in exercise for example both ventilationand oxygen consumption are increased, maintaining a normal arterial level of blood gases therefore ABG's during exercise are normal: PO 2 100 andpco 2 is 40 because both are increased in the same proportion. If you were to double the ventilation at rest you would expect the PCO 2 alveoli to double too since there is also increase in the production as well so the curve will shift to the left where alveolar PCO 2 is kept normal, constant. PCO 2 Oxygen consumption = 250 ml/ min. During exercise it increases VO 2 max, maximum oxygen consumption during maximum exercise... in marathon 1 2 VA runners it is equal to 5 L (20 * normal); normal people may reach 4 L. 5

You are born with high PO 2 max, mostly genetically determined but can be improved by exercise not more than 10%. Now back to the respiratory membrane: How much can you depend on your respiratory membrane when you need it to provide you with 5L, can you depend on it? if it cannot, you shouldn't run the race... so we have to perform a test to see the diffusion capacity of your respiratory membrane/ lung. Why do you need this? sometimes, diffusion capacity of the lung is reduced before any size and symptoms, so you can detect early changes in the respiratory membrane before even blood gases are affected here which means that we have respiratory reserve, if you are consuming it and you reach a certain point, it is too late, the liver you only need 25% of it, the kidneys 75% dead and you're ok. The respiratory membrane, you measure the diffusion capacity of the respiratory membrane which means how much oxygen can diffuse from the alveoli to the blood for every 1 mmhg pressure difference. There is no change for gas diffusion if there is no driving force. So now we return to Ohm's law: flow of oxygen is proportional to driving force PO 2 = PO 2 alveoli - PO 2 venous. Instead of resistance you use permeability (1/R) or diffusion capacity for oxygen (same concept). That is how you measure oxygen consumption. Ask a patient to breathe through a closed bad for 10 minutes with known oxygen content in10 minutes he consumed 2.5 L so in 1 minute = 250ml. To measure diffusion capacity therefore you need to know how much oxygen is being diffused per minute over the delta PO 2. The purpose: to detect any changes inthe respiratory membrane before any signs and symptoms. You also see how much destruction we have (how much is left), what percentage is still effective. 250 ml/ min over delta PO 2... how do we measure delta PO 2 PO 2 is alveolar venous - capillary difference. 100 45 40 1/3 2/3 PO 2 in lung 100, in the capillaries: 40 at the starting point, so the difference here is 60 but you have to measure the diffusion capacity across the pathway before you cross the 1/3 of the capillary it becomes 100 mmhg, so the difference here is 0 (we cannot use average since we don t know the exact point of disconnection), we can say that we are only using 1/3 of our lung and we have 2/3 of your lung reserved, 6

so if a person had a disease he still has good reserve. The same applies to CO 2... when you start it is 45 mmhg, goes down to 40. So you must use another method to measure the capacity if you find one, you can calculate the other, why? Because diffusion capacity in the lung for a gas (x) is equal to (area* solubility of the gas)/ (thickness * molecular weight ) -- (property of respiratory membrane and the properties of the gases... therefore you have the respiratory properties calculate) the larger the MW (molecular weight) the less diffusible the gas is according to the equation : DLx = (A/Dx)*(S/ MW). A=area, Dx = thickness, S=solubility A/Dx is the property of the membrane and S/ MW is the property of the gas. The diffusion coefficient (S/ MW) for oxygen = 1(standard unit) and that of CO2 is 20.3 because the solubility of CO2 is more; it is more attracted to water. What about CO? it is 0.8. So if you have the diffusion capacity for CO, you can calculate the diffusion capacity for oxygen and CO2 because they are all constant. Done by :Laith Al-Ghazawi. Special thanks to :ShaimaShahin and Ward Al-Muheisen. 7