Physiology (3) Pulmonary Function Test:

Pulmonary Function Test: Today we will continue with the pulmonary function test, and the question is: why do we do pulmonary function tests for patients? Can pulmonary function tests tell us what type of disease the patient has? 1. Pulmonary function tests (lung volumes and capacities) help in diagnosis, but they are not diagnostic themselves, they can tell us if the patient has some sort of a restrictive or obstructive disease (they show different patterns for restrictive and obstructive), so they can direct us to a proper diagnosis. 2. They can help us in following up the patient, is he responding to the treatment. For example, if the patient has asthma and is given bronchodilators, beta blockers, we can know if he is responding or not. 3.They can tell if the disease is reversible or irreversible, for example in the early stages of COPD, if he responds to bronchodilators, his condition may still be reversible. 4. Very quick prognostic tests, they can classify the disease, is it a mild COPD, or moderate or severe. 5. They can help us in screening workers, like phosphate mine workers where dust might infiltrate the lungs. So we do periodic tests every 6 months for example and see how much the lung is affected, if it is affected we take him away and put him in an office work. The tool that is used is called the spirometer: a hose through which you breath in and out measuring the volume you are breathing in and out. The spirometer only measures the air coming in and out, so if the air stays in the lung and doesn t come out, you cannot measure it. So the spirometer can measure the tidal volume, the inspiratory reserve volume IRV, the inspiratory capacity IC, expiratory reserve volume ERV, and vital capacity VC. But it cannot measure the residual volume RV(since it resides in the lung), and any capacity related to the residual volume thus cannot be measured too, for example FRC (functional residual capacity) cannot be measured because RV is a component of FRC. FRC= ERV+RV Also total lung capacity cannot be measured, because it also contains the residual volume. So we must have a second method to measure the residual volume. Now the question is how are we going to measure the residual volume? If you measure the FRC, then you can calculate the residual volume. So what we need is a method to measure FRC, since ERV can be measured using the spirometer RV= FRC-ERV 1

So we ask the person to breathe from a closed bag, this bag contains known volume of air with non absorbable gas, when the person inhales this non absorbable gas (helium) it will not cross the alveolar capillary wall, the respiratory membrane. Now we start the experiment at a known volume V1=10 L for example, and known concentration of helium C1. So C1 *V1= total amount of helium in the bag. Now we ask the person to breathe in and out of the bag several times (10 to 15 times), starting from FRC, to mix the outside air (bag air) with the inside air (lung air). At the end when we come to equilibrium, the helium will be diluted by how much air we have in the lung, therefore : C1*V1=C2*V2 (conservation of mass) helium remains the same. We know V1 which equals 10 L C1 is also known ( we put the helium in the bag, so we know its concentration) V2 is unknown, and it is V1 + FRC (new volume) C2 can be measured by taking a sample from the bag and measuring the concentration of helium. And thus we can calculate FRC, and by knowing FRC we can calculate total lung capacity etc. This is called the helium-dilutional method. Moving on to the Anatomic Dead Space: Anatomic dead space normally equals 150 ml. When you breathe in, anatomic dead space contains : PO2: 150 PCO2: 0 We only measure this volume and the alveoli contains: PO2:100 PCO2: 40 we ask the person to take a single breath of pure Oxygen, meaning 100% oxygen, meaning 760 mmhg as PO2, with no nitrogen. - Note : how much nitrogen is there in the anatomic dead space in a normal person, under normal conditions? We said before that PH2O= 47 So PN2= 760- (150+47)= 563 so normally there is nitrogen in the anatomic dead space.. but when you breathe in pure oxygen in one single breath, the anatomic dead space only contains oxygen (and of course H2O) but no nitrogen. The doctor might ask a question as the following: What is the PO2 in the anatomic dead space following a single breath of pure oxygen? The answer is: 713 (760-47) now we ask the person to exhale, and the exhale goes into a machine which measures two things: 1) the volume of the air. 2) the nitrogen content in this air. The anatomic dead space contains no nitrogen (only pure oxygen) 2

In relation to the nitrogen gas, there are two compartments: Compartment (1): there is nitrogen Compartment (2): no nitrogen (pure oxygen) (2) pure O2 no N2 (1) But at the transitional area between the two compartments we do have some nitrogen, because gases mix with each other by diffusion. So we do not expect to see abrupt increase in nitrogen, it s actually gradual (1) (2) (3) Anatomic dead space volume So there are three phases: Phase (1): no nitrogen at all Phase (2): nitrogen increasing gradually Phase (3): nitrogen reaches plateau, now the air comes purely from the alveoli containing nitrogen. The anatomic dead space volume equals the volume of phase (1) + half of phase (2) Physiologic dead space volume: When you have part of the lung (the apex) ventilated but not perfused, the air in that part of the lung is exactly like the outside air, so the PO2 will be 150, and PCO2 will be zero. When you exhale, you exhale from two areas, one area contains PCO2: 40 and PO2: 100 (normal alveoli), the other is devoid of PCO2 and contains PO2: 150 (ventilated but not perfused alveoli), and the two mix. The more the alveolar wasted volume, the less the CO2 in mixed expired air. Last lecture, we calculated the mixed expired air: (150*0) + (350*40) = 28 500 If there was more wasted volume it will be less than 28, for example 20. With more wasted volume, it will be 15 there will be dilution. 3

PO2: 150 PCO2: 0 Wasted volume PO2:100 PCO2:40 (alveolar) Vp: physiologic dead space volume VT:tidal volume PaCO2: arterial Vp= VT* ( PaCO2 PCO2 mixed expired air) PaCO2 Ex: in a normal human: VT= 500, PaCO2= 40, PCO2 mixed expired air= 28 Vp= 500*(40-28) = 500* 12 = 150 40 40 if PCO2 mixed expired air = 20: 500* (40-20) =250 40 Here the Vp= 250 = 150 (anatomic dead space ) + 100 (alveolar wasted volume) And that s how we measure the physiologic dead space by measuring the PCO2 of mixed expired air and the arterial pressure. And the anatomic dead space can be measured by analyzing the nitrogen in the expired air. Normally, in healthy normal people like you, anatomic dead space equals the physiologic dead space, and thus the alveolar wasted volume = zero By this we are done with the volumes and capacities. Elasticity: The lung is an elastic structure. And an elastic structure has two things: - To move the elastic structure from its resting state, you need to apply force, so its active. - Bringing it back is passive. Here we are going to repeat talking about: how do we normally breathe in? Normally we breathe in by making the pressure in the alveoli sub-atmospheric. How do we make it sub-atmospheric? By changing the volume. How do we change the volume? By making the surrounding pressure less negative. And how do we make the surrounding pressure less negative? By contracting the inspiratory muscles (external intercostals). So you need contraction it is active. 4

First you make the intra alveolar pressure: -1, second you force the air in. But of course these don t occur as two separate steps, they are usually combined. -1 When enough air molecules interbalance at the new volume, then again the pressure goes back to zero. P = F A We increased the area, but we also increased the air ( force is the number of molecules hitting the wall. So at the end of inspiration, the intra alveolar pressure comes back to zero. During inspiration the intra alveolar pressure must be sub-atmospheric. Once the alveolar pressure becomes zero, no more inspiration, because there is 0 no driving force. So at the end of inspiration we have larger volume and increased number of air molecules. Expiration: You compress the lung by relaxation of the diaphragm, so expiration is passive ( it needs relaxation of muscles). You compress the lung, so you are dealing with smaller volume but a larger number of molecules is still there. The alveolar pressure increases to +1. +1 +1 > 0 then you force air out. When enough air molecules leave the lung, the pressure of the alveoli goes back to zero ( it declines). When it reaches zero no more expiration.. at the end of expiration the intra alveolar pressure comes back to zero. lets think about it: - why did the inspiration even end? Because there was no driving force, which means the pressure is equal inside and outside. - Why did the expiration end? Because there was no driving force The inspiration is active, we pay for it with 5% of our total ATP expenditure. Expiration is passive, it is free, we don t pay for it. this is a gift But sometimes we have to pay for expiration, it costs us a lot of work of breathing, then we will spend most of our ATP to support the respiratory muscles. this will cause fatigue. This type of breathing is called negative pressure breathing, because we make one end negative (sub- atmospheric) 5

But that needs contraction of the diaphragm and if the patient can't contract the diaphragm (because of drug overdose, suppression of the respiratory neurons, no signal to skeletal muscles, etc) we must help him... We must intubate the patient. And when we put the tube we must be careful in tightening, if it's loose it may go to the right lung because the right main bronchus is more vertical and therefore anything that might be inhaled will go to R. bronchus... This is very dangerous because if air goes to right, the left will collapse... Therefore the intubation process; you should be very cautious with it. The tube reaches the trachea through a hose which has a machine making the pressure positive(increasing it), pushing air in, waiting for some time for making gas exchange, then making the pressure negative, driving air out - the doctor pointed to the ventilator, the respirator, the resuscitator, but he didn t mention them in the lecture I attended, so I don t know the drawing.. I m sorry.. This is kind of positive pressure breathing: you make one end positive. But it s not a physiologic pattern of breathing, it s artificial. What is the take home message? 1. our normal pattern of breathing is negative pressure breathing 2. positive pressure breathing: artifical 3. inspiration is active, expiration is passive Now to continue with the previous lecture: Yesterday we said that: 1) Every elastic structure tends to go back to its resting state if you move it from its resting state. 2) To move any elastic structure from its resting state, you need to apply force. To bring it back is free (passive). Therefore the lung is an elastic balloon(inflated): if outside the body it collapses to a minimal volume= 150 ml,which is less than residual volume, which means in-vivo (inside the chest) you cannot reach this volume, we can only reach the residual volume. So the lung has tendency to collapse and the thorax is compressed which means if we open the chest for a heart surgery, the thorax will expand- why? It expands to its resting state, because the negative intrapelural pressure was compressing it before. So there are two tendencies: one is tending to expand, the other is tending to collapse, and that s how negative pressure is created between them. The resting volume of the thorax = 75% of total lung capacity ( 4.5 L) Normally, at FRC, the thorax is compressed trying to expand (trying to reach its resting volume),and the lung is inflated and tries continuously to reach its resting volume (minimal volume) The most important of the lung capacitiess and volumes is FRC 6

lung chest wall 75% of TLC FRC+Vt FRC MV (1) (2) (3) (4) We said before that TLC= 5.7 At FRC 2.2, the lung is attempting to collapse, the thorax is tending to expand to 75% of TLC (or 4.5L). At FRC the tendency of the lung to collapse is equal to and opposite to the tendency of the thorax to expand. And therefore, the lung-thorax system is at rest. Column (2) in the figure above. So the FRC is resting volume of the system. We have to pay for moving the system from its resting volume. By taking the Vt, the tendency of the lung to collapse is more and the tendency of the thorax to expand is less, and now the system if left alone, with no force applying on it, will tend to collapse and therefore expiration is passive (elastic structure). Column (3) in the figure above. If we infalte the lung to TLC, the tendency to collapse is huge. - Let s try to do it: try to fill your lungs to the maximum, close your mouth and nose and relax your respiratory muscles, you will notice that the tendency to collapse is huge; you can t hold your breath anymore. Here the thorax is also tending to collapse because its resting volume is at 75%of TLC. Column (4) So both are tending to collapse, and the system now has a huge tendency to collapse. When we decrease the air to the RV (residual volume), which means performing expiration, expiration here is active. - The tendency of the lung to collapse becomes minimum, but it is still tending to collapse. Whereas the tendency of the thorax to expand becomes huge and the system now is tending to expand. - In this scenario, inspiration is passive and expiration is active. Column (1) So inspiration can be passive as in this example. We conclude that the lung is always tending to collapse. 7 NOTE: Whether you increase ERV to the upper extremity or decrease it to the lower extremity you have to pay for it

What are the collapsing forces in the lung? collapsing forces in the lung are of two types: - one is the strethching elastic fibers, elastin - and the other is surface tension Therefore surface tension with elastic fibers elongation/ stretching which try to recoil 2/3 of these elastic forces come from surface tension, 1/3 from elastic fibers. In order to overcome this, you need inflation pressure, an opposite pressure which is manifested in the intra-pleural pressure (-ve) - if the intra-plural pressure is: -4, then the collapsing force is +4 - if I have -14, then the collapsing force is 14 elastic fibers are unlikely to change, therefore any additional amount is from surface tension which is more prone to change. think of this experiment: let's inflate a lung and see how much inflation pressure we need. ( we said that at FRC we need -4, but it becomes -6 when we take the tidal volume.) How can we inflate the lung? - You can t put your mouth on the lung and blow in it. - Instead you put lung in a box, its floor can be moved down, and the lung is connected to a tube. - Inside the box, tube, lung: pressure is 0 P=0 P = 0 P=0 P=0 negative pressure - Now if you increase the volume surrounding the lung, you make the pressure negative, by doing so you automatically allow the lung to inflate which allows air to come in. The way to inflate the lung is to change the surrounding pressure. So we do the experiment by changing the pressure to more negative. In the graph next page, the x-axis: negative change in pressure( form -50 to zero) and y-axis: is volume. In each step we will change the pressure surrounding the lung and measure how much volume increment we have. So basically its delta V= change in volume per unit change in pressure delta p and this is the compliance. Compliance: is how much volume you can get by changing the force applied which is the negative pressure here. - If you get too much change in volume, this is a high compliance. (like in rubber bands) - If you get very little change, this is a stiff structure. 8

Deflation compliance curve 3 Inflation compliance curve 2 1 Phase 1 phase 2 phase 3 What you'll see in the graph is that in the first phase: you are changing the pressure but with no success in changing the volume... very minimal change: therefore in this phase the lung is not compliant. It's like a balloon, when you first blow into it it doesn't inflate, then it becomes easier. When the walls of the alveoli adhere with each other with water vapor, it is very difficult to separate them. So it s very difficult to inflate the lung from 0 volume. Second phase: At the critical opening pressure any increase in pressure is followed by an increase in volume. Here the slope of the curve becomes high. very compliant. The balloon before popping doesn t inflate anymore (non compliant) which is phase 3 It s not wise to inflate completely collapsed alveoli. And it s not wise to inflate already inflated alveoli. It takes too much effort to make the pressure more negative we need muscle contraction so work of breathing will cost too much. If the lung is not compliant 5% of ATP is not enough for respiration, 30% maybe enough, or even 70%. Now when you consume 70% of ATP on respiration what is left for the rest of body?! You will die from fatigue Compliance curve of lung has three phases: this is an advantage for us to breath from FRC. From FRC you take in tidal volume, which will consume very little work. The graph above represents the inflation compliance curve, and the deflation compliance curve. We notice that inflation and deflation did not come from the same path. It s like we are saying that the distance from the university to Sweileh is 4 Km, but the distance from Sweileh to the university is 5Km. 9

When Einstein said that time is not constant, everyone laughed at him, they thought he had some sort of hysteria. From here you can memorize the concept of inflation and deflation having two different paths as hysteresis. Hysteresis: is when backward process is not the same as the forward process, they don t follow the same path. And the question now is: why do we have hysteresis? - For example: lets say we have V1 as in the Graph. - To hold this volume we need P1 during expiration, to hold the same volume we need V1 more pressure (P2) during inspiration. IT DOESN T MAKE SENCE! P1 P2 Example 1: If the doctor is holding the overhead projector and he is standing one meter away, and someone measures the tension in his muscle, turns out to be 50. But if they lower the projector (at the same distance) the tension is 40. Although it s the same projector and same distance this is hysteresis. It seems like, to open the alveoli you need too much force, but to hold it open you need less force. Example 2: Weightlifters: the hardest part is lifting the weight, once they lift it it s easy to it hold it for 3 seconds then put it down. - So to inflate the lung takes too much, but to keep it inflated takes less effort. This is some sort of paradox So hysteresis is: when I inflate the lung I need more inflation pressure, when I deflate the lung I need less. B A Lets do another experiment: Filling the lung not with air but with saline, normal saline 0.9%, and seeing how much pressure is needed to inflate the lung with saline. - When you breathe in you take water vapor, and the alveoli is like a sphere, a sphere of air bubble has surface tension; which means the polar water molecules are attracted to each other, they try to bring the structure to the centre, so they try to collapse the structure this is a collapsing force. *surface tension: is a characteristic of water that makes it like a pseudo membrane because of waterair interface it allows some insects to walk on water. 10

When filling the alveoli with saline there is no water-air interface,(there is just saline) so you can cancel surface tension. Now there is only one force to overcome which is the elasticity of the elastic fibers.(elastin) Why do we need to have negative intraplueral pressure? Why do we need to overcome the collapsing force of the lung? The intrapleural pressure of the lung is -4; it reflects the collapsing force of the lung. The lungs have two collapsing forces, surface tension and elastic fibers that have been stretched. Surface tension is whenever you have air- water interface. - When filling the lung with saline I have only one force to overcome, that leads to reducing the amount of pressure needed less hysteresis is seen here. In the figure on the previous page, we can see the difference between the hysteresis in water filled and saline filled lungs In A (water filled) greater difference between the routes (more hysteresis). In B (saline filled) less difference (the routes are close to each other, less hysteresis). - Surface tension seems to be more during inflation and less during deflation When you have more surface tension you have more collapsing force you need more inflation pressure(which is the opposite force) to prevent this collapsing, manifested in the negative intrapleural pressure. Example: an air bubble is not stable, it will collapse but if you put detergent in it, that makes it stable since the detergent is a non-polar material, while water molecules are polar( attracted to each other) If tension in the air bubble is 10 then I need inflation pressure of 10 so the bubble will become stable. So this pressure is directly proportional to the surface tension. The more the surface tension the more the pressure you need to inflate. This is called LaPlace s law. P= 2T/r P: pressure, T: tension, r: radius. The radius of the alveolus at FRC is 100 micrometer. The radius is the same whether during inflation or deflation. So why is the surface tension different? Because tension changes. Summary: Inflating the lung occurs by changing the surrounding pressure; making it more negative. First I will inflate, second I will deflate. 3 Inflation needs making the pressure more negative, so I follow a certain path in three phases: 2 (1) uncompliant, (2) compliant, (3) uncompliant And FRC comes in the middle ( in phase 2) 1 Deflation comes in a different path hysteresis Why do we have hysteresis? Most likely due to surface tension. 11

To hold the lung at FRC you have -6 (for stretching the elastic fibers and surface tension), while holding it at FRC when filled with saline you need -2 (this is what s needed to stretch the elastic fibers). Which means that the surface tension forces are two times more than the elastic fiber forces. Your colleague: sarah qawasmeh Special thanks for: maram abu halaweh THE END 12