In most textbooks, you will encounter a vast array of "laws", which examination candidates in particular are encouraged to regurgitate, often with minimal understanding. For the record, here are some of them:-
A List of Laws|
Note that this mildly formidable table is mainly for reference purposes.
The wise reader will skip over it, and come back from time to time.
All equations are discussed in a friendly fashion in the body of the text!
Those we are on "first name" terms with (Henry, Charles & Graham) will be used less extensively!
|Boyle's Law||P.V = K||In a container filled with gas, if you decrease the volume, the pressure will correspondingly increase, and vice versa.|
|Dalton's Law||In a mixture of gases, each gas behaves as if it were on its own: it exerts a partial pressure that is independent of that exerted by other gases in the mixture.|
|Hooke's Law||L T||The change in length of a spring is proportional to the tension exerted on the spring.|
|Laplace's Law||P = 2.T/r||The pressure inside a bubble exceeds the pressure outside the bubble by twice the surface tension, divided by the radius. In other words, the smaller a bubble, the more the pressure inside it exceeds the pressure on the outside.|
|Poiseuille's Law||R = 8.L.eta/(pi.r4)|| Where laminar flow occurs, the resistance to flow
decreases with the fourth power of the radius
- if you double the radius, the resistance decreases
sixteen times! Resistance also depends on the eta,
(the viscosity of the gas or fluid), as well as
the length of the tube being assessed (L).|
Note that with turbulent flow, things are completely different - we can't even talk about "resistance" as the drop in pressure is not directly related to flow, but to flow squared!
|The Fanning Equation||P 1 / r5||With turbulent flow, for any particular flow rate, pressure drop depends on the fifth power of the radius of the tube.|
|Fick's Law||Vgas A * P / L||Gas transfer through a membrane is proportional to membrane surface area (A) and partial pressure gradient across the membrane(P), and inversely proportional to thickness (L).|
|Graham's Law||D sol / MW0.5||Diffusion of molecules is inversely proportional to the square root of their molecular weight, and directly proportional to their solubility.|
|Henry's Law||The number of molecules of gas dissolved in solution is proportional to the partial pressure of the gas.|
|Charles' Law||V = K'. T|| As the temperature of an amount of gas increases,
so does its volume (maintaining a constant pressure). We
can combine this with Boyle's law to get: |
PV = nRT
Where n is the number of moles of gas, and R is a constant, the universal gas constant. At standard temperature and pressure, a mole of gas occupies 22.4 litres. The actual value for CO2 and N2O is about 22.2 litres.
|Reynold's number||linear gas velocity * diameter * density / viscosity||Reynold's number is dimensionless. Turbulence occurs if Reynold's number is over 1000, and flow is entirely turbulent if it exceeds 1500.|
Atmospheric oxygen arose as a toxic by-product of the very first photosynthetic organisms, which were possibly quite similar to today's blue-green algae. Smarter organisms rapidly learned to use this oxygen, and minimise its toxic effects. When they possibly unwisely decided to abandon their individual identities and co-operate to form multicellular organisms, and moved onto land, then their problems really began! They needed:
All of these are more-or-less adequately fulfilled by the tightly entwined cardiovascular and respiratory systems. The respiratory system is a marvellous, efficient pump for passing air over the capillary bed of the lung, where oxygen moves into the blood and CO2 is removed from the blood. The inefficient and failure-prone cardiovascular system then takes over, finally distributing oxygen to oxygen-hungry cells throughout the body. The inefficiency with which this occurs can be seen if we look at the oxygen cascade, which documents the changes in partial pressure of oxygen from inspired air down to the mitochondrion where the oxygen is actually used. Oxygen moves down a gradient, from a partial pressure of about 160mmHg in the atmosphere, down to about 4-20mmHg in the mitochondrion! The steps are:
|Inspired oxygen||160 mmHg|
|Alveolar oxygen||~ 120 mmHg|
|Oxygen in the blood||~ 100 mmHg|
|Oxygen at tissue level||~ 4-20 mmHg|
Perhaps this is the PO2 that our ancient unicellular ancestors first found that they could effectively use, and there has been no (heh) pressure to subsequently change, or perhaps this low PO2 is a trade-off related to the number of capillaries needed to support the tissues, but we know one thing, and that is that we could sure use a bigger tolerance margin in critically ill patients!
In the following sections, we will look at the way some of the above steps have been "fine-tuned" to achieve near-optimal function. Our first consideration is the actual mechanics of the lung.
The respiratory tract may be seen as a branching tree-like structure, with about seventeen levels of branching between the trachea and the respiratory bronchioles. As on average the number of branches doubles at each level, we end up with about 217 respiratory bronchioles, or about 130 000 of them. Some authorities have introduced the concept of the "primary lobule", which is the zone supplied by one of these first order respiratory bronchioles. Each primary lobule contains about two thousand alveoli, and is about 3.5mm in diameter. Branches within the primary lobule give rise to alveolar ducts, which in turn give off alveoli. All in all, there are about twenty three intricate levels of branching within the respiratory tree!
A primary lobule at FRC has a volume of about 23 microlitres, and alveoli have on average a diameter of about 200 microns. We are interested in how air gets into and out of these primary lobules.
The diameter of an alveolus was, remarkably, estimated with astonishing accuracy by the Rev Stephen Hales in 1731.
We will not here discuss the anatomy and physiology of the upper airway, which deserves a whole page of its own! First we note that the respiratory system is remarkably effective in achieving movement of air - a normal inspiratory breath of say 500ml in an adult requires a distending pressure of under 3cm H20, and this distension occurs remarkably rapidly, with flow rates of a litre per second or more! How does this occur?
The lungs move in response to external forces - during normal inspiration these forces are the movement of the diaphragm, and movement of the chest wall by the intercostal muscles. Gentle resistances oppose this movement. These resistances are:
A useful analogy is to consider the lung as a spring - if we put energy
in (stretch the spring) then the volume increases, and when we release
the tension, the volume decreases again (the spring shortens). In an
analogy to Hooke's law, we say that:
We still have not explained why it is so easy to inflate the normal lung. Instead of explaining immediately, we will note a further problem. Consider the following diagram of two connected alveoli:
And a third problem! The surface tension of water is about 72mN/m, yet in alveoli we have remarkably low values of about 20mN/m, as noted above.
Fortunately, the answer to all our questions is at least partially contained in one word: surfactant! Surfactant, composed of mainly dipalmitoyl phosphatidyl choline, with a touch of phosphatidyl glycerol thrown in, not only lowers the surface tension of the alveolar fluid, but it lowers the surface tension more as the alveolar radius decreases! Also note that because the surface tension is lowered, the negative pressure in the fluid lining the alveolus is correspondingly decreased, and thus there may be a decrease in the pressure driving fluid from the vasculature into the alveolus!
It appears that even the above is a considerable over-simplification. In the above diagram, we considered just two alveoli, but remember that a 'primary lobule' has about two thousand adjacent alveoli. What will be the effect of partial collapse of one alveolus on surrounding alveoli? Surely a traction will be exerted on them? It is thought that the presence of surrounding alveoli is also important in preventing collapse of any particular alveolus.
We know that air flow is impeded by airway resistance, and also because of the elastic properties of the lung and chest wall. Let's examine these in more detail:
Resistance to airflow is a major contributor to work of breathing. In any system, flow may be laminar or turbulent. Analysis of laminar flow is far simpler than that of turbulent flow. Unfortunately for us, we encounter both within the respiratory system. Turbulent flow is seen with:
Laminar flow is governed by Poiseuille's law. Importantly, halving the radius of a tube will increase the resistance by sixteen times. Note that with laminar flow, the drop in pressure is related to the flow rate, and so we can talk about the "resistance" of a tube, independent of flow. That is:
With turbulent flow, the pressure drop depends on the square of the flow rate, and thus "resistance" will vary with flow. At any particular flow, the pressure change is also related to the fifth power of the radius (the Fanning equation).
With a mixture of turbulent and laminar flow, pressure drop is defined by:
In man we have a convenient approximation:(If you are working in kPa, then the constant multiplier is about 0.24 and not 2.4).
P = 2.4 (flow)1.3 cmH2O.
Above we said that the behaviour of the lung is analogous to that of a spring - change in pressure is accompanied by a proportional change in volume. We might expect that if we push air into the lung and then plot volume change versus pressure change that we would get a straight line. This is indeed more or less what happens on inspiration, but what happens on expiration? Consider the following plot that shows pressure changes that occur when varying volumes of air are very slowly pushed into a lung:
The expiratory limb of the curve does NOT follow the inspiratory limb! Also note that as the tidal volume increases, the loop widens! What is happening? For any particular volume, the pressure on the expiratory curve is less than that on the inspiratory one. This is because the elastic recoil on expiration is always less than the distending transmural pressure gradient required to inflate the lung. This is a manifestation of loss of energy, and is a property that is common to all bodies that obey Hooke's law.
We call the above property hysteresis. If we slowly inflate a lung, and then simply leave it inflated, the pressure in that lung will drop exponentially to a value about 70 to 80% of the initial value. Most of this change is complete after about a minute. We term the compliance calculated from this "final" pressure the static compliance. The corresponding compliance calculated using the initial, higher pressure value is the dynamic compliance, and it will always be lower than the static compliance.
Quite apart from the elastic hysteresis described above, the lung possesses other time-dependent behaviour. The lung appears to have a "memory" of its recent history, in that low-volume ventilation for a period of time tends to cause a reduction in compliance. This reduction may be reversed by taking subsequent deep breaths (even a single deep breath). This was the motivation for introducing a "sigh" mode to certain mechanical ventilator designs, a concept that has fallen into disfavour, although some are making spirited attempts to re-introduce such practices!
Causes for time-dependent lung elasticity.
There are many candidates, including:
It is vital to distinguish between the elastic properties of the lung and those of the surrounding chest wall. All too often, clinicians (especially those in ICU) confuse total thoracic compliance with lung compliance. When we come to discuss acute lung injury, we will see that it is the pressure distending the alveolus that is critical in determining whether we injure the lung with our ventilation. If we were to take a rabbit (for example), encase its chest wall in plaster of Paris, and then ventilate it using high transthoracic pressures, we would not necessarily be inflicting high transpulmonary pressures on the unfortunate animal. We know from the few studies that have looked at this, in the critically ill, that total thoracic compliance often bears little relationship to pulmonary compliance!
How do we separate pulmonary and chest wall compliance?
In order to do this, we need some measure of intrapleural pressure, that is, the pressure within the "potential" space between the pleura. Unfortunately, this is not easy to obtain, and the pressure also varies with the site of the transducer and the posture of the subject. The easiest method of obtaining a measure of this pressure is to use an intra-oesophageal balloon catheter, as a correctly positioned oesophageal balloon reflects intra-pleural pressure with 'reasonable' fidelity. Air-filled balloon catheters are commonly used for this purpose.
A noteworthy point is that if the thoracic cage is opened, the lungs tend to collapse, but the thoracic cage will tend to expand to a volume about one litre greater than FRC (in an adult). Interestingly, the diaphragm too contributes to this complex relationship, as even when relaxed it has a residual tone that enhances the functional residual capacity of the lung by about 400ml. (This tone is abolished during anaesthesia)!
Note the relationship between total thoracic compliance,
lung compliance, and chest-wall compliance:
Some people use the idea of elastance where the elastance is the reciprocal of the compliance. We can then add elastances, rather than adding the reciprocals of compliances. It seems terribly wanton to introduce new terms, for the inability to take a reciprocal!
Ventilation within the lungs is greatest near the bases, in the upright position. This is probably mainly due to variation in intra-pleural pressure as we move from apex to base - pressure is more negative near the apex. Effectively, this probably causes more expansion of the apices at FRC. As the person inhales, it is easier to expand the bases, as these are less distended than the apices! Note that at lower lung volumes, the situation may be reversed, with poor ventilation of the bases.
Clinicians especially, lay great emphasis on lung volume, its subdivisions,
and divergence of volumes from normal. This is peculiar, as there is
relatively little evidence that changes in volume, even quite gross
derangements, are consistent predictors of clinical outcome in the
individual patient, especially post-operatively. Physiologists (who are
often "splitters" at heart) have labelled a variety of components of the total
lung capacity. The following diagram shows the changes in volume (on the
vertical axis) against time (on the horizontal axis) as an individual
breathes, initially tidal volumes, and then inspires and expires maximally.
Perhaps the volume that has received most attention is the Functional Residual Capacity (FRC), the volume of gas in the lung after a normal expiration. The FRC is determined by the balance between the inward elastic recoil of the lungs, and the outward recoil of the thoracic cage, mentioned above. As already noted, the FRC decreases with paralysis and anaesthesia. Other factors influencing the FRC include:
There are Three main approaches to measuring FRC:
Not all the air that passes into the respiratory tract reaches alveoli. Even in normal individuals, about one third of a tidal volume is wasted in the anatomical dead space! (This is a remarkably constant proportion for most animals, even giraffes!) We often talk about the VD/VT ratio, in other words, the ratio of dead space to tidal volume. Dead space may be:
Physiological dead space can be calculated using Bohr's method.
This uses the equation:
In other words, the product of alveolar CO2 concentration and the amount of inspired air reaching the alveoli equals the expired CO2 concentration times the tidal volume. It is easy to measure the tidal volume and the expired concentration of CO2, so all we need to determine physiological dead space is the alveolar CO2 concentration. In most cases, we can simply substitute in the arterial PCO2, as the two are generally very similar.
The Anatomical dead space can be determined by watching the change in N2 concentration (using a rapid N2 analyser) following a single breath of 100% oxygen. N2 concentration is measured as the subject breathes out, increasing from zero (at the start of inspiration) to a plateau (where almost pure alveolar gas is being expired). Fowler showed that if a vertical line is drawn such that areas A and B are equal in the following diagram (after West), then the anatomical dead space is the volume expired up to the vertical line, indicated by the (red) arrow in the diagram.
Gas molecules move with remarkable ease between alveolar air and blood, traversing the 0.5 micron barrier by passive diffusion. This means that we can apply all those eponymous little rules which make pulmonary medicine so irritating - Fick's law, which tells us that more diffusion will occur if we increase the surface area, decrease the thickness of the alveolo-capillary membrane, or increase the partial pressure gradient across the membrane, and also Grahams law (from which we learn that bigger, or less soluble molecules move more slowly).
The consequences of these laws are:
Things become more complex, for two reasons:
( As an aside, normal individuals at high altitude may also show diffusion-limited O2 transfer across their alveolar walls, but otherwise this limitation is a manifestation of pulmonary disease.)
Based on the above, we define the Diffusing capacity of the lung
For example, the diffusing capacity of the lung for carbon monoxide,
DLCO is the volume of CO transferred
divided by the difference between alveolar and blood partial pressures
of CO. Experimental determination of DLCO
is thus rather easy, as owing to the rapid uptake of CO by haemoglobin,
the PaCO is always negligibly small provided we get the subject to inhale
a low concentration of CO. DLCO then becomes:
Practically, we determine DLCO using the single breath method where a single breath of CO is taken, and the rate of disappearance of CO is calculated after the subject has held their breath for ten seconds. (Derived from initial and final CO concentrations in the inspired & expired air). Note that this can be combined with inspiration of helium for VA determination, killing two birds with one stone!
An unfortunate metaphor, as the procedure is safe, its main limitation being the ability of subjects to hold their breath for ten seconds!
An alternative method of determining DLCO is the steady state method, where a tiny concentration of CO is inhaled until a steady state concentration is reached, and the rate of disappearance is then measured for a further short period, along with the alveolar concentration. This compensates for the inconstant aveolar CO concentration that we encounter in the single breath method.
The pulmonary circulation is not merely a pint-sized version of the systemic circulation. Important contrasts between systemic and pulmonary circulations exist. These are highlighted by considering:
The tissue surrounding the capillaries
There is very little of this - really just the extremely thin alveolo- capillary membrane, comprising attenuated pneumocytes and endothelial cells separated by a minute basement membrane. The capillaries can therefore easily collapse, especially if intra-alveolar pressure is raised. The peri-capillary tissue is thought to be under tension from the surrounding elastic lung parenchyma - it is easy to see how the transcapillary Starling forces might easily change to favour passage of fluid into the pulmonary interstitium!
Sites of resistance within the circulation
Pulmonary vascular resistance (PVR) is a convenient fiction, described by the ratio of pressure change to flow within the circulation. As the pressure drop within this circulation is normally so small, the PVR is about one tenth of the systemic vascular resistance. (To confuse things various units of resistance have been proposed, such as mmHg/l/min, and dynes.sec.cm-5. Normal values are about 1.8mmHg/l/min, or 140 dynes.sec.cm-5, or perhaps 0.24 kPa l-1min).
This convenient simplification masks vast differences. In the systemic circulation, the site of resistance is mainly arterial, while in the pulmonary circulation, there is a substantial contribution from the capillaries and even from the venous side of the circulation!! This may have profound implications for assessing the diseased pulmonary circulation.
Furthermore, as venous or arterial pressure rise, so the pulmonary vascular resistance falls! This is thought to be mainly due to recruitment of under-perfused vessels, but may also be related to distension of capillaries, especially at higher pressures. Pulmonary volume (that is, amount of air in the lung) also affects PVR in a complex fashion, PVR being increased at both extremely low and very high lung volumes!
In the systemic circulation, veins are the main capacitance vessels. Not so in the lungs, where capillaries distend markedly with pressure and are important for their capacitive effects.
Distribution of flow within the lungs.
There are remarkable inequalities in blood flow through various regions of the lung. These variations in flow are mainly related to height above the heart, which is not too remarkable when one considers the low pressures present in the pulmonary circulation - hydrostatic pressure alone will result in a pressure difference of approximately 30cm H20 from the base of the lung to the apex. This led West to propose his "Three Zones" of the lung [ West et al. J Appl Physiol 1964 19 p713 ] - in the topmost Zone 1, there is no flow because the pressure is not sufficient, in the lowest Zone 3 flow is continuous because intravascular pressure always exceeds alveolar pressure, while in the middle zone 2, flow depends remarkably on the difference between arterial and alveolar pressures - venous pressure is irrelevant as it is lower than alveolar pressure. Note that in the normal lung, there should be NO zone 1, as the pressure is just sufficient to perfuse the apices! Some have subsequenly proposed a "zone 4" which might occur in the bases where poorly expanded lung might actually result in narrowing of extra-alveolar vessels with reduced flow.
Of great importance in the lung, especially in disease states, is hypoxic vasoconstriction. Here, hypoxia in an alveolus causes marked contraction of that little smooth muscle present in the walls of nearby arterioles, markedly diminishing flow to the affected region. This can be seen as an 'attempt' by the lung to normalise ventilation/perfusion ratios (see below). This vasoconstriction tends to occur dramatically below a PO2 of about 70mmHg, and may therefore become important at altitude too.
It is clear that adequate lung ventilation and good perfusion are not enough to ensure that blood passing through the lung is well oxygenated, and that CO2 is removed. For this gas exchange to take place, there must be a matching of ventilation and perfusion. Bearing this in mind, let's take a practical look at causes of hypoxaemia. If the oxygen content of the blood is diminished despite having normal haemoglobin levels we have several possible explanations. We therefore take..
We can for practical purposes ignore diffusion in most individuals, so we are left with four main causes of hypoxaemia. We will here consider the three most problematical causes: hypoventilation, shunt, and finally ventilation/perfusion mismatch, often abbreviated to "V/Q mismatch".
The alveolar gas equation in one of its incarnations (already discussed above) allows us to see the impact of hypoventilation on oxygenation. It can be seen that at an FiO2 of 21%, hypoventilation will have a substantial effect on oxygenation. This is however easily compensated for by increasing the FiO2. At high FiO2, even minuscule ventilation can maintain alveolar PO2 for ages.
Note that there may be a lag of several minutes between an alteration in ventilation and equilibration of PaO2 (and especially, PaCO2). This is because of the buffering effect of reserves within the body (small in the case of oxygen, larger for CO2). During this transition period, values for respiratory quotient will be deranged.
If deoxygenated blood is shunted past the alveoli and not oxygenated, this will proportionally decrease the oxygen content of the arterial blood. In normal people, the amount of shunt is tiny (perhaps 1%, reflecting venous blood from the bronchi entering the pulmonary veins, as well as coronary venous blood entering the left ventricle via the Thebesian veins!). Generally, if we cannot determine the amount of oxygen in the "shunted" blood, we assume that this is the same as that of mixed venous blood, and make our calculations accordingly.
To calculate shunt, we must know the total amount of blood moving through the system (QT), and the oxygen content of the arterial, capillary and mixed venous blood (We will abbreviate these last three to CaO2, CcO2, and CvO2, the 'standard' abbreviations being a bit more clumsy ). Knowing these, we calculate as follows:
It is relatively easy to test for a shunt - simply give the subject 100% oxygen to breathe, and see if the PaO2 increases. If there is a true shunt, there will be no response, as the shunted blood is still not being exposed to the increased FiO2, and so will still make its evil contribution to arterial hypoxaemia!
V/Q mismatch is more tricky than shunt. Theoretically, the ratio of ventilation to perfusion in any one alveolus can range from zero to infinity: in the normal individual with a cardiac output of say 5 l/minute and an alveolar ventilation of perhaps 4l/minute, the ideal ratio would be 0.8, but even in normal people, there is some variation from this ratio, most alveolar units falling in the range of 0.5 to 2.0. As one ages, so the scatter of ratios increases, to perhaps 0.3 to 5.0 ! This is well shown in Nunn p 167, Fig 8.5.
A convenient method of cheating!
Determining the scatter of V/Q ratios in small sections of the lung is technically demanding. It is far more convenient (if less accurate) to regard the lung "as if" it had three compartments comprising:
Another convenience is to consider the relationship between PO2 and PCO2 within an alveolar unit as we alter the V/Q ratio. Think about it - if there is no blood flow, then PAO2 might be say 149mmHg (at sea level), while PCO2 will be zero. With no ventilation, the PCO2 will increase to that of venous blood (say 45mmHg) with a PO2 equal to the venous PO2, perhaps 40mmHg. We can therefore plot a curve of PO2 versus PCO2 that encompasses all possible ratios for alveoli within a particular individual.
Regional variation in V/Q ratios
There are substantial variations in these ratios in the upright lung. Ventilation increases gradually as we move from apex down to base of the lung, while perfusion is much more dramatically affected, being low at the apices and rich at the bases. Thus V/Q ratios decrease as we move from the apex downwards. This improves with exercise.
Gas transport to and from the peripery is very elegant. We consider it briefly:
Most oxygen is carried in the blood as oxyyhaemoglobin. The small contribution that dissolved oxygen makes to transport is usually negligible. (It can be calculated using Henry's law - for each mmHg of PO2 there is 0.003ml O2 dissolved per 100ml of blood, absolutely minuscule).
Haemoglobin (Hb) is much more effective in transporting oxygen, carrying about 1.39 ml of O2 per gram of pure Hb. We are all aware of the shape of the Hb:O2 dissociation curve and its importance in tissue oxygen delivery, as well as how the curve is right-shifted by:
The most convenient equation relating Hb saturation and PO2 is
This is carried in three forms:
As we have indicated, the biggest drop in the oxygen cascade is here at the level of the tissues. The standard textbooks on respiratory medicine hardly address this vital issue! I will update this section as I acquire more information - please feel free to contribute.
Control of breathing in man is immensely complex. We will conveniently look at three levels in the control of breathing:
The human respiratory system is interesting in its dual use of both the diaphragm and intercostal muscles for ventilation. Shneerson [Disorders of Ventilation Blackwell Scientific 1988, ISBN 0 632 01668 X ] describes the functional anatomy of the muscular components of the respiratory pump rather well. We will superficially consider the neuromuscular components.
Descending pathways to the anterior horn cells innervating the muscles of respiration are:
How does the respiratory system compensate for changes in load? This is very efficient, and compensation occurs within one breath! This is thought to occur because "instructions to shorten" go to both the muscle fibres and intrafusal fibres in the muscle spindles. Differential shortening (caused by a large load preventing shortening of normal fibres) will be picked up and a large feedback signal will result in further stimulation of the muscle. Note that this is more important in the intercostal muscles, as spindles are sparsely scattered in the diaphragm.
Formerly everyone except Ramon y Cajal thought that complicated pontine mechanisms controlled respiration. The neuroanatomist Cajal got it right in 1909, claiming that respiratory rhythms originate in the medulla! There are probably two important groups of neurones, a dorsal group near the tractus solitarius controlling timing of inspiration, and a more complex ventral group. The ventral group includes the (expiratory) nucleus retroambigualis, nucleus ambiguus, nucleus para-ambigualis (inspiratory), and Bötzinger complex. There are thought to be at least six types of specific neurones in the medulla that control respiration.
Pontine regulatory mechanisms do exist, and are thought to "fine-tune" the above. Various other centres influence breathing, especially in relation to sneezing, swallowing and coughing. There is a wide variety of other reflexes that affect breathing including:
Two sets of chemoreceptors regulate breathing:
There is a complex interaction between the peripheral and central responses to hypercapnia and hypoxia. The response to PCO2 is slower than that to PO2, linear, and varies widely from person to person. A typical slope for the CO2 response curve would be about 2 litres/minute/mmHgPCO2. The curve becomes steeper at lower PaO2's.
If the PCO2 is sufficiently lowered, apnoea may result, despite a low PaO2. This is termed the "apnoeic threshold", but may not be present in some individuals. Metabolic acidosis does not change the slope of the CO2 response curve, but shifts it left.
The relationship between PaO2 and minute ventilation at constant PCO2 is complex and non-linear, but if we plot saturation against minute ventilation, we obtain a convenient almost linear curve down to a saturation of about 70% !The response to hypoxia is enhanced by hypercarbia, acidosis and exercise. With gross hypoxia of rapid onset hypocapnia depresses respiration, but compensation occurs over about six days. After years of chronic hypoxia, hypoxic drive becomes markedly attenuated.
The readily available textbooks are adequate as an introduction to the physiology and testing of the lung. Consider using:
|Date of First Publication: 1999||Date of Last Update: 2006/10/24||Web page author: Click here|