Pressure-Volume Relationships in the Respiratory System

September 15, 2016 Physiology and Pathophysiology, Pulmonary Medicine, Respirology No comments , , , , , , , , , , , , ,

screen-shot-2016-09-15-at-3-04-48-pmThe relationship between changes in the pressure distending the alveoli and (transmural pressure) changes in the lung volume is important to understand because it dictates how easily the lung inflates with each breath. The alveolar-distending pressure is often referred to as the transpulmonary pressure. Strictly speaking, the transpulmonary pressure is equal to the pressure in the trachea minus the intrapleural pressure. Thus, it is the pressure difference across the whole lung. However, the pressure in the alveoli is the same as the pressure in the airways – including the trachea – at the beginning or end of each normal breath, that is, end-expiratory or end-inspiratory alveolar pressure is 0 cm H2O. Therefore, at the beginning or end of each lung inflation, alveolar-distending pressure can be referred to as the transpulmonary pressure.

Compliance of the Lung and the Chest Wall

Reference range: The total compliance of a nromal person near the FRC is about 0.1 L/cm H2O. The compliance of the lungs is about 0.2 L/cm H2O; that of the chest wall is also aobut 0.2 L/cm H2O.

Figure 2-6 shows that as the transpulmonary pressure increases, the lung volume increases. This relationship is not a straight line: The lung is composed of living tissue, and although the lung distends easily at low lung volumes, at high volumes the distensible components of alveolar walls have already been stretched, and large increases in trnaspulmonary pressure yield only small increases in volume.

The slope between 2 points on a pressure-volume curve is known as the compliance. Compliance is defined as the change in volume divided by the change in pressure (transmural pressure). Lungs with high compliance have a steep slope on their pressure-volume curves; that is, a small change in distending pressure will cause a large change in volume. It is important to remember that compliance is the inverse of elastance, elasticity, or elastic recoil. Compliance denotes the ease with which something can be stretched or distorted; elastance refers to the tendency for something to oppose stretch or distortion, as well as to its ability to return to its original configuration after the distorting force is removed.

There are several interesting things to note about the lung pressure-volume curve. From Figure 2-6 there is a difference between the pressure-volume curve for inflation and the deflation, as shown by the arrows. Such a difference is called hysteresis. One possible explanation for this hysteresis is the stretching on inspiration and the compression on expiration of the film of surfactant that lines the air-liquid interface in the alveoli. Surfactant has less effect on decreasing surface tension during inspiration than during expiration because of movement of surfactant molecules from the interior of the liquid phase to the surface during inspiration. Another explanationis that some alveoli or small airways may open on inspiration (recruitment) and close on expiration (decrecruitment); the recruitment of collapsed alveoli or small airways requires energy and may be responsible for the lower inflection point seen on  some inspiratory pressure-volume curves. Finally, it is helpful to think of each alveolus as having its own pressure-volume curve like that shown in Figure 2-6, although some researchers believe that lung volume changes primarily by recruitment and decrecruitment of alveoli rather than by volume changes of individual alveoli.

Clinical Evaluation of the Compliance of the Lung and the Chest Wall

The compliance of the lung and the chest wall provides very useful data for the clinical evaluation of a patient's respiratory system because many diseases or pathologic states affect the compliance of the lung, of the chest wall, or both. The lung and the chest wall are physically in series with each other, and therefore their compliances add as reciprocals:

screen-shot-2016-09-20-at-9-50-53-amConversely, the elastances of the lung and chest wall add directly.

Compliances in parallel add directly. Therefore, both lungs together are more compliant than either one alone; 2 alveoli in parallel are similarly more compliant than 1 alone.

Representative static compliance curves for the lungs are shown in Figure 2-7. Note that these curves correspond to the expiratory curve in Figure 2-6. Many pathologic states shift the curve to the right (i.e., for any increase in transpulmonary pressure there is less of an increase in lung volume). A proliferation of connective tissue called fibrosis may be seen in sarcoidosis or after chemical or thermal injury to the lungs. Such changes will make the lungs less compliant, or "stiffer," and increase alveolar elastic recoil. Conversely, emphysema increases the compliance of the lungs because it destroys the alveolar septal tissue that normally opposes lung expansion.

screen-shot-2016-09-20-at-10-26-47-amFor patients wtih decreased lung compliance, they must generate greater transpulmonary pressures to breath in the same volume of air. Therefore they must do more work to inspire than those with normal pulmonary compliance.

The compliance of the chest wall is decreased in obese people, for whom moving the diaphragm downward and the rib cage up and out is much more difficult. People suffering from a musculoskeletal disorder that leads to decreased mobility of the rib cage, such as kyphoscoliosis, also have decreased chest wall compliance. Similarly, people wtih decreased chest wall compliance must do more muscular work than people with normal chest wall compliance.

Lung Elastic Recoil and Alveoli Surface Tension

The elastic recoil of the lungs is partly due to the elastic properties of the pulmonary parenchyma itself. Elastin is more compliant or distensible and is important at low or normal lung volumes. Collagen is less compliant or distensible and is not usually stressed until lung volume is large. However, there is another component of the elastic recoil of the lung besides the elastin, collagen, and other constituents of the lung tissue. That other component is the surface tension at the air-liquid interface in the alveoli.

Surface tension is a force that occurs at any gas-liquid interface and is generated by the cohesive forces between the molecules of the liquid. These cohesive forces balance each other within the liquid phase but are unopposed at the surface of the liquid. Surface tension is what causes water to bead and form droplets. It causes a liquid to shrink to form the smallest possible surface area. The unit of measurement of surface tension is dynes per centimeter (dyn/cm).

Because the lung is inflated with air, an air-liquid interface is present in the lung, and surface tension forces contribute to alveolar elastic recoil. If all the gas is removed from the lung, and it is inflated again, but with saline instead of with air, the surface tension forces are absent because there is no air-liquid interface. In this circumstance, the elastic recoil is due only to the elastic recoil of the lung tissue itself. Thus, the hysteresis disappears under this condition.

Besides the surfactant's impact on elastic recoil, it has another critical importance, which would be described below. According to the Laplace's law, the transmural pressure of two alveoli with different radius would be different in the absence of surfactant (the surface tension of most liquids is constant and not dependent on the surface area of the air-liquid inteface). Consider what this would mean in the lung, where alveoli of different sizes are connected to each other by common airways and collateral ventilation pathways. If 2 alveoli of different sizes (radius) are connected by a common airway and the surface tension of the 2 alveoli is equal, then the pressure in the small alveolus must be greater than that in the larger alveolus and the smaller alveolus will empty into the larger alveolus. If surface tension is independent of surface area, the smaller the alveolus with smaller radius becomes, the higher the pressure in it. Thus, if the lung were composed of interconnected alveoli of different sizes with a constant surface tension at the air-liquid interface, it would be expected to be inherently unstable with a tendency for smaller alveoli to collapse into larger ones. Normally, this is not the case, which is fortunate because collapsed alveoli require very great distending pressures to reopen, partly because of the cohesive forces at the liquid-liquid interface of collapsed alveoli. At least two factors cause the alveoli to be more stable than this prediction based on constant surface tension. The first factor is a substance called pulmonary surfactant, which is produced by specialized alveolar cells, and the second is the structrual interdependence of the alveoli.

Mean Circulatory Filling Pressure and CVP

June 9, 2016 Cardiology, Critical Care, Hemodynamics, Physiology and Pathophysiology No comments , , , , , , , , , , ,

Mean Circulatory Filling Pressure

Screen Shot 2016-06-08 at 10.18.56 PMImagine the heart arrested in diastole with no flow around the circuit. It will take a certain amount of blood just to fill the anatomical space contained by the systemic system without stretching any of its walls or developing any internal pressure. This amount is 3.56 L. Normally, however, the systemic circuit contains approximately 4.5 L of blood and is thus somewhat inflated. Because the totoal systemic circuit compliance is 140 mL/mm Hg and the "just to fill" amount of blood is 3.56 L, an extra 1000 mL (4.5 L – 3.56 L) amount of blood generate an internal pressure (deltaP) of about 7 mm Hg (deltaP = deltaV/C = 1000/140 = ~ 7 mm Hg). This theoretical pressure is called the mean circulatory filling pressure and is the actual pressure that would exist throughout the system in the absence of flow.

The two major variables that affect mean circulatory filling pressure are the circulating blood volume and the state of the peripheral venous vessel tone. In contrast, squeezing on arterioles will have a negligible effect on mean circulatory filling pressure because arterioles contain so little blood in any state. The other major components of the system (arteries and capillaries) essentially do not actively change their volume.

Flow-Induced Change in Pressure From the Base of Mean Circulatory Filling Pressure

The presence of flow around the circuit does not change the total volume of blood in the system or the mean circulatory filling pressure. The flow caused by cardiac pumping action does, however, tend to shift some of the blood volume from the venous side of the circuit to the arterial side. This causes pressure on the arterial side to rise above the mean circulatory pressure, whereas pressures on the venous side fall below it. Because veins are approximately 50 times more compliant than arteries, the flow-induced decrease in venous pressure (due to blood volume shitfed away) is only approximately 1/50th as large as the accompanying increase in arterial pressure (due to blood volume shifted into). Thus, flow or no flow, pressure in the peripheral venous compartment is normally quite close to the mean circulatory filling pressure.

Central Venous Pressure

The central venous compartment corresponds roughly to the volume enclosed by the right atrium and the great veins in the thorax. Blood leaves the central venous compartment by entering the right ventricle at a rate that is equal to the cardiac output. Venous return, in contrast, is by definition the rate at which blood returns to the thorax from the peripheral vascular beds and is thus the rate at which blood enters the central venous compartment. In any stable situation, venous return must equal cardiac output or blood would gradually accumulate in either the central venous compartment or the peripheral vasculature. However, there are often temporary differences between cardiac output and venous return. Whenever such differences exist, the volume of the central venous compartment must be changing. Because the central venous compartment is enclosed by elastic tissues, any change in central venous volume produces a corresponding change in central venous pressure.

Central venous pressure equals to the RVEDP (right venticular end diastolic pressure)/cardiac filling pressure and has an extremely important positive influence on stroke volume. On the other hand central venous pressure has an equally important negative effect on venous return. Thus, central venous pressure is always automatically driven to a value that makes cardiac output equal to venous return.

The Venous Function Curve

Screen Shot 2016-06-09 at 3.41.50 PMAnatomically the peripheral venous compartment is scatered throughout the systemic organs, but functionally it can be viewed as a single vascular space that has a particular pressure (PPV) at any instant of time. The normal operating pressure in the peripheral venous compartment is usually very close to mean circulatory filling pressure. Moreover, the same factors that influence mean circulatory filling pressure have essentially equal influences on peripheral venous pressure. Thus, "Peripheral venous pressure" can be viewed as essentially equivalent to "mean circulatory filling pressure." The blood flow rate between the peripheral venous compartment and the central venous compartment is governed by the basic flow equation (Q = deltaP/R). When the peripheral venous pressure is assumed to be 7 mm Hg, there will be no venous return when the central venous pressure (PCV) is also 7 mm Hg.

How does CVP influecne venous return

If the peripheral venous pressure remains at 7 mm Hg, decreasing central venous pressure will increase the pressure drop across the venous reistance and consequently cause an elevation in venous return. This relationship is summarized by the venous function curve, which shows how venous return increases as central venous pressure drops. If central venous pressure reaches very low values and falls below the intrathoracic pressure, the veins in the thorax are compressed, which therefore tends to limit venous return. In the example in Figure 8-4, intrathoracic pressure is taken to be 0 mm Hg and the flat portion of the venous function curve indicates that lowering central venous pressure below 0 mm Hg produces no additional increase in venous return.

How does peripheral venous pressure influence venous return

If the central venous remains constant and the peripheral increases, the pressure difference between the two will be enhanced, which increases venous return as a drop in central venous pressure. The two ways in which peripheral venous pressure can change were: first, because veins are elastic vessels changes in the volume of blood contained within the peripheral veins would alter the peripheral venous pressure. Moreover, because the veins are much more compliant than any other vascular segment, changes in circulating blood volume produce larger changes in the volume of blood in the veins than in any other vascular segment. Second, peripheral venous pressure can be altered through changes in venous tone produced by increasing or decreasing the activity of sympathetic vasoconstrictor nerves supplying the venous smooth muscle. In addition, an increase in any force compressing veins from the outside has the same effect on the pressure inside veins as an increase in venous tone. Thus, such things as muscle exercise and wearing elastic stockings tend to elevate peripheral venous pressure.

Shift of the venous function curve

Whenever peripheral venous pressure is altered, the relationship between central venous pressure and venous return is also altered. For example, whenever peripheral venous pressure is elevated by increase in blood volume or by sympathetic stimulation, the venous function curve shifts upward and to the right. By similar logic, decreased peripheral venous pressure caused by blood loss or decreased sympathetic vasoconstriction of peripheral veins shifts the venous function curve downward and to the left.

Determination of Cardiac Output and Venous Return by Central Venous Pressure

The significance of the fact that central venous pressure simultaneously affects both cardiac output and venous return can be best seen by plotting the cardiac function curve and the venous function curve on the same graph (Figure 8-5).

Screen Shot 2016-06-07 at 3.21.01 PMCentral venous pressure, as defined earlier, is the filling pressure of the right heart. Strictly speaking, this pressure directly affects only the stroke volume and output of the right heart pump. In most contexts, however, "cardiac output" implies the output of the left heart pump. How is it then, as we have previously implied, that central venous pressure profoundly affects the output of the left side of the heart? The proper answer is that changes in central venous pressure automatically cause essentially parallel changes in the filling pressure of the left side of the heart (i.e., in left atrial pressure). Consider, for example, the following sequence of consequences that a small step increase in central venous pressure has on a heart that previously was in a steady state:

  • Increased central venous pressure.
  • Increased right ventricular stroke volume via Starling's law of the heart.
  • Increased output of the right side of the heart.
  • The right side of the heart output temporarily exceeds that of the left side of the heart.
  • As long as this imbalance exists, blood accumulates in the pulmonary vasculature and raises pulmonary venous and left atrial pressures.
  • Increased left atrial pressure increases left ventricular stroke volume via Starling's law.
  • Very quickly, a new steady state will be reached when left atrial pressure has risen sufficiently to make left ventricular stroke volume exactly equal to the increased right ventricular stroke volume.

The major conclusion here is that left atrial pressure will automatically change in the correct direction to match left ventricular stroke volume to the current right ventricular stroke volume. Consequently, it is usually an acceptable simplification to say that central venous pressure affects cardiac output as if the heart consisted only of a single pump.

Note that in Figure 8-5, cardiac output and venous return are equal (at 5 L/min) only when the central venous pressure is 2 mm Hg. If central venous pressure were to decrease to 0 mm Hg for any reason, cardiac output would fall (to 2 L/min) and venous return would increase (to 7 L/min). With a venous return of 7 L/min and a cardiac output of 2 L/min, the volume of the central venous compartment would necessarily increase and this would produce a prgoressive increasing central venous pressure. In this manner, central venous pressure would return to the original level (2 mm Hg) in a very short time. Conversely, in the same logic the similar thing would happen when cenral venous pressure were to increase. The conclusion is that the cardiovascular system automatically adjusts to operate at the point where the cardiac and venous function curve intersect.

Vascular Resistances and Compliance, MAP and Pulse Pressure

July 9, 2015 Cardiology, Physiology and Pathophysiology No comments , , , , , , ,

Resistances In A Single Organ

In an organ, the consecutive vascular segments are arranged in series within an organ. Therefore, the overall vascular resistance of the organ must equal the sum of the resistances of its consecutive vascular segments,

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Because arterioles have a large vascular resistance in comparison to the other vascular segments (see above), the overall vascular resistance of any organ is determined to a very large extent by the resistance of its arterioles. And according to its histologic characteristics, we can change the diameter of arterioles either spontaneously or with will (i.e., arterioles inside the penis). Thus, the blood flow through an organ is primarily regulated by adjustments in the internal diameter of arterioles caused by contraction or relaxation of their muscular arteriolar walls.

When the arterioles of an organ change diameter, not only does the flow (in general flow is decreased) to the organ change but also the manner in which the pressures drop within the organ is also modified. Arteriolar constriction causes a greater pressure drop  across the arterioles, and this tends to increase the arterial pressure while it decreases the pressure in capillaries and veins. Conversely, increased organ blood flow caused by arteriolar dilation is accompanied by decreased arterial pressure and increased capillary pressure. Because of the changes in capillary hydrostatic pressure, arteriolar constriction tends to cause transcapillary fluid reabsorption, whereas arteriolar dilation tends to promote transcapillary fluid filtration (see thread Transcapillary Transport at
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Resistances In A Whole Body

The overall resistance to flow through the entire systemic circulation is called the total peripheral resistance. Because the systemic organs are generally arranged in parallel, the vascular resistance of each organ contributes to the total peripheral resistance according to the following  parallel resistance equation:

Screen Shot 2015-07-08 at 10.51.03 PMAccording to the parallel vascular model, the TPR must always be less than that of any of the elements in the network (organ1, organ2, …, organn).

Compliance of Vassels

As indicated earlier, arteries and veins contribute only a small portion to the overall resistance to flow through a vascular bed. Therefore, changes in their diameters have no significant effect on the blood flow through systemic organs. The elastic behavior of arteries and veins is however every important to overall cardiovascular function because they can act as reservoirs and substantial amounts of blood can be stored in them.

Arteries or veins behave more like balloons with one pressure throughout rather than as resistive pipes with a flow-related pressure difference from end to end. Thus, we often think of an “arterial compartment” and a “venous compartment,” each with an internal pressure that is related to the volume of blood within it at any instant and how elastic its walls are.

The elastic nature of a vascular region is characterized by a parameter called compliance that describes how much its volume changes (ΔV) in response to a given change in distending pressure (ΔP): C = ΔV/ΔP. Distending pressure is the difference between the internal and external pressures on the vascular walls. The volume-pressure curves for the systemic arterial and venous compartments are shown in Figure 6-8. It is immediately apparent from the disparate slopes of the curve in this figure that the elastic properties of arteries and veins are very different. For the arterial compartment, the ΔV/ΔP measured near a normal operating pressure of 100 mm Hg indicates a compliance of approximately 2 mL/mm Hg. By contrast, the venous pool has a compliance of more than 100 mL/mm Hg near its normal operating pressure of 5 to 10 mm Hg.

Besides, arterial compliance also decreases with increasing MAP. Otherwise, arterial compliance is a relatively stable parameter.
Screen Shot 2015-07-09 at 8.35.11 PM

Because veins are so compliant, even small changes in peripheral venous pressure can cause a significant amount of the circulation blood volume to shift into or out of the peripheral venous pool. Standing upright, for example, increases venous pressure in the lower extremities, distends the compliant veins, and promotes blood accumulation (pooling) in these vessels, as might be represented by as shift from point A to point B in Figure 6-8. Fortunately, this process can be counteracted by active venous constriction. The dashed line in Figure 6-8 shows the venous volume-pressure relationship that exists when veins are constricted by activation of venous smooth muscle. In constricted veins, volume may be normal (point C) or even below normal (point D) despite higher-than-normal venous pressure. Peripheral venous constriction tends to increase peripheral venous pressure and shift blood out of the peripheral venous compartment.

Mean Arterial Pressure

Mean arterial pressure is a critically important cardiovascular variable because it is the average effective pressure that drives blood through the systemic organs. One of the most fundamental equations of cardiovascular physiology is that which indicates how mean arterial pressure is related to cardiac output and total peripheral resistance:

Screen Shot 2015-07-09 at 9.17.06 PM

This equation is simply a rearrangement of the basic flow equation (Q = ΔP/R) applied to the entire systemic circulation with the single assumption that central venous pressure is approximately zero so that ΔP = MAP. Of note is that all changes in MAP result from changes in either cardiac output or total peripheral resistance.

Arterial Pulse Pressure

The arterial pulse pressure (PP) is defined simply as systolic pressure minus diastolic pressure,

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To be able to use pulse pressure to deduce something about how the cardiovascular system is operating, one must do more than just define it. It is important to understand what determines pulse pressure; that is, what causes it to be what it is and what can cause it to change. As a consequence of the compliance of the arterial vessels, arterial pressure increases as arterial blood volume is expanded during cardiac ejection. The magnitude of the pressure increase (ΔP) caused by an increase in arterial volume depends on how large the volume change (ΔV) is and on how compliant (CA) the arterial compartment is: ΔP = ΔV/CA. If, for the moment, the fact that some blood leaves the arterial compartment during cardiac eject is neglected, then the increase in arterial volume during each heartbeat is equal to the stroke volume (SV). Thus, pulse pressure is, to a first approximation, equal to stoke volume divided by arterial compliance:

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If the stoke volume of a normal resting young man is approximately 80 mL and the arterial compliance is approximately 2 mL/mm Hg, arterial pulse should be approximately 40 mm Hg, according to the equation above. Because the compliance of arteries decrease as age grows, the arterial pulse pressure increases as age grows. Of note, arterial blood volume and mean arterial pressure tend to increase with age. The increase in mean arterial pressure is not caused by the decreased arterial compliance because compliance changes do not directly influence either cardiac output or total peripheral resistance, which are the sole determinants of MAP. And, the decrease in arterial compliance is sufficient to cause increased pulse pressure even through stroke volume tends to decrease with age.

In addition, MAP tends to increase with age because of an age-dependent increase in total peripheral resistance, which is controlled primarily by arterioles, not arteries.

The preceding equation for pulse pressure is a much-simplified description of some very complex hemodynamic processes. It correctly identifies stroke volume and arterial compliance as the major determinants of arterial pulse pressure but is based on the assumption that no blood leaves the aorta during systolic ejection. Obviously, this is not strictly correct. It is therefore not surprising that several factors other than arterial compliance and stroke volume have minor influences on pulse pressure. For example, because the arteries have viscous properties as well as elastic characteristics, faster cardiac ejection caused by increased myocardial contractility tends to increase pulse pressure somewhat even if stroke volume remains constant. Changes in peripheral resistance, however, have little or no effect on pulse pressure, because a change in total peripheral resistance causes parallel change in both systolic and diastolic pressures.