Download Cardiopulmonary Physiology

Cardiopulmonary Physiology
Millersville University
Dr. Larry Reinking
Chapter 1 - General Characteristics of the Cardiopulmonary System
Physiology
Physiology is the study of the function of living things. In particular, physiologists
attempt to explain the workings of living systems in terms of physical and chemical mechanisms.
Physiology is a vast area of study and can be divided into many subdivisions such as plant
physiology, neurophysiology, animal physiology, human physiology, insect physiology, etc.
Cardiopulmonary physiology is the study of the function of the heart, circulation and lungs
plus an array of processes associated with these organ systems. Many other organs, such as the
kidneys, are intimately associated with the cardiopulmonary system and must be studied to fully
appreciate cardiovascular and pulmonary function. In this course, our study of cardiopulmonary
physiology will have, primarily, a human emphasis. We will draw heavily on principles that you
have learned in previous courses dealing with chemistry, biochemistry, physics, cell biology,
anatomy and physiology.
Homeostasis
A central concept in vertebrate physiology is homeostasis, that is, the maintenance of a
constant internal environment. This principle was first stated by Claude Bernard, a 19th century
French physiologist and the term homeostasis was coined in 1929 by Walter Cannon of Harvard
University. For the purposes of this course, 'internal environment' refers to the fluid bathing the
cells. An adult human contains about 40 liters of water most of which (25 liters) is contained
within approximately 1014 cells. This water, in association with its dissolved and suspended
molecules, is called the intracellular fluid. The remaining 15 liters of water, outside of the
cells, is the basis for the extracellular fluids which are constantly moving and mixing.
Extracellular fluids include the interstitial fluid (that fluid in immediate contact with the cells),
plasma of the blood, synovial fluid, pleural fluid, cerebrospinal fluid and intraocular fluid. These
fluids provide a reservoir of molecules for cellular needs, mechanical protection, chemical
buffering and a vehicle for transportation and communication. Many aspects of the extracellular
fluids are kept at a constant level, for example, pH, [Na+] , [K+], volume, osmotic concentration
and dissolved gas content. These controlled variables, in the extracellular fluids, are what
constitute the 'constant internal environment'.
Feedback Control
Negative feedback control is widely used in biological systems to maintain a constant
internal environment. In this type of control some factor (e.g., blood pressure) is monitored by a
sensor. If this factor becomes too high or low, a series of changes are initiated to return the
factor to a set, average value. As these changes occur, the controlled factor is continually
monitored and the corrective changes are terminated when the system returns to the set point.
This process can be diagrammed as follows:
Chapter 1
1
disturbance
(+)
negative feedback
(decreased cardiac performance)
Figure 1.1
(-)
controlled
variable
(blood
pressure)
output
signal
process or amplifier
sensor
(nerve
(stretch in impulse)
artery)
(brain)
Negative Feedback
Control
A consequence of this type of regulation is that the controlled factor fluctuates around an
average value rather than being exactly constant. One sign that a physiologic system is 'in
trouble' is when the values for the controlled factor swing widely around the average set point.
In positive feedback control, rather than causing a correction, the feedback response
causes a further disturbance. A vicious cycle is established as the sensor receives a stronger
output, the processor responds with an enhanced positive feedback adjustment, causing an even
greater disturbance,..... and so on. Positive feedback occurs, for example, during the initiation of
an action potential as the entry of sodium into a nerve cell causes a cycle of increased sodium
entry. Positive feedback is also seen in many cases of pathophysiology such as during
progressive circulatory shock:
blood loss
diminished
cardiac
performance
poor
tissue
perfusion
Figure 1.2
Positive Feedback During
Circulatory Shock
release of
toxins from
tissues
Primary Purpose of the Cardiopulmonary System
The combined cardiac, vascular and pulmonary systems are complex and, from a clinical
point of view, trouble laden. By far, the leading cause of death is the failure of some part of this
system. In 1995, 43% (1,001,598 out of 2,312,203) of the deaths in the U.S. were attributed to
cardiopulmonary disorders (National Center for Health Statistics). Why must we have these
systems and why are they so complex? We will investigate these questions over the upcoming
weeks.
The primary purpose of these systems is simple, profound and, to many students, quite
surprising. When asked what these systems do, most will answer that they deliver O2 and carry
away CO2. First, let’s consider how these molecules move across membranes. Unlike most
biologically important molecules, O2 and CO2 do not have specific membrane transport systems.
They must, instead, pass directly through membranes by diffusion.
Chapter 1
2
Diffusion
Diffusion is the random movement of molecules due to thermal energy. The net
movement of a group of molecules will be from an area of high concentration to an area of low
concentration, that is, along a concentration gradient. In media such as water or air, diffusion is
extremely inefficient because of constant collisions with other molecules. A diffusing O2
molecule is, in essence, involved in a walk that involves constant, random turns. The time (t)
required to move a distance (x) by a diffusing molecule can be described by the following
equation, where D is the diffusion coefficient: t 
x2
. Note the general significance of this
2D
equation; a molecule moving twice as far as another will take four times longer! According to
this equation, a small particle will move a distance of 1 m (the width of a bacterium) in 0.5
msec. In order to travel across a test tube (1 cm) this same particle would take around 14 hours
(for a small molecule in water, at room temperature D  10-5 cm2/sec). Obviously, diffusion
over long distances will not work for an organism with a rapid, demanding metabolism.
Thus we reach the point of this exposition! The primary purpose of the cardiopulmonary
system is to overcome the limitations of diffusion. Diffusion is a crummy way to move
molecules, however, it will work if the distances are small. The cardiopulmonary system
delivers an oxygen rich solution very close to cells; the result is that multicellular organisms can
have organs several centimeters away from the atmosphere. The previous formula predicts that it
would take hundreds of hours for an oxygen molecule to diffuse from the atmosphere to the
organs. However, in a functional sense, these organs are only a few m from the atmosphere.
Capillary Fields
Extracellular fluid is transported to and from cells in two stages. First, blood is pumped
through the circulatory system. At rest, all of the blood passes through the entire circulatory
system in about a minute. This transport can be 5-6 times faster during exercise. Secondly, this
fluid moves across the capillary walls, circulates in the interstitial spaces and then returns to the
circulatory system. Most cells are within a few m of a capillary and very few are more than 2550 m away. Thus, most types of molecules can diffuse to cells in much less than a second.
Cells that are very active and have a high demand for oxygen and metabolic substrates are, as a
consequence, closest to capillaries. In skeletal muscle, capillaries feed an area of tissue that is
only about 12 times the cross sectional area of the capillary, thus no cell is more than 3.6 x
capillary radius away from the nutrition supply:
Figure 1.3
Capillary Field in Skeletal Muscle
Capillaries may be as small as 5 m in diameter. Some tissues are seriously affected by
even short interruptions in blood flow. In the brain, for example, cessation of blood flow leads to
unconsciousness in about seven seconds.
Fick's First Law
Fick's First Law is another useful, quantitative way of looking at diffusion:
Chapter 1
3
J  DA
dc
dx
Fick's First Law
Equation 1.1
J is the rate of diffusion, D the diffusion coefficient, A the area, c is concentration and x the
distance. dc/dx represent the concentration gradient. This equation gives us some insight into
the cardiopulmonary physiology system and gas exchange (which is a form of diffusion):
Diffusion Coefficient - In order to maximize diffusion we must have a large diffusion
coefficient or, in other words, very thin, permeable membranes at the exchange surfaces.
The endothelial cells of capillaries (i.e. the capillary wall) are extremely thin. Indeed, on a
light microscope it is difficult to see the thin cytoplasmic extensions of these cells; only
where the nucleus creates a bulge can they be easily visualized. Likewise, at the pulmonary
surface, the combined alveolocapillary membrane is quite thin (0.2-0.6 m) and presents
only a small diffusion barrier during normal (healthy) conditions. There is, however, a
'down-side' to highly permeable membranes. Since these membranes are so thin and
permeable they are highly susceptible to damage and are a favorite point of entry for
pathogens. This latter point, of course, is why we have respiratory therapists and
pulmonologists.
Area - A large area must be present at both the atmospheric interface and at the body tissue
level in order to have a large rate of diffusion. It is estimated that the lungs have 300
million alveoli with a combined surface of around 160 m2. In the body tissues there are,
perhaps, 10 billion capillaries having a total surface area of hundreds of square meters (the
estimates vary from 500 m2 to over 6000 m2). To put these numbers in perspective
consider the following: The alveolar surface area is about the same as that of a singles
tennis court. At any given time, the lungs contain about 100 ml of blood. Imagine
spreading 100 ml of water (about a half cup) evenly over a tennis court. This should give
you some idea of the diffusion distances involved and why gas exchange is so incredibly
efficient in the lungs.
Concentration Gradient - A third way of assuring a high rate of diffusion is to have a large
concentration gradient. As molecules diffuse they tend to evenly disperse and reach an
equilibrium concentration and, at this point, net diffusion stops. In the circulatory system,
equilibration is prevented by the constant movement of blood. In effect, the moving blood
continuously refreshes the concentration gradient. If blood flow is slow in relation to the
rate of oxygen consumption, the concentration gradient decreases and the tissues become
deficient in oxygen.
Preliminary Model of the Cardiopulmonary System
We can construct a model of what must be contained in the cardiopulmonary system
using the ideas derived from Fick’s First Law. In order to move blood we need a pump and
plumbing:
Chapter 1
4
Figure 1.4
Cardiopulmonary System Model
Gas exchange at the tissue and atmosphere
interfaces is indicated by the radiator-type
structures (i.e. capillary beds with large
surface areas).
Due to the pressure generated, the outlet or downstreamside of the pump requires heavier
walled plumbing (i.e. arteries) than the return side (veins).
This simplistic diagram is actually a fairly good representation of the cardiopulmonary
system in fish except for the placement of the pump. In fish the heart is placed just before the
gills.
An obvious problem in the above diagram (and in the fish) is that a pressure drop would
occur as blood flows from the large arteries to the small vessels of the first capillary bed.
Consequently, blood flow through the second capillary bed would be sluggish. Birds and
mammals have solved this problem by adding a second pump.
Expanded Model of the Cardiopulmonary System
In this more detailed model (Figure 1.5, below) note that the two pumps (i.e., left and
right heart) are fused into one organ. The left heart feeds the systemic circulation which has a
relatively high pressure head and contains the great majority of the blood (88% in this diagram).
Because of the larger volume of blood and greater amount of tissue that is supplied, this side of
the circuit is sometimes called the greater circulation. The right heart pumps into pulmonary
circulation (sometimes called the lesser circulation) which has about one fifth the pressure and
holds about 12% of the blood volume. Although their sizes are different, the volume of blood
moved over time (rate of blood flow) is the same in the systemic and pulmonary circulations.
Figure 1.5
Expanded Model of
Cardiopulmonary System
(numbers indicate the percent of
blood volume in different portions of
the circulation)
Types of Blood Vessels
We can describe five types of blood vessels:
Chapter 1
5
1. Arteries (conductive vessels) - Arteries are the ‘expressways’ that deliver blood
rapidly, under high pressure, to the peripheral areas of the circulation. As a consequence, arteries
have thick, elastic walls. As the heart pumps, arteries actually ‘balloon’ and store pressure that is
dissipated while the heart is at rest (depicted by dotted lines in the above diagram).
also consult Figure in the lecture pack for details of blood vessel structure
2. Arterioles (regulator vessels) - Arterioles are the terminal branch in the arterial
system and are control points for blood flow. The muscular walls of these vessels constrict or
dilate, thus altering blood flow to the downstream capillary beds. A major part of resistance to
blood flow occurs in the arterioles.
3. Capillaries (exchange vessels) - Capillaries are the exchange vessels of the
circulation. They are small (average diameter ≈8 m) and have thin, permeable walls. A
substantial amount of fluid actually ‘leaks’ in and out of these vessels. A lymphatic system is
needed to return leaked fluid from the tissue spaces back to the circulatory system.
4. Venules - The venules collect blood from the capillaries and coalesce to form veins.
5. Veins (capacitance vessels) - Veins are low pressure vessels that return blood to the
heart. They have a larger diameter and thinner walls when compared to arteries. Note that a
great proportion of the total blood volume is contained in these vessels. These vessels serve as a
dynamic reservoir since venodilation or venoconstriction will cause a shift of blood to or from
the arterial side of the circuit. Also note that veins contain one-way valves (see Figure 4 in the
lecture pack).
Lumen
Tunica Intima
endothelium and
inner elastic membrane
Tunica Media
elas tic fibers and
s mooth mus cle
Tunica Externa
connective
tis sue
Figure 1.6
Generalized Structure of
Blood Vessels
Table 1.1 Comparison of Various Blood Vessels
Vessel
Lumen
Wall
Type
Diameter Thickness Endothelium
Aorta
25 mm
2 mm

Artery
4 mm
1 mm

Arteriole
30 m
20 m

Capillary
6-8 m
1 m

Venule
20 m
2 m

Vein
5 mm
0.5 mm

Vena Cava 30 mm
1.5 mm

Elastic
Tissue







Smooth Connective
Muscle
Tissue












Principle of Flow Continuity
The following relationship provides further insight into events that take place in the
vasculature:
Chapter 1
6
rate of flow = velocity x cross sectional area
Flow Continuity
Equation 1.2
If velocity is in cm/sec and cross sectional area is cm2 then the rate of flow will be
(recall that cm3 = cc = ml). At all levels in the circulation the rate of flow must be the
same, otherwise one part of the system increases in volume. A lack of flow continuity is seen in
situations such as congestive heart failure. The following diagram illustrates the normal
relationship between velocity and cross sectional area:
cm3/sec
Figure 1.7
Cross-sectional Area and
Velocity of Blood Flow
Note that the conductive vessels, the arteries, have a small cross sectional area and as a
result of the above equation, must have a high velocity of blood movement. This means that
there is little opportunity for exchange in these vessels (also the thickness of the arterial walls
would not allow exchange). In the capillaries, velocity of blood flow is much slower, thus
allowing exchange with the tissue. Although each capillary has a small cross sectional area, a
vast number of them results in a large total area. A large cross sectional area, in the above
formula, translates into a low velocity of blood flow. As blood returns to the heart the velocity
increases due to decreasing cross sectional area in the veins. The maximum velocity in the veins,
however, is only about half of that in the aorta.
Pressure Changes in the Circulatory System
Figure 1.8, below, depicts pressure changes in the human cardiovascular system. In the
left ventricle pressure fluctuates from almost zero to 120 mm Hg. In the aorta, however, pressure
does not drop below ≈80 mm Hg. This is due to the aortic ballooning and energy storage that
was mentioned previously. In some arteries, reflected pressure waves can cause the pressure to
be greater than 120 mm Hg. Due to the tapering diameters and increased number of vessels, the
pulsatile blood pressure is progressively dampened and lost by the time the blood reaches the
capillary level. The drop in average blood pressure that is seen along the length of the arterial
system is due to resistance to blood flow (more on this in a later chapter). A similar pattern is
seen for the right side of the heart and the pulmonary circulation, but the pressure values are
much lower.
Chapter 1
7
Figure 1.8
Pressure
Changes in the
Cardiovascular
System
Lymphatics
As you may have noted on Figure 1.5, another set of plumbing, the lymphatic system, was
added to the diagram that depicts the expanded model of the cardiopulmonary system.
Remember that capillaries are very permeable and, as a consequence, fluid is lost to the tissue
spaces. A major function of the lymphatics is to drain excess fluid from the tissue spaces and
return this fluid to the circulation. Our leaky circulatory system simply would not work without
the recycling action of the lymphatic ducts. Diseases such as elephantiasis are the result of
blocked lymphatic channels. The lymphatics also have important immunologic functions that
will not be discussed in this course.
Kidneys
Figure 1.5 also lacks one key element needed for proper cardiovascular function - a renal
component. An important function of the kidneys is to monitor and regulate the state of the
blood. At rest, about 25% of the cardiac output is routed through the kidneys for this purpose.
The kidneys play a major role in regulating the volume, composition and pressure of the blood.
As we will see later, kidneys are filtration devices, endocrine organs, sensors and affectors.
Sources and Further Reading
Berg, H.C. 1993. Random Walks in Biology. Princeton University Press. 152 pp.
Rosenberg H.M., S.J. Ventura, J.D. Mauer, et al. 1996. Births and deaths: United States, 1995.
Monthly vital statistic report, 45(3), suppl 2, p 31. National Center for Health Statistics.
Chapter 1
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