Organization of the Cardiovascular System

The circulation is an evolutionary consequence of body size

Isolated single cells and small organisms do not have a circulatory system. They can meet their metabolic needs by the simple processes of diffusion and convection of solutes from the external to the internal milieu ( Fig. 17-1 A ). The requirement for a circulatory system is an evolutionary consequence of the increasing size and complexity of multicellular organisms. Simple diffusion (see p. 108 ) is not adequate to supply nutrients to centrally located cells or to eliminate waste products; in large organisms, the distances separating the central cells from the external milieu are too long. A simple closed-end tube (see Fig. 17-1 B ), penetrating from the extracellular compartment and feeding a central cell deep in the core of the organism, would not be sufficient. The concentration of nutrients inside the tube would become very low at its closed end because of both the uptake of these nutrients by the cell and the long path for resupply leading to the cell. Conversely, the concentration of waste products inside the tube would become very high at the closed end. Such a tube represents a long unstirred layer; as a result, the concentration gradients for both nutrients and wastes across the membrane of the central cell are very small.

In complex organisms, a circulatory system provides a steep concentration gradient from the blood to the central cells for nutrients and in the opposite direction for waste products. Maintenance of such steep intracellular-to-extracellular concentration gradients requires a fast convection system that rapidly circulates fluid between surfaces that equilibrate with the external milieu (e.g., the lung, gut, and kidney epithelia) and individual central cells deep inside the organism (see Fig. 17-1 C ). In mammals and birds, the exchange of gases with the external milieu is so important that they have evolved a two-pump, dual circulatory system (see Fig. 17-1 D ) that delivers the full output of the “heart” to the lungs (see pp. 683–684 ).

The primary role of the circulatory system is the distribution of dissolved gases and other molecules for nutrition, growth, and repair. Secondary roles have also evolved: (1) fast chemical signaling to cells by means of circulating hormones or neurotransmitters, (2) dissipation of heat by delivery of heat from the core to the surface of the body, and (3) mediation of inflammatory and host defense responses against invading microorganisms.

The circulatory system of humans integrates three basic functional parts, or organs: a pump (the heart ) that circulates a liquid (the blood ) through a set of containers (the vessels ). This integrated system is able to adapt to the changing circumstances of normal life. Demand on the circulation fluctuates widely between sleep and wakefulness, between rest and exercise, with acceleration/deceleration, during changes in body position or intrathoracic pressure, during digestion, and under emotional or thermal stress. To meet these variable demands, the entire system requires sophisticated and integrated regulation.

The heart is a dual pump that drives the blood in two serial circuits: the systemic and the pulmonary circulations

A remarkable pump, weighing ~300 g, drives the human circulation. The heart really consists of two pumps, the left heart, or main pump, and the right heart, or boost pump (see Fig. 17-1 D ). These operate in series and require a delicate equalization of their outputs. The output of each pump is ~5 L/min, but this can easily increase 5-fold during exercise.

During a 75-year lifetime, the two ventricles combined pump 400 million L of blood (enough to fill a lake 1 km long, 40 m wide, and 10 m deep). The circulating fluid itself is an organ, kept in a liquid state by mechanisms that actively prevent cell-cell adhesion and coagulation. With each heartbeat, the ventricles impart the energy necessary to circulate the blood by generating the pressure head that drives the flow of blood through the vascular system. On the basis of its anatomy, we can divide this system of tubes into two main circuits: the systemic and the pulmonary circulations (see Fig. 17-1 D ). We could also divide the vascular system into a high-pressure part (extending from the contracting left ventricle to the systemic capillaries) and a low-pressure part (extending from the systemic capillaries, through the right heart, across the pulmonary circulation and left atrium, and into the left ventricle in its relaxed state). The vessels also respond to the changing metabolic demands of the tissues they supply by directing blood flow to (or away from) tissues as demands change. The circulatory system is also self-repairing/self-expanding. Endothelial cells lining vessels mend the surfaces of existing blood vessels and generate new vessels (angiogenesis).

Some of the most important life-threatening human diseases are caused by failure of the heart as a pump (e.g., congestive heart failure), failure of the blood as an effective liquid organ (e.g., thrombosis and embolism), or failure of the vasculature either as a competent container (e.g., hemorrhage) or as an efficient distribution system (e.g., atherosclerosis). Moreover, failure of the normal interactions among these three organs can by itself elicit or aggravate many human pathological processes.

Blood flow is driven by a constant pressure head across variable resistances

To keep concepts simple, first think of the left heart as a constant pressure generator that maintains a steady mean arterial pressure at its exit (i.e., the aorta). In other words, assume that blood flow throughout the circulation is steady or nonpulsatile (below in the chapter, see the discussion of the consequences of normal cyclic variations in flow and pressure that occur as a result of the heartbeat). As a further simplification, assume that the entire systemic circulation is a single, straight tube.

To understand the steady flow of blood, driven by a constant pressure head, we can apply classical hydrodynamic laws. The most important law is analogous to Ohm's law of electricity:

That is, the pressure difference (Δ P ) between an upstream point (pressure P ₁ ) and a downstream site (pressure P ₂ ) is equal to the product of the flow (F) and the resistance (R) between those two points ( Fig. 17-2 ). Ohm's law of hydrodynamics holds at any instant in time, regardless of how simple or how complicated the circuit. This equation also does not require any assumptions about whether the vessels are rigid or compliant, as long as R is constant.

In reality, the pressure difference (Δ P ) between the beginning and end points of the human systemic circulation—that is, between the high-pressure side (aorta) and the low-pressure side (vena cava)—turns out to be fairly constant over time. Thus, the heart behaves more like a generator of a constant pressure head than like a generator of constant flow, at least within physiological limits. Indeed, flow (F) , the output of the left heart, is quite variable in time and depends greatly on the physiological circumstances (e.g., whether one is active or at rest). Like flow, resistance (R) varies with time; in addition, it varies with location within the body. The overall resistance of the circulation reflects the contributions of a complex network of vessels in both the systemic and pulmonary circuits.

Blood can take many different pathways from the left heart to the right heart ( Fig. 17-3 ): (1) a single capillary bed (e.g., coronary capillaries), (2) two capillary beds in series (e.g., glomerular and peritubular capillaries in the kidney), or (3) two capillary beds in parallel that subsequently merge and feed into a single capillary bed in series (e.g., the parallel splenic and mesenteric circulations, which merge on entering the portal hepatic circulation). In contrast, blood flow from the right heart to the left heart can take only a single pathway, across a single capillary bed in the pulmonary circulation. Finally, some blood also courses from the left heart directly back to the left heart across shunt pathways, the most important of which is the bronchial circulation.

The overall resistance ( R _total ) across a circulatory bed results from parallel and serial arrangements of branches and is governed by laws similar to those for the electrical resistance of DC circuits. For multiple resistance elements ( R ₁ , R ₂ , R ₃ , …) arranged in series,

For multiple elements arranged in parallel,

Blood pressure is always measured as a pressure difference between two points

Physicists measure pressure in the units of grams per square centimeter or dynes per square centimeter. However, physiologists most often gauge blood pressure by the height it can drive a column of liquid. This pressure is

where ρ is the density of the liquid in the column, g is the gravitational constant, and h is the height of the column. Therefore, if we neglect variations in g and know ρ for the fluid in the column (usually water or mercury), we can take the height of the liquid column as a measure of blood pressure. Physiologists usually express this pressure in millimeters of mercury or centimeters of water. Clinicians use the classical blood pressure gauge (sphygmomanometer) to report arterial blood pressure in millimeters of mercury.

Pressure is never expressed in absolute terms but as a pressure difference Δ P relative to some “reference” pressure. We can make this concept intuitively clear by considering pressure as a force applied to a surface area A.

If we apply a force to one side of a free-swinging door, we cannot predict the direction the door will move unless we know what force a colleague may be applying on the opposite side. In other words, we can define a movement or distortion of a mechanical system only by the difference between two forces. In electricity, we compare the difference between two voltages. In hemodynamics, we compare the difference between two pressures. When it is not explicitly stated, the reference pressure in human physiology is the atmospheric or barometric pressure (P b ). Because P b on earth is never zero, a pressure reading obtained at some site within the circulation, and referred to P b , actually does not express the absolute pressure in that blood vessel but rather the difference between the pressure inside the vessel and P b .

Because a pressure difference is always between two points—and these two points are separated by some distance (Δ x ) and have a spatial orientation to one another—we can define a pressure gradient (Δ P /Δ x ) with a spatial orientation. Considering orientation, we can define three different kinds of pressure differences in the circulation:

• 1

  Driving pressure. In Figure 17-4 , the Δ P between points x ₁ and x ₂ inside the vessel—along the axis of the vessel—is the axial pressure difference. Because this Δ P causes blood to flow from x ₁ to x ₂ , it is also known as the driving pressure. In the circulation, the driving pressure is the Δ P between the arterial and venous ends of the systemic (or pulmonary) circulation, and it governs blood flow. Indeed, this is the only Δ P we need to consider to understand flow in horizontal rigid tubes (see Fig. 17-2 ).

  

• 2

  Transmural pressure. The Δ P in Figure 17-4 between point r ₁ (inside the vessel) and r ₂ (just outside the vessel)—along the radial axis—is an example of a radial pressure difference. Although there is normally no pressure difference through the blood along the radial axis, the pressure drops steeply across the vessel wall itself. The Δ P between r ₁ and r ₂ is the transmural pressure; that is, the difference between the intravascular pressure and the tissue pressure. Because blood vessels are distensible, transmural pressure governs vessel diameter, which is in turn the major determinant of resistance.

• 3

  Hydrostatic pressure. Because of the density of blood and gravitational forces, a third pressure difference arises if the vessel does not lie in a horizontal plane, as was the case in Figure 17-2 . The Δ P in Figure 17-4 between point h ₁ (bottom of a liquid column) and h ₂ (top of the column)—along the height axis—is the hydrostatic pressure difference P ₁ − P ₂ . This Δ P is similar to the P in Equation 17-4 (here, ρ is the density of blood), and it exists even in the absence of any blood flow. If we express increasing altitude in positive units of h, then hydrostatic Δ P = −ρ g ( h ₁ − h ₂ ).

Total blood flow, or cardiac output, is the product (heart rate) × (stroke volume)

The flow of blood delivered by the heart, or the total mean flow in the circulation, is the cardiac output (CO). The output during a single heartbeat, from either the left or the right ventricle, is the stroke volume (SV). For a given heart rate (HR),

The cardiac output is usually expressed in liters per minute; at rest, it is 5 L/min in a 70-kg human. Cardiac output depends on body size and is best normalized to body surface area. The cardiac index ( units: liters per minute per square meter) is the cardiac output per square meter of body surface area. The normal adult cardiac index at rest is about 3.0 L/(min m ² ).

The principle of continuity of flow is the principle of conservation of mass applied to flowing fluids. It requires that the volume entering the systemic or pulmonary circuit per unit time be equal to the volume leaving the circuit per unit time, assuming that no fluid has been added or subtracted in either circuit. Therefore, the flow of the right and left hearts (i.e., right and left cardiac outputs) must be equal in the steady state. N17-1

Flow in an idealized vessel increases with the fourth power of radius (Poiseuille equation)

Flow (F) is the displacement of volume (Δ V ) per unit time (Δ t ):

In Figure 17-2 , we could be watching a bolus (the blue cylinder)—with an area A and a length L —move along the tube with a mean velocity . During a time interval Δ t, the cylinder advances by Δ x, so that the volume passing some checkpoint (e.g., at P ₂ ) is ( A · Δ x ). Thus,

This equation holds at any point along the circulation, regardless of how complicated the circulation is or how irregular the cross-sectional area.

In a physically well defined system, it is also possible to predict the flow from the geometry of the vessel and the properties of the fluid. In 1840 and 1841, Jean Poiseuille observed the flow of liquids in tubes of small diameter and derived the law associated with his name. In a straight, rigid, cylindrical tube,

This is the Hagen-Poiseuille equation,
N17-2 where F is the flow, Δ P is the driving pressure, r is the inner radius of the tube, l is its length, and η is the viscosity. The Poiseuille equation requires that both driving pressure and the resulting flow be constant.

Three implications of Poiseuille's law are as follows:

• 1

  Flow is directly proportional to the axial pressure difference, Δ P . The proportionality constant—(π r ⁴ )/(8η l )—is the reciprocal of resistance (R), as is presented below.

• 2

  Flow is directly proportional to the fourth power of vessel radius.

• 3

  Flow is inversely proportional to both the length of the vessel and the viscosity of the fluid.

Unlike Ohm's law of hydrodynamics ( F = Δ P / R ), which applies to all vessels, no matter how complicated, the Poiseuille equation applies only to rigid, cylindrical tubes. Moreover, discussion below in this chapter reveals that the fluid flowing through the tube must satisfy certain conditions.

Viscous resistance to flow is proportional to the viscosity of blood but does not depend on properties of the blood vessel walls

The simplest approach for expressing vascular resistance is to rearrange Ohm's law of hydrodynamics (see Equation 17-1 ):

This approach is independent of geometry and is even applicable to very complex circuits, such as the entire per­ipheral circulation. Moreover, we can conveniently express resistance in units used by physicians for pressure (millimeters of mercury) and flow (milliliters per second). Thus, the units of total peripheral resistance are millimeters of mercury/(milliliters per second)—also known as peripheral resistance units (PRUs).

Alternatively, if the flow through the tube fulfills Poiseuille's requirements, we can express “viscous” resistance in terms of the dimensions of the vessel and the viscous properties of the circulating fluid. N17-3 Combining Equation 17-9 and Equation 17-10 , we get

Thus, viscous resistance is proportional to the viscosity of the fluid and the length of the tube but inversely proportional to the fourth power of the radius of the blood vessel. Note that this equation makes no statement regarding the properties of the vessel wall per se. The resistance to flow results from the geometry of the fluid—as described by l and r —and the internal friction of the fluid, the viscosity (η). Viscosity is a property of the content (i.e., the fluid), N17-3 unrelated to any property of the container (i.e., the vessel).