IV The Cardiovascular System

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17 Organization of the Cardiovascular System

Emile L. Boulpaep

ELEMENTS 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. 17-1A). The requirement for a circulatory system is an evolutionary consequence of the increasing size and complexity of multicellular organisms. Simple diffusion (p. 56) is not adequate to supply nutrients to centrally located cells, nor 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. 17-1B), 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 re-supply 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. Maintaining 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. 17-1C). 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. 17-1D) that delivers the full output of the "heart" to the lungs (p. 695). 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 signalling to cells by means of circulating hormones or neurotransmitters, (2) dissipating heat by delivering heat from the core to the surface of the body, and (3) mediating inflammatory and host defense responses against invading microorganisms.
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Figure 17-1 Role of circulatory system in promoting diffusion In C, nutrients and wastes exchange across two barriers: a "surface for equilibration" between external milieu and blood, and another surface between blood and the "central cell." As shown in the inset, blood is the conduit that connects the external milieu (e.g., lumina of lung, gut, and kidney) to the internal milieu (i.e., extracellular fluid bathing central cells). In D, the system is far more efficient because it uses one circuit for exchanging gases with the stirred external milieu, and another circuit for exchanging nutrients and nongaseous wastes.
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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 approximately 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. 17-1D). These operate in series and require a delicate equalization of their outputs. The output of each pump is approximately 5 liters/min, but this can easily increase fivefold during exercise. Over a 75-year lifetime, the two ventricles combined pump 400 million liters 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. 17-1D). 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 pathologies.
Blood Is a Suspension of Cellular Elements in Plasma

Blood is a complex fluid. If you spin down a sample of blood containing an anticoagulant, the bottom fraction contains formed elements - red blood cells (RBCs), white blood cells (i.e., granulocytes, lymphocytes, and monocytes), and platelets - whereas the top fraction is blood plasma. The hematocrit (p. 51) is the fraction of the total column occupied by RBCs. Plasma is a pale-white watery solution of electrolytes, plasma proteins, carbohydrates, and lipids (Table 2-02). The electrolyte composition of plasma differs only slightly from that of interstitial fluid. The principal plasma proteins (p. 472) are albumin, globulins, fibrinogen, and other coagulation factors. The electrophoretic mobility of plasma proteins in decreasing order comprises albumins (lowest molecular weight), 1-globulins, 2-globulins, -globulins, fibrinogen, and -globulins. The -globulins include the circulating antibodies (i.e., immunoglobulins). The liver produces albumin and most of the globulins and coagulation factors. The remaining globulins are the immunoglobulins synthesized by B lymphocytes. Plasma Proteins Many proteins are involved in blood coagulation through a "coagulation cascade" in which serine proteases cleave inactive coagulation factors into active factors, which are themselves serine proteases. This cascade can begin via either the intrinsic or the extrinsic pathway, which converge. The end point of the cascade is the cleavage of fibrinogen into fibrin monomers, which assemble into a fibrin polymer. Cross-linked fibrin polymers form strands that trap red and white cells, platelets, and plasma inside the thrombus (i.e., blood clot). Subsequent interaction of myosin and actin in the platelets of the clot allows the clot to shrink to a plug that expels a slightly yellow-tinged fluid. This residual fluid is serum, which differs principally from plasma by the absence of fibrino-gen and other coagulation factors; however, serum still contains antibodies. Note that plasma can also form a clot, but a plasma clot does not retract because it lacks platelets. Hemostasis
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Figure 17-2 Flow through a straight tube The flow (F) between a high-pressure point (P1) and low-pressure point (P2) is proportional to pressure difference (P). A 1 and A2 are cross-sectional areas at these two points. A cylindrical bolus of fluid-between the disks at points 1 and 2-moves down tube with a linear velocity, v.

Blood is normally in a liquid state inside blood vessels because it does not come into contact with negatively charged surfaces (e.g., the collagen beneath endothelial cells) that activate the intrinsic coagulation pathway, nor does it contact tissue factors (e.g., thromboplastin released from damaged tissue) that activate the extrinsic pathway. Furthermore, thrombolytic pathways keep the coagulation pathways in check. Indeed, plasma contains plasminogen, which tissue plasminogen activator (t-PA) can convert to plasmin, a protease that digests fibrin and thereby lyses blood clots. Fibrinolysis
Printed from STUDENT CONSULT: Medical Physiology (on 09 August 2006) 2006 Elsevier