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The Microcirculation and Lymphatic System: Capillary Fluid Exchange, Interstitial Fluid, and Lymph Flow
The most purposeful functions of the microcirculation are the transport of nutrients to the tissues and removal of cell excreta . The small arterioles control blood flow to each tissue, and local conditions in the tissues, in turn, control the diameters of the arterioles. Thus, each tissue, in most cases, controls its own blood flow in relationship to its individual needs as discussed in Chapter 17 .
The walls of the capillaries are thin and constructed of single-layer, highly permeable endothelial cells. Therefore, water, cell nutrients, and cell excreta can all interchange quickly and easily between the tissues and circulating blood.
The peripheral circulation of the entire body has about 10 billion capillaries, with a total surface area estimated to be 500 to 700 square meters (about one eighth the surface area of a football field). It is rare that any single functional cell of the body is more than 20 to 30 micrometers away from a capillary.
Structure of the Microcirculation and Capillary System
The microcirculation of each organ is organized to serve that organ’s specific needs. In general, each nutrient artery entering an organ branches six to eight times before the arteries become small enough to be called arterioles, which generally have internal diameters of only 10 to 15 micrometers. Then, the arterioles branch two to five times, reaching diameters of 5 to 9 micrometers at their ends, where they supply blood to the capillaries.
The arterioles are highly muscular, and their diameters can change by many times. The metarterioles (the terminal arterioles) do not have a continuous muscular coat, but smooth muscle fibers encircle the vessel at intermittent points, as shown in Figure 16-1 .
At the point where each true capillary originates from a metarteriole, a smooth muscle fiber usually encircles the capillary. This structure is called the precapillary sphincter. This sphincter can open and close the entrance to the capillary.
The venules are larger than the arterioles and have a much weaker muscular coat. Yet, the pressure in the venules is much less than that in the arterioles, so the venules can still contract considerably, despite the weak muscle.
This typical arrangement of the capillary bed is not found in all parts of the body, although a similar arrangement may serve the same purposes. Most importantly, the metarterioles and precapillary sphincters are in close contact with the tissues they serve. Therefore, the local conditions of the tissues—such as the concentrations of nutrients, end products of metabolism, and hydrogen ions—can cause direct effects on the vessels to control local blood flow in each small tissue area.
Structure of the Capillary Wall
Figure 16-2 shows the ultramicroscopic structure of typical endothelial cells in the capillary wall as found in most organs of the body, especially in muscles and connective tissue. Note that the wall is composed of a unicellular layer of endothelial cells and is surrounded by a thin basement membrane on the outside of the capillary. The total thickness of the capillary wall is only about 0.5 micrometer. The internal diameter of the capillary is 4 to 9 micrometers, barely large enough for red blood cells and other blood cells to squeeze through.
Pores in the Capillary Membrane
Figure 16-2 shows two small passageways connecting the interior of the capillary with the exterior. One of these passageways is an intercellular cleft, which is the thin-slitted, curving channel that lies at the top of the figure between adjacent endothelial cells. Each cleft is interrupted periodically by short ridges of protein attachments that hold the endothelial cells together but, between these ridges, fluid can percolate freely through the cleft. The cleft normally has a uniform spacing, with a width of about 6 to 7 nanometers (60 to 70 angstroms [Å]), which is slightly smaller than the diameter of an albumin protein molecule.
Because the intercellular clefts are located only at the edges of the endothelial cells, they usually represent no more than 1/1000 of the total surface area of the capillary wall. Nevertheless, the rate of thermal motion of water molecules, as well as most water-soluble ions and small solutes, is so rapid that all these substances diffuse with ease between the interior and exterior of the capillaries through these slit pores , the intercellular clefts.
Present in the endothelial cells are many minute plasmalemmal vesicles , also called caveolae (small caves). These plasmalemmal vesicles form from oligomers of proteins called caveolins that are associated with molecules of cholesterol and sphingolipids . Although the precise functions of caveolae are still unclear, they are believed to play a role in endocytosis (the process whereby the cell engulfs material from outside the cell) and transcytosis of macromolecules across the interior of the endothelial cells. The caveolae at the surface of the cell appear to imbibe small packets of plasma or extracellular fluid that contain plasma proteins. These vesicles can then move slowly through the endothelial cell. Some of these vesicles may coalesce to form vesicular channels all the way through the endothelial cell, as shown in Figure 16-2 .
Special Types of Pores in Capillaries of Certain Organs
The pores in capillaries of some organs have special characteristics to meet the specific needs of the organs. Some of these characteristics are as follows:
- 1.
In the brain , the junctions between the capillary endothelial cells are mainly tight junctions that allow only extremely small molecules such as water, oxygen, and carbon dioxide to pass into or out of the brain tissues.
- 2.
In the liver , the clefts between the capillary endothelial cells are nearly wide open so that almost all dissolved substances of the plasma, including the plasma proteins, can pass from the blood into the liver tissues.
- 3.
The pores of the gastrointestinal capillary membranes are midway in size between those of the muscles and those of the liver.
- 4.
In the glomerular capillaries of the kidney , numerous small oval windows called fenestrae penetrate all the way through the middle of the endothelial cells so that tremendous amounts of small molecular and ionic substances (but not the large molecules of the plasma proteins) can filter through the glomeruli without having to pass through the clefts between the endothelial cells.
Flow of Blood in the Capillaries—Vasomotion
Blood usually does not flow continuously through the capillaries. Instead, it flows intermittently, turning on and off every few seconds or minutes. The cause of this intermittency is the phenomenon called vasomotion , which means intermittent contraction of the metarterioles and precapillary sphincters (and sometimes even the very small arterioles).
Regulation of Vasomotion
The most important factor affecting the degree of opening and closing of the metarterioles and precapillary sphincters that has been found thus far is the concentration of oxygen in the tissues. When the rate of oxygen usage by the tissue is great—so that tissue oxygen concentration decreases below normal—the intermittent periods of capillary blood flow occur more often, and the duration of each period of flow lasts longer, thereby allowing the capillary blood to carry increased quantities of oxygen (as well as other nutrients) to the tissues. This effect, along with multiple other factors that control local tissue blood flow, is discussed in Chapter 17 .
Average Function of the Capillary System
Despite the fact that blood flow through each capillary is intermittent, so many capillaries are present in the tissues that their overall function becomes averaged. That is, there is an average rate of blood flow through each tissue capillary bed, an average capillary pressure within the capillaries, and an average rate of transfer of substances between the blood of the capillaries and the surrounding interstitial fluid. In the remainder of this chapter, we are concerned with these averages, although it should be remembered that the average functions are, in reality, the functions of billions of individual capillaries, each operating intermittently in response to local conditions in the tissues.
Exchange of Water, Nutrients, and Other Substances Between the Blood and Interstitial Fluid
Diffusion Through the Capillary Membrane Is the Most Important Means of Transferring Substances Between Plasma and Interstitial Fluid
Figure 16-3 illustrates that as the blood flows along the lumen of the capillary, tremendous numbers of water molecules and dissolved particles diffuse back and forth through the capillary wall, providing continual mixing between the interstitial fluid and plasma. Electrolytes, nutrients, and waste products of metabolism all diffuse easily through the capillary membrane. The proteins are the only dissolved constituents in the plasma and interstitial fluids that do not readily pass through the capillary membrane.
Lipid-Soluble Substances Diffuse Directly Through the Cell Membranes of the Capillary Endothelium
If a substance is lipid-soluble, it can diffuse directly through the cell membranes of the capillary without having to go through the pores. Such substances include oxygen and carbon dioxide . Because these substances can permeate all areas of the capillary membrane, their rates of transport through the capillary membrane are many times faster than the rates for lipid-insoluble substances, such as sodium ions and glucose, which can go only through the pores.
Water-Soluble, Non–Lipid-Soluble Substances Diffuse Through Intercellular Pores in the Capillary Membrane
Many substances needed by the tissues are soluble in water but cannot pass through the lipid membranes of the endothelial cells; these include water molecules , sodium ions, chloride ions, and glucose. Although only 1/1000 of the surface area of the capillaries is represented by the intercellular clefts between the endothelial cells, the velocity of thermal molecular motion in the clefts is so great that even this small area is sufficient to allow tremendous diffusion of water and water-soluble substances through these cleft pores. To give an idea of the rapidity with which these substances diffuse, the rate at which water molecules diffuse through the capillary membrane is about 80 times greater than the rate at which plasma itself flows linearly along the capillary . That is, the water of the plasma is exchanged with the water of the interstitial fluid 80 times before the plasma can flow the entire distance through the capillary.
Effect of Molecular Size on Passage Through the Pores
The width of the capillary intercellular cleft pores, 6 to 7 nanometers, is about 20 times the diameter of the water molecule, which is the smallest molecule that normally passes through the capillary pores. The diameters of plasma protein molecules, however, are slightly greater than the width of the pores. Other substances, such as sodium ions, chloride ions, glucose, and urea, have intermediate diameters. Therefore, the permeability of the capillary pores for different substances varies according to their molecular diameters.
Table 16-1 lists the relative permeabilities of the capillary pores in skeletal muscle for various substances, demonstrating, for example, that the permeability for glucose molecules is 0.6 times that for water molecules, whereas the permeability for albumin molecules is very slight—only one 1/1000 that for water molecules.
Table 16-1
Relative Permeability of Skeletal Muscle Capillary Pores to
Different-Sized Molecules
Data from Pappenheimer JR: Passage of molecules through capillary walls. Physiol Rev 33:387, 1953.
| Substance | Molecular Weight | Permeability |
|---|---|---|
| Water | 18 | 1.00 |
| NaCl | 58.5 | 0.96 |
| Urea | 60 | 0.8 |
| Glucose | 180 | 0.6 |
| Sucrose | 342 | 0.4 |
| Inulin | 5000 | 0.2 |
| Myoglobin | 17,600 | 0.03 |
| Hemoglobin | 68,000 | 0.01 |
| Albumin | 69,000 | 0.001 |
A word of caution must be stated at this point. The capillaries in various tissues have extreme differences in their permeabilities. For example, the membranes of the liver capillary sinusoids are so permeable that even plasma proteins pass through these walls, almost as easily as water and other substances. Also, the permeability of the renal glomerular membrane for water and electrolytes is about 500 times the permeability of the muscle capillaries, but this is not true for the plasma proteins. For these proteins, the capillary permeabilities are very slight, as in other tissues and organs. When we study these different organs later in this text, it should become clear why some tissues require greater degrees of capillary permeability than other tissues. For example, greater degrees of capillary permeability are required for the liver to transfer tremendous amounts of nutrients between the blood and liver parenchymal cells and for the kidneys to allow filtration of large quantities of fluid for the formation of urine.
Diffusion Through the Capillary Membrane Is Proportional to the Concentration Difference Between the Two Sides of the Membrane
The greater the difference between the concentrations of any given substance on the two sides of the capillary membrane, the greater the net movement of the substance in one direction through the membrane. For example, the concentration of oxygen in capillary blood is normally greater than in the interstitial fluid. Therefore, large quantities of oxygen normally move from the blood toward the tissues. Conversely, the concentration of carbon dioxide is greater in the tissues than in the blood, which causes excess carbon dioxide to move into the blood and to be carried away from the tissues.
The rates of diffusion through the capillary membranes of most nutritionally important substances are so great that only slight concentration differences cause more than adequate transport between the plasma and interstitial fluid. For example, the concentration of oxygen in the interstitial fluid immediately outside the capillary is no more than a few percent less than its concentration in the plasma of the blood, yet this slight difference causes enough oxygen to move from the blood into the interstitial spaces to provide all the oxygen required for tissue metabolism—often as much as several liters of oxygen per minute during very active states of the body.
Interstitium and Interstitial Fluid
About one sixth of the total volume of the body consists of spaces between cells, which collectively are called the interstitium . The fluid in these spaces is called the interstitial fluid .
The structure of the interstitium is shown in Figure 16-4 . It contains two major types of solid structures: (1) collagen fiber bundles ; and (2) proteoglycan filaments . The collagen fiber bundles extend long distances in the interstitium. They are extremely strong and provide most of the tensional strength of the tissues. The proteoglycan filaments, however, are extremely thin, coiled or twisted molecules composed of about 98% hyaluronic acid and 2% protein. These molecules are so thin that they cannot be seen with a light microscope and are difficult to demonstrate, even with the electron microscope. Nevertheless, they form a mat of very fine reticular filaments aptly described as a brush pile .
Gel in the Interstitium
The fluid in the interstitium is derived by filtration and diffusion from the capillaries. It contains almost the same constituents as plasma except for much lower concentrations of proteins because proteins do not easily pass outward through the pores of the capillaries. The interstitial fluid is entrapped mainly in the minute spaces among the proteoglycan filaments. This combination of proteoglycan filaments and fluid entrapped within them has the characteristics of a gel ; it is therefore called tissue gel .
Because of the large number of proteoglycan filaments, it is difficult for fluid to flow easily through the tissue gel. Instead, fluid mainly diffuses through the gel; that is, it moves molecule by molecule from one place to another by kinetic thermal motion rather than by large numbers of molecules moving together.
Diffusion through the gel occurs about 95% to 99% as rapidly as it does through free fluid. For the short distances between the capillaries and tissue cells, this diffusion allows for rapid transport through the interstitium, not only of water molecules but also of substances such as electrolytes, low-molecular-weight nutrients, cellular excreta, oxygen, and carbon dioxide.
Free Fluid in the Interstitium
Although almost all the fluid in the interstitium normally is entrapped within the tissue gel, occasionally small rivulets of free fluid and small free fluid vesicles are also present, which means fluid that is free of the proteoglycan molecules and therefore can flow freely. When a dye is injected into the circulating blood, it often can be seen to flow through the interstitium in the small rivulets, usually coursing along the surfaces of collagen fibers or surfaces of cells.
The amount of free fluid present in most normal tissues is slight, usually less than 1%. Conversely, when the tissues develop edema, these small pockets and rivulets of free fluid expand tremendously until one half or more of the edema fluid becomes free-flowing fluid, independent of the proteoglycan filaments.
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