Physiology 5th Ed.


The term “microcirculation” refers to the functions of the smallest blood vessels, the capillaries and the neighboring lymphatic vessels. Delivery of blood to and from the capillaries is critically important because the capillaries are the site of exchange of nutrients and waste products in the tissues, as well as the site of fluid exchange between the vascular and interstitial compartments.

The anatomy of capillary beds has been discussed previously. To briefly review, blood is delivered to the capillary beds via the arterioles. The capillaries merge into venules, which carry effluent blood from the tissues to the veins. The capillaries are the site of the exchange of nutrients, wastes, and fluid. Capillaries are thin walled and are composed of a single layer of endothelial cells with water-filled clefts between the cells.

The degree of constriction or relaxation of the arterioles markedly affects blood flow to the capillaries (in addition to determining TPR). The capillaries themselves branch off metarterioles; a band of smooth muscle, called the precapillary sphincters, precedes the capillaries. The precapillary sphincters function like “switches”: By opening or closing, these switches determine blood flow to the capillary bed.

Exchange of Substances Across the Capillary Wall

The exchange of solutes and gases across the capillary wall occurs by simple diffusion. Some solutes can diffuse through the endothelial cells, and others must diffuse between the cells. Generally, the route for diffusion depends on whether the solute or gas is lipid soluble.

Gases such as O2 and CO2 are highly lipid soluble. These gases readily cross the capillary wall by diffusing through the endothelial cells; diffusion is driven by the partial pressure gradient for the individual gas. Recall that the rate of diffusion depends on the driving force (in the case of O2 and CO2, the partial pressure difference for the gas) and the surface area available for diffusion. Thus, the greater number of open capillaries, the greater the surface area for diffusion.

Water-soluble substances such as water itself, ions, glucose, and amino acids are not lipid soluble; thus, they cannot cross the endothelial cell membranes. The diffusion of water-soluble substances is limited to the aqueous clefts between endothelial cells; hence, the surface area for their diffusion is much less than that for the lipid-soluble gases.

By far, the most important mechanism for fluid transfer across the capillary wall is osmosis, driven by hydrostatic and osmotic pressures. These pressures are called the Starling pressures or Starling forces.

Proteins are generally too large to cross the capillary walls via the clefts between endothelial cells and are retained in the vascular compartment. In some tissues, such as brain, the clefts are particularly “tight,” and little protein leaves these capillaries. In the kidney and intestine, the capillaries are fenestrated or perforated, which permits the passage of limited amounts of protein. In other capillaries, proteins may cross in pinocytotic vesicles.

Fluid Exchange Across Capillaries

Fluid movement by osmosis is described in Chapter 1. Briefly, fluid will flow by osmosis across a biologic membrane (or the capillary wall) if the membrane has aqueous pores (i.e., permits the passage of water) and if there is a pressure difference across the membrane. The pressure difference can be a hydrostatic pressure difference, an effective osmotic pressure difference, or a combination of hydrostatic and effective osmotic pressures. In capillaries, fluid movement is driven by the sum of hydrostatic and effective osmotic pressures.

Recall that solutes with reflection coefficients of 1.0 contribute most to the effective osmotic pressure. When the reflection coefficient is 1.0, the solute cannot cross the membrane and it exerts its full osmotic pressure. In capillary blood, only protein contributes to the effective osmotic pressure because it is the only solute whose reflection coefficient at the capillary wall is approximately 1.0. The effective osmotic pressure contributed by protein is called the colloidosmotic pressure or oncotic pressure.

Starling Equation

Fluid movement across a capillary wall is driven by the Starling pressures across the wall and is described by the Starling equation as follows:




= Fluid movement (mL/min)


= Hydraulic conductance (mL/min • mm Hg)


= Capillary hydrostatic pressure (mm Hg)


= Interstitial hydrostatic pressure (mm Hg)


= Capillary oncotic pressure (mm Hg)


= Interstitial oncotic pressure (mm Hg)

The Starling equation states that fluid movement (Jv) across a capillary wall is determined by the net pressure across the wall, which is the sum of hydrostatic pressure and oncotic pressures. The direction of fluid movement can be either into or out of the capillary. When net fluid movement is out of the capillary into the interstitial fluid, it is called filtration; when net fluid movement is from the interstitium intothe capillary, it is called absorption. The magnitude of fluid movement is determined by the hydraulic conductance, Kf (water permeability), of the capillary wall. The hydraulic conductance determines how much fluid movement will be produced for a given pressure difference.

Figure 4-34 is a pictorial presentation of the Starling pressures. Each of the four Starling pressures is represented by an arrow. The direction of the arrow indicates whether that pressure favors filtration out of the capillary or absorption into the capillary. The size of the arrow shows the relative magnitude of the pressure. The numerical value of the pressure, in mm Hg, has a plus (+) sign if the pressure favors filtration and a minus (−) sign if the pressure favors absorption.


Figure 4–34 Examples of Starling pressures across the capillary wall. A, Net pressure favors filtration; B, net pressure favors absorption. Arrows pointing out of the capillary show the Starling pressures that favor filtration (+). Arrows pointing into the capillary show the Starling pressures that oppose filtration (−). Numbers give the magnitude of each pressure.

The net pressure, which is the net driving force, is the algebraic sum of the four pressures. In the example in Figure 4-34A, the sum of the four Starling pressures is a net pressure of +6 mm Hg, indicating that there will be net filtration out of the capillary. In the example in Figure 4-34B, the sum of the four pressures is a net pressure of −5 mm Hg, indicating that there will be net absorption into the capillary.

By understanding how each parameter of the Starling equation affects fluid movement across the capillary wall, it is possible to predict the effects of changes in these parameters. Each of the parameters in the Starling equation is described as follows:

image Kf, hydraulic conductance, is the water permeability of the capillary wall. It varies among different types of tissues, depending on the anatomic characteristics of the capillary wall (e.g., the size of the clefts between endothelial cells; whether the capillaries are fenestrated). Therefore, the magnitude of fluid movement for a given pressure difference is largest in capillaries with the highest Kf (e.g., glomerular capillaries), and it is lowest in capillaries with the lowest Kf (e.g., cerebral capillaries). Kf is not influenced by such factors as changes in arteriolar resistance, hypoxia, or buildup of metabolites. However, Kf is increased in capillary injury (e.g., toxins or in burns). Such increases in Kf will increase the capillary permeability to water and also will result in the loss of protein from the capillary.

image Pccapillary hydrostatic pressure, is a force favoring filtration out of the capillary. The value for Pc is determined by both arterial and venous pressures (the capillary being interposed between the arteries and veins), although the value for Pc is closer to arterial pressure than to venous pressure. Furthermore, Pc is more affected by changes in venous pressure than by changes in arterial pressure. Except in glomerular capillaries, Pc declines along the length of the capillary because of the filtration of fluid. Therefore, Pc is highest at the arteriolar end of the capillary and lowest at the venous end.

image Pi, interstitial hydrostatic pressure, is a force opposing filtration. Normally, Pi is nearly zero, or it may be slightly negative.

image πc, capillary oncotic pressure, is a force opposing filtration. As previously noted, πc is the effective osmotic pressure of capillary blood due to the presence of plasma proteins, and according to the van’t Hoff equation (see Chapter 1), it is determined by the protein concentration of capillary blood. Therefore, increases in protein concentration of blood cause increases in πc and decrease filtration, and decreases in protein concentration of blood cause decreases in πc and increase filtration.

image πiinterstitial oncotic pressure, is a force favoring filtration. πi is determined by the interstitial fluid protein concentration. Normally, because there is little loss of protein from capillaries, there is little protein in interstitial fluid, making πi quite low.

SAMPLE PROBLEM. In a skeletal muscle capillary, the following Starling pressures were measured:





Assuming that Kf is 0.5 mL/min • mm Hg, what is the direction and magnitude of fluid movement across this capillary?

SOLUTION. There are two approaches to solving this problem. One is to apply the Starling equation directly by substituting the values for the Starling pressures and Kf. The other is to use the pictorial approach shown in Figure 4-34 to calculate the net pressure and determine its direction, and then to multiply the net pressure by Kf to obtain the magnitude of fluid movement. The pictorial approach is preferred because there is no equation to memorize and the student must understand how each pressure affects fluid movement.

The numerical values in this problem are identical to those in Figure 4-34A. Use the figure to solve the problem pictorially. If the pressure favors filtration, the arrow points out of the capillary and the numerical value is assigned a plus sign. If the pressure favors absorption, the arrow points into the capillary and the numerical value is assigned a minus sign. Two pressures, Pc and πi, are assigned a plus sign because they favor filtration. Two pressures, πc and Pi, are assigned a minus sign because they favor absorption. The four pressures are now added algebraically to calculate the net pressure of +6 mm Hg (i.e., net pressure = +30 − 1 − 26 + 3 mm Hg = +6 mm Hg). The direction of the net pressure favors filtration because it carries a plus sign. The magnitude of fluid movement is calculated as Kf multiplied by the net pressure:


Changes in Starling Forces

Changes in Starling forces can influence the direction and magnitude of fluid movement across capillaries. For example, consider the various changes that would produce increased filtration out of capillaries. In principle, increases in filtration will be caused by an increase in any of the Starling forces that favor filtration or by a decrease in any of the Starling forces that favor absorption. Thus, increases in filtration would be produced by increases in Pc resulting from increases in arterial pressure or venous pressure (but more so from increases in venous pressure). Increases in filtration also would be produced by decreases in πc resulting from dilution of plasma protein concentration.


The lymphatic system is responsible for returning interstitial fluid and proteins to the vascular compartment. The lymphatic capillaries lie in the interstitial fluid, close to the vascular capillaries. The lymphatic capillaries possess one-way flap valves, which permit interstitial fluid and protein to enter, but not leave, the capillaries. These capillaries merge into larger lymphatic vessels and eventually into the largest lymphatic vessel, the thoracic duct, which empties lymph into the large veins. The lymphatic vessels have a smooth muscle wall, which has intrinsic contractile ability. Lymph flow back to the thoracic duct is promoted by contraction of the smooth muscle in the lymph vessels and by compression of the lymph vessels by activity of the surrounding skeletal muscle.

An increase in interstitial fluid volume is called edema (swelling). By definition, edema forms when the volume of interstitial fluid (due to filtration out of the capillaries) exceeds the ability of the lymphatics to return it to the circulation. Thus, edema can form when there is increased filtration or when lymphatic drainage is impaired (Table 4-6).

Table 4–6 Causes and Examples of Edema Formation



↑ Pc (capillary hydrostatic pressure)

Arteriolar dilation

Venous constriction

Increased venous pressure

Heart failure

Extracellular fluid volume expansion

↓πc (capillary oncotic pressure)

Decreased plasma protein concentration

Severe liver failure (failure to synthesize protein)

Protein malnutrition

Nephrotic syndrome (loss of protein in urine)

↑ Kf (hydraulic conductance)


Inflammation (release of histamine; cytokines)

Impaired lymphatic drainage

Standing (lack of skeletal muscle compression of lymphatics)

Removal or irradiation of lymph nodes

Parasitic infection of lymph nodes

Various mechanisms for producing increased filtration have been discussed previously in this chapter (e.g., increased Pc; decreased πc; increased Kf due to destruction of the capillary wall). Lymphatic drainage is impaired when the lymph nodes are surgically removed or irradiated (e.g., in malignancy); in filariasis, a parasitic infection of the lymph nodes; or when there is lack of muscular activity (e.g., a soldier standing at attention).