The microcirculation is perhaps the raison d’être for the cardiovascular system, as it is here that exchange between blood and tissues occurs. It consists of the smallest (terminal) arterioles and the exchange vessels capillaries and small venules (Chapter 16). Blood flow into the microcirculation is regulated by the vasoconstriction of small arterioles, activated by sympathetic stimulation through numerous nerve endings in their walls (Chapters 7 and 22). Each small arteriole feeds many capillaries via several terminal arterioles (Fig. 23a), which are not innervated. Instead, the vasoconstriction of terminal arterioles is mediated by local metabolic products (Chapter 24), allowing perfusion to be matched to metabolism. A few tissues (e.g. mesenteric, skin) have thoroughfare vessels connecting small arterioles and venules directly. Note that the term ‘pre-capillary sphincter’ is misleading and should be avoided, as no such anatomical structures exist.
Water, gases and other substances cross the capillary wall mainly by diffusion down their concentration gradients (Chapter 11). O2 and CO2 are highly lipophilic (soluble in lipids), and can cross the endothelial lipid bilayer membrane easily. This is, however, impermeable to hydrophilic (‘waterloving’, lipidinsoluble) molecules, such as glucose, and polar (charged) molecules and ions (electrolytes). Such substances mainly cross the wall of continuous capillaries through the gaps between endothelial cells. This is slowed by tight junctions between cells and by the glycocalyx (Chapter 21), so that diffusion is 1000–10 000 times slower than for lipophilic substances. This small pore system also prevents the diffusion of substances greater than 10 000 Da (e.g. plasma proteins). The latter can cross the capillary wall, but extremely slowly; this may involve large pores through endothelial cells. Fenestrated capillaries (gut, joints, kidneys) are 10fold more permeable than continuous capillaries because of pores called fenestrae (from the Latin for ‘windows’), whereas discontinuous capillaries are highly permeable due to large spaces between endothelial cells, and occur where red cells need to cross the capillary wall (bone marrow, spleen, liver) (Chapter 21).
Filtration (Fig. 23b)
The capillary walls are much more permeable to water and electrolytes than to proteins (see above). The concentration of electrolytes (e.g. Na+, Cl−), and therefore the osmotic pressure exerted by them (crystal- loid osmotic pressure), is very similar in plasma and interstitial fluid, and has little effect on fluid movement. The protein concentration in plasma however is greater than that in interstitial fluid, and the component of osmotic pressure exerted by proteins (colloidal osmotic or oncotic pressure) in the plasma (∼27 mmHg) is therefore greater than in the interstitial fluid (∼10 mmHg). Water tends to flow from a low to a high osmotic pressure, but from a high to a low hydrostatic pressure. The net flow of water across the capillary wall is therefore determined by the balance between the hydrostatic (P) and colloidal osmotic (π) pressures, according to Starling’s equation, flow ∝ (Pc − Pi) − σ(πp − πi), where (Pc − Pi) is the difference in hydrostatic pressure between capillary and interstitial fluid, and (πp − πi) is the difference in colloidal osmotic pressure between plasma and interstitial fluid; (πp − πi) has an average value of ∼17 mmHg. σ is the reflection coefficient (∼0.9), a measure of how difficult it is for plasma proteins to cross the capillary wall. Note that the interstitial protein concentration, and therefore πi, differs between tissues; in the lung for example (πp − πi) is ∼13 mmHg.
The capillary hydrostatic pressure normally varies from ∼35 mmHg at the arteriolar end to ∼15 mmHg at the venous end, whereas the interstitial hydrostatic pressure is approximately –2 mmHg. (Pc − Pi) is therefore greater than σ(πp − πi) along the length of the capillary, resulting in the net filtration of water into the interstitial space (Fig. 23b). Although arteriolar constriction will reduce capillary pressure and therefore lead to the reabsorption of fluid, this will normally be transient due to the concentration of interstitial fluid (i.e. increased πi). A reduction in plasma protein (e.g. starvation), or a loss of endothelium integrity and thus diffusion of protein into the interstitial space (e.g. severe inflammation, ischaemia), will similarly reduce (πp − πi), leading to enhanced filtration and loss of fluid into the tissues. This is also caused by a high venous pressure (oedema; see below).
Fluid filtered by the microcirculation (∼8 L per day) is returned to the blood by the lymphatic system. Lymphatic capillaries are blindended bulbous tubes (diameter, ∼15–75 μm) walled with endothelial cells (Fig. 23a). These allow the entry of fluid, proteins and bacteria, but prevent their exit. Lymphatic capillaries merge into collecting lymphatics and then larger lymphatic vessels, both containing smooth muscle and unidirectional valves. Lymph is propelled, by smooth muscle constriction and compression of the vessels by body movement, into afferent lymphatics and then the lymphatic nodes, where bacteria and other foreign materials are removed by phagocytes.
Most fluid is reabsorbed here by capillaries, with the remainder returning via efferent lymphatics and the thoracic duct into the subclavian veins. Lymphatics are also important for lipid absorption in the gut.
Oedema is swelling of the tissues due to excess fluid in the interstitial space. It is caused when filtration is increased to the extent that the lymphatics are unable to remove the fluid fast enough (see above), or by dysfunctional lymphatic drainage (e.g. elephantiasis, the blockage of lymphatics with filarial nematode worms). Inflammation (Chapter 10) causes swelling and oedema because it increases capillary permeability, allowing protein to leak into the interstitium and disrupt the oncotic pressure gradient, so filtration is increased. Reduced venous drainage (increased venous pressure) also increases filtration and can lead to oedema; standing without moving the legs prevents the opera tion of the muscle pump (Chapter 16), local venous pressure rises, and the legs swell. In congestive heart failure, reduced cardiac function results in increased pulmonary and central venous pressure (Chapter 20), leading, respectively, to pulmonary oedema (alveoli fill with fluid) and peripheral oedema [swelling of the legs and liver, and accumulation of fluid in the peritoneum (ascites)]. Severe protein starvation can cause generalized oedema and a grossly swollen abdomen due to ascites and an enlarged liver (kwashiorkor).