[box type=”download”] Overview of the structure of the microcirculation. Terminal arterioles, capillaries, lymphatic capillaries, postcapillary venules and venules . Transcapillary exchange Movement of lipophilic and hydrophilic substances Role of tight junctions, glycocalyx and pores in determining selective passage. Filtration. Role of interstitial oncotic pressure and capillary hydrostatic pressure Physiological basis of the net filtration of water within a capillary bed Clinical effects of poor endothelial quality, low oncotic pressure and high venous pressure Role of lymphatics [/box]
The microcirculation consists of the smallest (terminal) arterioles and the exchange vessels – capillaries and small venules.
Microcirculation is regulated by the sympathetic vasoconstriction of small arterioles.
Each small arteriole feeds many capillaries via several terminal arterioles, which are not innervated.
Instead, the vasoconstriction of terminal arterioles is mediated by local metabolic products.
A few tissues (e.g. mesenteric, skin) have thoroughfare vessels connecting small arterioles and venules directly.
Water, gases and other substances cross the capillary wall mainly by diffusion down the concentration
O2 and CO2 are highly lipophilic (soluble in lipids), and can cross the endothelial lipid bilayer membrane easily.
The hydrophilic (‘water-loving’, lipid-insoluble) molecules, such as glucose, and polar (charged) molecules and ions (electrolytes) mainly cross through the gaps between endothelial cells.
This is slowed by tight junctions between cells and by the glycocalyx, so that diffusion is 1000–10,000 times slower than for lipophilic substances.
This small pore system also prevents the diffusion of larger substances (10,000 Da – e.g. plasma proteins). which may need large pores through endothelial cells.
Fenestrated capillaries (gut, joints, kidneys) are 10-fold more permeable than continuous capillaries because of pores called fenestrae, whereas discontinuous capillaries are highly permeable due to large spaces between endothelial cells, and occur where blood cells need to cross the capillary wall (bone marrow, spleen, liver).
The protein concentration in plasma is greater than that in interstitial fluid (capillary wall is less permeable to proteins), and the 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.
Although arteriolar constriction will reduce capillary pressure and therefore lead to the reabsorption of fluid, this will normally be transient due to 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. inflammation, ischaemia), will similarly reduce (πp − πi), leading to enhanced filtration and loss of fluid into the tissues (oedema).
Oedema is also caused by high venous pressures.
Oedema is swelling of tissues due to excess fluid in the interstitial space.
It is caused when the lymphatics are unable to remove the increased filtration fast enough, or by dysfunctional lymphatic drainage (e.g. elephantiasis, blockage of lymphatics with filarial nematode worms).
Inflammation 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 operation of the muscle pump, local venous pressure rises, and the legs swell.
In congestive heart failure, reduced cardiac function results in increased pulmonary and central venous pressure, 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).
Fluid filtered by the microcirculation (∼8 L per day) is returned to the blood by the lymphatic system.
Lymphatic capillaries are blind-ended bulbous tubes which 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 while the remainder via thoracic duct into the subclavian veins.
Lymphatics are also important for lipid absorption in the gut.