Capillaries (// in US; // in UK) are the smallest of a body's blood vessels (and lymph vessels) that make up the microcirculation. Their endothelial linings are only one cell layer thick. These microvessels, measuring around 5 to 10 micrometres (µm) in diameter, connect arterioles and venules, and they help to enable the exchange of water, oxygen, carbon dioxide, and many other nutrients and waste substances between the blood and the tissues surrounding them. Lymph capillaries connect with larger lymph vessels to drain lymph collected in the microcirculation.
Transmission electron microscope image of a capillary with a red blood cell within the pancreas. The capillary lining consists of long, thin endothelial cells, connected by tight junctions.
During early embryonic development new capillaries are formed through vasculogenesis, the process of blood vessel formation that occurs through a de novo production of endothelial cells which then form vascular tubes. The term angiogenesis denotes the formation of new capillaries from pre-existing blood vessels and already present endothelium which divides.
Blood flows from the heart through arteries, which branch and narrow into arterioles, and then branch further into capillaries where nutrients and wastes are exchanged. The capillaries then join and widen to become venules, which in turn widen and converge to become veins, which then return blood back to the heart through the great veins.
Capillaries do not function on their own, but instead in a capillary bed, an interweaving network of capillaries supplying organs and tissues. The more metabolically active a cell or environment is, the more capillaries are required to supply nutrients and carry away waste products. Capillary beds can consist of two types of vessels: true capillaries, which branch from arterioles and provide exchange between cells and the blood, and short vessels that directly connect the arterioles and venules at opposite ends of the beds, metarterioles, only found in the mesenteric circulation.
Metarterioles are found primarily (or exclusively) in the mesenteric microcirculation and were erroneously thought to be present in most or all capillary beds. The physiological mechanisms underlying precapillary resistance is no longer considered to be a result of precapillary sphincters outside of the mesentery organ.
Lymphatic capillaries are slightly larger in diameter than blood capillaries, and have closed ends (unlike the blood capillaries open at one end to the arterioles and open at the other end to the venules). This structure permits interstitial fluid to flow into them but not out. Lymph capillaries have a greater internal oncotic pressure than blood capillaries, due to the greater concentration of plasma proteins in the lymph.
There are three main types of blood capillaries:
Continuous capillaries are continuous in the sense that the endothelial cells provide an uninterrupted lining, and they only allow smaller molecules, such as water and ions to pass through their intercellular clefts. However lipid-soluble molecules can passively diffuse through the endothelial cell membranes along concentration gradients. Tight junctions can be further divided into two subtypes:
Fenestrated capillaries (derived from fenestra, Latin for "window") have pores in the endothelial cells (60-80 nm in diameter) that are spanned by a diaphragm of radially oriented fibrils and allow small molecules and limited amounts of protein to diffuse. In the renal glomerulus there are cells with no diaphragms, called podocyte foot processes or pedicels, which have slit pores with a function analogous to the diaphragm of the capillaries. Both of these types of blood vessels have continuous basal laminae and are primarily located in the endocrine glands, intestines, pancreas, and the glomeruli of the kidney.
Sinusoidal capillaries (also known as a discontinuous capillary) are a special type of open-pore capillary, that have larger openings (30-40 µm in diameter) in the endothelium. These types of blood vessels allow red and white blood cells (7.5 µm - 25 µm diameter) and various serum proteins to pass, aided by a discontinuous basal lamina. These capillaries lack pinocytotic vesicles, and therefore utilize gaps present in cell junctions to permit transfer between endothelial cells, and hence across the membrane. Sinusoid blood vessels are primarily located in the bone marrow, lymph nodes, and adrenal glands. Some sinusoids are distinctive in that they do not have the tight junctions between cells. They are called discontinuous sinusoidal capillaries, and are present in the liver and spleen, where greater movement of cells and materials is necessary. A capillary wall is only 1 cell thick and is simple squamous epithelium.
The capillary wall performs an important function by allowing nutrients and waste substances to pass across it. Molecules larger than 3 nm such as albumin and other large proteins pass through transcellular transport carried inside vesicles, a process which requires them to go through the cells that form the wall. Molecules smaller than 3 nm such as water, ions and gases cross the capillary wall through the space between cells in a process known as paracellular transport. These transport mechanisms allow bidirectional exchange of substances depending on osmotic gradients and can be further quantified by the Starling equation. Capillaries that form part of the blood–brain barrier however only allow for transcellular transport as tight junctions between endothelial cells seal the paracellular space.
Capillary beds may control their blood flow via autoregulation. This allows an organ to maintain constant flow despite a change in central blood pressure. This is achieved by myogenic response, and in the kidney by tubuloglomerular feedback. When blood pressure increases, arterioles are stretched and subsequently constrict (a phenomenon known as the Bayliss effect) to counteract the increased tendency for high pressure to increase blood flow.
In the lungs special mechanisms have been adapted to meet the needs of increased necessity of blood flow during exercise. When the heart rate increases and more blood must flow through the lungs, capillaries are recruited and are also distended to make room for increased blood flow. This allows blood flow to increase while resistance decreases.
Capillary permeability can be increased by the release of certain cytokines, anaphylatoxins, or other mediators (such as leukotrienes, prostaglandins, histamine, bradykinin, etc.) highly influenced by the immune system.
The Starling equation defines the forces across a semipermeable membrane and allows calculation of the net flux:
- is the net driving force,
- is the proportionality constant, and
- is the net fluid movement between compartments.
By convention, outward force is defined as positive, and inward force is defined as negative. The solution to the equation is known as the net filtration or net fluid movement (Jv). If positive, fluid will tend to leave the capillary (filtration). If negative, fluid will tend to enter the capillary (absorption). This equation has a number of important physiologic implications, especially when pathologic processes grossly alter one or more of the variables.
According to Starling's equation, the movement of fluid depends on six variables:
Disorders of capillary formation as a developmental defect or acquired disorder are a feature in many common and serious disorders. Within a wide range of cellular factors and cytokines, issues with normal genetic expression and bioactivity of the vascular growth and permeability factor vascular endothelial growth factor (VEGF) appear to play a major role in many of the disorders. Cellular factors include reduced number and function of bone-marrow derived endothelial progenitor cells. and reduced ability of those cells to form blood vessels.
- Formation of additional capillaries and larger blood vessels (angiogenesis) is a major mechanism by which a cancer may help to enhance its own growth. Disorders of retinal capillaries contribute to the pathogenesis of age-related macular degeneration.
- Reduced capillary density (capillary rarefaction) occurs in association with cardiovascular risk factors and in patients with coronary heart disease.
Major diseases where altering capillary formation could be helpful include conditions where there is excessive or abnormal capillary formation such as cancer and disorders harming eyesight; and medical conditions in which there is reduced capillary formation either for familial or genetic reasons, or as an acquired problem.
- In patients with the retinal disorder, neovascular age-related macular degeneration, local anti-VEGF treatment to limit the bio-activity of vascular endothelial growth factor has been shown to protect vision by limiting progression. In a wide range of cancers, treatment approaches have been studied, or are in development, aimed at decreasing tumour growth by reducing angiogenesis.
Contrary to a popular misconception, William Harvey did not explicitly predict the existence of capillaries, but he clearly saw the need for some sort of connection between the arterial and venous systems. He wrote, "…the blood doth enter into every member through the arteries, and does return by the veins, and that the veins are the vessels and ways by which the blood is returned to the heart itself; and that the blood in the members and extremities does pass from the arteries into the veins (either mediately by an anastomosis, or immediately through the porosities of the flesh, or both ways) as before it did in the heart and thorax out of the veins, into the arteries…" [On the Motion of the Heart and Blood in Animals," Chapter XI, pp. 59–60 in 1653 edition.]
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