Hubbry Logo
CapillaryCapillaryMain
Open search
Capillary
Community hub
Capillary
logo
8 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Capillary
Capillary
Capillary
View on Wikipedia
from Wikipedia

Capillary
Diagram of a capillary
A simplified illustration of a capillary network
Details
PronunciationUS: /ˈkæpəlɛri/, UK: /kəˈpɪləri/
SystemCirculatory system
Identifiers
Latinvas capillare[1]
MeSHD002196
TA98A12.0.00.025
TA23901
THH3.09.02.0.02001
FMA63194
Anatomical terminology

A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima (the innermost layer of an artery or vein), consisting of a thin wall of simple squamous endothelial cells.[2] They are the site of the exchange of many substances from the surrounding interstitial fluid, and they convey blood from the smallest branches of the arteries (arterioles) to those of the veins (venules). Other substances which cross capillaries include water, oxygen, carbon dioxide, urea,[3] glucose, uric acid, lactic acid and creatinine. Lymph capillaries connect with larger lymph vessels to drain lymphatic fluid collected in microcirculation.

Etymology

[edit]

Capillary comes from the Latin word capillaris, meaning "of or resembling hair", with use in English beginning in the mid-17th century.[4] The meaning stems from the tiny, hairlike diameter of a capillary.[4] While capillary is usually used as a noun, the word also is used as an adjective, as in "capillary action", in which a liquid flows without influence of external forces, such as gravity.

Structure

[edit]
Transmission electron microscope image of a cross-section of a capillary occupied by a red blood cell

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 venae cavae. In the mesentery, metarterioles form an additional stage between arterioles and capillaries.

Individual capillaries are part of the capillary bed, an interweaving network of capillaries supplying tissues and organs. The more metabolically active a tissue is, the more capillaries are required to supply nutrients and carry away products of metabolism. There are two types of capillaries: true capillaries, which branch from arterioles and provide exchange between tissue and the capillary blood, and sinusoids, a type of open-pore capillary found in the liver, bone marrow, anterior pituitary gland, and brain circumventricular organs. Capillaries and sinusoids are short vessels that directly connect the arterioles and venules at opposite ends of the beds. Metarterioles are found primarily in the mesenteric microcirculation.[5]

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.[6]

Types

[edit]
Types of capillaries: (left) continuous with no big gaps, (center) fenestrated with small pores, and (right) sinusoidal (or 'discontinuous') with intercellular gaps

Blood capillaries are categorized into three types: continuous, fenestrated, and sinusoidal (also known as discontinuous).

Continuous

[edit]

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.[7][8] Lipid-soluble molecules can passively diffuse through the endothelial cell membranes along concentration gradients.[9] Continuous capillaries can be further divided into two subtypes:

  1. Those with numerous transport vesicles, which are found primarily in skeletal muscles, fingers, gonads, and skin.[10]
  2. Those with few vesicles, which are primarily found in the central nervous system. These capillaries are a constituent of the blood–brain barrier.[8]

Fenestrated

[edit]

Fenestrated capillaries have pores known as fenestrae (Latin for "windows") in the endothelial cells that are 60–80 nanometres (nm) in diameter. They are spanned by a diaphragm of radially oriented fibrils that allows small molecules and limited amounts of protein to diffuse.[11][12] In the renal glomerulus the capillaries are wrapped in 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

[edit]
Scanning electron micrograph of a liver sinusoid with fenestrated endothelial cells.
Scanning electron micrograph of a liver sinusoid with fenestrated endothelial cells. Fenestrae are approximately 100 nm in diameter.

Sinusoidal capillaries or discontinuous capillaries are a special type of open-pore capillary, also known as a sinusoid,[13] that have wider fenestrations that are 30–40 micrometres (μm) in diameter, with wider openings in the endothelium.[14] Fenestrated capillaries have diaphragms that cover the pores whereas sinusoids lack a diaphragm and just have an open pore. 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 use gaps present in cell junctions to permit transfer between endothelial cells, and hence across the membrane. Sinusoids are irregular spaces filled with blood and are mainly found in the liver, bone marrow, spleen, and brain circumventricular organs.[14][15]

Development

[edit]

During early embryonic development, new capillaries are formed through vasculogenesis, the process of blood vessel formation that occurs through a novel production of endothelial cells that then form vascular tubes.[16] The term angiogenesis denotes the formation of new capillaries from pre-existing blood vessels and already-present endothelium which divides.[17] The small capillaries lengthen and interconnect to establish a network of vessels, a primitive vascular network that vascularises the entire yolk sac, connecting stalk, and chorionic villi.[18]

Function

[edit]
See also: Microcirculation § Capillary exchange
Annotated diagram of the exchange between capillary and body tissue through the exchange of materials between cells and fluid

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 and gases cross the capillary wall through the space between cells in a process known as paracellular transport.[19] These transport mechanisms allow bidirectional exchange of substances depending on osmotic gradients.[20] Capillaries that form part of the blood–brain barrier only allow for transcellular transport as tight junctions between endothelial cells seal the paracellular space.[21]

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.[22]

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.[citation needed] Extreme exercise can make capillaries vulnerable, with a breaking point similar to that of collagen.[23]

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.[24]

Starling equation

[edit]
Diagram of the filtration and reabsorption in capillaries

The transport mechanisms can be further quantified by the Starling equation.[20] The Starling equation defines the forces across a semipermeable membrane and allows calculation of the net flux:

where:

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.[citation needed]

According to Starling's equation, the movement of fluid depends on six variables:

  1. Capillary hydrostatic pressure (Pc)
  2. Interstitial hydrostatic pressure (Pi)
  3. Capillary oncotic pressure (πc)
  4. Interstitial oncotic pressure (πi)
  5. Filtration coefficient (Kf)
  6. Reflection coefficient (σ)

Clinical significance

[edit]

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.[25] and reduced ability of those cells to form blood vessels.[26]

  • 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[27] and in patients with coronary heart disease.[26]

Therapeutics

[edit]

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.

Blood sampling

[edit]

Capillary blood sampling can be used to test for blood glucose (such as in blood glucose monitoring), hemoglobin, pH and lactate.[30][31] It is generally performed by creating a small cut using a blood lancet, followed by sampling by capillary action on the cut with a test strip or small pipette.[32] It is also used to test for sexually transmitted infections that are present in the blood stream, such as HIV, syphilis, and hepatitis B and C, where a finger is lanced and a small amount of blood is sampled into a test tube.[33]

History

[edit]

A 13th century manuscript by Ibn Nafis contains the earliest known description of capillaries. The manuscript records Ibn Nafis' prediction of the existence of the capillaries which he described as perceptible passages (manafidh) between pulmonary artery and pulmonary vein. These passages would later be identified by Marcello Malpighi as capillaries. He further states that the heart's two main chambers (right and left ventricles) are separate and that blood cannot pass through the (interventricular) septum.[34][35]

William Harvey did not explicitly predict the existence of capillaries, but he saw the need for some sort of connection between the arterial and venous systems. In 1653, 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..."[36]

Marcello Malpighi was the first to observe directly and correctly describe capillaries, discovering them in a frog's lung 8 years later, in 1661.[37]

August Krogh discovered how capillaries provide nutrients to animal tissue. For his work he was awarded the 1920 Nobel Prize in Physiology or Medicine.[38] His 1922 estimate that total length of capillaries in a human body is as long as 100,000 km, had been widely adopted by textbooks and other secondary sources. This estimate was based on figures he gathered from "an extraordinarily large person".[39] More recent estimates give a number between 9,000 and 19,000 km.[40][39]

See also

[edit]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Capillary

View on Grokipedia
from Grokipedia
A capillary is the smallest in the , characterized by a thin wall composed solely of endothelial cells that enables the exchange of oxygen, , nutrients, and waste products between the stream and surrounding tissues. Capillaries form extensive networks called capillary beds that connect arterioles and venules, distributing oxygenated throughout the body and facilitating of tissues. Their is typically 5–10 micrometers, allowing cells to pass in single file, which maximizes surface area for while minimizing flow resistance. Unlike larger vessels, capillaries lack and are supported only by a and occasional , making their walls highly permeable to support metabolic exchange. Based on endothelial structure and permeability, capillaries are classified into three types: continuous, fenestrated, and sinusoidal (also called discontinuous). Continuous capillaries feature complete endothelial lining with tight junctions, restricting passage to small molecules and lipid-soluble substances; they predominate in skeletal muscle, skin, and the blood-brain barrier. Fenestrated capillaries contain pores (fenestrae) of 20–100 nanometers in diameter covered by a diaphragm, enhancing filtration and reabsorption; these are found in endocrine glands, kidneys (glomeruli), and intestinal villi. Sinusoidal capillaries have irregular, discontinuous endothelium with large gaps up to 1 micrometer, permitting the transit of proteins, cells, and even bacteria; they occur in the liver, spleen, bone marrow, and lymph nodes. The primary function of all capillary types is bidirectional exchange via passive diffusion, facilitated diffusion, and pressure-driven filtration, ensuring homeostasis by delivering essentials like glucose and oxygen while removing metabolic byproducts. Capillary density varies by tissue needs, with high concentrations in metabolically active organs like the heart and kidneys, and blood flow is regulated by precapillary sphincters to match local demands. Pathologically, capillary dysfunction contributes to conditions such as edema, ischemia, and diabetic retinopathy, underscoring their critical role in vascular health.

Terminology

Etymology

The word capillary originates from the Latin adjective capillāris, meaning "of or pertaining to ," which itself derives from capillus, denoting "" (particularly of the head), ultimately tracing back to caput, meaning "head." This term entered English in the mid-17th century, initially describing structures resembling fine hairs in slenderness and elongation, a usage that aligned with early observations of the minute blood vessels now known as capillaries. The anatomical application reflects their hair-like appearance.

Definition and Characteristics

Capillaries are the smallest vessels in the , forming microscopic networks that connect arterioles to venules and serve as the primary site for the exchange of oxygen, nutrients, , and waste products between and surrounding tissues. These vessels are characterized by their extremely thin walls, which consist solely of a single layer of flattened endothelial cells, allowing for efficient across the vessel barrier. Unlike larger arteries and veins, capillaries lack cells and elastic fibers, relying instead on the surrounding arterioles for blood flow regulation. Structurally, the capillary wall includes the supported by a thin , with occasional embedded within or around this membrane to provide and regulate permeability. Capillaries typically measure 5 to 10 micrometers in diameter, just wide enough to allow red blood cells to pass through in single file, which minimizes the distance and enhances exchange efficiency. Their total surface area is vast due to extensive branching, estimated at around 800–1,000 square meters in an adult human, facilitating the high-volume transfer essential for tissue perfusion. Functionally, capillaries enable passive of small solutes (less than 3 nanometers in size) through endothelial junctions or fenestrations, while larger molecules like proteins require specialized transporters or vesicular transport mechanisms. This selective permeability is crucial for maintaining and preventing excessive leakage, with flow through capillary beds controlled by precapillary sphincters to match metabolic demands of tissues. In aggregate, these characteristics make capillaries indispensable for , as disruptions in their structure or function can lead to impaired delivery and tissue .

Anatomy

Microscopic Structure

Capillaries are the smallest vessels in the , typically measuring 5 to 10 micrometers in , which is just wide enough for red cells to pass through in single file. Their walls consist of a single layer of flattened endothelial cells, forming a that lines the lumen and facilitates the exchange of substances between and tissues. This endothelial layer is supported by a thin composed of proteins, such as type IV and , which provides structural integrity without impeding . Under light microscopy, capillaries appear as thin, tube-like structures with minimal visible wall thickness, often requiring special stains like to highlight the . Electron microscopy reveals greater detail, showing the endothelial cells connected by tight junctions or adherens junctions, with occasional fenestrations or gaps depending on the capillary type, though the general structure remains a continuous barrier in most tissues. , elongated contractile cells embedded in the , wrap around the exterior of capillaries at irregular intervals, comprising about 1 per 100 endothelial cells and contributing to vessel stability and regulation. The overall length of capillaries in the human body is estimated at around 40,000 kilometers, forming an extensive network that maximizes surface area for exchange, with a total cross-sectional area vastly exceeding that of larger vessels. In histological preparations, such as thin sections fixed with glutaraldehyde and stained with uranyl acetate, the capillary wall measures approximately 0.5 micrometers thick, underscoring its role as a semi-permeable interface. No smooth muscle layer is present, distinguishing capillaries from arterioles and venules, and their sparse connective tissue support allows for flexibility and proximity to tissue cells.

Continuous Capillaries

Continuous capillaries represent the most prevalent type of capillary throughout the body, comprising the majority of the approximately 10 billion capillaries in a typical human adult. These vessels feature a complete, uninterrupted layer of endothelial cells joined by tight junctions, which form a continuous barrier without intercellular gaps, pores, or fenestrations. The endothelial lining is supported by a continuous , and intermittently wrap around the exterior, providing structural support and regulatory influence over endothelial function. This architecture results in relatively low permeability compared to other capillary types, restricting the passage of substances primarily to small molecules such as , ions, and lipid-soluble compounds via through the endothelial cells or narrow intercellular clefts approximately 1 μm in length and 0.5–1 nm wide. In terms of function, continuous capillaries facilitate the essential exchange of oxygen, nutrients, and waste products between and surrounding tissues through paracellular diffusion for hydrophilic solutes and transcellular routes for larger entities. Transport mechanisms include via vesicles and caveolae—small invaginations of the endothelial plasma —that enable the shuttling of proteins, peptides, and other macromolecules across the without disrupting the barrier integrity. and further contribute to this selective permeability, ensuring controlled nutrient delivery while preventing unrestricted leakage. In specialized contexts, such as the in the , continuous capillaries exhibit enhanced complexity, minimal , and efflux transporters like , which actively exclude potentially harmful substances from neural tissue. These capillaries are distributed across a wide array of tissues, including skeletal and , , , lungs, and the , where they support routine metabolic demands. In the lungs, for instance, they enable efficient while maintaining barrier selectivity to avoid fluid leakage into alveoli. Their prevalence and regulated permeability underscore their role in maintaining tissue homeostasis, with disruptions implicated in conditions like or barrier dysfunction in neurodegenerative diseases.

Fenestrated Capillaries

Fenestrated capillaries represent a subtype of continuous capillaries distinguished by the presence of fenestrations—small pores or openings in the endothelial cells that permit enhanced transendothelial transport. These structures are essential in tissues where rapid exchange of fluids, solutes, and small molecules between blood and is required. Unlike non-fenestrated continuous capillaries, the fenestrations increase permeability while maintaining a through thin diaphragms spanning the pores. The endothelial lining of fenestrated capillaries consists of a single layer of flattened squamous cells, underpinned by a and sporadically supported by . Each fenestration typically measures 60-80 nm in and is sealed by a non-membranous diaphragm approximately 3-5 nm thick, composed of radially oriented protein such as plasmalemmal vesicles-derived components. This diaphragm selectively restricts the passage of larger macromolecules while allowing water, ions, and small solutes (up to ~40-60 ) to diffuse freely, contributing to a approximately 40-50 times greater than that of continuous capillaries. The overall capillary ranges from 5-10 μm, optimizing surface area for exchange without compromising structural integrity. These capillaries are predominantly located in organs involved in filtration, absorption, and secretion. In the kidneys, they form the glomerular capillary network, enabling of plasma during urine formation. They are also abundant in the small intestine's villi and mucosa, where they support and absorption, and in endocrine glands such as the and , facilitating hormone release into the bloodstream. Additional sites include the of the brain, underscoring their role in specialized barrier functions across vascular beds. Physiologically, fenestrated capillaries play a critical role in maintaining through regulated permeability. In renal glomeruli, the fenestrations, combined with slit diaphragms, achieve a barrier that excludes (66 kDa) while permitting smaller molecules, with a sieving coefficient near 1 for substances under 10 kDa. This selective prevents and supports efficient waste removal. In absorptive tissues like the intestine, the pores enhance the uptake of glucose, , and post-digestion. Disruptions in fenestration integrity, such as in , can lead to , highlighting their clinical significance.

Sinusoidal Capillaries

Sinusoidal capillaries, also known as sinusoids, represent a specialized subtype of discontinuous capillaries distinguished by their irregular, widened lumens and highly permeable walls. Unlike continuous or fenestrated capillaries, they feature large intercellular gaps between endothelial cells, often exceeding 100 nm in width, and a discontinuous or entirely absent , which collectively enable the passage of macromolecules, plasma proteins, and even intact cells such as erythrocytes and leukocytes. This structure is composed of a single layer of flattened endothelial cells that lack tight junctions, further enhancing permeability while maintaining a selective to the needs of specific tissues. These capillaries are predominantly located in organs requiring extensive filtration, blood cell production, or metabolic processing, including the liver (hepatic sinusoids), , , lymph nodes, adrenal glands, and other endocrine glands such as the pituitary. In the liver, sinusoids form a complex network surrounding hepatocytes, receiving blood from the hepatic portal vein and hepatic to facilitate absorption and toxin . Similarly, in the , they allow the release of newly formed blood cells into circulation, while in the , they support immune surveillance by permitting the passage of antigens and damaged cells for . Their strategic positioning in these sites underscores their role in high-volume exchange environments. The primary function of sinusoidal capillaries is to support rapid and extensive bidirectional exchange between and interstitial fluid, accommodating slower blood flow velocities that prolong contact time for and . This high permeability is crucial for physiological processes such as the liver's uptake of remnants and , the spleen's clearance of senescent red cells, and the marrow's egress of hematopoietic progenitors. In hepatic sinusoids, specialized endothelial cells are often interspersed with resident macrophages known as Kupffer cells, which enhance phagocytic activity against pathogens and debris, thereby integrating vascular exchange with immune defense. Overall, their design optimizes organ-specific by prioritizing permeability over selective restriction.

Formation and Development

Embryonic Development

The embryonic development of capillaries begins with vasculogenesis, the de novo formation of blood vessels from endothelial precursor cells known as angioblasts, which differentiate from mesodermal progenitors during early . In mammalian embryos, this process initiates in the extraembryonic around embryonic day 7.0-7.5 in mice (corresponding to approximately 3 weeks in human gestation), where hemangioblasts—bipotent progenitors giving rise to both endothelial and hematopoietic cells—aggregate into blood islands. These islands consist of an inner core of primitive erythroblasts surrounded by endothelial cells that fuse to form a primitive capillary , establishing the foundational vascular network essential for nutrient exchange and embryonic survival. Key molecular regulators drive this initial vasculogenesis, including (VEGF) and its receptor VEGFR-2 (Flk-1/KDR), which are critical for angioblast specification and migration. Transcription factors such as TAL1 (SCL), , and LMO2 orchestrate endothelial differentiation from , while fibroblast growth factors (FGFs) support proliferation and survival of these precursors. Intraembryonically, vasculogenesis extends to the splanchnic by embryonic day 8.0 in mice, forming paired dorsal aortae and cardinal veins from coalescing angioblasts, with the primitive plexus maturing into capillary beds that perfuse emerging embryonic tissues. Disruptions in these pathways, as seen in VEGF or TAL1 models, result in severe vascular defects and embryonic lethality, underscoring their indispensable role. As embryogenesis progresses, angiogenesis— the sprouting and branching of new vessels from pre-existing ones—supplements vasculogenesis to expand and refine the capillary network, particularly from embryonic day 8.5 onward in mice. Endothelial tip cells, guided by VEGF gradients and Delta-Notch signaling, lead filopodial extensions to form sprouts that connect and remodel into hierarchical capillary structures, ensuring adequate oxygenation of rapidly growing organs like the brain and heart. This phase involves pericyte recruitment for vessel stabilization and lumen formation, transforming rudimentary capillaries into functional units capable of fluid and solute exchange. In humans, this corresponds to weeks 4-8 of gestation, when the chorioallantoic placenta integrates with embryonic capillaries to support fetal circulation.

Adult Angiogenesis and Remodeling

In adults, —the formation of new blood vessels from pre-existing ones—primarily occurs in response to physiological demands such as , tissue repair, and exercise-induced muscle adaptation, or pathological conditions like cancer and ischemia. Unlike the extensive vascularization during embryonic development, adult is tightly regulated and episodic, maintaining vascular quiescence through balanced pro- and anti-angiogenic signals. The process begins with the activation of endothelial cells (ECs) in existing capillaries or venules, triggered by hypoxia-inducible factors (HIFs) that upregulate (VEGF), the principal stimulator of . Sprouting angiogenesis, the dominant mechanism in adults, involves the degradation of the by matrix metalloproteinases (MMPs) released from ECs and recruited inflammatory cells, allowing tip cells to lead filopodial extensions toward angiogenic cues. Stalk cells proliferate behind the tip cells, forming a lumenized sprout that anastomoses with neighboring vessels to establish ; this is followed by recruitment of and cells for vessel stabilization via (PDGF) and angiopoietin-1 (Ang-1) signaling. In parallel, intussusceptive angiogenesis enables rapid vascular remodeling without proliferation, where transcapillary pillars form and split existing vessels, enhancing network complexity in response to hemodynamic changes. Capillary remodeling in adults encompasses of inefficient branches, diameter adjustments, and network reorganization to optimize oxygen delivery and distribution. Flow-induced activates mechanosensors like and VEGFR2 in ECs, promoting (NO) production via endothelial (eNOS), which supports vessel dilation and stabilization of high-flow segments while inducing regression in low-flow ones through thrombospondin-1 and other inhibitors. This angioadaptation ensures metabolic efficiency; for instance, in during exercise, capillary density can increase by 10–25% through coordinated sprouting and remodeling, correlating with enhanced VEGF expression. Pathological remodeling, as in tumors, often results in leaky, tortuous vessels due to excessive VEGF and imbalanced Ang-2/Ang-1 ratios, impairing function.

Physiology

Exchange Mechanisms

Capillary exchange primarily occurs through three key mechanisms: , , and bulk flow, which collectively facilitate the transfer of gases, nutrients, solutes, and fluid between the and interstitial spaces. These processes are optimized by the thin structure of the capillary , typically 0.3–1 μm thick, and vary depending on the capillary type and tissue demands. Diffusion is the dominant mechanism for small molecules, allowing passive movement down concentration gradients across the capillary wall. Lipid-soluble substances, such as oxygen and , readily cross the bilayer of endothelial cells via simple , enabling rapid in tissues like muscles and lungs. Water-soluble molecules, including ions, glucose, and , traverse via paracellular pathways through intercellular clefts (about 0.6–0.7 nm wide in continuous capillaries) or through fenestrations and larger pores in specialized capillaries. This selective permeability ensures efficient nutrient delivery while restricting larger entities, with rates influenced by molecular size, charge, and . Transcytosis, or vesicular transport, handles the transcellular movement of larger or impermeable molecules, such as , immunoglobulins, and some hormones. Endothelial cells form vesicles—often caveolae (flask-shaped invaginations 50–70 nm in diameter)—that engulf extracellular material via on the luminal side, traverse the , and release contents via on the abluminal side. This process is energy-dependent and regulated by signaling pathways, playing a critical role in maintaining ; for instance, in the blood-brain barrier, it limits paracellular leakage while permitting selective macromolecular transport. Clathrin-coated vesicles may also contribute in specific contexts, though caveolae predominate in most systemic capillaries. Bulk flow provides a convective pathway for and accompanying small solutes, driven by pressure differences across the . In continuous capillaries, this occurs through small intercellular clefts, while fenestrated and sinusoidal capillaries feature diaphragmed or ungapped pores (up to 100 nm) that enhance rates, as seen in renal glomeruli where up to 180 liters of filter daily. Although integral to overall exchange, bulk flow's quantitative aspects, including net , are determined by transendothelial pressures and oncotic forces.

Fluid Dynamics and Starling Equation

The fluid dynamics within capillaries are characterized by laminar flow due to their small diameters (typically 5–10 μm) and low Reynolds numbers, which ensure that inertial forces are negligible compared to viscous forces. This steady, non-turbulent flow is primarily governed by Poiseuille's law, which quantifies the volume flow rate QQ through a cylindrical tube as Q=πr4ΔP8ηLQ = \frac{\pi r^4 \Delta P}{8 \eta L}, where rr is the radius, ΔP\Delta P is the pressure difference along the length LL, and η\eta is the fluid viscosity. In capillaries, blood behaves as a non-Newtonian fluid owing to the high hematocrit and deformation of red blood cells, but Poiseuille's law provides a useful approximation for understanding how flow velocity decreases dramatically toward the periphery, averaging around 0.3–1 mm/s, facilitating efficient nutrient and gas exchange. The pressure gradient driving this flow originates from the arteriolar resistance, with hydrostatic pressure dropping from approximately 35 mmHg at the arterial end to 15 mmHg at the venous end of a typical systemic capillary. Capillary extend beyond bulk flow to the transvascular exchange of fluid between plasma and space, which is critical for maintaining tissue . This exchange occurs via and across the endothelial wall, influenced by forces that balance hydrostatic and oncotic pressures. The seminal , formulated by Ernest Henry in 1896, describes the net fluid flux JvJ_v per unit surface area as: Jv=Kf[(Pc−Pi)−σ(πc−πi)]J_v = K_f \left[ (P_c - P_i) - \sigma (\pi_c - \pi_i) \right] where KfK_f is the filtration coefficient (reflecting and surface area), PcP_c and PiP_i are capillary and hydrostatic pressures, σ\sigma is the for proteins (indicating endothelial permeability to solutes), and πc\pi_c and πi\pi_i are capillary and oncotic pressures. Hydrostatic pressure favors out of the capillary, while oncotic pressure—primarily from plasma proteins like —promotes ; typically, filtration occurs at the arterial end (where Pc>πcP_c > \pi_c) and reabsorption at the venous end, with any excess interstitial fluid drained by lymphatics. Refinements to the classical , such as the revised model incorporating the endothelial layer, emphasize that sub oncotic pressure plays a dominant role in preventing by creating a barrier that sustains the near the endothelial junction. This model, supported by experimental evidence from microvascular studies, highlights how disruptions (e.g., in ) can shift the balance toward excessive , underscoring the equation's application in . Quantitative estimates indicate that under normal conditions, about 20–25 liters of filter daily across capillaries, with roughly 90% reabsorbed and the remainder returned via . These dynamics ensure precise regulation of volume, with deviations linked to conditions like or .

Clinical Aspects

Pathophysiology

Capillary encompasses disruptions in the structural integrity, permeability, and regulatory functions of these microvessels, leading to impaired nutrient exchange, tissue , and organ dysfunction. In inflammatory conditions such as , endothelial cells in capillaries release mediators like , , and cytokines, which increase by disrupting tight junctions and , resulting in fluid and protein leakage into the . This contributes to , third-spacing of fluids, and multi-organ failure. Systemic capillary leak syndrome represents a severe form of permeability dysfunction, where episodic or idiopathic increases in endothelial gap formation allow massive protein-rich fluid , causing , hemoconcentration, and life-threatening in organs like the lungs and heart. The underlying mechanisms involve endothelial degradation and storms, often triggered by infections, malignancies, or monoclonal gammopathies. In chronic metabolic disorders like diabetes mellitus, diabetic induces capillary thickening, loss, and , primarily driven by hyperglycemia-induced and , which impair and promote leakage in retinal, renal, and peripheral capillaries. This leads to , nephropathy, and neuropathy through localized ischemia and hemorrhage. Similarly, in , prolonged exposure to risk factors such as and causes endothelial activation, , and capillary rarefaction—a reduction in capillary density due to apoptosis and impaired —exacerbating tissue hypoxia even after large-vessel . Hereditary conditions like (HHT) involve genetic mutations in TGF-β signaling pathways, leading to fragile, dilated capillaries prone to rupture and arteriovenous malformations, resulting in recurrent epistaxis, mucocutaneous telangiectasias, and visceral bleeding. In neoplastic processes, aberrant driven by (VEGF) overexpression produces leaky, tortuous capillaries that support tumor growth but cause peritumoral and facilitation.

Diagnostics and Therapeutics

Diagnostics of capillary dysfunction often rely on non-invasive techniques to assess microvascular structure and function. Nailfold capillaroscopy, a simple and safe method, allows direct visualization of nailfold capillaries using a or dermatoscope to evaluate morphology, density, and blood flow patterns, aiding in the diagnosis of diseases and other microvascular abnormalities. In systemic capillary leak syndrome (SCLS), diagnosis is based on recurrent episodes of severe , hemoconcentration (elevated ), and generalized , confirmed by exclusion of other causes and sometimes supported by (MGUS). For cerebral small vessel disease (SVD), advanced imaging such as arterial spin labeling (ASL) MRI detects capillary dysfunction through impaired and elevated capillary transit time heterogeneity, correlating with cognitive decline. In coronary microvascular disease, diagnostic approaches include coronary flow reserve (CFR) measurement via (PET) or invasive catheterization to quantify capillary-level flow impairment, often revealing reduced CFR (<2.0) indicative of . Impedance cardiography provides hemodynamic insights in acute capillary leak scenarios, monitoring thoracic fluid content and to guide fluid management. Therapeutics targeting capillaries focus on stabilizing endothelial barriers, improving , and addressing underlying causes in specific disorders. For SCLS, acute attacks are managed supportively with cautious intravenous fluids and infusions to counteract without exacerbating leakage, while prophylactic therapy with oral (a β2-agonist) and (a ) reduces attack frequency by enhancing vascular tone, achieving remission in many patients. Intravenous immunoglobulin (IVIG) has shown efficacy in refractory cases by modulating endothelial permeability. In coronary microvascular disease, β-blockers (e.g., ) and alleviate and improve capillary dilation, while statins and inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) enhance endothelial function by reducing and , leading to symptom improvement. Emerging therapies, such as intracoronary infusion of + cells, promote and capillary repair in refractory microvascular , with trials reporting enhanced CFR and reduced episodes. For cerebral SVD involving capillary pathways, blood pressure control with ACEIs or ARBs prevents progression, while antiplatelet agents like aspirin reduce microvascular ; investigational therapies include donors and phosphodiesterase-5 inhibitors to boost capillary , showing promise in preclinical models for mitigating risk. In sepsis-related capillary leak, experimental approaches target permeability regulators like TRPV4 channels with selective antagonists to limit formation, though clinical translation remains limited. Emerging therapies as of 2025 include engineered exosomes for treating capillary-related neovascularization in ocular diseases such as and potential interventions targeting capillary dysfunction in neurodegenerative conditions like .

History

Early Observations

The earliest conceptualizations of capillary-like structures emerged in medieval Islamic , where the physician (1213–1288) described the in his commentary on Avicenna's . He proposed that blood from the right ventricle passes through the lungs via minute, invisible channels—effectively predicting capillaries—before reaching the left ventricle, challenging Galen's erroneous view of direct ventricular interconnection. In the , (1452–1519) made some of the first direct observations of fine vascular networks during anatomical dissections. Through detailed sketches and notes, he depicted small vessels branching from arteries and rejoining veins, inferring their role in connecting the two systems and facilitating distribution, though limited by the absence of tools. The definitive gap in understanding circulation was highlighted by William Harvey's 1628 treatise De Motu Cordis, which established systemic flow but left unexplained how arteries and veins interconnect, as these links were imperceptible to the . This puzzle was resolved in 1661 by Marcello Malpighi (1628–1694), who employed an early compound microscope—designed by Galileo—to examine frog tissue. Malpighi observed a continuous network of minute vessels, which he termed "capillaries," linking arterioles to venules and confirming 's unbroken circuit through the lungs and other organs. His findings, published in De Pulmonibus Observationes Anatomicae, marked the first microscopic visualization of capillaries and revolutionized vascular .

Key Scientific Advancements

The discovery of capillaries as the microscopic connections between arteries and veins represented a pivotal advancement in understanding blood circulation. In 1661, Italian anatomist Marcello Malpighi first observed these vessels using an early compound microscope while examining frog lung tissue, describing them as a network of fine tubules that completed the circulatory loop proposed by three decades earlier. This observation resolved a long-standing anatomical puzzle but initially sparked debates about the capillary wall's composition, with some early microscopists like describing them as simple porous tubes without clear cellular detail. Advancements in during the clarified the cellular nature of the capillary . In the 1830s, , a founder of , proposed that capillaries were lined by an inner layer of cells, a view initially contested but later supported by observations using staining. By the mid-1800s, anatomists such as Friedrich von Recklinghausen confirmed this lining as a continuous of flattened cells, distinguishing capillaries from larger vessels. In 1865, Swiss anatomist Wilhelm His coined the term "endothelium" to describe this specialized lining, marking a consensus on its basic structure after over two centuries of debate. Functional insights emerged in the late with Ernest Henry 's formulation of the principles governing exchange across capillary walls. In 1896, Starling demonstrated through experiments on capillaries that net movement—filtration at the arterial end and reabsorption at the venous end—results from the balance of hydrostatic and oncotic pressures, as encapsulated in what became known as the Starling equation. This hypothesis provided a mechanistic explanation for interstitial homeostasis and laid the foundation for modern microvascular physiology. A major leap in understanding capillary regulation came in the early through the work of Danish physiologist . In 1919, Krogh showed that capillaries actively open and close in response to metabolic demands, particularly oxygen needs, via a "motor mechanism" involving local vasoactive factors rather than passive flow alone. This discovery, for which he received the 1920 in Physiology or Medicine, highlighted the dynamic adaptability of the capillary bed and integrated anatomical findings with quantitative measurements of oxygen diffusion capacity. Subsequent electron microscopy studies in the mid-20th century further refined capillary classification into continuous, fenestrated, and sinusoidal types, revealing specialized endothelial features like pores and diaphragms that enhance selective permeability.

References

  1. https://www.ncbi.nlm.nih.gov/books/NBK546578/
  2. https://training.seer.cancer.gov/anatomy/cardiovascular/blood/classification.html
  3. https://www.ncbi.nlm.nih.gov/books/NBK470401/
  4. https://sdmiramar.edu/sites/default/files/2023-06/Physiol%2520Text%2520Ch%252016%2520Blood%2520Vessels.pdf
  5. https://books.byui.edu/bio_265_anatomy_phy_II/243___capillaries
  6. https://en.wiktionary.org/wiki/capillary
  7. https://www.oed.com/dictionary/capillary_adj
  8. https://www.etymonline.com/word/capillary
  9. https://www.merriam-webster.com/dictionary/capillary
  10. https://courses.lumenlearning.com/suny-ap2/chapter/structure-and-function-of-blood-vessels/
  11. https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Biology_%28Kimball%29/15%253A_The_Anatomy_and_Physiology_of_Animals/15.03%253A_Circulatory_Systems/15.3B%253A_How_the_Human_Circulatory_System_Works
  12. https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/General_Biology_1e_%28OpenStax%29/7%253A_Animal_Structure_and_Function/40%253A_The_Circulatory_System/40.4%253A_Blood_Flow_and_Blood_Pressure_Regulation
  13. https://histology.siu.edu/crr/cvguide.htm
  14. https://cbs-histology02.oit.umn.edu/slidebox/09-cardiovascular-system.html
  15. https://www.kenhub.com/en/library/anatomy/capillaries
  16. https://www.ncbi.nlm.nih.gov/books/NBK553217/
  17. https://www.jove.com/science-education/v/15288/capillaries-and-their-types
  18. https://www.sciencedirect.com/topics/immunology-and-microbiology/capillary
  19. https://mospace.umsystem.edu/xmlui/bitstream/handle/10355/1026/Capillaries.pdf?sequence=1
  20. https://med.libretexts.org/Bookshelves/Anatomy_and_Physiology/Human_Anatomy_%28OERI%29/18%253A_Cardiovascular_System_-_Blood_Vessels_and_Circulation/18.02%253A_Structure_and_Function_of_Blood_Vessels
  21. https://books.byui.edu/bio_461_principles_o/capillaries
  22. https://pmc.ncbi.nlm.nih.gov/articles/PMC2681366/
  23. https://www.kenhub.com/en/library/anatomy/fenestrated-capillaries
  24. https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/expphysiol.1984.sp002805
  25. https://my.clevelandclinic.org/health/body/21988-capillaries
  26. https://ohiostate.pressbooks.pub/vethisto/chapter/6-capillaries-and-sinusoids/
  27. https://www.histology.leeds.ac.uk/circulatory/capillaries.php
  28. https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/sinusoid
  29. https://pmc.ncbi.nlm.nih.gov/articles/PMC3548208/
  30. https://www.ahajournals.org/doi/10.1161/01.atv.0000183609.55154.44
  31. https://anatomypubs.onlinelibrary.wiley.com/doi/full/10.1002/%28SICI%291097-0177%28199905%29215:1%253C2::AID-DVDY2%253E3.0.CO%253B2-U
  32. https://www.sciencedirect.com/science/article/pii/S0143400499905258
  33. https://pmc.ncbi.nlm.nih.gov/articles/PMC10777330/
  34. https://pubmed.ncbi.nlm.nih.gov/10742145/
  35. https://pmc.ncbi.nlm.nih.gov/articles/PMC4063884/
  36. https://pmc.ncbi.nlm.nih.gov/articles/PMC4280154/
  37. https://pmc.ncbi.nlm.nih.gov/articles/PMC11072276/
  38. https://onlinelibrary.wiley.com/doi/10.1111/sms.14442
  39. https://cvphysiology.com/microcirculation/m016
  40. https://www.ncbi.nlm.nih.gov/books/NBK53447/
  41. https://teachmephysiology.com/cardiovascular-system/circulation/capillary-exchange/
  42. https://journals.physiology.org/doi/pdf/10.1152/advances.1999.277.6.S203
  43. https://www.ahajournals.org/doi/pdf/10.1161/01.res.59.4.367
  44. https://pmc.ncbi.nlm.nih.gov/articles/PMC6629499/
  45. https://journals.physiology.org/doi/10.1152/ajplung.00436.2006
  46. https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2018.01019/full
  47. http://www.columbia.edu/~kj3/Chapter2.htm
  48. https://pubmed.ncbi.nlm.nih.gov/1798043/
  49. https://pmc.ncbi.nlm.nih.gov/articles/PMC8056939/
  50. https://pubmed.ncbi.nlm.nih.gov/20200043/
  51. https://pubmed.ncbi.nlm.nih.gov/28318633/
  52. https://pubmed.ncbi.nlm.nih.gov/28137665/
  53. https://pubmed.ncbi.nlm.nih.gov/31878229/
  54. https://pmc.ncbi.nlm.nih.gov/articles/PMC4918046/
  55. https://pmc.ncbi.nlm.nih.gov/articles/PMC2947962/
  56. https://pmc.ncbi.nlm.nih.gov/articles/PMC4759673/
  57. https://pmc.ncbi.nlm.nih.gov/articles/PMC7901821/
  58. https://pubmed.ncbi.nlm.nih.gov/20104463/
  59. https://pubmed.ncbi.nlm.nih.gov/10375339/
  60. https://www.amjmed.com/article/S0002-9343(17)30602-2/fulltext
  61. https://pmc.ncbi.nlm.nih.gov/articles/PMC8151216/
  62. https://pmc.ncbi.nlm.nih.gov/articles/PMC4832291/
  63. https://pubmed.ncbi.nlm.nih.gov/32227554/
  64. https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-025-03589-3
  65. https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1458455/full
  66. https://pmc.ncbi.nlm.nih.gov/articles/PMC2612469/
  67. https://pubmed.ncbi.nlm.nih.gov/17851250/
  68. https://karger.com/ene/article/58/4/253/125024/Malpighi-and-the-Discovery-of-Capillaries
  69. https://www.nobelprize.org/prizes/medicine/1920/krogh/lecture/
  70. https://www.researchgate.net/publication/6145165_The_history_of_the_capillary_wall_Doctors_discoveries_and_debates
  71. https://www.ncbi.nlm.nih.gov/books/NBK57145/
  72. https://www.nobelprize.org/prizes/medicine/1920/krogh/facts/
  73. https://journals.physiology.org/doi/full/10.1152/ajpheart.00704.2007
Add your contribution
Related Hubs
User Avatar
No comments yet.