Capillaries

Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries are organized into capillary beds, which are extensive networks of branches and anastomoses. Blood flows from the metarterioles, into the capillaries, out the thoroughfare channel, and into venules. Continuous, fenestrated, and sinusoid (discontinuous) capillaries are the 3 primary types, and each has a slightly different structure. Capillary dysfunction can occur either as a result of or a contribution to the clinical manifestation of many clinical conditions.

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General Characteristics

Definition

Capillaries are the smallest of the blood vessels. Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF).

Structure

  • Simple tubes made up of a single layer of endothelial cells
  • Diameter:
    • Approximately 5 µm in diameter at the arterial end
    • Approximately 9 µm in diameter at the venous end 
    • RBCs are approximately 7 µm in diameter → RBCs are forced through capillaries 1 at a time 
  • Endothelial cells are separated from surrounding tissue by basal lamina.
  • Capillaries are surrounded by pericytes (epithelial cells within the endothelial basal lamina, which play a role in neurovascular signaling).
  • Arranged in vast networks known as capillary beds (groups of 10–100 individual capillary vessels supplied by a single metarteriole)
  • Massive total surface area: estimated at > 6,300 m2
Cross section of an arteriole

Cross-section of an arteriole (left) and a capillary (right) with a surrounding pericyte (labeled pericyte nucleus)

Image by Geoffrey Meyer, PhD.

Blood flow through and around capillaries

  • Blood enters the capillary beds through the arterioles → metarterioles → capillaries
  • Blood drains into the thoroughfare channel → venules
  • Metarterioles contain precapillary sphincters of smooth muscle at the entrance to each individual capillary:
    • Regulate the amount of blood flow into the capillary bed
    • When sphincters are closed, blood bypasses the capillaries and flows straight into the thoroughfare channel.
  • Arteriovenous (AV) anastomoses/shunts: Vessels bypass the capillary beds and directly connect arteries and veins.
    • AV shunts are present when precapillary sphincters are closed.
    • Numerous in the dermis (help regulate body heat)
Capillary bed

Capillary bed demonstrating arteriole, metarteriole, and precapillary sphincters

Image: “Capillary bed” by OpenStax College. License: CC BY 3.0

Location

  • Capillaries are the connection between the smallest arteries (arterioles) and the smallest veins (venules).
  • Found within 60–80 µm of essentially every cell in the body 
  • Capillary beds are located in all tissues except:
    • Cartilage
    • Epithelia
    • Eye cornea and lens
  • Tendons and ligaments have some capillaries, but much less than most other tissue.

Physiology

  • Functions:
    • Gas exchange: Oxygen exits RBCs, carbon dioxide enters RBCs.
    • Nutrient delivery
    • Blood picks up cellular and interstitial waste.
  • Mechanisms of exchange:
    • Transcytosis/pinocytosis: Substances are taken into the endothelial cells in vesicles via endocytosis, transported across the cell, and released on the other side.
    • Direct filtration: relies on Starling forces
  • Starling forces applied to capillaries:
    • Relatively higher hydrostatic pressure in the arterioles pushes fluid, nutrients, and other cellular material into the surrounding ECF.
    • Plasma proteins generally cannot pass through the capillary walls → plasma oncotic pressure ↑ towards the venous end of the capillary
    • Relatively higher oncotic pressure in the venules allows waste to be absorbed into the vessels
Starling forces within a capillary

Starling forces:
Starling forces within a capillary determine the flow of molecules into and out of the vessel.

Image: “Net filtration” by Phil Schatz. License: CC BY 4.0

Types of Capillaries

3 primary types of capillaries:

  1. Continuous capillaries
  2. Fenestrated capillaries
  3. Sinusoid, or discontinuous, capillaries
Types of capillaries

Types of capillaries

Image: “Types of capillaries” by Phil Schatz. License: CC BY 4.0

Continuous capillaries

Continuous capillaries are the most common type of capillary.

  • Structure:
    • Endothelial cells are connected via occluding tight junctions.
    • Continuous basal lamina
    • Prevents diffusion of fluid, protein, and other molecules
    • Some tissues contain small clefts (approximately 4 nm wide) → allow the passage of very small molecules (e.g., glucose)
  • Primary mechanism of exchange: transcytosis/pinocytosis
  • Location (found in organs requiring passage of only select molecules):
    • Central nervous system
    • Lungs
    • All muscle: cardiac, skeletal, and smooth
    • Connective tissue
    • Skin
Continuous capillaries

Diagram of a continuous capillary

Image: “Continuous capillaries” by Phil Schatz. License: CC BY 4.0

Fenestrated capillaries

Fenestrated capillaries are important in organs requiring rapid absorption and filtration, or with high metabolic activity.

  • Structure:
    • Wall contains multiple fenestrations, or “pores”, with continuous basal lamina.
    • Fenestrations are approximately 20–100 nm in diameter.
    • Allows for the rapid passage of small molecules, but keeps proteins and larger particles within the blood vessel
  • Primary mechanism of exchange: filtration 
  • Location:
    • Kidneys
    • Endocrine organs (e.g., pancreas)
    • Intestinal tract
Fenestrated capillaries

Diagram of a fenestrated capillary

Image: “Fenestrated capillaries” by Phil Schatz. License: CC BY 4.0

Sinusoid (discontinuous) capillaries

Sinusoid, or discontinuous, capillaries allow larger proteins and full cells to pass through larger gaps.

  • Structure:
    • Large gaps (up to 0.5 µm) in the cytoplasm of the endothelium
    • Basal lamina has large gaps or may be completely absent.
    • May appear as larger, blood-filled spaces between other tissues
  • Mechanism of exchange: direct filtration/diffusion
  • Locations:
    • Liver
    • Spleen
    • Bone marrow
  • Specialized functions: 
    • Allows larger structures to enter circulation, for example:
      • Proteins synthesized in the liver (e.g., albumin and clotting factors) 
      • Blood synthesized in the bone marrow
    • Allows for “aggressive” communication between the perivascular cells and the blood itself
Sinusoid capillaries

Diagram of a sinusoid capillary

Image: “Sinusoid capillaries” by Phil Schatz. License: CC BY 4.0

Clinical Relevance

Thrombotic microangiopathies

Thrombotic microangiopathies (TMAs) are a group of conditions characterized by abnormalities in the walls of arterioles and capillaries, which lead to microvascular thrombosis. The most common primary TMAs are thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Drugs can also induce a TMA.

  • Thrombotic thrombocytopenic purpura: a life-threatening condition due to either a congenital or an acquired deficiency of ADAMTS-13, a metalloproteinase cleaving multimer of von Willebrand’s Factor (vWF). Without metalloproteinase, the large multimers aggregate excessive platelets, resulting in microvascular thrombosis and an increase in consumption of platelets. The classic clinical presentation includes thrombocytopenia, hemolytic anemia, kidney disease, neurological symptoms, and fever. 
  • Hemolytic uremic syndrome: a clinical phenomenon most commonly seen in children consisting of the classic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Hemolytic uremic syndrome is most commonly associated with a prodrome of diarrheal illness caused by Shiga-like, toxin-producing bacteria.

Increased hydrostatic pressure within the capillaries

Any condition preventing blood flow from moving forward can lead to an increase in hydrostatic pressure within the vessels, which ultimately may get transmitted to the capillaries. Increasing the hydrostatic pressure within the capillaries affects the exchange of substances through the capillaries, pushing more fluid and substrates into the ECF. The types of conditions may include:

  • Congestive heart failure: the inability of the heart to supply the body with the cardiac output required to meet the body’s metabolic needs. Patients typically present with dyspnea on exertion and/or at rest, orthopnea, and peripheral edema. Because blood is not effectively pumped out of the heart, pressure builds up in venous circulation and ultimately backs up into the capillaries. Diagnosis can be made with an echocardiogram.
  • Cirrhosis: late stage of hepatic necrosis and scarring. Chronic cellular damage causes extensive distortion of the normal hepatic architecture, which can lead to impairment of normal blood flow through the liver. The most common causes of cirrhosis are chronic, excessive alcohol use, viral hepatitis, and nonalcoholic steatohepatitis (NASH). Decompensation occurs late in the disease with manifestations including jaundice, ascites, portal hypertension, and liver failure. 
  • Lower-extremity deep vein thrombosis (DVT): occlusion of a deep vein by a thrombosis, most commonly occurring in the calves. The affected veins may include the femoral, popliteal, iliofemoral, or pelvic veins. Hydrostatic pressure increases distal to the DVT, which leads to edema and pain seen on presentation. Ultrasound can visualize the thrombus and anticoagulation is the primary mode of treatment. 

Decreased capillary oncotic pressure

Decreased capillary oncotic pressure (usually due to a loss of albumin) is the failure to retain fluid within the capillaries, leading to increased capillary leakage. Hypoalbuminemia may result from:

  • Nephrotic syndrome: a broad category of glomerular diseases characterized by severe proteinuria, hypoalbuminemia, edema, and hyperlipidemia. In most cases, a kidney biopsy is necessary for diagnosis. Management varies with etiology and usually involves glucocorticoids.
  • Cirrhosis (above): Severe liver disease may lead to a decrease in albumin synthesis.

Increased capillary permeability

Some conditions lead to increases in capillary permeability independent of changes in hydrostatic or oncotic pressure. The conditions are often due to the release of inflammatory cytokines. Some conditions include:

  • Sepsis: a clinical syndrome resulting from a dysregulated, systemic, host response to infection. Systemic release of inflammatory molecules leads to activation of endothelial cells and an increase in capillary permeability. Sepsis also results in a significant decrease in the number of functioning capillaries (likely due to compression by surrounding tissue edema) and plugging of the capillaries by blood cells, which lose their deformability.
  • Angioedema: a localized, self-limited, potentially life-threatening, nonpitting, asymmetrical edema occurring in the deep layers of the skin and mucosal tissue. The common underlying pathophysiology involves inflammatory mediators, which trigger significant vasodilation and increased capillary permeability. Angioedema presentation includes swelling around the eyes, lips, tongue, mouth, bowel wall, extremities, or genitalia. The airway may be compromised.
  • Idiopathic systemic capillary leak syndrome: a rare disorder characterized by episodes of severe hypotension, hypoalbuminemia, and hemoconcentration. The etiology is unknown. Clinical presentation results from systemic, capillary leakage of fluid with protein and larger molecule retention within the vessels.

Other clinical conditions associated with abnormal capillaries

  • Diabetes mellitus: Chronic hyperglycemia can cause diabetic microangiopathy, a thickening of the capillary basal lamina reducing the metabolic exchange between blood and tissues. The microangiopathy may ultimately lead to tissue ischemia (especially in the kidneys, eyes, and limbs) and result in renal failure, blindness, and/or limb amputations, respectively.
  • Telangiectasia: Small, dilated blood vessels (usually arterioles, venules, or capillaries) appear as thin, red lines on the skin or mucous membranes.

References

  1. Taylor, A.M., and Bordoni, B. (2021). Histology, blood vascular system. In StatPearls. Retrieved April 26, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK553217/ 
  2. Saladin, K.S., Miller, L. (2004). Anatomy and physiology. (3rd Ed., Pp. 750‒752). 
  3. Moore, K.L., and Dalley, A.F. (2006). Clinically oriented anatomy. (5th Ed., Pp 44).

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