What are the differences between continuous, fenestrated, and sinusoidal (or discontinuous) capillaries?

Differentiation of Capillary Types

The three types of capillaries are distinguished primarily by their endothelial structure: continuous capillaries have uninterrupted endothelium with tight junctions, fenestrated capillaries contain pores (fenestrae) with diaphragms that allow selective passage of molecules, and sinusoidal (discontinuous) capillaries have large gaps without diaphragms and an incomplete or absent basement membrane, permitting free exchange of cells and large molecules.

Structural Characteristics

Continuous Capillaries

• Endothelial integrity: Feature uninterrupted endothelial cells connected by tight junctions that restrict paracellular movement 1
• Basement membrane: Possess a complete, organized basement membrane 2
• Permeability: Most restrictive type, limiting passage primarily to small lipophilic solutes and water through transcellular pathways 3
• Transport mechanisms: Substances cross via endothelial cell membranes (active transport, facilitated diffusion, passive diffusion) or limited vesicular transport, with paracellular movement severely restricted 1
• Examples: Found in brain (blood-brain barrier), lung alveolar capillaries, skeletal muscle, and heart 1, 3

Fenestrated Capillaries

• Fenestrae structure: Contain circular pores (fenestrae) 60-80 nm in diameter covered by thin diaphragms with negative charges 4, 5
• Transendothelial channels: Also possess channels fitted with two diaphragms, with the luminal diaphragm being uncharged 4
• Basement membrane: Maintain a continuous basement membrane beneath the endothelium 2
• Permeability characteristics: Higher hydraulic conductivity than continuous capillaries, allowing enhanced passage of water and small solutes while still restricting large plasma proteins based on size and charge 4, 3
• Regional variation: Surface density of fenestrations varies by organ—highest in kidney cortex (1.35 fenestrations/μm), intermediate in intestinal mucosa (0.92/μm), and lowest in exocrine pancreas (0.58/μm) 4
• Charge selectivity: Electronegative fixed charges at the luminal endothelial surface and along the basement membrane restrict passage of anionic plasma proteins 5
• Examples: Kidney glomeruli, intestinal mucosa, endocrine glands, and exocrine pancreas 4

Sinusoidal (Discontinuous) Capillaries

• Endothelial discontinuity: Characterized by large fenestrae (100-200 nm) without diaphragms, creating true gaps in the endothelium 1, 2
• Basement membrane: Lack an organized basement membrane, making the microvascular endothelium truly discontinuous 2
• Space of Disse: In liver sinusoids, fenestrae connect the sinusoidal space with the Space of Disse, an interstitial space between endothelial and parenchymal cells 1
• Permeability: Most permeable capillary type—fenestrae are large enough that erythrocytes remain confined to vascular space, but albumin, sodium, and sucrose freely penetrate the interstitial space 1
• Pathological changes: In disease states (chronic liver disease, alcoholism), sinusoids undergo "capillarization"—developing basement membranes, losing fenestrae (defenestration), and transforming into continuous-type capillaries, which compromises bidirectional exchange 2, 6
• Examples: Liver sinusoids, bone marrow, and spleen 1, 2

Functional Implications

Permeability Hierarchy

• Hydraulic conductivity: Fenestrated > continuous capillaries, with sinusoidal being most permeable 3
• Small molecule transport: Sinusoidal capillaries allow essentially free passage; fenestrated capillaries permit selective passage based on size and charge; continuous capillaries are most restrictive 4, 3
• Protein permeability: Despite structural differences, fenestrated and continuous capillaries have similar permeabilities to plasma proteins, while sinusoidal capillaries allow much greater protein exchange 3, 2

Clinical Relevance

• Drug penetration: The blood-brain barrier (continuous capillaries) severely limits drug penetration into the CNS, with most beta-lactam antibiotics having limited diffusion that increases only with meningeal inflammation 7
• Pathological transformation: Chronic liver injury causes sinusoidal capillarization with defenestration and basement membrane formation, leading to hepatocellular dysfunction by compromising material exchange 2, 6
• Tumor vasculature: Many tumors develop discontinuous endothelium similar to sinusoidal capillaries, which can be exploited for drug delivery 1