The microcirculation is composed of arterioles, capillaries, and postcapillary venules. These vessels regulate tissue perfusion, exchange gases and nutrients, and maintain tissue fluid balance.
Arterioles
Arterioles are the smallest arterial vessels (20-100 microns diameter) and are the primary site of vascular resistance.
Structure
Tunica intima:
- Endothelium with minimal subendothelial layer
- Thin internal elastic lamina (disappears in terminal arterioles)
Tunica media:
- 1-3 layers of smooth muscle
- Circularly arranged
- Richly innervated by sympathetic nerves
- No external elastic lamina
Tunica adventitia:
- Thin layer of connective tissue
- Fibroblasts
- Pericytes (at terminal arteriole level)
Terminal Arterioles
The smallest arterioles (10-20 microns) have:
- Single layer of smooth muscle
- Pericytes at the transition to capillaries
- Precapillary sphincters at capillary origins
- No internal elastic lamina
Precapillary Sphincters
Precapillary sphincters are rings of smooth muscle at the origin of capillaries from metarterioles.
Function:
- Regulate entry of blood into individual capillaries
- Respond to local metabolic signals
- Contract and relax independently of arteriolar tone
- Control the number of perfused capillaries (capillary recruitment)
Physiologic Role
| Function | Mechanism |
|---|---|
| Resistance regulation | Determine 50-60% of total peripheral resistance |
| Blood pressure regulation | Systemic vasoconstriction increases BP |
| Flow distribution | Selective constriction/dilation of organ beds |
| Capillary pressure regulation | Precapillary resistance determines hydrostatic pressure |
| Autoregulation | Myogenic and metabolic responses maintain flow |
Regulation of Arteriolar Tone
Neural regulation:
- Sympathetic: Norepinephrine -> alpha-1 receptors -> vasoconstriction
- Sympathetic: Epinephrine -> beta-2 receptors -> vasodilation (in some beds)
- Parasympathetic: Limited direct innervation
Local metabolic regulation:
- Vasodilators: Adenosine, CO2, H+, K+, lactate, PO2 decrease
- Functional hyperemia: Increased metabolism causes vasodilation
Endothelial regulation:
- Nitric oxide (NO): Shear stress-induced vasodilation
- Endothelin-1: Potent vasoconstrictor
- Prostacyclin: Vasodilation
Hormonal regulation:
- Angiotensin II: Vasoconstriction
- Vasopressin: Vasoconstriction
- Atrial natriuretic peptide: Vasodilation
Capillaries
Capillaries are the smallest blood vessels (5-10 microns diameter) and serve as the primary site of exchange between blood and tissues.
Structure
Wall composition:
- Single layer of endothelial cells
- Basement membrane
- Pericytes (spaced along the capillary)
Dimensions:
- Diameter: 5-10 microns (just wide enough for a single RBC)
- Wall thickness: 0.2-0.5 microns
- Length: 0.5-1.0 mm
- Density: 300-600 capillaries per mm² in metabolically active tissues
Total Capillary Surface Area
- Total body capillaries: 10-40 billion
- Total surface area: 500-700 m²
Types of Capillaries
| Type | Structure | Location | Permeability |
|---|---|---|---|
| Continuous | Uninterrupted endothelium, tight junctions | Muscle, skin, lung, brain (CNS) | Low (tight in CNS: blood-brain barrier) |
| Fenestrated | Endothelial pores (fenestrae) with diaphragm | Kidney, intestine, endocrine glands | Moderate |
| Sinusoidal (discontinuous) | Large gaps, incomplete basement membrane | Liver, spleen, bone marrow | High |
Continuous Capillaries
Features:
- Endothelial cells joined by tight junctions
- Continuous basement membrane
- Transport: Diffusion, transcytosis, paracellular (limited)
Blood-brain barrier:
- Endothelial cells with very tight junctions
- No fenestrations
- Pericyte coverage (30-40%)
- Astrocyte foot processes surround the capillary
- Specialized transporters (GLUT1, etc.)
Fenestrated Capillaries
Features:
- Endothelial cells with circular pores (50-80 nm)
- Diaphragm across most fenestrations
- Continuous basement membrane
- High permeability to water and small solutes
Locations and function:
- Renal glomerulus: Filtration (fenestrations without diaphragm)
- Intestinal villi: Absorption of nutrients
- Endocrine glands: Hormone release
- Choroid plexus: CSF production
Sinusoidal Capillaries
Features:
- Large intercellular gaps (100-1000 nm)
- Discontinuous or absent basement membrane
- Wide diameter (30-40 microns)
- Sluggish flow
Locations and function:
- Liver (hepatic sinusoids): Exchange with hepatocytes
- Bone marrow: Release of blood cells
- Spleen: Red pulp, blood filtration
Ultrastructure of Capillary Wall
Endothelial cell features:
- Thin cytoplasm (0.1-0.5 microns)
- Caveolae (plasmalemmal vesicles): Transcytosis
- Weibel-Palade bodies: von Willebrand factor storage
- Organelles: Sparse near periphery, more near nucleus
Basement membrane:
- Type IV collagen
- Laminin
- Fibronectin
- Proteoglycans (perlecan)
- Nidogen/entactin
Function:
- Structural support
- Filtration barrier
- Cell attachment scaffold
- Growth factor binding
Pericytes
Pericytes are contractile cells that wrap around capillaries.
Structure:
- Cell body on the abluminal surface
- Processes extending along and around the capillary
- Embedded in the basement membrane
Functions:
- Contractile: Regulate capillary diameter
- Stabilizing: Maintain capillary integrity
- Angiogenic: Guide new vessel growth
- Phagocytic: Immune surveillance
- Stem cell: Can differentiate into other cell types
Exchange Across Capillary Walls
Diffusion
The primary mechanism for gas and small molecule exchange:
- O2, CO2: Lipid-soluble, diffuse through endothelial cells
- Water: Diffuses through aquaporins and paracellularly
- Small solutes: Glucose, amino acids via paracellular route (fenestrations/gaps) or transporters
- Proteins: Transcytosis (caveolae)
Filtration and Reabsorption
Described by Starling forces:
Net filtration pressure = (Pc + πi) - (Pi + πp)
Where:
- Pc = Capillary hydrostatic pressure (arterial end: 35 mmHg, venous end: 15 mmHg)
- Pi = Interstitial hydrostatic pressure (-3 mmHg)
- πp = Plasma oncotic pressure (25 mmHg)
- πi = Interstitial oncotic pressure (8 mmHg)
Balance:
- Arterial end: Net filtration (fluid leaves capillary)
- Venous end: Net reabsorption (fluid enters capillary)
- Net filtration exceeds reabsorption -> lymphatics remove excess
Transcytosis
Vesicular transport across endothelial cells:
- Caveolae form from the plasma membrane
- Carry macromolecules across the cell
- Receptor-mediated or non-specific
Capillary Density and Tissue Metabolism
| Tissue | Capillary Density | Metabolic Rate |
|---|---|---|
| Brain | High | High (O2 dependent) |
| Heart | Very high | Very high |
| Skeletal muscle | Moderate (varies) | Variable |
| Liver | High | High |
| Kidney | Very high | High |
| Adipose | Moderate | Low |
| Cartilage | Very low | Very low (avascular) |
Clinical Significance
Capillary Leak Syndrome
Increased capillary permeability causing fluid shift to interstitium:
- Sepsis: Cytokine-mediated endothelial injury
- Anaphylaxis: Histamine-mediated gap formation
- ARDS: Pulmonary capillary leak
- Systemic capillary leak syndrome (Clarkson disease)
Diabetic Microangiopathy
Thickening of capillary basement membrane:
- Diabetic retinopathy: Retinal capillary damage, neovascularization
- Diabetic nephropathy: Glomerular capillary damage, proteinuria
- Diabetic neuropathy: Vasa nervorum capillary damage
Hypertension and Microcirculation
- Arteriolar remodeling: Increased wall-to-lumen ratio
- Rarefaction: Reduced capillary density
- Impaired autoregulation: End-organ damage
- Target organ damage: Kidney, brain, retina
Shock and Microcirculation
| Shock Type | Microvascular Changes |
|---|---|
| Hypovolemic | Vasoconstriction, capillary underperfusion |
| Cardiogenic | Vasoconstriction, tissue hypoperfusion |
| Septic | Vasodilation, capillary leak, maldistribution |
| Neurogenic | Vasodilation, relative hypovolemia |
Capillary Hemangiomas
Benign tumors of capillary endothelium:
- Infantile hemangioma: Proliferation then involution
- Cherry hemangioma: Senile, commonly on trunk
- Port wine stain: Capillary malformation (not true hemangioma)
Angiogenesis
Formation of new capillaries from existing vessels:
- Physiologic: Wound healing, menstrual cycle, exercise
- Pathologic: Tumor growth, diabetic retinopathy, macular degeneration
- Therapeutic targets: Anti-VEGF therapy