Capillary Circulation

Introduction

Capillaries are the principal sites of exchange between blood and tissues, facilitating the transfer of gases, nutrients, water, and metabolic waste products. Fluid movement across capillary walls is governed by hydrostatic and oncotic forces, disturbances of which may lead to edema formation.

Concept of Microcirculation

• Microcirculation refers to blood flow from arterioles through capillaries to venules.
• Although only about 5% of the total blood volume is present in capillaries at any moment, this compartment is physiologically crucial.
• Capillaries are known as exchange vessels because they facilitate the transfer of oxygen, nutrients, water, hormones, and metabolic waste products between blood and tissues.
• Capillaries are located in close proximity to metabolically active cells, ensuring efficient exchange across the thin capillary wall.
• Adequate microcirculatory flow is essential for cellular survival and normal tissue function.
• Most body cells lie within a short diffusion distance of capillaries.
• The cornea and lens are exceptions because they are avascular structures.
• These tissues obtain oxygen and nutrients from the aqueous humor and surrounding ocular fluids.

Functional Morphology

• Capillaries form extensive branching networks that provide a large surface area for efficient exchange between blood and tissues.
• Each capillary consists of a single layer of endothelial cells resting on a basement membrane.
• Endothelial cells are connected by intercellular junctions, and the absence of a tunica media contributes to the high permeability of capillary walls.
• Small gaps between endothelial cells permit the exchange of water and dissolved substances.
• True capillaries arise from arterioles or metarterioles and drain into venules through interconnected vascular networks.
• In many tissues, a direct vascular channel called a thoroughfare channel connects metarterioles to venules, allowing blood to bypass some capillary networks.

Types of Capillaries

Capillaries are classified as continuous, fenestrated, or sinusoidal (discontinuous) based on endothelial structure and permeability.

Continuous Capillaries

• Continuous capillaries are the most abundant type in the body.
• Their endothelial lining is uninterrupted, with only narrow intercellular clefts measuring approximately 4 to 10 nanometers.
• The basement membrane is continuous throughout the capillary length.
• These capillaries permit selective movement of water and small solutes while restricting the passage of large molecules.
• Continuous capillaries are found in skeletal muscle, smooth muscle, connective tissue, and the lungs.
• In the central nervous system, endothelial cells are joined by tight junctions with virtually no intercellular clefts, forming the blood-brain barrier.

Fenestrated Capillaries

• Fenestrated capillaries contain numerous transcellular pores or fenestrations measuring approximately 20 to 100 nanometers in diameter.
• These pores greatly increase capillary permeability and facilitate rapid exchange of fluids and small proteins.
• The basement membrane remains continuous despite the presence of fenestrations.
• Fenestrated capillaries are typically associated with tissues involved in absorption, secretion, or filtration.
• They occur in intestinal villi, endocrine glands, choroid plexuses, ciliary processes of the eye, and renal glomeruli.

Sinusoidal or Discontinuous Capillaries

• Sinusoidal capillaries possess large endothelial gaps and an incomplete or discontinuous basement membrane.
• Intercellular openings may exceed 400 nanometers and can reach several micrometers in diameter.
• These structural features permit the passage of plasma proteins and even cellular elements between blood and tissues.
• Sinusoids are specialized for extensive exchange and cellular trafficking.
• They are characteristically present in the liver, spleen, and bone marrow.

Capillary Flow

• Capillary pressure varies among different tissues according to local vascular resistance and metabolic activity.
• In skeletal muscle, capillary hydrostatic pressure is approximately 35–37 millimeters of mercury at the arteriolar end and about 15–17 millimeters of mercury at the venular end.
• Although individual capillaries are short, blood flow through them is very slow because the total cross-sectional area of all capillaries is extremely large.
• Average capillary blood velocity is approximately 0.03 to 0.07 centimeters per second.
• Slow blood flow prolongs the contact time between blood and tissues, thereby enhancing exchange.
• Pulse pressure is markedly dampened within capillaries and becomes minimal at the venular end.
• Consequently, capillary flow is only slightly pulsatile.

Functional Specialties of Capillaries

• Capillary density determines the efficiency of exchange between blood and tissues.
• Metabolically active tissues, such as cardiac muscle, skeletal muscle, endocrine glands, and the brain, possess a high capillary density.
• Tissues with low metabolic activity, such as cartilage and subcutaneous connective tissue, contain fewer capillaries.
• Capillary diameter varies among tissues.
• The diameter of a true capillary is approximately 5 micrometers at the arterial end and 8 micrometers at the venous end.
• Because most capillaries are narrower than erythrocytes, red blood cells traverse them in single file.
• During passage, erythrocytes undergo reversible deformation and closely appose the endothelial surface.
• This intimate contact facilitates efficient exchange of respiratory gases and solutes.
• Capillaries lack a tunica media and therefore contain no vascular smooth muscle.
• Consequently, capillaries do not respond directly to autonomic vasoconstrictor or vasodilator influences.
• Capillary blood flow is regulated primarily by changes in arteriolar and metarteriolar tone.
• At the origin of many capillaries, rings of smooth muscle known as precapillary sphincters regulate entry of blood into the capillary network.
• These sphincters respond predominantly to local metabolic factors, including oxygen tension, carbon dioxide concentration, hydrogen ion concentration, adenosine, and other vasoactive substances.
• Relaxation of precapillary sphincters increases capillary perfusion, whereas contraction decreases it.
• Although capillaries lack true smooth muscle, endothelial cells are associated with pericytes.
• Pericytes possess contractile properties and participate in regulation of capillary stability, permeability, angiogenesis, and limited changes in capillary caliber.
• Capillaries are ideally suited for exchange because they have extremely thin walls composed of a single endothelial layer and because blood flow within them is slow.
• Sympathetic innervation of capillaries is sparse and has little direct influence on capillary diameter.
• Capillaries are easily compressible because of their delicate structure and low intraluminal pressure.
• If capillary pressure falls below surrounding tissue pressure, capillaries collapse and blood flow ceases.
• The intravascular pressure below which flow stops is termed the critical closing pressure.
• Some vascular beds contain direct channels connecting arterioles and venules, known as thoroughfare channels or preferential channels.
• In resting tissues, a substantial portion of blood may pass through these channels, bypassing many true capillaries.
• During increased metabolic activity, perfusion through true capillaries rises substantially to meet tissue demands.
• Capillary blood flow is often intermittent rather than continuous.
• Periodic contraction and relaxation of arterioles and precapillary sphincters produce rhythmic fluctuations in capillary perfusion, a phenomenon called vasomotion.
• Vasomotion usually occurs several times each minute and is influenced by local metabolic factors and endothelial mediators such as nitric oxide.
• Despite the high resistance of individual capillaries, total capillary resistance remains relatively low because millions of capillaries are arranged in parallel.
• Endothelial cells contain numerous vesicles that participate in transcytosis, transporting water-soluble substances and selected macromolecules across the capillary wall.
• In fenestrated capillaries, transcellular pores further facilitate rapid exchange of fluids and solutes.

Active vs Inactive Capillaries

• In resting tissues, many capillaries remain functionally closed, and blood flows predominantly through thoroughfare channels.
• During increased metabolic activity, arterioles and precapillary sphincters relax, allowing perfusion of previously unperfused capillaries.
• Recruitment of these active capillaries increases the surface area available for exchange, thereby enhancing delivery of oxygen and nutrients to tissues.

Capillary Exchange

• Exchange of substances across capillary walls occurs primarily by diffusion, vesicular transport, and filtration.
• These mechanisms ensure delivery of nutrients to tissues and removal of metabolic waste products.

Diffusion

• Diffusion is the principal mechanism of capillary exchange in most tissues.
• It occurs down a concentration gradient and does not require energy expenditure.
• Respiratory gases such as oxygen and carbon dioxide readily diffuse across capillary walls.
• Water-soluble nutrients, including glucose, amino acids, and many hormones, also cross capillaries by diffusion through intercellular clefts or fenestrations.
• Lipid-soluble substances diffuse directly through endothelial cell membranes.
• In organs containing sinusoidal capillaries, particularly the liver, large molecules such as plasma proteins can move easily between blood and interstitial id.
• Newly synthesized proteins, including albumin and fibrinogen, enter the circulation through hepatic sinusoids by this mechanism.

Vesicular Transport

• Vesicular transport involves the movement of substances across endothelial cells by endocytosis and exocytosis.
• During this process, macromolecules are internalized into membrane-bound vesicles, transported across the endothelial cell, and released on the opposite side.
• Because substances traverse the endothelial cell, this process is also termed transcytosis.
• Vesicular transport is particularly important for large, lipid-insoluble molecules that cannot pass through endothelial junctions or cell membranes by diffusion.
• Examples include certain plasma proteins, peptides, and other macromolecules.

Capillary Filtration

• Capillary filtration is the principal mechanism responsible for movement of fluid between the intravascular and interstitial compartments.
• Filtration occurs because of pressure differences across the capillary wall.
• The balance between these forces determines whether fluid moves out of or into the capillary.
• The pressures governing fluid movement are collectively termed Starling forces.
• Starling forces consist of hydrostatic and colloid osmotic pressures acting across the capillary membrane.

Pressures promoting filtration are:

• Two forces favor movement of fluid from the capillary into the interstitial space.
• The first is capillary hydrostatic pressure, which represents the pressure exerted by blood on the capillary wall.
• Capillary hydrostatic pressure pushes water and dissolved solutes outward into the interstitial fluid.
• The second force is the interstitial fluid colloid osmotic pressure, generated by proteins present in the interstitial space.
• This pressure tends to draw water out of the capillary.
• Under normal conditions, interstitial colloid osmotic pressure is relatively low because interstitial protein concentration is low.

Pressures that oppose filtration are:

• Two forces oppose filtration and favor retention or reabsorption of fluid into the capillary.
• The most important opposing force is the plasma colloid osmotic pressure or oncotic pressure, which is primarily produced by plasma proteins, especially albumin.
• Plasma oncotic pressure averages approximately 25 millimeters of mercury and pulls fluid into the capillary.
• The second opposing force is interstitial hydrostatic pressure, which exerts pressure on the outer surface of the capillary and resists outward fluid movement.
• In many tissues, interstitial hydrostatic pressure is close to zero or slightly negative.

Hydrostatic Pressure Gradient

• The hydrostatic pressure gradient is the difference between capillary hydrostatic pressure and interstitial hydrostatic pressure.
• In skeletal muscle, capillary hydrostatic pressure is approximately 35 to 37 millimeters of mercury at the arteriolar end and about 15 to 17 millimeters of mercury at the venular end.
• Interstitial hydrostatic pressure is usually close to 1 millimeter of mercury.
• Consequently, the outward hydrostatic gradient is greatest at the arteriolar end and decreases toward the venular end.
• This decline in capillary pressure occurs because resistance to blood flow causes progressive pressure loss along the capillary length.

Osmotic Pressure Gradient

• The osmotic pressure gradient depends mainly on the difference between plasma oncotic pressure and interstitial colloid osmotic pressure.
• Plasma oncotic pressure retains fluid within the vascular compartment.
• Because interstitial colloid osmotic pressure is low, the net osmotic gradient is usually directed inward, favoring absorption of fluid into the capillary.

Net Filtration

• At the arteriolar end of capillaries, hydrostatic forces generally exceed oncotic forces, producing net filtration of fluid into the interstitial space.
• Toward the venular end, the reduction in capillary hydrostatic pressure allows inward-directed oncotic forces to predominate, favoring reabsorption.
• However, current evidence indicates that sustained reabsorption under normal physiological conditions is limited, and most filtered fluid returns to the circulation through the lymphatic system.
• Lymphatic vessels drain excess interstitial fluid and proteins and ultimately return them to the venous circulation.

Capillary Permeability

• The rate of filtration also depends on capillary permeability, which reflects the integrity and structural characteristics of the endothelial barrier.
• Continuous capillaries are less permeable than fenestrated or sinusoidal capillaries.
• Inflammatory mediators such as histamine increase endothelial permeability by widening intercellular junctions.
• Increased capillary permeability promotes leakage of proteins and fluid into tissues and contributes to edema formation.

Edema

Definition

• Edema is the abnormal accumulation of excess free fluid within the interstitial tissue spaces.
• It develops when filtration of fluid from capillaries exceeds its removal by venous and lymphatic pathways.

Mechanisms of Edema Formation

Edema occurs through two major mechanisms: increased movement of fluid into the interstitial space or impaired removal of interstitial fluid.

Increased Filtration of Fluid into the Interstitial Tissues Space

Excess filtration may result from increased capillary hydrostatic pressure, reduced plasma oncotic pressure, or increased capillary permeability.

Increased Hydrostatic Pressure of Capillaries

• Elevated venous pressure raises capillary hydrostatic pressure and promotes fluid filtration into tissues.
• This mechanism commonly occurs in congestive heart failure.
• Obstruction or compression of veins, such as by tumors or thrombosis, also increases capillary pressure and causes localized edema.
• Expansion of extracellular fluid volume due to sodium and water retention increases capillary hydrostatic pressure.
• Arteriolar dilation during inflammation enhances blood flow and raises capillary pressure, favoring edema formation.

Decreased Oncotic Pressure

• Reduction in plasma protein concentration lowers oncotic pressure, thereby diminishing fluid reabsorption into capillaries.
• Hypoproteinemia may result from chronic liver disease due to reduced albumin synthesis.
• Renal disorders, especially nephrotic syndrome, cause excessive urinary protein loss.
• Severe protein-energy malnutrition decreases protein intake and plasma protein production.
• Extensive burns lead to loss of protein-rich fluid from damaged tissues.

Increased Capillary Permeability

• Inflammatory mediators such as histamine, bradykinin, and certain bacterial toxins increase endothelial permeability.
• Enhanced permeability permits leakage of plasma proteins into the interstitial space, increasing interstitial oncotic pressure and promoting edema.
• This mechanism is characteristic of inflammatory edema.

Decreased Removal of Fluid into the Interstitial Tissues Space

• The lymphatic system normally removes excess interstitial fluid and proteins.
• Impaired lymphatic drainage leads to accumulation of protein-rich fluid, producing lymphedema.
• Lymphatic obstruction may occur because of inflammation, surgical removal of lymph nodes, malignant infiltration, or parasitic infections such as filariasis.
• Lymphedema is typically non-pitting because of increased protein deposition and tissue fibrosis.

Treatment of Edema

• Treatment of edema is directed primarily at correcting the underlying cause.
• Generalized edema associated with heart failure is managed with appropriate treatment of heart failure, dietary sodium restriction, and diuretic therapy when indicated.
• Localized inflammatory edema is treated by addressing the underlying inflammatory process and may require anti-inflammatory medications.
• Management of specialized forms of edema, such as cerebral edema or pulmonary edema, depends on the underlying etiology and severity.
• High-altitude pulmonary edema is treated with oxygen therapy, descent to lower altitude, and appropriate pharmacological agents such as nifedipine or glucocorticoids in selected cases.

Arteriovenous Anastomoses

• Arteriovenous anastomoses are specialized vascular channels that directly connect arterioles to venules, bypassing the capillary bed.
• These vessels possess thick muscular walls and receive dense sympathetic innervation.
• They are abundant in the fingers, palms, toes, and ear lobes, where they play an important role in thermoregulation by controlling cutaneous blood flow.