Microcirculation

Capillaries

• Small exchange vessels, about 1 mm long with a 5-10 µm inner diameter
• Consist of highly attenuated endothelial cells surrounded by a basement membrane
• Lack smooth muscle
• Large surface area and high permeability make capillaries the primary exchange site for fluids, electrolytes, gases, and macromolecules
• Precapillary sphincters regulate the number of perfused capillaries in some organs

Structural Classifications of Capillaries

• Continuous capillaries are located in muscle, skin, lung, and the central nervous system
• They feature a continuous basement membrane and tight intercellular clefts, resulting in the lowest permeability
• Fenestrated capillaries are in exocrine glands, renal glomeruli, and intestinal mucosa
• Perforations (fenestrae) in the endothelium lead to relatively high permeability
• Discontinuous capillaries are present in the liver, spleen, and bone marrow
• Large intercellular gaps and gaps in the basement membrane give extremely high permeability

Capillary Network

• Arteriolar diameter influences capillary flow
• Metarterioles connect arterioles and venules and have scattered smooth muscle cells
• Precapillary sphincters contract or relax based on the metabolic activity of the tissue
• The body has approximately 1 × 10^10 open capillaries
• The average capillary diameter is 6 µm
• Total cross-sectional area of capillaries is 2827 cm²
• Blood flow velocity in capillaries is 0.03 cm/s
• Distance from any cell to a capillary is very short, around 20-30 μm
• Blood volume in capillaries: 6 %

Mechanisms of Capillary Exchange

• Fluid, electrolytes, gases, and molecules of various sizes can cross the capillary endothelium through varied mechanisms
• Diffusion is one mechanism
• Bulk flow is another mechanism
• Vesicular transport, specifically for macromolecules
• Active transport, it is considered an exceptional mechanism

Diffusion

• Vital for exchanging gases (O2 and CO2), lipid-soluble substances, nutrients, and metabolic end products
• Fluids and electrolytes are also exchanged, partially through diffusion
• Fick's First Law of Diffusion: Describes the rate of diffusion
• The movement (or flux) of a molecule is directly related to its diffusion constant, surface area, and concentration gradient
• Increasing the partial pressure of oxygen (pO2) in plasma, or increasing the surface area for exchange, enhances O2 movement from blood to tissue

Diffusion Coefficient

• Diffusion coefficient, also known as constant (diffusivity), is a physical constant, dependent on molecular weight and other characteristics
• It depends on the diffusing particles, second power of the diffusion velocity, fluid viscosity, and diffusion environment (pressure, and temperature)
• Determined experimentally with units in m²/s; available in reference tables

Bulk Flow (Convection)

• Fluid and electrolytes undergo bulk flow through pores and intercellular clefts
• Important in renal glomerular capillaries, and occurs to different extents in nearly all tissues
• Dependent on pressure driving forces, either hydrostatic or osmotic
• Size of "pores" or intercellular clefts also affects it
• Contraction of capillary endothelial cells by substances such as histamine increases intercellular pore size and greatly augments movement

Vesicular Transport

• Translocates macromolecules across capillary endothelium

Active Transport

• Some molecules like ions, glucose, and amino acids are moved by vascular endothelial cells via transport mechanisms
• Typically, this is for exchange between an individual cell and its surroundings, rather than between plasma and interstitium

Hydrostatic and Oncotic Pressures: Starling Forces

• Two hydrostatic, and two oncotic pressures, affect transcapillary fluid exchange
• Capillary hydrostatic pressure (Pc)
• Tissue (interstitial) hydrostatic pressure (Pif)
• Capillary (plasma) oncotic pressure (Πp)
• Tissue (interstitial) oncotic pressure (Πif)

Capillary Hydrostatic Pressure (Pc)

• Drives fluid out of the capillary (filtration)
• Highest at the arteriolar end and lowest at the venular end
• Increases with either arterial or venous pressure
• More influenced by changes in venous pressure due to lower resistance in venules
• Increased by precapillary vasodilation, but decreased by precapillary vasoconstriction
• It is increased by venous constriction, and decreased by venous dilation
• Typically ranges from 30 to 35 mmHg

Tissue (Interstitial) Hydrostatic Pressure (Pif)

• Determined by interstitial fluid volume and the compliance of the tissue
• Normally near zero
• Tissue compliance is generally low, so small increases in tissue volume cause dramatic increases in Pif
• Increased interstitial fluid volume leads to a rise in Pif, decreasing the hydrostatic gradient across the capillary, thus limiting filtration

Capillary Plasma Oncotic Pressure (Πp)

• Osmotic pressure within the capillary, primarily determined by relatively impermeable plasma proteins
• Referred to as "oncotic" or "colloid osmotic" pressure because it is generated by colloids
• Albumin accounts for approximately 70% of the oncotic pressure
• Typically 25-30 mmHg
• The oncotic pressure increases along the length of the capillary, as filtering fluid leaves behind proteins, increasing protein concentration

Tissue (Interstitial) Oncotic Pressure (Πif)

• Depends on interstitial protein concentration and the permeability of the capillary wall
• More permeable capillary barrier to proteins yields a higher interstitial oncotic pressure
• Also determined by the amount of fluid filtration into the interstitium
• Increased capillary filtration decreases interstitial protein concentration and reduces oncotic pressure
• Tissue oncotic pressure in a "typical" tissue is around 3-5 mmHg, which is much lower than capillary plasma oncotic pressure

Net Filtration Pressure

• Net filtration pressure calculation: (Pc + πif) - (πc + Pif)

Summary of Physical Factors Determining Capillary Fluid Exchange

• Water, electrolytes, and small molecules are freely exchanged between intravascular and extravascular compartments, with the capillary network as the primary site
• The most important mechanisms of exchange are bulk flow and diffusion
• Rate of exchange is determined by factors like hydrostatic pressure, oncotic pressure, and the permeability of the capillary wall

Summary: Opposing Forces in Capillary Fluid Exchange

• Capillary hydrostatic pressure (Pc) and tissue hydrostatic pressure (Pif) are the two major opposing hydrostatic forces
• Pc is normally much greater than Pif
• The net hydrostatic pressure gradient across the capillary is positive, which causes fluid to move out of the capillary into the interstitium
• Two opposing oncotic pressures are capillary plasma oncotic pressure (Πp) and tissue (interstitial) oncotic pressure (Πif)
• Πp is much greater than Πif
• The oncotic pressure gradient across the capillary would reabsorb fluid from the interstitium into the capillary
• The net driving force for fluid movement is the net pressure gradient, which is determined by the sum of the individual hydrostatic and oncotic pressures

Summary: Filtration, Reabsorption, and Edema

• Filtration occurs across the arteriolar end, and reabsorption occurs across the venular end
• In general, typically there is net filtration across capillary beds, taken up by the lymphatics
• Edema results if net filtration exceeds the capacity of the lymphatics