Understanding Microcirculation

• Microcirculation involves capillaries, the lymphatic system, and fluid exchange
• It refers to the function of arterioles, capillaries, venules, and neighboring lymphatic vessels

Microcirculation Function

• Blood circulates through the smallest blood vessels
• Nutrients, gases, and waste products are exchanged in tissues
• Fluid is exchanged between vascular and interstitial compartments
• Capillaries deliver blood and act as sites for nutrient and waste exchange
• They also facilitate fluid exchange between vascular and interstitial compartments

Macro vs Microcirculation

• Macrocirculation includes arteries that are greater than 400 micrometers
• Arteries are conduit vessels with 5% of total resistance
• Microcirculation includes pre-arterioles (100-400 micrometers), arterioles (40-100 micrometers), and capillaries (less than 10 micrometers)
• Pre-arterioles and arterioles regulate flow through metabolic control and flow regulation
• They contribute 20% and 60% of total resistance, respectively
• Capillaries are exchange vessels made of endothelial cells only, and contribute 15% of total resistance

Vessels

• Arterioles, which are the smallest branches of arteries, have a high smooth muscle composition
• They are highly innervated
• Arterioles respond to sympathetic stimulation or vasoactive substances and have the highest resistance to blood flow
• Capillaries have a single layer of endothelial cells surrounded by a basal lamina
• They allow for the exchange of nutrients, gases, water, and solutes between blood and tissues
• Capillaries can be selectively perfused with blood
• Venules are thin-walled, lack smooth muscle, and have elastic tissue, which increases capacitance and causes low pressure

Capillary Beds

• In capillary beds, terminal arterioles flow into metarterioles, then precapillary sphincters, forming true capillaries, postcapillary venules, and ultimately venules
• Blood is delivered to capillary beds via arterioles
• Constriction or relaxation of arterioles affects blood flow to the capillaries
• Precapillary sphincters are bands of smooth muscle that control blood flow into the capillaries, functioning as switches
• True capillaries merge into venules, carrying blood from tissues to veins and back to the macrocirculation

Capillary Bed Pathway

• In the capillary bed blood flows from the:
  • Arteriole
  • Meta-arteriole
  • Capillary bed
  • Venule
  • Vein
• Arteriovenous anastomoses have no nutrient or fluid exchange
• They help control skin temperature through volume changes in the superficial venous bed

Substance Exchange across the Capillary Wall

• Exchange of solutes and gases across capillary walls occurs by simple diffusion
• Some solutes diffuse through endothelial cells, while others diffuse between them, depending on whether they are lipophilic
• Capillaries contain a single endothelial layer and water-filled clefts between cells
• O₂ and CO₂ (non-polar), diffuse through endothelial cells because they are highly lipid-soluble, as are N₂ and NO
• Water-soluble molecules (hydrophilic) must diffuse through aqueous clefts between endothelial cells (pores)
• Examples include H₂O, charged ions, glucose, and amino acids
• Proteins are generally too large to cross capillary walls via clefts and are, therefore, retained in the vascular compartment
• Some tissues can have capillaries with 'tight' clefts (brain-blood-barrier)
• Other capillaries may have ‘fenestrations’ allowing few small proteins to pass
• Proteins may cross through pinocytotic vesicles (transcytosis)

Simple Diffusion

• During simple diffusion, solutes and gases exchange across the capillary wall if the membrane is permeable to them
• Molecules move either through the membrane or between the endothelial cells (clefts)
• It’s driven by a partial pressure/concentration gradient in which individual gases or solutes move downwards until equilibrium is achieved
• The rate of diffusion depends on driving force and surface area, and more capillaries increase surface area

Osmosis and Hydrostatic Pressure

• Osmosis and hydrostatic pressure drive fluid movement across the capillary wall
• Osmosis is the flow of water across a semipermeable membrane that is impermeable to the solute
• Solute concentration needs to be equalized on each side of the membrane
• Concentration differences of impermeate solutes create osmotic pressure differences, causing water to flow by osmosis
• Solute concentration contributes to the effective osmotic pressure
• Capillary hydrostatic pressure is the pressure of blood inside capillaries, pushing fluid out into surrounding tissues (interstitial area)

Tonicity

• Tonicity measures effective osmotic pressure gradient
• Isotonic solutions have the same “isos" meaning equal, similar
• In isotonic, effective osmotic pressure is the same
• Lower osmotic pressure is hypotonic; higher osmotic pressure is hypertonic
• Water flows from hypotonic to hypertonic solutions
• The reflection coefficient measures how well a membrane prevents the passage of certain solutes, and ranges from 0 to 1
• A reflection coefficient of 0 means the membrane allows all solutes to pass freely
• A reflection coefficient of 1 means the membrane completely blocks the passage of solutes
• If σ = 1.0, the membrane is impermeable to the solute, effective osmotic pressure is maximal, and it causes maximal water flow
• An example is serum albumin inside capillaries

Effective Osmotic Pressure

• In the capillaries, capillary walls have a reflection coefficient of 1.0 (impermeable to proteins)
• Proteins cannot cross the wall, and they apply their full osmotic pressure inside of the capillaries, pulling fluid from the interstitial space
• In capillary blood, proteins (mainly albumin) contribute to the effective osmotic pressure
• The effective osmotic pressure contributed by protein can also be called colloid osmotic pressure or oncotic pressure

Starling Equation

• Starling pressures, described by the Starling Equation, describe the passive exchange of fluid between capillary microcirculation and the interstitial space with fluid movement across a capillary wall
• Jv = Net fluid movement (mL/min)
• Kf = Vascular permeability coefficient (mL/min per mm Hg)
• Pc = Capillary hydrostatic pressure (mm Hg)
• Pi = Interstitial hydrostatic pressure (mm Hg)
• πc = Capillary oncotic pressure (mm Hg)
• πi = Interstitial oncotic pressure (mm Hg)
• Fluid movement (Jv) across the capillary wall is determined by the net pressure across the wall
• Jv = Kf [(Pc – Pi) – (πc – πi)]
• Hydrostatic pressure is (Pc – Pi) and Oncotic pressure is (πc – πi)
• Direction of fluid movement can be either out of the capillary or into the capillary
• Movement out of the capillary to the interstitial fluid is called filtration
• Jv is a positive number
• Movement from the interstitium into the capillary is called reabsorption
• Jv will be a negative number
• Magnitude of fluid movement is determined by hydraulic conductance (Kf)
• Kf, the vascular permeability coefficient of the capillary wall, is highly dependent on the type of capillary
• This regulates how much fluid movement will take place at a certain pressure difference
• Pc capillary hydrostatic pressure forces filtration and is mainly arterial pressure, decreasing from blood resistance, along the capillary length
• Pi interstitial hydrostatic pressure opposes filtration
• Pi is normally nearly zero or slightly negative
• πc capillary oncotic pressure opposes filtration, is the oncotic pressure of the capillary blood, from protein plasma, and increases protein conc and decreased filtration
• πi interstitial oncotic pressure favors filtration, is determined by intersitital fluid protein conc, and it normally low due to low protein conc instertitial fluid

Summary of Starling Pressures

• In Filtration the Arterial end has net filtration pressure = +10 mm Hg
• Fluid exits here because the capillary hydrostatic pressure is greater than the blood colloidal osmotic pressure
• At mid capillary there is no net movement, and thus net filtration pressure = 0 mm Hg as capillary hydrostatic pressure = blood colloidal osmotic pressure
• In reabsoprtion, at the venous end net filtration pressure = -7 mm HG
• Fluid re-enters because capillary hydrostatic pressure is less thatn blood colloidal osmotic pressure

Changes in Starling Pressure

• Can influence the direction and magnitude of fluid movement across capillaries
• Several changes can produce increased filtration (fluid movement out of capillaries)
• Increasing the Starling forces that favor filtration or decreasing the Starling forces that favor absorption will increase fluid movement
• Increase in Pc i.e., caused by increased arterial pressure
• Decrease in πc i.e., caused by reduction of plasma protein concentration

Lymphatic System

• It controls returning interstitial fluid and small proteins to the vascular compartment
• The lymphatic capillaries are located close to the capillary bed
• They have one-way flap valves, allowing interstitial fluid and small proteins to enter, but not to leave the lymphatic vessels
• These lymphatic capillaries merge into larger lymphatic vessels and into the thoracic duct, taking lymph into the large veins
• Lymphatic vessels have smooth muscle walls that contract
• Lymph return flow is aided by smooth muscle contraction and compression by skeletal muscle around it

Edema

• Occurs from an increase in interstitial fluid volume, which is defined as edema or swelling
• Occurs when the amount of fluid that leaks out of capillaries exceeds the lymphatic system's capacity to drain and return it to the larger circulation
• Edema can form when there is increased filtration, decreased reabsorption, or reduced/impaired lymphatic drainage
• Starling Equation: Jv = Kf [(Pc – Pi) – (πc – πi)]