Microcirculation Capillaries & Lymphatic System PDF

MICROCIRCULATION Capillaries, Fluid Exchange, and the Lymphatic System VP Summer 2023 Clara Camargo, DVM Study guide 1. Define the different parts of the microcirculatory system and their functions 2. Explain the structure of capillary beds and its implication for circulation 3. Explain how d...

MICROCIRCULATION Capillaries, Fluid Exchange, and the Lymphatic System VP Summer 2023 Clara Camargo, DVM Study guide 1. Define the different parts of the microcirculatory system and their functions 2. Explain the structure of capillary beds and its implication for circulation 3. Explain how different substances can cross the capillary wall 4. Define fluid movement across membranes: diffusion versus osmosis 5. Explain how osmosis works 6. What does the term tonicity mean? How does it affect fluid movement? 7. Explain the Starling equation and what it means for fluid movement across capillary walls 8. List and define the individual Starling pressures 9. Explain hydraulic conductance, and what factors can influence it 10. How do changes in Starling forces affect fluid movement across capillary walls? 11. Explain the role of the lymphatic system regarding microcirculation 12. Define edema and explain what factors can cause it MICROCIRCULATION Circulation of the blood in the smallest blood vessels  Terminal arterioles, metarterioles, capillaries, and venules  Exchange of nutrients, gases and waste products in tissues  Fluid exchange between vascular and interstitial compartments Arterioles: smallest branches of arteries; extensive smooth muscle; highest resistance to blood flow; highly innervated and can be contracted or relaxed in response to sympathetic nerve stimulation or vasoactive substances Capillaries: thin-walled with single layer of endothelial cells surrounded by basal lamina; sites of exchange of nutrients, gases, water and solutes between blood and tissues. Can be selectively perfused with blood Venules and veins: also thin-walled, contain endothelial cell layer and some elastic tissue, smooth muscle and connective tissue; ↓elastic tissue = ↑capacity; veins contain largest percentage of blood in cardiovascular system; blood volume under low pressure MICROCIRCULATION CAPILLARY BEDS Capillary bed: termainal arterioles → metarterioles → precapillary sphincters → capillaries → postcapillary venules → venule Capillaries are thin-walled, single endothelial layer, containing waterfilled clefts between cells Blood is delivered to capillary beds via arterioles Constriction or relaxation of arterioles distinctly affects blood flow to the capillaries Precapillary sphincter: band of smooth muscle controlling blood flow into the capillaries  These sphincters function like switches to determine blood flow to the capillary bed  Capillaries merge into venules, they carry efferent blood from tissues to veins MICROCIRCULATION 1. Arteriole (bringing blood from the heart) 2. Smaller arteriole (metaarteriole) 3. Capillary (interconnected) 4. Venous system (venule) 5. Vein (blood back to the heart) Press on your fingernail. What happens? MICROCIRCULATION EXCHANGE OF SUBSTANCES ACROSS THE CAPILLARY WALL Exchange of solutes and gases across capillary wall occurs by simple diffusion  Some solutes diffuse through the endothelial cells  Others must diffuse between the cells  depends on whether it is lipophilic/lipid soluble or not O2 and CO2: diffuse through endothelial cells, highly lipid soluble (N and NO also can diffuse) Water-soluble substances: must diffuse through aqueous clefts between endothelial cells (pores) H2O, (charged) ions, glucose, amino acids MICROCIRCULATION EXCHANGE OF SUBSTANCES ACROSS THE CAPILLARY WALL Proteins: generally too large to cross capillary walls via clefts, thus retained in vascular compartment; some tissues have particularly ‘tight’ clefts  little proteins leave capillaries here (brain); others have ‘fenestrations’  Proteins may cross in pinocytotic vesicles (transcytosis) DIFFUSION – Fluid movement Exchange of solutes and gases across capillary wall occurs by simple diffusion  either through or between the endothelial cells Diffusion is driven by the partial pressure gradient for the individual gas or solute Rate of diffusion depends on: o The driving force (the partial pressure difference for the gas or solute), o The surface area available for diffusion  the greater the number of open capillaries = the greater the surface area for diffusion OSMOSIS FLUID MOVEMENT BY OSMOSIS The most important mechanism for fluid transfer across the capillary wall is OSMOSIS  Driven by hydrostatic and osmotic pressures  Starling pressures (synonym Starling forces) • Osmosis is the flow of water across a semipermeable membrane because of differences in solute concentration • Concentration differences of impermeate solutes create osmotic pressure differences, which cause water to flow by osmosis Osmosis of water is not diffusion of water: • osmosis occurs because of a pressure difference, • diffusion occurs because of a concentration difference OSMOSIS 1 2 1 2 OSMOSIS ACROSS A SEMIPERMEABLE MEMBRANE • Two aquous solutions, open to the atmosphere • Separating membrane: permeable to water, but impermeable to the solute! • Solution 2 (higher concentration of solute) • Higher [solute] in solution 2 creates an osmotic pressure and causes a reduction of hydrostatic pressure in solution 2 The resulting hydrostatic pressure difference across the membrane then causes water to flow from solution 1 to solution 2  With time, water flow causes the volume of solution 2 to increase and the volume of solution 1 to decrease =pressure/concentration equilibrium OSMOSIS - TONICITY TONICITY: measure of effective osmotic pressure gradient Different effective osmotic pressures: Isotonic Solution: • From Greek “isos” meaning equal, similar, same • Isotonic means two solutions have the same effective osmotic pressure Inside the cell: 20% solute, 80% water Outside the cell: 20% solute, 80% water No water will flow between the membranes as there is no pressure difference across them Lower osmotic pressure = hypotonic Higher osmotic pressure = hypertonic Hypotonic Hypertonic solution solution 1 2 1 2 Osmolarity: concentration solute per L (mOsm/L) Osmolality: concentration of a solute per Kg (mOsm/kg) RBC placed in different solution concentrations: https://en.wikipedia.org/wiki/Tonicity#/media/File:Osmotic_pressure_on_blood_cells_diagram.svg FLUID EXCHANGE ACROSS CAPILLARIES Reflection coefficient (σ): a dimensionless number ranging between 0 and 1 that describes the ease with which a solute crosses a membrane, describes permeability of a membrane for specific solutes  Reflection coefficients can be described for the following three conditions: A. σ = 1.0: membrane is impermeable to the solute, solute will be retained in the original solution and exert its full osmotic effect  effective osmotic pressure is maximal, will cause maximal water flow. Ex.: serum albumin, intracellular proteins B. σ = a value between 0 and 1: most solutes are neither impermeant or freely permeant, but somewhere between  effective osmotic pressure will be less than maximal possible value, but greater than zero C. σ = 0: membrane is freely permeable to solute, solute will diffuse across membrane along its concentration gradient until solute concentrations are equal  no effective osmotic pressure difference across membrane, no driving force for osmotic water flow. Ex.: urea OSMOTIC PRESSURE FLUID EXCHANGE ACROSS CAPILLARIES • In capillaries, fluid movement is driven by the sum of hydrostatic and effective osmotic pressures  Recall: solutes with reflection coefficient of 1.0 contribute most to the effective osmotic pressure • With a reflection coefficient of 1.0, solutes cannot cross the membrane and apply their full osmotic pressure • In capillary blood, only protein contributes to the effective osmotic pressure • The effective osmotic pressure contributed by protein is called the colloid osmotic pressure or oncotic pressure STARLING PRESSURES STARLING EQUATION Starling pressures: control the passive exchange of water between capillary microcirculation and the interstitial fluid (fluid movement across a capillary wall) Starling Equation: Jv = Kf [( Pc - Pi) - ( πc - πi)] Where: 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) Ernest Starling 1866 - 1927 STARLING PRESSURES The Starling equation states: • Fluid movement (Jv) across a capillary wall is determined by the net pressure across the wall: the sum of hydrostatic and oncotic pressures • Direction of fluid movement: can be either out of or into the capillary • Net fluid movement out of the capillary into the interstitial fluid: Filtration • Net fluid movement from interstitium into the capillary: Absorption (reabsorption) • Magnitude of fluid movement: determined by hydraulic conductance → Kf (water/vascular permeability) of the capillary wall  hydraulic conductance regulates how much fluid movement will take place at a certain pressure difference! STARLING PRESSURES Pc capillary hydrostatic pressure: • Force favouring filtration out of capillary • Value is determined by arterial and venous pressures (more influence from arterial pressure) • Decreases along length of capillary due to resistance Pi interstitial hydrostatic pressure: • Force opposing filtration • Is normally nearly zero or slightly negative Jv = Kf [( Pc - Pi) - ( πc - πi)] 𝝅𝝅c capillary oncotic pressure: • Force opposing filtration • Is the oncotic pressure of capillary blood due to presence of plasma proteins • Determined by protein concentration in capillary blood • ↑ protein conc.  ↑ πc, ↓ filtration πi interstitial oncotic pressure: • Force favouring filtration out of capillary • Determined by interstitial fluid protein concentration  normal low STARLING PRESSURES Jv = Kf [( Pc - Pi) - ( πc - πi)] Four Starling pressures: • Direction of arrows: indicates if pressure favors filtration or absorption • Size of arrows: magnitude of pressure • Numerical value of pressure in mm Hg: (+) favours filtration, (-) favours absorption Net pressure (= net driving force): the algebraic sum of the four Starling pressures • • A: sum of 4 Starling pressures = net pressure of +6 mm Hg  net filtration out of capillary B: sum of 4 Starling pressures = net pressure of -5 mm Hg  net absorption into the capillary STARLING PRESSURES Jv = Kf [( Pc - Pi) - ( πc - πi)] Kf vascular permeability coefficient (hydraulic conductance):  Water permeability of the capillary wall  Varies between tissues depending on anatomy of capillary wall Degree of fluid movement (at given pressure) is:  largest in capillaries with highest Kf (e.g. glomerular capillaries) lowest at lowest Kf (e.g. cerebral capillaries) Kf is NOT influenced by • changes in arteriolar resistance, hypoxia, metabolites buildup Kf is influenced by • Capillary injury (e.g. toxins, burns)  will increase capillary permeability to water and loss of protein from capillary STARLING PRESSURES STARLING PRESSURES CHANGES IN STARLING PRESSURES • Can influence the direction and scale of fluid movement across capillaries • Several changes can produce increased filtration out of capillaries:  Increases in any of the Starling forces that favour filtration or  Decrease in any of the Starling forces that favour absorption • Increases in filtration:  Increases in Pc caused by increases in arterial pressure or venous pressure  Decreases in πc caused by dilution/reduction of plasma protein concentration LYMPH LYMPHATIC SYSTEM • The lymphatic system is in control of returning interstitial fluid and proteins to the vascular compartment • The lymphatic capillaries lie in the interstitial fluid, close to the vascular capillaries • Lymphatic capillaries have one-way flap valves, allowing interstitial fluid and protein to enter, but not leave the capillaries • These capillaries merge into larger lymphatic vessels and finally into the thoracic duct, which empties lymph into the large veins • Lymphatic vessels have smooth muscle wall  contraction • Lymph return flow is aided by smooth muscle contraction and compression by skeletal muscle around it LYMPH EDEMA FORMATION • An increase in interstitial fluid volume: edema (swelling) • Edema forms when the volume of interstitial fluid (due to filtration out of capillaries) exceeds the ability of the lymphatics to drain it and send it back to the circulation • Edema can form when there is increased filtration or when lymphatic drainage is diminished Jv = Kf [( Pc - Pi) - ( πc - πi)] MICROCIRCULATION Capillaries and Lymph Capillary Exchange and Edema https://www.youtube.com/watch?v=6ecmOuCIoNc Capillary Blood Flow https://www.youtube.com/watch?v=M-vNa3NdGmA HAPPY STUDYING Clara Camargo, DVM [email protected] ©2021 Ross University School of Veterinary Medicine. All rights reserved.