Microcirculation Capillary Exchange VP 2024 PDF

MICROCIRCULATION Capillaries, Lymphatic system and Fluid Exchange VP 2024 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/blood perfusion 3. Explain how diff...

MICROCIRCULATION Capillaries, Lymphatic system and Fluid Exchange VP 2024 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/blood perfusion 3. Explain how different substances (solutes and gases) 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 MICROCIRCULATION Circulation of the blood in the smallest blood vessels  Exchange of nutrients, gases and waste products in tissues  Fluid exchange between vascular and interstitial compartments Body fluid compartments https://www.youtube.com/watch?v=zT1jmPyP1Yc&t=1s MICROCIRCULATION The term “microcirculation” refers to the functions of the smallest blood vessels (arterioles and venules), the capillaries and the neighboring lymphatic vessels Delivery of blood to and from the capillaries is critically important because the capillaries are:  site of exchange of nutrients and waste products in the tissues  site of fluid exchange between the vascular and interstitial compartments Arterioles: smallest branches of arteries High smooth muscle composition; highly innervated can respond to sympathetic stimulation or vasoactive substances highest resistance to blood flow Capillaries: thin-walled with single layer of endothelial cells surrounded by basal lamina; exchange of nutrients, gases, water and solutes between blood and tissues Can be selectively perfused with blood Venules : thin-walled ↓elastic tissue = ↑capacitance; low pressure, no smooth muscle MICROCIRCULATION CAPILLARY BEDS Capillary bed: terminal arterioles → metarterioles → precapillary sphincters → true capillaries → postcapillary venules → venule Blood is delivered to capillary beds via arterioles Constriction or relaxation of arterioles 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 True capillaries merge into venules, they carry blood from tissues to veins and back to the macrocirculation MICROCIRCULATION Capillary bed blood pathway 1. Arteriole (bringing blood from the heart) 2. Meta-arteriole (smaller arteriole) 3. Capillary bed 4. Venule 5. Vein (blood back to macro circulation) Press on your fingernail. What happens? Arteriovenous anastomoses helps controlling the skin temperature through volume changes in the superficial venous bed 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 Capillaries are thin-walled, single endothelial layer, containing water-filled clefts between cells MICROCIRCULATION EXCHANGE OF SUBSTANCES ACROSS THE CAPILLARY WALL O2 and CO2:  diffuse through endothelial cells, highly lipid soluble (N2 and NO also can diffuse) Water-soluble molecules (hydrophilic):  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 they are retained in vascular compartment.  Some tissues have particularly ‘tight’ clefts (brain) - little quantities of small proteins can leave capillaries  Other capillaries have ‘fenestrations’ allowing few small protein to pass  Proteins may cross in pinocytotic vesicles (transcytosis) DIFFUSION – Solute and gases movement Exchange of solutes and gases across capillary wall occurs by simple diffusion (membrane must be permeable to solutes and gases)  either through or between the endothelial cells  Diffusion is driven by the partial pressure/concentration gradient for the individual gas or solute solute will move towards the concentraiton gradient (from higher to lower concentrations) until equilibrium is reached Rate of diffusion depends on: The driving force (the partial pressure/concentration difference for the gas or solute) 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 movement 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 (impermeable to the solute but permeable to water) to equalize the solute concentration in each side of the membrane  Concentration differences of impermeate solutes create osmotic pressure differences, which cause water to flow by osmosis Solute contributes to the effective osmotic pressure OSMOSIS - TONICITY TONICITY: measures of effective osmotic pressure gradient 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 Different effective osmotic pressures: Lower osmotic pressure = hypotonic Higher osmotic pressure = hypertonic Hypotonic solution 1 Hypertonic solution 2 1 2 Water will flow from the hypotonic solution into the hypertonic solution RBC placed in different solution concentrations: https://en.wikipedia.org/wiki/Tonicity#/media/File:Osmotic_pressure_on_blood_cells_diagram.svg REFLECTION COEFFICIENT OF THE MEMBRANE 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 FLUID EXCHANGE ACROSS CAPILLARIES EFFECTIVE OSMOTIC PRESSURE In capillaries, fluid movement is driven by the sum of:  Hydrostatic pressure (related to the blood pressure) and  Effective osmotic pressure Capillary walls (membrane) have a reflection coefficient of 1.0 (impermeable) to proteins Proteins cannot cross the membrane and apply their full osmotic pressure inside of the capillaries In capillary blood, only proteins (mainly albumin) contributes to the effective osmotic pressure The effective osmotic pressure contributed by protein can also be called  colloid osmotic pressure or  oncotic pressure STARLING PRESSURES (STARLING EQUATION) Describes the passive exchange of water between capillary microcirculation and the interstitial fluid → fluid movement across a capillary wall 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 Fluid movement (Jv) across a capillary wall is determined by the net pressure across the wall:  Hydrostatic (Pc – Pi)  oncotic pressures (πc – πi) Jv = Kf [( Pc - Pi) - ( πc - πi)] 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 (Jv will be a positive number) Net fluid movement from interstitium into the capillary: Reabsorption (Jv will be a negative number) Magnitude of fluid movement: determined by hydraulic conductance (Kf) Kf vascular permeability of the capillary wall regulates how much fluid movement will take place at a certain pressure difference! STARLING PRESSURES Pc capillary hydrostatic pressure: Force favouring filtration Value is determined mainly by arterial pressure Decreases along length of capillary due to blood vessel 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 (mainly albumin) ↑ protein conc.  ↑ πc, ↓ filtration πi interstitial oncotic pressure: Force favouring filtration Determined by interstitial fluid protein concentration  normally low due to low protein concentration in instertitial fluid Starling Pressures Jv = Kf [( Pc - Pi) - ( πc - πi)] Direction of arrows indicates if pressure favors filtration or absorption Size of arrows: magnitude of pressure Numerical value of pressure in mm Hg: (+) favors filtration (-) favors absorption Net pressure 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:  Higher in capillaries with higher Kf (e.g., sinusoid and fenestrated capillaries)  Lower at lower Kf (e.g., continuous capillaries - blood brain barrier) Kf is NOT influenced by changes in arteriolar resistance, hypoxia, metabolites buildup Kf is influenced by Capillary injury (e.g. toxins, burns, inflammation)  will increase capillary permeability to water and loss of protein from capillary STARLING PRESSURES CHANGES IN STARLING PRESSURES Can influence the direction and magnitude of fluid movement across capillaries Several changes can produce increased filtration (fluid movement out of capillaries):  Increase in any of the Starling forces that favor filtration or  Decrease in any of the Starling forces that favor absorption Increase in filtration:  Increase in Pc → i.e., caused by increased arterial pressure  Decrease in πc → i.e., caused by reduction of plasma protein concentration LYMPHATIC SYSTEM The lymphatic system is in control of returning interstitial fluid and proteins to the vascular compartment The lymphatic capillaries lie close to the capillary bed 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 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 lymphatic system to drain it and send it back to the macrocirculation Edema can form mainly when there is  increased filtration  lymphatic drainage is diminished Jv = Kf [( Pc - Pi) - ( πc - πi)] MICROCIRCULATION Capillaries and Lymph Supplemental video - Diffusion and osmosis https://www.youtube.com/watch?v=Xxp6oponwkg 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.