Presentation on theme: "Microcirculation: introduction"— Presentation transcript:
1Microcirculation: introduction 1) Capillaries are the site of diffusion of nutrients and waste between blood and tissue 2) Transcapillary exchange of fluidMaintains plasma & interstitial flluidVolumeOpposes edema formation ( Capillary Starling forces)Lymphatic structure & functionEdema formation
2Microvascular unit Venule Metarteriole Capillaries Arteriovenous shunt (S)Pre-capillary sphincters exist at the origin of each capillaryArteriole
4Capillary Structure Capillaries: Site of exchange by diffusion (some diffusion occurs in venules also).Capillary walls are porous to small molecules:Intercellular cleftsFused vesicle channels
5The Permeability Surface area term for diffusion across a capillary wall The rate of diffusion of a molecule is proportional to area & concentration gradient, & inversely proportional to distance:n = amount, t = time, D = diffusion coefficient, A = area, dC = concentration gradient, dx = distance.Applied to the circulation, the equation for diffusion of molecules across the capillary wall is:Where P is permeability of the capillary & S is surface area. Under most conditions P is constant & determined by the structure of the capillary wall.Physiologically, the area S available for diffusion can be increased by recruiting more capillaries, which also decreases the distance (shorter intercapillary distance).
6Transcapillary exchange of lipid soluble substances Lipid soluble substances such as CO2, O2 & many anesthetics penetrate the capillary wall by diffusing via the lipid component of the endothelial cell membranes.Capillary area for diffusion of lipid soluble molecules is maximal.Transcapillary movement of macromolecules & cellsMolecules > 40 A can be transported across the endothelium by pinocytosis.Leucocytes & lymphocytes migrate through intercellular clefts by ameboid movement.
7Transcapillary exchange of water soluble substances H2O, monosaccharides, amino acids, small peptides & organic acids and inorganic ions (Na+, K+, Ca++, etc) diffuse rapidly through intercellular clefts.The area for diffusion of water soluble molecules is less than for lipid soluble molecules.Capillaries have two types of endothelium:Discontinuous endothelium capillaries have large clefts & gaps in basement membrane, relatively high permeability.Continuous endothelium: basement membrane is continuous, intercellular clefts are ~ 40 angstroms diameter & have tight junctions. Molecules larger than 40 A, like proteins, cannot cross the wall by diffusion.Discontinuous endothelium (liver, spleen, glomerulus, small intestine, endocrine glands, bone marrow)Continuous endothelium (muscle, skin, lung, CNS)
8Flow & diffusion limits on exchange` Flow limited exchange: exchange of molecules that diffuse rapidly is limited by the rate of blood flow (examples: H2O and small molecules)Diffusion limited exchange: exchange limited by diffusion because eitherThe molecules diffuse slowly (macromolecules) orDiffusion distances are largeFlow-limited; Diffusion is rapidflowDiffusion limited;Diffusion is slowflowWith edema increased diffusion distance may limit supply of nutrients to tissues
9Transcapillary exchange of fluid impacts plasma & interstitial fluid volumes Total body water content is maintained nearly constant by control mechanisms that operate through thirst (input) and kidney function (output)Total body water can be divided intoExtracellular fluid (ECF)PlasmaInterstitial fluid including lymphIntracellular fluid (ICF)The distribution of fluid between plasma and interstitium depends on:1. Osmotic pressure due to plasma proteins2. Capillary hydrostatic pressure3.Osmotic pressure due to proteins in interstitial fluid4. Interstitial fluid hydrostatic pressure(These are the Starling Forces)Imbalances in these factors may produce edema & decrease blood volume.Edema is “a palpable swelling produced by expansion of the interstitial fluid volume.”
10OsmosisOsmotic pressure is pressure created by a difference in solute concentration across a semi-permeable membrane.Osmosis is the passive diffusion of water from a region of low solute concentration (dilute solution, low osmotic pressure) to a region of high solute concentration (concentrated solution, high osmotic pressure).Osmotic pressure due to protein molecules is called oncotic pressure.
11Definition of an osmole Osmotic Pressure depends on the concentration of particles in a solution..An osmole is a unit that refers to the total number of particles dissolved in a solution. One osmole = x 1023 particles (Avogadro’s number).One gram molecular weight of glucose dissolved in water will liberate one osmole of particles.One mole of NaCl dissolved in water will yield two osmoles (Na+ and Cl-) of particles.One osmole of glucose in one liter of water will yield a one osmolar solution.Osmolarity is the number of osmoles/liter of solution.Osmolality is the number of osmoles/kilogram of solvent.The difference between osmolarity & osmolality for biological solutions is insignificant.
12Normal plasma osmolality Plasma solutes, millimoles/literCationsAnionsNa+135Cl-108K+3.5HCO3-24Ca++2Lactate1Sum140.5Albumin0.6133.6Glucose 5Urea 5Grand total284.1mM = millimole = 1/1000th of a molemOsm = milliosmole = 1/1000th of an osmoleNormal plasma osmolality = 280 to 296 mOsm/liter
13Starling forces in capillaries OUT INF = K [(Pcap + i) – (Pi + cap)]F = net movement of fluid across the capillary wall (ml/min)Pc ap = capillary hydrostatic pressure (mmHg)cap = capillary oncotic pressure* (mmHg)Pi = interstitial fluid hydrostatic pressure (mmHg)I = interstitial fluid oncotic pressure (mmHg)K = filtration constant: (determined by capillary surface area and permeability to water (ml/min)/mmHg)*oncotic pressure = osmotic pressure due to proteins
14Calculation of net filtration pressure F ~ Pcap – capF = K [(Pcap + i) – (Pi + cap)]Blood flow Pc ap = 37 mm Hgi= 0Pi = 1 mm Hgcap = 25 mm HgArterial end: Pcap > capNet filtration pressure =(37 + 0) - (1 + 25) = 11 mm HgVenous end: Pcap < cap(17 + 0) - (1 + 25) = - 9 mm HgPcap =17 mm HgNegative value for net filtration pressure indicates net force favors absorption
15Starling forces & lymph flow in various tissues PcapPicapiLymph flowNFP**Hind limb (dog)13.0-52140.015+1.0Skeletal muscle (rest)10.1-32080.005+1.1Intestine (rest)16.0223100.08Intestine (digesting)350.10-5.0Liver7.0622-1.0Lung12Cardiac muscle23.115130.12+0.1Glomerulus50.0282.0+7.0Peritubular capillary*25.0732-7.0*in the kidney** NFP = net filtration pressurePressures are all mm Hg; lymph flow units are ml/min per 100 g tissue
16Factors that influence lymph flow Lymph flow is increased by Interstitial hydrostatic pressure Lymphatic contractions (smooth muscle) & valves Sympathetic stimulation of lymph vesselsSkeletal muscle pump
17Lymphatic circulation 2 to 4 liters of fluid per day is filtered out of the capillaries, taken up by the lymphatics and returned to the systemic circulation.systemic capillariesVenous systemInterstitial fluidFiltration 20 liters/dayAbsorption 16 to 18 liters/dayLymph flow 2 to 4 liters/daysystemic arteriesRight heartPulmonary circulationLeft heartTerminal lymphatics are highly permeable to proteinLymphatics are the only route for return to circulation of protein that leaves capillaries
18Arteriolar Tone and Capillary Hydrostatic Pressure Arteriolar constriction decreases PcapArteriolar dilation increases PcapChanges in PCap will affect filtration & absorptionEffect on mean arterial pressure:MAP = CO x TPRConstriction of arterioles in one organ or tissue may be offset by dilation elsewhere, without causing a change in TPR and MAPWidespread arteriolar constriction in many tissues will increase TPR and MAP (if CO doesn’t change).Arterial pressureCapillary hydrostatic pressuredilationconstrictionCapillaryArteryArteriole
19Absorption of interstitial fluid into the circulation compensates in hemorrhage MAP = CO x TPRHemorrhage sympathetic nerve activity heart rate cardiac contractilityRestore MAP TPRCardiovascular reflexeshypotension absorption of fluid into capillariesRestore blood volume COVasoconstriction(skin, kidney, GI tract) capillary hydrostatic pressure hematocrit
20Three physiological roles of arteriolar tone Support arterial blood pressureDirect distribution of flow between organs & tissuesInfluence capillary filtration & absorption
21Capillary hydrostatic pressure, mm Hg Edema safety factors30(cap - i), mm HgA30Lymph flowB30Pi, mm HgCCapillary hydrostatic pressure, mm HgA: As capillary hydrostatic pressure & filtration increase, tissue protein is diluted, i decreases, so cap - i increases, limiting further filtration.(The y-axis in panel A is cap - I, the oncotic pressure gradient influencing filtration)B: As filtration increases, lymph flow increases, limiting accumulation of fluid in the interstitium.C: As filtration increases, fluid added to the interstitium increases Pi, decreasing the hydrostatic pressure gradient favoring filtration (Pcap – Pi)
22Edema formationEdema is a pathological accumulation of excess fluid in the interstitial spaceCauses of edema:Decreased plasma oncotic pressureKidney disease urinary excretion of plasma proteinLiver disease inadequate albumin synthesisIncreased capillary permeability to proteinsTissue traumaAnaphylactic shockIncreased venous & capillary hydrostatic pressureCongestive heart failureBlockage of lymphaticsTumorsParasites