1„Secret fluids” - biological fluids overview, modelling, problems Anna Kucaba-PiętalRzeszów University of Technology,PolandBiological fluids due to its vital function in living organism have highly complicated structure which changes up to the health and living conditions. They are composed mainly of water and specific nano- and microstructures formed by organic substances or morphotic elements .In the last few decades the fluid-dynamic and rheological study of biological fluids has received more and more attention for its influence on several phenomena linked to human health.It is well known that several diseases imply changes both in the properties of human biofluids and their components,It seems, that crucial point is the general use of rheology in the medical field, which should be seen as an interesting support, for instance, in diagnosis.School of Engineering, University of Liverpool Liverpool L69 3GH, UK , May 13th 2013
2ContentsOverview of biological fluids, contents, modelling, problem formulationFundamentalbiofluidrheologyBloodrheological parameters of bloodfactors which effect on blood viscositydiasesesSynovial fluidrheological parameters of s.ffactors which effect on s. f. viscosityPlasma and lymph as Newtonian fluidConclusion
3Aim of Lectures Questions: What influences the change of rheological properties of biological fluids and what are the consequences?Why is it important to predict rheologicalparameters of biofluid?Answers:Due to the formulation bioflow equationsTo maintain nonbiological fluids that hasrheological properties comparble to real biofluidTo use it in diagnostics of clinical disordersStarting from a mean value of about 3,51 cP (with share rate = 100 sec.-1), the viscosity grows (for share rates up to 0,1 sec.-1) until 57,09 cP . Therefore the knowledge of the viscosity, including its variations, is extremely important in the study of the blood rheology.3
5Body fluidsTotal amount of fluid in the human body is approximately 70% of body weightBody fluid has been divided into two compartments –Intracellular fluid (ICF)Inside the cells55% of total body waterExtracellular fluidOutside the cells45% of total body waterBody fluid, bodily fluids, or biofluids are liquids originating from inside the bodies of living people. They include fluids that are excreted or secreted from the body as well as body water that normally is not.The dominating content of body fluids is body water. Approximately 60-65% of body water is contained within the cells (in intracellular fluid) with the other 35-40% of body water contained outside the cells (in extracellular fluid). This fluid component outside of the cells includes the fluid between the cells (interstitial fluid), lymph and blood. There are approximately 6 to 10 liters of lymph in the body, compared to 3.5 to 5 liters of blood
6Body fluid compartments Extracellular fluid includes:Interstitial fluidPresent between the cellsApproximately 80% of ECFPlasmaPresent in bloodApproximately 20% of ECFAlso includesLymphsynovial fluidaqueous humorcerebrospinal fluidvitreous bodyendolymphperilymphpleural, pericardial and peritoneal fluids
7Body fluid compartments The dominating content of body fluids is body water. Approximately 60-65% of body water is contained within the cells (in intracellular fluid) with the other 35-40% of body water contained outside the cells (in extracellular fluid). This fluid component outside of the cells includes the fluid between the cells (interstitial fluid), lymph and blood. There are approximately 6 to 10 liters of lymph in the body, compared to 3.5 to 5 liters of bloodIn some animals, including mammals, the extracellular fluid can be divided into two major subcompartments, interstitial fluid and blood plasma. The extracellular fluid also includes the transcellular fluid; making up only about 2.5 percent of the ECF.In humans, the normal glucose concentration of extracellular fluid that is regulated by homeostasis is approximately 5 mM.The pH of extracellular fluid is tightly regulated by buffers around 7.4.The volume of ECF is typically 15L (of which 12L is interstitial fluid and 3L is plasma).Interstitial Fluid makes up 16% of your body weight and blood plasma 4% of your body weight.
9Barriers separate ICF, interstitial fluid and plasma Plasma membraneSeparates ICF from surrounding interstitial fluidBlood vessel wallSeparate interstitial fluid from plasma
10Composition of body fluids Organic substancesGlucoseAmino acidsFatty acidsHormonesEnzymesInorganic substancesSodiumPotassiumCalciumMagnesiumChloridePhophateSulphate
11Difference Na+ /K+ pumps play major role in keeping K+ high Most abundant cation - Na+,muscle contractionImpulse transmissionfluid and electrolyte balanceMost abundant anion - Cl-Regulates osmotic pressureForms HCl in gastric acidMost abundant cation - K+Resting membrane potentialAction potentialsMaintains intracellular volumeRegulation of pHAnion are proteins and phosphates (HPO42-)Na+ /K+ pumps play major role in keeping K+ highinside cells and Na+ high outside cell
12Control of body fluid volume (Homeostasis) In health the volume and composition of various body fluid compartments are maintained within physiological limits even in face of wide variations in intake of water and solutes .
13Body fluids Amniotic fluid Aqueous humour and vitreous humour Bile BloodBreast milkCerebrospinal fluidCerumen (earwax)ChyleChymeEndolymph and perilymphFeces - see diarrheaFemale ejaculateGastric acidGastric juiceLymphMucus (including nasal drainage and phlegm)Pericardial fluidPeritoneal fluidPleural fluidPusRheumSalivaSebum (skin oil)SemenSputumSweatSynovial fluidTearsVaginal secretionVomitUrine
14Specialized fluids of the body LymphMilkCerebrospinal fluidAmniotic fluidAqueous humorSweatTears
15Transport problems Microscopic level Macroscopic level Transport MechanismsMembrane TransportIntracellular membrane transportICF-ECF ExchangeISF-Plasma ExchangeCapillary PressuresMacroscopic levelBlood Flow CFD simulation synovial fluidThis section reviews the basic forces of diffusion, membrane transport of solutes, andthe osmosis of water across membranes. Since the section probably repeatsinformation from your undergraduate studies, you may safely skip it if you feelcompletely comfortable with its definitions and demonstrations.Fluid movement is caused primarily by the application of pressure. In a macroscopicsense, the application of hydrostatic pressure causes bulk flow, e.g. blood flowingthrough your artieries.Pressure also moves fluid at a microscopic level. Through pores within cellmembranes, and between the cells, pressure causes water and its dissolved particlesto move. The amount of movement is equal to the pressure gradient, the area, andthe leakiness of the barriers.The random movement of particles in the presence of a concentration gradient iscalled diffusion, which also acts as a microscopic pressure that causes movementwithin solutions and across membranes.The mechanism by which water and other solutes move across cell membranes isreviewed here in the section on membrane transport.Diffusion of water is called osmosis, which is another critical microscopic pressurecontrolling fluid movement.These forces control the exchange of water and solutes between the intracellular andextracellular fluids as well as between the interstitial and the plasma compartmentsof the ECF.Follow these sections to examine these forces in more detail.
16Navier-Stokes equations Wstawie pozniejIn physics and engineering, a constitutive equation or constitutive relation is a relation between two physical quantitiesshear stresses or forces to strains or deformations.(especially kinetic quantities as related to kinematic quantities) that is specific to a material or substance, and approximates the response of that material to external stimuli, usually as applied fields or forces. They are combined with other equations governing physical laws to solve physical problems; for example in fluid mechanics the flow of a fluid in a pipe, in solid state physics the response of a crystal to an electric field, or in structural analysis, the connection between applied stresses or forces to strains or deformations.
17Rheological parameters, a constitutive equation The viscosity and elasticity determine the pressure required to produce bioflows.Viscosity is an assessment of the rate of energy dissipationElasticity is an assessment of the elastic storage of energyHow is relations between shear stress and deformation?In physics and engineering, a constitutive equation or constitutive relation is a relation between two physical quantitiesshear stresses or forces to strains or deformations.(especially kinetic quantities as related to kinematic quantities) that is specific to a material or substance, and approximates the response of that material to external stimuli, usually as applied fields or forces. They are combined with other equations governing physical laws to solve physical problems; for example in fluid mechanics the flow of a fluid in a pipe, in solid state physics the response of a crystal to an electric field, or in structural analysis, the connection between applied stresses or forces to strains or deformations.
19Rheology as an interdisciplinary science PhysicsChemistryRheology(of Liquids)MechanicsofContinuumTechnology/EngineeringRheology is the science of plastic deformation and the flow of materials under stress.Rheology is the study of the flow of matter, under conditions in which they respond with plastic flow rather than deforming elastically in response to an applied force.Rheology is the science of plastic deformation and the flow of materials under stress. The term "rheology" was proposed under the influence of the suggestions inspired by the famous statement of Heraclitus: “Panta Rhei”, or "everything flows".Ideal solids deform as elastics. Energy consumed to produce deformation is completely recovered after removal of stress.When an elastic material is deformed due to an external force, it experiences internal forces that oppose the deformation and restore it to its original state if the external force is no longer applied.The ideal fluid deforms in an irreversible way - flows. In the complex continuous energy used for deformation is dissipation and can not be recovered after removal of stress. Viscosity is a measure of flow resistance due to the internal friction.Viscoelasticity defines the fluid tends to respond to stress. It is a feature of elastic solids and viscous fluids. Viscous and viscoelastic properties of fluids are expressed by a coefficients, which can be determined experimentally.Quantitative and qualitative changes of biological fluid microstructure affect the reaction. Different conditions cause specific changes in nano-and microstructures of a biological fluid, resulting in change in value of the rheological coefficients1919
20Viscosity Viscosity = F(S,T,p,s,t, V) S- physico-chemical properties of substances,T-temperature, p- pressure, s-velocity of shear, t-time, V-voltageThe shear viscosity of a fluid expresses its resistance to shearing flows, where adjacent layers move parallel to each other with different speeds.If the speed of the top plate is small enough, the fluid particles will move parallel to it, and their speed will vary linearly from zero at the bottom to at the top. Each layer of fluid will move faster than the one just below it, and friction between them will give rise to a force resisting their relative motion. In particular, the fluid will apply on the top plate a force in the direction opposite to its motion, and an equal but opposite to the bottom plate. An external force is therefore required in order to keep the top plate moving at constant speed.The magnitude of this force is found to be proportional to the speed and the area of each plate, and inversely proportional to their separation . That is,One of the major tasks of rheology is to empirically establish the relationships between deformations and stresses, respectively their derivatives by adequate measurements, although a number of theoretical developments (such as assuring frame invariants) are also required before using the empirical data. These experimental techniques are known as rheometry and are concerned with the determination with well-defined rheological material functions. Such relationships are then amenable to mathematical treatment by the established methods of continuum mechanics.
21Models . t = f(g) NEWTONIAN FLUID F y u(y) NON-NEWTONIAN FLUID 21 Newton's law of viscosity is a constitutive equation (like Hooke's law, Fick's law, Ohm's law): it is not a fundamental law of nature but an approximation that holds in some materials and fails in others.A fluid that behaves according to Newton's law, with a viscosity μ that is independent of the stress, is said to be Newtonian. Gases, water and many common liquids can be considered Newtonian in ordinary conditions and contexts. There are many non-Newtonian fluids that significanly deviate from that law in some way or other. For example:Shear thickening liquids, whose viscosity increases with the rate of shear stress.Shear thinning liquids, whose viscosity decreases with the rate of shear stress.Thixotropic liquids, that become less viscous over time when shaken, agitated, or otherwise stressed.Rheopectic liquids, that become more viscous over time when shaken, agitated, or otherwise stressed.Bingham plastics that behave as a solid at low stresses but flows as a viscous fluid at high stresses.Shear thinning liquids are very commonly, but misleadingly, described as thixotropic.NON-NEWTONIANFLUID.t = f(g)21
22BloodBlood is a concentrated suspension of Red Blood Cells; outside the range of dilute suspensionParticles change their shape in response to the fluid forcesThe nature of RBC membrane and its deformation stress/strain is much less establishedRBC tends to form agregates known as rouleaux
24Blood – formed elements TYPES OF LEUKOCYTESPLATELETSRBCs
25Physical properties of blood RANGEDensity (g/cm3)Viscosity (cP)pHPROPERTYFactors affecting the blood rheology:a) hematocritb) deformation and agregation of red blood cellsc) biochemical properties of plasmad) temperaturee) the geometry and flow parameters
26Composition of blood plasma: Plasma is the straw-colored liquid in which the blood cells are suspended.Composition of blood plasma:ComponentPercentWater~92Proteins6–8Salts0.8Lipids0.6Glucose (blood sugar)0.1
27Plasma Water : 90% Solids: 10% organic constituents: proteins, lipids, carbohydrates , hormones, enzymes,Ketone bodies , and other organic compounds.Inorganic compounds: Na, K Ca,Cl,and CO2.
28Comparison of Newtonian plasma and blood viscosity
29Lymph Clear and colorless fluid 96% water and 4% solids Solids – Proteins2-6% of solidsalbumin, globulin, fibrinogen, prothrombin, clotting factors, antibodies, enzymesLipids5-15%ChylomicronsLipoproteinsCarbohydratesGlucose mainlyNPNUrea and creatinineElectrolytesSodium, calcium, potassium, chloride, bicarbonates
30Functions of lymph Return protein from tissue spaces into blood Redistribution of fluidRemoval of bacteria, toxins and other foreign bodies from tissuesMaintain structural and functional integrity of tissueRoute for intestinal fat absorptionTransport lymphocytes
31Lymphatic fluidWhat is it? It is a fluid that resembles plasma but with a much lower concentration of suspended proteinsFunctions?Transports hormones, nutrients, and waste products from peripheral tissues to the general circulationReturns fluid and solute from peripheral tissues to the bloodMaintains blood volume and eliminates local variations in the composition of the interstitial fluid
32Newtonian behaviorNewtonian fluid: constant viscosity at all shear rates at a constant pressure and temperature. Relationship between shear stress and shear rate is linear.
33Synovial fluidThe synovial fluid is a dialysate of blood plasma. It consists to 94% of water. Moreover, it contains a very specific and very important polymer known as a hyaluronic acid (HA - hyaluronate). It also contains some macromolecular components like glycoproteins, phospholipids and low molecular compounds e.g. liquid crystalline cholesterol ester and ions. Hyaluronan is a water soluble polysacharide and can create, under suitable concentration, liotropic liquid crystalline phase within the range of physiological temperatures.33
34Synovial fluid Contents value Dry matter 0,133,5 Density(20oC) 1,00811,015pH7,27,4viscosity (20oC)water, g/kg960988hyaluronic acid(HA )2-3%The content of dry matter g/kg1240Albumins, globulins g/lPhospholipids,glycoprotein's10,721,310,20,5Mucyns, g/l0,681,35Glucoses, g/ljak w surowicy krwiUrynial Acid, mg/l73,4The synovial fluid is a dialysate of blood plasma. It consists to 94% of water. Moreover, it contains a very specific and very important polymer known as a hyaluronic acid (HA - hyaluronate). It also contains some macromolecular components like glycoproteins, phospholipids and low molecular compounds e.g. liquid crystalline cholesterol ester and ions. Hyaluronan is a water soluble polysacharide and can create, under suitable concentration, liotropic liquid crystalline phase within the range of physiological temperatures.34
35FunctionsMinimise the friction between during bones movement or weight bearingProvides nutrition for cartilage.ml
36Synovial fluid Main Factors affecting the rheological properties: a) Hyaluronic Acid concentationc) Molecular weigh of Hyaluronic Acidd) TemperatureSodium Hyaluronate, HyaluronanMade up of repeating glucuronic acid and N-acetylglucosamine subunitsHigh molecular weight: 0.2 to 10 million DaltonMajor component of synovial fluidExhibits viscoelastic properties. Hyaluronan is a water soluble polysacharide and can create, under suitable concentration, liotropic liquid crystalline phase within the range of physiological temperatures36
37Perspectives Pathophysiological significance of biofluid rheology Develop an understanding of how the micro- and nano-structure of blood influences its rheologyExplore to use of rheological parameters in diagnostics and menagement of clinical disorders and inoptimisation of blood processingExplore new methods of measurement suited for clinical applicationMaintain new type apparatus for such measurements