CIRCULATION CIRCULATION Major Role in Homeostasis - PowerPoint Presentation

1. CIRCULATION

2. CIRCULATIONMajor Role in HomeostasisOnly ONE FunctionTRANSPORTOxygen and Nutrients to tissueMetabolic end products to excretory organsHormones to target tissues

3. SEGEMENTS IN CIRCULATIONSystemic circulationArteries, arterioles, capillaries, veinules & Veins84% of total bloodVeins – 64%Arteries – 13%Arterioles & Caps – 7%Coronary circulationBlood supply to heartPart of systemic circulation7% of total bloodPulmonary Circulation9% of total blood

4. CHARACTERS OF VASCULAR SYSTEMBlood vessels in each tissue Some special charactersSome common charactersCapillaries - Exchange vesselsExchange fluids, nutrients, respiratory gases, electrolytes, hormones etc. with ISFThin Permeable wallsBlood volume in capillaries is lowArterioles completely closed/dilated several foldregulate blood flow into capillaries and tissues as per needsArteries Rapid blood flow under pressureStrong muscular wallsVeinulesCollect blood from capillariesGradually coalesce into veinsVeinsCarry blood back to heartAct as blood reservoirsBlood flow slow and under lower pressureWalls relatively thin Under go constriction and expansion several folds

5. CROSS SECTIONAL AREAS IN SYSTEMIC CIRCULATIONCSA of venous system is 5X to arterial systemFacilitates blood storageCSA of capillaries is 8X to venous systemCSA of capillaries is 40X to arterial systemFacilitates exchangeVelocity of blood flow reducedFrom arteries to capillaries Av.velocity 1/∞ to CSAAorta 33cm/S0.33cm/S in capillarieslength of capillaries 0.3-1.0mmBlood stays only for 1-3SExchange takes place during that brief period

6. BLOOD PRESSURE IN DIFFERENT SEGMENTS OF CIRCULATIONHeart pumps blood into arteriesPulsatile pumpingTherefore pressure fluctuates 120 - 80mmHgBP falls progressively Reaches almost zero in the right atriumBP in capillariesArterial end 35 mm HgVenous end 10mmHgAv. Functional pressure 17mmHgLow enough to prevent considerable leakage of fluidHigh enough to cause exchangePulmonary circulationPulsatile pressureMuch lower than in systemic circulationSP in pulmonary artery: 25mmHgDP in Pulmonary artery: 08mm HgMean Pulmonary artery pressure: 16mm HgMean Pulmonary capillary pressure: 7mm HgBut the amount blood flow/min. is equal in pulmonary & systemic CirculationsLow pressure consistent with short distance35mmHg10mmHg17mmHg

7. PRINCIPLES OF CIRCULATIONThree fundamental principlesBlood flow to tissues controlled exactly as per needsBlood flow to tissues controls cardiac output (COP)Arterial pressure controlled independent ofblood flow to tissues and COP control

8. LOGIC OF PRINCIPLES OF CIRUCLATIONMicro vessels in each tissueContinuously monitor tissue needs for oxygen, nutrients etc.Precise control of blood flow to the level requiredWhen tissues become activeBlood flow needs could increase 25-30XBlood flow through a tissue increasesAdditional blood returns to heart through the veinsCOP increased to pump back additional blood receivedCOP can be increased 4-5XSo increase in COP alone cannot meet tissue needsNot necessary to increase blood flow to all tissues when only some tissues become activeExtensive pressure regulatory mechanisms Do not allow MAP to change under different physiological conditionsBLOOD FLOW TO TISSUES CONTROLLED EXACTLY AS PER NEEDSBLOOD FLOW TO TISSUES CONTROLS CARDIAC OUTPUT (COP)AP CONTROL INDEPENDENT OF TISSUE BLOOD FLOW & COP

9. RELATIONSHIP BETWEEN PRESSURE, FLOW AND RESISTANCEBlood flow through a vessel determined byPressure difference between the two endsPressure gradient but not absolute pressureImpediment to blood flow through the vesselCalled vascular resistanceQ = P ÷ R Q= quantity of blood flowP = pressure gradient betn. two ends of the vesselR= resistance to blood flowOhm’s Law1209070405010

10. BLOOD FLOWQuantity of blood that passes a given point in a unit timeml/min or L/minblood flow in circulation/Kg/minCattle: 113±11ml/Kg/minSheep: 131±39ml/kg/min Horse: 86±13ml.Kg/minAdult man: 70ml/Kg/minCalled the cardiac outputAmount of blood pumped by heart each minuteStreamline /Laminar flow of BloodSteady rate flow of blood in long smooth vesselsEach layer of blood remains at the same distance from vessel wallsCentral portion of the blood remains at the centerVelocity of flow at the center is higher than at peripheryAlso called parabolic flowTurbulent flowBlood flows in all directions in a vesselOccurs rarelyConsidered opposite of laminar flow

11. BLOOD PRESSUREForce exerted by flowing blood against unit area of vessel wallMeasured in mm Hg100 mm HgSufficient pressure to push a column of mercury by 100mm.

12. RESISTANCE AND CONDUCTANCE OF BLOOD FLOWCannot be measured directlycalculated from flow and pressure gradient using Ohm’s lawQ = P ÷ R R = P ÷ Q Measured in peripheral resistance units (PRU)If P = 1mm Hg and Q = 1ml/S, then R = 1 PRUEx: In man Q = 100ml/S and P= 100mm (betn .systemic arteries and systemic veins)So the resistance is 1PRUPowerful vasoconstriction: Resistance 4X (4 PRU) Extreme Vasodilatation: Resistance 5X (0.2PRU)In pulmonary circulation the resistance = 0.14 PRUConductance is the reciprocal of resistanceblood flow through a vessel for a given pressure gradientml/S/mm Hg.Slight change in diameter of blood vessel causes tremendous changes in conductance especially when the blood flow is laminarConductance increase in proportion to (diameter)4If the diameter increase 4X the conductance increase by 256 times

13. POISEUILLE’S LAWDetermines blood flow by integratinglength and radius of blood vessels and viscosity of bloodQ = П P r4 ÷ 8ηLη = Viscosity of bloodL = Length of blood vessel Except the radius others are fairly constant Therefore radius of blood vessel ordinarily determines blood flowArterioles change their radius between 8-30mmSo blood flow could change ~256 times

14. viscosity and pressure in determining blood flowViscosity force Opposes blood flowDetermined byHaematocrit, & Conc. of proteins and lipidsNormal viscosity of whole blood = 33 times more force needed to move equal amount of blood relative to waterPolycythemiaHaematocrit raises to 60-70%May increase viscosity up to 10Increases BPBlood pressureIf blood pressure increases blood flow also increasesNot only because P increasesBut increased blood pressure causes vasodilatationThis reduces resistance to flowBlood flow 100 mm Hg is 4X to that 50 mm Hg

15. VASCULAR DISTENSIBILITYAll blood vessels are distensibleVolume increases with internal pressurePressure pulsations of heart beat averaged out by arterial distensionResults in continuous smooth flow of bloodVeins are the most distensible6-10X distensible than arteriesbecause of less muscular wallsDistensibility = Increase in volume Increase in pressure X original VolumeIncrease in pressure = 1mm Hg Original volume = 10 mlIncrease in volume = 1mlWhat is the distensibility ?0.1 or 10%Distensibility is a ratio (proportion)

16. VASCULAR COMPLIANCEAlso known as capacitanceVolume of additional blood accommodated in a vessel for every mmHg increase in pressureCompliance and distensibility are not sameA highly distensible vessel may be less compliantBut less distensible vessel may be more complaintWhat is the relationship between compliance and distensibility?Compliance = distensibility x volumeORCompliance = Increase in volume ÷ Increase in pressureCompliance of vein is 24X to that of a corresponding arteryVeins are 8 times more distensibleVeins are 3X voluminousAbsolute valueVolume = 1mlDistensibility = 100%Volume = 100mlDistensibility = 50%

17. PRESSURE VOLUME RELATIONSHIP IN CIRCULATIONInteresting relationshipIf arterial blood volume is 750ml the MAP = 100mm HgIf arterial blood volume is 500ml, the MAP falls to ZEROBlood volume is critical to maintenance of blood pressureIn the venous system normal blood volume is 2500mlBut the Mean Venous Pressure is <20 mmHgLarge changes in volume are needed to change venous pressureBecause veins are more compliant than arteriesSympathetic stimulation increases MAP at each blood volume by causing vascular constrictionSimilarly sympathetic inhibition decreases MAP by vasodilatationTherefore sympathetic stimulation/inhibition are used to shift blood between arterial and venous compartments. Thus sympathetic stimulation could influence the COP

18. MEAN ARTERIAL PRESSURENot the average of systolic pressure and diastolic pressureMAP is nearer to diastolic pressureMAP = 40% of SP + 60% of DPArterial pressure = COP X Total Peripheral Resistance

19. DAMPING OF PULSATILE PRESSURESmooth and continuous flow of blood is due to vascular complianceOtherwise blood flows only during systole not diastoleDistensibility and resistance of a vessels progressively decrease the pressureThis progressive reduction is ‘DAMPING”Damping ∞ resistance X complianceBecause of damping tissue blood flow is not affected by pulsatile pumping by heart

20. PULSE PRESSUREDetermines Blood flow into capillaries Pulse pressure = systolic pressure (minus) diastolic pressureIn adult dog Pulse pressure = 120-70=50 mmHgblood flows into capillaries with a pressure of 50 mm Hg.Factors that determine pulse pressureStroke volume output of the heartGreater the stroke volume greater is the systolic pressureBecause larger volumes are being pumpedSo pulse pressure increasesCompliance of arteriesLess the compliance of the arterial system greater the systolic pressure for a give stroke volumeSo again pulse pressure increasesPulse pressure increases by 2 times in old ageDue to arteriosclerosisNarrowing of arteries

21. MEASUREMENT OF BLOOD PRESSUREClinically measured by auscultationPressure pulsation in major arteries heard with a stethoscopeEx: radial artery, Femoral artery, coccygeal arteryWhen external pressure equal to systolic pressure is applied to a major artery blood flow through that artery is stopped and no sounds are heardAs the external pressure is slowly released blood flow resumes sounds begin to be heard - this pressure is systolic pressureAs release of external pressure continues sounds disappear - this pressure is diastolic pressure The sounds are called KOROTOKOFF sounds Oscillometric method for continuous recording

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23. SpeciesSystolic(mm Hg)Diastolic(mm Hg)Mean(mm Hg) Equine13095107Bovine14095110Ovine14090107Porcine14080100Canine1207087Feline14090106Giraffe260160193

24. 8-10ft.1-1.5 ft

25. MEASUREMENT OF BLOOD PRESSURE IN ANIMALSNot routinely undertaken in animals during clinical examinationMeasured by direct / indirect techniquesDirect techniquesPenetration of a peripheral artery with a needle and connect it pressure transducerAccurate measurementBut requires anesthesiaAnesthesia may change the blood pressureIndirect TechniquesPlacement of a cuff over an extremity - Limb / tailCuff is inflated and then deflated mannually to detect restoration of blood flowUltrasonic dopplers, oscillometric / photoplethysmographic principlesMeasurement of blood pressure induces stress

26. VEINS AND THEIR FUNCTIONSPassage of blood from tissues back to heartFunctions to tune circulation to body needsAbility to constrict and dilateStore large volumes of bloodOperate venous pump to move blood back to heartVenous return to heart is critical regulator of COPBlood flows from all veins into right atriumRight atrial pressure is called central venous pressure (CVP) = ZERORight atrial pressure is regulated byAbility of heart to pump blood out of RAStrong pumping decreases and weak pumping increasesEfficiency of blood to flow back into RA via the peripheral veinsIncreased inflow increases RA pressure and decreased inflow decreasesIncreased blood volume, increased large vessel tone, dilatation of arterioles increase venous return to right atrium

27. VENOUS PRESSUREIn the peripheral veins : 4-7 mmHg > CVPSo when the CVP increases blood backs up in peripheral veins opening themAs the blood accumulates in peripheral veins, peripheral venous pressure might increaseBut normally it does not unless CVP > 6mmHgIn the standing position, CVP is still zero but pressure in the legs could reach 90mmHg due to hydrostatic pressureBut for the presence of valves in the veins venous pressure in feet could always be 90mm Hg. While standingWhen the organism moves its legs, tightens the muscles in the legs it squeezes blood out of veinsValves in the veins allow blood flow only towards heartThus every time legs are moved some amount of blood moves towards the heart and the pressure in veins is reducedThis pumping system is known as venous pump or muscle pumpVenous pump does not allow the venous pressure in legs to be > 25mm HgIf an organism stands absolutely still, then venous pump cannot workThis reduces venous return to heart over a period of time

28. VENOUS BLOOD RESERVOIR SYSTEMTwo reasons to call veins as blood reservoir systemVeins are the most compliant blood vessels> 60% of blood in the body is in veinsVenous reservoirsLarge abdominal veinsSubcutaneous venous plexusSpleen When Mean Arterial Pressure starts to fallVeins constrict to shift additional blood to heartVeino-constriction compensate ~20% of blood lossHeart and lungs also act as blood reservoirs although not a part of venous system

29. MICRO CIRCULATIONCirculation in the tissuesIncludes arterioles, capillaries, veinules & lymph channelsExchange takes place in the micro circulationSmall arterioles control blood flow to each tissue Diameter of small arterioles are controlled by tissue needsTherefore each tissue controls its own blood flow

30. STRUCTURE OF MICRO CIRCULATIONOrganized to meet tissue needsArtery to each organ branches 6-8XBecomes small to be called arterioleInternal diameter < 20mmHighly muscularDiameter changes several foldArterioles branch 2-5 timesMetarterioles & capillariesPreferential / thoroughfare channelsInternal diameter 5-9mmSupply to capillariesPrecapillary sphinctersMet arterioles and and precapillary sphincters very near to tissues servedDirect influence of Tissue conditions Ex: nutrient & metabolic end product conc.VenulesConsiderably larger than arteriolesMuch weaker muscular wallsPressure in veinules < in arterioles So contract considerably despite weak walls

31. CAPILLARIESExtremely thin wallsSingle layer of highly permeable endothelial cells10 billion capillaries TSA = 500 – 700M2 in man Any tissue or cell away from capillary by <20-30mmWall thickness 0.5 micronsTwo passageways through the wallInter cellular cleftSlit between endothelial cells Water & other small molecules pass rapidly Plasma vesicles PinocytosisCoalesce to form vesicular channels

32. BLOOD FLOW IN CAPILLARIESNot continuous but intermittentTurning on and off every few secondsDue to vasomotion( )Intermittent contraction of metarteriole and precapillary sphincterBut blood flow to any tissue is not discontinuous Large number of capillaries in each tissueSome are closed and others open at any given timeTherefore capillary function gets averaged outAverage of billions of capillaries each operating intermitently in response to local tissue conditions Average rate of blood flow, Average blood pressure and Average Exchange rate in each tissue

33. EXCHANGE THROUGH CAPILLARY WALL Water and other dissolved molecules diffuse back and forthResults in continuous mixing of plasma and ISFRate of transfer of Lipid soluble substances several times more Oxygen & Carbon dioxide most importantThrough pores water , sodium and glucose also move rapidlysmall size and great velocity of thermal molecular motionEx: Velocity of water molecules 80X to the velocity of plasma flowwater of plasma is exchanged 80 times with the water of ISF before blood moves from arterial to venous end of a capillaryPore size is another factor that determines exchange rateNormal size is 7nm 20X to the size of water moleculeIf water permeability is considered to be 1, Permeability of Nacl = 0.96; Glucoes = 0.60; Albumin = 0.001Permeability characters differ from tissue to tissueEx: capillary membrane in liver highly permeable to proteins alsoGlomerular membrane in kidney permeable to water and electrolytes 500X than in muscle

34. EXCHANGE THROUGH CAPILLARY WALL Net rate of diffusion ∞ Concentration gradient x permeabilityCapillary membrane permeability to nutritionally important substances is very highSlight concentration gradient cause net diffusion of large quantities

35. INTERSTITIUM AND INTERSTITIAL FLUID1/6th of body is space between cellsCalled interstitiumFluid in interstitium is interstitial fluid (ISF)Filtered from capillariesComposition similar to plasmaBut lower protein concentrationSolid structures in interstitiumCollagen fiber bundlesProteoglycan filamentsISF trapped among proteoglycans has gel charactersTissue gelIt cannot flow but diffusesDiffusion is 95% as rapid as fluid flowSmall quantity of ISF (1%) also flows as free f fluidFree fluid portion increases in case of edemaShort distance of any tissue cell to a capillary (20mm)Allows rapid exchange

36. DISTRIBUTION OF FLUID BETWEEN PLASMA AND INTERSTITIAL FLUIDFluid flow from capillaries into ISF or in the opposite direction Determined by four primary forces Called starlings forcesCapillary pressure – blood pressure in the capillarymoves fluid out of the capillary Interstitial fluid pressure Forces fluid into capillaryPlasma colloid osmotic pressureRetains fluid in the capillaryISF colloid osmotic pressureRetains fluid in the initerstitiumBPISF PISF PCOPCOPCOP

37. Art.EndVen.EndBP:30mmHgBP:10mmHgBP:17mmHgISF Pressure: -3mm HgISF Pressure: -3mm HgCOP: 28mm HgCOP: 8mm HgISF Pressure: -3mm HgISF Pressure: -3mm HgCOP: 8mm Hg Negative ISF pressure is due to pumping of fluid out by the lymphatics COP of plasma and ISF is due to Proteins Considerable amounts of proteins leak into ISF from capillaries Absolute quantity of proteins in ISF > in Plasma But Volume of ISF is 4X to Plasma volume Therefore concentration of proteins in ISF < in Plasma COP of plasma, ISF and negative ISF pressure remain same at the venous endSTARLINGS FORCESCOP: 28mm HgCOP: 8mm HgCOP: 8mm Hg

38. Art.EndVen.EndBP:30mmHgBP:10mmHgBP:17mmHgISF Pressure: -3mm HgISF Pressure: -3mm HgCOP: 28mm HgCOP: 8mm HgISF Pressure: -3mm HgISF Pressure: -3mm HgCOP: 8mm HgCOP: 28mm HgCOP: 8mm HgCOP: 8mm HgForces that move fluid Out of the CapillaryCapillary pressure: 30 mm HgISF Pressure (-ve): 03 mm HgCOP of ISF: 08 mm HgTotal: 41 mm Hg Forces that move fluid into the CapillaryCOP of Plasma: 28 mm HgNet Filtration Pressure41-28 = 13 mm HgCapillary pressure: 10 mm HgISF Pressure (-ve): 03 mm HgCOP of ISF: 08 mm HgTotal: 21 mm HgCOP of Plasma: 28 mm Hg21-28 = -07 mm HgNet Reabsorption PressureArterial EndVenous EndReabsorption pressure < filtration pressureVenous ends of capillaries are more permeable90% fluid filtered at arterial end gets reabsorbed at the venous endRemaining absorbed through lymphatics

39. NET FLUID FILTRATION IN THE CAPILLARIESState of near equilibrium exists at the capillary membrane Amount fluid filtered out = amount of fluid reabsorbedMean forces tending to move fluid out of capillariesMean capillary pressure 17.3mm HgISF Pressure (-Ve) 03.0mm HgCOP of ISF 08mm HgTotal 28.3mm HgMean forces tending to move fluid into capillariesCOP of Plasma 28.0 mm HgNet filtration Pressure 28.3 – 28.0 = 0.3mm HgSlight imbalance existsCompensated by reabsorption into lymphatics Net rate of filtration through out body = 2ml/minNet filtration pressure = 0.3mm HgHow much is the filtration for each mm Hg of net filtration pressure?6.67ml/minFiltration coefficientIf filtration forces increase then edema occursIf reabsorption forces increase it leads to dehydration

40. THE LYMPHATIC SYSTEMLymphatics drain excess fluid from interstitiumAll tissues except the following have lymphatic channelsSuperficial skin, CNS, Endomysium of muscles, bonesPrelymphatics in the tissues without lymphatics connect to lymphaticsLymph is formed from ISFComposition same as ISFProtein conc. In lymph: 2G/dlIn liver lymph protein conc. : 6G/dl

41. LYMPH CAPILLARIESThin walled like blood capillariesAnchoring elementsAttach endothelial cells to surrounding tissuesOverlapping of adjacent endothelial cells Flap valve that opens only into the capillary ISF can push these valves openLarger lymphatics also have one way valves similar to venous valvesSmooth muscles in the walls of lymph capillaries

42. LYMPH PUMPIntrinsic contraction of lymph vessels Accumulation of fluid in lymph vesselStretching of wallsReflex contraction of smooth musclesIntra vessel pressure increasesOpens the valves Successive segments operate IndependentlyIntra vessel pressure upto 50mm HgExtrinsic contraction of lymph vesselsContraction of musclesMovement of body partsArterial pulsationsCompression of tissue by objects outside bodyExercise increases lymph flow 10-30XRest reduces lymph flow

43. RATE OF LYMPH FLOWDetermined mainly byInterstitial fluid pressureLymph flow increases with ISF pressureAs the –ve , ISF pressure increases above zero, lymph flow increases 20XAny factor that increases ISF pressure also increases the lymph flowElevation of capillary pressureDecreased plasma COPIncreased conc. Of protein in ISFIncreased permeability of capillariesIncrease in ISF pressure >2-3 mm HgNo further increase in lymph flow bec. Large lymph vessels collapseDegree of activity of lymph pump

44. FUNCTIONS OF LYMPHAccessory route for flow of fluids from ISF into circulationRemoves proteins from ISF into circulationBlood capillaries cannot reabsorb proteinsIf proteins are not removed from ISF an animal would die within 24hRegulates ISF volume, conc. & pressureRemove bacteria from tissues and carry them to lymph glands for destructionResponsible for negative ISF pressure-ve pressure holds tissue cells togetherMajor route of absorption in the GIT

45. LOCAL CONTROL OF BLOOD FLOW BY TISSUESEach tissue controls its own blood flow as neededTherefore blood flow varies with tissue needsGreater is the metabolism greater is the blood flowEx: muscles receive 15% of COP (4ml/min/100G) at restMuscles constitute 40% of body weightBrain receives 14% COP (50ml/min/100G)In some tissue s blood flow requirements not related to their own metabolismEx: Kidneys receive 22% COP (360ml/min/100G) skin receives a large portion of COP in hot environment

46. LOCAL BLOOD FLOW CONTROLAcute controlOccurs within seconds/minutesrapid changes in constriction of arterioles, metarterioles and precapillary sphinctersAppropriate blood flow to meet immediate tissue needs Long-term controlSlow changes in blood flow over days/weeks/monthsIncrease/decrease in size and number of blood vessels

47. ACUTE CONTROL OF LOCAL BLOOD FLOWRate of MetabolismRate of Blood FlowArterial Oxygen saturation (%)Rate of Blood Flow1x2x3x4x123456781x2x3x4x1oo755025HOW THESE CHANGES IN BLOOD FLOW ARE AFFECTED?

48. BLOOD FLOW REGULATION THEORIESVasodilator TheoryOxygen Demand Theory

49. BLOOD FLOW REGULATION THEORIESVasodilator TheoryDecreased / lack of oxygen supply to tissuesIncrease in metabolism, decrease in blood flow, decrease in availability of oxygen and other nutrientsRelease of vasodilator substancesAdenosineCO2Lactic acidAdenosine phosphate compounds Histamine Potassium and hydrogen ionsDiffuse back to arterioles, metarterioles and precapillary sphinctersCause relaxation / dilatation of blood vesselsNo single vasodilator is produced in sufficient quantitiesMust be combined effect of several vasodilators

50. BLOOD FLOW REGULATION THEORIESOxygen Demand TheoryAlso known as “Nutrient Demand Theory”Oxygen, glucose, amino acids, vitamins (B-complex)[B1,B2,Niacin]Needed for maintenance of sufficient vascular muscle contractionDeficiency causes vasodilatationTissue UnitMetarteriole, single capillary & surrounding tissuePrecapillary sphincters are completely closed / open - VasomotionEach minute precapillary sphincters open/close cyclically several timesOpen phase ∞ tissue needs for nutrientsNumber of open precapillary sphnicters ∞ tissue needs for nutrientsHigh tissue oxygen and nutrient levelsPrecapillary sphincters closed till they are utilizedLow tissue oxygen and nutrient levelsPrecapillary sphincters kept opened till tissue levels restored

51. BLOOD FLOW REGULATION THEORIESOxygen demand or vasodilator theories alone can explain blood flow regulationBut in life it is a combination of both Special instances of local blood flow controlActive hyperemiaIncrease in blood flow when a tissue becomes highly activeIncrease may be up to 20XExplained by the two theories discussedEx: muscular exerciseReactive hyperemiaIncrease in blood flow after temporary blockade of blood flowManifestation of metabolic blood flow regulation

52. AUTOREGULATION OF BLOOD FLOW WITH ARTERIAL PRESSURE CHANGESAcute increase / decrease in arterial pressureCauses changes in blood flow to tissuesBut within a minute blood flow is brought back to normal levelsSuch regulation is called “autoregulation”Two theoriesMetabolic theoryMyogenic theory

53. AUTOREGULATION OF BLOOD FLOW WITH ARTERIAL PRESSURE CHANGESMetabolic theoryExplained by of local blood flow controlWhen increase in AP increases blood flowTissues get excess of oxygen and nutrientsCauses vasoconstrictionRestores blood flow back to normal although arterial pressure continues to be high

54. AUTOREGULATION OF BLOOD FLOW WITH ARTERIAL PRESSURE CHANGESMYOGENIC THEORYBased on a principle Sudden stretch of smooth muscles causes reflex contractionIncreased AP stretchs smooth muscles in the vessel wallsCauses reflex contraction and vasoconstriction & Reduces blood flowReduced AP leads to reduced stretch on vessl wallsVessels relaxNot routinely used mechanismImportant in protecting small vessels &capillariesSmall vessels & capillaries have thin wallsHigh AP if passed on to them could break themProtected by shut down through vasoconstrictionMay cause death if extensively usedIf increased AP causes vasoconstriction through out the bodyThis will further increase AP which in turn increases vasoconstrictionThis will loop into a vicious cycle till death occurs

55. SECONDARY DILATATION OF LARGE ARTERIESLocal blood flow control mechanisms dilate vessels located in tissues onlyBut when blood flow through microcirculation increases2ndary dilatation of large arteries upstream occursEndothelia derived relaxing factor (EDRF)Synthesized by endothelium of small vesselsIn response to shear of rapid blood flow2ndary dilatation important in maintaining tissue blood flow

56. MECHANISMS FOR BLOOD FLOW CONTROL IN SPECIAL TISSUESIn addition to local flow control mechanismsSpecial mechanisms in kidney, brain and skinKidneyTubulo-glomerular feed backBrainDecrease in oxygen acts as explainedIncreased CO2 and / or H+ also stimulate blood flow controlImportant because brain function depends on CO2 and H+ ion concentrationsSkinBlood flow increases in hot environments to dissipate heat

57. LONG TERM BLOOD FLOW REGULATIONAcute blood flow regulation acts within seconds to minutesBut adjust blood only to 75% of exact requirementsEx: AP increased from 100 to 150 mm HgBlood flow increased by 100% instantaneouslyBrought back to ~ 15% above normal by acute controlTherefore acute control is rapid BUT INCOMPLETELong term control regulates the blood flow to exact levelsIf the AP remains at 150 mm Hg for days/weeksLong term regulation brings back blood flow to exactly normal

58. 2001501005002.52.01.51.00.5ARTERIAL PRESSUREBlood Flow (x normal)AcuteLongtermLONG TERM VS ACUTE CONTROL OF BLOOD FLOW WITH CHANGES IN ARTERIAL PRESSURE

59. Mechanism of long term blood flow regulationChanges in tissue vascularityChange in the number and size of blood vesselsEx: If the AP decreases the number and size of blood vessels increasesIf the AP increases the opposite takes placeSimilarly chronic changes in tissues (hypertrophy) would bring similar changes in vascularityReconstruction of tissue vasculature to meet needsRapid reconstruction in young and growing tissuesSlow reconstruction in old and established tissuesLong term regulation in young tissues (/animals) meets tissue needs perfectlyBut in old tissues (/animals) lags behind

60. FACTORS INFLUENCING TISSUE VASCULARITYAvailability of oxygen appears to be criticalHigh tissue vascularity in animals at high altitudesLow partial pressure of oxygen at high altitudesHigh tissue vascularity in chicken hatched in low oxygen environmentAngiogenic factors Released fromIschemic tissuesRapidly growing tissuesTissues with excessively high metabolic rate> 12 angiogenic factors identifiedMost important three ECGF –Endothelial cell growth factorFGF – fibroblast growth factorAngiogeninAnti angiogenic factorsCause dissolution of vascular cells and disappearance of vesslesMost important anti angiogenic factors – glucocorticoidsAppropriate interplay between angiogenic and anti angiogenic factors To regulate blood flow on long term basis

61. DEVELOPMENT OF COLLATERAL CIRCULATIONWhen an artery / vein is blockedDilatation of any vascular loops that already exist during first few minutesRepresents metabolic relaxationMeets tissue requirements to the extent of 25% onlyAdditional channels open during next 24h to meet 50% needsWithin a few days 100% tissue needs may be satisfiedGrowth of collateral vesselsContinuous for weeks/months after fully opening existing loopsSmall multiple channels formedSufficient blood flow at restNot sufficient during exerciseBy age 60 at least one coronary artery is blocked in man Not detected because of collateral circulation Heart attacks occur ifRapid block developmentNot compensated by collaterals

62. FICK’S PRINCIPLEBLOOD FLOW IS PROPRTIONAL TO THE DIFFERENCE IN CONCENTRATION OF SUBSTANCE BETWEEN THE BLOOD ENTERING AND LEAVING AN ORGANCommonly used to measure COP

63. BLOODACC.ROUTENot bloodRate knownBLOODRate of entry = Rate of blood flow X blood conc. (I) + Acc. input Rate of exit = Rate of blood flow X Blood conc. (O)If the amount in the compartment is not changing Rate of entry = Rate of exitRate of blood Flow X I + Acc.input = Rate of blood Flow X OAcc.input = Rate of blood Flow X O – Rate of blood Flow X I = Rate of blood Flow (O – I)Acc.input = Rate of blood Flow O – I 2700.20 – 0.15LUNGSOXYGEN INSPIRED / MIN = 270mlOXYGEN IN PUL.ARTERIES= 0.15ml/mlOXYGEN IN PUL.VEINS= 0.20ml/ml= 5400ml/minRate of blood flow through lungsRate of blood flow through lungs = COP

64. HUMORAL REGULATION OF CIRCULATIONBy substances secreted /absorbed into body fluidsEx:HormonesDivided intoVasoconstrictorsNorepinephrineAngiotensinVasopressinCalcium ionsVasodilatorsBradykininSerotoninHistaminProstaglandinsCarbon dioxideIons : K, Mg, Na, H, Acetate, Citrate

65. VASOCONSTRICTORSNorepinephrine is a powerful vasoconstrictorReleased due to sympathetic stimulation during exerciseExcites heart, veins and arteriolesEpinephrine is less powerful vasoconstrictorCauses mild dilatation of coronary vessels AngiotensinOne of the most powerful vasoconstrictorInduces overall vasoconstriction Increases peripheral resistance & blood pressureImportant in blood pressure regulationVasopressin (ADH)Synthesized in hypothalamus – SON (supra optic nucleus)Most powerful vasoconstrictor in the bodyBut quantitatively not significant bec. Small amounts releasedCalcium ionsVasoconstriction by contracting smooth muscles in the vessel walls

66. VASODILATORSBradykininFormed from a-2macroglobulin in circulationPowerful arteriolar dilatation Increased capillary permeabilityRegulates blood flow and capillary permeability in inflamed tissuesSerotonin (5-OH tryptamine)High conc. In platelets, chromaffin tissue of intestine and other abdominal structuresDilatation/constriction depending on conditions/areaBut its effects on general circulation are limitedNot an important regulator of blood flow normallyHistamineReleased by every tissue in the body when damaged / exposed to allergensMostly derived from basophils and mast cellsPowerful dilatation of arteriolesIncreases capillary porocityLeads to leakage of fluids and proteins into tissuesResults in edema

67. VASODILATORSProstaglandinsProduced by all tissues in the bodySome are vasoconstrictors but most others are dilatorsImportant in control of local vascular areasMay not be important in general regulation of blood flowPotassium and magnesium ionsIncrease leads to vasodilatationSodium ionsIncrease leads to mild arteriolar dilatation due to osmolar effectsAny substance which increases ECF osmolality causes vasodilationAcetate and citrate induce vasodilatationHydrogen ionsIncrease causes dilatation of arteriolesDecrease causes mild constrictionBut excessive decrease again causes vasodilatationCarbon dioxideIncreases causes moderate vasodilatation in most tissuesintense vasodilatation in brainCO2 acting on vasomotor centers causes intense vasodilatation through sympathetic system

68. NERVOUS REGULATION OF CIRCULATIONIn addition to local blood flow regulationDoes not adjust blood flow tissue by tissueBrings about global changesRedistribution of blood flow to different areasIncreasing the pumping by heartVery rapid control of blood pressureEffects implemented through ANSSympathetic system - regulation of circulationParasympathetic system - regulation of heart

69. SYMPATHETIC REGULATION OF CIRCULATIONMost sympathetic fibers are vasoconstrictorSmall number of vasodilator fibersSympathetic fibers to blood vessels innervateAll vessels except capillaries, precapillary sphincters and most metarteriolesInnervation of arteries and arteriole allows to increase resistance and there by blood flowSympatheitc innervation of large vessels especially veins could change the volume of these vesselsThus it changes the volume of peripheral circulationCould cause translocation of blood Therefore plays a major role in regulation of CVS functionSympathetic Vasoconstrictor distribution is powerful inKidneyGutSpleenSkin

70. VASOMOTOR CENTERSBilateral in medulla & lower ponsControl blood vessels via SC sympathetic fibersArea C1 /vasoconstrictor areaSecrete norepinephrineExcite neurons of sympathetic system in SCVasoconstrictor fibers of SC also secrete norepinephrineSo norepinephrine is the vasoconstrictor Stimulate adrenal medulla to secrete epi & norepResponsible for sympathetic vasoconstrictor toneArea A1/Vasodilator areaInhibit area C1 to cause vasodilatationSensory area/Area A2Sensory siganls from vagus and GP nervesOutput regulates C1 & A1 areasReflex control of circulatory functionsControl of Heart by vasomotor centersVia sympathetic and vagus fibersIncrease in vasoconstrictor activity increases heart rateDecrease in vasoconstrictor activity decreases heart rate

71. CONTROL OF VASOMOTOR CENTERReticular formation pons, mid brain and cortexExcite / inhibitLateral & superior RF exciteMedial & Inferior RF inhibitHypothalamus powerful control

72. CONTROL OF ARTERIAL PRESSURE BY NERVOUS SYSTEMMost rapid of all control systems for APSympathetic vasoconstriction & cardiac acceleration act as oneSimultaneous reciprocal inhibition of PSS signals to heartThese activities lead to1. Constriction of almost all arteriolesIncreases peripheral resistanceIncreases arterial pressure2. Venoconstriction dislocates blood towards heartVR to heart increasedCOP increasedSo AP increased3. Stimulation of heartEnhanced cardiac pumpingIncreases APThese activities increase AP 2X within 5-15 secondsSudden decrease in the above activities decreases AP by half in 5-15 seconds

73. INCREASE IN ARTERIAL PRESSURE DURING EXERCISE AND STRESSDuring exercise muscles need more oxygen & nutrients1. Partly met by local vasodilatation2. Additional increase in blood supply results from increased APHeavy exercise AP increases by 30-40%Increase blood flow to muscles by 2xExercise is initiated by stimulation of motor areas of brainSimultaneous stimulation of vasoconstrictor and cardiac accelerator areas in brain stem increases AP3. Exercising muscles compress veins and translocate blood to heartIncreases VR to heartLeads to increased COP and APAny stress mainly acts via the vasoconstrictor and cardiac accelrator areas

74. REFLEX MECHANISMS FOR MAINTENANCE OF ARTERIAL PRESSUREIn addition to exercise and stress Several negative feed back mechanism maintain normal APBaroreceptor reflexChemoreceptor reflexAtrial and Pulmonary artery reflexVolume reflexBain-Bridge reflexAbdominal compression reflexCNS Ischemic responseRespiratory waves in arterial pressureVasomotor waves in arterial pressure

75. BARORECEPTOR REFLEXBest known mechanism for maintenance of APInitiated by stretch sensitive receptorsCalled baro /presso receptorsPresent in the walls of every large arteriesBut more in carotid sinus & walls of aortic archCarotid sinus receptorsNot stimulated by AP between 0-60 mm HgAP>60mm Hg stimulates them progressively highlyReach max response at 180mm Hg of APAortic arch receptors operate similarly but within a range of 90-210 mm Hg of APTogether the whole normal range of AP is coveredRespond better to changing pressure rather than constant pressureRespond better if the pressure is rising than fallingSignals increase during systole & decrease during diastole

76. Increased Arterial PressureBaroreceptors in Aortic ArchBaroreceptors in Carotid SinusNUCLEUS TRACTUS SOLITARIUS IN MEDULLAVagus NerveGlossopharyngealINHIBITION OF VASOCONSTRICTOR AREA & EXCITATION OF VASODILATOR AREA IN AVASOMOTOR CENTERDilatation of veins & arteriolesDecreased rate & strength of cardiac contractionNORMAL ARTERIAL PRESSURE

77. Significance of baroreceptor systemMaintain normal AP independent of postureOpposes increase/decrease in normal APCalled pressure buffer system & buffer nervesExtreme variability in AP in the absence BRSExtremely important for day to day maintenance of APLittle value for long term regulation of APIf the increase/decrease in AP persists for >2 days baroreceptors would adapt to new level of AP0200100

78. CHEMORECEPTOR REFLEXChemoreceptors are sensitive to Decrease in oxygenIncrease in carbon dioxide and / or Hydrogen ionsLocated in carotid and aortic bodies adjacent to aortaExcite fibers in Herrings nerve and vagus Connect to vasomotor center

79. Fall in arterial PressureDecreased blood flow through carotid & aortic bodiesDecreased oxygen and increased Co2 & Hydrogen at chemoreceptorsExcitation of chemoreceptorsVASOMOTOR CENTERExcitation of Vasoconstrictor area and inhibition of vasodilator area & increased heart rate and forceAP restored to normal levelsNot as powerful as baroreceptor reflexStimulated only when AP falls below 80mm HgImportant in preventing fall of AP belwo 80 mm Hg

80. ATRIAL AND PULMONARY ARTERY REFLEXLow pressure receptors in walls of both the atria and pulmonary artery stretch receptors Minimize changes in AP as the blood volume changesEx: 300 ml of blood transfused into a normal dog AP increased by 15 mm HgIf baroreceptors are removed AP increases by 50mm HgIf low pressure receptors are also removed AP increases by 120mm Hg Cannot detect changes in systemic APDetect changes in pressure in low pressure areas of circulationAs induced by changes in blood volumeCauses reflex peripheral vasodilatation to reduce the AP

81. Volume Reflex / Atrial Reflex to KidneyActivation of Atrial stretch receptorsReduced ADH releaseDilatation of afferent arterioles in kidneyIncreased GFRDecreased renal fluid reabsorptionIncreased Urine outputDecreased blood volumeAP Restored to normalIncreased APIncreased blood volume

82. BAINBRIDGE REFLEX(Atrial Reflex Control of Heart Rate)Increased Atrial PressureIncreased Heart RateStretching of SA nodeIncreased pulse frequencyVASOMOTOR CENTERAtrial stretch receptorsVagusVagus & SympatheticPrevents damning of blood in veins atria & Pulmonary circulation

83. ABDOMINAL COMPRESSION REFLEXStimulation of Vasoconstrictor systemBaroreceptor reflexChemoreceptor reflexOther factorsVASOMOTOR CENTERSpinal nervesIncreased tone of sk.muscles esp. in the abdomenCompression of abd. Venous reservoirsTranslocation of blood towards HeartIncreased COPIncreased AP

84. CNS ISCHEMIC RESPONSEWhen AP falls below 60mm HgNutritional deficiency to vasomotor centersincreased CO2 concentration at VMCCNS ischemic response becomes operationalMost powerful sympathetic vasoconstriction AP increases to as high as 250mm Hg for 10minRenal blood flow & Urine formation completely stoppedNot a normal AP regulator but an emergency mechanismBut beyond 10min this reflex fails and AP falls Cushing’s reactionWhen CSF pressure becomes equal to APCerebral arteries are compressedBrain suffers ischemiaCNS ischemic response increases AP to restore blood supply to brain

85. RESPIRATORY WAVES IN ARTERIAL PRESSUREIn each cycle of respiration AP rises and falls by 4-6mm HgPressure increases during early expirationBut falls during the remaining parts of the cycleCaused by1. Spill over of signals from respiratory center to VMC2. Inspiration reduces intrathoracic pressureLeads to reduction in return of blood to left side of heartCauses temporary decrease in COP and therefore AP3. Intrathoracic pressure changes influence vascular and atrial stretch receptors

86. VASOMOTOR WAVES IN ARTERIAL PRESSUREIn addition to respiratory waves Fluctuations of AP by 20-40 mm HgSlower waves than respiratory wavesLast for upto 26 seconds in dogsAlso called Mayer wavesOscillation of pressure control mechanismsBaroreceptor reflexChemoreceptor reflexCNS ischemic response

87. LONGTERM CONTROL OF BLOOD PRESSURE BY KIDNEYSNervous regulation of APRapid , powerful but short termWhen AP changes slowly over several days/weeksNervous system cannot controlBut kidneys exercise a dominant regulationTwo renal mechanismsRenal body fluid systemRenin-angiotensin system

88. RENAL REGULATION OF APRenal Body Fluid SystemIncrease in ECF volume raises APBut increase in AP increases GFR & UOP to restore APIncrease in AP by only a few mm Hg doubleswater loss (pressure diuresis ) & salt loss (pressure natriuresis )Pressure diuresis and natriuresis continue till AP is restoredIf AP falls water & salt loss in urine reduced till AP is restoredRenal body fluid system restores AP exactly to normal infinite gain systemAP = COP X TPRLongterm increase in TPR does not increase AP but reduces COPLongterm decrease in TPR does not decrease AP but increases COPSignificance of salt in regulation of APIf body salt content increases water content (ECF) also increasedIncreased salt content also increases ADH release which reduces urinary water loss

89. RENIN – ANGIOTENSIN SYSTEMDECREASED ARTERIAL PRESSUREARTERIAL PRESSURE RESTOREDReninFrom JG cell in kidneyAngiotensinogenAngiotensin IAngiotensin I IRenal retention of salt & waterVasoconstrictionACE from Lungs

90. SIGNIFICANCE OF RENIN ANGIOTENSIN SYSTEMVery powerful mechanismRegulates blood pressure in case of hemorrhageLife saving abilityTakes about 20 min to become fully operationalSlower than nervous reflex mechanisms

91. SUMMARY OF BLOOD PRESSURE REGULATIONMechanisms grouped intoRapidExclusively nervous reflexesCNS ischemic responseBaroreceptor reflexChemoreceptor reflexIntermediateRenin-Angiotensin systemStress relaxation of vasculatureShift of fluids in and out of circulation to adjust blood volumeLongterm Renal body fluid system

92. HYPERTENSIONWhen the MAP is above normalMAP raised by >50% short life expectancyLethal effects of hypertension Excessive work load on heartLeads to early heart failure, and / or CHDHeart attackFrequent rupture of major vessels in brainCerebral infarctParalysis, dementia, blindnessMultiple hemorrhages in kidneyRenal destruction and failure

93. REGULATION OF CARDIAC OUTPUTCardiac out put (COP): Vol. of blood pumped into aorta each min.This is the amount that flows through circulationVenous return (VR): Vol. of blood flowing into right atrium /minSum of all local blood flow regulatory mechanismsCOP must be equal to VRVR is the prime regulator of COPCOP regulation is sum of all local blood flow regulationAny factor that alters VR also alters COPVR is altered by factors outside of heartFactors in regulation of COPFrank-Starlings lawWithin physiological limits - up to 2.5 times to normal venous returnInfluence of stretching on SA node and HRBain-Bridge reflexTotal Peripheral ResistanceCOP = Arterial pressure ÷Total peripheral resistanceHyper affective heartHypertrophy & Extreme sympathetic stimulationHypo affective heart Pathological conditions

94. REGULATION OF BLOOD FLOW TO MUSCLE DURING EXERCISEStrenuous exercise is the most stressful condition to circulatory systemBlood flow to Sk. muscles could increase by 20XAt rest: 3-4ml/min/100GExercise: 50-80ml/min/100GSk. Muscles form 40% of body weightCOP needs to be increased 5-7XMechanisms to increase muscle blood flowOpening of capillaries0nly 25% of capillaries open at rest100% open during exerciseLocal blood flow regulatory mechanismsArteriolar vasodilatationDecreased oxygen, increased carbon dioxideRelease of vasodilators – adenosine, acetyl choline, potassium ions, lactic acidSympathetic innervation of musclesMass sympathetic dischargeMuscle reflex

95. REGULATION OF BLOOD FLOW TO MUSCLE DURING EXERCISESympathetic innervation of musclesMost species vasoconstrictor fibersDivert blood from muscles to other organsNorepinephrine excites symp. vasoconstrictor fibersEpinephrine causes vasodilatationCat sympathetic vasodilator fibersVasodilator fibers secrete acetylcholine

96. REGULATION OF BLOOD FLOW TO MUSCLE DURING EXERCISEMass sympathetic dischargeAt the beginning of exercise signals from voluntary motor centersto sk. muscles to contractto vasomotor centers to initiate sympathetic discharge andGreatly reduce parasympathetic signals to heart increased rate and force of cardiac contractionperipheral vasoconstriction except in the exercising muscles ( due to local control mechanisms)Contraction of capacitance vessels to increase VR to heart

97. REGULATION OF BLOOD FLOW TO MUSCLE DURING EXERCISEMuscle ReflexIn addition to sympathetic dischargeSensory input from exercising muscles into vasomotor centerLeads to additional sympathetic dischargeGreat increase in cardiac output due toStimulation of heartIncreased VR to heartPeripheral vasoconstriction and increased AP

98. CORONARY CIRCULATIONMain coronary arteries lie on the surface of the heartSmall vessels penetrate cardiac muscle5-100mm endocardial surface takes up nutrients directly from blood in LVRemaining cardiac muscle supplied by coronary circulation7-8ml/min/G = ~5% of COPPhasic Coronary blood flow follows cardiac cycleReduced blood flow during systoleIncreased blood flow during diastoleStrenuous exercise Work done by heart increases 6-8XCoronary blood flow increases 4XRegulation of coronary blood flowBy local tissue needsOxygen supply the most importantAutonomic regulation Acetyl choline (PSS)Norepinephrine (SS)Both cause coronary vasodilatation

99. CIRCULATORY SHOCKInsufficient blood flow to all tissues in the bodyTissues damage due to inadequate oxygen supplyEven CVS suffers for want of oxygenShock becomes progressive Significant decrease in COP causes shockMyocardial pathology – cardiogeneic shockDecreased VR to heartHemorrhageObstruction to venous return pathwayShock with normal / > normal COPExcessive metabolism of tissuesAbnormal tissue perfusion patternBlood is passing through non nutrient blood vesselsArterial Pressure in shockOften falls to half the normalBut not necessaryReduction is blood pressure is not an indication of shock

100. CLASSIFICATION OF SHOCKBased on the causeHypovolemic shockNeurogenic shockAnaphylactic shockSeptic shockEndotoxin shock

101. HYOPVOLEMIC SHOCKDue to decreased blood volumeHemorrhageLoss of 10% blood volume tolerated>10% lossDecreased COPFollowed by decreased APSympathetic stimulation of Baroreceptor, chemoreceptor and CNS ischemic responses Increase AP and tachy cardia (>200/min)Symp. Stimulation does not cause vasoconstriction in brain and coronary arteriesTherefore blood supply to these organs is maintained at normal levelsIntact operation of above blood loss of 35-40% toleratedIn the absence of the above reflexes blood loss of 20% lethalDecreased ECF volumeBurnsDehydrationIntestinal strangulation

102. OTHER TYPES OF SHOCKNeurogenic shockAnesthesiaBrain damageVasovagal syncope (emotional fainting)Anaphylactic shockAdministration of foreign proteinsVaccines, sera, antibiotics etc. Septic shockAlso called blood poisoningMost common form of shockWidely disseminated infection Accompanied by high fever unlike othersExtension of urinary tract infection into GIT

103. STAGES IN SHOCKThree stagesNon-progressive stageProgressive stageIrreversible stage

104. NON-PROGRESSIVE STAGEAlso called compensated stageFull recovery without external helpFunctional compensatory mechanismsBaroreceptor reflex, CNS ischemic response, reverse stress relaxation of vascular smooth muscles, ADH - increased renal reabsorption of water and salt Angiotensin – vasoconstriction to increase APabsorption of large volumes of fluid from GIT,and ISF increased thirst,

105. PROGRESSIVE SHOCKVicious cycle effects dominateDecrease in COP decrease in coronary circulationDecreased blood flow to vasomotor centersDecreased efficiency of vasomotor reflexesFormation of blood clots in small blood vessels due to accumulation of acid & end products of metabolismNot removed because blood flow is slowThese clots (thrombi) further reduce blood flow in the tissueBlood accumulates in the blood vessels – sludged bloodIncreased capillary permeabilityAfter several hours of hypoxiaShift of fluid from circulation to ISFFurther reduction in blood volumeToxins from hypoxic tissuesHistamine, serotonin, tissue enzymesFurther deteriorate circulationEndotoxinFrom dead gram negativee bacteriaExtensive vascular dilatation & increased cellular metabolismGeneralized cellular deteriorationIn liver especiallyDecreased activity of Na-K pump, mitochondrial activity, dissolution of lysosomesPulmonary edema, acidosis, coma and death

106. IRREVERSIBLE SHOCKAll known forms of therapy inadequate to save lifeTherapyReplacement of lost body fluidsAdminstration of sympathomimeticsProviding additional oxygen in the respiratory airAdminstration of glucocorticoids (anaphylactic shock)Adminstration of antibiotics (septic shock)

107. CIRCULATORY ARRESTSimilar to shockEncountered during surgeryDue to cardiac arrest / ventricular fibrillationToo little of oxygen provided along anesthetic gasTherapyRemoval of anesthetic and provide oxygenBut brain damage may have already occurred