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  • Capillary filtration coefficient: number & size of pores in each capillary + number of capillaries
  • *in response to the stretch, arteriolar vascular smooth muscle contracts, decreasing the arteriolar radius and returning wall tension back to normal. This relationship is explained by the law of Laplace, which states that T = P × r. If pressure (P) increases and radius (r) decreases, then wall tension (T) can remain constant. (Of course, the other consequence of the decreased radius, discussed previously, is increased arteriolar resistance; in the face of increased pressure, increased resistance allows blood flow to be maintained constant, i.e., autoregulation.)
  • Normally SNS is active…..baroR mechanism increases parasympathetic NS and ‘snubs’ SNS
  • Discharges (vertical lines) in a single afferent nerve fiber from the carotid sinus at various levels of mean arterial pressures, plotted against changes in aortic pressure with time.Baroreceptors are very sensitive to changes in pulse pressure as shown by the record of phasic aortic pressure.*esp at lower pressures….at higher pressures they seem to respond during both systolic and diastolic pressure phases
  • *The degree of sympathetic vasoconstriction caused by intense cerebral ischemia is often so greatthat some of the peripheral vessels become totally or almost totally occluded.
  • *discussed in detail later
  • * Nearly equal due to low compliance of pulmonary tree
  • Coupling of heart & circulation: corollary-1*Consider a situation in which the heart pumps blood at a constant flow of 100 mL/sec (6 L/min) into rigid arteries with a resistance of 16.6 peripheral resistance units (PRUs) for 4 seconds. This would then generate a constant pressure of 100 mm Hg, and cardiac work over the 4 seconds would be simply pressure (P) × volume (V) or 100 mm Hg × 400 mL = 40,000. If the heart pumped intermittently and ejected blood at 100 mL/sec into noncompliant arteries during the first half-second of the cycle only (i.e., 200 mL/sec for 0.5 seconds), pressure would rise to 200 mm Hg during each ejection and drop to 0 mm Hg during relaxation. Although no work would be done during relaxation, work done during the contraction would be 80,000. If this same intermittent flow was ejected into arteries with infinite compliance (flexibility), pressure would not rise during systole or fall during diastole and would remain at an average of 100 mm Hg. Work in this situation would then again equal 40,000. In reality, arteries are neither totally rigid nor infinitely compliant. **even if all other factors, such as arterial pressure, stroke volume, and heart rate, do not change. For this reason, the heart of an older person is confronted by increased oxygen demand from the simple fact that arterial compliance decreases with aging.
  • *CO Is Increased by an Increase in Venous Filling Pressure, but Venous Filling Pressure Is Decreased by an Increase in CO
  • Normal equilibrium point
  • *Changes in venous compliance produce effects similar to those produced by changes in blood volume. Decreases in venous compliance cause a shift of blood out of the unstressed volume and into the stressed volume and produce changes similar to those caused by increases in blood volume, a parallel shift to the right. Likewise, increases in venous compliance cause a shift of blood into the unstressed volume and out of the stressed volume and produce changes similar to those caused by decreased blood volume, a parallel shift to the left.
  • In applying this Fick procedure for measuring cardiac output in the human being, mixed venous blood is usually obtained through a catheter inserted up the brachial vein of the forearm, through the subclavian vein, down to the right atrium, and, finally, into the right ventricle or pulmonary artery. And systemic arterial blood can then be obtained from any systemic artery in the body. The rate of oxygen absorption by the lungs is measured by the rate of disappearance of oxygen from the respired air, using any type of oxygen meter.
  • This is why angina pectoris due to deficient delivery of O2 to the myocardium is more common in aortic stenosis than in aortic insufficiency
  • Difference between loading-induced enhanced contraction Vs contractibility (inotropism)!
  • circulation2

    1. 1.
    2. 2. Veins<br />Reservoir function<br />60% blood in veins<br />Specific reservoirs in spleen, liver, skin, lungs and heart!<br />Effect of gravity<br />Venous pump<br />Valves (varicose veins)<br />Abdominal pump<br />Thorax pump<br />Central venous pressure (CVP) – Right Atrial Pressure<br />Ability of the heart to pump<br />Venous return<br />Values: normal is 0 mmHg<br />Increased (straining, heart failure, massive transfusion)<br />Decreased (extraordinary heart contractions, haemorrhage)<br />
    3. 3. Veins<br />Measuring CVP<br />Noninvasive:<br />Height to which external jugular veins are distended when the subject lies in recumbent position<br />Vertical distance b/w rt. atrium and the place the vein collapses (the place where the pressure =0) =venous pressure (in mm of Hg)<br />Invasive:<br />Inserting a catheter into the thoracic great veins<br />Direct pressure reading<br />
    4. 4. Microcirculation<br />Capillaries <br />Arterial end<br />Venous end<br />Filtration across capillaries: Starling Forces<br />Capillary pressure (Pc)<br />Interstitial fluid pressure (Pif)<br />Plasma colloid osmotic pressure (πp)<br />Interstitial colloid osmotic pressure (πif)<br />NFP = Pc – Pif – πp + πif<br />Filtration = NFP x Kf<br />Where, Kf is Capillary filtration coefficient<br />
    5. 5. Starling’s Forces<br />
    6. 6. Edema<br />Accumulation of interstitial fluid in abnormally large amounts<br />Causes:<br />Increased filtration pressure    <br />Arteriolar dilation<br />Venular constriction  <br />Increased venous pressure (heart failure, incompetent valves, venous obstruction, increased total ECF volume, effect of gravity, etc)<br />Decreased osmotic pressure gradient across capillary    <br />Decreased plasma protein level <br />Severe liver failure, Protein malnutrition, Nephrotic syndrome  <br /> Accumulation of osmotically active substances in interstitial space<br />
    7. 7. Edema<br />Increased capillary permeability    <br />Substance P  <br />Histamine and related substances   <br />Kinins, etc<br />Inadequate lymph flow (lymphedema)<br />Elephantiasis (In filariasis, parasitic worms migrate into lymphatics & obstruct them)<br />
    8. 8. Lymphatics<br />Normal 24-h lymph flow is 2 - 4 L<br />Lymphatic vessels divided into 2 types:<br />Initial lymphatics<br />Lack valves <br />Lack smooth muscle<br />Found in regions such as intestine or skeletal muscle<br />Fluid enters thru loose junctions<br />Drain into collecting lymphatics<br />Collecting lymphatics<br />
    9. 9. Lymphatics<br />Return of filtered proteins<br />Very important fn<br />amount of protein returned in 1 day = 25–50% of the total circulating plasma protein<br />Transport of absorbed long-chain fatty acids and cholesterol from the intestine<br />
    10. 10. Local Control of Blood Flow<br />Why control blood flow?<br />Blood flow is variable between one organ and another, <br />Depends on overall demands of each organ system<br />These inter-organ differences in blood flow are the result of differences in vascular resistance<br />
    11. 11. Local Control of Blood Flow:Mechanisms<br />Local:<br />Matching blood flow to metabolic needs<br />Exerted through direct action of local metabolites on arteriolar resistance<br />Acute: rapid changes in local vasoconstriction/ dilation of arterioles, metarterioles, precap-sphincters<br />Long-term: slow, controlled (days, weeks & months) – increase in physical size, number<br />Nervous / Hormonal:<br />SNS<br />Histamine, bradykinin, & prostaglandins<br />
    12. 12. Acute Mechanisms<br />Autoregulation<br />Reactive hyperemia<br />Active hyperemia<br />
    13. 13. Acute Mechanisms:Autoregulation<br />Maintenance of constant blood flow to an organ in the face of changing arterial pressure<br />Kidneys, brain, heart, & skeletal muscle + others exhibit autoregulation<br />
    14. 14. Acute Mechanisms:Active hyperemia<br />Blood flow to an organ is proportional to its metabolic activity<br />Example:<br />Metabolic activity in skeletal muscle increases as a result of strenuous exercise<br />Blood flow to muscle will increase proportionately to meet the increased metabolic demand<br />
    15. 15. Acute Mechanisms:Reactive hyperemia<br />Increase in blood flow in response to or reacting to a prior period of decreased blood flow<br />Example:<br />Arterial occlusion to an organ occurs<br />During the occlusion, an O2 debt is accumulated<br />Longer the period of occlusion, the greater the O2 debt <br />Greater the subsequent increase in blood flow above the preocclusion levels. <br />The increase in blood flow continues until the O2 debt is "repaid."<br />
    16. 16. Explanation <br />Myogenic hypothesis<br />Explains autoregulation<br />Not active or reactive hyperemia<br />If arterial pressure - suddenly increased - arterioles are stretched - vascular smooth muscle - contracts in response to this stretch*<br />Metabolic hypothesis<br />O2 demand theory<br />Vasodilator theory<br />CO2, H+, K+ lactate, and adenosine<br />
    17. 17. Long-term Mechanisms for Blood Flow Control<br />Vascularity changed – acc. to metabolic profile <br />Role of oxygen<br />Role of vascular endothelial growth factors<br />VEGF<br />Fibroblast growth factor<br />Angiogenin<br />Vascularity is determined by max. tissue need (not average)<br />Collateral circulation<br />
    18. 18. Humoral control of Blood Flow<br />Vasocontrictor agents (NE, epinephrine, Angiotensin-II)<br />Vasodilatory agents (bradykinin, histamine)<br />Ions & other agents<br />Increase in Ca++: vasoconstriction<br />Increase in K+: vasodilation<br />Increase in Mg++: powerful vasodialtion<br />Increase in H+: vasodilation<br />Acetate and citrate: vasodilation<br />Increase in CO2: vasodilation<br />
    20. 20. General<br />The ‘large water tower’ example<br />MAP is maintained – hence tissues can ‘tap into’ the general blood flow<br />CVS needs to maintain just MAP !<br />Nervous and hormonal factors play major roles<br />Timeline: <br />Acute<br />Intermediate<br />Long term<br />
    21. 21. CNS areas controlling BP<br />
    22. 22.
    23. 23.
    24. 24.
    25. 25.
    26. 26.
    27. 27. Baroreceptor Reflex<br />
    28. 28. Baroreceptor Features: Sensitivity<br />Carotid sinus baroR are not stimulated at all by pressures between 0 and 50 to 60 mm Hg<br />Above these levels, they respond rapidly and reach a maximum at ~180 mm Hg<br />Around 100 mmHg – very sensitive<br />Responses of the aortic baroR – similar<br />But they operate about 30 mm Hg higher<br />
    29. 29. Baroreceptor Features: Speed<br />Respond extremely rapidly to BP changes<br />Increases in the fraction of a second during each systole<br />Decreases again during diastole<br />BaroRs respond much more to rapidly changing pressure than to a stationary pressure<br />
    30. 30. Baroreceptor Features: Posture <br />Standing – BP in head and upper body falls <br />Marked reduction may cause cause loss of consciousness. <br />Normally, <br />Falling BP at the baroreceptors elicits – BaroR reflex<br />Resulting in strong sympathetic discharge <br />Maintenance of BP!<br />
    31. 31. Baroreceptor Features: Buffer Control<br />BaroR reflex is a pressure buffer system<br />
    32. 32. Baroreceptor Features: Accomodation<br />Role in long-term regulation of BP<br />‘Resets’ in 1-2 days to ‘new’ pressure<br />
    33. 33.
    34. 34. Baroreceptors are more sensitive to pulsatile pressure than to constant pressure*<br />Especially at lower pressures<br />
    35. 35. CNS Ischemic Response<br />Cerebral ischemia<br />Vasoconstrictor & cardioaccelerator neurons in the vasomotor center b/c strongly excited <br />Accumulating local concentration of CO2<br />Causes strong neuronal +++<br />This BP elevation in response to cerebral ischemia is known as the CNS ischemic response*<br />Emergency pressure control system only<br />Kicks in only when BP falls 60 mm Hg and below<br />Cushing’s reaction<br />
    36. 36. Intermediate Control Mechanisms<br />Fluid shift <br />Stress relaxation<br />Renin-angiotensin vasoconstrictor mechanism<br />Biogenic amines<br />Vasoconstrictors (Epinephrine via α1, Serotonin etc) <br />Vasodilators (Epinephrine via β2, Histamine, ANP etc)<br />
    37. 37. Long-term BP Control Mechanism<br />Pressure natriuresis<br />Pressure diuresis<br />Renin-Angiotensin-Aldosterone<br />
    38. 38. Long-term BP Control Mechanism<br />
    39. 39. Cardiac Output<br />Quantity of blood pumped into the aorta each minute by the left ventricle<br />Normal values: 5.6 L/min (males), 4.9 L/min (females)<br />Cardiac index: C.O./min/m2<br />Average: 3.2 L (@ rest)<br />Maximum value @ age 10 – then decreases <br />
    40. 40. Cardiac Output<br />
    41. 41. Cardiac Output<br />Mean circulatory filling pressure<br />
    42. 42. CO Regulation: Conceptual Overview<br />Cardiac <br />Heart rate <br />Contractibility <br />Coupling factors* <br />Preload<br />Afterload<br />Ancillary factors<br />All factors affecting venous return<br />
    43. 43. CO Regulation: DetailedCO = SV x HR<br />Stroke Volume<br />SV = EDV – ESV<br />= 120 – 50 = 70 ml<br />EDV<br />Preload (Myocardial fiber length)<br />Affected by VR<br />Filling time of diastole<br />Rapid HR – diastole time decreases – EDV decreases<br />Atrial contraction <br />Inadequate contraction affects EDV<br />Ventricular distensibility<br />if decreases – EDV decreases<br />ESV<br />Afterload (Aortic pressure – arterial BP)<br />Affects myocardial fiber shortening ability<br />Contractility <br />SNS (NE via β1)<br />Heart Rate<br />HR and SV are inversely proportional<br />ANS<br />
    44. 44. CO Regulation: Another angle<br />
    45. 45. Conditions affecting CO<br />No change<br />Sleep<br />Moderate changes in temperature<br />Increased <br />Anxiety/Excitement<br />Exercise<br />Increased temperature<br />Pregnancy<br />Epinephrine/histamine<br />Anemia & hyperthyroidism<br />Decreased <br />Sitting/standing<br />Rapid arrhythmias<br />Heart disease<br />
    46. 46. Mean Circulatory Filling Pressure<br />With heart stopped – after pressure equilibrates – pressure throughout CVS – MCFP<br />MSFP Vs MCFP*<br />Factors affecting:<br />BV (more raises MCFP)<br />Sympathetic +++ (raises MCFP)<br />Directly proportional to VR<br />
    47. 47. Venous Return<br />VR = MSFP* – Rt. Atrial Pressure / Resistance in venous return<br />VR = 7 – 0/1.4 = 5 litres<br />VR is affected by:<br />Blood volume<br />Skeletal muscle contraction<br />Venous valves<br />Thoracoabdominal pump<br />Myocardial contractibility<br />
    48. 48. Coupling of Cardiac & Vascular Function<br />Characteristics of arteries and veins (vascular compliance, BV & vascular resistance) <br />affect heart fn & its other variables <br />However, it is also true that performance of the heart influences volumes and pressures within the vasculature<br />So vasculature affects heart & vice versa<br />Equilibrium must exist between cardiac and vascular function<br />
    49. 49. Changes in Arterial Compliance Change Cardiac Work<br />One of the more important consequences of the elastic nature of large arteries is that it reduces cardiac work*<br />Increased arterial compliance (increase in arterial elasticity / afterload reduction) <br />Reduces cardiac work <br />Decreased compliance <br />Increases cardiac work<br />Myocardial O2 demand will be increased by any factor that reduces arterial compliance**<br />
    50. 50. Relationship b/w Venous filling P. & CO : Tricky!*<br />CVP - key determinant of filling of the right heart - key determinant of cardiac output <br />Starling's Law<br />However!<br />Increased cardiac output into the arterial segment should result in ‘depletion’ in venous pressure & volume<br />Q(1) How are values of cardiac output above or below the resting level ever achieved or maintained, <br />Q(2) What determines the resting equilibrium between cardiac output and central venous pressure?<br />
    51. 51. Cardiac & Vascular fn Curves<br />Cardiac fn Curve<br />plots CO as a function of CVP<br />An extension of Starling's law<br />Position and slope depends on ‘cardiac’ factors<br />Vascular fn Curve<br />shows how CVP changes as a function of VR<br />Position and slope depends on ‘vascular’ factors (BV,SVR,compliance)<br />
    52. 52. Cardiac & Vascular fn Curves<br />Combining the curves provides a useful tool for predicting the changes in CO <br />That will occur when various CVS parameters are altered<br />CO can be altered by:<br />Changes in the cardiac function curve <br />By changes in the vascular function curve <br />By simultaneous changes in both curves<br />
    53. 53. Inotropic agents alter cardiac fn curve<br />Vice versa<br />CO is increased and CVP is decreased<br />
    54. 54. Changes in BV* alter MSP : alter vascular fn curve<br />CO is increased and CVP is increased<br />Vice versa<br />
    55. 55. Changes in TPR alter both curves<br />Cardiac fn curve shifts downward (increased afterload)<br />Counterclockwise rotation of vascular fn curve<br />Vice versa<br />
    56. 56. CO Measurement<br />Principle of mass balance<br />Introducing a known conc. of a dye (A) into an unknown volume of a fluid (V)<br />By calculating conc. of dye in fluid (C) along with A – V can be calculated via:<br />C1V1=C2V2<br />A=CxV<br />C=A/V<br />
    57. 57. CO Measurement<br />Indicator dilution method<br />Known amount of indicator (Indocyanine green – Cardiogreen) injected into venous circulation (A)<br />Blood sampled serially from distal artery<br />Concentration of dye (C) in serial samples:<br />Rises<br />Peaks<br />Declines<br />C is then averaged between T1 (time of appearance of dye in blood) and T2 (time of appearance of dye in blood) - Cave<br />
    58. 58. CO Measurement<br />Thermodilution method<br />Variation of indicator dilution method<br />More used in clinical practice<br />Swan-Ganz catheter placed via vein – threaded to the pulmonary artery<br />Catheter releases ice-cold saline into right heart via a side port<br />Saline changes temperature of the blood coming in contact with it – reflected by CO – to be measured by thermistor on catheter tip (placed downstream into pulmonary artery)<br />Equations similar to indicator dilution technique employed here<br />
    59. 59. CO Measurement<br />Fick’s principle – principle of mass balance taking into account oxygen entry/exit<br />1 liter blood can take 40 ml O2<br />How many 1-liter ‘units’ will it take to carry 200 ml in a min? – 5 L <br />This much needs to supplied by heart – CO!<br />
    60. 60. Energetics of Cardiac Function<br />Oxidative phosphorylation of either carbohydrates or fatty acids<br />Steady supply of O2 required (via coronary blood flow)<br />Cardiac energy consumption = cardiac O2 consumption<br />Work done by heart<br />External: ejection of blood from the ventricles (Volume work)<br />Internal: stretching elastic tissue, overcoming internal viscosity, rearranging muscular architecture of heart as it contracts (Pressure work)<br />
    61. 61. “Pressure Work” Vs “Volume Work”<br />Ventricles have to do external & internal work:<br />If the external work of the heart is raised by increasing SV, but not MAP, the O2 consumption of heart increases very little<br />Alternatively, if MAP is increased, O2 consumption/beat goes up much more<br />Pressure work by the heart is far more expensive in terms of O2 consumption than volume work<br />In other words, an increase in afterload causes greater increase in cardiac O2 consumption than does an increase in preload<br />
    62. 62. “Pressure Work” Vs “Volume Work”<br />Which one would produce angina due to less O2 delivery to myocardium?<br />Aortic stenosis or Aortic regurgitation<br />
    63. 63. “Pressure Work” Vs “Volume Work”<br />Increase in O2 consumption produced by increased SV (when myocardial fibers are stretched) – preload increase<br />An example of operation of law of Laplace<br />More the stretch – bigger the radium – more the tension developed – more the O2 consumption<br />In comparison, SNS induced increase in cardiac performance<br />Via intracellular Ca++ manipulation – not so much to do with radius – less O2 consumption<br />