1. Nikki Jones

2. Session Outline  Cardiac function Determinants of cardiac output, preload, afterload and contractility  Haemodynamics Factors affecting pressure and flow Venous return, veins, venous tone  Control of blood vessels Peripheral resistance Vascular tone

3. Determinants of cardiac output, preload, afterload and contractility

4. Objectives  Define the terms cardiac output, heart rate and stroke volume and give approximate (± 10%) values for these in a healthy adult at rest.  Describe briefly how heart rate and stroke volume interact to increase or decrease cardiac output.  State the influence of venous return on cardiac output.  Define the terms preload, afterload and contractility and describe how a change in each of these will affect cardiac performance.  Define Starling’s Law of the heart (the Frank-Starling relationship) and, as one practical expression of this Law, draw a graph relating left ventricular end diastolic volume to stroke volume.  Describe the influence of noradrenaline and adrenaline on the Frank- Starling curve.  Describe the influence of myocardial ischaemia on the Frank-Starling curve.  Describe the influence of myocardial failure (heart failure; CVS 12) on the Frank-Starling curve.  Describe the influence of digitalis in the failing heart (CVS 13) on the Frank-Starling curve

5. Cardiac Output  Definition: “the volume of blood pumped out by the ventricles in a given time” CO = HR x SV (L/min) (beats/min) (L/beat)  Heart rate = number of beats per minute  Stroke volume = the volume of blood ejected by each ventricle with each beat

6. Question 1  If the patient’s heart rate is 72 beats/min at rest and has a stroke volume of 70ml/beat, what is their cardiac output?  CO = HR x SV  CO = 72 beats/min x 0.07 L/min  CO = 5.04L/min

7. Question 2  Following strenuous exercise, the patient’s heart rate goes upto 200 beats/min, which results in their cardiac output increasing to 22.0L/min. What is their stroke volume?  SV = CO/HR  SV = 22.0/200 = 0.11L/beat = 110 ml/beat

8. Factors affecting cardiac output  Factors affecting heart rate Sympathetic nervous system Parasympathetic nervous system Hormones Alterations in membrane potential  Factors affecting stroke volume Preload Cardiac contractility Afterload

9. Frank-Sterling Curve   stretch =  EDV =  force of contraction =  contractility   EDV =  stroke volume

10. ?  symp. ns activity Calcium +ve ionotropic drugs e.g. digoxin ?  symp. ns activity Heart failure Hypoxia Acidosis

11. Factors affecting pressure and flow Venous return, veins, venous tone

12. Objectives  State how flow through a blood vessel is influenced, include by: a. The pressure gradient along the vessel. b. The length of the vessel. c. The fourth power of the radius of the vessel lumen (r4). d. The viscosity of the blood. e. Turbulent flow.  Given values for the perfusion pressure and for the resultant flow through a vascular bed, calculate a numerical value of the resistance to flow and state its units.  Define the term total peripheral resistance in relation to mean systemic arterial pressure and cardiac output.  State the meaning of the term compliance as applied to arteries and state what structures in the arterial wall confer elasticity; state simply what structural pathology of arteries reduces compliance.  State what is meant by the term capacitance vessels and how an increase in venomotor tone affects the central venous pressure and effective circulating blood volume

13. Darcy’s Law of Flow  Flow = ΔP R Where: ΔP = pressure difference between arteries and veins (created by pumping action of the heart) R = resistance of the blood vessel against blood flow Poiseuille’s Law of Flow  Flow = ΔP. r 4 η. L Where: ΔP = pressure differencer 4 = radius of the tube η = viscosity of fluid L = length of tube

14.  i.e. Flow is DIRECTLY proportional to pressure difference and radius of the tube  Flow is INDIRECTLY proportional to viscosity of the fluid and length of the tube

15. Question 3  What will happen to flow if: a) P i = P o b) P i > P o PiPi PoPo PiPi PoPo NO FLOW FLOW

16. Question 3 cont. c) Increase the length of the vessel d) Increase the radius of the vessel e) Increase the viscosity of the fluid  FLOW  FLOW  FLOW

17. Summary of Flow  Increased flow if: Greater pressure difference Increased radius of vessel Decreased length of vessel Decreased viscosity of fluid Resistance is largely determined by the radius of the blood vessel

18. Blood vessels  Arteries and arterioles have the greatest capacity to change radius, as they contain large amounts of smooth muscle  Known as “resistance vessels” Largest drop in pressure in these vessels

19. Vascular beds  Cardiac output is distributed to vascular beds – usually arranged in parallel  Total peripheral resistance will be less than any individual resistance  Remember: Resistance = ΔP flow

20. Vascular beds 3 litres/min 2 litres/min 1 litre/min Resistance = 120/3 = 40 units Resistance = 120/2 = 60 units Resistance = 120/1 = 120 units Resistance (total) = 120/6 = 20 units Pi = 120 mmHg Po = 0 mmHg Flow = 6 litres/min ArterialVenous

21. Problems with haemodynamics  Blood is a complex solution Contains RBCs, WBCs, platelets, proteins etc.  Blood vessels are not uniform straight rigid tubes Multibranched Variable elasticity Variable diameters Can get non-laminar flow ○ Turbulent flow needs higher driving pressure to achieve the same flow

22. Compliance  Compliance = the change in volume for a given change in pressure  Determined by the extent of elasticity  Arterial compliance – filtering/ smoothing out of pressure  compliance with ? Age  Venous compliance – capacity for storage

23. Question 4  Where is most of the blood volume found in the body?  Veins i.e. they are “capacitance” vessels Contain ⅔ of the body’s blood volume

24. Venous return   venomotor tone (i.e.  constriction) =  venous capacity =  venous pressure =  blood return to the heart (venous return) =  effective circulating blood volume  Venous return also affected by: Venous valve competence Skeletal muscle pump Respiration

25. Peripheral resistance and vascular tone

26. Objectives  Describe, in simple mechanistic terms, how the calibre of an arteriole may be altered.  Define sympathetic noradrenergic vasomotor nerves.  Define vasoconstriction and vasodilatation.  Define vasomotor tone.  Define venomotor tone.  Define precapillary sphincter.  List the sequence of events whereby the generation of action potentials in noradrenergic vasomotor nerves leads to an increase in arteriolar vascular resistance, naming the class of adrenoceptors involved.  List four vasoactive hormones together with the organs or cells from which their release is initiated.  Propose a mechanism by which a drug might act to relax nonselectively vascular smooth muscle; give an example of a nonselective vasodilator.  Define the term blood flow autoregulation; name two vascular beds that demonstrate autoregulatory control of blood flow.

27. Vascular resistance  Resistance is largely determined by the radius of the blood vessel  radius =  resistance  Radius depends on Active tension exerted by vascular smooth muscle (constriction/dilatation) Passive elastic properties of wall (elastin, collagen) Blood pressure inside the vessel (Veins only – tissue pressure outside the vessel)

28. Law of Laplace  Important in altering vessel calibre  Distending pressure = wall tension radius  Balance between distending pressure and wall tension maintain vessel calibre CLINICAL RELEVANCE If there is an increase in diameter e.g. aneurysm, there is an increase in wall tension If the distending pressure becomes too high, there is a risk of rupture

29. Question 5  Would wall tension be more or less in small vessels, compared to larger vessels?  Less E.g. Aorta: P=100 mmHg, r = 12mm ○ Wall tension (Tw) = P x r = 100 x 12 = 1200 Capillary: P = 30mmHg, r = 4μm ○ Tw = 30 x 0.004 = 0.12

30. Why is this important?  Allows redistribution of blood flow  Control of pre/post-capillary sphincters  Regulation of vascular tone and control of blood pressure

31. Definitions  Vasomotor tone = degree of active vasoconstriction/ dilatation in arterioles or arteries  Venomotor tone = degree of constriction/ dilatation in venules/ veins  Vasoconstriction = contraction of smooth muscle cells in wall of vessel =  active tension,  passive tension  Vasodilation = relaxation of smooth muscle =  active tension,  passive tension

32. Noradrenergic vasomotor nerves Symp. nerve varicosity Arteriole α1α1 α2α2 β2β2 VasoconstrictionVasodilatation NA Neuropeptide Y, ATP

33. Vasoactive hormones  Catecholamines E.g. Noradrenaline, adrenaline Act on α/β adrenoceptors, depending on which are present on individual vascular bed to bring about constriction/ dilatation  Peptides Angiotensin + vasopressin – play a role in constriction ○ Vasopressin – important in long-term control of BP Bradykinin – plays a role in dilatation

34. Vascular smooth muscle contraction  Intrinsic mechanisms: Endothelium-derived vasorelaxants ○ Local control mechanism – not under CNS control ○ Incl. prostacyclin, nitric oxide Metabolites ○ Metabolically active tissues:  lactate/ H + / K + /adenosine = dilatation Myogenic ○ i.e. stretch (from  pressure) = vasoconstriction ○ Particularly important in cerebral vasculature

35. Systemic vs. pulmonary vasculature  Systemic  O 2  CO 2 = ?  CO 2  O 2 = ?  Pulmonary  O 2  CO 2 = ?  CO 2  O 2 = ? Directs blood to area with the most oxygen to pick up  increased perfusion in well-ventilated areas CONSTRICTION DILATATION

36. Autoregulation of blood flow  Keep blood flow relatively constant to that vascular bed through adaptation to environmental changes  Good autoregulation shown by: Cerebral vascular bed Cardiac Renal

37. Summary  Cardiac function Determinants of cardiac output, preload, afterload and contractility  Haemodynamics Factors affecting pressure and flow Venous return, veins, venous tone  Control of blood vessels Peripheral resistance Vascular tone

38. mzydnlj@nottingham.ac.uk