1. Cardiac Output, Blood Flow, and Blood Pressure
Chapter 14
Cardiac Output, Blood Flow, and Blood Pressure

2. Objectives
Explain the intrinsic regulation of SV (Frank-Starling Law of the Heart).
List the factors that affect the venous return of blood to the heart.
Explain how ADH helps to regulate blood volume, plasma osmolality, and blood pressure.
Describe the renin-angiotensin-aldosterone system and discuss its significance in CV regulation.

3. Objectives (continued(
Define TPR and explain how vascular resistance is regulated by extrinsic control mechanisms.
Explain the mechanisms by which blood flow to the heart and skeletal muscles is regulated.
Describe the changes that occur in the CO and distribution of blood flow during exercise.
List the factors that regulate the arterial blood pressure.
Describe the baroreceptor reflex and explain its significance in blood pressure regulation.

4. Cardiac Output (CO) Volume of blood pumped/min. by each ventricle.
Pumping ability of the heart is a function of the beats/ min. and the volume of blood ejected per beat.
CO = SV x HR
Total blood volume averages about 5.5 liters.
Each ventricle pumps the equivalent of the total blood volume each min. (resting conditions).

5. Regulation of Cardiac Rate
Without neuronal influences, the heart beats according to the rhythm set by SA node.
Regulation of HR (chronotropic effect):
May be + or – effect.
Autonomic control:
Sympathetic and parasympathetic nerve fibers to the heart modify the rate of spontaneous depolarization.
Innervate the SA node.
NE and Epi stimulate opening of Na+/Ca2+ channel.
ACH promotes opening of K+ channel.
Major means by which cardiac rate is regulated.
Cardiac control center (medulla):
Coordinates activity of autonomic innervation.

6. Regulation of SV Stroke volume is regulated by 3 variables: EDV:
Volume of blood in the ventricles at the end of diastole.
Total peripheral resistance (TPR):
Frictional resistance or impedance to blood flow in the arteries.
Contractility:
Strength of ventricular contraction.

7. EDV Workload on the heart prior to contraction (preload).
SV directly proportional to preload.
Increase in EDV results in an increase in SV.
SV directly proportional to contractility.
Strength of contraction varies directly with EDV.
Ejection fraction:
SV/ EDV.
Normally is 60%.
Clinical diagnostic tool.

8. TPR Total Peripheral Resistance: SV inversely proportional to TPR.
Impedance to the ejection of blood from ventricle.
Afterload.
In order to eject blood, pressure generated in the ventricle must be greater than pressure in the arteries.
Pressure in arteries before ventricle contracts is a function of TPR.
SV inversely proportional to TPR.
Greater the TPR, the lower the SV.

9. Frank-Starling Law of the Heart
Relationship between EDV, contraction strength, and SV.
Intrinsic mechanism:
Varying degree of stretching of myocardium by EDV.
As EDV increases:
Myocardium is increasingly stretched.
Contracts more forcefully.

10. Frank-Starling Law of the Heart (continued)
As the ventricles fill, the myocardium stretches; This increases the number of interaction between actin and myosin.
Allows more force to develop.
Explains how the heart can adjust to rise in TPR.

11. Extrinsic Control of Contractility
Strength of contraction at any given fiber length.
Depends upon sympathoadrenal system:
NE and Epi produce an increase in contractile strength.
+ inotropic effect:
More Ca2+ available to sarcomeres.

12. Extrinsic Control of Contractility (continued)
Parasympathetic stimulation:
- chronotropic effect.
Does not directly influence contraction strength.
CO affected 2 ways:
+ inotropic effect on contractility.
+ chronotropic effect on HR.

13. Venous Return Return of blood to the heart via veins.
Venous pressure is driving force for return of blood to the heart.
Veins have thinner walls, thus higher compliance.
Capacitance vessels.
2/3 blood volume is in veins.
EDV, SV, and CO are controlled by factors which affect venous return.

14. Blood Volume Distribution of H20 within the body:
Intracellular compartment:
2/3 of total body H20 within the cells.
Extracellular compartment:
1/3 total body H20.
80% interstitial fluid.
20% blood plasma.
Maintained by constant balance between H20 loss and gain.

15. Blood Volume (continued)

16. Exchange of Fluid between Capillaries and Tissues
Distribution of ECF between plasma and interstitial compartments is in state of dynamic equilibrium.
Balance between tissue fluid and blood plasma.
Hydrostatic pressure:
Exerted against the inner capillary wall.
Promotes formation of tissue fluid.
Net filtration pressure.
Colloid osmotic pressure:
Exerted by plasma proteins.
Promotes fluid reabsorption into circulatory system.

17. Net Filtration Pressure
Hydrostatic pressure of blood capillaries minus the hydrostatic pressure in the interstitial fluid.
Blood hydrostatic pressure (arteriolar pressure) = 37 mm Hg.
Blood hydrostatic pressure (venular end) = 17 mm Hg.
Interstitial hydrostatic pressure = 1 mm Hg.

18. Colloid Osmotic Pressure
Pressure exerted by plasma proteins or interstitial proteins.
Difference between plasma osmotic pressure and interstitial osmotic pressure is called oncotic pressure.
Plasma osmotic pressure = 25 mm Hg.
Interstitial osmotic pressure = 0 mm Hg.

19. Fluid Movement Starling force=(Pc + Pi) - (Pi + Pp) Pc = Pi = Pi =
Hydrostatic pressure in the capillary.
Pi =
Colloid osmotic pressure of the interstitial fluid.
Pi =
Hydrostatic pressure in the the interstitial fluid.
Pp =
Colloid osmotic pressure of the blood plasma.

20. Fluid Movement (continued)

21. Causes of Edema Excessive accumulation of tissue fluid.
Edema may result from:
High arterial blood pressure.
Venous obstruction.
Leakage of plasma proteins into interstitial fluid.
Myexedema.
Decreased plasma [protein].
Obstruction of lymphatic drainage.

22. Regulation of Blood Volume by the Kidney
Formation of urine begins by filtration of plasma through glomerular capillary pores.
Volume of urine excreted can be varied by changes in reabsorption of filtrate.
Adjusted according to needs of body by action of hormones.

23. Regulation by ADH
Released by posterior pituitary when osmoreceptors detect an increase in plasma osmolality.
Dehydration or excess salt intake:
Produces sensation of thirst.
Stimulates H20 reabsorption from urine.

24. Regulation by Aldosterone
Steroid hormone secreted by adrenal cortex.
Mechanism to maintain blood volume and pressure through absorption and retention of Na+ and Cl-.
Stimulates reabsorption of NaCl.
Indirectly increases H20 reabsorption.
Does not dilute osmolality.
Release stimulated:
During salt deprivation.
Reduced blood volume and pressure.

25. Renin-Angiotension-Aldosterone System
When blood pressure and flow are reduced in renal artery, juxtaglomerular apparatus secretes renin.
Renin converts angiotensinogen to angiotensin I.
Angiotensin I is converted to angiotensin II by ACE.
Angiotensin II:
Powerful vasoconstrictor.
Stimulates production of aldosterone.
Stimulates thirst.

26. Juxtaglumerular Apparatus

27. Renin-Angiotension-Aldosterone System (continued)

28. Atrial Natriuretic Peptide (ANP)
Produced by the atria of the heart.
Stretch of atria stimulates production of ANP.
Antagonistic to aldosterone and angiotensin II.
Promotes Na+ and H20 excretion in the urine by the kidney.
Promotes vasodilation.

29. Vascular Resistance to Blood Flow
Physical laws describing blood flow:
The flow of blood through the vascular system is due to the difference in pressure at the two ends (DP).
Flow = DP/R
R = TPR (sum of all vascular resistance within the systemic circulation).
Blood flow directly proportional to pressure differences.
Inversely proportional to resistance.

30. Resistance Opposition to blood flow.
Resistance is directly proportional to length of vessel and to the viscosity of the blood.
Inversely proportional to 4th power of the radius of the vessel.
R = _L  _ r4
L = length of the vessel
 = viscosity of blood
r = radius of the vessel

31. Poiseuille’s Law Blood flow = DPr4(p) L(8)
Vessel length and blood viscosity do not vary significantly.
Major regulators of blood flow through an organ are:
Mean arterial pressure.
Vascular resistance to flow.

32. Resistance and Blood Flow

33. Extrinsic Regulation of Blood Flow
Controlled by autonomic nervous system and endocrine system.
Sympathoadrenal:
Increase CO.
Increase TPR:
Alpha-adrenergic stimulation:
Vasoconstriction of arteries in skin and viscera.
Cholinergic sympathetic fibers:
Vasodilate to skeletal muscles.

34. Extrinsic Regulation of Blood Flow (continued)
Parasympathetic nervous system:
Parasympathetic innervation limited.
Promotes vasodilation to the digestive tract, external genitalia, and salivary glands.
Less important than sympathetic nervous system in control of TPR.
Parasympathetic endings in arterioles promote vasodilation.

35. Paracrine Regulation of Blood Flow
Endothelium produces several paracrine regulators:
Endothelium of arterioles contains eNOS, which produces NO:
NO diffuses into smooth muscle:
Activates guanylate cyclase:
Converts GTP to cGMP (2nd messenger).
Lowers cytoplasmic [Ca2+].
Production of NO can be increased by Ach:
Stimulates opening of Ca2+ channels.
Ca2+ binds to calmodulin.
Calmodulin activates an enzyme to produce NO.
Bradykinin, prostacyclin: Vasodilate.
Endothelin-1: Vasoconstrict

36. Intrinsic Regulation of Blood Flow (Autoregulation)
Myogenic control mechanism:
Occurs because of the stretch of the vascular smooth muscle.
A decrease in systemic arterial pressure causes cerebral vessels to dilate.
Maintains adequate flow.
A increase in systemic arterial pressure causes cerebral vessels to contract

37. Intrinsic Regulation of Blood Flow (Autoregulation) (continued)
Metabolic control mechanism:
Intrinsic receptors sense chemical changes in environment.
Vasodilation:
Decreased 02:
Increased metabolic rate.
Increased C02:
Decreased ventilation.
Decreased pH:
Lactic acid.
Increased adenosine or increased K+:
From tissue cells.

38. Aerobic Requirements of the Heart
Survival requires that the heart and brain receive adequate blood supply at all times.
Coronary arteries supply an enormous # of capillaries.
Each myocardial cell is within 10 mm of a capillary.
Systole contracts the coronary blood vessels.
Diastole increases blood flow to the heart muscle.
Myocardium contains large amounts of myoglobin.
Myoglobin stores 02 during diastole to release during systole.
Heart muscle contains increased number of mitochondria and aerobic respiratory enzymes.

39. Regulation of Coronary Blood Flow
Sympathetic nervous system:
a receptors:
Vasoconstriction at rest.
b receptors:
Vasodilation.
Intrinsic:
Metabolism of the myocardium increases causing accumulations of C02, K+, and adenosine; decreased 02.
Acts directly on vascular smooth muscle to cause relaxation.

40. Regulation of Blood Flow Through Skeletal Muscles
Decreased blood flow when muscles contract and constrict arterioles.
Sympathetic:
a-adrenergic receptors:
Vasoconstrict at rest.
Sypothetic cholinergic and b-adrenergic receptors:
Vasodilate.
Intrinsic control primary mechanisms as exercise progresses:
Increased accumulations of C02, K+, and adenosine; decreased 02.
Vasodilate arterioles.

41. Circulatory Changes During Exercise
Vascular resistance decreases to skeletal muscles. Blood flow to skeletal muscles increases.
SV and CO increase.
Blood flow to brain stays same.
Metabolic vasodilation.
Diversion of blood away from vicera and skin.
HR increases to maximum of 190 beats/min.
Ejection fraction increases due to increased contractility.
Vascular resistance:
Decreases to skeletal muscle.
Increases to GI tract and skin.

42. Circulatory Changes During Exercise (continued)

43. Circulatory Changes During Exercise (continued)

44. Cerebral Circulation
Cerebral blood flow is not normally influenced by sympathetic nerve activity.
Normal range of arterial pressures:
Cerebral blood flow regulated almost exclusively by intrinsic mechanisms:
Myogenic:
Dilate in response to decreased pressure.
Cerebral arteries also sensitive to [C02].
Dilate due to decreased pH of crebrospinal fluid.
Metabolic:
Sensitive to changes in metabolic activity.
Areas of brain with high metabolic activity receive most blood.
May be caused by [K+].

45. Cutaneous Blood Flow Thermoregulation: Bradykinin:
Blood flow through the skin is adjusted to maintain deep-body temperatures at about 37o C.
Occurs due to:
Vasoconstriction/vasodilation ordinary arteries and arteriovenous anastomosis.
Bradykinin:
Sweat glands secrete bradykinin which increases blood flow to skin and sweat glands.
Changes in cutaneous blood flow, occur as a result to changes in sympathetic nerve activity; which is controlled by the brain.

46. Arteriovenous Anastomosis
Controlled by sypothetic nervous system
Divert blood from arterioles to depp venules
In hands, toes, ear, nose and lips.
Ambient temperature is low
Arteriovenous anastomosis constrict and divert blood in to superfical capillary

47. Blood Pressure (BP)
Pressure of arterial blood is regulated by blood volume, TPR, and cardiac rate.
MAP=CO  TPR
Arteriole resistance is greatest because they have the smallest diameter.
Capillary BP is reduced because of the total cross-sectional area.
3 most important variables are HR, SV, and TPR.
Increase in each of these will result in an increase in BP.
BP can be regulated by:
Kidney and sympathoadrenal system.

48. MAP TPR CO HR SV Chemicals Viscosity Blood vessel length EDV ANS
Hormones
Lytes
Body temp
Brain
EDV
Venous Return
Kidney
Angiotensin
Aldosterone
ADH
Respiratory pump
Skeletal muscle pump
Chemicals
Viscosity
Blood vessel length
Blood vessel diameter
Local factors

49. Blood Pressure (BP) (continued)

50. Baroreceptor Reflex
Stretch receptors located in the aortic arch and carotid sinuses.
An increase in pressure causes the walls of these regions to stretch, increasing frequency of APs.
Baroreceptors send APs to vasomotor control and cardiac control centers in the medulla.
Baroreceptor reflex activated with changes in BP.
More sensitive to decrease in pressure and sudden changes in pressure.

51. Baroreceptor Reflex (continued)

52. Baroreceptor Reflex (continued)

53. Atrial Stretch Reflexes
Located in the atria of the heart.
Receptors activated by increased venous return.
Stimulate reflex tachycardia.
Inhibit ADH release.
Promote secretion of ANP.

54. Measurement of Blood Pressure
Auscultation:
Art of listening.
Laminar flow:
Normal blood flow.
Blood in the central axial stream moves faster than blood flowing closer to the artery wall.
Smooth and silent.
Turbulent flow and vibrations produced in the artery when cuff pressure is greater than diastolic pressure and lower than systolic pressure.

55. Measurement of Blood Pressure (continued)
Blood pressure cuff is inflated above systolic pressure, occluding the artery.
As cuff pressure is lowered, the blood will flow only when systolic pressure is above cuff pressure, producing the sounds of Korotkoff.
Korotkoff sounds will be heard until cuff pressure equals diastolic pressure, causing the sounds to disappear.

56. Measurement of Blood Pressure (continued)
Different phases in measurement of blood pressure are identified on the basis of the quality of the Korotkoff sounds.
Average arterial BP is 120/80 mm Hg.
Average pulmonary BP is 22/8 mm Hg.

57. Pulse Pressure
The expansion of the artery in response to the volume of blood ejected by the left ventricle.
Pulse pressure = systolic pressure – diastolic pressure
Mean arterial pressure (MAP):
Represents the average arterial pressure during the cardiac cycle.
Is closer to diastolic pressure, as the period of diastole is longer than the period of systole.
MAP = diastolic pressure + 1/3 pulse pressure

58. Hypertension (HTN)
Blood pressure in excess of normal range for age and gender.
> 140/90 mm Hg.
Primary or essential hypertension:
Is the result of a complex or poorly understood process.
Secondary hypertension:
Is a result of a known disease process.

59. Essential Hypertension
Majority of the population with hypertension.
Increase in TPR is a universal characteristic.
CO and HR elevated in many.
Secretion of renin, angiotensin II, and aldosterone is variable.
Sustained high stress (via sympathetic nervous system) and high Na+ intake act synergistically in development of hypertension.
Adaptive response is thickening of arterial wall, resulting in atherosclerosis.
Kidneys may not be able to properly excrete Na+ and H20.
A shared characteristic of all cases of essential HTN.

60. Dangers of Hypertension
Silent killer:
Patients are asymptomatic until substantial vascular damage occurs.
Atherosclerosis.
Increases afterload.
Increases workload of the heart.
Congestive heart failure.
Damage cerebral blood vessels.
Cerebral vascular accident (stroke).

61. Treatment of Hypertension
Modification of lifestyle:
Cessation of smoking.
Moderation in alcohol intake.
Weight reduction.
Programmed exercise.
Reduction in Na+ intake.
Diet high in K+.

62. Treatment of Hypertension (continued)
Medications:
Diuretics:
Increase urine volume.
Beta-blockers:
Decrease HR.
Calcium antagonists:
Block Ca2+ channels.
ACE inhibitors:
Inhibit conversion to angiotensin II.
Angiotension II-receptor antagonists:
Block receptors.

63. Circulatory Shock Hypovolemic shock: Compensations:
Circulatory shock that is due to low blood volume.
Decreased CO and blood pressure.
Bleeding, dehydration, and burns.
Compensations:
Baroreceptor reflex:
Tachycardia.
Vasoconstriction to GI, skin, kidneys, and muscles.
Kidneys stimulate production of renin-angiotensin-aldosterone system.
Vasoconstriction.
Increase in ADH.

64. Circulatory Shock (continued)
Septic shock:
Dangerously low blood pressure as a result of sepsis.
Occurs through the action of endotoxin.
Endotoxin activates nitric oxide synthetase, producing NO.
NO causes vasodilation.
Treat with drugs that inhibit the production of NO.

65. Other Causes of Circulatory Shock
Anaphylactic shock:
Severe allergic reaction.
Widespread release of histamine.
Vasodilation.
Neurogenic shock:
Rapid fall in BP.
Sympathetic tone is decreased.
Cardiogenic shock:
Cardiac failure.
CO inadequate to maintain perfusion.

66. Congestive Heart Failure
CO is insufficient to maintain the blood flow required by the body.
Increased venous volume and pressure.
Caused by:
MI (most common cause).
Congenital defects.
Hypertension.
Aortic valve stenosis.
Disturbances in electrolyte concentrations.
K+ and Ca++.
Compensations similar to those of hypovolemic shock.
Treated with medications:
Digitalis, vasodilators, and diuretics.

67. Xuesong Chen xchen@medicine.nodak.edu
Department of Pharmacology, Physiology and Therapeutic.
Room 5730