1. Chapter 14
Cardiac Output,
Blood Flow,
and Blood
Pressure
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2. Chapter 14 Outline Cardiac Output Blood and Body Fluid Volumes
Factors Affecting Blood Flow
Blood Pressure
Hypertension
Circulatory Shock
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3. Cardiac Output
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4. Cardiac Output (CO) Is volume of blood pumped/min by each ventricle
Stroke volume (SV) = blood pumped/beat by each ventricle
CO = SV x HR
Total blood volume is about 5.5L
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5. Regulation of Cardiac Rate
Without neuronal influences, SA node will drive heart at rate of its spontaneous activity
Normally Symp and Parasymp activity influence HR (chronotropic effect)
Autonomic innervation of SA node is main controller of HR
Symp and Parasymp nerve fibers modify rate of spontaneous depolarization
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6. Regulation of Cardiac Rate continued
NE and Epi stimulate opening of pacemaker HCN channels
This depolarizes SA faster, increasing HR
ACH promotes opening of K+ channels
The resultant K+ outflow counters Na+ influx, slowing depolarization and decreasing HR
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7. Regulation of Cardiac Rate continued
Cardiac control center of medulla coordinates activity of autonomic innervation
Sympathetic endings in atria and ventricles can stimulate increased strength of contraction
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8. 14-8

9. Stroke Volume Is determined by 3 variables:
End diastolic volume (EDV) = volume of blood in ventricles at end of diastole
Total peripheral resistance (TPR) = impedance to blood flow in arteries
Contractility = strength of ventricular contraction
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10. Regulation of Stroke Volume
EDV is workload (preload) on heart prior to contraction
SV is directly proportional to preload and contractility
Strength of contraction varies directly with EDV
Total peripheral resistance = afterload which impedes ejection from ventricle
Ejection fraction is SV/ EDV
Normally is 60%; useful clinical diagnostic tool
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11. Frank-Starling Law of the Heart
States that strength of ventricular contraction varies directly with EDV
Is an intrinsic property of myocardium
As EDV increases, myocardium is stretched more, causing greater contraction and SV
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12. Frank-Starling Law of the Heart continued
(a) is state of myocardial sarcomeres just before filling
Actins overlap, actin-myosin interactions are reduced and contraction would be weak
In (b, c and d) there is increasing interaction of actin and myosin allowing more force to be developed
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13. Extrinsic Control of Contractility
At any given EDV, contraction depends upon level of sympathoadrenal activity
NE and Epi produce an increase in HR and contraction (positive inotropic effect)
Due to increased Ca2+ in sarcomeres
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14. 14-14

15. Venous Return Is return of blood to heart via veins
Controls EDV and thus SV and CO
Dependent on:
Blood volume and venous pressure
Vasoconstriction caused by Symp
Skeletal muscle pumps
Pressure drop during inhalation
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16. Venous Return continued
Veins hold most of blood in body (~70%) and are thus called capacitance vessels
Have thin walls and stretch easily to accommodate more blood without increased pressure (=higher compliance)
Have only mm Hg pressure
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17. Blood and Body Fluid Volumes
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18. Blood Volume Constitutes small fraction of total body fluid
2/3 of body H2O is inside cells (intracellular compartment)
1/3 total body H2O is in extracellular compartment
80% of this is interstitial fluid; 20% is blood plasma
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19. Exchange of Fluid between Capillaries and Tissues
Distribution of ECF between blood and interstitial compartments is in state of dynamic equilibrium
Movement out of capillaries is driven by hydrostatic pressure exerted against capillary wall
Promotes formation of tissue fluid
Net filtration pressure= hydrostatic pressure in capillary (17-37 mm Hg) - hydrostatic pressure of ECF (1 mm Hg)
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20. Exchange of Fluid between Capillaries and Tissues
Movement also affected by colloid osmotic pressure
= osmotic pressure exerted by proteins in fluid
Difference between osmotic pressures in and outside of capillaries (oncotic pressure) affects fluid movement
Plasma osmotic pressure = 25 mm Hg; interstitial osmotic pressure = 0 mm Hg
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21. Overall Fluid Movement
Is determined by net filtration pressure and forces opposing it (Starling forces)
Pc + Pi (fluid out) - Pi + Pp (fluid in)
Pc = Hydrostatic pressure in capillary
Pi = Colloid osmotic pressure of interstitial fluid
Pi = Hydrostatic pressure in interstitial fluid
Pp = Colloid osmotic pressure of blood plasma
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23. Edema
Normally filtration, osmotic reuptake, and lymphatic drainage maintain proper ECF levels
Edema is excessive accumulation of ECF resulting from:
High blood pressure
Venous obstruction
Leakage of plasma proteins into ECF
Myxedema (excess production of glycoproteins in extracellular matrix) from hypothyroidism
Low plasma protein levels resulting from liver disease
Obstruction of lymphatic drainage
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24. Regulation of Blood Volume by Kidney
Urine formation begins with filtration of plasma in glomerulus
Filtrate passes through and is modified by nephron
Volume of urine excreted can be varied by changes in reabsorption of filtrate
Adjusted according to needs of body by action of hormones
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25. ADH (vasopressin)
ADH released by Post Pit when osmoreceptors detect high osmolality
From excess salt intake or dehydration
Causes thirst
Stimulates H2O reabsorption from urine
ADH release inhibited by low osmolality
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26. Aldosterone Is steroid hormone secreted by adrenal cortex
Helps maintain blood volume and pressure through reabsorption and retention of salt and water
Release stimulated by salt deprivation, low blood volume, and pressure
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27. Renin-Angiotension-Aldosterone System
When there is a salt deficit, low blood volume, or pressure, angiotensin II is produced
Angio II causes a number of effects all aimed at increasing blood pressure:
Vasoconstriction, aldosterone secretion, thirst
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28. Angiotensin II
Fig shows when and how Angio II is produced, and its effects
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29. Atrial Natriuretic Peptide (ANP)
Expanded blood volume is detected by stretch receptors in left atrium and causes release of ANP
ANP inhibits aldosterone, promoting salt and water excretion to lower blood volume
And promotes vasodilation
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30. Atrial Natriuretic Peptide (ANP) continued
ANP, together with decreased ADH, acts in a negative feedback system to lower blood volume
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31. Factors Affecting Blood Flow
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32. Vascular Resistance to Blood Flow
Determines how much blood flows through a tissue or organ
Vasodilation decreases resistance, increases blood flow
Vasoconstriction does opposite
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34. Physical Laws Describing Blood Flow
Blood flows through vascular system when there is pressure difference (DP) at its two ends
Flow rate is directly proportional to difference (DP = P1 - P2)
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35. Physical Laws Describing Blood Flow continued
Flow rate is inversely proportional to resistance
Flow = DP/R
Resistance is directly proportional to length of vessel (L) and viscosity of blood ()
Inversely proportional to 4th power of radius
So diameter of vessel is very important for resistance
Poiseuille's Law describes factors affecting blood flow
Blood flow = DPr4()
L(8)
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37. Physical Laws Describing Blood Flow continued
Mean arterial pressure and vascular resistance are the 2 major factors regulating blood flow
Blood is shunted from one organ to another by degree of constriction of their arterioles
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38. Total Peripheral Resistance
Sum of all vascular resistances within the systemic circulation is total peripheral resistance
Arteries supply tissues and organs in parallel circuits
Changes in resistance in these circuits determines relative blood flow
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39. Extrinsic Regulation of Blood Flow
Sympathoadrenal activation causes increased CO and resistance in periphery and viscera
Blood flow to skeletal muscles is increased
Because their arterioles dilate in response to Epi and their Symp fibers release ACh which also dilates their arterioles
Thus blood is shunted away from visceral and skin to muscles
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40. Extrinsic Regulation of Blood Flow continued
Parasympathetic effects are vasodilative
However, Parasymp only innervates digestive tract, genitalia, and salivary glands
Thus Parasymp is not as important as Symp
Angiotenin II and ADH (at high levels) cause general vasoconstriction of vascular smooth muscle
Which increases resistance and BP
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41. Paracrine Regulation of Blood Flow
The endothelium produces several paracrine regulators that promote relaxation:
Nitric oxide (NO), bradykinin, prostacyclin
NO is involved in setting resting “tone” of vessels
Levels are increased by Parasymp activity
Vasodilator drugs such as nitroglycerin or Viagra act thru NO
Endothelin 1 is vasoconstrictor produced by endothelium
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42. Intrinsic Regulation of Blood Flow (Autoregulation)
Maintains fairly constant blood flow despite BP variation
Myogenic control mechanisms occur in some tissues because vascular smooth muscle contracts when stretched and relaxes when not stretched
E.g. decreased arterial pressure causes cerebral vessels to dilate and vice versa
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43. Intrinsic Regulation of Blood Flow (Autoregulation) continued
Metabolic control mechanism matches blood flow to local tissue needs
Low O2 or pH or high CO2, adenosine, or K+ from high metabolism cause vasodilation which increases blood flow (= active hyperemia)
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44. Aerobic Requirements of the Heart
Heart (and brain) must receive adequate blood supply at all times
Heart is most aerobic tissue--each myocardial cell is within 10 m of capillary
Contains lots of mitochondria and aerobic enzymes
During systole coronary, vessels are occluded
Heart gets around this by having lots of myoglobin
Myoglobin is an O2 storage molecule that releases O2 to heart during systole
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45. Regulation of Coronary Blood Flow
Blood flow to heart is affected by Symp activity
NE causes vasoconstriction; Epi causes vasodilation
Dilation accompanying exercise is due mostly to intrinsic regulation
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46. Regulation of Blood Flow Through Skeletal Muscles
At rest, flow through skeletal muscles is low because of tonic sympathetic activity
Flow through muscles is decreased during contraction because vessels are constricted
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47. Circulatory Changes During Exercise
At beginning of exercise, Symp activity causes vasodilation via Epi and local ACh release
Blood flow is shunted from periphery and visceral to active skeletal muscles
Blood flow to brain stays same
As exercise continues, intrinsic regulation is major vasodilator
Symp effects cause SV and CO to increase
HR and ejection fraction increases vascular resistance
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50. Cerebral Circulation Gets about 15% of total resting CO
Held constant (750ml/min) over varying conditions
Because loss of consciousness occurs after few secs of interrupted flow
Is not normally influenced by sympathetic activity
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51. Cerebral Circulation
Regulated almost exclusively by intrinsic mechanisms
When BP increases, cerebral arterioles constrict; when BP decreases, arterioles dilate (=myogenic regulation)
Arterioles dilate and constrict in response to changes in CO2 levels
Arterioles are very sensitive to increases in local neural activity (=metabolic regulation)
Areas of brain with high metabolic activity receive most blood
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53. Cutaneous Blood Flow
Skin serves as a heat exchanger for thermoregulation
Skin blood flow is adjusted to keep deep-body at 37oC
By arterial dilation or constriction and activity of arteriovenous anastomoses which control blood flow through surface capillaries
Symp activity closes surface beds during cold and fight-or-flight, and opens them in heat and exercise
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54. Blood Pressure
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55. Blood Pressure (BP)
Arterioles play role in blood distribution and control of BP
Blood flow to capillaries and BP is controlled by aperture of arterioles
Capillary BP is decreased because they are downstream of high resistance arterioles
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56. Blood Pressure (BP)
Capillary BP is also low because of large total cross-sectional area
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57. Blood Pressure (BP)
Is controlled mainly by HR, SV, and peripheral resistance
An increase in any of these can result in increased BP
Sympathoadrenal activity raises BP via arteriole vasoconstriction and by increased CO
Kidney plays role in BP by regulating blood volume and thus stroke volume
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58. Baroreceptor Reflex Is activated by changes in BP
Which is detected by baroreceptors (stretch receptors) located in aortic arch and carotid sinuses
Increase in BP causes walls of these regions to stretch, increasing frequency of APs
Baroreceptors send APs to vasomotor and cardiac control centers in medulla
Is most sensitive to decrease and sudden changes in BP
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61. Atrial Stretch Receptors
Are activated by increased venous return and act to reduce BP
Stimulate reflex tachycardia (slow HR)
Inhibit ADH release and promote secretion of ANP
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62. Measurement of Blood Pressure
Via auscultation (to examine by listening)
No sound is heard during laminar flow (normal, quiet, smooth blood flow)
Korotkoff sounds can be heard when sphygmomanometer cuff pressure is greater than diastolic but lower than systolic pressure
Cuff constricts artery creating turbulent flow and noise as blood passes constriction during systole and is blocked during diastole
1st Korotkoff sound is heard at pressure that blood is 1st able to pass thru cuff; last occurs when one can no long hear systole because cuff pressure = diastolic pressure
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63. Measurement of Blood Pressure continued
Blood pressure cuff is inflated above systolic pressure, occluding artery
As cuff pressure is lowered, blood flows only when systolic pressure is above cuff pressure, producing Korotkoff sounds
Sounds are heard until cuff pressure equals diastolic pressure, causing sounds to disappear
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65. Pulse Pressure
Pulse pressure = (systolic pressure) – (diastolic pressure)
Mean arterial pressure (MAP) represents average arterial pressure during cardiac cycle
Has to be approximated because period of diastole is longer than period of systole
MAP = diastolic pressure + 1/3 pulse pressure
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66. Hypertension
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67. Hypertension
Blood pressure in excess of normal range for age and gender (> 140/90 mmHg)
Afflicts about 20% of adults
Most common type is primary or essential hypertension
Caused by complex and poorly understood processes
Secondary hypertension is caused by known disease processes
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68. Essential Hypertension
Increase in peripheral resistance is universal
CO and HR are elevated in many
Secretion of renin, Angio II, and aldosterone is variable
Sustained high stress (which increases Symp activity) and high salt intake act synergistically in development of hypertension
Prolonged high BP causes thickening of arterial walls, resulting in atherosclerosis
Kidneys appear to be unable to properly excrete Na+ and H2O
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69. Dangers of Hypertension
Patients are often asymptomatic until substantial vascular damage occurs
Contributes to atherosclerosis
Increases workload of the heart leading to ventricular hypertrophy and congestive heart failure
Often damages cerebral blood vessels leading to stroke
These are why it is called the "silent killer"
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70. Treatment of Hypertension
Often includes lifestyle changes such as cessation of smoking, moderation in alcohol intake, weight reduction, exercise, reduced Na+ intake, increased K+ intake
Drug treatments include diuretics to reduce fluid volume, beta-blockers to decrease HR, calcium blockers, ACE inhibitors to inhibit formation of Angio II, and Angio II-receptor blockers
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71. Circulatory Shock
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72. Circulatory Shock
Occurs when there is inadequate blood flow to, and/or O2 usage by, tissues
Cardiovascular system undergoes compensatory changes
Sometimes shock becomes irreversible and death ensues
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73. Hypovolemic Shock Is circulatory shock caused by low blood volume
E.g. from hemorrhage, dehydration, or burns
Characterized by decreased CO and BP
Compensatory responses include sympathoadrenal activation via baroreceptor reflex
Results in low BP, rapid pulse, cold clammy skin, low urine output
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74. Septic Shock
Refers to dangerously low blood pressure resulting from sepsis (infection)
Mortality rate is high (50-70%)
Often occurs as a result of endotoxin release from bacteria
Endotoxin induces NO production causing vasodilation and resultant low BP
Effective treatment includes drugs that inhibit production of NO
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75. Other Causes of Circulatory Shock
Severe allergic reaction can cause a rapid fall in BP called anaphylactic shock
Due to generalized release of histamine causing vasodilation
Rapid fall in BP called neurogenic shock can result from decrease in Symp tone following spinal cord damage or anesthesia
Cardiogenic shock is common following cardiac failure resulting from infarction that causes significant myocardial loss
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76. Congestive Heart Failure
Occurs when CO is insufficient to maintain blood flow required by body
Caused by MI (most common), congenital defects, hypertension, aortic valve stenosis, disturbances in electrolyte levels
Compensatory responses are similar to those of hypovolemic shock
Treated with digitalis, vasodilators, and diuretics
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