This document discusses cardiac output, blood flow, and blood pressure. It defines cardiac output as the volume of blood pumped per minute by each ventricle, which is determined by heart rate and stroke volume. Stroke volume depends on factors like preload, contractility, and afterload. The document also discusses regulation of heart rate and contractility by the autonomic nervous system as well as intrinsic properties like the Frank-Starling law. Additional topics covered include blood volume, factors influencing blood flow, vascular resistance, blood pressure regulation via baroreceptors, and measurement of blood pressure.

1. Cardiac Output, Blood Flow, and
Blood Pressure

2. • Chapter 14 Outline
• Cardiac Output
• Blood & Body Fluid Volumes
• Factors Affecting Blood Flow
• Blood Pressure
• Hypertension
• Circulatory Shock

3. Cardiac OutputCardiac Output

4. Cardiac Output (CO)
Is volume of blood pumped/min by each
ventricle
Heart Rate (HR) = 70 beats/min
Stroke volume (SV) = blood pumped/beat by
each ventricle
◦ Average is 70-80 ml/beat
CO = SV x HR
Total blood volume is about 5.5L
14-4

5. Regulation of Cardiac Rate
• Without neuronal influences, SA node will
drive heart at rate of its spontaneous activity
• Normally Symp & Parasymp activity
influence HR (chronotropic effect)
▫ Mechanisms that affect HR: chronotropic
effect
 Positive increases; negative decreases
• Autonomic innervation of SA node is main
controller of HR
▫ Symp & Parasymp nerve fibers modify rate of
spontaneous depolarization
14-5

6. Regulation of Cardiac Rate continued
• NE & 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, slows
depolarization &
decreasing HR
Fig 14.1
14-6

7. Regulation of Cardiac Rate continued
• Vagus nerve:
▫ Decrease activity: increases heart rate
▫ Increased activity: slows heart
• Cardiac control center of medulla coordinates activity
of autonomic innervation
• Sympathetic endings in atria & ventricles can
stimulate increased strength of contraction
14-7

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
14-9

10. Regulation of Stroke Volume
• EDV is workload (preload) on heart prior to
contraction
▫ SV is directly proportional to preload & contractility
• Strength of contraction varies directly with EDV
• Total peripheral resistance = afterload which impedes
ejection from ventricle
▫ SV is inversely proportional to TPR
• Ejection fraction is SV/ EDV (~80ml/130ml=62%)
▫ Normally is 60%; useful clinical diagnostic tool
14-10

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 & SV
Fig 14.2
14-11

12. Frank-Starling Law of the Heart continued
• (a) is state of myocardial
sarcomeres just before
filling
▫ Actins overlap, actin-
myosin interactions are
reduced & contraction
would be weak
• In (b, c & d) there is
increasing interaction of
actin & myosin allowing
more force to be
developed
Fig 14.3
14-12

13. • At any given EDV,
contraction
depends upon level
of
sympathoadrenal
activity
▫ NE & Epi produce
an increase in HR &
contraction (positive
inotropic effect)
 Due to increased Ca2+
in sarcomeres
Fig 14.4
14-13

14. Extrinsic Control of Contractility
• Parasympathetic stimulation
▫ Negative chronotropic effect
 Through innervation of the SA node and myocardial
cell
▫ Slower heart rate means increased EDV
 Increases SV through Frank-Starling law

15. Fig 14.5
14-14

16. Venous Return
• Is return of blood to
heart via veins
• Controls EDV & thus
SV & CO
• Dependent on:
▫ Blood volume & venous
pressure
▫ Vasoconstriction caused
by Symp
▫ Skeletal muscle pumps
▫ Pressure drop during
inhalation
Fig 14.7 14-15

17. Venous Return continued
• Veins hold most of
blood in body (70%)
& are thus called
capacitance vessels
▫ Have thin walls &
stretch easily to
accommodate more
blood without
increased pressure
(=higher
compliance)
 Have only 0-
10 mm Hg pressure Fig 14.6
14-16

18. Blood Volume
• Constitutes small
fraction of total body
fluid
• 2/3 of body H20 is
inside cells
(intracellular
compartment)
• 1/3 total body H20 is
in extracellular
compartment
▫ 80% of this is
interstitial fluid; 20% is
blood plasma
Fig 14.8
14-18

19. Exchange of Fluid between
Capillaries & Tissues
• Distribution of ECF between blood & 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)
14-19

20. Exchange of Fluid between
Capillaries & Tissues
• Movement also affected by colloid osmotic
pressure
▫ = osmotic pressure exerted by proteins in fluid
▫ Difference between osmotic pressures in & outside
of capillaries (oncotic pressure) affects fluid
movement
 Plasma osmotic pressure = 25 mm Hg; interstitial
osmotic pressure = 0 mm Hg
14-20

21. Overall Fluid Movement
• Is determined by net filtration pressure & forces
opposing it (Starling forces)
▫ Pc + Πi (fluid out) - Pi + Πp(fluid in)
• Pc = Hydrostatic pressure in capillary
• Πi = Colloid osmotic pressure of interstitial fluid
• Pi = Hydrostatic pressure in interstitial fluid
• Πp = Colloid osmotic pressure of blood plasma
14-21

22. Fig 14.9
14-22

23. Edema
• Normally filtration, osmotic reuptake, &
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
14-23

24. Regulation of Blood Volume by Kidney
• Urine formation begins with filtration of plasma in
glomerulus
• Filtrate passes through & 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
14-24

25. ADH (vasopressin)
• ADH released by Post
Pit when osmoreceptors
detect high osmolality
▫ From excess salt
intake or dehydration
▫ Causes thirst
▫ Stimulates H20
reabsorption from
urine
• ADH release inhibited
by low osmolality Fig 14.11
14-25

26. Aldosterone
• Is steroid hormone secreted by adrenal cortex
• Helps maintain blood volume & pressure
through reabsorption & retention of salt & water
• Release stimulated by salt deprivation, low
blood volume, & pressure
14-26

27. Renin-Angiotension-Aldosterone System
• Decreased BP and flow (low blood volume)
• Kidney secreted Renin (enzyme)
▫ Juxaglomerular apparatus
• Angiotensin I to AngiotensinII
▫ By angiotensin-converting enzyme (ACE)
• Angio II causes a number of effects all aimed
at increasing blood pressure:
 Vasoconstriction, aldosterone secretion, thirst
14-27

28. Angiotensin II
• Fig 14.12
shows when
& how Angio
II is
produced, &
its effects
14-28

29. Atrial Natriuretic Peptide (ANP)
• Expanded blood volume is detected by
stretch receptors in left atrium & causes
release of ANP
▫ Inhibits aldosterone, promoting salt & water
excretion to lower blood volume
▫ Promotes vasodilation
14-29

30. Vascular Resistance to Blood Flow
• Determines how much blood flows through a tissue
or organ
▫ Vasodilation decreases resistance, increases blood
flow
▫ Vasoconstriction does opposite
14-31

31. 14-32

32. Physical Laws Describing Blood Flow
• Blood flows
through vascular
system when there
is pressure
difference (∆P) at
its two ends
▫ Flow rate is directly
proportional to
difference
▫ (∆P = P1 - P2)
Fig 14.13
14-33

33. Physical Laws Describing Blood Flow
• Flow rate is inversely proportional to
resistance
▫ Flow = ∆P/R
▫ Resistance is directly proportional to length of vessel
(L) & viscosity of blood (η)
 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 = ∆Pr4
(π)
ηL(8)
14-34

34. Fig 14.14. Relationship
between blood flow,
radius & resistance
14-35

35. Extrinsic Regulation of Blood Flow
• Sympathoadrenal activation causes increased
CO & resistance in periphery & viscera
▫ Blood flow to skeletal muscles is increased
 Because their arterioles dilate in response to Epi &
their Symp fibers release ACh which also dilates
their arterioles
 Thus blood is shunted away from visceral & skin to
muscles
14-36

36. Extrinsic Regulation of Blood Flow
continued
• Parasympathetic effects are vasodilative
▫ However, Parasymp only innervates digestive
tract, genitalia, & salivary glands
▫ Thus Parasymp is not as important as Symp
• Angiotensin II & ADH (at high levels) cause
general vasoconstriction of vascular smooth
muscle
▫ Which increases resistance & BP
14-37

37. Paracrine Regulation of Blood Flow
• 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
14-38

38. 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 & relaxes when not stretched
▫ E.g. decreased arterial pressure causes cerebral vessels
to dilate & vice versa
14-39

39. 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)
14-40

40. Aerobic Requirements of the Heart
• Heart (& 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 & aerobic enzymes
• During systole coronary vessels are occluded
▫ Heart gets around this by having lots of myoglobin
 Myoglobin is an 02 storage molecule that releases 02 to heart
during systole
14-41

41. 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
14-42

42. 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
14-43

43. Circulatory Changes During Exercise
• At beginning of exercise, Symp activity causes
vasodilation via Epi & local ACh release
▫ Blood flow is shunted from periphery & visceral to active
skeletal muscles
▫ Blood flow to brain stays same
• As exercise continues, intrinsic regulation is major
vasodilator
• Symp effects cause SV & CO to increase
▫ HR & ejection fraction increases vascular resistance
14-44

44. Fig 14.19
14-45

45. Fig 14.20
14-46

46. 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
14-47

47. Cerebral Circulation
• Is regulated almost exclusively by intrinsic
mechanisms
▫ When BP increases, cerebral arterioles constrict;
when BP decreases, arterioles dilate (=myogenic
regulation)
▫ Arterioles dilate & constrict in response to
changes in C02 levels
▫ Arterioles are very sensitive to increases in local
neural activity (=metabolic regulation)
 Areas of brain with high metabolic activity receive
most blood
14-48

48. Fig 14.21
14-49

49. Cutaneous Blood Flow
• Skin serves as a heat
exchanger for
thermoregulation
• Skin blood flow is
adjusted to keep deep-
body at 37o
C
▫ By arterial dilation or
constriction & activity of
arteriovenous anastomoses
which control blood flow
through surface capillaries
 Symp activity closes surface
beds during cold & fight-or-
flight, & opens them in heat &
exercise
Fig 14.22
14-50

50. Blood Pressure (BP)
• Arterioles play role in blood distribution &
control of BP
• Blood flow to capillaries & BP is controlled by
aperture of arterioles
• Capillary BP is decreased because they are
downstream of high resistance arterioles
Fig 14.23
14-52

51. Blood Pressure (BP)
• Capillary BP
is also low
because of
large total
cross-
sectional area
Fig 14.24
14-53

52. Blood Pressure (BP)
• Is controlled mainly by HR, SV, & peripheral
resistance
▫ An increase in any of these can result in increased BP
• Sympathoadrenal activity raises BP via arteriole
vasoconstriction & by increased CO
• Kidney plays role in BP by regulating blood volume &
thus stroke volume
14-54

53. Baroreceptor Reflex
• Is activated by changes in BP
▫ Which is detected by baroreceptors (stretch receptors)
located in aortic arch & carotid sinuses
 Increase in BP causes walls of these regions to stretch,
increasing frequency of APs
 Baroreceptors send APs to vasomotor & cardiac control
centers in medulla
• Is most sensitive to decrease & sudden changes in BP
14-55

54. Fig 14.26
14-56

55. Fig 14.27
14-57

56. Atrial Stretch Receptors
• Are activated by increased venous return & act to
reduce BP
• Stimulate reflex tachycardia (slow HR)
• Inhibit ADH release & promote secretion of ANP
14-58

57. Measurement of Blood Pressure
• Is 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 & noise as blood
passes constriction during systole & is blocked during
diastole
▫ 1st Korotkoff sound is heard at pressure that blood is 1st able
to pass thru cuff; last occurs when can no long hear systole
because cuff pressure = diastolic pressure
14-59

58. 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 Fig 14.29
14-60

59. Fig 14.30
14-61

60. 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
14-62

61. Hypertension
14-63

62. Hypertension
• Is blood pressure in excess of normal range for age &
gender (> 140/90 mmHg)
• Afflicts about 20 % of adults
• Primary or essential hypertension is caused by
complex & poorly understood processes
• Secondary hypertension is caused by known disease
processes
14-64

63. Essential Hypertension
• Constitutes most of hypertensives
• Increase in peripheral resistance is universal
• CO & HR are elevated in many
• Secretion of renin, Angio II, & aldosterone is
variable
• Sustained high stress (which increases Symp
activity) & 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 H20
14-65

64. Dangers of Hypertension
• Patients are often asymptomatic until substantial
vascular damage occurs
▫ Contributes to atherosclerosis
▫ Increases workload of the heart leading to ventricular
hypertrophy & congestive heart failure
▫ Often damages cerebral blood vessels leading to stroke
▫ These are why it is called the "silent killer"
14-66

65. 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, & Angio II-receptor blockers
14-67

66. Circulatory Shock
• Occurs when there is inadequate blood flow to, &/or O2
usage by, tissues
▫ Cardiovascular system undergoes compensatory changes
▫ Sometimes shock becomes irreversible & death ensues
14-69

67. Hypovolemic Shock
• Is circulatory shock caused by low blood volume
▫ E.g. from hemorrhage, dehydration, or burns
▫ Characterized by decreased CO & BP
• Compensatory responses include sympathoadrenal
activation via baroreceptor reflex
▫ Results in low BP, rapid pulse, cold clammy skin, low
urine output
14-70

68. 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
& resultant low BP
▫ Effective treatment includes drugs that inhibit
production of NO
14-71

69. 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
14-72

70. 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, & diuretics
14-73