Cardiac Output, Blood Flow, and Blood Pressure

•Chapter 14 Outline

•Cardiac Output•Blood & Body Fluid Volumes•Factors Affecting Blood Flow•Blood Pressure•Hypertension•Circulatory Shock

Cardiac Output Cardiac Output

Cardiac Output (CO)

Is volume of blood pumped/min by each ventricle

Heart Rate (HR) = 70 beats/minStroke volume (SV) = blood

pumped/beat by each ventricle◦Average is 70-80 ml/beat

CO = SV x HRTotal blood volume is about 5.5L

14-4

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

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

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

14-8

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

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

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

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 14.314-12

•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 14.414-13

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

Fig 14.514-14

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

inhalationFig 14.7 14-15

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 pressureFig 14.6

14-16

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 14.814-18

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

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

Overall Fluid Movement

•Is determined by net filtration pressure & forces opposing it (Starling forces)

▫Pc + i (fluid out) - Pi + p (fluid in)

•Pc = Hydrostatic pressure in capillary•i = Colloid osmotic pressure of interstitial

fluid•Pi = Hydrostatic pressure in interstitial fluid•p = Colloid osmotic pressure of blood plasma

14-21

Fig 14.9

14-22

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

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

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 14.1114-25

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

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

Angiotensin II

• Fig 14.12 shows when & how Angio II is produced, & its effects

14-28

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

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

14-32

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 14.1314-33

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 () 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() L(8)

14-34

Fig 14.14. Relationshipbetween blood flow, radius & resistance

14-35

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

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

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

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

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

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 systole14-41

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

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

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

Fig 14.19

14-45

Fig 14.20

14-46

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

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

Fig 14.2114-49

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 & 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 14.2214-50

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

Blood Pressure (BP)

•Capillary BP is also low because of large total cross-sectional area

Fig 14.24 14-53

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

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

Fig 14.2614-56

Fig 14.27

14-57

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

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

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 14.2914-60

Fig 14.3014-61

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

Hypertension

14-63

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

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

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

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

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

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

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

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

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