Circ Sys Physio Notes

8/6/2019 Circ Sys Physio Notes

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Circulatory System

BME 5010 - EngineeringPhysiology

Objectives

1. Describe components of circulatory system

2. Explain mechanical physiology of heart

3. Detail mechanisms of cardiac output control

4. Describe vascular system and the role of eachcomponent in blood and nutrient distribution

5. Describe mechanisms of vascular control

6. Define lymphatic system

7. Discuss major forms of cardiovascular disease

Circulatory System

Designed to move substances from one

region of the body to another

Oxygen - Carbon dioxide

Metabolites - Waste products

Hormones - Metabolic end products

Required in large, multicellular organismswhere diffusion is not sufficiently rapid to

meet the metabolic needs of cells


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Blood

Composed of cells and plasma

Erythrocytes - red blood cellsn Transport oxygen

Leukocytes - white blood cellsn Immune system

Platelets - cell fragmentsn Blood clotting

Plasman Fluid containing proteins and dissolved molecules

ErythrocytesContain a large amount of hemoglobinn Iron in hemoglobin binds to oxygen to transport a greater

amount than could dissolve in plasma

High surface-volume ratio to allow oxygen to diffuserapidly to the center of the cell

Do not have nuclei or organellesn Cannot reproduce

Produced in the red bone marrown All bones in children

n Chest, base of skull, ends of long bones in adults

Destruction of old cells occurs in liver and spleen

Typical life span of 120 days

Cardiovascular System

Consists of heart, arteries, capillaries, andveins

Almost all cells are within a few cell diametersof a capillaryn Allows for movement of materials between the cell

and the capillary by diffusion and mediatedtransport

Two vascular systemsn Systemic circulation

n Pulmonary circulation


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Pulmonary Circulation

Right atrium

Right ventricle

Pulmonary trunk

Pulmonary arteries

Capillaries within lungs

Pulmonary veins

Left Atrium

Blood picks up oxygen and deposits carbondioxide in the lungs

Systemic Circulation

Left atrium

Left ventricle

Aorta

Arteries

Arterioles

Capillaries

Venules

Veins

Superior/inferior venacava

Right atrium

Oxygenated blood carriedfrom heart to tissues

Blood returning from

heart contains low levelsof oxygen and high levels

of carbon dioxide

Blood also transportsmetabolites, waste

products, and hormones

to and from organs andtissues

Blood Pressure and Flow

Blood flows from regions of high pressure to regions oflow pressure

Blood pressure is originally created by the contractionforce of the heart

Blood flow through a region is related to:

n the pressure difference between the inlet and outlet

n the resistance of the blood vessels to fluid flow

F = P/R

F = P r4/8l

n r = radius

n = viscosity


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Vascular Resistance

Resistance is dependent onn fluid viscosity

n vessel length vessel diameter

Viscosity depends on the concentration of redblood cells in the blood (hematocrit)n Not a physiologically controlled variable

n Pathologies can affect resistance

Vessel length is constant

Resistance is controlled through variations invessel diametern (R 1/r4)

n 2 fold decrease in radius --> 16 fold increase inresistance

The HeartFour chamber organ composed primarily of cardiacmuscle (myocardium) lined with epithelium cells

Valves exist betweenn Atrium and ventricle

n Ventricle and large arteries

Healthy valves offer little resistance to flown Diseased valves may become narrowed and cause high

resistance to flow

Receives substantial innervention from sympatheticand parasympathetic nervesn Regulate cardiac function (via messengers)

Receives blood supply through coronary arteries

coming off aorta

Atrioventricular Valves

Tricuspid valve is between the right atriumand ventricle

Mitral valve is between the left atrium andventricle

Valves open passively on contraction of theatria to allow blood to flow to the ventricles

Valves close passively on contraction of theventricles to prevent backflow into the atrian Chordae tendinae attach valve leaflets to

ventricular wall to prevent inversion of the valves


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Semilunar Valves

Between the ventricles and the large arteriesto prevent backflow from the arteries

Pulmonary valve is between the rightventricle and the pulmonary trunk

Aortic valve is between the left ventricle andthe aorta

Open passively on contraction of theventricles

Close passively on relaxation of the ventriclesn Do not have chordae tendinae

Mechanics of CardiacContraction

Cardiac contraction can be divided into two major andadditional minor phases

Systole - ventricular contraction and blood ejection (0.3seconds)

Step 1- Isovolumetric contraction:

n Increase in pressure closes tricuspid and mitral valves

n Pressure increases but not enough to open semilunarvalves

n Ventricular blood volume remains constant

Step 2- Ventricular ejection:

n Ventricular pressure exceeds vascular pressure,semilunar valves open

n Blood is forced from the ventricles


Diastole - ventricular relaxation and blood filling (0.5seconds)

Part 1- Isovolumetric relaxation:n Ventricular pressure drops below vascular pressure, semilunar

valves close

n Ventricular pressure remains above atrial pressure, mitral andtricuspind valves remain closed

n Relaxation reduces ventricular pressure but no blood flows in toincrease volume

Part 2 - Ventricular filling:n Ventricular pressure drops below atrial pressure, mitral and

tricuspid valves open

n Ventricles begin filling (about 80% of volume)

n Atial contraction finishes filling (remaining 20% of volume)


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Pressure-Volume Curves

Volume

Pressure

Isovolumetric

Contraction

Isovolumetric

Relaxation

Cardiac Volumes

Stroke Volume (SV): amount of blood ejectedfrom each ventricle during a singlecontraction

End Diastolic Volume (EDV): amount of bloodin the ventricle at the end of diastole

End Systolic Volume (ESV): amount of bloodremaining in the ventricle at the end ofsystole

SV = EDV - ESV

Pressure-Volume Curves

Volume

Pressure

EDV ESV

SV


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Ventricular Pressure-VolumeCurve

Describesrelationshipbetween pressureand volumethroughout cardiaccycle

Two curves:n Passive filling

curve

n Active contractilitycurve

Ventricular

Volume

Ventricular

Pressure

Passive

Filling

Active

Contractility

ESVEDV


Pressures and volumes change within the heartschambers and the vascular system during the cardiaccyclen Aorta and pulmonary artery

n Left and right atria

n Left and right ventricles

See Figures 14-25 and 14-26

Systemic arterial pressures typically vary between 120and 70 mmHg

Pulmonary arterial pressures typically vary between 24and 8 mmHg

Right ventricle pumps the same amount of blood over a

given time period as the left ventricle


Important Notes:

Most ventricular filling occurs before atrial contractionoccurs

Heart rates of 200 beats/minute or higher do not allowadequate time for full ventricular filling

Ventricular contraction does not completely enter theventricles

As ventricular pressure increases during isovolumiccontraction, vascular pressure is also decreasing asblood flows further into the system

The myocardium has some components of springbehavior and recoils on relaxationn Creates a slight negative pressure which draws blood into the

ventricle during filling


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Cardiac Output

Volume of blood pumped by each ventricle per minuten Flow through either the systemic or pulmonary circuit

per minute

A function of the heart rate and the stroke volume

CO = HR x SV

Example:n HR = 72 beats/minute SV = 0.07 liter/beat

n CO = 5.0 liter/beat

Normal total blood volume = 5 liters

n Total blood volume pumped through one circuitevery minute

Control of Heart Rate

Controlled by natural pacemaker of heart (SA

Node)

Modified by sympathetic and parasympatheticinnervation

n Details to be discussed during cardiacelectrophysiology

Control of Heart Rate

Hormonal influences:

n Epinephrine speeds heart rate

wActs at same receptors as sympathetic

neurotransmitter norepinepherineOther minor influences:

n Body temperature

n Plasma electrolyte concentrations

n Additional hormones


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Control of Stroke Volume

A more forceful contraction can cause anincrease in stroke volume

Force of contraction is influenced by:n End-diastolic volume (pre-load)

n Sympathetic innervention of ventricles

n Arterial pressure

wF = P/R

w Lower pressure differential (due to increasedarterial pressure) reduces flow from ventricleand thus stroke volume

Frank-Starling LawDefines how contraction stroke volume relates to

EDV

Ventricle contracts more forcefully when it is filled to

a greater extent before contraction

Relationship is defined by a ventricular function curve

0 100 200 300 400

200

100

0StrokeVolume(ml)

EDV (ml)

Normal Resting Value

Frank-Starling LawBased on the length-tension relationship ofcardiac musclen Stretch of cardiac muscle results in increased

muscular contraction force up to a maximal limit

n Normal resting length for cardiac muscle is not at

optimal length for contraction, but on rising curveIncreased flow of blood from the veins(venous return) results in an automaticincrease in end diastolic volume and strokevolumen If right heart begins to pump more than left,

increased venous return to left ventricle brings leftheart CO to correct level


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Neural Control of Stroke Volume

Norepinephrine from sympatheticnerves acts to ventricular contractility

n Strength of contraction at any givenEDV

Shifts ventricular function curve up

Contractility can be measured throughejection fraction (EF)EF = SV/EDV

Normal ejection fraction is about 67%

Increases rate of cross-bridge cyclingas well as cytosolic calciumconcentration

SV

EDV

Vascular System

Arteries

Arterioles

Capillaries

Venules

Veins

Composed of various amounts ofn Smooth muscle

n Elastin

n Collagen

Lined with endothelial cells

Arteries

Large radii

Low resistance tubes to conduct blood flow

Arterial pressure depends on:n Volume of blood within arteries

n Compliance (stretchability) of vessel walls

Compliance defined as the amount of volumechange per unit pressure change

C = V/P


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Arteries

Blood in the amount of SV flows into the arteriesduring systole

Only 1/3SV leaves arteries during systole

Remainder remains in arteries, resulting in arterialdistension

n Increases arterial pressure (systolic pressure)

During diastole, recoil in arterial walls causessecondary pumping of arterial blood to moveadditional portion of SV

n Arterial pressure gradually declines to its minimumlevel (diastolic pressure)

Some blood remains in arteries at all times, sodiastolic pressure is not zero

Arterial Pulse Pressure

Pulse pressure is defined as the differencebetween systolic and diastolic pressures

The magnitude of the pulse pressure isdetermined by:n Stroke volume - determines systolic pressure

n Speed of stroke volume ejection - influencestransition between systolic and diastolic pressure

n Arterial compliance - determines systolic anddiastolic pressure

wDecreased compliance due to atherosclerosis

increases pulse pressure

Mean Arterial Pressure

Average arterial pressure over the length ofone cardiac cyclen Due to asymmetric pressure curve, not the value

halfway between the systolic and diastolicpressure

n Approximated by:MAP = DP + 1/3(SP - DP)

Pressure driving blood into tissues over entirecardiac cycle

Arterial tree has minimal resistance (due tolarge diameter), so acts as single pressurereservoir with pressure equal to MAP


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Arterioles

Distribute blood to vicinity of tissues and organsBlood pressure drops from mean value of 90 mmHgto 35 mmHg between beginning and end ofarterioles

Determine relative blood flow to the organs andtissues

n Resistance of arterioles locally controlled bycontrolling diameter

n Regions of higher resistance have less blood flow

n Contain smooth muscle which acts to constrict ordilute vessels

wVaried from natural state of myogenic tonewhich resutls from spontaneous contraction ofsmooth muscle

Local Control of ArterioleResistance

Control mechanisms independent of nervesor hormones which allow organs to controlown blood flow

Active Hyperemia: increased blood flow inresponse to increased metabolic activityn Results from local chemical changes in

extracellular fluid around arterioles

n Most highly developed in skeletal muscle, cardiacmuscles, and glands

Local Control of ArterioleResistance

Flow Autoregulation: results when a tissue or organsuffers a change in its blood supply as a result of achange in blood pressure

n Change in resistance acts to maintain blood flow

n Decreased resistance triggered by:

wReduction of oxygen concentration, increased CO 2,increased H+, increased metabolites

wSame triggers as active hyperemia

n Acts in cases of decreased or increased bloodpressure

n Can also be triggered by stretch-response of smoothmuscle

w Increased pressure --> stretch --> vasoconstriction


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Local Controls of ArterioleResistance

Reactive Hyperemia: results after a tissue ororgan has had its blood supply completelyoccludedn Blood supply increased substantially as soon as

occlusion removed

n During occlusion, arterioles in region dilatecompletely due to autoregulation triggers

n Arterioles are wide open when occlusion isremoved

Response to Injury: injured cells and tjissuesrelease various substancesn Trigger vasodilation to increase blood supply to

injured site

Extrinsic Control of ArterioleResistance

Sympathetic Nerves:

n Rich supply to arterioles

n Release norepinepherine

n Increased activity causes vasoconstriction

n Decreased activity causes vasodilation

wBased on steady stimulation of vessels

n Control global blood flow to serve wholebody needs

Extrinsic Control of ArterioleResistance

Noncholinergic, Nonadrenergic AutonomicNeuronsn Release nitric oxide (not acetylcholine or

norepinephrine)

n Plays a major role in control of blood supply to GItract

n Mediate penile erection

Hormonesn Epinephrine

n Angiotensin II

n Vasopressin


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Hormonal Control of Arteriole

Resistance

Epinephrinen Binds to alpha-adrenergic receptors on smooth

muscle to cause vasoconstriction

n Binds to beta-adrenergic receptors on smoothmuscle to cause vasodilation

n Alpha receptors generally outnumber betareceptors, with the exception of skeletal muscle

Angiotensin IIn Constricts arterioles

n Increases sympathetic nervous activity

Hormonal Control of Arteriole

Resistance

Vasopressin

n Plasma borne hormone

n Released by posterior pituitary gland

n Causes constriction of arterioles

Paracrine Control of ArterioleResistance

Endothelial cells lining arterioles respond to hormonaland neurological stimulation, releasing paracrine agentsthat affect nearby smooth muscle cells

Nitric oxide

n Contributes to basal levels of vasodilation

n Increased levels released in response to chemicalmediators, result in increased dilationw example: inflammation processes

Prostacyclin (PGI2)

n Minimal basal secretion

n Increased secretion in response to chemical inputresults in vasodilation

n Participates in blood clotting


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Paracrine Control of ArterioleResistance

Paracrine agents can also act asvasoconstrictorsn Endothelin-1 (ET-1)

In arteries, shear stress in endothelial cellsdue to blood flow also causes release ofparacrine agentsn Increased stress -->

w Increased PGI 2w Increased NO

w Decreased endothelin-1

n Flow-induced arterial vasodilation

Capillaries

At any moment, 5% of total circulating bloodis flowing through the capillaries

Blood in capillaries performs ultimate functionof exchanging gases, nutrients, andmetabolic end products

Approximately 25,000 miles of capillaries inan adultn 5 m in diameter - one cell

n Each is about 1 mm long

Capillary AnatomyThin-walled tube of endothelial cells

n No smooth muscle

Endothelial cells separated by intercellular clefts

n No firm attachment between cells

n Form channels from capillary to extracellular fluid

Fused-vessical channels within cells also formchannels from capillary to extracellular fluid

Blood flow generally controlled by arteriole resistance

Capillaries branch off from metarterioles

n Connect arterioles to venules

n Site of capillary exit is surrounded by precapillarysphincter (smooth muscle) to control flow


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Capillary Blood Flow

Velocity of blood flow is inversely proportionalto total cross-sectional area of vessel type

n Arteries and arterioles have lower total cross-

sectional area, and thus higher blood flow rate

Aorta Arteries VeinsCapillaries

Total X-section

Area (cm2)

Mean Linear

Velocity (cm/s)

Capillary ExchangeThree mechanisms of exchange between capillariesand extracellular fluid

n Bulk flow

n Diffusion

n Vesicle transport

Diffusion is predominant transport mechanism for

n Nutrients

n Metabolic end products

n Oxygen

Exception is brain due to blood-brain barrier

n Requires carrier-mediated transport of water-

soluble molecules

Capillary Exchange - Diffusion

Lipid-soluble molecules diffuse throughmembrane of endothelial cells

Ions and polar molecules diffuse throughintracellular clefts and fused vesicle channels

n Water-filled channelsn Reasonably high permeability, but lower than that

of lipid-soluble molecules

n Only small amounts of proteins can di ffuse throughmost channels


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Capillary Exchange -- Diffusion

Size of channels determines leakiness ofcapillaries in various tissues/organsn Brain - no intracellular clefts

n Liver - large clefts and plasma membranewindows

wAllows diffusion of even large proteins

Diffusion depends on tissue and bloodconcentrations of materialsn Increased cellular activity reduces tissue

concentration of O2 and nutrients, increasesconcentration of CO2- and metabiolic endproducts

n Change in concentration gradient increasesdiffusion

Capillary Exchange -- VesicleTransport

Additional mechanism for transport ofsmall amounts of protein

n Endocytosis of protein-containing plasmaat blood-side of endothelial cell

n Exocytosis of proteins into extracellar fluid

by resultant vesicle

Capillary Exchange - BulkFlow

Bulk flow of plasma acts to distribute extracellularfluid

If there exists a hydrostatic pressure differenceacross capillary wall, endothelial cells act as porousfilter allowing transport of protein-free plasma*ultrafiltrate) through water-filled channels

Normally, capillary blood pressure is higher thaninterstitial hydrostatic pressuren Capillaries --> extracellular fluid

Hydrostatic driving pressure offset by osmotic forcedue to protein concentration in plasma (high) vs.extracellular fluid (low) which drives water to flow intocapillaries


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Capillary Exchange - BulkFlow

Starling forces are the four factors whichgovern bulk flow of fluid

n Capillary hydrostatic pressure (Pc)

n Interstitial hydrostatic pressure (Pt)

n Plasma protein concentration (pc)

n Interstitial fluid protein concentration (pt)

F = K[(Pc - Pt) - (pc - pt)]

Capillary Exchange -- BulkFlow

At the beginning of the capillary hydrostatic

pressure difference is 35 mmHg, osmoticpressure difference is 25 mmHg

n Fluid flows into tissue (filtration)

At end of capillary, hydrostatic pressuredifference is 15 mmHg, osmotic pressuredifference is 25 mmHg

n Fluid flows out of tissue (absorption)

Capillary Exchange -- BulkFlow

Filtration and absorption along length of capillary tend tocancel each other out

Net filtration in systemic circulation (not includingcapillaries in kidneys) of about 4 liters/day

n Fluid then transported by lymphatic system

Dilation of arterioles leading to a capillary bed increasescapillary pressure, increasing filtration (and vice versa)

Capillary filtration and absorption are not significantmechanisms of nutrient and waste product transport

In pulmonary circulation, low resistance means lowcapillary pressures

n Normal hydrostatic pressure of 15 mmHg means netabsorption


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Veins

First blood flows into venulesn Exchange of materials can occur in venules

Peripheral veinsn Outside of the chest

n Have valves that permit flow only towards theheart

n Pressure is low as greatest resistance occurs inarterioles and capillary beds

n Act as low resistance conduits to heart

n Diameters altered through smooth muscle tomaintain peripheral venous blood pressure andblood return to the heart

Venous Pressure -Determinants

Total blood volume

n Most of blood in veins at any given moment due tohigh compliance

Constriction of veins

n Smooth muscle innervated by sympathetic neurons

n Sympathetic activation causes vasoconstriction toreturn more blood to right heart

Skeletal muscle pump and respiratory pump

n Veins through muscles are compressed with musclecontraction

n Increased abdominal pressure during inspiration

compresses intrabdominal veins, decreased thoracicpressure assists in venous return

Venous Return

Must be identical to cardiac outputexcept for brief instances

Assisted by muscular and respiratory

pumpsValves prevent gravity or pumps fromdriving blood away from heart


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Lymphatic System

Network of lymph nodes and lymphatic vessels thattransport a fluid derived from interstitial fluid (lymph)

Interstitial fluid enters lymphatic capillaries by bulkflow

n The four liters not reabsorbed into capillariesfollowing filtration

Fluid returned to vascular system via one-way valvesat the subclavian veins of the neck

Failure to return lymph through this system results inedema, fluid build-up in the tissues

Lymph is pumped through the lymphatic system byrhythmic contraction of the smooth muscle in thevessels

Regulation of Systemic ArterialPressure

Mean arterial pressure of the systemic circulation is themain controlled variable in the circulatory system

n Driving force for all blood flow except pulmonary

MAP = CO x TPR

n Function of cardiac output and total peripheral resistance

n Resistance sums like electrical resistors

wRT = R1 + R2 for vessels in series

w 1/RT = 1/R1 + 1/R2 for vessels in parallel

If resistance in one area decreases (ex: arterioles toskeletal muscles relax during exercise), TPR can bemaintained if resistance in another area is increased (ex:kidneys, GI)

n Brain arterioles maintain constant resistance

Regulation of Systemic ArterialPressure

Juggling of resistances can only work withina limited range

If resistance in one area drops drastically(such as in hemorrhage), constriction of other

vessels cannot maintain systemic bloodpressure

Short-term control is through baroreceptorreflexes

Long-term control is through blood volumechanges


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Pulmonary Arterial Pressure

Mean Pulmonary Arterial Pressure =n CO x Total Pulmonary Vascular Resistance

CO is the same for pulmonary and systemiccirculations

Mean pulmonary arterial pressure is less thanmean systemic arterial pressure

THEREFORE, Total pulmonary vascularresistance is less than total systemic vascularresistance

Arterial Baroreceptors

1. Located in the carotid arteries of the neck

n Carotid sinus

n Numerous afferent nerve endings

2. Located in the aortic arch

Respond to stretch of arterial wall

n Rate of neural discharge is proportional to theMAP (for steady pressures) or the pulse pressure(for pulsatile flow)

Medullary CardiovascularCenter

Main integrating center for baroreceptor reflexes

Increase in baroreceptor discharge results in:

n Decrease in sympathetic stimulation to vasculature

wVasodilation (decreased vasoconstriction)

n Increase in parasympathetic stimulation to heartwDecreased heart rate

Also affect secretion of vasopressin and angiotensin II

Short-term effect

n Long term changes in MAP or pulse pressure willresult in resetting of baroreceptor threshold


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Hemorrhage and Hypotension

Baroreceptor reflexes and absorption through capillariescan compensate for loss of up to 1.5 liters of blood (30%

total volume) with only slight reductions in MAP or CO

n Increased heart rate above normal

n Increased stroke volume towards normal

n Increased total peripheral resistance above normal

Any loss of fluid results in a decrease in circulatory

volume and reaction based on cardiovascular reflexes

n Hemorrhage

n Dehydration

n Diarrhea or vomiting

Shock

Denotes any situation where a decrease inblood flow results in damage to organs ortissues

Can result from:n Severe hemorrhage

n Loss of fluid

n Excessive release of vasodilators (allergy orinfection)

n Loss of sympathetic stimulation of cardiovascularsystem

n Severe bodily damage (general)

Hypertension

Chronically elevated systemic blood pressure

n Over 140/90 mmHg (systolic/diastolic)

Most common cause is increased TPR due toreduced arteriolar radius

Can result in left ventricular hypertrophyn Left ventricle has to pump against increased

resistance

n Changes in myocardium can result in heart failure

Increases risk of:

n Atherosclerosis and heart attacks

n Kidney damage

n Rupture of cerebral blood vessel (stroke)

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Circ Sys Physio Notes