Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011

CHARACTERISTICS OF THE CARDIOVASCULAR SYSTEM, ABNORMALITIES AND DISEASES PART 1

Miklós Székely and Márta BalaskóMolecular and Clinical Basics of Gerontology – Lecture 8

Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011

TÁMOP-4.1.2-08/1/A-2009-0011

Mortality data

In 1995 the leading causes of death were:1 Cardiovascular 50.7% 2 Malignancies 22.9%3 Diseases of the GI tract 8.1% 4 Injuries, poisons, violence 7.8%

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Prevalence

Leading cause of death in both gender was cardiovascular (even preceding malignancies)• 65-74 years 50-52%• above 75 years 60%

TÁMOP-4.1.2-08/1/A-2009-0011Age-related physiological changesin the heart 1• Each ventricle pumps 200,000 m3 blood in 60

years through 40,000 km long capillary system with 1,000 m2 surface

• The aging of the cardiovascular system determines survival and longevity (100-120 years).

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Autonomicmodulation

Autonomicmodulation

Growth factors (AII, NE, ET,

TGFβ)

Cardiac factors:

Contractility Stretch

(systolic, diastolic)

Vascular factors: Pulsatile

elastance reflected

waves Nonpulsatile

PVR

Age-related physiological changesin the heart 2

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• In normotensive individuals a moderate, age-related thickening of the ventricular wall may be physiological

• The size of the left atrium and the internal diameter of ventricle also increases with age (not always statistically significant)

• On a chest X-ray an increase of heart contours is observed

• Hypertrophy of the myocytes is mostly behind the thickening of the ventricular wall, but increase in the connective tissue (fibrosis) also contributes

• Fibrosis and calcification may be observed everywhere within the heart (aortic valve, annulus fibrosus), ventricular compliance decreases

Age-related physiological changesin the heart 3

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• Early diastolic filling of the heart decreases (at the age of 80 years ca. 50%, in the young 2× as much blood flows into the ventricle than in later phases)

• The mitral valve closes more slowly• The late diastolic filling is quicker/more

effective (due to the contraction of the heart) (filling in the elderly early:late=1:1)

• EDV mostly increases particularly in males

Age-related physiological changesin the heart 4

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During ExerciseAt rest

Youngheart

Oldheart

Size at the end of heart beat

is smaller than at rest

Size at the start of heart beat

is the same as at rest

Size at the start of heart beat

is larger than at rest

Size at the end of heart beat

is the same as at rest

At the end ofheart beat, at

rest

At the start ofheart beat, at

rest

At the start ofheart beat, at

rest

At the end ofheart beat, at

rest

Age-related physiological changesin the heart 5

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• The number of the atrial pace-maker cells decreases 50-75% by the age of 50 – pulse decreases

• The cell count of the AV node is maintained, but the speed of conduction is slower

• His cell count decreases – fibrosis• The heart rate at rest remains normal, but

exercise induced maximum decreases by 30% (by the age of 80) the maximal possible heart rate and cardiac output decreases to the same extent

• The responsiveness to b-adrenergic effects decreases (changes in the membrane G-proteins)

Age-related physiological changesin the heart 6

TÁMOP-4.1.2-08/1/A-2009-0011Cardiac output measured at rest and at exhausting exercise (upright position) vs. age in athletes and sedentary individuals

D

A

B

C

20

16

12

8

4

20 40 60 80Age (years)

Card

iac

outp

ut (L

/min

) r=.14, p>.26

r=.47, p<.001

r=.16, p>.23

r=.70, p<.001

TÁMOP-4.1.2-08/1/A-2009-0011Age-related physiological changesin the circulation 1• The arterial wall becomes more rigid, the

aorta shows distension: due to the quantitative and qualitative changes in elastin and collagen fibers.

• Calcium deposition and collagen cross-links make the vessels even more rigid.

• Glycoprotein disappears from the elastic fibers, they become fragile/brittle, the mineral content of the elastin increases, the polar amino acid content also rises.

• The elasticity of the aorta is diminished, during diastole the pressure falls steeply!(It decreases coronary circulation!)

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• Remodelling of the small vessels, the functional capillary number decreases – the oxygen supply of the tissues decreases!

• The thickness of the tunica intima and media increases, e.g. in the a. carotis communis the normal mean of 0.35 mm – may increase to 2-3-times higher (higher levels of growth factors, smooth muscle proliferation, transformation)

• The tone of the vessels changesNO decreases, ROS, TxA2 PGH2 increase Ca-dependent vasoconstriction is Ca-activated or voltage-dependent K+-channel a-subunit density decreases in the vascular smooth muscle membranes

• Besides all these, atherosclerosis further increases the rigidity of the vessels (depending on severity)

Age-related physiological changesin the circulation 2

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• The myocardial contractility decreases• The duration of both the systole, and the

diastole increases (slower) (ionflux of the L type Ca++ channels increases, their activity becomes longer)

• Due to the fall of the diastolic pressure the coronary circulation decreases

Age-related physiological changesin the coronary circulation

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Changes in the cardiovascular function 1Ventricular filling, preload • The early filling becomes progressively

slower after the age of 20, by 80-y it is only half of the original• despite this, the EDV does not decrease in

healthy old people, because the major part of the filling takes place in the second phase

• The enlargement of the atria and their stronger contraction is responsible for the late filling (at 20-y 20%, 80-y 40%)

TÁMOP-4.1.2-08/1/A-2009-0011Comparison between theearly diastolic and atrial contribution toleft ventricular filling in persons of a broad age range

90

80

70

60

500 20 40 60 80 100Age (years)

Early

dia

stol

ic fil

ling

volu

me

(% o

f to

tal fi

lling

volu

me)

50

40

30

20

100 20 40 60 80 100Age (years)La

te d

iast

olic

fillin

g du

e to

atri

al c

ontra

ctio

n(%

of

tota

l fillin

g vo

lum

e)

men women

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Changes in the cardiovascular function 2Ventricular filling , preload• In auscultation 4th (atrial) sound

appears – gallop rhythm • In acute atrial fibrillation the loss of

coordinated atrial contraction leads to a loss of this function. In people with chronic left ventricular failure it leads to an acute heart failure

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Changes in the cardiovascular function 3Afterload• the vessels are more rigid• the speed of the pulse wave is up – with a quick

reflection of the pulse wave, already within the systole, interference of waves may decrease the coronary circulation

• the sensitivity of the baroreceptor reflex decreases• the systolic blood pressure increases • the ventricular emptying is impaired • dilatation of the left ventricle• the thickening of the ventricular wall may have

benefits according to the LaPlace law), normalizing the systolic function and the ejection fraction

In case of an abnormal blood pressure, treatment is necessary – isolated systolic hypertension

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Myocardial contractility

The myocardial performance, i.e. the cardiac output depends (besides the pre- and afterload) on the contractility of the heart

TÁMOP-4.1.2-08/1/A-2009-0011The interplay of vascular and adaptive cardiac changes during aging

arterialstiffenin

g

pulse wave

velocityandearly

reflected waves

systolicblood

pressure with late

peak

LVwall

tension

LVhyper-trophy

Normali-sation ofLV wall tension

normalend-systolic volume and

ejection fraction

aorticroot size

prolonged contraction

early diastolic

filling

atrialsize

atrialfilling and

contraction

Normalend-diastolic

volume