Transcript Image Atlas of Aging - University of Massachusetts Medical School

The Aging
Heart
Age-Related Changes in Cardiac Structure
and Function
Emily Kaditz
UMMS Donald W. Reynolds Foundation
Summer Intern 2012
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Why Care About Pictures of the
Normal Aging Process?
Images of Normal
vs. Pathology
Text on
Normal vs.
Aged
Images
of
Aged
Almost no resources
available
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Why Should You Care?
 The % of people 65 years and older is projected to rise from 13% to
20% between 2010 and 2030.
Older US Population by Age: 1950-2050
Percent 60+, Percent 65+, and 85+
30%
% 60+
% 65+
Regardless of
the field of
medicine you
choose, you
will treat more
patients who
are 65 years or
older than any
previous
generation of
physicians.
% 85+
25%
20%
15%
10%
5%
0%
1950
1960
1970
1980
1990
2000
2010
2020
2030
2040
2050
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Aging ≠ Disease
And disease is not inevitable with aging
However, the chance of developing some diseases increases with
age…
This is a function of HOMEOSTENOSIS.
Normal
young
Normal
aged
PASSAGE OF TIME
Disease
(sometimes)
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Homeostasis vs. Homeostenosis
Homeostasis = the process through which the body
maintains internal equilibrium.
 With aging, more physiologic reserves are
needed to maintain homeostasis when the body is
not at rest.
Homeostenosis = the normal decline in the body’s
functional reserves.
 With aging, homeostenosis increases the
vulnerability of organs to certain disease states, but
a homeostenotic organ is not necessarily diseased.
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Homeostenosis
Physiologic reserves allow us to
maintain homeostasis in the
presence of environmental,
emotional, or physiological stress.
+
HOMEOSTASIS
STENOSIS
= HOMEOSTENOSIS
With homeostenosis, an insult that may
be withstood in a younger person pushes
the elderly beyond their functional
capacity, causing decompensation,
disease, or death.
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Homeostenosis
•
Exertion requires the body to engage its physiologic reserves.
•
The homeostasis line can be thought of as the state of the heart at rest.
•
Think of the red arrow as representing the physiologic reserve
required to carry 20 lbs. up a flight of stairs.
You
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Consider a Case…
A normal 78 year old woman comes in for her regular check-up. She
reports feeling fine at rest, and is able to do most of her activities of daily
living (ADL) without any problems. Recently, however, she has noticed
that when carrying things up stairs in her home she becomes short of
breath, and has even had to stop and rest if her load is too heavy.
What is causing her shortness of breath?
• It is normal for the capacity for physical exertion to decline with
aging.
• In the heart, normal aging brings about changes that contribute to
this decreased tolerance for exertion.
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Homeostenosis in the Aging Heart
In other words, a homeostenotic heart is one that has undergone
the normal aging process.
Compared with a normal young heart, the aged heart has a
decreased functional capacity, but is not diseased.
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Homeostenosis: Visual Evidence
While homeostenosis is a
physiologic
phenomenon, its
anatomic basis can be
seen on a gross and
histological level.
Let’s turn to consider
this…
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Quick Review:
Heart Structure & Blood Flow
Superior
Inferior
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Cardiac Homeostenosis:
Changes with Normal Aging
1. Structural
a.  LV wall thickness,  LV
chamber size
2. Histologic/Cellular
b. Aortic valve calcification
c.
Mitral annulus calcification
3. Molecular
4. Functional
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Left Ventricular Structural Changes
 left ventricular (LV) wall thickness,  LV chamber size
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Valvular Changes
Insert image Normal Aortic Valve
image such as can be viewed via
http://www.heart-valvesurgery.com/Images/normal-aorticvalve.jpg
Insert image Normal Mitral Valve
image such as can be viewed via
http://dx.doi.org/10.1016/j.carrev.2009.
10.004
Normal mitral valve
Normal aortic valve
Leaflet
calcification
Insert image Annulus
Calcification image such as can
be viewed via http://www.heartvalve-surgery.com/Images/mitralvalve-calcification.jpg.
Annulus
calcification
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Cardiac Homeostenosis:
Changes with Normal Aging
1. Structural
2. Histologic/Cellular
3. Molecular
4. Functional
a.  # of cardiomyocytes
b. ( apoptosis, necrosis)
c.
 myocyte size
(hypertrophy)
d.  lipid deposits
e.  lipofuscin deposition
f.
 collagen deposition and
fibrosis in myocardium
g. Thickening of arterial intima
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
 Myocyte #,  Myocyte Size (Hypertrophy)
Medium Power
Low Power
Normal
Aged
Normal
High Power
Note: Clear spaces
between the muscle
fibers are artifacts
due to slide
processing and are
not present in living
tissue, however there
is a slight increase in
inter-myocyte space
in the aged heart.
Aged
Muscle fibers
thicken
Nuclei of
hypertrophic
myocytes are
larger and
darker
Normal
Aged
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
 Lipid Deposits  Lipofuscin Deposition
Lipofuscin (black
arrows) is a brownish
“wear and tear” pigment
that accumulates with
age.
The pigment is a product
of lipid oxidation, and is a
sign of free radical
damage.
UMMS CC License Guido Majno
Collagen
deposition/
fibrosis
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Thickening of Arterial Intima
UMMS CC License Guido Majno
Normal
UMMS CC License Guido Majno
Aged
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Cardiac Homeostenosis:
Changes with Normal Aging
1. Structural
2. Histologic/Cellular
3. Molecular
a. Altered Ca2+ handling
b.  β-adrenergic
4. Functional
responsiveness
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Altered Ca2+ Handling
• At rest, intracellular Ca2+ is largely sequestered in the sarcoplasmic
reticulum (SR). This is the same in the old and young heart (the
figures above are mirror images of one another).
• Contraction of cardiac muscle depends on the release of Ca2+ from
the SR.
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Changes in Ca2+ Contribute to  Contractility
Normal
shown
as
dashed
lines
Changes in Ca2+ channel activity
contribute to the prolongation of
APs in the aged heart.
These changes also decrease the
Ca2+ stored in the SR, which
means action potentials trigger a
smaller rise in intracellular [Ca2+].
This is important because the force of
myocardial contraction is proportional
to the amount of Ca2+ released.
Thus, these changes in Ca2+ handling
contribute to the decreased contractility
of the aged heart.
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
 β-adrenergic Responsiveness
Isoproterenol is a β-agonist (it
stimulates β-receptors), similar to
epinephrine (think of an adrenaline
rush). Isoproterenol increases
calcium release, and thus the force
of myocyte contraction.
Normal
Aged
The decline in β–adrenergic
responsiveness means that the
aged heart gets less of a boost
in contractility when stimulated
by the sympathetic nervous
system compared to the young
heart.
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Cardiac Homeostenosis:
Changes with Normal Aging
1. Structural
2. Histologic/Cellular
3. Molecular
4. Functional
a.  Afterload
b. Diastolic dysfunction
c.
Decreased contractility
d.  Maximum HR
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
 Compliance of larger arteries
+  Cross-sectional area of arterioles
 Systemic vascular resistance
 Afterload
 Afterload means that
during systole, the LV must
work harder to eject blood
into the less compliant
aorta.
Q: What happens when a muscle is
forced to work harder for an
extended period?
This can contribute to LV
hypertrophy (LVH).
Look for it in lab!
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
LV Changes
 Afterload
 LV wall
thickness
 LV Stiffness
 LV
chamber
size
RF = risk factor for heart
failure
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
 LV
stiffness
Diastolic
dysfunction
1.  LV filling in
early diastole
1
2.  Importance
of the LA “kick”
(atrial systole)
late LV filling
2
2
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
 LV
stiffness
 LV
compliance
 EDV
65+
How would you
expect decreased
EDV to affect the
aged heart?
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Determinants of Stroke Volume
Recall Dr. Fahey’s
lecture:
Any other consequences of
a decreased EDV?
A smaller EDV
means a
smaller SV
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Frank Starling & PV Curves
Parameters
represented in
the PV curve.
 EDV
 Preload
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
What about
contractility?
 Contractility
decreases with
age.
This is in part due to the molecular changes considered earlier:
1.
Decreased β–adrenergic responsiveness
2.
Impaired Ca2+ handling
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Functional Changes
So far we have seen that with normal aging, the heart can not
augment SV as effectively due to:
1.  Afterload
2. Diastolic dysfunction
3.  Contractility
These changes contribute to the decline in COmax that
reduces the exercise tolerance of older adults.
CO =
SV x HR
Now let’s consider the last part of the equation
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Age-Associated Decline in Exercise Tolerance:
Decreased HRmax
With aging, HRmax decreases progressively from age 10
by about 1 bpm per year.
HRmax = 220 – age
Why?
So glad you asked! Let’s find out.
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
What Determines HR at Rest?
Parasympathetic Tone
• Pacemaker cells of the sino-atrial node
(SAN) depolarize spontaneously. In the
young heart, the intrinsic heart rate
(HRint) of pacemaker cell depolarization is
about 100 bpm.
Then why is the average normal resting HR
70 bpm?
• The SAN is under control of the
autonomic nervous system (ANS). At
rest, parasympathetic input from the
vagas nerve slows the rate of pacemaker
cell depolarization from 100 to
approximately 70 bpm.
Parasympathetic
(vagal) input
HR
SAN
Cardiac action
potential
 When parasympathetic
input to the SAN is
removed, HR increases to
HRint
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Resting HR vs. Intrinsic HR
Evidence for a decreased intrinsic HR with age
• When vagal tone is removed from
the aged heart, HR may only
increase to 80 bpm.
• This is less than the increase to
~100 bpm seen in the young heart.
 HRint decreases with
aging.
But…
The resting HR of the aged heart is the same as that of a young heart: ~60 – 70 bpm.
What does this mean?
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Resting HR vs. Intrinsic HR
 Vagal tone diminishes with aging.
• In a 20 y.o., HRint is ~100 bpm.
 At rest, vagal tone decreases HR by
~30 – 40 bpm.
• In an 80 y.o., HRint may be ~70 bpm.
 The effect of vagal tone is to decrease
HR by ~5-10 bpm.
This is important because it means the aged heart gets a smaller
increase in CO by removing vagal tone than the younger heart.
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Maximum HR
• HR rises above HRint when the SAN is
stimulated by the sympathetic nervous
system.
• The decreased HRint, vagal tone, and –
adrenergic responsiveness all contribute
to the decreased HRmax of the aged
heart.
This may be a
more familiar
depiction of the
same concept.
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Back to Our Case…
Why is our 75 year old
patient becoming short of
breath during an activity that
she used to be able to do
without difficulty?
What changes have we
considered that might
account for her decreased
tolerance for exertion?
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Summary of Normal Physiological
Changes During Exercise
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Age-Related Cardiac Changes that
Decrease Exercise Tolerance
 Cardiac
Output
 Max HR
 Stroke
Volume
CO = SV x HR
 Intrinsic
HR
Note: Ejection
fraction is the
clinically
measured index
of contractility.
 Ejection
Fraction
 Myocardial
Contractility
 Preload
 β-adrenergic
Responsiveness
 Afterload
 LV Filling
Altered
Myocardial
Ca2+ Handling
 Aortic
Compliance
 Systemic
Vascular
Resistance
 LV
Stiffness
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Homeostenosis
• Any exertion requires the body to engage its physiologic reserves.
• The homeostasis line can be thought of as the state of the heart at rest.
• Think of the red arrow as representing the physiologic reserve required
to carry 20 lbs. up a flight of stairs.
You
So, what is going on with our patient? Normal aging!
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
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Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
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Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation
Acknowledgements
Gary Blanchard, MD
Megan Janes, MS2
Colleen Burnham, MBA*
Krista Johansen, MD*
Henri Cuenoud, MD*
Mary Ellen Keough, MPH
Michael Fahey, MD
Sarah McGee, MD*
Jerry Gurwitz, MD
Erica Oleson, DO
*author
Advancing Geriatrics Education (AGE): A UMMS initiative funded by the Donald W. Reynolds Foundation