its all down hill after.... physiologic changes associated with aging
TRANSCRIPT
Its all down hill after...
20 30 40 50 60 70 80
age (years)
Physiologic Changes Associated with Aging
Why Distinguish Normal vs Disease?
avoid harm educate patients health behavior counseling public health prognosis and care planning
“Senile” - relating to old age
senile dementia senile cataracts arcus senilis senile emphysema senile osteoporosis age-related macular degeneration
Definition of Aging
A ubiquitous intrinsic biologic process with a progressive, predictable, inevitable evolution and maturation of an organismuntil death
Not the accumulation of diseases
Defining Normal
rate of change in the process of aging mean or average value from healthy people a Gauassian distribution within the normal range
2 standard deviations
Aging and Variation
The physiologic differences betweenold individuals is greater than between young individuals
There may be greater difference within an aged cohort than betweenthe means of young and old cohorts
Young and Old Cohorts
youngold
Standard Deviation vs Percent Predicted
200
225
250
275
300
325
350
375
400
0 10 20 30 40 50 60 70 80
age (years)
Acceptable lower limit70% of predicted
Standard Deviation vs Percent Predicted
200
225
250
275
300
325
350
375
400
0 10 20 30 40 50 60 70 80
age (years)
2 Standard Deviations
Studies of Normal Aging
assume achieved maximal development age as an exposure
absence of disease absence of risk factors for disease absence of occult symptoms or signs of disease
recruitment and maintenance consent
Age-physiology Study Design
Cross-sectional
cohort born 1920-29vs
cohort born 1930-39vs
cohort born 1940-49
Longitudinal
cohort born 1920-29
measure @ time 1
measure @ time 2
measure @ time 3
Cross-sectional Cohort
enroll more patients only method for invasive data cohort effect retrospective
lack of exposure or risk factors age-associated not rate of change
Cohort Effect
height infectious exposure
influenza epidemic polio
environmental exposure pollution fluoride milk intake
Cohort Effect Bone Mineral Density
0 10 20 30 40 50 60 70 80 90
age years
Bon
e D
ensi
ty
healthy normal
Cohort Effect Bone Mineral Density
0 10 20 30 40 50 60 70 80 90
age years
Bon
e D
ensi
ty
healthy normal
rickets
Cohort Effect Bone Mineral Density
0 10 20 30 40 50 60 70 80 90
age years
Bon
e D
ensi
ty
healthy normal
rickets
anorexia nervosa
Cohort Effect Bone Mineral Density
0 10 20 30 40 50 60 70 80 90
age years
Bon
e D
ensi
ty
healthy normal
rickets
anorexia nervosa
hyperthyroidism
Rate of Change
0
50
100
150
200
250
300
350
30 35 40 45 50 55 60
Age (years)
Rate of Change
0
50
100
150
200
250
300
350
30 35 40 45 50 55 60
Age (years)
-20 per year
LongitudinalRate of Change
0
50
100
150
200
250
300
350
30 35 40 45 50 55 60
Age (years)
-5 per year
Cross-sectionalDifference in Level
0
50
100
150
200
250
300
350
30 35 40 45 50 55 60
Age (years)
Longitudinal Cohort
expensive years for data changes in technology changes in disease classification invasive testing temporal order
absence of other exposures
Longitudinal Data Points
0
50
100
150
200
250
300
350
0 1 2 3 4 5
Time
n = 1
Longitudinal Data Points
0
50
100
150
200
250
300
350
0 1 2 3 4 5
Time (years)
n = 1
Longitudinal Data Points
0
50
100
150
200
250
300
350
0 1 2 3 4 5
Time (days)
n = 1
Tissue and Cellular Changes
atrophy hyperplasia hypertrophy dilatation loss elastin loss collagen calcification
Brain
Cross-section MRI Brain Findings
nondemented independently functioning no medical illness
including HTN no medications no previous evaluation for cognitive changes
young-old (77 years) vs old-old (89 years)
JAGS 1999;47:330
Cross-section MRI Brain Findings
age-associated decrease brain volume/intracranial volume r = -.72 (p = 0.001)
age-associated increase periventricular signal r = .45 (p = 0.001)
JAGS 1999;47:330
Cardiac
Baltimore Longitudinal Study
exclusion criteria CAD BP > 140/90 valvular heart disease LVH by ECG
inclusion criteria sinus rhythm ETT negative normal wall motion and EF >50% on GHPS
Circulation 1977;56:273
BLSA Resting Echocardiogram
no change with age resting HR LV ejection time LV chamber size EF
Circulation 1977;56:273
BLSA Resting Echocardiogram
age-associated increase aortic root diameter LV wall thickness late diastolic filling
Circulation 1977;56:273
Diastolic Changes
Young
diastolee a
Diastolic Changes
Old
diastolee a
Diastolic Changes
Old
Young
diastolee a
BLSA Resting GHPS
no change with age cardiac output HR EDV or ESV EF
age-associated increase systolic BP
Circulation 1984:69:203
BLSA GHPS Exercise 100 watts
no change with age cardiac output EF peak systolic BP
Circulation 1984:69:203
BLSA GHPS Exercise 100 watts
age-associated increase EDV ESV overall increase SV
age-associated blunted peak HR response
Circulation 1984:69:203
BLSA Conclusions
CO maintained w/exercise despite lower HR
SV increased by increasing preload
?loss intrinsic contractility ?loss of sympathetic tone ?loss of ß-receptor function
BLSA Catecholamines with Age
at rest epinephrine increased
exercise epinephrine increased norepinephrine increased
J Appl Physiol 1985;59:1033
Beta-adrenergic Receptors
receptor density ? lymphocyte models decreased in explanted hearts
agonist binding affinity G protein-adenylate cyclase uncoupling
Circulation 1994;90:1225
Frank-Starling
LV-EDP (mm Hg)
Car
diac
Out
put (
L/m
in)
geriatric
young
Frank-Starling
LV-EDP (mm Hg)
Car
diac
Out
put (
L/m
in)
geriatric
young
+ inotrophic state
Clinical Application with Age
dependent on late diastolic filling tachycardia atrial arrhythmia
volume sensitive syndrome of heart failure
without significant heart disease
Pulmonary
Lung Histologic Changes
calcification cartilage ribs/spine/airways decreased parenchymal collagen airspace dilatation
Airspace Size with Age
surgical or autopsy n=38 lifelong nonsmokers 21-93 years old histology by electronic scanner airspace: surface area/volume
Thorax 1993;48:39
Airspace Area/Volume vs AgeThorax 1993;48:39
0
5
10
15
20
25
age years
airs
pac
e su
rfac
e ar
ea/v
olu
me
mm
2 /mm
3
30 40 50 70 80 90
r = -0.78p < 0.001
Lung Compliance
0
20
40
60
80
100
120
Pressure (cm H2O)
Vol
um
e (m
l) Normal
Lung Compliance
0
20
40
60
80
100
120
Pressure (cm H2O)
Vol
um
e (m
l) Normal
volume
volume
Lung Compliance
0
20
40
60
80
100
120
Pressure (cm H2O)
Vol
um
e (m
l) 73 ml/cm H2O
99 ml/cm H2Op <0.01
Respiratory Muscle Function
inspiration diaphragm external intercostals
MIP - maximal inspiratory pressure MVV - maximal voluntary ventilation
Structural Ventilatory Changes
decreased chest wall compliance increased lung compliance decreased alveolar surface area decreased muscle strength
Lung Volumes
no change TLC increased
FRC RV
decreased VC decreased FEV1
decreased FEV1/FVC
Lung Volumes
0%
20%
40%
60%
80%
100%
young old
IRV
VT
ERV
RV
vital capacity
FRC
Lung Volumes with Age
RV
FRC
TLC
VC
normal aging
0
1000
2000
3000
4000
5000
6000
volu
me
(ml)
PFT Assumptions
FEV1 declines after age 25 men 29 ml/year women 25 ml/year
Cross-sectional vs Longitudinal
-90
-75
-60
-45
-30
-15
0
20 25 30 35 40 45 50 55 60 65 70 75
age years
an
ua
l ch
an
ge
in F
EV 1 m
l
longitudinal
cross sectional
Am J Epidemiology 1990;132:685
Cohort EffectAm J Respir Crit Care Med 1994;149:1218-1226
2300
2500
2700
2900
3100
3300
3500
20 30 40 50 60
Age (years)
FEV
1 (m
illi
lite
rs)
Cohort EffectAm J Respir Crit Care Med 1994;149:1218-1226
2300
2500
2700
2900
3100
3300
3500
20 30 40 50 60
Age (years)
FEV
1 (m
illi
lite
rs)
Cohort EffectAm J Respir Crit Care Med 1994;149:1218-1226
2300
2500
2700
2900
3100
3300
3500
20 30 40 50 60
1959195519511943
1935192919191915
Age (years)
FEV
1 (m
illi
lite
rs)
Source of Variation Aged CohortAm J Respir Crit Care Med 1996;154:S208
0
20
40
60
80
100
0 10 20 30 40 50 60 70 80 90
age years
FE
V1
% a
t a
ge
20 healthy normal
submaximal growth
Gas Exchange
increased dead space increased shunt
base
increased DLCO/VA
An 85 year old has the following room air ABG pH 7.42 Pco2 40
Po2 72 A-a 28
An 85 year old has the following room air ABG pH 7.42 Pco2 40
Po2 72 A-a 28
Is the oxygenation appropriate for age?
An 85 year old with no prior lung disease presents to the ER with sudden onset of dyspnea and pleurtic chest pain and has the following room air ABG pH 7.42 Pco2 40
Po2 72 A-a 28
Is the oxygenation appropriate for age?
Age-Adjusted PO2
PO2 = 104.2 - 0.27(age)
PO2 = 100.1 - 0.325(age)
PO2 = 109 - 0.43(age)
Age-Adjusted PO2
PO2 = 104.2 - 0.27(age) PO2 81
PO2 = 100.1 - 0.325(age) PO2 72
PO2 = 109 - 0.43(age) PO2 75
Age-Adjusted A-a gradient
A-a gradient = 2.5 + 0.21(age)
A-a gradient = 4 + age/4
A-a gradient = 1.4 + 0.43(age)
Age-Adjusted A-a gradient
A-a gradient = 2.5 + 0.21(age) A-a 20
A-a gradient = 4 + age/4 A-a 25
A-a gradient = 1.4 + 0.43(age) A-a 38