Block 8C Aging Week 2

Front 1

adverse effects of drugs are expensive

Back 1

1.33$ on SE for every 1$ on meds

Front 2

risk factors for adverse drug effects

Back 2

6 or more concurrent chronic conditions

12 or more dises of drugs/day

9 or more meds

prior adverse rxn

low body weight / BMI

>85 yo

Creatinine clearance <50ml

Front 3

old people in studies

Back 3

not in the drug studies bc they make the studies less likely to accept the drug by FDA

also because you can't be on any other drugs to be part of the study

can't include pt with alzheimer in a heart failure trial...

Front 4

dynamics vs kinetics

Back 4

dynamics what the drug does to the body

kinetics - what the body does to the drug

Front 5

absorption of drugs on old

Back 5

less surface area but more exposure due to low motility

this cancels out

old don't make as much acid - and some drugs can't be absorbed ex: Fe (give with vit C)


divalet cations (ca mg fe) can affect the absorption of fluoroquinolones (ciprofloxacin) (Fe + Thephylline)

enteral (tube) feeding interfere with some aborpsion (theophilline)

Front 6

drug absorption from skin

Back 6

increasing amounts through skin

-thin skin favors absorption
-decreased perfusion of skin delays absorption
-Nitroglycerin, estrigen, pain meds, blood pressyre meds,

aged skin is thinner (+ abs)

BUT the blood flow is less (- abs)

so it's more unpreductable in aging

Front 7

distribution

Back 7

old ppl have more fat and less water

depending on the drug solubility - it'll be more or less concentrated

ex: the valium mobilized from fat stores

from 25 to 75 yo:
fat + 100%
water - 10%
cell solids -35%
bone mineral -20%

Front 8

changes in binding proteins for drugs in aging

Back 8

albumin has 2 binding sites - but can bind about 5 drugs each

If albumin drops --> amount free will go up; but normally the lvl is unchanged in healthy old person;
healthy old ppl have nl albumn 4

BUT:
Illness in older ppl - decrease in albumin and

big INcrease in a-1-glycoprotein
(this protein binds the antidepressants - which goes up when you're sick - so you're sad and sick - have to increase the dose of their antidepressants)

Front 9

Dilantin (Phenytoin)

Back 9

OK if it's lower in elderly

if older pt is seizure free with total pheytoin of 7, don't increase it unless they're seizing. - it's bc the there is more free available (the bound % decreases and then the free is the same 10)

Front 10

metabolism Isosorbide dinitrate

Back 10

extensive metabolism in liver first pass

young liver can metabolize 12-15mg oral dose

old liver can metabolize less

so 10mg isosorbide is placepo dose in young and reasonable first dose in old

don't expect linear effect of isosorbide on BP as you may be tripling dose by increasing from 10 to 20

doubling dose is NOT good:

10mg young sees 0, old sees 5
20mg young sees 5 , old sees 15


probably due to blood flow mainly

Front 11

metabolism

example: Valium

Back 11

Overall decline in metabolic capacity due to decreased liver mass and hepatic blood flow

metabolic capacity is highly variable; no good estimation algorithm exists

decreased first pass metabolism in old

phase I (P450 --> oxidation, reduction, hydrolysis) is more likely to decrease with advancing age

phase II (conjugation) usually unchanged

induction decreased for some enzymes


Valium: lasts longer in old people
-elimination half life 24y in young but 90yrs in old
-highly metabolized by P450 enzymes including active metabolites (and highly fat soluble)
-pharmacokinetic effects add to pharmacodynamic effects
-other benzodiazepines have shorter, predictable half life
-we use lorazepam (Ativan)[shorter half life and only metabolized by glucuronidation] but don't like Benzo's in general

Front 12

estimating renal fct

how does it change with age?

Back 12

creatinine clarance decreases with age

decreased by 35% in healthy older men (no HTN, no DM, no drugs)

decreased concentrating and diluting capacity

increased number sclerotic glomeruli to 30% of total

dependence on prostaglandins to maintain filtration

decreased renal blood flow and renal mass

serum creatinine does not change with age (TEST Q)

when you use the formula to estimate the CrCl, use the ideal body weight

overall they still have decreased renal excretion:
so this means:
-elimination is prolonger
-serum lvls of drug are increased as are toxicity
-evidence from gentamycin or digoxin or vancomycin, all highly water soluble drugs

Front 13

Pharmacodynamics

Back 13

lower lvls in older ppl are ok

receptor numbers, affinity, or post-receptro cellular effets can change

changes in the homeostatic mechanisms can increase or decrease drug sensitivity

Front 14

Versed

Back 14

drug before colonoscopy - sedating sleep -

how much Versed needed to not have a EEG changes w/o flinching

the amount needed for an older was half of what's needed for younger pt.

Front 15

Coumadin

Back 15

less needed in older ppl

noone over 85 needed more than 5mg/day to be on target INR

Front 16

Atropine

Back 16

older have LESS response, so you need more

old person will have less of a HR increase

it gets rid of the vagal tone -

Front 17

b-adrenergic drugs -isoproterenol

Back 17

older ppl are less responsive to b-adrenergic drugs -isoproterenol

Front 18

mechanisms of dynamic changes

3 +
drug drug interaction

Back 18

receptors are less responsive (b-adrenergic)

homoeostatic mechanisms down (vagal) [antiHTN induced orthostasis]

increased responsiveness (Benzodiazepines, digoxin, neuroleptics, opioid, antigoac(warfarin), anti-cholinergic)


D-D interactions are worse with dementia - because this induces sensitvity and paradoxical reactions to drugs with CNS or anti-cholinergic efects
-obesity alters volume of distribution of lipophilic drugs
-ascites alters VD of hydrophilic drugs
-renal or hepatic impairment may impair drug detox

Front 19

Beers criterias

should never be used in old people

Back 19

Beers bad boys

propoxephen for pain (Darvon) bad - crappy pain med- makes the confused - one of the worst

Robazin - muscle relaxant - makes them confused

Librium - long acting benzos - last even longer than valium - bad too

Benadryl - Diphenhydramine[ON TEST] - the anti-cholinergic effect again causes them to be confused (also Soma - that's Diphenhydramine) [only time to use with old ppl it's for a blood transfusion - every once in a while an old person gets confused after a transfusion]

indomethacin

Front 20

glucose in age

why?

Back 20

fasting gluc stays the same,

BUT

the system doesn't respond as well to an OGTT. Post prandial glucose:
if it's <100 + age = normal

the post prandial glucose curve is higher and it takes longer

manifest: small but significant increase in HgA1c

why? because they're insulin resistant

Front 21

why is there higher HgA1C / post prandial

Back 21

because they're insulin resistant

less receptors?
or less sensitivity?

they have a lower affinity - it takes higher conc to be saturated

to get the same gluc uptake, insulin infusion needed is 3x higher

Front 22

some mechanisms of insulin resistance (4)

Back 22

increase in visceral body fat with aging is mediated by inflammation and obesity

decreased lean body weight LBW

glucose utilization markedly impaired

decreased fat cell insulin dependent (glut4) glucose transporters, also muscle in rat

sedentary lifestyle has had in impact


decreased suppression of hepatic glucose output

decreased alternative agonist IGF-1

Front 23

prevalence of DM

Back 23

8.6% 20-44yo
23% 45-54
28% 55-64
40.8% 65-74

effect of aging on fasting glucose is 0, so that's DM

Front 24

when old people get sick, what happens with the glucose

Back 24

worsening insulin resistance - hyperglycemia! don't label as DM, check again in 6wk

Front 25

glucagon in age

Back 25

not changed

Front 26

thyroid H with age

Back 26

t3 t4 serum not changed, BUT free T3 is decreased slightly

t4 prodiction decreases 25%
T3 production decreases 35%

euthyroid SICK sydrome
-deiodinases prefer reverse T3, and if you're sick the rT3 accumulates because they body says "I don't want any more T3"

-subtle decreases in free T3 in healthy men

no change in free T4

Lower T4 and Lower T3 is correlated with longer survival

Front 27

if you have to give more meds

Back 27

they're not taking their meds

Front 28

One Growth Hormone measurement during the day?

Back 28

worthless, because it's too variable. You could measure IGF-1 instead.

Aging resembles growth hormone deficiency in certain characteristics. Low GH levels result in thin skin, decreased muscle mass, decreased bone mass and increased fat mass. All these changes occur with aging as well, however GH administration has not proven to be the Fountain of Youth. In fact many long lived mouse models are GH ir IGF-1 deficient.

1. GH is primarily secreted by the pituitary in discrete pulses which
are highest at night. The nocturnal pulses decrease in men, but
baseline levels unaltered. Overall, 24 hour integrated levels
decrease up to 50% by age 70.
2. Pulses decrease to a much smaller extent in women until after
menopause, but then decrease rapidly.
3. Pituitary response to Growth Hormone Releasing Hormone (GHRH) is
decreased, but can be restored to youthful function during chronic treatment
with GH-releasing peptides.
4. IGF-1 is decreased by 30-50% from age 20-80 in most old persons due mostly
to decrease in GH pulses but also to decreased responsiveness of the old liver
to GH..
5. Low IGF-1 may contribute to senile osteoporosis (which occurs in both men and
women.)
6. Slightly lower IGF-1 over long term may be associated with increased longevity.
7. Somatostatin, which opposes GHRH, is unchanged.
8. Exercise, though it will maintain muscle mass, does not change the decreases in IGF-1 with age.

Front 29

IGF-1 in age

are we like the mouse in the lab - challenge poor or challenge rich?

Back 29

decreases

also lower paracrine effects
deceases more in certain tissues

you can get a random IGF-1 and see the decrease

lower lvls -- longer life

why give IGF-1?

the dwarf mouse did poorely in the real environment but had a longer survival in the lab.

Front 30

DHEA with age

Back 30

decrease in normal men

it's used as a precursor for sex=steroids; there are resceptors for it in the CNS, but the DHEA is sulfated so it can't pass the BBB..

but ppl still buy it


Adrenal Cortex

1. No aging change (some report an increase) in basal or stimulated cortisol
2. Increased responsiveness to ACTH administration
3. Less suppression of cortisol by dexamethasone acutely
4. May be harder to turn off after stimulation with stress (especially surgery)
5. Old more likely to develop adrenal suppression and insufficiency after chronic
steroid therapy.
6. Marked decrease in (Dehydroepiandrosterone) DHEA, DHEAS

Front 31

cortisol in age

Back 31

decreased ability to maximally produce cortisol in response to maximal stress, but adequate release for most stresses

decrease synthetic ability

cortisol release is less completely suppressed by Dex, but also more difficult to normalize once suppressed with long term corticosteroid treatment.

the old guys still had elevated lvl of cortisol long after the stress/illness

Front 32

testosterone in aging

Back 32

large variability, but overall decrease

increase in sex hormone binding globulin in older men

fall in T may be accentuated by any chronic or acute illness


less sperm produced - less Sertoli cells

Front 33

Glucose Tolerance

how are the tests different in older people?

Back 33

1. Glucose regulation is decreased markedly by age and elevations in circulating glucose are implicated in accelerating the aging process by facilitating glycosylation of proteins (HgA1c is also up)

2. Fasting glucose increases by only 1% per decade

3. Post carbohydrate challenge glucose increases significantly. Peak post-prandial glucose increases by 10 mg/dl decade. Almost all normal 70 year olds have impaired glucose tolerance after oral glucose challenge (75 gm) using criteria applied to twenty year olds.

I allow for post-prandial (and any other non-fasting) glucose up to 100 + Age.

Front 34

Why do they have Glucose intolerance??

Back 34

4. Proposed mechanisms for impaired glucose tolerance in the elderly.
a. Changes in body composition (increased fat and decreased muscle) play some role
b. Plasma insulin levels normal or elevated
c. Release of insulin by pancreas impaired mildly
d. Delayed suppression of hepatic glucose output
e. Decline in insulin clearance
f. No change in pancreas insulin content
g. Decreased rate of peripheral glucose uptake in men and women.
h. Glucose utilization impaired
(1) Anaerobic pathways and production of lactate are decreased in muscle in the older person.
(2) Glucose monophosphate, stops loss of glucose from cell and is produced by hexokinase, which has decreased activity in older person.

i. Peripheral tissues less responsive to insulin in the elderly
(1) Insulin receptors may be decreased
(2) Decreased concentrations of alternative agonist IGF-1
(3) Decreased Glucose transporters Glut4 (insulin dependent) vs Glut 1 (don’t need insulin) in skeletal muscle and fat

j. Physical activity plays an important mediating role and most elderly are sedentary. In a few studies physical fitness and adiposity were surrogates for
age.

k. Metabolic Syndrome=hypertension, central obesity, augmented sympathetic nervous system stimulation=> impaired glucose tolerance

l. Normal older persons will have elevations in HgBA1C(glycosylated hemoglobin) especially when they are ill. The age effects on stress mediated hyperglycemic mechanisms are smaller than the hypoglycemic mechanisms. If a person has a moderately elevated glucose while acutely ill then treat the glucose, but re-evaluate the person for diabetes mellitus when they are not sick usually 6 weeks after discharge.

m. AGE are advanced glycosylation end-products. They form when glucose non-enzymatically attacks proteins and reduce the function of the proteins. They accumulate with age in skin and tendon and some other long lived proteins rich areas, but not found in other similar areas. They can cause cateracts. Caloric restriction decreases serum glucose and the formation of AGE. AGE will stimulate atherosclerosis. Some implicate these AGE as a major cause of aging.

n. Exercise training improves but does not erase the aging effects.

o. Glucagon metabolism, control and responsiveness is unchanged with age. Also no change in hyperglycemic effects of norepinephrine and cortisol. The result is what is observed in #L.

Front 35

When will the normal older persons have elevations in HgBA1C even if they're not DM?

Back 35

Normal older persons will have elevations in HgBA1C(glycosylated hemoglobin) especially when they are ill. The age effects on stress mediated hyperglycemic mechanisms are smaller than the hypoglycemic mechanisms. If a person has a moderately elevated glucose while acutely ill then treat the glucose, but re-evaluate the person for diabetes mellitus when they are not sick usually 6 weeks after discharge.

if they have hyperglycemia while ill, label the as hyperglycemic but not as diabetic. reevaluate in 6wks

Front 36

Thyroid changes

Back 36

1. No changes in circulation levels of hormones (T3 and T4), but decreased metabolism (turnover) of hormones. The amount and percent that is free hormone is also unchanged.
2. Decreased end organ responsiveness to T3 with aging
3. Decreased conversion of T4 to T3.
Peripheral site is where age-related decrease occurs vs.
Intra-thyroid conversion which is preserved
4. No change in TSH
5. Early evidence that being a minimally hypothyroid may be better associated with increased longevity

Front 37

Growth Hormone

Back 37

Aging resembles growth hormone deficiency in certain characteristics. Low GH levels result in thin skin, decreased muscle mass, decreased bone mass and increased fat mass. All these changes occur with aging as well, however GH administration has not proven to be the Fountain of Youth. In fact many long lived mouse models are GH ir IGF-1 deficient.

1. GH is primarily secreted by the pituitary in discrete pulses which
are highest at night. The nocturnal pulses decrease in men, but
baseline levels unaltered. Overall, 24 hour integrated levels
decrease up to 50% by age 70.
2. Pulses decrease to a much smaller extent in women until after
menopause, but then decrease rapidly.
3. Pituitary response to Growth Hormone Releasing Hormone (GHRH) is
decreased, but can be restored to youthful function during chronic treatment
with GH-releasing peptides.
4. IGF-1 is decreased by 30-50% from age 20-80 in most old persons due mostly
to decrease in GH pulses but also to decreased responsiveness of the old liver
to GH..
5. Low IGF-1 may contribute to senile osteoporosis (which occurs in both men and
women.)
6. Slightly lower IGF-1 over long term may be associated with increased longevity.
7. Somatostatin, which opposes GHRH, is unchanged.
8. Exercise, though it will maintain muscle mass, does not change the decreases in IGF-1 with age.

Front 38

1. List the primary aging changes in the cardiovascular system.

Back 38

A. Because of the High prevalence of hypertension, atherosclerosis, and coronary artery disease in Western Society, it has been difficult to dissect disease changes from age changes. None of the above (HTN, ASCVD, CAD) are normal.

B. Aorta and Peripheral Vessels

1. Age-related Changes in Structure:

a. Calcification of media
b. Increased lumen diameter and length
c. Increased mural thickness
d. Increased collagen, especially in subendothelium
e. Fragmentation of elastin in media
f. Increased mucopolysaccharide and glycosaminoglycans
g. Irregularities in size and shape of endothelial cells
h. Variability of all these changes in extent from degree and site
i. Increased tendency of old vascular smooth muscle to proliferate which may put older person at higher risk for atherosclerosis.
j. Age-related changes are different from atherosclerosis

2. Age-related Changes in Arterial Function:

a. Reduced compliance, stiffer large arteries
b. Increase in systolic blood pressure with no change (or a decrease) in diastolic blood pressure
c. Decreased blood pressure response to most vasodilator drugs
d. Increased impedance, much smaller changes in peripheral vascular resistance.
e. Endothelium production of vasoactive substances, especially nitric oxide, are decreased.
f. These changes occur where the blood flow is pulsatile or where the arteries are big enough to have a name.

C. Heart

1. Age-related Changes in Structure:

a. Gross changes:

1. Increased left atrial size
2. Mild Left ventricular hypertrophy
3. Small decrease in left ventricular cavity size
4. Increased fat

b. Microscopic changes:
1. Reduced number of pacemaker cells in the
Sino-Atrial node (90% dead by age 70)
2. Mild myocyte hypertrophy in ventricles
3. Increase in lipofuscin (a waste product of long chain fatty acids)
4. Increase in fibrous tissue in the atria and
ventricles
5. Accumulation of fat and collagen between the
muscle bundles

2. Age-related impact on cardiac function:

a. At Rest:

1. Left Ventricular Ejection Fraction-Unchanged
2. Resting Heart rate-unchanged
3. Resting Cardiac Output-unchanged
4. Contraction time is increased
5. Ventricular stiffness increased
6. Diastolic function-decreased
7. Left Atrial Systole contribution to left ventricular filling- increased
8. Contractility unchanged




b. With increased demand (like during exercise or an acute illness):

1. Peak Ejection Fraction-decreased
2. Maximum Heart rate-decreased
3. Maximum Cardiac Output-decreased
4. Contraction time increased
5. Ventricular stiffness increased
6. Diastolic function-decreased

Front 39

2. Explain how these changes affect cardiovascular function during the
stress of exercise or acute illness.

Back 39

2. Age-related impact on cardiac function:

a. At Rest:

1. Left Ventricular Ejection Fraction-Unchanged
2. Resting Heart rate-unchanged
3. Resting Cardiac Output-unchanged
4. Contraction time is increased
5. Ventricular stiffness increased
6. Diastolic function-decreased
7. Left Atrial Systole contribution to left ventricular filling- increased
8. Contractility unchanged



With increased demand (like during exercise or an acute illness):

1. Peak Ejection Fraction-decreased
2. Maximum Heart rate-decreased
3. Maximum Cardiac Output-decreased
4. Contraction time increased
5. Ventricular stiffness increased
6. Diastolic function-decreased

Some of the decrements in function seen at peak exercise in healthy elders are also present when the elderly are given infusions of beta-adrenergic agonists like isoproterenol.
When young people are given beta-adrenergic antagonists like propranolol and then ask to exercise, they resemble older people in terms of decreased maximum heart rate and decreased maximum cardiac output.

3. There is no change with age in the cardiac output measured at any given level of exercise achieved, but obviously old people cannot attain the highest levels that young people can.
That is old people are just as efficient as young people.

4. Determinants of cardiac output (CO)
C.O.=HR x S.V.

a. Heart rate. The average heart rate achieved during activities of daily living are lower in the old compared to in the young. During aerobic exercise, maximum achievable heart rate decreases with increasing age regardless of the level of physical fitness.

The average maximal heart rate during upright exercise decreases from about 200 beats per minute at age 20 to 150 beats per minute at age 70 for men. Rough formula for men: 220-age gives maximum heart rate. For Women, its 85% of men. So when you see a person who is ill and has sinus tachycardia, don’t just think of the absolute heart rate, but consider what it is in proportion to the person’s maximal heart rate.

b. Stroke volume increases with exercise in the elderly. This is accomplished by increasing the end- diastolic volume with a smaller increase in end systolic volume. Because of the aged person’s inability to increase his heart rate, the C.O. needed is attained if possible, by increasing the volume expelled with each contraction.

c. In a young person, C.O. is increased without an increase in left ventricular filling pressure (healthy young people do not use Frank-Starling mechanism). Because the elderly cannot increase heart rate to the same extent, they rely on increasing left ventricular filling and therefore left ventricular filling pressures increase with exercise in the old. Additionally inotropic state of the old heart is less responsive to the sympathetic stimulation associated with exercise so the old heart relies on the Frank-Starling curve to increase cardiac output.

d. With exercise the relevant arteries dilate maximally in the young. In the old the responsiveness of arteries and veins to the vasodilating effect of beta-adrenergic agonists and other mediators is decreased leading to relatively increased vascular resistance.

Front 40

1. List the primary aging changes in the cardiovascular system.
2. Explain how these changes affect cardiovascular function during the
stress of exercise or acute illness.
3. Explain how primary aging changes place the older patient at increased risk for congestive heart failure.

Back 40

D. Clinical implications with respect to heart failure

An S4 is a normal finding in an older person because the ventricle is stiffer and atrial systole contributes a greater amount to ventricular filling.

Congestive heart failure, a common clinical syndrome in older people is characterized by accumulation of sodium and water and congestion of the pulmonary veins and lungs, the systemic veins and liver and by increased diastolic pressure within the ventricles of the heart. In young and middle aged individuals the prevalent cause of heart failure is poor systolic function of the heart (as shown by decreased ejection fraction).

In a significant number of older patients with congestive failure, systolic function of the heart is not impaired and the problem is diastolic heart function. For more than half of older patients with heart failure, the pathophysiology of their heart failure is different and treatment must be tailored appropriately. Physicians caring for these patients will have to alter their therapeutic plans based on these pathophysiologic considerations.

Front 41

BP: 160/60 means what?

Back 41

Aortic regurgitation in young people
(Regurgitant flow reduces the diastolic pressure --> The pulse pressure widens, systolic blood pressure remains normal or slightly elevated. This is because sympathetic nervous system and the renin-angiotensin-aldosterone axis of the kidneys compensate for the decreased cardiac output.)

but

stiff arteries in the old can cause this (reduced compliance - not to do with "resistance" - the impedance doesn't really change with age)

Front 42

what's so bad about stiffer arteries with age?

change in S vs Diastole??

Back 42

they provide less cushioning and pressure reflections occur

the systolic increases with age while the diastolic stays.

Front 43

atherosclerosis is NOT...

Back 43

aging

it is unique to western man, compromises lumen, it has an inflammatory component, cholesterol is a cofactor;


changes that ARE related to aging:
-in most species, uniform, lumen enlarges, not with WBC, independent of cholesterol

Front 44

Aorta and Peripheral Vessels
Age-related Changes in Structure

Back 44

Calcification of media.
Increased lumen diameter and length.
Increased mural thickness.
Increased collagen, especially in subendothelium.
Fragmentation of elastin in media.
Increased mucopolysaccharide and glycosaminoglycans.
Irregularities in size and shape of endothelial cells.
Variability of all these changes in extent from degree and site.
Increased tendency of old vascular smooth muscle to proliferate which may put older person at higher risk for atherosclerosis.
Age-related changes are different from atherosclerosis.

Front 45

Aorta and Peripheral Vessels
Age-related Changes in Arterial Function

Back 45

Reduced compliance, stiffer large arteries.
Increase in systolic blood pressure with no change (or a decrease) in diastolic blood pressure.
Decreased blood pressure response to most vasodilator drugs.
Increased impedance, much smaller changes in peripheral vascular resistance.
Endothelium production of vasoactive substances, especially nitric oxide, are decreased.

Front 46

Changes in Structure
of the heart

Back 46

Gross changes:
Increased left atrial size
Mild Left ventricular hypertrophy
Small decrease in left ventricular cavity size (and hypertrophy of the cells in the ventricles)
Increased fat

Microscopic changes:
Reduced number of pacemaker cells in the Sino-Atrial node (90% dead by age 70)
Mild cellular hypertrophy in ventricles (while the myocytes are swelling, everything else is dissapearing)
Increase in lipofuscin (a waste product of long chain fatty acids)
Increase in fibrous tissue in the atria and ventricles
Accumulation of fat and collagen between the muscle bundles

Front 47

Changes in Function
of heart

at rest

Back 47

At Rest:
Left Ventricular Ejection Fraction-Unchanged
Resting Heart rate-unchanged (decreased HR response to sympathetic and parasympathetic response)
Resting Cardiac Output-unchanged
Contraction time is increased
Ventricular stiffness increased
Diastolic function-decreased
Left Atrial Systole contribution to left ventricular filling- increased
Contractility- unchanged
With increased demand (like during exercise):
Peak Ejection Fraction-decreased
Maximum Heart rate-decreased
Maximum Cardiac Output-decreased
Contraction time increased
Ventricular stiffness increased
Diastolic function-decreased

Experiment: we give propranolol to ablate all the input to the heart --> intrinsic HR decreases 5-6beats/10yrs

Multiple longitudinal study of aging: found that for men 220-age = maximal HR for exercise testing. No matter how hard they exercised, they still fit on this trend.

Front 48

change in CO with aging?

Back 48

Decrements in function seen at peak exercise in healthy elders are also present when they are given beta-adrenergic agonists (isoproterenol).

Giving young people beta-adrenergic antagonists like propranolol decreases their maximum heart rate and maximum cardiac output to the levels seen in the elderly.
No change with age in the cardiac output measured at any given level of exercise achieved.
But obviously old people cannot attain the highest levels that young people can.
Translation: old people are just as efficient as young people.


the ability of the heart to reload becomes critical (since the max HR can't get faster)- so the SV is where the money is to maintain CO

relaxation and contraction require 50/50% of the energy!


Determinants of cardiac output: CO = HR x SV
Heart Rate:
Average heart rate achieved during activities of daily living are lower in the old than the young.
During aerobic exercise, maximum achievable heart rate decreases with increasing age regardless of the level of physical fitness.
The average maximal heart rate during upright exercise decreases from about 200 beats per minute at age 20 to 150 beats per minute at age 70 for men.
Rough formula for men: 220-age gives maximum heart rate.
For women, it’s 85% of men.
Stroke volume increases with exercise in the elderly:
Increased end- diastolic volume.
Smaller increase in end systolic volume.
Increased LV filling pressures: the elderly cannot increase heart rate to the same extent, so to maintain CO, they rely on increasing left ventricular filling.
Inotropic state of the old heart is less responsive to the sympathetic stimulation associated with exercise so the old heart relies on the Frank-Starling curve to increase cardiac output.
Relative increase in vascular resistance:
With exercise, the relevant arteries dilate maximally in the young.
In the old, the responsiveness of arteries and veins to the vasodilating effect of beta-adrenergic agonists and other mediators is decreased leading to relatively increased vascular resistance.


there's no age related change in LV-ejection fraction - 65% is nl for old and young -

the papillary muscles have impaired relaxation - impairs diastole

Front 49

with exercise, what happens to the HR young vs old

Back 49

young remove their large vagal tone - get to their intrinsic HR and then they add the increase via the sympathetic response.

old have less vagal tone to remove - have lower intrinsic - and then less stimulated by sympa

Front 50

Who is sick, the 80 yr old with 120 heart rate or the 25 year old with HR of 170? (both have signs of pneumonia)

Back 50

Both very sick - both are at 75% of max HR

Front 51

what part of the heart muscle actually has the lesion causing the decreased maximal CO?

who picks up the slack?

Back 51

the lesion is in the Ca-pump that replenishes the SR - so the diastolic filling is the problem.

so atrial systole has to work a lot harder and makes up for 50% of the diastolic LV filling (vs 15% in young) and so atrial fibrillation can produce --> CHF

to measure how much more you need the atria, you can measure the lower the ratio E/A, or the VO2max

despite the cardiac hypertrophy, E/A in athletes is higher than in sedentary control. Exercise trained ppl have augmented diastolic fct


determinants of diastolic fct:
1) active relaxation
2) passive stiffness (for really slow HR this is important factor)
3) uniformity of LV (critical)

Front 52

starling's law of the heart

old or young?

Back 52

the young people increase CO by HR and by increasing LV filling. the pressures Never go up.

in old people, starling's law IS used to increase CO - because the other responses (b-adrenergic..)are inadequate.

Front 53

S4 in old person

Back 53

is normal because they have "A Stiff Heart"
= Atrial gallop

deceased respone to some CV drugs

CHF becomes more common
-especially with primary diastolic dysfunction (systolic is preserved, Ejection fraction is preserved)

Front 54

MI mortality with age

Back 54

increases drastically after 65

the heart has less homeostatic response mechanisms - ex the young heart tries to fix it by laying down new alpha-actin; the old can't do that they're already compensating - they have ANF already "ON"

Front 55

why are old people prone to orthostatic hypotension

Back 55

decreased baroreceptor sensitivity
decreased arterial compliance
decreased ....

Front 56

type of heart failure?

Back 56

diastolic dysfunction

Front 57

efficiency of the old with CO and work input

Back 57

no difference in efficiency

but old people can't increase the CO as much


can become more efficient with exercise

Front 58

loss of atrial systole

Back 58

old: huge change in CO
normal older people have increased reliance on atrial systole

Front 59

get a random during the day GH

Back 59

it doesn't tell you anything?