Clinical Implications of the Aging Physiology

Anita Chopra, MDDirector, NJISAUMDNJ-SOM

Clinical Implications of theAging Physiology

This Care of the Aging Medical Patient in the Emergency Room (CAMPER) presentation is offered by the Department of Emergency Medicine in coordination with the

New Jersey Institute for Successful Aging.

This lecture series is supported by an educational grant from the Donald W. Reynolds Foundation

Aging and Quality of Life program.

Learning Objectives

• Describe the concept of homeostenosis

• Review the physiological changes associated with age in various systems of the body

• Discuss the significance of age associated physiologic changes on the clinical presentation and management of older patients

An 82 year old female presents with increasing shortness of breath and fatigue for the last few days. She has a history of hypertension, diabetes mellitus type 2, and osteoarthritis of the knees. Her medications include glyburide 5 mg daily, hydrochlorothiazide 25 mg daily, lisinopril 10 mg daily, and Ibuprofen 200 mg once daily as needed. BP is 110/70, resp. 20/minute, pulse is irregular. Lungs reveal bibasilar crackles and there is trace pedal edema. PaO2 on room air is 65. EKG reveals

Which age-related physiologic change makes her more vulnerable to develop symptoms of CHF?

A. Decline in renal functionB. HypoxiaC. Increase in atrial natriuretic

peptide (ANP) levelsD. Increase in BPE. Tachycardia and loss of atrial kick

An 80 year old white male complains of mild shortness of breath on exertion. He denies any chest pain, wheezing, or cough. There is no history of hypertension or CAD. He denies a history of smoking. On examination, his lungs are clear with no crackles or wheezing. X-ray of the chest and electrocardiogram reveal normal findings. Patient is referred for pulmonary function testing.

Which of the following describes expected age- related changes in pulmonary function?A. Decreased total lung capacity,

decreased FEV1, decreased residual volume

B. Increased total lung capacity, decreased FEV1 and decreased residual volume

C. Increased total lung capacity, decreased FEV1 and increased residual volume

D. Stable total lung capacity, decreased vital capacity, decreased residual volume

E. Stable total lung capacity, decreased vital capacity, increased residual volume

Which aspect of renal function is relatively maintained with aging ?

A. Ability to excrete acid loadB. Concentrating capacityC. Diluting capacityD. Erythropoietin productionE. Metabolism of parathyroid

hormone

Aging

• Normal aging is not a disease• Chronologic age & physiologic

age are not the same• Individuals “age” at different

rates and there is significant variability

• Increased susceptibility to diseases

Spectrum Of Aging

• Aging, with disease and disability• Usual aging, with the absence of

overt pathology, but with some declines in function

• Successful aging or healthy aging, with little or no pathology and little or no functional loss

Aging and Disease

• “Homeostenosis”: Diminished ability to maintain homeostasis under stress

• Diseases can present atypically in old age

• Disease in old age is usually modified (presentation, clinical course, response to treatment, outcomes) by interaction with age-related changes

• Geriatric Syndromes are the result of interaction of physiologic changes of aging, diseases and risk factors

Aging and Physiologic Rhythms

• Attenuation of pulsatile secretion of hormones (e.g., melatonin, ACTH, TSH, LH/FSH, GH)

• Reduction in circadian amplitude of physiologic processes– Plasma cortisol– Sleep– Body temperature

• Loss of complexity in physiologic functions may contribute to impaired response to stressors

Age-related decline in heart rate variability could be due to: (1) dropout of sinus node cells, (2) altered ß-adrenergic receptor responsiveness, and (3) an apparent reduction in the parasympathetic tone

Aging and Homeostatic Challenges

• Blood pressure regulation• Volume regulation• Temperature regulation

An 80 year old male presents with complaints of dizziness, especially in the early afternoon. He reports that that he has "fainted" once, but was not seriously injured at this time. His medical history includes COPD, peripheral vascular disease, and hypertension. His hypertension is currently treated with hydrochlorothiazide 25mg QD and felodipine 5 mg QD.

What age related changes are contributing to his dizziness/syncope?

A. Decreases fluid volumeB. Impaired cerebral auto regulation C. Orthostatic hypotensionD. Postprandial hypotensionE. All of the above

Aging and Blood Pressure Regulation

• Baroreflex response to arterial pressure changes progressively decline with age, resulting in increased risk of orthostatic hypotension

• Reduced adrenergic responsiveness by the aged heart diminishes baroreflex-mediated cardioacceleration in response to hypotension

• Decrease in cerebral blood flow by 20%• Cerebral autoregulation process impaired

in chronic hypertension

Clinical Implications• Postprandial hypotension: Decline in

blood pressure after a meal is prevalent among older persons

• Increased risk of orthostatic and postprandial hypotension with medications, e.g. nitrates, diuretics, antihypertensive meds

• Older patients vulnerable to cerebral ischemia and syncope

Aging and Volume Regulation

Ms. K., 25 years old• Fluid deprivation for

72 hours due to sore throat (strep plus mononucleosis)

• Sodium: No change• BUN: No change• Serum Creatinine: No

change• Mild hypotension with

sinus tachycardia of 130

Mrs. L., 80 years old• Fluid deprivation for

24 hours (made NPO by an

intern, no IV fluids ordered)

• Sodium: 146 – 150• BUN: 32 - 40• Serum Creatinine: No

change• Cardio-vascular

changes: hypotension with sinus tachycardia of 100

Which of the following statements about age-related changes in sodium and water homeostasis is not true? A. There is impaired conservation of

Na and waterB. Hypernatremia may occur without

clinical signs of dehydrationC. Atrial natriuretic peptide (ANP)

levels are decreasedD. There is decrease in renal response

to ANP

Clinical Implications

• Predisposition to Dehydration– Decrease in total body water as a percentage

of body weight– Decreased thirst drive – Decreased antidiuretic hormone (ADH)

response to hypovolemia– Decreased maximum urinary concentration– Impaired access to water due to physical or

cognitive disorders• Hyponatremia & CHF

– Decreased ability to excrete free water load leading to hyponatremia and fluid overload

Aging and Thermoregulation

• Basal heat production decreases by 20% from age 30 years to age 70 years due to active muscle loss

• With age, the ability to regulate body temperature and to adapt to different thermal environments declines

• Elderly are more prone to hyper- and hypothermia

Mrs. S is an 88-year-old woman who lives alone. She has history of osteoarthritis of her hips and knees. One night while going to the bathroom, she fell. Unable to get up or call for help, Mrs. S lay on the bathroom floor until her daughter found her the next day and called an ambulance to bring her to the ER. She does not complain of pain. On examination, she is lethargic and somewhat confused. Her skin is cold and pale. BP is 110/60, pulse 60/min., rectal temp 95 F. X-rays reveal no fracture.

What age-related changes make her more vulnerable to develop hypothermia?A. Decreased production of thyroid

hormone B. Impaired blood redistribution from

splanchnic circulationC. Impaired skin vasodilation responseD. Reduced muscle activity and less

shiveringE. Decrease in basal metabolic rate

Hypothermia: Risk Factors

• Reduced muscle activity and less shivering

• Impaired vasoconstrictor response to cooling by skin arterioles, which results in impaired ability to conserve heat

• Reduced meal-induced thermogenesis

• Delayed perception of being cold• Difficulty in discriminating

temperature differences

An 80 year old female is found unresponsive in her apartment on a hot summer day. The apartment does not have air-conditioning. She has history of mild dementia, CHF, and Parkinson’s disease. Her medications include enalapril, furosemide, and levodopa/carbidopa. In the emergency room, her BP is 85/50, pulse 100/min, and rectal temp is 105 F. Her skin is hot and dry.

What age-related changes predispose an elderly person to heat stroke and its consequences?

A. Reduced muscle activityB. Increased threshold to initiate

sweatingC. Impaired vasoconstrictor responseD. Impaired ability to conserve heatE. Increased output of eccrine sweat

glands

Hyperthermia: Risk Factors

• Impaired skin vasodilatation response and impaired blood flow redistribution from splanchnic and renal circulations

• Decreased thirst• Increased threshold temperature to

initiate sweating• Decreased output of eccrine sweat glands • Drugs that impair the response to heat

(such as anticholinergic agents [hypohydrosis], diuretics [hypovolemia], and ß-blockers [impaired cardiovascular responsiveness]) increase the risk of heat stroke

Fever Response In The Elderly

• The ability to raise body temperature (generate fever response) in response to pyrogens (bacterial endotoxins) is blunted with age

• Up to 25% of older persons with sepsis do not exhibit a febrile reaction

• Another definition of fever is a temperature increase of > 2°F (1.1°C) over baseline (if a baseline temperature is available)– This definition has a sensitivity of 82.5% and

specificity of 89.9% in the institutionalized older population

Which of the following is not true about age-related cardiac changes?

A. Resting cardiac output unchangedB. Ejection fraction reducedC. Early diastolic filling reducedD. End diastolic filling increased

Cardiovascular: Structure

Age-associated change

Consequence

↓ compliance of arterial tree ↑ after load on left ventricle and LVH ↑ Systolic and pulse pressure

Myocardial cell hypertrophy, ↑ interstitial fibrosis, drop out of cardiac myocytes

Slowing of ventricular relaxation, ↓ LV compliance, ↑ contribution of atrial contraction to LV end diastolic volume

Apoptosis of S-A pacemaker cells, fibrosis and loss of his bundle cells

Slower intrinsic heart rate, varying degrees of heart block

Cardiovascular: Structure (cont’d)

Age-associated change

Consequence

Decreased responsiveness to beta adrenergic stimulation and reactivity to baroreceptors and chemoreceptors

↑ circulating catecholamines

Fibrosis and calcification of heart valves

Aortic valve sclerosis and stenosis

The early diastolic left ventricular filling rate progressively slows after age 20, so that by age 80, the rate is reduced by up to 50%

Source: The Merck Manual of Geriatrics, 3rd Edition, edited by Mark H. Beers, and Robert Berkow. Copyright 2000 by Merck & Co., Inc., Whitehouse Station, NJ.

Cardiovascular Physiology

• ↓ maximal heart rate • ↓ maximal cardiac output at

exercise• ↓ maximal aerobic capacity• ↓ cardiovascular reserve• ↓ threshold for congestive heart

failure and atrial fibrillation

Clinical Implications• Systolic HTN and widened pulse pressure

are risk factors for stroke, renal failure, and heart disease

• Age is the strongest predictor of mortality following Acute MI– Diagnosis more difficult due to atypical

presentation• Diastolic heart failure (EF ≥ 50%) accounts

for as many as 50% of CHF patients over age 65

• Atrial fibrillation becomes more of a physiologic burden to the old heart because of age-related slowing of diastolic filling due to LV stiffness and greater dependence for adequate filling on atrial contraction

An 82 year old female presents with increasing shortness of breath and fatigue for the last few days. She has a history of hypertension, diabetes mellitus type 2, and osteoarthritis of the knees. Her medications include glyburide 5 mg daily, hydrochlorothiazide 25 mg daily, lisinopril 10 mg daily, and Ibuprofen 200 mg once daily as needed. BP is 110/70, resp. 20/minute, pulse is irregular. Lungs reveal bibasilar crackles and there is trace pedal edema. PaO2 on room air is 65. EKG reveals

Which age-related physiologic change makes her more vulnerable to develop symptoms of CHF?

A. Decline in renal functionB. HypoxiaC. Increase in atrial natriuretic

peptide (ANP) levelsD. Increase in BPE. Tachycardia and loss of atrial kick

Aging Respiratory System

Stiffness of chest walls

Work of breathing

Alveolar surface area

• Enlargement of alveolar ducts

• Calcification of bronchial and costal cartilage

• Decreased lung elasticity and elastic recoil• Lower respiratory muscle strength and endurance• Decrease in cough and mucociliary clearance

Effects of Aging on Lung Function

• Lower maximum expiratory flows: FEV1, FEV1/FEV loss of approximately 15-30cc/year in FEV1 from the peak achieved at age 25-30 years

• Increased FRC and RV, lower VC, but stable TLC

• PaO2 declines linearly with aging until age 75, at which time it stabilizes at about 80 mm Hg in healthy nonsmokers. – This gradual decline is mostly attributable to V/Q

mismatch caused by age-related collapse of peripheral airways, leading to shunting of blood through nonventilated alveoli. PaO2 at any age can be roughly estimated by the equation PaO2 = 100 - (0.3 x age)

Effects of Aging on Lung Function

• Lower diffusing capacity• Reduced respiratory drive for

hypoxia and hypercarbia

Clinical Implications• Higher risk for developing respiratory failure

in response to an acute illness• Non-pulmonary conditions such as

congestive heart failure, cerebrovascular accidents, and nutritional disorders can also precipitate respiratory failure in the elderly

• The complaint of dyspnea must be taken seriously because, compared with younger adults, older adults may not develop this symptom until they are at a later stage in their illness

• The elderly have a 5-10 fold increased risk of pneumonia as compared to younger adults and are much more likely to die from this disease than their younger counterparts

An 80 year old white male complains of mild shortness of breath on exertion. He denies any chest pain, wheezing, or cough. There is no history of hypertension or CAD. He denies a history of smoking. On examination, his lungs are clear with no crackles or wheezing. X-ray of the chest and electrocardiogram reveal normal findings. Patient is referred for pulmonary function testing.

Which of the following describes expected age- related changes in pulmonary function?A. Decreased total lung capacity,

decreased FEV1, decreased residual volume

B. Increased total lung capacity, decreased FEV1 and decreased residual volume

C. Increased total lung capacity, decreased FEV1 and increased residual volume

D. Stable total lung capacity, decreased vital capacity, decreased residual volume

E. Stable total lung capacity, decreased vital capacity, increased residual volume

Renal System• General decline in glomerular filtration rate

by about 1 ml/year after 40– 30% showed no deterioration (BLSA)

• Progressive decline in ability to excrete a concentrated or a dilute urine

• Delayed or slowed response to sodium deprivation or a sodium load

• Decreased levels of renin and aldosterone • Increased dependence on renal

prostaglandins to maintain perfusion• Decreased Vitamin D activation

Lindeman RD, Tobin J, Shock NW. J Am Geriatr Soc 1985;33(4):278-285.

Clinical Implications• Creatinine clearance should always be

calculated before starting or increasing doses of a medication cleared by the kidney

• Serum creatinine values are not reliable estimates of renal function

• Nephrotoxic drugs should be avoided whenever possible

• Use of drugs that inhibit the renin-angiotensin-aldosterone system (such as ACE inhibitors and angiotensin and aldosterone receptor antagonists) can contribute to hyperkalemia in older adults.

• Acute renal failure develops faster, with relatively minor stressors, and carries a higher mortality

Calculating Creatinine Clearance

• Estimate by Cockcroft - Gault formula

• MDRD ( modification of diet in renal disease)

(140 - age [yr]) x weight [kg] --------------------------------------- x 0.85 (if patient is female) 72 x serum cr (mg/dL)

170 x [Scr]-0.999 x [age]-0.0176 x [0.762 if patient is

female; 1.180 if patient is black] x [SUN]-0.0170 x [albumin]+0.318

Which aspect of renal function is relatively maintained with aging ?

A. Ability to excrete acid loadB. Concentrating capacityC. Diluting capacityD. Erythropoietin productionE. Metabolism of parathyroid

hormone

Mrs. S is a 70 year old retired school teacher, who comes for a routine follow-up of her blood pressure. During her visit, she comments that she is concerned about her memory. She notes that she's having more difficulty remembering the names of individuals she knows when she meets them. She also complains of misplacing her keys .

Which of the following is least consistent with normal aging?A. Delayed retrievalB. Decreased speed of processingC. Forgetfulness that interferes

with independent livingD. Decreased multitasking

performance

Aging Nervous System

Memory• Immediate memory (sensory)

– No change

• Short term memory– No change– It is widely believed that one type of memory, called

working memory, is most affected by age. Working memory is the retention of information that must be manipulated or transformed in some way.

• Long-term memory– Late in the aging process, “semantic memory” declines,

referring to memories of facts or concepts. “Procedural memory” remains unaffected.

Aging Nervous System

Intellect•Crystallized intelligence (learning and experience stable or improves with age)

•Fluid intelligence (problem-solving with novel material requiring complex relations) declines rapidly after adolescence

Processing speed • Mental processing and reaction time

become slower with age

Aging Nervous SystemLanguage• Vocabulary - increases into 50s and 60s -

errors or failures in naming occur with increasing frequency, beginning in mid-life; encoding strategies very helpful

• Syntactic skills - combine words in meaningful sequence - no decline with age

Attention• No change

Executive function• Ability to conceptualize, plan does not

change

Age Associated Memory Impairment

(AAMI)• Decreased multitasking performance• Decreased processing speed• Impaired or delayed retrieval

Clinical manifestations• Retrieving the name of a vague

acquaintance• Remembering every item to buy from a

grocery store without a list• Recalling where an object was placed

Vision and Hearing

Vision• Decline in accommodation (presbyopia),

low-contrast acuity, glare tolerance, adaptation, and color discrimination. These changes affect reading, balance, and driving.

Hearing• High frequency sensory neural hearing

loss (presbycussis). Consequences include difficulty in localizing sound and understanding speech.

Improving Communication

• Provide a respectful and supportive environment

• Allow sufficient time for the older patient to process new information.

• Speak slowly facing the patient. Do not speak louder

• Provide written materials to complement oral instructions.

• Use repetition to ensure that instructions were clear and that your communication has been effective.

Laboratory Values In Old AgeUNCHANGED

DECREASED

INCREASEDLiver function

testsCoagulation testsArterial blood Gasesp

HpCO2

Serum electrolytes

Calcium, phosphorus

Serum creatinine

Total proteinT4, TSHComplete Blood Count

Serum albuminCreatinine clearance

paO2

Alkaline phosphatase

Sed rate

Post-prandial blood sugar

Total cholesterol Triglycerides

Interaction of Aging and Hospitalization

Modified from: Creditor MC. Hazards of hospitalization of the elderly. Ann Int Med 1993;118(3):219-223

Age-Related Changes

Contribution of Hospitalization

Effects Consequences

Loss of muscle mass and strength

Bed rest, restraints, tethers Deconditioning Dependency, falls

Baroreceptor insensitivity, less thirst drive, less body water

Inaccessibility to fluids, disease-associated dehydration

Postural hypotension

Falls & related injuries, dizziness, syncope

Lower maximum expiratory flows, reduced paO2

Reduced ventilation from bed rest

Hypoxia, respiratory failure

Delirium, increased mortality from pneumonia

Reduced bladder capacity, prostate enlargement, pelvic floor relaxation

Barriers, unfamiliar environment

Tendency to incontinence

Functional incontinence, catheters

Fragile skinReduction in vascularity

Bed rest, shearing, incontinence

Increased pressure on buttocks, heals

Pressure sores

Vision & hearing loss Sensory deprivation (e.g., glasses, hearing aid)Sensory overstimulation (e.g., sleep deprivation, noisy environment)

ConfusionDelirium

RestraintsLonger length of stayPsychotropic drugs

Conclusions

• Aging is associated with reduced functional reserve and a compromised ability to cope with stressors

• Elderly are a heterogeneous group and there is great individual variability

• Always think of interventions which may be useful in helping patients cope with and/or overcome some of the changes brought by normal aging

• Start building your reserves NOW