PHYSIOLOGY OF AGINGPHYSIOLOGY OF AGING

Special considerations when Special considerations when dealing with older patients dealing with older patients

Dr. Jos. Zebley MAFP February 2010Annapolis Md

Physiology of AgingPhysiology of Aging

“We are all amateurs; we don’t live long enough to become anything else.”

Charlie Chaplin

Significance of Human AgingSignificance of Human Aging People live longer now than ever before By 2030, 20% of the US population will be 65 and older Significant challenge to medicine - ethical, financial, etc.

Question # 1Question # 1

Patients over 60 make up

a 20% b 30% c 40%

of all physician visits

Demographic ImperativeDemographic Imperative

Patients over 60 make up 40% of all physician office visits and average 11 physician visits a year compared to an aggregate average of 5 visits a year for those under 65

There are over 1.5 M elderly nursing home residents and this number is expected to increase dramatically as the Baby Boom generation enters its seventh decade

Baltimore Sun 7/19/2009Baltimore Sun 7/19/2009

Question # 2Question # 2

What would improve life expectancy more:

A Finding cures for diabetes, cancer, heart disease, and stroke

B Slowing down the rate of aging

Significance of Human AgingSignificance of Human Aging Gender and genetics are significant factors Lifestyle and genetic expression are major factors Various theories of aging attempt to explain the process

- bottom line, there is disruption of homeostasis

Stages of LifeStages of Life Chronological age has typically been used to note life’s transitions We need to think in physiological terms rather than these old chorological terms

Stages of Life - 2Stages of Life - 2

Physiological adulthood is attainment of optimally integrated function

Function in adulthood is the “standard measure” It is incorrect to state that the changes with aging

are necessarily “abnormal” they are however deviations from the standard ranges for young adults.

Four observations of the elderly:– Greater heterogeneity in responses to stressors– Changes in function do not occur simultaneously– Changes in function no longer occur to the same degree

_ There is reduced redundancy and ability to repair

Old age should not be viewed as a “disease” nor should a time clock be put on aging

Human LongevityHuman Longevity Significant increase in longevity over past centuries Due to decline in deaths resulting from accidents and

infectious diseases along with improved public health Heart disease, cancer and stroke now most common

cause of death Death rates have actually declined in the elderly

ETHICAL ISSUE Is there a limit to the human life span and should we

prolong life at the expense of overall health? Should be speaking of “health span” not life span

Life span vs Health spanLife span vs Health span

Concepts of AgingConcepts of Aging

Chronologic age and physiologic age are not the same as noted before

They vary based on the complex interactions of genetics and the environment

So individuals age at different rates and there is significant variability in physiological response

Successful Aging - 2Successful Aging - 2

The prevalence of disease increases with age

Different forms of aging:– Aging with disease and disability– Usual aging; absence of pathology but

presence of decline in function– Ideal healthy aging; no pathology or

functional loss

Healthy AgingHealthy Aging

Successful Aging - 3 Successful Aging - 3 H Homeostasis less efficient, but still presentomeostasis less efficient, but still present

Question # 3Question # 3

Watching Television reduces longevity:

A True

B False

Physiological ChangesPhysiological Changes

Heterogeneity of various values and functions Many associated with physical inactivity

Successful Aging - 4 Successful Aging - 4

Recent research:– Elderly individuals with weak muscles are at greater

risk for mortality than age-matched individuals

– Increase in amount and rate of loss of muscle increases risk of premature death (i.e. TV, computers)

– Circulation Jan 2010 Dunstan, Barr, et al

– Physical inactivity is 3rd leading cause of death in US and plays role in chronic illnesses of aging

New techniques for exerciseNew techniques for exerciseWii golf and bowl

Aging and DiseaseAging and Disease

Aging is associated with increase in incidence and

severity of disease

Many disparate factors predispose individuals to functional losses later in life

Many conditions have suspected either genetic and/or environmental etiologies

Cell Senescence and DeathCell Senescence and Death

Cell senescence is much like apoptosis– Occurs throughout life– It arrests the growth of damaged/dysfunctional

cells– Beneficial early in life; it may contribute to

aging later on

Cellular AgingCellular Aging

Gene inducers can cause cancer

Senescence allows cells to more easily respond to inducers, but then cells withdraw from growth cycle are are less likely to move to tumorigenesis

Other contributions of cell senescence to aging:– Altered secretions of cells– Proteases, inflammatory cytokines, growth factors– Erosion of structure and integrity of tissues

System ReviewSystem Review

Cardiovascular Respiratory Renal Neurological Hematological Endocrine/Immune System Hormonal/Metabolic Musculoskeletal Gastrointestinal Special Senses Skin

Question # 4Question # 4

The aging Cardiovascular System has a:

A Reduced Cardiac output B Increased Stroke Volume C Reduced Peripheral Resistance

Cardiovascular SystemCardiovascular System

Reduced - Resting and maximal cardiac output - Stroke Volume - Maximal heart rate - Response to sympathetic nervous system stimulation

Increased - Systolic Blood Pressure - Peripheral resistance - Total cholesterol and LDL particle number

The resting cardiac output can remain stable with conditioning exercise in the absence of disease however the CO with exercise will be reduced even in healthy aging

Heart to HeartHeart to Heart

Question # 5Question # 5

Senile emphysema is due to:

A Chest wall StiffnessB Alveolar StiffnessC KyphosisD All the above

Respiratory SystemRespiratory System Reduced - Lung surface area

- Alveolar elasticity - Forced Expiratory Volume (FEV 1)

- Maximal Oxygen Consumption (VO2 max) - P O2 Increased - Chest wall stiffness

Osteoporosis and kyphosis can reduce the thoracic capacity. That and alveolar stiffness leads to “senile emphysema” with an FEV1/FVC < 70% of the predicted for age and gender

Home OxygenHome Oxygen

Question # 6Question # 6

Reduced Spirometric Parameters are associated with:

A 1 of 5B 2 of 5C 3 of the 5 leading causes of death in men

Respiratory System - 2Respiratory System - 2

Impaired ability to clear secretions Increased tendency to aspiration The reduced activity of effector T cells increases

risk of pneumonia Reduced spirometric parameters are associated

with all cause mortality and specifically with - CVD - COPD -

Lung cancer (3 out of 7 leading causes for women and 3 of the 5 leading causes for men)

Question # 7Question # 7

Average creatinine clearance decreases 10ml/min for every decade after age 30

TrueFalse

Renal systemRenal systemDecreased renal mass and size

- 150 to 200 gms at 30 yrs but only 110 to 150 by 85 yrs

- Mostly loss of renal cortex 40% less glomeruli by age 80 Reduced Renal blood Flow

- 10% reduction per decade after age 20 - Afferent and efferent arterioles to the cortex atrophy

Number and length of tubules decreases Average Creatinine clearance decreases

0.75ml/min/yr based on the healthy volunteers of the BLSA with 30% showing NO loss. This decline begins in the fourth decade and averages 10 ml/min every decade. Reduced muscle mass makes the serum creatinine an unreliable marker for renal function.

With age comes new skillsWith age comes new skills

Renal functionRenal function The ability to concentrate urine declines --> frequency. Ability to elaborate dilute urine can be reduced. Water

overload can easily lead to CHF and hyponatremia. SIADH like pattern

Total body water is reduced from 60% at age 20 to only 45 % of body mass by age 80. Thirst is blunted with age with an increased risk of dehydration and volume depletion

There is greater sensitivity to drug induced nephrotoxicity (ACEIs, aminoglycosides)

Reduced volume of distribution of water soluble drugs (dig) can lead to toxicity

Increased fat and reduced muscle mass lead to an increased volume of distribution of lipophilic drugs (Benzos) with reduced clearance and risk of toxicity

Question # 8Question # 8

Cognitive function is affected more than recall memory in normal aging

A TrueB False

Neurological SystemNeurological System Neuronal loss is normal in the aging brain but the

ability to learn remains generally unchanged There is loss of dendritic arborization Recall memory is affected more than cognitive

function in normal aging Cerebral atrophy shows up on CTs and MRI scans Lowered seizure threshold Reduced Sympathetic nervous system activity Reduced Neurotransmitter levels Changes in sleep patterns Abnormalities in EEG tracings Increased risk of stroke

New skillsNew skills

Nervous System - 2Nervous System - 2Aging leads to increased cerebral amyloidAverage amount of brain protein is reduced

with a marked loss in multiple enzymes (carbonic anhydrase and the dehydrogenases) but with a relative increase in abnormal proteins such as amyloid in tangles and plaques.

Loss of RNA (messenger and transcription) but not DNA

Loss of lipids, and lipid turnover rate, and a decrease in catabolism and synthesis.

HematologicalHematological The age related reduced marrow production is

not necessarily associated with anemias. Many complex factors involved.

Hemoglobin of 12g/dl is now considered the current lower limit of normal in the elderly (over 75)

There is however diminished reserve capacity

Balance in agingBalance in aging

Common causes of Anemia Common causes of Anemia Hypoproliferative Hypoproliferative

Hypoproliferative anemias in the elderly Iron Deficient erythropoiesis

- Nutritional Iron Deficiency - Chronic disease - Inflammation

Erythropoietin Lack - Renal - Endocrine

Stem cell dysfunction - Aplastic anemia - Red blood cell aplasia

Causes of anemia Causes of anemia Ineffective erythropoiesis Ineffective erythropoiesis

Megaloblastic - Vitamin B 12 deficiency - Folate deficiency - Refractory anemia

Microcytic - Thalassemia - Sideroblastic anemia

Normocytic Anemias - Stromal disease - Dimorphic anemia

- Blood Loss

Hemolytic Anemias in the ElderlyHemolytic Anemias in the ElderlyImmunologic

- Idiopathic - Secondary to drugs, tumour, or chronic disease

Intrinsic - Metabolic - Abnormal hemoglobin

Extrinsic - Mechanical - Lytic substances

Endocrine SystemEndocrine SystemInsulin production increases and then decreasesInsulin receptors become less effectiveAdrenal androgens decline with reduction in

libido and sexual functioning. There is no known alteration of the HPA axis but there is an increase in stress mediated Cortisol secretion

Reduction in episodic release of Growth HormoneDisorders of Vitamin D absorption, bone and

mineral metabolism, and parathyroid disordersChanges in testicular and ovarian functionHyperthyroidism more prevalent in the elderlyHypothyroidism in over 4% of people over 60

Question # 9Question # 9

Fractures are related to:

A Visual impairmentB OsteoporosisC Reduced muscle massD All the above

Musculoskeletal SystemMusculoskeletal SystemOsteoarthritis

- Changes in cartilage chemistry and thickness - Changes in synovial fluid - Changes in the intervertebral discs - Changes in the menisci

Osteoporosis - Reduced calcium reserves or increased loss - Increased osteoclastic activity over osteoblasts

Polymyalgia RheumaticaReduced muscle mass

These all present multiple risk factors for fractures

GastrointestinalGastrointestinal

Question # 10Question # 10

Elderly patients require more PPIs for longer periods of time than younger patients

- True - False

Gastroenterology Gastroenterology Multiple functional changes

- Dry mouth, reduced sense of taste, dental issues - Swallowing disorders, risk of aspiration

- Impaired peristalsis (presbyesophagus) - Reduced gastric secretions - Reduced intestinal absorption - Impaired colonic motility and impaired ano rectal function

- Reduced gallbladder emptying

- Reduced hepatic function

Dyspepsia, bloating, constipation, flatulence

PPIs in the elderlyPPIs in the elderlyOveruse of PPIs is associated with

- Increased incidence of pneumonia - Increased incidence of hip fractures - Increased incidence of C. Difficile

Wean patients off PPIs and H2 Blockers if possible

CMAJ August 12, 2008; 179 (4).Targonik LE, Lix LM, et al CMAJ September 26, 2006; 175 (7) Dial S, Delaney C, et al

Gastric AcidityGastric Acidity

Reduced gastric secretions lead to an increased post prandial gastric pH (6.5)

Fasting pH (1.3) in over 75 yr olds is statistically different from average young patients and 11% had a median fasting pH of >5

The rate of return to pH 2.0 was significantly longer than in younger cohorts (> 4 hrs)

Pharm Res 1993 Feb;10(2):187-96.Upper gastrointestinal pH in seventy-nine healthy, elderly,

North American men and women. Russell TL, Berardi RR, et al.

Immune SystemImmune System Diminished cell mediated immunity Increased incidence of anergy Reduced helper,cytotoxic and effector T cells Increased cytokine antagonists Changes in neutrophil and macrophage function

Clinical implications Atypical presentations of infectious illnesses Poor or delayed response to antibiotic therapies Reduced protection of the urinary or the respiratory

mucosae

Special SensesSpecial Senses

VisionHearingSmellTasteTouch

TouchTouch

Treatment ImplicationsTreatment ImplicationsThe normal elderly person can undergo most of the

same urgent or emergent interventions as the younger adult as long as attention is paid to the physiological changes discussed above

Consider earlier and more aggressive treatment of infections BUT with attention to renal function

Pay closer attention to nutrition and bowel functionPay close attention to CNS changes as harbingers

of other pathologiesScreen carefully for metabolic disorders: thyroid,

anemias, bone disease, vit deficiencies etc…

Current Areas of ResearchCurrent Areas of Research

Caloric Restriction Altered dietary intake

Genetic causes of age related illnesses

Effects of IGF (insulin growth factors), TNF (tumor necrosis factors), and inflammatory cytokines etc…

Pharmaceuticals and pharmacogenomics in the aging individual

ConclusionConclusionAging is not for sissiesMaintain a maximal muscle mass. Exercise of

some form is ALWAYS better than less exercise of any kind at any age and in any condition

Develop and nurture a close relationship between the physician and the elderly patient and the family. This allows the Doc to pick up on subtle changes early in any disease process

Maintain careful hydration and nutritional statusAvoid excess weight gain BUT protect against

weight loss. Dropping LDL, triglycerides, albumin are all red flags for senesence and decline.

Go Granny GoGo Granny Go

ConclusionConclusion

Discuss end of life care and review regularlyLearn the principles of palliative and end of life

careApply common sense to protocols and screening

guidelinesDon’t do anything to your patient that you would

not want done to you ~ unless the family and / or patient insist and understand some of the unintended consequences

The EndThe End