Post on 27-May-2015
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