Physiologi Aging

7/27/2019 Physiologi Aging

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Physiology of Aging


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Significance 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.


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Baltimore Sun 7/19/2009


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Significance 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


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Stages of Life

Chronological age has typically been used to note lifes

transitions We need to think in physiological terms rather than these old

chorological terms


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Concepts of Aging

They vary based on the complex

interactions of genetics and theenvironment

So individuals age at different rates and

there is significant variability inphysiological response


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Healthy Aging


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Successful Aging

Homeostasis less efficient, but still present


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New techniques for exercise golf and bowl


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Aging and Disease

Aging is associated withincrease in incidence andseverity of disease

Many disparate factorspredispose individuals tofunctional losses later inlife

Many conditions havesuspected either geneticand/or environmentaletiologies


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Cell Senescence and Death

Cell senescence is much like apoptosis

Occurs throughout life

It arrests the growth of damaged/dysfunctionalcells

Beneficial early in life; it may contribute to

aging later on


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Cellular Aging

Gene inducers can cause cancer

Senescence allows cells to more easily respondto 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


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System Review

Cardiovascular

Respiratory

Renal

Neurological

Hematological

Endocrine/Immune System

Hormonal/Metabolic

Musculoskeletal

Gastrointestinal Special Senses

Skin


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Cardiovascular 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 withconditioning exercise in the absence of diseasehowever the CO with exercise will be reduced evenin healthy aging


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Heart to Heart


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Respiratory 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 thoraciccapacity. That and alveolar stiffness leads tosenile emphysema with an FEV1/FVC < 70% ofthe predicted for age and gender


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Home Oxygen


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Respiratory System - 2

Impaired ability to clear secretions

Increased tendency to aspiration

The reduced activity of effector T cells increasesrisk of pneumonia

Reduced spirometric parameters are associatedwith all cause mortality and specifically with

- CVD

- COPD

- Lung cancer(3 out of 7 leading causes for women and 3 of the5 leading causes for men)


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Renal system

Decreased renal mass and size

- 150 to 200 gms at 30 yrs but only 110 to 150 by 85 yrs- Mostly loss of renal cortex40% less glomeruli by age 80

Reduced Renal blood Flow- 10% reduction per decade after age 20

- Afferent and efferent arterioles to the cortex atrophyNumber and length of tubules decreases

Average Creatinine clearance decreases0.75ml/min/yr based on the healthy volunteers of theBLSA with 30% showing NO loss. This decline begins inthe fourth decade and averages 10 ml/min every decade.Reduced muscle mass makes the serum creatinine anunreliable marker for renal function.


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With age comes new skills


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Renal function The ability to concentrate urine declines --> frequency.

Ability to elaborate dilute urine can be reduced. Wateroverload can easily lead to CHF and hyponatremia.SIADH like pattern

Total body water is reduced from 60% at age 20 to only45 % of body mass by age 80. Thirst is blunted with age withan 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) withreduced clearance and risk of toxicity


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Neurological 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 cognitivefunction 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


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New skills


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Nervous System - 2

Aging leads to increased cerebral amyloid

Average amount of brain protein is reducedwith a marked loss in multiple enzymes(carbonic anhydrase and the dehydrogenases)but with a relative increase in abnormalproteins such as amyloid in tangles andplaques.

Loss of RNA (messenger and transcription)

but not DNA Loss of lipids, and lipid turnover rate, and a

decrease in catabolism and synthesis.


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Hematological

The age related reduced marrow production isnot necessarily associated with anemias.Many complex factors involved.

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

There is however diminished reserve capacity


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Balance in aging

Common causes of Anemia


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Common causes of Anemia

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

C f i


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Causes of anemia

Ineffective erythropoiesis

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

Microcytic- Thalassemia- Sideroblastic anemia

Normocytic Anemias

- Stromal disease- Dimorphic anemia

- Blood Loss


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Hemolytic Anemias in the Elderly Immunologic

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

Intrinsic- Metabolic- Abnormal hemoglobin

Extrinsic- Mechanical

- Lytic substances


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Endocrine System Insulin production increases and then decreases

Insulin receptors become less effective Adrenal androgens decline with reduction in

libido and sexual functioning. There is no knownalteration of the HPA axis but there is an increase

in stress mediated Cortisol secretion Reduction in episodic release of Growth Hormone

Disorders of Vitamin D absorption, bone andmineral metabolism, and parathyroid disorders

Changes in testicular and ovarian function

Hyperthyroidism more prevalent in the elderly

Hypothyroidism in over 4% of people over 60

M l k l l S


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Musculoskeletal System

Osteoarthritis

- 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 Rheumatica

Reduced muscle mass

These all present multiple risk factors for fractures

Gastrointestinal


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Gastrointestinal


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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


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PPIs in the elderly Overuse 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 ifpossible

CMAJAugust 12, 2008; 179 (4).Targonik LE, Lix LM, et al

CMAJ September 26, 2006; 175 (7) Dial S, Delaney C, et al


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Gastric Acidity

Reduced gastric secretions lead to an increasedpost 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 significantlylonger 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, BerardiRR, et al.

S


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Immune 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 respiratorymucosae


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Special Senses

Vision

Hearing

Smell Taste

Touch

Touch


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Touch

Treatment Implications


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Treatment Implications

The normal elderly person can undergo most of

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

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

Pay closer attention to nutrition and bowelfunction

Pay close attention to CNS changes as harbingersof other pathologies

Screen carefully for metabolic disorders: thyroid,

anemias, bone disease, vit deficiencies etc


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Current Areas of Research

Caloric Restriction Altered dietary intake

Genetic causes of age related illnesses

Effects of IGF (insulin growth factors),TNF (tumor necrosis factors), andinflammatory cytokines etc

Pharmaceuticals and pharmacogenomics inthe aging individual


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Go Granny Go


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The End

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Physiologi Aging