View
218
Download
0
Category
Preview:
Citation preview
7/27/2019 Physiologi Aging
1/43
Physiology of Aging
7/27/2019 Physiologi Aging
2/43
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.
7/27/2019 Physiologi Aging
3/43
Baltimore Sun 7/19/2009
7/27/2019 Physiologi Aging
4/43
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
7/27/2019 Physiologi Aging
5/43
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
7/27/2019 Physiologi Aging
6/43
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
7/27/2019 Physiologi Aging
7/43
Healthy Aging
7/27/2019 Physiologi Aging
8/43
Successful Aging
Homeostasis less efficient, but still present
7/27/2019 Physiologi Aging
9/43
7/27/2019 Physiologi Aging
10/43
New techniques for exercise golf and bowl
7/27/2019 Physiologi Aging
11/43
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
7/27/2019 Physiologi Aging
12/43
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
7/27/2019 Physiologi Aging
13/43
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
7/27/2019 Physiologi Aging
14/43
System Review
Cardiovascular
Respiratory
Renal
Neurological
Hematological
Endocrine/Immune System
Hormonal/Metabolic
Musculoskeletal
Gastrointestinal Special Senses
Skin
7/27/2019 Physiologi Aging
15/43
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
7/27/2019 Physiologi Aging
16/43
Heart to Heart
7/27/2019 Physiologi Aging
17/43
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
7/27/2019 Physiologi Aging
18/43
Home Oxygen
7/27/2019 Physiologi Aging
19/43
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)
7/27/2019 Physiologi Aging
20/43
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.
7/27/2019 Physiologi Aging
21/43
With age comes new skills
7/27/2019 Physiologi Aging
22/43
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
7/27/2019 Physiologi Aging
23/43
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
7/27/2019 Physiologi Aging
24/43
New skills
7/27/2019 Physiologi Aging
25/43
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.
7/27/2019 Physiologi Aging
26/43
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
7/27/2019 Physiologi Aging
27/43
Balance in aging
Common causes of Anemia
7/27/2019 Physiologi Aging
28/43
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
7/27/2019 Physiologi Aging
29/43
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
7/27/2019 Physiologi Aging
30/43
Hemolytic Anemias in the Elderly Immunologic
- Idiopathic- Secondary to drugs, tumour, or chronic disease
Intrinsic- Metabolic- Abnormal hemoglobin
Extrinsic- Mechanical
- Lytic substances
7/27/2019 Physiologi Aging
31/43
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
7/27/2019 Physiologi Aging
32/43
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
7/27/2019 Physiologi Aging
33/43
Gastrointestinal
7/27/2019 Physiologi Aging
34/43
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
7/27/2019 Physiologi Aging
35/43
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
7/27/2019 Physiologi Aging
36/43
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
7/27/2019 Physiologi Aging
37/43
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
7/27/2019 Physiologi Aging
38/43
Special Senses
Vision
Hearing
Smell Taste
Touch
Touch
7/27/2019 Physiologi Aging
39/43
Touch
Treatment Implications
7/27/2019 Physiologi Aging
40/43
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
7/27/2019 Physiologi Aging
41/43
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
7/27/2019 Physiologi Aging
42/43
Go Granny Go
7/27/2019 Physiologi Aging
43/43
The End
Recommended