PHYSIOLOGY OF AGING Special considerations when

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PHYSIOLOGY OF AGING Special considerations when

  1. 1. PHYSIOLOGY OF AGING Special considerations when dealing with older patients <ul><li>Dr. Jos. Zebley </li></ul><ul><li>MAFP February 2010 </li></ul><ul><li>Annapolis Md </li></ul>
  2. 2. Physiology of Aging <ul><li>“We are all amateurs; we don’t live long enough to become anything else.” </li></ul><ul><li>Charlie Chaplin </li></ul>
  3. 3. Significance of Human Aging <ul><li>People live longer now than ever before </li></ul><ul><li>By 2030, 20% of the US population will be 65 and older </li></ul><ul><li>Significant challenge to medicine - ethical, financial, etc. </li></ul>
  4. 4. Question # 1 <ul><li>Patients over 60 make up </li></ul><ul><li>a 20% </li></ul><ul><li>b 30% </li></ul><ul><li>c 40% </li></ul><ul><li>of all physician visits </li></ul>
  5. 5. Demographic Imperative <ul><li>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 </li></ul><ul><li>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 </li></ul>
  6. 6. Baltimore Sun 7/19/2009
  7. 7. Question # 2 <ul><li>What would improve life expectancy more: </li></ul><ul><li>A Finding cures for diabetes, cancer, heart disease, and stroke </li></ul><ul><li>B Slowing down the rate of aging </li></ul>
  8. 8. Significance of Human Aging <ul><li>Gender and genetics are significant factors </li></ul><ul><li>Lifestyle and genetic expression are major factors </li></ul><ul><li>Various theories of aging attempt to explain the process - bottom line, there is disruption of homeostasis </li></ul>
  9. 9. Stages of Life <ul><li>Chronological age has typically been used to note life’s transitions </li></ul><ul><li>We need to think in physiological terms rather than these old chorological terms </li></ul>
  10. 10. Stages of Life - 2 <ul><li>Physiological adulthood is attainment of optimally integrated function </li></ul><ul><li>Function in adulthood is the “standard measure” </li></ul><ul><li>It is incorrect to state that the changes with aging are necessarily “abnormal” they are however deviations from the standard ranges for young adults. </li></ul><ul><li>Four observations of the elderly: </li></ul><ul><ul><li>Greater heterogeneity in responses to stressors </li></ul></ul><ul><ul><li>Changes in function do not occur simultaneously </li></ul></ul><ul><ul><li>Changes in function no longer occur to the same degree </li></ul></ul><ul><li>_ There is reduced redundancy and ability to repair </li></ul><ul><li>Old age should not be viewed as a “disease” nor should a time clock be put on aging </li></ul>
  11. 11. Human Longevity <ul><li>Significant increase in longevity over past centuries </li></ul><ul><li>Due to decline in deaths resulting from accidents and infectious diseases along with improved public health </li></ul><ul><li>Heart disease, cancer and stroke now most common cause of death </li></ul><ul><li>Death rates have actually declined in the elderly </li></ul><ul><li>ETHICAL ISSUE </li></ul><ul><li>Is there a limit to the human life span and should we prolong life at the expense of overall health? </li></ul><ul><li>Should be speaking of “health span” not life span </li></ul>
  12. 12. Life span vs Health span
  13. 13. Concepts of Aging <ul><li>Chronologic age and physiologic age are not the same as noted before </li></ul><ul><li>They vary based on the complex interactions of genetics and the environment </li></ul><ul><li>So individuals age at different rates and there is significant variability in physiological response </li></ul>
  14. 14. Successful Aging - 2 <ul><li>The prevalence of disease increases with age </li></ul><ul><li>Different forms of aging: </li></ul><ul><ul><li>Aging with disease and disability </li></ul></ul><ul><ul><li>Usual aging; absence of pathology but presence of decline in function </li></ul></ul><ul><ul><li>Ideal healthy aging; no pathology or functional loss </li></ul></ul>
  15. 15. Healthy Aging
  16. 16. Successful Aging - 3 H omeostasis less efficient, but still present
  17. 17. Question # 3 Watching Television reduces longevity: A True B False
  18. 18. Physiological Changes <ul><li>Heterogeneity of various values and functions </li></ul><ul><li>Many associated with physical inactivity </li></ul>
  19. 20. Successful Aging - 4 <ul><li>Recent research: </li></ul><ul><ul><li>Elderly individuals with weak muscles are at greater risk for mortality than age-matched individuals </li></ul></ul><ul><ul><li>Increase in amount and rate of loss of muscle increases risk of premature death (i.e. TV, computers) </li></ul></ul><ul><ul><li>Circulation Jan 2010 Dunstan, Barr, et al </li></ul></ul><ul><ul><li>Physical inactivity is 3rd leading cause of death in US and plays role in chronic illnesses of aging </li></ul></ul>
  20. 21. New techniques for exercise <ul><li>Wii golf and bowl </li></ul>
  21. 22. Aging and Disease <ul><li>Aging is associated with </li></ul><ul><li>increase in incidence and severity of disease </li></ul><ul><li>Many disparate factors predispose individuals to functional losses later in life </li></ul><ul><li>Many conditions have suspected either genetic and/or environmental etiologies </li></ul>
  22. 23. Cell Senescence and Death <ul><li>Cell senescence is much like apoptosis </li></ul><ul><ul><li>Occurs throughout life </li></ul></ul><ul><ul><li>It arrests the growth of damaged/dysfunctional cells </li></ul></ul><ul><ul><li>Beneficial early in life; it may contribute to aging later on </li></ul></ul>
  23. 24. Cellular Aging <ul><li>Gene inducers can cause cancer </li></ul><ul><li>Senescence allows cells to more easily respond to inducers, but then cells withdraw from growth cycle are are less likely to move to tumorigenesis </li></ul><ul><li>Other contributions of cell senescence to aging: </li></ul><ul><ul><li>Altered secretions of cells </li></ul></ul><ul><ul><li>Proteases, inflammatory cytokines, growth factors </li></ul></ul><ul><ul><li>Erosion of structure and integrity of tissues </li></ul></ul>
  24. 25. System Review <ul><li>Cardiovascular </li></ul><ul><li>Respiratory </li></ul><ul><li>Renal </li></ul><ul><li>Neurological </li></ul><ul><li>Hematological </li></ul><ul><li>Endocrine/Immune System </li></ul><ul><li>Hormonal/Metabolic </li></ul><ul><li>Musculoskeletal </li></ul><ul><li>Gastrointestinal </li></ul><ul><li>Special Senses </li></ul><ul><li>Skin </li></ul>
  25. 26. Question # 4 <ul><li>The aging Cardiovascular System has a: </li></ul><ul><li>A Reduced Cardiac output </li></ul><ul><li>B Increased Stroke Volume </li></ul><ul><li>C Reduced Peripheral Resistance </li></ul>
  26. 27. Cardiovascular System <ul><li>Reduced - Resting and maximal cardiac output - Stroke Volume - Maximal heart rate - Response to sympathetic nervous system stimulation </li></ul><ul><li>Increased - Systolic Blood Pressure - Peripheral resistance - Total cholesterol and LDL particle number </li></ul><ul><li>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 </li></ul>
  27. 28. Heart to Heart
  28. 29. Question # 5 <ul><li>Senile emphysema is due to: </li></ul><ul><li>A Chest wall Stiffness </li></ul><ul><li>B Alveolar Stiffness </li></ul><ul><li>C Kyphosis </li></ul><ul><li>D All the above </li></ul>
  29. 30. Respiratory System <ul><li>Reduced </li></ul><ul><li>- Lung surface area - Alveolar elasticity </li></ul><ul><li>- Forced Expiratory Volume (FEV 1) - Maximal Oxygen Consumption (VO2 max) </li></ul><ul><li>- P O2 </li></ul><ul><li>Increased </li></ul><ul><li>- Chest wall stiffness </li></ul><ul><li>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 </li></ul>
  30. 31. Home Oxygen
  31. 32. Question # 6 <ul><li>Reduced Spirometric Parameters are associated with: </li></ul><ul><li>A 1 of 5 </li></ul><ul><li>B 2 of 5 </li></ul><ul><li>C 3 of the 5 </li></ul><ul><li>leading causes of death in men </li></ul>
  32. 33. Respiratory System - 2 <ul><li>Impaired ability to clear secretions </li></ul><ul><li>Increased tendency to aspiration </li></ul><ul><li>The reduced activity of effector T cells increases risk of pneumonia </li></ul><ul><li>Reduced spirometric parameters are associated with all cause mortality and specifically with </li></ul><ul><li>- CVD </li></ul><ul><li>- COPD - Lung cancer (3 out of 7 leading causes for women and 3 of the 5 leading causes for men) </li></ul>
  33. 34. Question # 7 <ul><li>Average creatinine clearance decreases 10ml/min for every decade after age 30 </li></ul><ul><li>True </li></ul><ul><li>False </li></ul>
  34. 35. Renal system <ul><li>Decreased renal mass and size - 150 to 200 gms at 30 yrs but only 110 to 150 by 85 yrs </li></ul><ul><li>- Mostly loss of renal cortex 40% less glomeruli by age 80 </li></ul><ul><li>Reduced Renal blood Flow - 10% reduction per decade after age 20 </li></ul><ul><li>- Afferent and efferent arterioles to the cortex atrophy </li></ul><ul><li>Number and length of tubules decreases </li></ul><ul><li>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. </li></ul>
  35. 36. With age comes new skills
  36. 37. Renal function <ul><li>The ability to concentrate urine declines --> frequency. </li></ul><ul><li>Ability to elaborate dilute urine can be reduced. Water overload can easily lead to CHF and hyponatremia. SIADH like pattern </li></ul><ul><li>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 </li></ul><ul><li>There is greater sensitivity to drug induced nephrotoxicity (ACEIs, aminoglycosides) </li></ul><ul><li>Reduced volume of distribution of water soluble drugs (dig) can lead to toxicity </li></ul><ul><li>Increased fat and reduced muscle mass lead to an increased volume of distribution of lipophilic drugs (Benzos) with reduced clearance and risk of toxicity </li></ul>
  37. 38. Question # 8 <ul><li>Cognitive function is affected more than recall memory in normal aging </li></ul><ul><li>A True </li></ul><ul><li>B False </li></ul>
  38. 39. Neurological System <ul><li>Neuronal loss is normal in the aging brain but the ability to learn remains generally unchanged </li></ul><ul><li>There is loss of dendritic arborization </li></ul><ul><li>Recall memory is affected more than cognitive function in normal aging </li></ul><ul><li>Cerebral atrophy shows up on CTs and MRI scans </li></ul><ul><li>Lowered seizure threshold </li></ul><ul><li>Reduced Sympathetic nervous system activity </li></ul><ul><li>Reduced Neurotransmitter levels </li></ul><ul><li>Changes in sleep patterns </li></ul><ul><li>Abnormalities in EEG tracings </li></ul><ul><li>Increased risk of stroke </li></ul>
  39. 40. New skills
  40. 41. Nervous System - 2 <ul><li>Aging leads to increased cerebral amyloid </li></ul><ul><li>Average 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. </li></ul><ul><li>Loss of RNA (messenger and transcription) but not DNA </li></ul><ul><li>Loss of lipids, and lipid turnover rate, and a decrease in catabolism and synthesis. </li></ul>
  41. 42. Hematological <ul><li>The age related reduced marrow production is not necessarily associated with anemias. Many complex factors involved. </li></ul><ul><li>Hemoglobin of 12g/dl is now considered the current lower limit of normal in the elderly (over 75) </li></ul><ul><li>There is however diminished reserve capacity </li></ul>
  42. 43. Balance in aging
  43. 44. Common causes of Anemia Hypoproliferative <ul><li>Hypoproliferative anemias in the elderly </li></ul><ul><li>Iron Deficient erythropoiesis - Nutritional Iron Deficiency - Chronic disease - Inflammation </li></ul><ul><li>Erythropoietin Lack - Renal - Endocrine </li></ul><ul><li>Stem cell dysfunction - Aplastic anemia - Red blood cell aplasia </li></ul>
  44. 45. Causes of anemia Ineffective erythropoiesis <ul><li>Megaloblastic - Vitamin B 12 deficiency - Folate deficiency - Refractory anemia </li></ul><ul><li>Microcytic - Thalassemia - Sideroblastic anemia </li></ul><ul><li>Normocytic Anemias - Stromal disease - Dimorphic anemia </li></ul><ul><li>- Blood Loss </li></ul>
  45. 46. Hemolytic Anemias in the Elderly <ul><li>Immunologic - Idiopathic - Secondary to drugs, tumour, or chronic disease </li></ul><ul><li>Intrinsic - Metabolic - Abnormal hemoglobin </li></ul><ul><li>Extrinsic - Mechanical - Lytic substances </li></ul>
  46. 47. Endocrine System <ul><li>Insulin production increases and then decreases </li></ul><ul><li>Insulin receptors become less effective </li></ul><ul><li>Adrenal 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 </li></ul><ul><li>Reduction in episodic release of Growth Hormone </li></ul><ul><li>Disorders of Vitamin D absorption, bone and mineral metabolism, and parathyroid disorders </li></ul><ul><li>Changes in testicular and ovarian function </li></ul><ul><li>Hyperthyroidism more prevalent in the elderly </li></ul><ul><li>Hypothyroidism in over 4% of people over 60 </li></ul>
  47. 48. Question # 9 <ul><li>Fractures are related to: </li></ul><ul><li>A Visual impairment </li></ul><ul><li>B Osteoporosis </li></ul><ul><li>C Reduced muscle mass </li></ul><ul><li>D All the above </li></ul>
  48. 49. Musculoskeletal System <ul><li>Osteoarthritis - Changes in cartilage chemistry and thickness - Changes in synovial fluid - Changes in the intervertebral discs - Changes in the menisci </li></ul><ul><li>Osteoporosis - Reduced calcium reserves or increased loss - Increased osteoclastic activity over osteoblasts </li></ul><ul><li>Polymyalgia Rheumatica </li></ul><ul><li>Reduced muscle mass </li></ul><ul><li>These all present multiple risk factors for fractures </li></ul>
  49. 50. Gastrointestinal
  50. 51. Question # 10 <ul><li>Elderly patients require more PPIs for longer periods of time than younger patients </li></ul><ul><li>- True </li></ul><ul><li>- False </li></ul>
  51. 52. Gastroenterology <ul><li>Multiple functional changes - Dry mouth, reduced sense of taste, dental issues - Swallowing disorders, risk of aspiration </li></ul><ul><li>- Impaired peristalsis (presbyesophagus) </li></ul><ul><li>- Reduced gastric secretions </li></ul><ul><li>- Reduced intestinal absorption </li></ul><ul><li>- Impaired colonic motility </li></ul><ul><li>and impaired ano rectal function </li></ul><ul><li>- Reduced gallbladder emptying - Reduced hepatic function </li></ul><ul><li>Dyspepsia, bloating, constipation, flatulence </li></ul>
  52. 53. PPIs in the elderly <ul><li>Overuse of PPIs is associated with </li></ul><ul><li>- Increased incidence of pneumonia </li></ul><ul><li>- Increased incidence of hip fractures </li></ul><ul><li>- Increased incidence of C. Difficile </li></ul><ul><li>Wean patients off PPIs and H2 Blockers if possible </li></ul><ul><li>CMAJ August 12, 2008; 179 (4).Targonik LE, Lix LM, et al </li></ul><ul><li>CMAJ September 26, 2006; 175 (7) Dial S, Delaney C, et al </li></ul>
  53. 54. Gastric Acidity <ul><li>Reduced gastric secretions lead to an increased post prandial gastric pH (6.5) </li></ul><ul><li>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 </li></ul><ul><li>The rate of return to pH 2.0 was significantly longer than in younger cohorts (> 4 hrs) </li></ul><ul><li>Pharm Res 1993 Feb;10(2):187-96. </li></ul><ul><li>Upper gastrointestinal pH in seventy-nine healthy, elderly, North American men and women. Russell TL, Berardi RR, et al. </li></ul>
  54. 55. Immune System <ul><li>Diminished cell mediated immunity </li></ul><ul><li>Increased incidence of anergy </li></ul><ul><li>Reduced helper,cytotoxic and effector T cells </li></ul><ul><li>Increased cytokine antagonists </li></ul><ul><li>Changes in neutrophil and macrophage function </li></ul><ul><li>Clinical implications </li></ul><ul><li>Atypical presentations of infectious illnesses </li></ul><ul><li>Poor or delayed response to antibiotic therapies </li></ul><ul><li>Reduced protection of the urinary or the respiratory mucosae </li></ul>
  55. 56. Special Senses <ul><li>Vision </li></ul><ul><li>Hearing </li></ul><ul><li>Smell </li></ul><ul><li>Taste </li></ul><ul><li>Touch </li></ul>
  56. 57. Touch
  57. 58. Treatment Implications <ul><li>The 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 </li></ul><ul><li>Consider earlier and more aggressive treatment of infections BUT with attention to renal function </li></ul><ul><li>Pay closer attention to nutrition and bowel function </li></ul><ul><li>Pay close attention to CNS changes as harbingers of other pathologies </li></ul><ul><li>Screen carefully for metabolic disorders: thyroid, anemias, bone disease, vit deficiencies etc… </li></ul>
  58. 59. Current Areas of Research <ul><li>Caloric Restriction Altered dietary intake </li></ul><ul><li>Genetic causes of age related illnesses </li></ul><ul><li>Effects of IGF (insulin growth factors), TNF (tumor necrosis factors), and inflammatory cytokines etc… </li></ul><ul><li>Pharmaceuticals and pharmacogenomics in the aging individual </li></ul>
  59. 60. Conclusion <ul><li>Aging is not for sissies </li></ul><ul><li>Maintain a maximal muscle mass. Exercise of some form is ALWAYS better than less exercise of any kind at any age and in any condition </li></ul><ul><li>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 </li></ul><ul><li>Maintain careful hydration and nutritional status </li></ul><ul><li>Avoid excess weight gain BUT protect against weight loss. Dropping LDL, triglycerides, albumin are all red flags for senesence and decline. </li></ul>
  60. 61. Go Granny Go
  61. 62. Conclusion <ul><li>Discuss end of life care and review regularly </li></ul><ul><li>Learn the principles of palliative and end of life care </li></ul><ul><li>Apply common sense to protocols and screening guidelines </li></ul><ul><li>Don’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 </li></ul>
  62. 63. The End

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