PHYSIOLOGY OF AGING Special considerations when dealing with older patients

1. PHYSIOLOGY OF AGING Special considerations when  dealing with older patients Dr. Jos. Zebley MAFP February 2010 Annapolis Md

2. Physiology of Aging �We are all amateurs; we don�t live long enough to become anything else.� Charlie Chaplin

3. 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.

4. Question # 1 Patients over 60 make up a 20% b 30% c 40% of all physician visits

5. Demographic 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

6. Baltimore Sun 7/19/2009

7. Question # 2 What would improve life expectancy more: A Finding cures for diabetes, cancer, heart disease, and stroke B Slowing down the rate of aging

8. 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

9. Stages 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

10. Stages 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

11. Human 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

12. Life span vs Health span

13. Concepts 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

14. Successful 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

15. Healthy Aging

16. Successful Aging - 3  Homeostasis less efficient, but still present

17. Question # 3

18. Physiological Changes Heterogeneity of various values and functions Many associated with physical inactivity

20. 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

21. New techniques for exercise Wii golf and bowl

22. Aging 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

23. Cell 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

24. Cellular 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

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

26. Question # 4 The aging Cardiovascular System has a: A Reduced Cardiac output B Increased Stroke Volume C Reduced Peripheral Resistance

27. 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 with conditioning exercise in the absence of disease however the CO with exercise will be reduced even in healthy aging

28. Heart to Heart

29. Question # 5 Senile emphysema is due to: A Chest wall Stiffness B Alveolar Stiffness C Kyphosis D All the above

30. 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 thoracic capacity. That and alveolar stiffness leads to �senile emphysema� with an FEV1/FVC < 70% of the predicted for age and gender

31. Home Oxygen

32. Question # 6 Reduced Spirometric Parameters are associated with: A 1 of 5 B 2 of 5 C 3 of the 5 leading causes of death in men

33. Respiratory 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)

34. Question # 7 Average creatinine clearance decreases 10ml/min for every decade after age 30 True False

35. 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 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.

36. With age comes new skills

37. Renal 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

38. Question # 8 Cognitive function is affected more than recall memory in normal aging A True B False

39. 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 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

40. New skills

41. Nervous System - 2 Aging leads to increased cerebral amyloid 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. Loss of RNA (messenger and transcription) but not DNA Loss of lipids, and lipid turnover rate, and a decrease in catabolism and synthesis.

42. Hematological 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

43. Balance in aging

44. 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

45. 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

46. Hemolytic Anemias in the Elderly Immunologic - Idiopathic - Secondary to drugs, tumour, or chronic disease Intrinsic - Metabolic - Abnormal hemoglobin Extrinsic - Mechanical - Lytic substances

47. 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 known alteration 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 and mineral metabolism, and parathyroid disorders Changes in testicular and ovarian function Hyperthyroidism more prevalent in the elderly Hypothyroidism in over 4% of people over 60

48. Question # 9 Fractures are related to: A Visual impairment B Osteoporosis C Reduced muscle mass D All the above

49. 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

50. Gastrointestinal

51. Question # 10 Elderly patients require more PPIs for longer periods of time than younger patients - True - False

52. 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

53. 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 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

54. Gastric 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.

55. 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 respiratory mucosae

56. Special Senses Vision Hearing Smell Taste Touch

57. Touch

58. Treatment Implications 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 Consider earlier and more aggressive treatment of infections BUT with attention to renal function Pay closer attention to nutrition and bowel function Pay close attention to CNS changes as harbingers of other pathologies Screen carefully for metabolic disorders: thyroid, anemias, bone disease, vit deficiencies etc�

59. 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), and inflammatory cytokines etc� Pharmaceuticals and pharmacogenomics in the aging individual

60. Conclusion Aging is not for sissies 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 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 status Avoid excess weight gain BUT protect against weight loss. Dropping LDL, triglycerides, albumin are all red flags for senesence and decline.

61. Go Granny Go

62. Conclusion Discuss end of life care and review regularly Learn the principles of palliative and end of life care Apply common sense to protocols and screening guidelines 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

63. The End