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Physiology of Aging Min H. Huang, PT, PhD, NCS Reading assignments • Guccione: Ch 3, Ch 7 (pp. 104-113 only), (Ch 15, pp. 272-278 prn) Learning objectives • Identify and interpret physiologic changes that occur with aging. • Adapt physical therapy management to address age-related and life-style related declines in physiological systems. A geriatric client at ICU 73-year-old, active woman with a past history of hypertension and atrial fibrillation. She underwent a routine cardioversion for atrial fibrillation but developed multiple complications, including sepsis and respiratory failure. The patient spent 3 weeks of limited activity in the ICU and was transferred to long-term acute care hospital. 4 Questions to consider • What is your assumption about this patient’s expected outcomes? • How might your personal biases/assumptions affect your interview with this patient? • How might your knowledge of age-related declines in physiological systems affect your clinical decision making? OVERVIEW OF AGEDRELATED PHYSIOLOGICAL CHANGES Ropper 2009 (in Adams and Victor’s) Age-Related Changes in Body Composition/Metabolism Age-Related Changes in Body Composition/Metabolism • Most of the fat increase occurs inside the peritoneum • Fat significantly contribute to increased whole body inflammation, age-related declines, and diseases • Exercise increases metabolic rate and can burn fat as energy sources Age-Related Changes in Body composition/Metabolism • Decreases ―Lean body mass ―Strength ↓ about 8% per decade after 30 y.o, not linear but slow in the beginning and accelerates as age ―Healthy 80-90 y.o. have shown 20-40% ↓ n in max isometric force • Increases ―Fat Mass (contributes to strength and mobility limitations) ―LDL cholesterol Sarcopenia vs. Cachexia Sarcopenia Cachexia • Age-related loss of muscle mass; decreased muscle strength and rate of force production • Amenable to change • Strengthening exercise can significantly ↑ muscle mass and strength • Contribute to the decline in functional ability and frailty • Muscles will NOT respond to exercises • Complex pathophysiology including changes in body metabolism • Ongoing loss of muscle loss, loss of nutrition, caused by negative balance between protein and energy. Cachexia “… a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and lead to progressive functional impairment..………. pathophysiology is characterized by a negative protein and energy balance driven by ↓food intake and abnormal metabolism.” Fearon, 2011 Stage of Cachexia Fearon, 2011 Age-Related Changes in Skeletal Tissue • Basic metabolic unit (BMU) ―Osteoclast, osteoblast, osteocyte • Aging ―↑ bone breakdown rate (osteoclast activity) ―↓ bone accretion rate (osteoblast activity) • Decline in bone mineral with age ―Begins in the 3rd decade at a rate 0.5% to 1% yearly ―~ 2% yearly for the 5-year peri- and menopausal era • Non-modifiable risk factors for bone loss • Modifiable risk factors for bone loss Hip Fracture: How big is the problem in people age 65+ years? • In 2007, 281,000 hospital admissions for hip fractures • Over 90% of hip fractures are caused by falling, most often by falling sideways • In 1990, it was estimated that by 2040, the number of hip fractures would exceed 500,000, although the rate of hip fracture has in fact, declined in recent years. • In 1991, Medicare costs for hip fractures were estimated to be $2.9 billion. Age-Related Changes in Collagenous Tissues and Clinical Consequences Age-Related Changes in Cardiovascular Tissues and Clinical Consequences Age-Related Changes in Nervous System and Clinical Consequences Age-Related Changes in Immune System and Clinical Consequences Age-related changes Clinical Consequence Increase in proinflammatory cytokines (e.g. interleukin 1 and 10, tumor necrosis factor-α) Increase in systemic inflammation, leading to Alzheimer’s disease, atherosclerosis, cancer, diabetes Metabolic syndrome Fat mass, an inflammatory organ, shift from the periphery to the abdomen; an increase in intraabdominal fat Muscle wasting Affect function of body systems (reducing the window of homeostasis) Age-Related Changes in Hormonal Axis • Loss of sex hormones with age ↓ muscle mass and muscle strength • Testosterone levels gradually decline at ~ 1% a year after age 30. By about age 70, the decrease can be as much as 50%. • Testosterone replacement in men ↑ lean muscle mass, but resistance exercise + testosterone replacement is required to ↑ muscle strength Age-Related Changes in Hormonal Axis • Estrogen replacement in women ↑ in strength and lean mass in postmenopausal women • Findings from the Women’s Health Initiative (WHI), a 15-year study launched in 1991 ―Hormone medication (whether estrogen + progestin or estrogen only) resulted in an increased risk of stroke and blood clots ―Estrogen + progestin resulted in an increased risk of heart attack and breast cancer http://nccam.nih.gov/health/menopause/menopausesymptoms#hed1 Estrogen Loss and Manifestations of Health Risks Over Time Menopause Is Associated With an Accelerated Loss of Bone Mass • Decreased cortical thickness is associated with hip fracture After adjustment for age and race, the women not using Hormone Therapy in the previous year had a 55% increased risk of hip fracture http://www.medscape.com/viewarticle/752892_3 AGE-RELATED CHANGES IN SENSORIMOTOR AND NERVOUS SYSTEM http://www.youtube.com/watch?v=HmuBnYVh6xE Neuro-ophthalmologic Signs • Progressive smallness of pupils • Decreased reactions to light and accommodation • Far-sightedness (hyperopia or presbyopia) • Insufficiency of convergence (problem with focus and depth perception) • Restricted range of upward conjugate gaze • Diminished dark adaptation • Increased sensitivity to glare Age-Related Visual Changes • Visual acuity & field decrease with aging • Increased difficulty seeing blues & greens • Spatial visual changes occur making it difficulty to see slow moving objects • Changes with accommodation, contrast, & depth perception • Control of smooth pursuits and saccade is decreased Problems in Vision • Glaucoma (98% blindness preventable) ―Peripheral vision lost 1st then central • Cataracts: opacity of the lens ―Medicare: #1 surgery ―Central vision lost 1st ―Sunglasses for prevention • Macular Degeneration ―Risk increases with age 28% those older than 75 ―Central vision primarily affected ―Quality of life with reading, tv, sewing J. Blackwood What is this an example of? J. Blackwood J. Blackwood What is this? J. Blackwood Other areas of visual loss • Diabetic retinopathy • Retinal detachment • Legal blindness J. Blackwood PT Considerations in Visual Deficits Associated with Aging • • • • • • • Adaptation of HEP instructions PT gym/room, hallways with deco Patterns of flooring Safety in environment, provide adequate light Use of contrasting colors for safety Avoid abrupt changes in light, nightlights Large print, low vision aids, assistance both verbal and tactile J. Blackwood Hearing Loss with Aging • May be masked as dementia • More loss with high tones • Peripheral hearing loss (conduction hearing loss) • Sensorineural loss • Presbycusis ―decrease in auditory acuity resulting from degenerative changes in the inner ear with age (a reduction of the number of hair cells) • Tinnitus J. Blackwood Communication Aids • Hearing aids, amplification devices • Written word • What PTs can do ―Be sure to have the Pt’s attention ―Place yourself between 2-3 feet in front of the Pt ―Speak slowly & clearly. Do NOT shout. ―Talk naturally with a slower pace & more pauses ―Lower the pitch of your voice ―Avoid background noise ―Write J. Blackwood Vestibular System Changes • Disequilibrium and dizziness • Hair cell receptors decline begins at age 30 • 20% decrease in hair cells of saccule and utricle • 40% decrease in hair cells of semicircular canals • Vestibular receptor ganglion cells decrease by age 55-60 PNS Sensory System Changes with Aging • Decreased number of unmyelinated and myelinated nerve fibers • Blood vessels become atherosclerotic ―Loss of blood supply to nerve fibers ―Major factor of the increased prevalence of peripheral neuropathies with age • Sensory conduction velocity slows by 2–4 m/s after age of 20 years Impairment or Loss of Vibratory Sense in the Toes and Ankles • Proprioception impaired very little or not at all • ↑ thresholds for the perception of cutaneous stimuli such as touch, tactile sensitivity ―requires refined methods of testing for detection (e.g. monofilament, 128 Hz tuning fork) • Sensory changes correlate with ―loss of sensory fibers on sural nerve biopsy ―↓amplitude of sensory nerve action potentials ―loss of dorsal root ganglion cells Motor Signs • ↓ speed and amount of motor activity • Slowed reaction time • Impaired fine coordination and agility • ↓ muscular power ―legs more than arms ―proximal muscles more than distal ones • Thinness of muscles ―particularly the dorsal interossei, thenar, anterior tibial muscles, due to a progressive ↓ in the # of anterior horn cells Changes in Tendon Reflexes • ↓ Ankle DTR compared to Knee DTR in persons >70+ years • Loss of Achilles DTR in people >80+ years • +Palmomental reflexes in ~50% people >60+ years ―An involuntary contraction of the mentalis muscle of the chin caused by stimulation of the thenar eminence. ―Its presence may suggest cerebral pathology ―? sensitivity and specificity Effects of Aging on Stance and Gait • Motor agility begins to decline by the 3rd decade ―decrease in neuromuscular control ―Changes in joints and other structures • Gait with normal aging ―Steps shorten ―Slower ―Stooping ―More cautious ―Habitually touches (relaying on sensory cues) Differential Diagnosis of Gait Abnormalities • Abnormal gait patterns associated with degenerative disease of the brain are mostly accompanied by mental changes ―e.g. frontal lobe–basal ganglionic degeneration, normal-pressure hydrocephalus • Other neurologic symptoms and signs present Effects of Aging Other Motor Impairments • Urinary incontinence • Compulsive, repetitive movements ―Mouthing, stereotyped grimacing, protrusion of the tongue, side-to-side or to-and-fro tremor of the head ―Odd vocalizations (sniffing, snorting, and bleating) ―Some of these may resemble tics but they are not really voluntary • ↓ forward trunk angular displacement during stand to sit ―Increased risk of anterior disequilibrium Dubost 2005 PNS Motor System Changes with Aging • Loss of αMN ―remaining αMN will innervate the muscle cells ―remaining MU become larger which can reduce motor coordination for finely tuned movements • Signs of reinnervation ―space between nodes in myelin was reduced • ↓ in the NCV • Motor conduction slows by 0.4–1.7 m/s per decade after 20 years (sensory by 2–4 m/s) PNS Changes with Aging • Wallerian degeneration is delayed • Regeneration takes longer because secretion of trophic factors is slower than in younger adults • Density of regenerated neurons is reduced • Less collateral sprouting ANS Changes with Aging • Sympathetic control of dermal vasculature is reduced, resulting in reduced wound repair efficiency • In aging animal models, TENS improved vascular response through increasing activity of sympathetic nerves Benign Senescent Forgetfulness • Other terms ―age-associated memory impairment (AAMI) ―minimal cognitive impairment • Worsens very little or not at all over years • Does not interfere significantly with work or ADL Benign Senescent Forgetfulness • Diagnostic criteria of AAMI ―age of 50 + years ―a subjective sense of decline in memory ―impaired performance on tests of memory function (at least one SD below the mean) ―absence of any other signs of dementia Neurotrophins (neurotrophic factors) • Proteins secreted by target tissue ―Nerve growth factor (NG), Brain-derived neurotrophic factor (BDNF), Neurotrophin 3, 4, 5 (NT-3, NT-4, NT5) • Bind to receptors on cell membranes • Stimulate neurogenesis • Induce the survival, development, function of neurons • Prolong the life of neurons • Suppress apoptosis (programmed cell death) Blesch 2009 Free Radicals and Oxidative Stress with Aging • Free radicals can cause oxidative stress in brain injury and disease and trigger apoptosis • Enhanced antioxidant status associated with reduced risk of some NS diseases • Oxidative stress is a secondary complication of many progressive NS disorders ―Alzheimer’s Disease ―Parkinson’s Disease ―Amyotrophic Lateral Sclerosis (ALS) Oxidative stress exists when there is an excess of free radicals over antioxidant defences. As a consequence, free radicals attack and oxidise other cell components such as lipids (particularly polyunsaturated lipids), proteins, and nucleic acids. Kelly F J Occup Environ Med 2003;60:612-616 Loss of Brain Weight with Aging • Loss of brain weight correlates roughly with enlargement of the lateral ventricles and widening of the sulci • Possibly due to neuronal degeneration and replacement gliosis • Recent research suggests that cerebral cell loss with aging is LESS PRONOUNCED than previously thought • Hippocampal atrophy < 2%/year in healthy elderly vs. 4-8%/year in Alzheimer’s Loss of Brain Weight with Age • Brain shrinkage is accounted for in part by the reduction in SIZE of large neurons, not their disappearance. • Nerve cell shrinkage may be more significant to function than actual nerve cell loss. • More substantial reduction in neuronal number occurs in ―substantia nigra (↓dopamine) ―locus ceruleus (↓ norepinephrine) ―basal forebrain nuclei (↓ acetycholine) Morphological changes in cortical pyramidal neurons during aging During normal aging, the dendritic arbors and synaptic contacts of individual neurons can expand to compensate for neuronal loss. Prolla 2001 Loss of Brain Weight with Age • Atrophy of Brain (gyrus) • Increased size of ventricles • Deposit of Lipofuscin in cells ―6-7% increase by age 90 • Senile plaques and neurofibrillary tangles ―10% in people age 60 years ―60% in people age 80 years Loss of Brain Weight with Age • Loss of neuronal dendrites in the aging brain ―particularly the horizontal dendrites of the 3rd and 5th layers of the neocortex. • Others showed that the surviving neurons in the neocortex actually exhibit expanded dendritic trees ―even aging neurons have the capacity to react to cell loss by developing NEW SYNAPSES. Cerebral Atherosclerosis • In the normotensive, occur in scattered, discrete plaques ―aorta ―cervical arteries (carotid bifurcation and higher segments) ―proximal MCA ―vertebrobasilar junction ―basilar portions of the cerebral arterial system Cerebral Atherosclerosis • In the hypertensive and diabetic ―more diffuse and extends into finer branches of the cerebral and cerebellar arteries • Can be severe in some 30s-40s years old but absent in some octogenarians! Loss of Functional Reserve with Aging • Normally, a significant loss of neural tissue can occur before functional change occurs • In older adults, there are less redundant neurons to take over the function so functional changes occur more readily