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THE AGEING PROCESS TERMINAL STATES. Prof. M. Tatár, MD, PhD Dept. of Pathophysiology. Gerontology - searching the biochemical and biological background of the ageing process. Geriatrics - practical medical problems of the
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THE AGEING PROCESSTERMINAL STATES Prof. M. Tatár, MD, PhD Dept. of Pathophysiology
Gerontology - searching the biochemical and biological background of the ageing process Geriatrics - practical medical problems of the old people Ageing process is a biologically determined phenomenon (primary ageing) influenced by hostile environmental factors (diseases, trauma, socioeconomic state - secondary ageing)
WHO: - middle age: (45 - 59 yrs) - presenium: (60 - 74 yrs) - senium (old age): (75 - 89 yrs) - very old age (90 and more years)
Estimated population, proportion of population, and growth of population above age 60 for the world and for selected countries in 1970 and 1997 and projected for 2025
100 50 0 1980 % SURVIVED 1930 1900 1840 0 20 40 60 80 100 AGE IN YEARS
Deaths per 1000 women at ages 80 to 89 from 1950 to 1995 Japan France Sweden U.K. U.S.A.
THE AGEING PROCESS - main characteristics from the medical point • Increased mortality with age • Changes in biochemical composition in tissues • Progressive deteriorative physiological changes • decreased ability to respond adaptively to environmental changes • increased vulnerability to many diseases
THEORIES OF AGEING 1 I.Stochastic theories consider ageing as a tear and wear process at molecular, subcellular, cellular and organ level - what are the damaging agents? Somatic mutation theory and failure of DNA repair theory - genes includedin proteosynthesis overall deterioration of the precision of protein synthesis - genes for enzymes of the terminal oxidation localised in mitochondrial DNA (lack DNA repair mechanisms) Theory of random postsynthetic modification - bioreactive forms of oxygen, nonenzymatic glycation - ability of defence mechanisms to prevent and repair random postsynthetic damage (accumulation of faultymolecules)
THEORIES OF AGEING 2 II. Genetic or pacemaker theories (ageing is a continuation of the development and maturation). Ageing might be programmed by a genetic clock 1. Maximal life span of different species is constant 2. Normal cells growing in tissue culture are not able to divide indefinitely and their mitotic capacity decreases with the age of donor. Neuroendocrine theory claimsthat the hypothalamo-pituitary-adrenal axis is the main regulator of the ageing process
THEORIES OF AGEING 3 Reconciliation of the stochastic and genetic theories The actual damage due to stochastic events depends to a great extent on the integrity and ability of the defence and repair mechanisms which are genetically coded and regulated
TERMINAL STATES 1 Tanatology:mechanisms of dying resulting in irreversible disintegration of the organism as a whole 1.Preagonal stage - interaction of two antagonistic tendencies a) damage resulting from pathological situations (ischemia, acidosis) developing especially in CNS b)defensive and compensatory reactions (tachypnoea, tachycardia, vasoconstriction) tending to counterbalance the impaired functions - exhaustion of compensatory reserves: preterminal apnoea, preautomatic pause followed by arrhythmias, progressive hypotension and tisue hypoperfusion
TERMINAL STATES 2 2. Agonal stage:chaotic function of various systems escaped from cortical control; they are altered by subcortical regulatory centers and reflex mechanisms a) Cheyne-Stokes breathing, gasping B) unconsciousness 3.Clinical death:coma, apnoea, pulslessness - progressive damage to most organs and systems -prompt resuscitation attempts can sometimes result in full recovery
4. Biological death - development of irreversible changes depends on the sensitivity of the organs to the lack of oxygen and nutrients supply - irreversible brain damage, destruction includes brainstem and cerebellum Brain death Clinical criteria: 1. Unresponsive coma 2. No spontaneous respiration 3. Absent cephalic reflexes, no ocular responses, fixed pupils 4. Isoelectric EEG 5. Absence of cerebral circulation
Cerebral death - deathof the cerebral hemispheres exclusive of the brainstem and cerebellum - individual is unable forever to respond behaviourally in any significant way to the environment - internal homeostasis is maintained (normal CVS, respiratory and GIT functions, normal temperature control)
Glasgow coma scale 1 • Eye opening arousal mechanisms - reticular formation • Verbal response cognitive functions • Motor response
Glasgow coma score 2 Eye opening 4 spontaneous 3 to speach 2 to pain 1 none
Glasgow coma score 3 Verbal response 5 oriented 4 confused - converses but disoriented 3 inappropriate words - no conversation 2 incomprehensible - no recognizable words 1 none (with pain stimuli)
Glasgow coma score 4 Motor response 6 obeys commands (if not, pain is applied) 5 localises pain - tries to remove stimulus 4 flexion withdrawal - no attempt to stop stimulus 3 abnormal flexion - decorticate posture 2 abnormal extension - decerebrate posture 1 none, flaccide