1. THE AGEING PROCESS TERMINAL STATES Prof. M. Tatár, MD, PhD Dept. of Pathophysiology

2. Gerontology - searching the biochemical and biological background of the biological background of the ageing process ageing process Geriatrics - practical medical problems of the old people old people Ageing process is a biologically determined phenomenon (primary ageing) influenced by hostile environmental factors (diseases, trauma, socioeconomic state - secondary ageing)

3. WHO: WHO: - middle age: (45 - 59 yrs) - presenium: (60 - 74 yrs) - senium (old age): (75 - 89 yrs) - very old age (90 and more years)

4. 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

5. 0 20 40 60 80 100 100 50 0 1840 1900 1930 1980 % SURVIVED AGE IN YEARS

6. Deaths per 1000 women at ages 80 to 89 from 1950 to 1995 Japan France Sweden U.K. U.S.A.

7. 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

8. 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 included in 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 faulty molecules)

9. 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. THEORIES OF AGEING 2 Neuroendocrine theory claims that the hypothalamo- pituitary-adrenal axis is the main regulator of the ageing process

10. THEORIES OF AGEING 3 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 Reconciliation of the stochastic and genetic theories

12. TERMINAL STATES 1 Tanatology: Tanatology: mechanisms of dying resulting in irreversible disintegration of the organism as a whole 1. Preagonal stage - interaction of two antagonistic tendencies 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

13. 2. Agonal stage: chaotic function of various systems escaped from cortical control; they are altered by escaped from cortical control; they are altered by subcortical regulatory centers and reflex mechanisms subcortical regulatory centers and reflex mechanisms a) Cheyne-Stokes breathing, gasping B) unconsciousness 3. Clinical death: coma, apnoea, pulslessness - prompt resuscitation attempts can sometimes result in full recovery - progressive damage to most organs and systems TERMINAL STATES 2

14. 4. Biological death - development of irreversible changes depends on the sensitivity of the organs to the lack of oxygen and nutrients supply 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 - irreversible brain damage, destruction - irreversible brain damage, destruction includes brainstem and cerebellum includes brainstem and cerebellum

15. Cerebral death - death of 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)

19. Glasgow coma scale 1 Eye opening arousal mechanisms - reticular formation Verbal response cognitive functions Motor response

20. Glasgow coma score 2 Eye opening 4spontaneous 3to speach 2 to pain 1none

21. Glasgow coma score 3 Verbal response 5oriented 4confused - converses but disoriented 3inappropriate words - no conversation 2incomprehensible - no recognizable words 1none (with pain stimuli)

22. Glasgow coma score 4 Motor response 6obeys commands (if not, pain is applied) 5localises pain - tries to remove stimulus 4flexion withdrawal - no attempt to stop stimulus 3abnormal flexion - decorticate posture 2abnormal extension - decerebrate posture 1none, flaccide