Transcript THE AGEING PROCESS TERMINAL STATES

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
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
% SURVIVED
100
1980
1930
1900
1840
50
0
0
20
40
60
80
AGE IN YEARS
100
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 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)
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 claims that the hypothalamopituitary-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
Brain death - irreversible brain damage, destruction
includes brainstem and cerebellum
1.
2.
3.
4.
5.
Clinical criteria:
Unresponsive coma
No spontaneous respiration
Absent cephalic reflexes, no ocular responses, fixed pupils
Isoelectric EEG
Absence of cerebral circulation
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)
Glasgow coma scale 1
• Eye opening
arousal mechanisms - reticular formation
• Verbal response
cognitive functions
• Motor response
Glasgow coma score 2
Eye opening
4
3
2
1
spontaneous
to speach
to pain
none
Glasgow coma score 3
Verbal response
5
4
3
2
1
oriented
confused - converses but disoriented
inappropriate words - no conversation
incomprehensible - no recognizable
words
none (with pain stimuli)
Glasgow coma score 4
Motor response
6
5
4
obeys commands (if not, pain is applied)
localises pain - tries to remove stimulus
flexion withdrawal - no attempt to stop
stimulus
3 abnormal flexion - decorticate posture
2 abnormal extension - decerebrate posture
1 none, flaccide