PENYAKIT DEGENERATIF

Resti Arania

PENYAKIT DEGENERATIF

dihub dengan penuaan/ aging

kehilangan fungsi satu atau
beberapa organ
karena destruksi sel progresif

Primary aging refers to changes

that are gradual, inevitable,
universal and insidious, same as
senescence
Secondary aging refers to the
processes that affect the rate at
which primary aging occurs

Why do we age?

Normal aging/ senescence:

proses biologik degeneratif,
perlahan tapi pasti seiring waktu
sesudah proses regenerasi/
pertumbuhan
Aging : perubahan fungsi dan
fisiologik sesudah masa dewasa

WEAR & TEAR THEORY

This theory equates man as

machine.
care, guaranty
Aging is the result of use.

What particular
breakdowns lead to aging?

The genetic mutation theory

suggests that aging is caused by
mutations in the DNA of the cells in
vital organs of the body
The genetic switching theory
suggests that certain genes cease
to operate, causing aging

Error catastrophe theory states

that aging is caused by damage to
RNA, enzymes, and certain other
proteins rather than by errors in
DNA
Free radical theory hinges on
the fact that certain molecules
within a cell display a violent
reaction when they encounter

FREE RADICAL THEORY

Product of metabolism

Accumulate & damage the cell

membrane
Decrease efficiency
Body produce antioxidant

CELLULAR AGING

Penuaan seluler

Terjadi akibat penurunan progresif

kemampuan proliferasi dan life
span
dari sel
Paparan terus menerus pengaruh
eksogen yang mengakibatkan
akumulasi progresif kerusakan
seluler dan molekuler

mekanisme

Genetik

Lingkungan

Nutrisi

Faktor yg mempengaruhi
penuaan biologik

Fungsi metabolik menurun

Penurunan
Fosforilasi
Enzim & sintesa protein
Peningkatan
Kerusakan DNA
Timbunan protein & lipid
Produk sisa

Non-modifiable Aspects of
Aging

Arterial wall rigidity

Cataract formation
Graying of hair
Kidney reserve
Thinning of hair
Elasticity of skin

Modifiable Aspects of Aging

Cardiac reserve
Dental decay
Glucose tolerance
Intelligence tests
Memory
Osteoporosis
Physical endurance
Physical strength
Pulmonary reserve
Reaction time
Serum cholesterol
Social ability
Skin aging
Elevated blood pressure

Exercise, nonsmoking
Prophylaxis, diet
Weight control, exercise, diet
Training, practice
Training, practice
Weight-bearing exercise, diet
Exercise, weight control
Exercise
Exercise, nonsmoking
Training, practice
Diet, weight control, exercise
Practice
Sun avoidance
Salt limitation, weight control,
exercise

Aging and the

neuroendocrine system

Age-related development of
hypertension possibly related to
increased sympathetic system
activity
Impaired glucose intolerance
Diminished thyroid function
Decline in gonadal function

Aging and the brain:

Selective loss of isolated neurons

No evidence that the function of
the brain significantly deteriorates
with aging
Normal age-related forgetfulness
vs. dementia

Changes in Physical
Appearance with Age

Male pattern baldness; this hair

loss begins at the temples,
proceeds to the top of the head,
and continues until the entire top
of the head is bare (the monks
spot)
Men experience height decreases
of inch between 30 and 50, and
another 1 inch between 50 and 70

Age-Dependent Diseases

Cataracts
Hearing Impairment
Osteoporosis
Osteoarthritis
Vulvovaginalatrophy
Nodular prostatic hyperplasia
(BPH)

Age-Related Diseases

Atherosclerosis
Temporal arteritis
Myelodysplasticsyndro
me
Hypertension
Type II diabetes
Vulnerability to
infections

Alzheimers disease
Parkinsons disease
Some cancers, e.g.,
prostate, breast, colon
Calcificaortic stenosis
Multiple myeloma
Glaucoma
Metabolic syndrome

Osteoporosis is a disease that

involves significant losses in bone
calcium and increased bone
brittleness
Osteopenia, mild losses in bone
density

Estrogen replacement, maintaining

a balanced diet, and engaging in
physical exercise on a regular basis
are associated with a decreased
likelihood of osteoporosis
Age is associated with an
increased likelihood of
osteoporosis

Changes in Hormone
Regulation and Reproduction

Female reproduction system

undergoes hormonal changes with
aging

Changes in ovary function determine

the timing of the events leading to
irregular cycles
Age-related changes in follicle
stimulating hormones (FSH) levels are
one of the earliest hallmarks of
reproductive aging

Changes in Circulation and

Respiration

Diseases of the circulatory system,

such as heart disease,
hypertension, atherosclerosis, are
serious problems
Although the incidence of heart
disease is decreasing, it is still the
leading cause of death in the U.S.

Heart Disease and

Lifestyle

Coronary heart disease is the

leading cause of death for men
and women
Almost 25% of those who die from
coronary heart disease experience
sudden death due to cardiac
arrest, most often ventricular
fibrillation, the rapid, uncontrolled
beating of the heart

A heart attack (myocardial infarction)

is the end result of atherosclerosis,
the narrowing of the arteries that supply
blood to the heart muscle due to
buildup of fatty deposits or plaques
Cardiovascular disease (CVD)
includes coronary disease, stroke,
congestive heart failure, and high blood
pressure or hypertension

Eighty percent of men and seventy

percent of women under age 65
who have heart failure will die
within eight years
Stroke is the leading cause of
serious, long-term disability in the
U.S.

Simpulan

Universal
Alamiah, tidak terelakkan, irreversible,
progresif seiring waktu
Bervariasi antar individu
Laju bervariasi antar organ, jaringan
Dipengaruhi fx nonbiologis
proses penyakit
Rentan sakit
perubahan terkait penuaan faktor
risiko

Important Diseases of the

Elderly

Osteoporosis
Dementia
Metabolic syndrome

Major Components of the

Brain

A neuron is the basic unit of the

brain and nervous system
Every neurons has 3 basic
components:

Soma (cell body)

Axon
Dendrites

Apoptosis is used to refer to

programmed neuron death and the
loss of neurons
Neuronal viability, in addition to
apoptosis, is a key factor in normal
and abnormal brain aging

Neuronal viability refers to the

efficiency of neural functioning

Degenerative disease
affecting
cortex

Alzheimer (most common)

Frontotemporal dementia
Pick disease
progressive supranuclear palsy

Alzheimers Disease

A form of dementia whose

primary symptoms is the abnormal
deteriorations of mental
functioning
The threshold model observes
that a significant amount of
damage occurs before
consequences are noticed

Alzheimer disease

Genetic (chromosome 21 : gene

APP --- associated Down syndrome)
Sporadic most cases
progresive---- 10 year
Problem social, medical, economic
gross : cortical atrophy

Neurons communicate with each

other by secreting chemical
substances called
neurotransmitters
Acetylcholine, a large reduction
may be responsible for the severe
memory loss associated with
Alzheimers disease
Dopamine, a massive reduction is
associated with the loss of motor
control, as seen in Parkinsons

Alzheimer disease,
morphology

Tangled bundles of protein

filaments known as
neurofibrillary tangles
Also studies have reported a large
decline in the amount of white
matter (the fatty myelin sheath
that surrounds and insulates long
axons)

With normal aging, the

extracellular spaces within the
hippocampus, cerebral cortex, and
other brain regions gradually
accumulate spherical deposits
called senile plaques
These plaques are aggregates of a
small molecule known as betaamyloid protein(A protein)

neurofibrilar tangles :
hyperphosphorylated protein tau
- axonal microtubules protein
not spesific to Azlheimer

Causes of Alzheimers
Disease

Cholinergic hypothesis states that AD

is caused by decreases in acetylcholine
Genetic hypothesis is based on the
discovery that early-onset familial AD
(FAD) runs in families (APP gene defect,
chromosome 21)
Researchers also know that a mutation
on chromosome 21 is responsible for
encoding an amyloid precursor
protein (APP)

amiloid : congo
red

Morphology Alzheimer

plaque neuritic/ senilis----- tu.

amiloid
neurofibrillary tangles
granulovacuolar degeneration,
angiopathy amiloid, deposit
lipofuscin

Other Dementias

Multi-Infarct- 20-25% of all

dementias
Mixed Dementia-2 forms of
dementia coexist (AD and multiinfarct- 18% of diagnosed)
Creutzfeldt-Jakob Disease-rare
form of dementia caused by a slow
acting virus
AIDS Dementia Complex-the result
of a brain infection by AIDS, a

Degenerasi Ganglia
basalis dan batang otak

Parkinson disease
Huntington disease
multiple system atrofi

Parkinsons Disease-associated
with dementia in 15-40% of cases
Pseudodementia-the clinical
picture of depression in the elderly
Symptoms may be apathy,
psychomotor retardation, impaired
concentration, confusion
Drugs, alcohol, toxins and physical
illnesses may also cause reversible
dementia

Parkinson disease

familial form (otosom

dominan/resesive)
sporadic
parkinsonism, dementia

Morfologi Parkinson
disease

pallor substansia nigra

causa : depigmented neuron
characteristic : Lewy bodies (large
neuron w. eosinophilic
intracytoplasmic inclusion)

Parkinson disease
substansia nigra, Lewy
bodies

Huntington disease,
otosom dominan

Morphology Huntington
disease

atrophy nucleus caudatus, lobus

frontoparietal
ventricles dilated
neuronal loss, gliosis

Huntington disease

Pathogenesa : deg. / loss neuron

dysregulate motoric - choreiform
movements
genetic molecular : gene HD on
chromosome 4 : coding repeat
trinucleotide CAG (normal 6-35
copy repeat)trinucleotide repeat
disorder

Huntington disease

clinical features
decades 4/5
early : dementia
affective
severe dementia
suicide
infection death

Mutiple system atrophy

neurodegenerative multiple neural

system
glial cytoplasmic inclusion
oligodendrocytes
deposit -synuclein

morphology
atrofi serebelum, pons
neuronal loss, cytoplasmic and
nuclear inclusion
Gejala :
Parkinsonism dan disfungsi otonom
(hipotensi ortostatik)

Spinocerebellar
degeneration
Ataxia spinocerebellar tdd :
- ataxia Friedreich
ataxia teleangiectasia
Otosom resesive

DEGENERATIVE MOTOR
NEURON
Lower motor neuron
lower motor neuron cranial
upper motor neuron
Gejala : denervasi otot : otot lemah,
atrofi, fasikulasi
Tanda klinis : paresis, spastis,
hiperefleksi

Amyotrophic Lateral
Sclerosis

atrofi otot
Sering wanita, dekade ke 5
5-10% otosom dominan
cornu anterior korda spinalis :
menipis
girus precentral atrofi
mikroskopik : neuron cornu
anterior berkurang

klinis : kelemahan tangan

sulit melakukan tugas motorik
kram, kaku lengan dan otot
lanjut : fasikulasi
kena otot napas pneumoni
progressive muscular atrophy

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