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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

perlahan tapi pasti seiring waktu sesudah proses regenerasi/ pertumbuhan Aging : perubahan fungsi dan fisiologik sesudah masa dewasa .Why do we age?   Normal aging/ senescence: proses biologik degeneratif.

 care. guaranty Aging is the result of use. .WEAR & TEAR THEORY   This theory equates man as machine.

causing aging .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.

enzymes.  Error catastrophe theory states that aging is caused by damage to RNA. 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 .

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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 .

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

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 .

this hair loss begins at the temples.Changes in Physical Appearance with Age   Male pattern baldness. and continues until the entire top of the head is bare (the “monk’s spot”) Men experience height decreases of ½ inch between 30 and 50. and another 1 inch between 50 and 70 . proceeds to the top of the head.

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        Alzheimer’s disease Parkinson’s disease Some cancers. colon Calcificaortic stenosis Multiple myeloma Glaucoma Metabolic syndrome . prostate. breast.g. e.

  Osteoporosis is a disease that involves significant losses in bone calcium and increased bone brittleness Osteopenia. mild losses in bone density .

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 .  Estrogen replacement.

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

the rapid. most often ventricular fibrillation.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. uncontrolled beating of the heart .

  A heart attack (myocardial infarction) is the end result of atherosclerosis. stroke. congestive heart failure. and high blood pressure or hypertension . 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.

long-term disability in the U. .  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.S.

progresif seiring waktu Bervariasi antar individu Laju bervariasi antar organ. tidak terelakkan. irreversible.Simpulan        Universal Alamiah. 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 .

Alzheimer’s 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 --. medical. economic gross : cortical atrophy .associated Down syndrome) Sporadic most cases progresive---.10 year Problem social.

   Neurons communicate with each other by secreting chemical substances called neurotransmitters Acetylcholine. a massive reduction is associated with the loss of motor control. a large reduction may be responsible for the severe memory loss associated with Alzheimer’s disease Dopamine. as seen in Parkinson’s .

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(Aβ protein)

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

Causes of Alzheimer’s
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----. angiopathy amiloid.tu. amiloid neurofibrillary tangles granulovacuolar degeneration. deposit lipofuscin .

Other Dementias     Multi-Infarct.20-25% of all dementias Mixed Dementia-2 forms of dementia coexist (AD and multiinfarct. a .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.

Degenerasi Ganglia basalis dan batang otak    Parkinson disease Huntington disease multiple system atrofi .

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

dementia .Parkinson disease    familial form (otosom dominan/resesive) sporadic parkinsonism.

eosinophilic intracytoplasmic inclusion) .Morfologi Parkinson disease    pallor substansia nigra causa : depigmented neuron characteristic : Lewy bodies (large neuron w.

Parkinson disease substansia nigra. Lewy bodies .

otosom dominan .Huntington disease.

lobus frontoparietal ventricles dilated neuronal loss. gliosis .Morphology Huntington disease    atrophy nucleus caudatus.

/ 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   Pathogenesa : deg.

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 α-synuclein .

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

ataxia Friedreich  ataxia teleangiectasia  Otosom resesive  .Spinocerebellar degeneration Ataxia spinocerebellar tdd : .

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

dekade ke 5 5-10% otosom dominan cornu anterior korda spinalis : menipis girus precentral atrofi mikroskopik : neuron cornu anterior berkurang .Amyotrophic Lateral Sclerosis       atrofi otot Sering wanita.

      klinis : kelemahan tangan sulit melakukan tugas motorik kram. kaku lengan dan otot lanjut : fasikulasi kena otot napas pneumoni progressive muscular atrophy .

T H A N K Y O U .