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 oxygen
FREE RADICAL THEORYProduct 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 proteinPeningkatan 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 “monk’s spot”)
Men experience height decreases of ½ 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
Alzheimer’s disease Parkinson’s 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 affectingcortex 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 --- 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 Alzheimer’s disease
Dopamine, a massive reduction is associated with the loss of motor control, as seen in Parkinson’s disease
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 beta-amyloid 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----- 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 multi-infarct- 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 predictable part of the disease
Degenerasi Ganglia basalis dan batang otak Parkinson disease Huntington disease multiple system atrofi
Parkinson’s 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 diseasesubstansia 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 α-synuclein
morphology atrofi serebelum, pons neuronal loss, cytoplasmic and
nuclear inclusionGejala :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 neuronGejala : denervasi otot : otot lemah,
atrofi, fasikulasiTanda 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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