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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