14 Pathology of Degeneraton and Aging

Pathology ofPathology of Degeneration & AgeingDegeneration & Ageing

dr. Al Munawir, M.Kes., Ph.D.Laboratorium Patologi

AnatomiFakultas Kedokteran Universitas Jember

Cell Injury:

When I look into the future, When I look into the future, it's so bright it burns my eyes…!it's so bright it burns my eyes…!

– Oprah Winfrey

Ageing

Cell Injury:

Ageing:“Progressive time related loss of

structural and functional capacity of cells leading to death”

Senescence, Senility, Senile changes. Ageing of a person is intimately related

to cellular ageing. Blood vessel damage precedes ageing.

PHYSICAL AGING PROCESS

WHEN DOES OLD AGE BEGIN?

Cell Injury:

DEFINITION OF AGING Old and aging depends on the age

and experience of the speaker. Chronological age - number of

years lived Physiologic age - age by body

function Functional age - ability to

contribute to society

Cell Injury: CHRONOLOGICAL CATEGORIES

Young-Old - (ages 65 - 74)

Middle-Old - (ages 75 - 84)

Old-Old - (age 85 and older)

Cell Injury: FRAIL ELDERLY

Characteristics: Poor mental and

physical health Low socioeconomic

status Predominantly female Possibly isolated living

conditions More and longer

hospital stays, and More money spent on

health care and drugs

PHYSICAL THEORIES OF AGING

What causes the body to age?

PROGRAM THEORY

Cells replicate a specific number of times and then die. Happens again, and again in lab experiments.

Cell Injury:

ERROR THEORY

The structure of DNA is altered as people age

Due to alterations, DNA not read correctly

Results in transcription and translation malfunction

Results in aging/illness/ cancer directly, or indirectly

CELLULAR THEORY

Normal wear and tear causes cells to function

improperly

Cell Injury:

FREE RADICAL THEORY

Lipids in cell membranes are exposed to radiation or free radicals

Cell membrane ruptures and cell dies

In test tubes this actually occurs

Cell Injury: NUTRITIONAL MODEL THEORY

If animal fed 50-60% less than it eats on its own - lives longer

Assumption: Lean mass, as opposed to adipose tissue results in greater health

COLLAGEN THEORY OF AGING

As we age, collagen in body ages also. Causes hypertension and other

organ malfunctions

Cell Injury: MUTATING AUTO-IMMUNE THEORY

Cells have normal functions - secrete normal proteins

As cells age - mutate and secretions viewed as foreign by body

Solicits immune response Shuts cell down Cause biological errors and entire

organ malfunctions

Cell Injury:

NEURO-AGING THEORY

All cells undergo nervous system degeneration

Results in changes in hormonal release

Leads to decline in cell function

NONE OF THESE THEORIES TOTALLY ACCEPTED

Scientists hypothesize it might be combination of

several or all

Cell Injury:

PHYSIOLOGICAL AGING OF THE HUMAN BODY

BY SYSTEMS

Cell Injury:

SKIN, HAIR, NAILS Loss of subcutaneous fat Thinning of skin Decreased collagen Nails brittle and flake Mucous membranes drier Less sweat glands Temperature regulation

difficult Hair pigment decreases Hair thins

Cell Injury:

EYES AND VISION Eyelids baggy and wrinkled Eyes deeper in sockets Conjunctiva thinner and

yellow Quantity of tears decreases Iris fades Pupils smaller, let in less

light Night and depth vision less “Floaters” can appear Lens enlarges

Cell Injury: EYES AND VISION CONT.

Lens becomes less transparent

Can actually become clouded

Results in cataracts

Cell Injury: EYES AND VISION CONT.

Accommodation decreases Results in presbyopia Impaired color vision, also -

especially greens and blues Because cones degenerate

Cell Injury: EYES AND VISION CONT.

Predisposed to glaucoma

Increased pressure in eye

Decreased absorption of intraocular fluid

Can result in blindness

Cell Injury:EYES AND VISION

CONT.

Macular degeneration becoming more frequent

This is the patch of retina where lens focuses light

Ultimately results in blindness

Reason for current increase in this condition unknown

Cell Injury: EARS AND HEARING LOSS

Irreversible, sensorineural loss with age

Men more affected than women

Called presbycusis Loss occurs in higher

range of sound By 60 years, most adults

have trouble hearing above 4000Hz

Normal speech 500-2000Hz

Cell Injury: RESPIRATORY SYSTEM

Lungs become more rigid

Pulmonary function decreases

Number and size of alveoli decreases

Vital capacity declines Reduction in

respiratory fluid Bony changes in chest

cavity

Cell Injury: CARDIOVASCULAR SYSTEM

Heart smaller and less elastic with age

By age 70 cardiac output reduced 70%

Heart valves become sclerotic

Heart muscle more irritable

More arrhythmias Arteries more rigid Veins dilate

Cell Injury: GASTROINTESTINAL SYSTEM

Reduced GI secretions

Reduced GI motility Decreased weight of

liver Reduced

regenerative capacity of liver

Liver metabolizes less efficiently

Cell Injury:

RENAL SYSTEM After 40 renal function

decreases By 90 lose 50% of function Filtration and

reabsorption reduced Size and number of

nephrons decrease Bladder muscles weaken Less able to clear drugs

from system Smaller kidneys and

bladder

Cell Injury: REPRODUCTIVE SYSTEM

Male: Reduced testosterone level Testes atrophy and soften Decrease in sperm

production Seminal fluid decreases

and more viscous Erections take more time Refractory period after

ejaculation may lengthen to days

Cell Injury: REPRODUCTIVE SYSTEM

Female: Declining estrogen and

progesterone levels Ovulation ceases Introitus constricts and

loses elasticity Vagina atrophies -

shorter and drier Uterus shrinks Breasts pendulous and

lose elasticity

Cell Injury: NEUROLOGICAL SYSTEM

Neurons of central and peripheral nervous system degenerate

Nerve transmission slows Hypothalamus less effective in

regulating body temperature Reduced REM sleep, decreased

deep sleep After 50% lose 1% of neurons

each year

Cell Injury: MUSCULOSCELETAL SYSTEM

Adipose tissue increases with age

Lean body mass decreases Bone mineral content

diminished Decrease in height from

narrow vertebral spaces Less resilient connective

tissue Synovial fluid more viscous May have exaggerated

curvature of spine

Cell Injury:

IMMUNE SYSTEM Decline in immune function Trouble differentiating

between self and non-self - more auto-immune problems

Decreases antibody response

Fatty marrow replaced red marrow

Vitamin B12 absorption might decrease - decreased hemoglobin and hematocrit

Cell Injury:

ENDOCRINE SYSTEM Decreased ability to

tolerate stress - best seen in glucose metabolism

Estrogen levels decrease in women

Other hormonal decreases include testosterone, aldosterone, cortisol, progesterone

Cell Injury:

Factors affecting Ageing: Genetic 60% & Environmental 40% Clock genes, (fibroblast culture) Werner’s syndrome. Age gene on Chromosome 1. “Age” is a character from female

parent. Mammalian mitochondria come from

ovum.

Cell Injury:

Factors affecting Ageing: Environmental factors (40%) Trauma Diseases – Atherosclerosis, diabetes Diet – malnutrition, obesity etc. Psychological & Social health –

stress.

Cell Injury:Ageing – Morphologic changes:

Easy bruising – fragile capillaries. Glycosylation of lens proteins – Accumulation of Lipofuscin pigment

– Brown atrophy. Blood vessel hardening –

arteriosclerosis, atherosclerosis.

Cell Injury:Ageing – Morphologic changes:

Skin – elastosis, hairloss, atrophy, bruising.

Joints – osteoarthritis. Immunity – immunosuppression. Heart – Brown atrophy, CVS – arterio & atherosclerosis, MI,

stroke. Neoplasms CNS – cerebral degeneration.

Cell Injury:Atrophy – Senile / Alzheimer's

Cell Injury:

Elastosis of skin:

Cell Injury:

Pathology of elderly

Cell Injury: