HISTORY, CONCEPT AND ITS IMPORTANCE IN DRUG DEVELOPMENT.pptx
3.CELLULAR ADAPTATION, INJURY and DEATH 2012.ppt
1. CELLULAR ADAPTATION, INJURY and
DEATH
Introduction
• When confronted with stresses that endanger
its normal structure and function, the cell
undergoes adaptive changes that permit
survival and maintenance of function
2. Introduction
• reactions of cells and tissues to injurious agents,
including genetic defects, is key for the
understanding of disease processes.
• cellular changes can occur due to the
-adaptation,
-injury,
-neoplasia,
-aging
-death.
3. Cellular Adaptation
• Cellular adaptation is a state that lies intermediate between
the normal, unstressed cell and the injured, over-stressed
cells.
• Cells must constantly adapt, even under normal
conditions, to changes in their environment.
• Somewhat more excessive physiologic stress or
some pathologic stimuli can bring about a number of
physiologic and morphologic changes in which a new but
altered steady state is achieved, preserving the viability of the
cells - called cellular adaptation.
4. Cell Injury
• If the limit of adaptive response to a stimulus is exceeded, or in certain
instances when adaptation is not possible, a sequence of events follows,
termed as cell injury.
• Cell injury is reversible up to a certain point but if the stimulus persists or
severe enough from the beginning, the cell reaches the point of no return
and suffers irreversible cell injury and cell death. Cell death is the ultimate
result of cell injury.
• Reversible cell injury, irreversible cell injury, necrosis and apoptosis are
morphologic patterns of acute cell injury.
• There are other patterns of morphologic alteration, such as subcellular
alteration, which occur largely as a response to more chronic or persistent
injurious stimuli;
– intracellular accumulation, which occur as a result of derangement in the
metabolism or excessive storage;
– pathologic calcification, an accumulation of Calcium in the cell -a
common consequence of cell and tissue injury.
6. Types of Cellular Adaptation
• Physiologic Adaptation
–Usually represents responses of the cells to normal stimulation
by hormones or endogenous chemical substances, e.g.
enlargement of breast and induction of lactation by
pregnancy.
• Pathologic Adaptation
–May share the same underlying mechanism, but they provide
the cells with ability to survive in their environment and
perhaps escape injury.
7. General Mechanism of Cellular
Adaptation
• Up- or down-regulation of specific cellular receptors involved in metabolism
of certain components, e.g. in the regulation of cell surface receptors
involved in the uptake and degradation of low-density lipoproteins (LDL).
• Induction of new protein synthesis by the target cells, e.g. heat-shock
response.
• Production of one type a family of proteins to another or markedly
overproducing one protein e.g. cells producing various types of collagens
and ECM proteins in chronic inflammation and fibrosis.
8. Adaptation involves all steps of cellular
metabolism of proteins – receptor binding, signal
transduction, transcription or regulation of
protein packaging and release.
9. • Different types of cellular injuries
- hypoxic (lack of sufficient oxygen),
- free radical
- infectious.
These types of injuries can have different clinical and
pathologic manifestation. When cells of a living
human organism are exposed to a noxious(physically
harmful)agents, they become injured.
10.
11. Cellular Reaction Pattern To Stress
Depends On:
1. Type, duration, and severity of stress.
2. Type, state and adaptability of cell.
I-Irreversible Cell Injury:
Severe stimuli leads to necrosis .& Apoptosis
II-Reversible Cell Injury:
Mild stress for short duration leads to biochemical change or
mild form of morphologic change in the affected cells
( hydropic swelling).
12. Cellular adaptation
• When cells of a living human organism are
exposed to a noxious agent, they become
injured.
• They are four ways of respond
- get bigger,
- get smaller,
- proliferate or
- die.
13. Persistent prelethal stress
leads to cellular adaptation.
1-Adaptation of growth.
a) Increased growth and cellular activity e. g. Hypertrophy & Hyperplasia
b) Decreased growth and cellular activity e.g. Atrophy.
2-Disturbances of cellular differentiation and
morphology e.g. Metaplasia,& Dysplasia.
14. Persistent prelethal stress
leads to cellular adaptation.
.
3-Intra and Extra cellular accumulations
e. g.
Lipids as in fatty change & Cholesterol deposits.
Proteins as in Hyaline change& Amyloidosis.
Pigments as in Pathologic pigmentation.
Calcium as in Pathologic Calcification
Enzymatic metabolic deficiency as in Gout& lyzosomal storage
disease.
15. Cellular adaptation …
• Cells adapt to their environment to escape
and protect themselves from injury.
• An adapted cell is neither normal nor injured.
• In many disease conditions, cellular
adaptation are common.. The most significant
adaptive changes in cells are;
16. Cellular adaptation …
The most significant adaptive changes in cells
are;
• atrophy -decrease in cell size
• hypertrophy – increase in cell size
• hyperplasia – increase in cell number, and
17. Cellular adaptation …
• dysplasia – deranged cellular growth which is
an atypical hyperplasia and can not be
considered as true cellular adaptation.
• metaplasia – reversible replacement of one
mature cell type by another, less mature cell
type
18. Terminology:
• Necrosis: Morphologic changes seen in dead
cells within living tissue.
• Autolysis: Dissolution of dead cells by the cells
own digestive enzymes.
• Apoptosis: Programmed cell death.
Physiological, for cell regulation.
19. Atrophy
Is a decrease or shrinkage in cellular size
• it can affect any organ,
• but it is most common in skeletal muscle, the
heart, secondary sex organs and the brain.
20. Atrophy…
The cause of atrophy can be decreases in;
• workload
• use
• blood supply
• nutrition
• hormonal stimulation and
• nervous stimulation
21. Atrophy…
• when individual immobilized in bed for prolonged
time exhibit a type of skeletal muscle atrophy called
disuse atrophy.
• in aging individuals brain cells become atrophic due
to decrease of blood supply.
• gonads to shrink due to decrease in hormonal
stimulation.
All atrophic cells exhibit the same basic changes.
24. Hypertrophy
Is an increase in the size of cells and
consequently in size of the affected organ
• increased in cellular size is associated with an
increased accumulation of protein in the
cellular components and not with an increase
in cellular fluid
25. Hypertrophy…
• An example of normal or physiologic hypertrophy is
the increased growth of the uterus and mammary
glands in response to pregnancy.
• Pathologic hypertrophy occurs as the result of
disease conditions .
• may be adaptive or compensatory.
• the thickening of the urinary bladder and myocardial
hypertrophy are example of pathological hypertrophy
26. Hyperplasia
• is an increase in the number of cells resulting
from an increased rate of cellular division.
• response to injury.
• can either be compensatory or hormonal but
often, the cause for hyperplasia is hormonal
stimulation. .
27. Hyperplasia…
• Compensatory hyperplasia is an adaptive
mechanism to regenerate
-if the part of the liver is removed, the remain
liver cells (hepatocytes) will regenerate to
compensate
- 70% of the liver regeneration can be
completed within 2 weeks
- is enhanced by HGF which acts as mediator
of liver regeneration.
28. Hyperplasia…
• Hormonal hyperplasia occurs chiefly in
estrogen- dependent organs, such as the
uterus and breast.
• Pathologic hyperplasia is the abnormal
proliferation of normal cells e.g. pathologic
endometrial hyperplasia.
29. Pathologic Hyperplasia
Most forms of pathologic hyperplasia are
instances of excessive hormonal stimulation or
are effects of growth factors on target cells,–
e.g.
hyperplasia of endometrium,
hyperplasia of prostate,
hyperplasia of connective tissue cells in wound healing,
skin warts.
30. Dysplasia
Abnormal changes in size, shape and
organization of mature cells
• it is not a true adaptive process but rather
called atypical hyperplasia
• it can be classified as mild, moderate or severe
• is a strong predictor of breast cancer
development.
31. Metaplasia
Is the reversible replacement of one mature cell type
by another.
– the replacement of normal columnar ciliated epithelial
cells by stratified squamous epithelial in bronchial.
– bronchial metaplasia can be reversed by the removal of
the stimulus.
– With prolonged exposure to the stimulus however,
cancerous transformation can occur.
32. (A) Epithelium metaplasia
1. Squamous metaplasia: 2. Columnar
metaplasia
( 1) Squamous metaplasia
a) From pseudo-stratified columnar:
* Trachea and bronchi in chronic bronchitis, cigarette smoking
and bronchiectesis.
* Nasal sinuses in chronic sinusitis and hypovitaminosis A.
b) From transitional epithelium in bilharziasis of U.B.
c) From simple columnar epithelium:
* Endocervical mucosa and glands in cervical erosion.
* Gall bladder with stones.
d) From mesothelium of the pleura and peritoneum.
33. 2.Columnar metaplasia
From squamous: in the lower oesophagus e.g. Barrett
oesophagitis (Precancerous).
Intestinal metaplasia of the specialized gastric
mucosa in chronic atrophic gastritis.
Apocrine, pink cell, hyperplasia seen in fibrocystic
disease of the breast.
In mesothelium of pleura, peritoneum and synovium.
34.
35. (B) Connective tissue metaplasia
• It is the formation of cartilage, bone or
adipose tissue, in tissues that normally do not
contain these elements.
• Osseous metaplasia: occurs in:
Sites of dystrophic calcification e.g. in scars, old
T.B.
In muscles, in post-traumatic myositis ossificans.
36. Enzymes increased
mechanism
It is an adaptive change that occurs in the cells
• by inactivating or detoxifying drugs or
chemicals by means of the enzymes present in
the SER.
37. Extracellular and intracellular
accumulations
It occurs when the cell injury is sublethal and sustained,
as well as in normal cells.
• electrolytes, triglycerides (lipids), glycogen, calcium,
uric acid, proteins, melanin and bilirubin are
common accumulations.
• Abnormal accumulations occur when a substance is
produced at a rate that exceeds its metabolism or
removal.
38. Accumulations
• Substances can be either;
• normal body substances in abnormally large
amounts
-lipids, proteins, carbohydrates, melanin and
bilirubin
• abnormal endogenous products or
• exogenous products from the environment
and pigments
40. Accumulations…
Causes of intracellular accumulation can be
• production of substances that exceeds the
metabolism
• genetic disorders,.
-in von Gierke's disease - deficiency of the enzyme
glucose-6-phosphatase
-in Tay-Sachs disease - abnormal lipids accumulation
in the brain and other tissues,
41. Accumulations…
Causes of intracellular accumulation can be
• cellular injuries of different level and causes
• over production of different pigments e.g. (Bilirubin,
Lipofuscin, melanin etc)
-Pigments can be endogenous or exogenous-
• accumulation from outside e.g. carbon, lead etc
43. Pathologic calcification
It is the abnormal tissue deposition of calcium
salts;
• Dystrophic - occurs in dead or dying tissue
• Metastatic - occurs in normal tissue
44. CELL INJURY AND ADAPTATION
The basis of all diseases is injury to the
smallest living unit of the body, namely the
cell.
Cell encounters many stresses as a result of
changes in their internal and external
environments.
However, the normal cell is in steady state
able to handle physiologic demand according
to its adaptive capacity.
45. CELL INJURY AND ADAPTATION
Causes of cell injury:
1. Hypoxia (deficiency of oxygen) due to:
Ischaemia
decrease of oxygen carrying capacity of blood due to anaemia
cardiac or respiratory failure and
CO poisoning.
2. Physical agent: burns, deep cold, radiation, mechanical trauma and
electric shock.
3. Biological agents e.g. viruses, bacterial toxins, fungi and parasites.
4. Chemical agents and drugs e.g. alkalis, acids, insecticides, alcohol and
narcotic drugs & air pollutants et..
46. CELL INJURY AND ADAPTATION
Causes of cell injury:
5. Endogenous toxins as in case of uremia, jaundice and diabetic
ketosis.
6. Immunologic reactions (hypersensitivity).
7. Nutritional imbalance such as protein calorie malnutrition,
starvation, obesity, diabetes mellitus and deficiency of other
substances and vitamins.
8. Genetic abnormalities as in Down syndrome & sickle cell
anemia.
47. Cellular Injury
The ways of which cells are injured are grouped into five
categories;
–physical injury
–chemical injury
–biologic agents injury
–nutritional imbalances injury
–radiation injury
48. Cellular Injury
• most diseases begin with cell injury.
• cell injury can either be reversible or irreversible.
• causes of both types of injury are similar
• many of the causes can result initially in reversible
injury.
49. Reversible vs. irreversible
cell injury
Reversible injury
* Decreased ATP levels
* Ion imbalance
* Swelling
• Decreased pH
• Fatty change (liver)
Irreversible injury
* Amorphous densities in
mitochondria
* Severe membrane damage
* Lysosomal rupture
• Extensive DNA damage
50. Cellular Injury
Early changes
• these are reversible and include:
-cytoplasmic swelling and vacuolation
-mitochondrial and endoplasmic reticulum
swelling
-clumping of nuclear chromatin.
51. Cellular Injury…
Late changes
• These are irreversible and include:
• densities in mitochondrial matrix
• cell membrane disruption
• nuclear shrinkage (pyknosis)
52. Cellular Injury…
Late changes
• nuclear dissolution (karyolysis)
• nuclear break up (karyorrhexis)
• lysosome rupture.
Death of the cell will follow the
development of the late morphological
changes.
53. General mechanism of cell
injury
The mechanism by which injurious agents cause
injury and death are complex.
• some agents such as heat produce direct cell injury
and other factors indirectly.
• there are at least three major mechanisms in
which injurious agents exert their effects.
54. General mechanism of cell
injury…
Three major mechanisms in which injurious
agents exert their effects;
• hypoxia and ATP depletion
• free radical formation and
• disruption of intracellular calcium homeostasis
55. Pathogenesis of cell
injury:
Hypoxic and ischemic injury to the cells occur through:-
ATP depletion
Over production of oxygen – derived free radicals due to
imbalance between free radicals generation and radical
defense system.
56. Pathogenesis of cell
injury:
Other mechanisms caused by all forms of cell injury
include:-
Defect in membrane selective permeability
Damage of the nucleus
Increased intracellular ca+ and loss of ca+
homeostasis that result from damage of both cell
membrane & mitochondrial membrane and ER.
The increased intracellular Ca+ cause activation of
degenerative cellular enzymes as protease,
ATPase, phospholipase and endonuclease.
(that cause damage & mutation of the nucleus)
57.
58. HYPOXIA
Ischemia ( loss of blood
supply ).
Inadequate oxygenation
( cardiorespiratory failure ).
Loss of oxygen-carrying capacity of the
blood anemia
CO poisoning ).
59. HYPOXIC INJURY
• Loss of oxidative phosphorylation and ATP
generation by mitochondria.
• Decreased ATP (with increase in AMP): stimulating
fructokinase and phosphorylation, resulting in
aerobic glycolysis.
• Depleted glycogen.
• Reduced intracellular pH: Lactic acid and inorganic
phosphate.
• Clumping of nuclear chromatin.
60. Four biochemical themes
• Oxygen-derived free radicals.
• Loss of calcium homeostasis and
increased intracellular calcium.
• ATP depletion.
• Defects in membrane permeability.
61. Free radicals
Formation of free radicals
Normal metabolic processes
(mitochondria, phagocytosis)
Radiant energy
Drugs / other exogenous
compounds
63. Cell Injury Caused by Oxygen
Free Radicals
• Superoxide anion
–may be formed via the cytochrome P450 system,
which metabolizes many drugs and toxins –
removed by superoxide dismutase
• Hydrogen peroxide – removed by catalase or
glutathione peroxidase
• Hydroxyl radical (.OH)
64. Effects of Free Radicals
• Lipid peroxidation of membranes
• Oxidative modification of proteins
• DNA damage
65. Mechanism Of Bacterial And Viral
Injury
By production of cytotoxic lymphokins & activation of
lytic complement substance
Direct effect of bacterial toxins on the cell membrane &
mitochondrial damage, through incorporation of viral
genome to cell DNA and their alteration
Irreversible mitochondrial damage.
66. Cellular death
Death is the cessation of life of the cell
• cell death can involve apoptosis (from Greek
word apo for apart and ptosis for fallen) or
necrosis.
• apoptotic cell death is a controlled cell
destruction.
• necrosis refers to cell death in an organ or
tissue that is still part of living person.
67. Apoptosis
It is an active process of cellular self destruction in
both normal and pathologic tissue changes
• it is controlled by the system of CASPASES
• initiator (apical) caspases and effectors (executioner)
caspases.
• initiator caspases like (CASP2, CASP8, CASP9 and
CASP10)
• effectors caspases like (CASP3, CASP6 and CASP7)
68. Apoptosis
• Failure of apoptosis will lead to cancer
development and autoimmune diseases
• Unwanted apoptosis can lead to ischemia and
Alzheimers’ disease, prakinson disease and
amyotrophic lateral sclerosis (ALS)
69. Apoptosis…
Apoptosis determines the size, patterning, function of
many tissues; It is responsible in
• embryonic development
• neurons dying in synaptogenesis
• lymphocytes dying during receptor repertoire
selection
• in endocrine-dependent tissues undergoing atrophic
change (endometrial cell loss, mammary glands)
• production of free radical in haemopoietic cells
70. Apoptosis…
Examples of pathological apoptosis:
• tumours: the balance between apoptosis and
cell proliferation is disturbed in neoplasia
• atrophy: cell loss in atrophic tissues is by
apoptosis (viral illness: e.g. hepatitis—
individual hepatocytes, HIV)
71. Apoptosis…
Morphologically
• apoptotic cells shrink and the nucleus
condenses.
• the organelles and nucleus break.
• the cell breaks into fragments called apoptotic
bodies with ligands on their surface
• phagocytes recognize them and engulf
72. Initiation for apoptosis
Factors predisposes to apoptosis
Nontoxic stimuli can lead to apoptosis
Loss of growth factors.
Direct action of cytokines (e.g., tumor necrosis factor)
Immune system action (e.g., natural killer cells or
cytotoxic T lymphocytes).
Viral infection.
Adult tissue homeostasis .
Sublethal damage to the cells (e.g., by ionizing radiation,
hyperthermia, toxins.)
Loss of cell-cell or cell-matrix attachments.
73. ROLE (VALUE)OF
APOPTOSIS
1-Defense:
Against nonself multicellular organisms (cell commits
suicide when infected by a virus may protect other cells
from further spread of the virus)
2-Digestion:
The cellular DNA destroy the genetic information of any
external stimulus.
3-Protecting:
Protection of the organism from unregulated growth of
individual cells
75. Necrosis
It is the sum of cellular changes after local cell
death
• karyolysis (nuclear dissolution from the action
of hydrolytic enzymes
• karyorhexis – the fragmentation of the
nucleus into clear dust takes place.
76. General effects of necrosis
1.Release of enzymes from the breakdown
tissue into the blood forms the basis of clinical
tests for diagnosis e.g. detection of
transamenase in myocardial infarction and
liver necrosis in hepatitis.
2.Absorption of dead products into the
circulation leads to leukocytosis and fever (Not
diagnostic).
77. Types of Necrosis:
• Coagulative – e.g. Infarction
• Liquifactive - Brain, abscess
• Caseous - Bacterial / Tuberculosis
• Gangrene - With infection
• Fatty necrosis - found in the breast, pancreas
and other abdominal structures
78. Types of Necrosis…
Coagulative necrosis
• denaturation of intracellular protein (analogous to
boiling the white of an egg).
• the cells show the microscopic features of cell death.
• architecture of the tissue and cell ghosts remain
• is the commonest type seen in e.g. the kidney and
heart, and is usually caused by ischaemia.
84. Types of Necrosis …
Liquefactive (colliquative) necrosis
• this is characterised by tissue softening with
destruction of architecture.
• the result is an accumulation of semi-fluid tissue.
• it is usually seen in the brain and spinal cord.
85. Liquifactive necrosis…
The necrosed tissue undergoes rapid softening e.g. infarction
of the nervous tissue which has abundant lysosomal
enzymes.
Also, this type of necrosis occurs in case of suppurative
inflammation (Abscess) where liquefaction occurs under
the effect of proteolytic enzymes of PNLs liquefaction of
the amoebic abscess occurs due to the effect of strong
proteolytic enzymes and hyaluronidase secreted by E.
Histolytica.
Grossly: the affected tissue appears as homogenous
amorphous substance. Microscopically: it appears as
homogenous eosinophilic structure.
89. Types of Necrosis …
Fat necrosis
• direct trauma (common in the fatty tissues of the
female breast)
• enzyme release from the diseased pancreas.
• adipocytes rupture and released fat undergoes
lipolysis catalysed by lipases.
• macrophages ingest the oily material
• combination of calcium with the released fatty acids
(saponification).
90. Types of Necrosis …
Fibrinoid necrosis
This is characterized by swelling, fragmentation,
increased eosinophilia of collagen fibers and
accumulation of mucopolysaccharides and fibrin due
to vascular exudation of fibrinogen at the site of
lesion, e.g.:
a) Collagen diseases (Rheumatic fever, Rheumatoid,
Sclerodermia, Lupus erythematosus and Polyarteritis
nodosa).
b) In the wall of blood vessels in malignant
hypertension
92. Types of Necrosis …
Zenker’s necrosis:
Of the rectus abdominus muscle and
diaphragm as a complication of :
bacterial infection particularly typhoid fever.
The striated muscles lose its striation,
swell and fuse together in homogeneous
structureless mass.
93. Gangrene
Definition: necrosis of big tissue with superadded
putrefaction, black, foul-smelling appearance.
Necrosis of big tissue putrefactive black, green
Or organ or limb organisms infection appearance
(black or green due to breakdown of haemoglobin)
Types of Necrosis …
94. Types of Necrosis …
Gangrenous necrosis (gangrene)
• coagulative necrosis of tissues is associated with superadded
infection by putrefactive anaerobic Gram-positive bacteria
Clostridium spp.
• gangrenous tissue is foul smelling and black.
• the bacteria produce toxins which destroy collagen and
enable the infection to spread rapidly;
• it can become systemic (i.e. reach the bloodstream,
septicaemia).
95. Types of Necrosis …
Gangrenous necrosis (gangrene)
• gangrene can be dry, wet or gaseous
dry gangrene is usually due to a coagulative necrosis
Wet gangrene develops when neutrophils invade the site
and cause liquefactive necrosis
Gas gangrene is due to bacterial infection of injured tissue by
clostridium perfringens
96. a. Dry gangrene:
Conditions: only occurs on the skin surface
following arterial obstruction. It is
particularly liable to affect the limbs,
especially the toes.
Character: mummification
Types of gangrene :
99. b. Wet gangrene:
Conditions: Both arterial and venous
obstruction; wet in environment;
Character: wet swollen, foul-smelling, black
or green.
Commonly in small intestine, appendix, lung,
and uterus, also in limbs.
Types of gangrene :
101. c. Gas gangrene:
Conditions: deep contaminated wounds in which there is
considerable muscle damaged by gas formation bacteria.
Character: swollen obviously, gas bubbles formation. The
infection rapidly spreads and there is associated severe
toxaemia.
Only occasionally in civilian practice but is a serious
complication of war wounds.
Types of gangrene :
102. Fate and local effects OF
NECROSIS :
1. A small area undergoes repair:
A) The products of the necrotic cells irritate the surrounding
tissue forming a zone of inflammation.
B) The accumulated neutrophils in the zone of inflammation
soften the necrotic tissue and make its removal by
macrophages and blood stream easy and help the process
of healing.
C) Repair by regeneration or fibrosis depends upon the type
of cells affected (labile-stable-permanent).
103. 2. If the necrotic area is wide, its products can’t be
removed and a fibrous capsule form around it in order to
separate it from the living tissue. Areas of necrotic
softening in the brain become surrounded by proliferated
neuroglia (gliosis).
3. Old unabsorbed caseous lesions and fat necrosis usually
becomes heavily calcified (dystrophic calcification).
4-when the necrotic tissue is infected with putrefactive
Organism------Gangrene
106. Apoptosis and Necrosis
(prev.diagram)
• The sequential ultrastructural changes seen in
necrosis (left) and apoptosis (right). In
• apoptosis, the initial changes consist of nuclear
chromatin condensation and fragmentation,
• followed by cytoplasmic budding and phagocytosis
of the extruded apoptotic bodies.
• Signs of cytoplasmic blebs, and digestion and
leakage of cellular components.
107. Features of Necrosis and Apoptosis
Feature Necrosis Apoptosis
Cell size Enlarged Reduced
Nucleus Pyknosis/karyorrhexis/karyolysis Fragmentation
Plasma membrane Disrupted Intact
Cellular contents Enzymatic digestion Intact
Inflammation Frequent None
110. 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.
111. Theories of aging
• Developmental – genetic theories
Resides with genetic influences that
determine physical condition, occurrence of
disease, age of death, cause of death and
other factor contributing to longevity
• Stochastic theories
112. Theories of aging…
• Stochastic theories-
Propose that aging is caused by random
damage to vital cell molecules
Somatic mutation theory of aging
Oxidative free radical theory
The wear and tear theory
113. Factors affecting
Ageing:
• Genetic – Clock genes, (fibroblasts)
• Diet – malnutrition, obesity etc.
• Social conditions -
• Diseases – Atherosclerosis, diabetes etc.
• Werner’s syndrome.
114. Cellular mechanisms of
ageing
• Cross linking proteins & DNA.
• Accumulation of toxic by-products.
• Ageing genes.
• Loss of repair mechanism.
• Free radicle injury
• Telomerase shortening.
116. Ageing –changes:
• Gradual atrophy of tissues and organs.
• Dementia
• Loss of skin elasticity
• Greying and Loss of hair
• BV damage – atherosclerosis/bruising.
• Loss of Lens elasticity opacity vision
• Lipofuscin pigment deposition – Brown atrophy in
vital organs.
