Injury (lesion), Adaptation and

Cell Death
Didik Setiawan, Apt
Content
• Cell Injury
• caused of cell injury
• Mechanism of cell injury
• Cellular adaptation
• Cell death
• aging
 Cell injury

The caused of cell injury and it’s

mechanism
 Cell can defend it’s homeostasis
Stress Pathologic
Physiology response

Adaptation
•Atrophy : ???
•Hypertrophy : ???
•Hyperplasia : ???

Over Stress Over

Physiology Pathologic
response
injury

Reversible vs irreversible
 A
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 Basic
Principle of
Cell
Adaptation
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 Cell Death

• Usually caused by the lost of blood supply

or toxin
Necrosis • Characterized by cell swelling, protein
denaturation, and organelle destruction

• Suicide program controlled internally

• Death cell removed safely and doesn’t
Apoptosis disrupt other tissue
• It happen in physiology and pathology
condition
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Caused of cell injury
 Oxygen deprivation
Hypoxia
• Disrupt aerobic oxidative respiration
• Frequent caused of cell injury
• Caused by ischemic, inadequate blood
oxygenation (ie. Pneumonia), oxygen
transport disruption (ie anemia, CO
intoxication)

Hypoxia vs ischemic
 Chemical
Infectious agent
Compound
• Almost all chemical can • From submicroscopic
cause cell injury virus  ricketsia 
• it cause changes of : bacterial  fungi 
– Membrane permeability huge helminthes
– Osmotic homeostatic
– Enzyme or co-factor
nature
 Immunologic
Reaction
Genetic Defect
• Abnormal reaction of • Congenital
immunologic systems, malformation
such as: • Down syndrome
– Anaphylactic reaction to • Sickle cell
stranger protein
– Autoimmune • etc
– Immune deficiency
 Nutritional
Imbalance
Physical Agent
• Nutrition Insufficiency • Trauma
• Temperature
• Over nutrition • Radiation
• Electrical shock
• Dramatic Atmosphere
changes
 Aging
• Unfinished repair of injured cell
• Repeated trauma  tissue degeneration
Mechanism of cell injury
General Principle of cell injury

Cellular response depend on type, duration, and

severity of harmful stimulus

Cell response depend on type, status, adaptation

ability and genetic profile of injured cell
• Skeletal vs myocardial in the response of ischemic

common influenced Intracellular system

• Cellular membrane
• ATP formation by aerobic respiration
• Protein synthesis
• Genetic properties
General Principle of cell injury

Structural and biochemical

component of cell all connected
comprehensively

Cell function will be lost long

before cell death
• Myocard: 1-2 minutes (non-contractile) 
20-30 minutes (death)
 Mechanism of Cell Injury
• General Biochemistry Mechanism
• Ischemic injury and hypoxia
• Free radicals induced injury
• Chemical injury
General Biochemistry Mechanism

Oxygen Oxygen reactive

ATP depletion
deprivation formation

Defect of plasma
Lost of calcium Mitochondria
membrane
homeostasis destruction
permeability
 Ca increase in
cytosol

ATPase phospholipase Protease Endonuclease

Membrane
Decrease of protein and Chromatin
ATP depletion
phospholipids cytoskeleton destruction
disruption
 Ischemic injury and hypoxia
The first effect of hypoxia is anaerobic respiration or oxidative
phosphorilation

ATP Depletion

Decrease Na-pump Anaerobe glicolysis

activity

Acute Cellular Fast reduction of Decrease

Edema glycogen deposit intracellular pH

Ribosome release from Rough ER  decrease protein synthesis

Free radicals induced injury

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content/uploads
/2009/09/free-
radicals-
formation.jpg
Effect of free radicals
Peroxidation of membrane lipid
• Create peroxide which is unstable and reactive 
autocatalytic chain reaction

DNA fragmentation

Protein cross bond

• Sulfhydril mediated cross bonding  disruption of
enzymatic ability

Polypeptide fragmentation
Antioxidant
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 Free radicals inactivation systems
• Superoxide Dismutase
(SOD)
• Glutathione Peroxides
(GSH)
• Catalase
• Endogenous Antioxidant
(vitamin A, E, and C also
beta carotene)
– Inhibits free radicals
formation
– Collect free radicals http://www.amazing-
glutathione.com/images/GPx-process.jpg
 Chemical injury
• Direct mechanism • Indirect mechanism
– Chemical compound – Chemical substance
directly attached to converted into reactive
molecular component toxic metabolite
or organelle – CCl4  CCl3-  SER
– HgCl bind to sulfhydril swelling and ribosome
group of membrane dissociation from RER
protein