CELL INJURY
Dr. Shoaib Raza
CELL INJURY
 When the adaptive capabilities of the cell are exceeded, the cell is
said to be injured
 Abnormal homeostasis
• Change in the internal environment of the cell
 Certain stimulus (triggering agent) is required to produce such
change
CAUSES OF CELL INJURY
 Hypoxia is the most frequent cause
• Hypoxic hypoxia
• High altitude
• Ischemic hypoxia
• Secondary to ischemia
• Anemic hypoxia
• Secondary to anemia
• Histotoxic (Cytotoxic) hypoxia
• Cyanide poisoning
CAUSES OF CELL INJURY
 Nutritional disorders
• Deficiency:
• Protein Caloric Malnutrition (Kwashiorkor)
• Vitamin deficiencies
• Beri beri, Scurvy, Anemia, etc.
• Excess of nutrition:
• Hyperlipidemia
• Pick wick disorder
• Obesity
CAUSES OF CELL INJURY
 Biological agents:
• Infection
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Bacteria
Virus
Fungi
Protozoa
Helminths
CAUSES OF CELL INJURY
 Physical agents:
• Temperature:
• Increased: Thermal injury, syncope
• Decreased: Frost bite
• Pressure:
• Trauma
• pH
CAUSES OF CELL INJURY
 Chemical agents:
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Corrosive agents
Toxins and poisons
Drugs
Increased or decreased concentration of usual cellular chemicals
• Glucose
• Oxygen derived free radicals
CAUSES OF CELL INJURY
 Immunological causes:
• Immune system provides defense against foreign antigens
• Autoimmune disorders:
• Immune response against self antigens
• Immunodeficiency disorders:
• AIDS, Di-George Syndrome, Hyper IgM Syndrome
CAUSES OF CELL INJURY
 Genetic abnormalities:
• Mutation
• Sickle cell anemia, Thalassemia etc
• Chromosomal disorders
• Down Syndrome, Klienefelter Syndrome
• Other genetic abnormalities
CAUSES OF CELL INJURY
 Aging:
• Telomerase activity
REVERSIBLE CELL INJURY
 In early stages or mild forms of injury, the functional and
morphological changes are reversible if the stimulus is removed
 Hallmark features of hypoxic injury are:
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↓ Oxidative phosphorylation
↓ ATP synthesis
Cellular swelling
Alterations in intracellular organelles
HYPOXIA AS A LEADING
CAUSE OF CELL INJURY
 Deficiency of oxygen impairs oxidative phosphorylation, this in
turn causes:
• Deficient aerobic glycolysis
• Anaerobic glycolysis
• Accumulation of lactic acid
• Reducing pH
• Displacement of ribosomes from RER
• Clumping of chromatin network
• Inactivation of Na + - K+ pump
INACTIVATION OF NA + K +
PUMP
 Na+ K+ pump is ATPase dependent, thus ATP deficiency leads to
inactivation of Na+ K+ pump
 Inactivation leads to:
• ↑ Na+ influx inside the cell
• Intracellular water accumulation
• Cell swelling
• Swelling of cytoplasmic organelles
• Mitochondrial swelling
• Lysosomal swelling
• ER swelling
REVERSIBLE CELL INJURY
 Due to cellular swelling and impaired function of the cell
membrane, certain enzymes (stored in particular cells) are released
and their serum levels are raised
• Lipase, amylase etc during pancreatic cell injury
• CK-MB, LDH etc during myocardial injury
• AST, ALT, CPK etc during hepatocellular damage
ANY QUESTION?