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

• 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:• 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:• ↓ Oxidative phosphorylation• ↓ ATP synthesis• Cellular swelling• Alterations in intracellular organelles

HY POXIA AS A LEADIN G CAU SE OF CEL L INJU RY

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?