NORMAL CELL(HOMEOSTASIS)

STRESS

ADAPTATION CELL INJURYINABILITY TO

ADAPT

REVERSIBLE INJURY

MILDTRANSIENT

SEVEREPROGRESSIVE

IRREVERSIBLE INJURY

NECROSIS APOPTOSISCELLDEATH

Learning objectives

• General mechanisms of cell injury• Causes of cell injury• Pathogenesis of cell injury• Free radical induced cell injury• Examples of reversible cell injury

Cell Injury – General Mechanisms

• Four very interrelated cell systems are particularly vulnerable to injury:– Membranes (cellular and organellar)– Aerobic respiration– Protein synthesis (enzymes, structural

proteins, etc)– Genetic apparatus (e.g., DNA, RNA)

What causes cell injury?

• Hypoxia

• Hypoxia– Reduced blood flow [ischemia]– Inadequate oxygenation of the blood due to

cardiorespiratory failure– Decreased oxygen carrying capacity of the

blood as in anemia and CO poisoning– Severe blood loss

• Physical agents• Chemical agents• Infectious agents• Immunologic reactions• Genetic causes• Nutritional• Iatrogenic• Idiopathic

Pathogenesis

• Basic principles• Nature of injury, duration and severity• Type , state and adaptability of the injured cell• Biochemical mechanisms acting on several

essential cellular components.

The principal mechanisms of cell injury, and their biochemical and functional effects

REVERSIBLE

IRREVERSIBLE

FREE RADICAL MEDIATED CELL INJURY

• These are the chemical species that have single unpaired electron in their outer orbit.

• Highly reactive, unstable chemicals• Associated with cell injury

– Chemicals/drugs, reperfusion injury, inflammation, irradiation, oxygen toxicity, carcinogenesis

Free radicals

• Superoxide oxygen• Hydroxyl radical• Hydrogen peroxide

• Nitric oxide• Peroxynitrite• Hypochlorous acid

Antioxidant mechanisms

• Catalase• Superoxide dismutase• Glutathione peroxidase

Antioxidants

• Endogenous or exogenous substances which inactivate free radicals

– Vitamins A, C , E– Sulphydryl containing compounds

• Cysteine and glutathione– Serum proteins

• Ceruloplasmin and transferrin

Hydroxyl free radical ( the most reactive)

Lipid

peroxidation

Protein oxidation

DNA damage

Cytoskeletal damage

Cell death

Mechanism of injury

Morphology of cell injury

Reversible Irreversible

Hydropic change

• Accumulation of water in the cytoplasm• Cloudy swelling, vacuolar degeneration• Appears when cells are incapable of

maintaining ionic and fluid homeostasis• It is the first manifestation of almost all

forms of cell injury• Reversible cell injury• Due to impaired regulation of sodium &

potassium on cell membrane.

Hydropic swelling. A needle biopsy of the liver of a patient with toxic hepatic injury shows severe hydropic swelling in the centrilobular zone. The affected hepatocytes exhibit central nuclei and cytoplasm distended (ballooned) by excess fluid.

Ultrastructural changes in reversible cell injury

Summary

• General mechanisms of cell injury• Causes of cell injury• Pathogenesis of cell injury• Free radical induced cell injury• Examples of reversible cell injury

Thank you