Cell injury (causes)

When the limits of adaptive capacity are exceeded or when no adaptive response is possible then it is termed as cell injury.

A.     Reversible cell injury:

It denotes pathologic changes that can be reversed when the stimulus J(or stress) is removed or if the cause of injury is mild.

B.     Irreversible cell injury:

It denotes pathologic changes that are permanent and cause cell death.

Causes of cell injury:

1.       Hypoxia

2.       Chemical agents

3.       Metabolic

4.       Genetic

1.     Hypoxia:

Low oxygen to the tissue, which is due to:

Ø  Ischemia (loss of blood supply) due to arterial occlusion

Ø  Problem in respiratory system

Ø  Problem in circulatory system

Ø  Abnormality of hemoglobin

Ø  Decreased tissue perfusion as in hypotension, shock and cardiac failure

All leads to hypoxic cell injury, which may be reversible or irreversible.

Reversible injury:

If the nucleus is intact then it is termed as reversible cell injury. Hypoxia affects mitochondria which results in decreased synthesis of ATP. The reversible changes include:

         i.            Cellular swelling

       ii.            Desegregation of ribosomes and failure of protein synthesis

      iii.            Reduced intracellular pH

     iv.            Appearance of myelin figures and cell blebs

        i.            Cellular swelling:

Ø  Failure of Na, K ATPase pump due to deficiency of ATP results in accumulation of Na ions inside and K ions outside the cell.

Ø  Excess Na ions inside the cell exert osmotic pressure and pulls water inside, resulting in cellular swelling.

      ii.            Ribosomal desegregation:

Ribosomes become detached from the rough endoplasmic reticulum due its swelling and therefore protein synthesis is reduced.

   iii.            Reduced intracellular pH:

Ø  Lack of ATP synthesis increases rate of anaerobic respiration (anaerobic glycolysis) which leads to production of pyruvic acid and subsequently (at last) lactic acid.

Ø  Accumulation of lactic acid decreases intracellular pH which causes clumping (aggregation) of nuclear chromatin and further disruption (breakdown) of cytoplasmic organelles.

    iv.            Appearance of Myelin Figures and Cell Blebs:

Myelin Figures:

Intracellular whorl likes structures originating from damaged membrane.

Cell Blebs:

An outward cell membrane deformity

Irreversible injury:

If the nucleus is not intact then it is termed as irreversible injury. The irreversible changes are:

         i.            Nuclear changes

       ii.            Cytoplasmic changes

Nuclear changes:

Nucleus may show one of the following three patterns of changes.

Pyknosis:

The nucleus becomes shrunken due to clumping of chromatin called pyknosis.

Karyorrhexis:

The pyknotic nucleus may break (disintegration) into numerous small particles, the process called karyorrhexis.

Karyolysis:

The nucleus undergoes lysis (disintegration) without pyknosis called karyolysis.

Cytoplasmic changes:

§  Mitochondrial Vacuolization

§  Loss of plasma membrane (cell membrane, nuclear membrane etc)

§  Excess influx of calcium into cell

§  Release of lysosomal enzymes causing Autolysis (self breaking)

2.     Chemical injury:

Chemical causes cell injury by the following mechanisms:

a)     Direct attack:

Some chemicals attack directly on critical molecular component or cellular organelle (cell membrane, ribosome, mitochondria etc).

b)     Attack through free radicals:

Mostly chemicals cause injury by the formation of free radicals.