Surgical Pathology

Cell Injury

There are numerous causes of cell injury. Injury occurs because the cell is forced to function outside the range of normal homeostatic capabilities. In response to some insults there may be a level of adaptation initially but eventually a point is reached at which adaptive mechanisms can no longer cope and cell death occurs.

The particular type of injury suffered by a cell will reflect both the type of cell involved and the nature of the insult. The response to injury will also depend on the ability of a cell type to divide.

Hepatocytes, an example of ‘stable cells‘, can regenerate when driven to re-enter the cell cycle by growth factors produced by surrounding cells. Neurons and cardiac myocytes, examples of ‘permanent cells‘, have no ability to re-enter the cell cycle and undergo cell division. Dead cells in these tissues may however become replaced by fibrous tissue composed mainly of collagen. This is the basis, for example, for the fibrotic changes which occur in the heart following a period of tissue hypoxia.

Types of Cell Injury

Cell membrane damage:

  • eg. complement pathway attack or free radicals

Mitochondrial damage:

  • eg. hypoxia or cyanide poisoning

Ribosomal damage:

  • eg. effects of alcohol on hepatocytes

Nuclear damage:

  • eg. radiation or viruses

There is a spectrum of events associated with cell death. The ends of the spectrum are referred to as necrosis, a pathological event, and apoptosis, a normal physiological event.


Necrosis refers to the series of events which result from cell death occurring in a living tissue. It is a process which involves a large number of cells and it generates a potentially damaging inflammatory response. This may be provoked by the release of cell contents following cell rupture. Necrosis is a slow process.


Apoptosis is a physiological event and is often described by terms such as ‘programmed cell death’ or ‘cell suicide’. This reflects the fact that the cell may itself produce proteins which cause the cell to die. Apoptosis is a very fast process and the whole event may only last a few minutes. As an example, it is a feature of the restructuring of tissues which occurs during embryonic development. A further example is the endometrial cell loss which occurs during the menstrual cycle.

Why does necrotic tissue swell?

Necrotic tissue is inadequately supplied with oxygen and therefore ATP production is limited. Cells need an adequate supply of ATP to maintain ion gradients and therefore water distribution, across cell membranes.

Because the sodium pump expels three Na+ ions for every two K+ ions pumped into the cell, failure of the pump leads to a net accumulation of ions inside the cell. An osmotic gradient therefore develops which means water enters the cell causing it to swell.

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