Cell Injury

In this post we'll take a look at cell injury and what causes it. If you have any questions please feel free to let me know in the comments section at the end of the post :)

Cellular injury is defined as anything that disturbs homeostasis. Many different factors can cause cellular injury and the effect of these factors depends on the severity, type and duration of the injury. An example that illustrates this is sunlight. Sunlight can be beneficial in modest amounts (it helps your body synthesis vitamin D) or harmful in excess (as I’m sure you all know, it causes sunburn). The severity (e.g. the sun is strongest at mid-day), the type (some frequencies of light are more harmful than others) and the duration (how long you stay in the sun) affect whether or not sunlight is beneficial or harmful for your body.

When cellular membranes, aerobic respiration, protein synthesis or genetic function are damaged, cell injury occurs.

Different types of cells also have different vulnerabilities to injury. For example, the lack of oxygen (hypoxia) affects tissues differently. Your brain can’t survive for very long without oxygen while connective tissue cells may last for quite a while.

What Causes Cellular Injury?

There are many possible causes of cell injury and these can be categorised as follows:

o   Ageing

o   Hypoxia: this is reduced oxygen availability to the tissues. This may be a result of anaemia, hypoperfusion, impaired gas exchange in the lungs or from reduced oxygen in the air inspired.

o   Hyperoxia: this is an excess of oxygen in the tissues. An increased oxygen tension in the tissues is associated with an increased release of oxygen-derived free radicals and this can cause injury.

o   Ischaemia: this refers to reduced blood flow to a tissue or organ and results in a reduced availability of oxygen and nutrients. In addition, there is reduced removal of waste products, which can be harmful.

o   Nutritional: reduced or excessive protein, energy, vitamins and minerals may lead to cell injury.

o   Biological Agents: viruses, bacteria, prions, fungi, protozoa and helminths are all able to cause cell injury.

o   Immunological: many diseases are either immune mediated (that is there is an excessive immune response) or autoimmune (an inappropriate immune response to self-antigens).

o   Chemical: many chemicals are able to cause injury to cells (e.g. Cyanide).

o   Physical: excessive physical force, extreme temperatures and irradiation are all able to cause injury.

o   Genetic: a healthy genome forms the basis for normal cellular function.     

Mechanisms of Reversible Cellular Injury

Hypoxia, ischaemia or toxins can reduce oxidative phosphorylation because they reduce the amount of oxygen supplied to the cell. As a result, ATP levels drop and inorganic phosphate levels rise. The drop in ATP means that the Na/K ATPase pump cannot work and so sodium flows into the cell along its concentration gradient and water follows. In addition, potassium leaves the cell along its concentration gradient and these iron and water influxes cause the organelles and the cell itself to swell.

Because of the rise in inorganic phosphate levels, glycolysis increases and intracellular glycogen stores are depleted which causes a build-up of lactic acid in the cell. This decreases the pH which causes chromatin to clump.

In addition, ribosomes become detached from mRNA strands and this reduces protein synthesis this leads to a dispersal of the cytoskeleton, and the loss of surface specialisations (such as microvilli). The cell is also unable to export fat effectively and fat may accumulate within the cell.

Mechanisms of Irreversible Cellular Injury

Irreversible injury leads to cell death. Before we get into the mechanisms of irreversible injury we need to discuss some terminology. Necrosis refers to the process of local cell death, with subsequent degradation, in a living animal. This definition excludes post-mortem changes and the universal cell death that happens after the body dies. Necrosis occurs in one (or more) particular place (called a focus) while the rest of the body’s cells are alive.

Autolysis refers to the disintegration of cells or tissues by their endogenous enzymes. An example of this is the autolysis that occurs after death. Heterolysis is the destruction of one type of cell by the enzymes of another.

We’ll now go into some more detail about how irreversible cell injury actually occurs. It’s important to know, though, that some of the hallmarks or key events of irreversible injury are similar to those seen in reversible injury. Sometimes, it may be difficult to distinguish between reversible and irreversible injury because of this.

The first key step of irreversible injury is the presence of high amplitude mitochondrial swelling which accompanies condensation of the nucleus (this is known as pyknosis which can be seen under a microscope).

The second key event is cell membrane damage which is more serious than what may be seen in reversible injuries. There is often lysosomal swelling as a result of the membrane damage.

The third hallmark is nuclear breakdown. Because of the lysosomal swelling, some enzymes are released and activated (such as acid hydrolases) which cause DNA and RNA to break down inside the cell. Calcium also flows into the cell. These events can be seen histologically by karyorrhexis (fragmentation of the nucleus) and karyolysis (break down of the nucleus) and autolysis. Often, the influx of calcium causes the mitochondria to crystallise. 

That's all for now, in the next post we'll discuss free radicals. See you then :)