Monday 30 January 2006
One of the manifestations of metabolic derangements in cells is the intracellular accumulation of abnormal amounts of various substances.
The stockpiled substances fall into three categories:
(1) a normal cellular constituent accumulated in excess, such as water, lipids, proteins, and carbohydrates;
(2) an abnormal substance, either exogenous, such as a mineral or products of infectious agents, or endogenous, such as a product of abnormal synthesis or metabolism;
(3) a pigment.
These substances may accumulate either transiently or permanently, and they may be harmless to the cells, but on occasion they are severely toxic. The substance may be located in either the cytoplasm (frequently within phagolysosomes) or the nucleus.
In some instances, the cell may be producing the abnormal substance, and in others it may be merely storing products of pathologic processes occurring elsewhere in the body.
Many processes result in abnormal intracellular accumulations, but most accumulations are attributable to three types of abnormalities.
A normal endogenous substance is produced at a normal or increased rate, but the rate of metabolism is inadequate to remove it. An example of this type of process is fatty change in the liver because of intracellular accumulation of triglycerides.
A normal or abnormal endogenous substance accumulates because of genetic or acquired defects in the metabolism, packaging, transport, or secretion of these substances. One example is the group of conditions caused by genetic defects of specific enzymes involved in the metabolism of lipid and carbohydrates resulting in intracellular deposition of these substances, largely in lysosomes.
Another is alpha1-antitrypsin deficiency, in which a single amino acid substitution in the enzyme results in defects in protein folding and accumulation of the enzyme in the endoplasmic reticulum of the liver in the form of globular eosinophilic inclusions.
An abnormal exogenous substance is deposited and accumulates because the cell has neither the enzymatic machinery to degrade the substance nor the ability to transport it to other sites. Accumulations of carbon particles and such nonmetabolizable chemicals as silica particles are examples of this type of alteration.
Whatever the nature and origin of the intracellular accumulation, it implies the storage of some product by individual cells.
If the overload is due to a systemic derangement and can be brought under control, the accumulation is reversible. In genetic storage diseases, accumulation is progressive, and the cells may become so overloaded as to cause secondary injury, leading in some instances to death of the tissue and the patient.