Hyperplasia
Definition: Hyperplasia is an increase in the number of cells in an organ or tissue, usually resulting in increased volume of the organ or tissue.
Pathogenesis
Although hyperplasia and hypertrophy are two distinct processes, frequently both occur together, and they may be triggered by the same external stimulus. For instance, hormone-induced growth in the uterus involves both increased numbers of smooth muscle and epithelial cells and the enlargement of these cells. Hyperplasia takes place if the cellular population is capable of synthesizing DNA, thus permitting mitotic division; by contrast, hypertrophy involves cell enlargement without cell division. Hyperplasia can be physiologic or pathologic.
Physiologic Hyperplasia
Physiologic hyperplasia can be divided into: (1) hormonal hyperplasia, which increases the functional capacity of a tissue when needed, and (2) compensatory hyperplasia, which increases tissue mass after damage or partial resection.
Hormonal hyperplasia is best exemplified by the proliferation of the glandular epithelium of the female breast at puberty and during pregnancy and the physiologic hyperplasia that occurs in the pregnant uterus.
The experimental model of partial hepatectomy has been especially useful in examining the mechanisms that stimulate proliferation of residual liver cells and regeneration of the liver.
Similar mechanisms are likely involved in other situations when remaining tissue grows to make up for partial tissue loss (e.g., after unilateral nephrectomy, when the remaining kidney undergoes compensatory hyperplasia).
Hyperplasia is generally caused by increased local production of growth factors, increased levels of growth factor receptors on the responding cells, or activation of particular intracellular signaling pathways.
All these changes lead to production of transcription factors that turn on many cellular genes, including genes encoding growth factors, receptors for growth factors, and cell cycle regulators, and the net result is cellular proliferation.2 In hormonal hyperplasia, the hormones may themselves act as growth factors and trigger the transcription of various cellular genes.
The source of growth factors in compensatory hyperplasia and the stimuli for the production of these growth factors are less well defined. The increase in tissue mass after some types of cell loss is achieved not only by proliferation of the remaining cells but also by the development of new cells from stem cells.
For instance, in the liver, intrahepatic stem cells do not play a major role in the hyperplasia that occurs after hepatectomy but they may participate in regeneration after certain forms of liver injury, such as chronic hepatitis, in which the proliferative capacity of hepatocytes is compromised.
Recent data from clinical observations and experimental studies have demonstrated that the bone marrow contains stem cells that may be able to give rise to many types of differentiated, specialized cell types, including some liver cells.
Pathologic Hyperplasia
Most forms of pathologic hyperplasia are caused by excessive hormonal stimulation or growth factors acting on target cells. Example: endometrial hyperplasia
Pathologic hyperplasia, however, constitutes a fertile soil in which cancerous proliferation may eventually arise. Thus, patients with hyperplasia of the endometrium are at increased risk for developing endometrial cancer.
Hyperplasia is also an important response of connective tissue cells in wound healing, in which proliferating fibro-blasts and blood vessels aid in repair.
Under these circumstances, growth factors are responsible for the hyperplasia. Stimulation by growth factors is also involved in the hyperplasia that is associated with certain viral infections, such as papillomaviruses, which cause skin warts and a number of mucosal lesions composed of masses of hyperplastic epithelium.
Types
- glandular hypeplasias
- endocrine hyperplasias
See also