Growth

Contents

Introduction

Although discussions of growth are dominated by neoplasia, there are other processes that represent modification of cell growth. These phenomena may be physiological or pathological.


Hypertrophy

Hypertrophy is an increase in the size of a tissue or organ due to an increase in the size of the cells, without an increase in the number of the cells. It typically occurs in stable or permanent tissues that have little to no capacity for cell division and regeneration and is therefore encountered in smooth muscle and skeletal muscle.

Hypertrophy is the normal physiological response of a muscle to a constant or repeated increase in the load placed upon it. This is the basis behind weight lifing and other exercises which seek to build up muscle bulk by challenging the muscles with an elevated load.

Hypertrophy of smooth muscle can be seen pathologically if there is partial obstruction to a hollow organ. A more powerful contraction is required to move the contents of the lumen of that organ past the obstruction and the smooth muscle hypertrophies to deliver this elevated effort. Examples are hypertrophy of the destrusor muscle of the bladder when the prostatic urethra is narrow by prostatic enlargement and hypertrophy of the muscularis propria of the large bowel in some cases of stricturing lesions.

Pathological hypertrophy is also observed in primary hypertrophic cardiomyopathy which is an autosomal dominant disease that affects that contractile proteins of cardiac muscle. Secondary pathological cardiac hypertrophy can be found in aortic stenosis or hypertension, both of which are diseases in which the load placed on the ventricle is higher.


Hyperplasia

Hyperplasia is the counterpart to hypertrophy. In hyperplasia the tissue or organ responds to a stimulus by increasing the number of cells. The main physiological example is the hyperplasia of the breast tissue that occurs at puberty and again during pregnancy.

The stimulus that drives hyperplasia is often hormonal, as in the case of the example of breast hyperplasia above.

Pathological examples of hyperplasia include Graves' disease in which an autoantibody binds to the TSH receptor of thyroid follicular cells and mimics that action of TSH and endometrial hyperplasia which develops in response to aberrant, unopposed oestrogen stimulation of the endometrium. Acromegaly is a form of multitissue hyperplasia and hypertrophy that is due to excess secretion of growth hormone in adults (in childhood gigantism results).


Atrophy

Atrophy is the opposite process to hypertrophy and hyperplasia. An atrophic organ has shrunk in size due either to a reduction in the size of its cells and/or a decrease in the number of cells. Although atrophy is often considered to be a pathological process, it nevertheless has a physiological function and only becomes pathological if it occurs for the wrong reason or to excess.

Organs that can suffer from atrophy tend to be those which are dependent on some form of stimulus to maintain their bulk. Examples include skeletal muscle and many endocrine organs (such as the adrenal glands (adrenocorticotrophic hormone) and the gonads (follicle stimulating hormone and luteinising horome)). Under physiological circumstances a long term reduction in the stimulus implies a reduction in the need for the function / product of that organ. Reducing the size of that organ is therefore biologically beneficial because the cell mass is not necessary but is still consuming metabolic resources. In other words, the body maintains tissues of this type at a level that fits the requirements of the organism.

Physiological atrophy of this sort is usually not dramatic and instead only fine tunes the size of an organ; the term hypotrophy might be preferable, although probably does not exist. Nevertheless, in the case of the thymus, physiological atrophy is considerable.

Atrophy becomes pathological when the process that drives the atrophy is abnormal either in origin or degree. Examples include atrophy of the adrenal cortex if the supply of ACTH from the pituitary is diminished (as could occur with a pituitary tumour) or muscle atrophy that follows prolonged immobility of a limb after a fracture. Aplastic anaemia is also a type of atrophy and has a variety of causes.


Agenesis

Atrophy applies to an organ that has formed normally in the first place. Agenesis is the term that is given to an organ that fails to reach its normal full size during embyrogenesis. In some instances this will be true agenesis in which the organ does not form at all, in others it will be hypogenesis in which the organ is present but has not attained its usual size. Aplasia is used synonymously with agenesis (or inappropriately in the case of aplastic anaemia). Hypoplasia is the equivalent to hypogenesis and is the preferred term to the latter.


Dysgenesis

Dysgenesis is a rarely encountered term and is related to agenesis. However, whereas an agenic organ is smaller than it should be but is otherwise appropriately organised, a dysgenic organ is malformed. In practice, agenesis may be employed to denote both situations.


Metaplasia

Metaplasia is the phenomenon in which a tissue changes from one phenotype to another and is most frequently found in epithelial tissues. A physiological example is the metaplasia from the columnar endothelium of the endocervix to the squamous epithelium of the ectocervix that takes place at the external aspect of the cervical canal. This metaplasia is a protective adaptation. Stratified squamous epithelium is better placed to deal with lining an exposed surface like the ectocervix than glandular epithelium, while the mucin forming ability of the glandular epithelium is nevertheless required within the endocervical canal itself.

Most other examples of metaplasia are pathological and the result of an attempt by the affected tissue to respond to a persisting harmful stimulus. The metaplasia of oesophageal squamous epithelium to columnar epithelium that is found in Barrett's oesophagus is an endeavour by the oesophageal epithelium to adapt to the abnormal reflux of acid from the stomach into the oesophagus. Mucin-secreting columnar epithelium is more resistant to acid than squamous epithelium. The conversion of bronchial ciliated columnar epithelium to squamous epithelium happens in smokers in response to some of the harmful chemicals that are present in cigarrete smoke is another form of pathological metaplasia.

Metaplasia requires alteration of the genes that a cell expresses and those that it does not express. For this reason it can be a very early precursor lesion for some tumours because it represents an initial step in altering the DNA expression of the cell.