Adaptations of Cellular Growth

Dr Debasis Mukhopadhyay Associate ProfessorDept. of Pathology

What is cellular adaptation?

• Adaptations are reversible changes in the size, number,phenotype, metabolic activity, or functions of cells in response to changes in their environment.

What are the different forms of cellular adaptations?

• Hypertrophy• Hyperplasia• Atrophy/hypoplasia• Metaplasia

Definition of hypertrophy

• Hypertrophy refers to an increase in the size of cells, that results in an increase in the size of the affected organ.

Mechanism of hypertrophy

• Key fact : Hypertrophy is the result of increased production of

cellular proteins.

Few examples• Bulging muscles of bodybuilders engaged in “pumping iron” result from enlargement of

individual muscle fibers in response to increased demand.

• In the heart, the stimulus for hypertrophy is usually chronic hemodynamic overload, resulting from either hypertension or faulty valves.

In both tissue types the muscle cells synthesize more proteins and the number of myofilaments increases. This increases the amount of force each myocyte can generate, and thus increases the strength and work capacity of the muscle as a whole.

• The massive physiologic growth of the uterus duringpregnancy is a good example of hormone-induced enlargement an organ that results mainly from hypertrophy of muscle fibers . Uterine hypertrophy is stimulated by estrogenic hormones acting on smooth muscle through estrogen receptors.

Definition of Hyperplasia

• Hyperplasia is defined as an increase in the number of cells in an organ or tissue in response to a stimulus.

Mechanism of hyperplasia

• Key fact: • Hyperplasia is the result of growth factor-driven

proliferation of mature cells and, in some cases, by increased output of new cells from tissue stem cells

Different types• Physiologic Hyperplasia

Physiologic hyperplasia due to the action of hormones or growth factors occurs in several circumstances: when there is a need to increase functional capacity of hormonesensitive organs; when there is need for compensatory increase after damage or resection.

• Pathologic HyperplasiaMost forms of pathologic hyperplasia are caused byexcessive or inappropriate actions of hormones or growthfactors acting on target cells.

Few examples

• Physiologic hyperplasia Hormonal hyperplasia is well illustrated by the

proliferation of the glandular epithelium of the female breast at puberty and during pregnancy, usually accompanied by enlargement (hypertrophy)of the glandular epithelial cells.

liver regeneration after trasnplantation.

Few examples

• Pathologic hyperplasia• Endometrial hyperplasia is an example of abnormal hormone-

induced hyperplasia.• Benign prostatic hyperplasia is another common example of

pathologic hyperplasia induced in responses to hormonal stimulation by androgens.

• Hyperplasia is a characteristic response to certain viralinfections, such as papillomaviruses, which cause skinwarts and several mucosal lesions composed of masses ofhyperplastic epithelium.

Definition of atrophy

• Atrophy is defined as a reduction in the size of an organ or tissue due to a decrease in cell size and number.

Types of atrophy

• Physiologic atrophy• Pathologic atrophy

Mechanism of atrophy

• Key facts: • The initial response is a decrease in cell size and organelles, which may reduce

the metabolic needs of the cell sufficiently to permit its survival.• Atrophy results from decreased protein synthesis and increased

protein degradation in cells.• Protein synthesis decreases because of reduced metabolic activity.• The degradation of cellular proteins occurs mainly by the ubiquitin proteasome

pathway.• Nutrient deficiency and disuse may activate ubiquitin ligases, which attach the

small peptide ubiquitin to cellular proteins and target these proteins for degradation in proteasomes.

Mechanism (causes) of atrophy(pathologic)

• Decreased workload (atrophy of disuse).

• Decreased workload (atrophy of disuse). • Diminished blood supply.

• Inadequate nutrition.

• Loss of endocrine stimulation.

• Pressure.

Few examples• Physiologic atrophy Some embryonic structures, such as the notochord and thyroglossal duct, undergo

atrophy during fetal development. The decrease in the size of the uterus that occurs shortly after parturition is another

form of physiologic atrophy.• Pathologic atrophy prolonged immobilization- disuse atrophy of muscles of lower limb senile atrophy of brain and heart in old age due to diminished blood supply due to

atherosclerosis The loss of estrogen stimulation after menopause results in physiologic atrophy of the

endometrium, vaginal epithelium, and breast.

Definition of metaplasia

• Metaplasia is a reversible change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type.

Mechanism of metaplasia

• Key facts:• Metaplasia does not result from a change in the

phenotype of an already differentiated cell type; instead it is the result of a reprogramming of stem cells that are known to exist in normal tissues, or of undifferentiated mesenchymal cells present in connective tissue.

Few examples• The most common epithelial metaplasia is columnar to squamous, as occurs in the respiratory tract

in response to chronic irritation. In the habitual cigarettesmoker, the normal ciliated columnar epithelial cells of the trachea and bronchi are often replaced by stratified squamous epithelial cells.

• A deficiency of vitamin A (retinoic acid) induces squamous metaplasia in the respiratory epithelium.

• Metaplasia from squamous to columnar type may also occur, as in Barrett esophagus, in which the esophageal squamous epithelium is replaced by intestinal-like columnar cells under the influence of refluxed gastric acid.

• Connective tissue metaplasia is the formation of cartilage, bone, or adipose tissue (mesenchymal tissues) in tissues that normally do not contain these elements. For example, bone formation in muscle, designated myositis ossificans, occasionally occurs after intramuscular hemorrhage.

QUIZ TIME

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Dx??

Answer is

• Physiological hypertrophy of uterus during pregnancy

Dx??

Answer is

• Picture A- Normal brain• Picture B- Senile atophy of the brain in old age

Dx??

Answer is

• Squamous metaplasia of respiratory ciliated columnar epithelium in a habitual smoker

Thank you………..