Cellular Adaptations of Growth and Differentiation

By Dr: Nassar Ayoub

Overview

• Adaptability of cells to an altered environment– Physiological and pathological stimuli

• Changes in growth pattern– Hyperplasia, hypertrophy, atrophy,

involution, metaplasia• Apoptosis• Growth factors – Role in altered environment

Why is this important?

• Extremely common responses in disease• Certain adaptations in growth act as a fertile

ground for the later development of neoplasia - cancer formation…

• Nomenclature is used in clinical work.

Adaptability of cells to an altered environment

• Cells are constantly exposed to changes in their environment

• Cells can adapt to acceptable changes in their environment by modifying metabolism or growth pattern

• Environmental changes can be physiological or pathological

In respond to excessive physiologic stresses or pathologic stimuli cell may adapt, where a new altered steady state is achieved preserving cell viability.

Adaptation

Examples of pathological stimuli

• Nutritional

• Immune

• Endocrine

• Physical agents

• Chemical agents

• Infections

• Anoxia

• Genetic

Metabolic regulation• Cells may adapt by

metabolic regulation– Induction of enzyme– Downregulation of enzyme– Increased synthesis of

product– Reduced secretion of

product

• Metabolic adaptation is usually not associated with morphological changes

Increased functional demand

• Increased functional demand can be met by two main responses

– Increase in cell size: hypertrophy– Increase in cell number: hyperplasia

• These may occur independently or together.• Reflected by an increase in size and weight of

an organ

• 1- Physiological adaptations They represent response of cells to normal

stimulation by hormones or endogenous chemical substances

e.g. a. enlargement of the breast and induction of

lactation by pregnancy. b. replacement of labile tissues, e.g. skin, bone

marrow c. cyclic as endometrium.

• 2-Pathological adaptations

• adaptations occurring as a result of certain stimuli which are not lethal,

• i.e. a state intermediate between normal unstressed cells and injured overstressed ones.

Adaptive changes in cell growth and differentiation include: a- hyperplasia b- hypertrophy c- atrophy d- metaplasia

Hyperplasia

• Definition:

It is an increase in the size of an organ or tissue due to increase in the number of constituent parenchymal cells. It may be physiological or pathological.

• Physiological hyperplasia• hormonal as in the female breast during

puberty and pregnancy • compensatory as in hyperplasia of liver

hepatocytes after partial hepatectomy due to increase in its functional demands.

Physiological hyperplasia

Normal uterus

Pregnant uterus

• Pathological hyperplasia

• Increased level of circulating hormones produce hyperplasia in the target organs

e.g. a- hyperplasia of the endometrium due to hyperestrinism b-senile prostatic hyperplasia due to increase in the level of

androgen and estrogen.

However, hyperplasia due to certain stimuli stops with removal of these stimuli and may serve a useful function.

Hypertrophy • Definition

• It is an increase in the size of an organ or tissue due to enlargement of individual cells without increase in the number of cells.

• It usually occurs in organs in which proliferation and mitosis are restricted

e.g. skeletal muscle and heart muscles.

• It may be physiological or pathological.

• 1- Physiological hypertrophy

e.g. pregnant uterus, and muscles of athletes.

• 2- Pathological hypertrophy

(adaptive hypertrophy)e.g. a- hypertrophy of the

stomach in pyloric stenosis b- cardiac muscle

hypertrophy in chronically hypertensive patients.

Hypertrophy of the heart

Hypertrophy and hyperplasia are closely related and both may contribute to an overall increase in the organ size.

Atrophy

Definition• Reduction of the size of an organ

after reaching its normal adult size.• As a result of decrease in both

the number and size of the cells.• Often associated with fibrosis.• May be physiological or pathological

• Physiological atrophy• Involution: • A form of physiologic atrophy. • Return to normal size after hyperplasia and

hypertrophy, if the causative stimuli are removed and equilibrium returns back..

Eg• uterus after labour. • atrophy of the ovary after menopause• senile atrophy of geriatrics.

• Pathological atrophy• It depends on the cause. It may be

localized or generalized

• Eg.

a- Ischemic atrophy: due to decrease of blood supply e.g. atherosclerosis

Renal artery stenosis

• b- Pressure atrophy: due to long continued

pressure on a tissue leading to decrease in its blood supply with atrophy of its cells

• e.g. amyloidosis of the liver in which the extracellular deposition of amyloid substance leads to pressure atrophy of hepatocytes.

Amyloidosis of the liver

• c-Neuropathic atrophy: • e.g. when a motor nerve

supplying a muscle is affected as in poliomyelitis

• d- Decreased work load: • e.g. immobilized limb• e- Starvation: leading to

generalized atrophy. The atrophic cells in all

cases, are still surviving cells, but with diminished function.

Metaplasia Definition• It is a reversible change in which an adult cell

type (epithelial or mesenchymal) is replaced by another adult cell type of the same tissue.

It may represent an adaptive substitution of cells more sensitive to stress by other cell types better able to withstand the adverse environment.

Metaplasia is thought to arise by genetic 'deprogramming" of epithelial stem cell or of undifferentiated mesenchymal cells in connective tissue.

• Epithelial squamous metaplasia

e.g. a- uterine endocervical glandular epithelium due to chronic irritation

b-transitional epithelium of urinary bladder, ureter or renal pelvis due to chronic irritation by bilharziasis or stones

c-columnar epithelium of gall bladder due to chronic irritation by stones or inflammation

d-pseudostratified ciliated columnar respiratory epithelium due to chronic irritation by habitual cigarette smoking or in vitamin A deficiency.

Squamous metaplasia Respiratory epithelium

• The adaptive metaplastic epithelium is better able to survive, but important protective mechanisms (such as mucus secretion and ciliary clearance of particulate matter in the respiratory epithelium) are lost.

• If the influences that induce metaplastic transformation of the epithelium are persistent, they may lead to cancer transformation in the metaplastic epithelium, e.g. squamous metaplasia of transitional epithelium of the urinary bladder by bilharziasis will lead to squamous cell carcinoma.

• Mesenchymal cell metaplasia:

Myxomatous change of fibrous tissue. Transformation of fibroblasts to osteoblasts or chondroblasts to produce bone or cartilage in soft tissues in foci of injury.

Examples of metaplasia

Bladder transitional epithelium (T) with metaplasia to squamous epithelium (S) in response to a bladder stone…

• Hypoplasia

It is the decrease in size of an organ due to incomplete development in embryonic or fetal life e.g. kidney and uterus.

• Agenesis

• Complete absence of an organ or a part of an organ e.g. solitary kidney, in such case the other kidney is absent.

• Dysplasia

• Dysplasia (dys-, "bad" or "difficult" and plasis, "formation") is an ambiguous term used in pathology to refer to Abnormal development or growth of tissues,

organs, or cells.