2. Cellular Response and Adaptation Modified

Mohammad Abdul Hamid Alqudah, M.D.Assistant Prof. – Faculty of Medicine.Consultant Pathologist – KAUH.

Normal cell needs special conditions “environment” to function properly.

(Everything should be titrated to our needs).

Cells try to adapt to surrounding stimuli or changes so it can survive.

The normal condition or the standard environment that the cell looks to live in is called: (Homeo-stasis).

Homeo : home or environment. stasis: stable or standing still or fixed .

Things that might change around the cell: PH, Temp., Electrolytes level, Glucose.

Adaptation: hypertrophy, hyperplasia, atrophy, metaplasia.

Injury: reversible and irreversible (cell death).

Intracellular accumulation; calcification

Cellular aging.

Reversible changes in size, number, phenotype, metabolic activity or function in response to changes in their environment.

Adaptation can be both physiologic (we want to happen) and/or pathologic (disease).

Hypertrophy is an increase in cell size resulting in increase in the size of the organ.

Alone in nondividing cells (cardiac myocytes or muscles).

Coexisting with hyperplasia in dividing cells (skin or GI tract cells).

Physiologic vs pathologic.

Muscle

Heart: left ventricle hypertrophy.

Uterus

Increased functional demand (workload) or stimulation by hormones or growth factors.

Mechanism: increased production of cellular structural proteins and organelles.

There is a limit for hypertrophy.

Subcellular organelle may undergo selective hypertrophy. (drugs causing smooth ER hypertrophy).

Increased number of cells resulting in increased mass of the organ or tissue.

Takes place in cells capable of dividing.

Physiologic vs pathologic.

• Physiological Hyperplasia (hormonally induced or compensatory), Examples:

– Uterine enlargement during pregnancy– Female breast in puberty & lactation– Compensatory hyperplasia in partial liver

resection.

• Pathological– Hyperplasia of the endometrium (excessive

hormone stimulation) and prostate hyperplasia.– Wound healing (Effects of growth factors).– Infection by papillomavirus (skin warts).

• Hyperplasia can be a fertile soil for development of malignancy.

Prostate

Endometrium

Mechanism: it is the result of growth factor-driven proliferation of mature cells.

In some cases by increased output of new cells from tissue stem cells.

Not increased work load as in Hypertrophy.

Reduced size of cell, tissue or organ as a result from loss of cell substance (size and number).

Physiologic : Embryonic development. involuting gravid uterus.

Pathologic: - Decreased workload (Disuse atrophy)

- Loss of innervation (Denervation atrophy)

- Diminished blood supply.- Inadequate nutrition.- Loss of endocrine stimulation.

- Aging.

Atrophy muscle fibers.

Brain (frontal lobe)

Undescended testis

Mechanisms: - decreased protein synthesis and increased

protein degradation.

- Reduced metabolic activity, which causes decreased protein synthesis also.

- Ubiquitin-proteasome pathway: protein binds organells signals (kill me) decrease # of organells.

- Autophagy (self eating) to find sources of protein. (starvation).

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

New epithelium is better in dealing with the current stress or irritation.

Persistence of factors causing metaplasia may lead to progression into malignant transformation.

Replacement of ciliated columnar epithelium by stratified squamous epithelium in the respiratory tract of a smoker.

Columnar epithelium in esophagus.

Mechanism: reprogramming of stem cells that are known to exist in normal tissues or undifferentiated mesenchymal cells present in connective tissue.

Signals generated by cytokines, growth factors and extracellular matrix promote expression of genes toward a new differentiation.

Some functions might be lost.Malignant transformation if the cause for

metaplasia persists.

If cells are no longer able to adapt the stress OR exposed to damaging agents from the start.

Reversible.Irreversible (death).

Hypertrophy: increased cell and organ size, often in response to increased workload; induced by mechanical stress and by growth factors; occurs in tissues incapable of cell division.

Hyperplasia: increased cell numbers in response to hormones and other growth factors; occurs in tissues whose cells are able to divide

Atrophy: decreased cell and organ size, as a result of decreased nutrient supply or disuse; associated with decreased synthesis and increased proteolytic breakdown of cellular organelles

Metaplasia: change in phenotype of differentiated cells, often a response to chronic irritation that makes cells better able to withstand the stress; usually induced by altered differentiation pathway of tissue stem cells; may result in reduced functions or increased propensity for malignant transformation.