Cellular Adaptations

Cellular Adaptations

Session 4: Cellular Adaptations to Stress

Pathology — CMT/CDT NTA Level 4

Kolandoto College of Health Sciences Mwanza

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Learning tasks

Learning tasks

At the end of this session, students are expected to be able to:

Define cellular adaptation.

Explain the relationship between adaptation, cell injury and cell death.

Describe the types of cellular adaptation.

Identify physiologic and pathologic examples of each type of adaptation.

Explain the mechanisms underlying cellular adaptations.

Explain the clinical significance of cellular adaptation.

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Introduction

Introduction

Cells are constantly exposed to changes in their internal and external environment. To survive, they must adjust their structure and function to accommodate these changing demands.

When physiologic or pathologic stress is applied, the cell responds by achieving a new steady state — this response is called adaptation.

Adaptation preserves the viability and function of the cell. If the adaptive capacity is exceeded, or if the stress is inherently harmful, cell injury develops.

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Definition

Definition

Cellular adaptation

A reversible change in the size, number, phenotype, metabolic activity or function of cells in response to changes in their environment, which allows the cell to reach a new steady state and survive the stress.

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Adaptation, injury and death

Adaptation, injury and death

Normal cell → (increased demand or stress) → Adaptation.

If the stress exceeds the adaptive capacity → Reversible cell injury.

If the stress is severe, persistent or rapid in onset → Irreversible cell injury → Cell death (necrosis or apoptosis).

Adaptations are therefore an intermediate state between the normal cell and the injured cell.

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Key characteristics of adaptation

Key characteristics of adaptation

Adaptations are reversible — when the stimulus is removed, the cell returns to its normal state.

They occur while the cell is still viable and functioning.

They may be physiologic (normal response to a normal stimulus) or pathologic (response to disease).

They protect the cell, but may themselves have harmful consequences.

For example, cardiac hypertrophy compensates for pressure overload, but eventually leads to heart failure.

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Types of cellular adaptation

Types of cellular adaptation

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Types of cellular adaptation

Types of cellular adaptation

Hypertrophy — increase in the size of cells.

Hyperplasia — increase in the number of cells.

Atrophy — decrease in the size and function of cells.

Metaplasia — change from one differentiated cell type to another.

Dysplasia — disordered growth and maturation (considered a pre-neoplastic change).

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Hypertrophy

Hypertrophy

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Hypertrophy

Hypertrophy

An increase in the size of cells, resulting in an increase in the size of the affected organ. There are no new cells — only larger cells, with increased synthesis of structural proteins and organelles.

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Hypertrophy — occurrence

Hypertrophy — occurrence

Occurs in tissues incapable of cell division (permanent cells).

Cardiac muscle.

Skeletal muscle.

Caused by increased functional demand or by stimulation from hormones and growth factors.

May occur together with hyperplasia in tissues capable of division, e.g. the pregnant uterus.

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Hypertrophy — examples

Hypertrophy — examples

Physiologic hypertrophy

Skeletal muscle enlargement in body builders and manual labourers (increased workload).

Enlargement of the uterus during pregnancy (oestrogen stimulation) — with hyperplasia.

Enlargement of the breast during lactation.

Physiologic hypertrophy of the left ventricle in athletes.

Pathologic hypertrophy

Left ventricular hypertrophy in systemic hypertension (pressure overload).

Cardiac hypertrophy in valvular disease, e.g. aortic stenosis.

Hypertrophy of the urinary bladder wall in benign prostatic hyperplasia (outflow obstruction).

Hypertrophy of the remaining kidney after unilateral nephrectomy (compensatory).

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Mechanisms of hypertrophy

Mechanisms of hypertrophy

Mechanical stretch and trophic signals (growth factors, hormones, vasoactive agents) act on cell surface receptors.

These activate signal transduction pathways that switch on transcription factors.

Transcription factors increase the synthesis of structural proteins and organelles.

There is also a switch to embryonic or fetal forms of contractile proteins — e.g. the fetal form of myosin heavy chain, which contracts more efficiently and uses less energy.

Beyond a limit, the enlarged muscle mass outgrows its blood supply, leading to ischaemia, myocyte death, fibrosis and finally cardiac failure.

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Hyperplasia

Hyperplasia

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Hyperplasia

Hyperplasia

An increase in the number of cells in an organ or tissue, in response to a stimulus. It occurs only in cells capable of division (labile and stable cells) and results from proliferation of mature cells and of tissue stem cells.

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Hyperplasia — examples

Hyperplasia — examples

Physiologic hyperplasia

Hormonal: proliferation of the glandular epithelium of the female breast at puberty and during pregnancy.

Hormonal: hyperplasia of the endometrium under oestrogen stimulation.

Compensatory: regeneration of the liver after partial hepatectomy.

Hyperplasia of bone marrow erythroid precursors at high altitude or in chronic blood loss.

Pathologic hyperplasia

Endometrial hyperplasia due to excessive oestrogen stimulation — a cause of abnormal uterine bleeding.

Benign prostatic hyperplasia due to androgen stimulation.

Hyperplasia of the thyroid gland in Graves' disease and in iodine deficiency (goitre).

Viral hyperplasia — warts and other lesions caused by human papilloma virus.

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Hyperplasia — important notes

Hyperplasia — important notes

Hyperplasia is a controlled process; it stops when the stimulus is removed.

This distinguishes it from cancer, in which growth is autonomous and unregulated.

However, pathologic hyperplasia constitutes fertile soil in which cancer may eventually arise.

Patients with endometrial hyperplasia are at increased risk of endometrial carcinoma.

HPV-induced hyperplasia may progress to cervical cancer.

Benign prostatic hyperplasia, however, does not progress to prostatic carcinoma.

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Atrophy

Atrophy

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Atrophy

Atrophy

A reduction in the size of a cell by loss of cell substance, resulting in reduced size and function of the organ. The cells are not dead, but their metabolic activity is diminished.

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Causes of atrophy

Causes of atrophy

Decreased workload (disuse atrophy) — a limb immobilised in a plaster cast; prolonged bed rest.

Loss of innervation (denervation atrophy) — poliomyelitis, nerve injury.

Diminished blood supply (ischaemia) — senile atrophy of the brain in atherosclerosis.

Inadequate nutrition — marasmus, cachexia of chronic illness and malignancy.

Loss of endocrine stimulation — atrophy of the endometrium, vaginal epithelium and breast after menopause.

Pressure — tissue compressed by an expanding tumour or aneurysm.

Ageing (senile atrophy) — affecting the brain and the heart.

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Mechanisms of atrophy

Mechanisms of atrophy

Atrophy results from decreased protein synthesis and increased protein degradation.

Protein degradation occurs mainly through the ubiquitin-proteasome pathway.

Nutrient deficiency and disuse activate ubiquitin ligases.

These attach ubiquitin to cellular proteins, targeting them for degradation in proteasomes.

Atrophy is also accompanied by increased autophagy — the cell digests its own components in autophagic vacuoles to survive.

Residues of undigested organelles may persist as lipofuscin granules, giving the tissue a brown colour (brown atrophy).

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Metaplasia

Metaplasia

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Metaplasia

Metaplasia

A reversible change in which one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type that is better able to withstand the adverse environment.

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Metaplasia — mechanism

Metaplasia — mechanism

Metaplasia does not result from a change in the phenotype of an already differentiated cell.

It arises by reprogramming of tissue stem cells, which then differentiate along a new pathway.

This reprogramming is driven by signals generated by cytokines, growth factors and components of the extracellular matrix.

Vitamin A (retinoic acid) regulates gene transcription and differentiation; its deficiency or excess may cause metaplasia.

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Examples of metaplasia

Examples of metaplasia

Squamous metaplasia — bronchus

Ciliated columnar epithelium replaced by stratified squamous epithelium in habitual cigarette smokers.

Squamous metaplasia — cervix

Columnar epithelium of the endocervix replaced by squamous epithelium at the transformation zone.

Barrett oesophagus

Stratified squamous epithelium replaced by intestinal-type columnar epithelium due to gastric acid reflux.

Squamous metaplasia — bladder

Transitional epithelium replaced by squamous epithelium in chronic schistosomiasis or stones.

Osseous metaplasia

Formation of bone in soft tissue, e.g. within areas of injury or in the wall of an artery.

Myeloid metaplasia

Haematopoiesis occurring in the spleen and the liver in chronic haemolysis or marrow fibrosis.

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Consequences of metaplasia

Consequences of metaplasia

Metaplasia is adaptive — the new epithelium is more resistant to the stress.

However, protective mechanisms of the original epithelium are lost.

Squamous metaplasia in the bronchus loses ciliary action and mucus secretion, predisposing to infection.

If the influence that induced metaplasia persists, it may predispose to malignant transformation.

Squamous metaplasia of the bronchus may progress to squamous cell carcinoma of the lung.

Barrett oesophagus may progress to adenocarcinoma of the oesophagus.

Metaplasia is reversible if the stimulus is removed early.

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Dysplasia

Dysplasia

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Dysplasia

Dysplasia

Disordered growth of cells, characterised by loss of uniformity of individual cells and loss of their architectural orientation. It is not a true adaptation but is often grouped with them, and it is a pre-neoplastic change.

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Metaplasia versus dysplasia

Metaplasia versus dysplasia

Metaplasia

One mature cell type replaced by another mature cell type.

Cells are normal in size, shape and nucleus.

Orderly architecture is maintained.

Fully reversible when the stimulus is removed.

Not itself pre-malignant, but may predispose.

Dysplasia

Cells show variation in size and shape (pleomorphism).

Nuclei are large, hyperchromatic, with increased nuclear-cytoplasmic ratio.

Loss of orderly architecture; mitoses appear above the basal layer.

Reversible in mild forms; severe dysplasia may not regress.

A recognised pre-malignant change (e.g. cervical dysplasia).

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Dysplasia — clinical importance

Dysplasia — clinical importance

Dysplasia is commonly graded as mild, moderate or severe according to the proportion of the epithelium involved.

When dysplastic changes involve the full thickness of the epithelium but remain confined by the basement membrane, the lesion is termed carcinoma in situ.

Detection of dysplasia at an early stage — for example by cervical cytology screening (Pap smear) — allows treatment before invasive cancer develops.

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Summary of cellular adaptations

Summary of cellular adaptations

Hypertrophy

Increased cell size. Cardiac hypertrophy in hypertension; skeletal muscle in body builders.

Hyperplasia

Increased cell number. Endometrial hyperplasia; benign prostatic hyperplasia; liver regeneration.

Atrophy

Decreased cell size and function. Disuse, denervation, ischaemia, malnutrition, loss of hormonal stimulation.

Metaplasia

One differentiated cell type replaced by another. Bronchial squamous metaplasia in smokers.

Dysplasia

Disordered growth and maturation. Pre-neoplastic; graded mild to severe.

Intracellular accumulation

Adaptive storage of lipids, proteins, glycogen and pigments within the cell.

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Key points

Key points

Cellular adaptation is a reversible change that allows a cell to survive stress and reach a new steady state.

Adaptation lies between the normal cell and the injured cell; when adaptive capacity is exceeded, cell injury follows.

Hypertrophy is an increase in cell size; hyperplasia is an increase in cell number.

Atrophy results from decreased protein synthesis, increased proteasomal degradation and increased autophagy.

Metaplasia arises from reprogramming of stem cells, not from transformation of differentiated cells.

Dysplasia is disordered growth and is a recognised pre-malignant change.

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Evaluation

Evaluation

Define cellular adaptation and state its importance to the cell.

Differentiate between hypertrophy and hyperplasia, giving two examples of each.

List five (5) causes of atrophy.

Explain the mechanism by which metaplasia occurs.

Why is squamous metaplasia of the bronchus considered harmful even though it is adaptive?

Differentiate between metaplasia and dysplasia.

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References

References

Kumar V.; Abbas A. K.; Aster J. C.; (2013): Robbins and Cotran Pathologic Basis of Disease (9th Ed.) Elsevier Saunders, China. Pg. 31-40.

Mohan H.; (2010): Text book of Pathology (6th Ed.) Jaypee Brothers Medical Publishers, India. Pg. 21-27.

Bezabeh M.; Tesfaye A.; Ergicho B. et al (2004): General Pathology Lecture Notes for Health Sciences Students. Ethiopia Public Health Training Initiative. Pg. 14-20.

Goljan E.; (2007): Rapid Review Pathology (2nd Ed.) Elsevier Saunders, USA. Pg. 5-10.

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