Pathology chapters
Cellular adaptations: hypertrophy, hyperplasia, atrophy and metaplasia
How cells adapt to stress by changing their size, number or type, with physiological and pathological examples of hypertrophy, hyperplasia, atrophy and metaplasia, and how these link to dysplasia and cancer.
- Cells adapt to stress by changing size (hypertrophy, atrophy), number (hyperplasia) or type (metaplasia); adaptations are usually reversible when the stimulus is removed.
- Hypertrophy occurs in cells that cannot divide (heart, skeletal muscle); hyperplasia in cells that can (endometrium, prostate, liver); the pregnant uterus shows both.
- Metaplasia replaces one adult cell type with another, more resistant type (bronchial squamous metaplasia in smokers, Barrett oesophagus), and may progress to dysplasia and cancer.
On this page
Overview
When cells face increased demand, decreased supply or chronic irritation, they adapt to survive. Adaptations change the cell's size, number or type. They are usually reversible when the stimulus is removed, but if the stress continues or worsens, the cell may be injured or, in some cases, become cancerous.
Hypertrophy
Increase in the size of cells, and therefore of the organ, without new cells. The cells contain more structural proteins and organelles.
Occurs especially in cells with little or no capacity to divide: cardiac and skeletal muscle.
| Type | Examples |
|---|---|
| Physiological | Skeletal muscle of weightlifters; uterus in pregnancy (with hyperplasia); breast in lactation |
| Pathological | Left ventricular hypertrophy in hypertension or aortic stenosis; right ventricular hypertrophy in pulmonary hypertension |
Causes: increased functional demand (mechanical stretch) and growth factors or hormones.
Pathological cardiac hypertrophy eventually fails: the enlarged heart becomes stiff, outgrows its blood supply and may develop heart failure and arrhythmias.
Hyperplasia
Increase in the number of cells, from cell division. Only in tissues whose cells can divide (labile and stable cells).
| Type | Examples |
|---|---|
| Physiological – hormonal | Breast at puberty and in pregnancy; endometrium in the proliferative phase |
| Physiological – compensatory | Liver regrowth after partial removal (liver donation) |
| Pathological | Endometrial hyperplasia (excess oestrogen); benign prostatic hyperplasia (androgens); skin warts (HPV); thyroid hyperplasia in Graves' disease |
Pathological hyperplasia stops when the stimulus stops, but it provides fertile ground for cancer: endometrial hyperplasia increases the risk of endometrial carcinoma.
The pregnant uterus shows both hypertrophy and hyperplasia. Benign prostatic hyperplasia is hyperplasia, not a precursor of prostate cancer.
Atrophy
Decrease in the size of cells (and organ) from loss of cell substance.
Causes
- Disuse: a limb in a plaster cast; bed rest.
- Denervation: muscle after nerve injury or polio.
- Reduced blood supply (ischaemia): brain atrophy in atherosclerosis.
- Inadequate nutrition: muscle wasting in malnutrition (marasmus) and cancer cachexia.
- Loss of hormonal stimulation: endometrium, breast and vagina after menopause.
- Pressure: a growing benign tumour compressing tissue.
- Ageing (senile atrophy): brain and heart.
Mechanism
- Less protein synthesis.
- More protein breakdown, mainly by the ubiquitin-proteasome pathway.
- Autophagy ("self-eating"): the cell digests its own components; residual bodies may contain lipofuscin (brown atrophy).
Metaplasia
A reversible change in which one adult (differentiated) cell type is replaced by another adult cell type that can better withstand the stress. It comes from reprogramming of stem (reserve) cells, not change of mature cells.
| Example | Change | Cause | Risk |
|---|---|---|---|
| Bronchi of smokers | Ciliated columnar → stratified squamous | Cigarette smoke | Squamous cell carcinoma of the lung |
| Barrett oesophagus | Squamous → columnar (intestinal type with goblet cells) | Chronic acid reflux | Adenocarcinoma of the oesophagus |
| Bladder | Transitional → squamous | Stones, schistosomiasis | Squamous cell carcinoma |
| Cervix (transformation zone) | Columnar → squamous | Normal at puberty and with irritation | Site where cervical cancer develops (with HPV) |
| Stomach | Gastric → intestinal metaplasia | H. pylori, chronic gastritis | Gastric adenocarcinoma |
| Vitamin A deficiency | Columnar → squamous (eye, airway) | Lack of vitamin A | Keratomalacia |
| Mesenchymal metaplasia | Connective tissue → bone | Injury to muscle | Myositis ossificans |
Smoker's bronchus: columnar → squamous. Barrett oesophagus: squamous → columnar.
Metaplasia is not cancer and is reversible, but persistent irritation can lead to dysplasia (disordered growth) and then carcinoma. See neoplasia.
Squamous metaplasia protects but has a cost: in the bronchi, loss of cilia and mucus impairs clearance of particles and microbes.
Summary
| Adaptation | Change | Cell type needed | Typical example |
|---|---|---|---|
| Hypertrophy | ↑ cell size | Any; only option for non-dividing cells | LVH in hypertension |
| Hyperplasia | ↑ cell number | Dividing cells | BPH, endometrial hyperplasia |
| Atrophy | ↓ cell size | Any | Disuse atrophy in a plaster cast |
| Metaplasia | Change of cell type | Stem (reserve) cells | Barrett oesophagus |
Most questions give an example and ask the adaptation. Know: heart and muscle (hypertrophy only), pregnant uterus (both), BPH and endometrial hyperplasia, causes of atrophy, the metaplasias of the bronchus, Barrett oesophagus, bladder and stomach, myositis ossificans, and the metaplasia-dysplasia-carcinoma sequence.
Quick revision
- Hypertrophy: bigger cells (heart, skeletal muscle).
- Hyperplasia: more cells (endometrium, prostate, liver).
- Pregnant uterus: both.
- Atrophy: smaller cells (disuse, denervation, ischaemia, hormones, ageing); ubiquitin-proteasome and autophagy.
- Metaplasia: adult cell type replaced; reversible; may lead to dysplasia.
- Smoker: columnar → squamous. Barrett: squamous → columnar (adenocarcinoma risk).
Written by The House Job from standard pathology references (Robbins and Cotran Pathologic Basis of Disease is the book named in the UHS PGET syllabus).
FAQ
What is the difference between hypertrophy and hyperplasia?
Hypertrophy is an increase in cell size; hyperplasia is an increase in cell number.
What is metaplasia?
A reversible change in which one adult cell type is replaced by another adult cell type better able to withstand stress.
What change occurs in Barrett oesophagus?
Squamous epithelium of the lower oesophagus is replaced by columnar epithelium with goblet cells, raising the risk of adenocarcinoma.
Which adaptations occur in the pregnant uterus?
Both hypertrophy and hyperplasia of smooth muscle.