Q3 LONG ANSWER 10M ★ High-yield

Describe the cellular adaptations to stress with examples. Add a note on intracellular accumulations.

Pathology · 2nd Professional — Para-Clinical

Definition

Cellular adaptations are reversible changes in the size, number, phenotype or metabolic activity of cells, by which they achieve a new steady state and survive a persistent stress.

They lie between the normal cell and the injured cell; when the capacity to adapt is exceeded, cell injury follows

Types of Adaptation

Adaptation	Definition	Mechanism
Hypertrophy	Increase in the size of cells and so of the organ	Increased synthesis of structural protein and organelles
Hyperplasia	Increase in the number of cells	Only in tissues capable of division; growth-factor driven
Atrophy	Decrease in the size and number of cells	Ubiquitin–proteasome degradation and autophagy
Metaplasia	Reversible replacement of one differentiated cell type by another	Reprogramming of stem cells, not transdifferentiation
Dysplasia	Disordered growth with atypia — not a true adaptation but a pre-malignant change	Accumulated genetic damage

Hypertrophy and Hyperplasia

	Physiological	Pathological
Hypertrophy	Skeletal muscle in an athlete; uterus in pregnancy	Left ventricle in hypertension or aortic stenosis; bladder in prostatic obstruction
Hyperplasia	Breast at puberty and in pregnancy; liver after partial hepatectomy; bone marrow at altitude	Endometrial hyperplasia from unopposed oestrogen; benign prostatic hyperplasia; thyroid in Graves disease

The two often occur together in tissues that can divide — the pregnant uterus shows both
Permanent cells can only hypertrophy — cardiac and skeletal muscle and neurones cannot divide
Pathological hyperplasia is a fertile soil for cancer, as in endometrial hyperplasia progressing to carcinoma — though hyperplasia itself is not malignant

CLINICAL PEARL

Cardiac hypertrophy has a ceiling. The muscle mass grows but the capillary supply does not keep pace, so the enlarged myocardium becomes relatively ischaemic. Beyond a certain point the adaptation fails and gives way to dilatation, fibrosis and heart failure — adaptation turning into injury.

Atrophy

Causes — disuse (immobilised limb), denervation (poliomyelitis), loss of blood supply (senile brain atrophy), inadequate nutrition (cachexia, marasmus), loss of endocrine stimulation (endometrium after the menopause), pressure (tumour compressing adjacent tissue), and ageing
Autophagy — the cell digests its own organelles in autophagic vacuoles; undigested residue persists as lipofuscin, the "wear and tear" pigment of brown atrophy
The cells are smaller but not dead, and function is diminished rather than lost

Metaplasia

Site	Change	Stimulus
Bronchus	Ciliated columnar → stratified squamous	Cigarette smoke
Lower oesophagus	Stratified squamous → columnar with goblet cells (barrett)	Acid reflux
Stomach and small bowel	Gastric → intestinal type	Chronic gastritis, Helicobacter pylori
Cervix	Columnar → squamous at the transformation zone	Acid vaginal pH
Urinary bladder	Transitional → squamous	Stones, schistosomiasis
Connective tissue	Fibrous tissue → bone or cartilage (osseous metaplasia)	Injury, myositis ossificans

Metaplasia is adaptive but has a price — squamous epithelium in the bronchus resists smoke but loses cilia and mucus secretion, so clearance fails
It is a soil for malignancy — squamous carcinoma of the bronchus and adenocarcinoma in Barrett oesophagus arise in metaplastic epithelium
The direction of change follows the stress: where a tougher lining is needed, squamous appears; where secretion is needed, columnar

Intracellular Accumulations

Substance	Example	Note
Fat (steatosis)	Liver in alcoholism, diabetes, obesity, protein malnutrition, toxins	Reversible; large droplets displace the nucleus
Protein	Russell bodies in plasma cells; Mallory hyaline in alcoholic liver disease; hyaline droplets in proteinuria	—
Glycogen	Diabetes; glycogen storage diseases	—
Lipofuscin	"Wear and tear" pigment of ageing; brown atrophy of heart and liver	Harmless marker of free radical injury
Melanin	Skin; naevi and melanoma	Endogenous, brown-black
Haemosiderin	Bruises; haemochromatosis; heart failure cells in the lung	Prussian blue positive
Carbon (anthracosis)	Lungs and hilar nodes of city dwellers	Exogenous; usually harmless

Applied Aspects

Left ventricular hypertrophy on the ECG or echocardiogram is a marker of long-standing hypertension and an independent predictor of cardiac events
Barrett oesophagus requires surveillance endoscopy, since it may progress through dysplasia to adenocarcinoma
Metaplasia and hyperplasia are reversible if the stimulus is removed — bronchial metaplasia regresses after stopping smoking, which is the strongest argument to give a patient
Dysplasia is graded as mild, moderate and severe; severe dysplasia merges with carcinoma in situ and is treated as pre-malignant
Pathological calcification — dystrophic occurs in dead or dying tissue with a normal serum calcium (atheroma, damaged heart valves, caseous nodes); metastatic occurs in normal tissue with hypercalcaemia (hyperparathyroidism, bone metastases, vitamin D excess)
Metastatic calcification favours acid-secreting tissues — gastric mucosa, kidney, lung and systemic arteries — because their internal alkalinity promotes precipitation
Psammoma bodies are laminated calcific concretions seen in papillary carcinoma of the thyroid, serous ovarian tumours and meningioma
Benign prostatic hyperplasia is hyperplasia, not hypertrophy, despite the older name "prostatic hypertrophy" — a distinction examiners enjoy
Brown atrophy of the heart in cachexia and old age is due to lipofuscin accumulation, and is of no functional consequence
Anthracosis is harmless; silicosis and asbestosis are not — the difference lies in whether the particle provokes fibrosis, not in whether it is deposited
Hepatic steatosis is reversible if alcohol is stopped, but progresses through steatohepatitis to cirrhosis if it is not — the single most useful thing to tell a patient
Fatty change in the liver of protein-energy malnutrition reflects impaired apolipoprotein synthesis, and is a feature of kwashiorkor
Autophagy is now recognised as a survival mechanism in starvation, and its failure contributes to neurodegenerative disease and to ageing

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