Cellular adaptation
Cellular adaptation: hypertrophy, hyperplasia, atrophy, metaplasia and dysplasia
Hypertrophy, hyperplasia, atrophy, metaplasia and dysplasia explained with LVH, endometrial hyperplasia, BPH, Barrett and CIN. The deciding question is always whether the cells can divide and what stimulus drives them.
The logic of adaptation
- Cells under stress change their size, number or type. Which response occurs depends on whether the cells can divide:
| Tissue | Can divide? | Response to increased demand |
|---|---|---|
| Cardiac and skeletal muscle | No (permanent cells) | Hypertrophy only |
| Epithelium, glands, marrow | Yes (labile or stable) | Hyperplasia, often with hypertrophy |
| Pregnant uterus | Yes | Both hypertrophy and hyperplasia of smooth muscle |
- Adaptations are reversible when the stimulus stops; persistent stimulus can push cells on to injury or, through dysplasia, to cancer.
Hypertrophy
- Increase in cell size from synthesis of more structural proteins and myofilaments. In the hypertensive heart, the extra mass is due to larger myocytes with more myofilaments, not more myocytes. Fetal genes (ANP, beta-myosin heavy chain) are re-expressed.
| Pattern | Cause | Heart at autopsy |
|---|---|---|
| Concentric LVH | Pressure overload: hypertension, aortic stenosis | Thick wall, small cavity; sarcomeres added in parallel |
| Eccentric LVH | Volume overload: aortic or mitral regurgitation | Dilated cavity, wall thickness near normal; sarcomeres added in series |
- LVH gives tall QRS voltages and left axis deviation on ECG. Physiological hypertrophy: skeletal muscle with exercise, driven partly by testosterone and growth factors.
Hyperplasia
- Increase in cell number, only in cells able to divide.
- Physiological: hormonal (breast at puberty and in pregnancy, proliferative endometrium); compensatory (liver regrowth after partial hepatectomy).
- Pathological, driven by excess hormone or growth factor:
| Example | Driver | Cancer risk |
|---|---|---|
| Endometrial hyperplasia | Unopposed oestrogen (anovulation, PCOS, obesity, oestrogen-only HRT); heavy irregular bleeding | Yes; highest with cytological atypia (atypical hyperplasia, endometrial intraepithelial neoplasia), which carries a high chance of coexisting or future carcinoma |
| Benign prostatic hyperplasia | Dihydrotestosterone (testosterone converted by 5-alpha reductase in stromal cells); transition zone | None: BPH is not premalignant |
| Erythroid hyperplasia | Erythropoietin in haemolysis (hereditary spherocytosis) or bleeding; film shows large bluish polychromatic cells (reticulocytes) | None; give folate, or the marrow turns megaloblastic |
| Megakaryocytic hyperplasia | Peripheral platelet destruction in immune thrombocytopenia (bruising, epistaxis, very low platelets) | None |
| Crypt hyperplasia | Compensates for villous loss in coeliac disease | Small-bowel lymphoma risk if untreated |
| Graves thyroid; adrenal | TSH-receptor antibodies; ACTH | None |
- Coeliac disease: duodenal biopsy shows villous atrophy, crypt hyperplasia and intraepithelial lymphocytes; iron deficiency and the itchy blistering rash of dermatitis herpetiformis fit. The key advice is a lifelong gluten-free diet. (Villous atrophy with many PAS-positive macrophages is Whipple disease instead.)
Atrophy
- Reduced cell size (and often number) in a previously normal organ, through less protein synthesis, more degradation by the ubiquitin–proteasome pathway, and autophagy (leaving lipofuscin).
| Cause | Example |
|---|---|
| Disuse | Limb muscles in a plaster cast after fracture |
| Denervation | Polio, nerve injury |
| Reduced blood supply | Renal artery stenosis, ageing brain |
| Malnutrition | Cachexia (TNF) |
| Loss of hormone | Postmenopausal endometrium; adrenal cortex on long-term steroids |
| Pressure | Tumour, hydronephrosis |
| Physiological | Thymus after puberty, uterus after delivery |
- Hypoplasia and aplasia are developmental failures, not atrophy.
Metaplasia
- Reversible replacement of one adult cell type by another better able to withstand the stress, by reprogramming of stem cells. The new tissue protects but loses function, and continued stress can lead to dysplasia. Metaplasia itself is not cancer.
| Change | Example | Consequence |
|---|---|---|
| Columnar to squamous | Smokers' bronchi; cervical transformation zone; ducts with stones; vitamin A deficiency | Lost mucociliary clearance; squamous carcinoma |
| Squamous to intestinal columnar with goblet cells | Barrett oesophagus: columnar lining extending 3 cm or more above the gastro-oesophageal junction in reflux | Adenocarcinoma |
| Gastric to intestinal | *H. pylori* or autoimmune gastritis | Intestinal-type gastric cancer |
| Urothelium to squamous | Schistosomiasis, chronic stones | Bladder squamous carcinoma |
| Osseous metaplasia | Myositis ossificans: hard mass with bone in muscle weeks after a severe bruise | Can mimic sarcoma |
- Apocrine metaplasia in fibrocystic breast change is harmless.
Dysplasia and carcinoma in situ
- Dysplasia means atypical cells growing in a disordered way, without invasion: loss of uniformity and polarity, pleomorphism, hyperchromatic nuclei, a high nuclear-to-cytoplasmic ratio, and mitoses above the basal layer.
- Low-grade dysplasia can regress; high-grade often progresses.
- Carcinoma in situ is dysplasia through the full thickness of the epithelium with the basement membrane intact, so it cannot metastasise: CIN 3, DCIS, Bowen disease.
- Cervical dysplasia (CIN) is most strongly associated with high-risk HPV types 16 and 18: viral E6 inactivates p53 and E7 inactivates Rb. Screening with HPV testing and cytology aims to find CIN before invasion.
- Related terms: anaplasia (lack of differentiation, a hallmark of malignancy); hamartoma (disorganised native tissue, for example lung hamartoma, Peutz–Jeghers polyp); choristoma (normal tissue in the wrong place, for example gastric mucosa in Meckel diverticulum).
Remember Heart enlarges by hypertrophy, uterus in pregnancy by both, liver after resection by hyperplasia.
Exam trap Endometrial hyperplasia can become cancer; BPH cannot.
Exam trap Metaplasia is an adaptive change and not premalignant by itself, but it is the soil in which dysplasia grows.
How FCPS asks about this
- Thick LV wall with small cavity in hypertension: concentric hypertrophy from larger myocytes with more myofilaments.
- Endometrial hyperplasia with the highest cancer risk: hyperplasia with cytological atypia; caused by unopposed oestrogen.
- Hormone driving BPH: dihydrotestosterone.
- Bone in thigh muscle after a bruise: osseous metaplasia (myositis ossificans).
- Smear with high N:C ratio, basement membrane intact: dysplasia (CIN) linked to HPV 16 and 18.
- Marrow in hereditary spherocytosis: erythroid hyperplasia; give folate.
- Villous atrophy, crypt hyperplasia and intraepithelial lymphocytes with an itchy blistering rash: coeliac disease, lifelong gluten-free diet.
Test yourself on this topic
5 of the 62 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
In Graves' disease, the thyroid follicles are lined by tall crowded cells with scalloped colloid. What change has the gland undergone?
Answer: Hyperplasia and hypertrophy
In Graves' disease, IgG antibodies stimulate the TSH receptor, mimicking TSH. Follicular cells multiply (hyperplasia) and enlarge into tall columnar cells (hypertrophy), crowding into papillary infoldings. Active hormone production resorbs colloid, which looks pale with scalloped edges. The result is a diffuse goitre with hyperthyroidism. Granulomatous inflammation is de Quervain thyroiditis; Hürthle cell change and lymphoid infiltrate suggest Hashimoto thyroiditis.
Graves' thyroid
- TSH-receptor stimulating antibodies
- Tall hyperplastic follicles
- Scalloped pale colloid
- Diffuse goitre + hyperthyroidism
Remember Antibody acts like TSH: gland grows and works.
Why the other options are wrong
- Atrophy Opposite: shrinkage of cells.
- Squamous metaplasia Not seen in Graves' disease.
- Dysplasia No atypia in Graves' disease.
- Granulomatous inflammation De Quervain (subacute) thyroiditis.
Cervical cytology shows mild dyskaryosis, and biopsy shows dysplasia confined to the lower third of the epithelium. How is this classified?
Answer: CIN 1
Cervical intraepithelial neoplasia is graded by how much of the epithelial thickness shows dysplasia: CIN 1 lower third (mild, often regresses), CIN 2 lower two-thirds (moderate), CIN 3 full thickness (severe dysplasia / carcinoma in situ). The basement membrane is intact in all. CIN 1 is usually monitored; CIN 2–3 are treated, usually by large loop excision of the transformation zone.
CIN grading
- CIN 1: lower third, often regresses
- CIN 2: two-thirds
- CIN 3: full thickness (CIS)
- Basement membrane intact
- Treat CIN 2–3: LLETZ
Remember One-third, two-thirds, full: CIN 1, 2, 3.
Exam trap High-risk HPV (16, 18) drives progression.
Why the other options are wrong
- CIN 2 Two-thirds of the thickness.
- CIN 3 Full thickness.
- Carcinoma in situ Same as CIN 3.
- Microinvasive carcinoma Invasion through the basement membrane.
A 7-year-old boy has a waddling gait, rises from the floor by climbing up his legs and has large firm calves. His mother's brother died of the same disease at 19. What has caused the calf enlargement?
Answer: Fat and fibrous tissue replacing muscle
Duchenne muscular dystrophy is X-linked recessive and is passed through carrier women, as in this family. Absent dystrophin leaves the sarcolemma fragile, so fibres tear, necrose and are slowly replaced by fat and connective tissue. The calves get bigger while getting weaker, which is pseudohypertrophy. Creatine kinase is very high from early childhood.
Pseudohypertrophy
- X-linked recessive, absent dystrophin
- Fibres tear and necrose
- Replaced by fat and fibrosis
- Gowers sign, very high CK
Remember Big but weak calves = fat, not muscle.
Exam trap Pseudohypertrophy means the muscle is enlarged by fat and fibrous tissue, so the bigger calf is the weaker one.
Why the other options are wrong
- Hypertrophy of the remaining muscle fibres True hypertrophy would make the muscles stronger, not weaker.
- Oedema from active inflammation Inflammatory myositis causes pain and weakness, not big calves.
- Glycogen stored in muscle fibres Glycogen storage is seen in metabolic myopathies such as Pompe disease.
- Calcification of necrotic fibres Calcification is not the cause of the enlargement.
A 64-year-old man with a long-standing pelviureteric junction obstruction has a markedly dilated pelvicalyceal system with a renal cortex only 4 mm thick. What process has thinned the cortex?
Answer: Pressure atrophy
Prolonged back-pressure from obstruction compresses the renal parenchyma between the dilated collecting system and the capsule. Compression reduces blood flow and causes the tubular cells to shrink and be lost, a form of atrophy. Over time the kidney becomes a thin-walled sac with little functioning tissue. Hypoplasia is a developmental failure to grow, not loss of tissue that was once normal.
Pressure atrophy
- Long-standing obstruction
- Parenchyma compressed
- Cortex thins
- Ends as a sac of urine
Remember Back-pressure squeezes the kidney thin.
Exam trap Cortical thinning from obstruction can be permanent even after the obstruction is relieved.
Why the other options are wrong
- Disuse atrophy Disuse atrophy follows loss of function, as in an immobilised limb.
- Hypoplasia Hypoplasia is congenital underdevelopment.
- Coagulative necrosis Infarction would give a wedge-shaped defect.
- Apoptosis from radiation No radiation is involved.
At autopsy of an 80-year-old woman with Alzheimer disease, the brain weighs 950 g, the gyri are narrow, the sulci are widened and the lateral ventricles are enlarged. What best explains the ventricular enlargement?
Answer: Generalised cerebral atrophy
When brain tissue is lost, as in Alzheimer disease or ageing, the ventricles and sulci enlarge together to fill the space: hydrocephalus ex vacuo. CSF pressure and flow are normal. True hydrocephalus enlarges the ventricles out of proportion to the sulci, which are compressed rather than widened. Aqueductal stenosis dilates the lateral and third ventricles only, and normal pressure hydrocephalus shows ventricles larger than expected for the sulci.
Atrophy vs hydrocephalus
- Atrophy: ventricles and sulci both large
- Ex vacuo: normal CSF pressure
- Hydrocephalus: ventricles out of proportion
- Hydrocephalus: tight sulci
Remember Big ventricles with big sulci means lost brain, not trapped CSF.
Exam trap Do not call every large ventricle hydrocephalus; compare with the sulci.
Why the other options are wrong
- Normal pressure hydrocephalus Ventricles would be disproportionately large compared with the sulci.
- Aqueductal stenosis Would dilate the lateral and third ventricles with a normal fourth and tight sulci.
- Obstruction at the foramina of Monro Would dilate the lateral ventricles only.
- Choroid plexus overproduction Rare, usually from a papilloma in a child.
Where this sits in the CPSP syllabus
- Paper 1: General pathology, Cellular adaptation: atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia
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