How adaptation is tested on Step 1
Vignettes describe a stress — hypertension, a pregnant uterus, an immobilized limb, chronic acid reflux, a smoker's bronchus — and ask you to name the adaptation or predict the cancer risk.
Ask two questions: does the tissue divide? (if not, it can only hypertrophy) and is the change still orderly? (adaptation) or disordered? (dysplasia, a step toward cancer).
The four adaptations
Each adaptation changes cell size, cell number, or cell type in response to a demand or a loss of support.
| Adaptation | Physiologic example | Pathologic example |
|---|---|---|
| Hypertrophy | Skeletal muscle with weight training; uterus in pregnancy | Left ventricular hypertrophy from hypertension or aortic stenosis |
| Hyperplasia | Breast at puberty and lactation; liver regrowth after partial resection | Endometrial hyperplasia (unopposed estrogen); benign prostatic hyperplasia |
| Atrophy | Thymus in adulthood; uterus after menopause | Disuse, denervation, ischemia, malnutrition, pressure |
| Metaplasia | — | Barrett esophagus; squamous metaplasia of the bronchus in smokers; myositis ossificans |
Physiologic adaptations follow normal demands; pathologic adaptations follow disease.
Hypertrophy and hyperplasia
Hypertrophy adds structural proteins and organelles to existing cells; hyperplasia adds new cells through stem-cell proliferation and growth-factor signaling. Which one a tissue uses depends on its capacity to divide.
| Tissue type | Ability to divide | Examples | Adapts by |
|---|---|---|---|
| Labile | Continuously dividing | Skin, GI mucosa, bone marrow | Hyperplasia (and hypertrophy) |
| Stable | Quiescent; can re-enter the cycle | Liver, kidney tubules, fibroblasts | Hyperplasia when stimulated |
| Permanent | Cannot divide | Cardiac muscle, skeletal muscle, neurons | Hypertrophy only |
Because cardiac myocytes are permanent cells, a pressure-loaded heart grows only by hypertrophy.
Endometrial hyperplasia from unopposed estrogen is a precursor of endometrial carcinoma. Benign prostatic hyperplasia is not a precursor of prostate cancer — the two arise in different zones of the gland.
Atrophy
Atrophy shrinks tissue by reducing cell size and, often, cell number. Cells degrade their own components through two pathways: the ubiquitin-proteasome system breaks down cytoskeletal proteins, and autophagy digests organelles inside autophagic vacuoles.
- Decreased workload — an immobilized limb in a cast.
- Loss of innervation — muscle wasting after nerve injury.
- Diminished blood supply — brain atrophy with chronic ischemia.
- Inadequate nutrition — muscle wasting in cachexia.
- Loss of hormonal stimulation — endometrium after menopause.
- Pressure — tissue adjacent to an enlarging mass.
Indigestible residues of autophagy accumulate as lipofuscin, a yellow-brown "wear-and-tear" pigment. It is a marker of atrophy and aging in the heart, liver, and brain, not a cause of dysfunction.
Metaplasia — and when it turns into dysplasia
Metaplasia reprograms stem cells to produce a different, more resistant cell type. It protects against the immediate stress but can sacrifice function and, if the stress persists, lead to dysplasia.
| Metaplasia | Stress | Change | Risk |
|---|---|---|---|
| Barrett esophagus | Chronic acid reflux | Squamous → intestinal columnar with goblet cells | Esophageal adenocarcinoma |
| Bronchial (smokers) | Cigarette smoke | Columnar → squamous | Squamous cell carcinoma of the lung |
| Cervical transformation zone | Acidic vaginal environment, HPV | Columnar → squamous | Cervical squamous cell carcinoma |
| Vitamin A deficiency | Lack of retinoic-acid signaling | Specialized → keratinizing squamous (eye: keratomalacia) | Loss of function |
| Myositis ossificans | Muscle trauma | Connective tissue → bone | Benign |
Apocrine metaplasia of the breast (fibrocystic change) is the classic metaplasia that does not raise cancer risk.
A 55-year-old man with 20 years of heartburn undergoes endoscopy. Biopsy of the distal esophagus shows columnar epithelium with goblet cells and no nuclear atypia. What is the change, and what is he at risk for?
- Chronic acid reflux is the stress; the normal distal esophagus is lined by stratified squamous epithelium.
- Columnar epithelium with goblet cells replacing squamous epithelium is intestinal metaplasia.
- No atypia means there is no dysplasia yet.
Answer. Barrett esophagus (intestinal metaplasia). It raises the risk of esophageal adenocarcinoma, so it is followed with surveillance endoscopy to detect dysplasia.