Pathomechanism of atrophy and hypertrophy, examples

1. Hypertrophy

• ↑ cell size → ↑ organ size; no new cells (vs hyperplasia = ↑ number); they can coexist.
• Affects cells with limited division capacity (cardiac, skeletal muscle).
• Triggers: mechanical (↑demand), trophic/hormonal, growth factors → ↑protein synthesis, gene expression, ECM remodeling.
• Physiological: exercise; uterus in pregnancy, breast in lactation. Pathological: cardiac hypertrophy from HTN / valve disease.

Cardiac patterns

Pattern	Stimulus	Sarcomeres	Causes
Concentric LV	Pressure overload	Added in parallel (↑wall, small cavity)	HTN, aortic stenosis, coarctation
Eccentric LV	Volume overload	Added in series (↑cavity)	Aortic/mitral insufficiency
Right ventricle	↑pulmonary resistance	—	Cor pulmonale (emphysema, bronchiectasis, fibrosis, PE, kyphoscoliosis)

• Consequences: diastolic failure (stiff wall → poor filling), CIHD (supply can’t meet enlarged demand) → terminal dilation (Frank-Starling), apoplexia (hemorrhagic stroke, Charcot-Bouchard aneurysm in chronic HTN), renal failure (hyaline arteriolosclerosis). RV failure → backward congestion (nutmeg liver).

2. Atrophy

• ↓ cell size (autophagy + ubiquitin-proteasome) and ↓ cell number (apoptosis) → shrinkage + diminished function; cell “reprograms” to survive smaller.

Causes

• ↓ functional demand (disuse): immobilized fractured limb.
• Inadequate O₂/nutrition: partial ischemia → brain shrinkage, centrilobular liver (nutmeg).
• Hormonal: hypercortisolism (Cushing → skin atrophy, osteoporosis), estrogen deprivation in breast cancer Rx.
• Aging: permanent-cell organs (brain, heart, muscle).

Mechanism

• ↓protein synthesis, ↑protein degradation (ubiquitin-proteasome tagging), ↓gene expression, ↑autophagy (autophagic vacuoles fuse with lysosomes).

Examples

• Brown atrophy of heart (lipofuscin in aged myocardium), cerebral atrophy, cachexia (tumor-associated).

💡 High-yield: Hypertrophy = bigger cells (concentric = pressure/parallel; eccentric = volume/series). Atrophy = smaller/fewer cells via autophagy + ubiquitin-proteasome. Disuse, ischemia, hormones, and aging are the main atrophy triggers.