Cellular adaptation through increased cell size
Hypertrophy is defined as an increase in the size of individual cells resulting in an enlarged organ or tissue without an increase in cell number. This occurs when cells synthesize more structural components including proteins, organelles, and cytoplasmic elements.
Key Concept: Hypertrophy increases cell size (not number) through increased protein synthesis and organelle production, enhancing functional capacity.
During regular exercise training, muscle fibers increase in size through enhanced protein synthesis. This allows for greater force generation. Resistance training stimulates mTOR pathways leading to increased contractile proteins (actin and myosin) and sarcoplasmic expansion.
In endurance athletes, the left ventricle undergoes eccentric hypertrophy (chamber dilation) to accommodate increased blood volume. In strength athletes, concentric hypertrophy (wall thickening) occurs to generate greater contractile force. Both adaptations improve cardiac output.
The uterus undergoes both hypertrophy (smooth muscle cell enlargement) and hyperplasia (cell number increase) during pregnancy. Estrogen and mechanical stretch stimulate growth to accommodate the developing fetus, increasing uterine weight from ~50g to ~1000g.
Chronic hypertension increases afterload, forcing the left ventricle to work harder. Cardiomyocytes enlarge (concentric hypertrophy) initially as compensation, but eventually develop fibrosis, reduced compliance, and diastolic dysfunction. LVH increases risk of heart failure 2-3 fold.
A genetic disorder (often sarcomere protein mutations) causing asymmetric septal hypertrophy. Myofibril disarray and fibrosis lead to diastolic dysfunction and potential outflow obstruction. HCM is the most common cause of sudden cardiac death in young athletes.
Chronic lung diseases (COPD, pulmonary fibrosis) or pulmonary hypertension increase right ventricular afterload. The RV wall thickens to overcome increased pulmonary vascular resistance, but eventually fails (cor pulmonale) due to limited compensatory capacity.
Integrins, stretch-activated channels, and cytoskeletal elements detect mechanical stress, activating signaling pathways (FAK, ILK) that initiate hypertrophy.
PI3K/Akt/mTOR (physiological) and calcineurin/NFAT (pathological) pathways regulate protein synthesis and sarcomere organization.
Fetal gene program reactivation (ANP, BNP, β-MHC) occurs in pathological hypertrophy, altering contractile protein isoforms.
Pathological hypertrophy shifts from fatty acid to glucose metabolism and develops mitochondrial dysfunction, reducing ATP availability.
Hypertrophy represents cellular adaptation through increased size (not number) by synthesizing more proteins and organelles. Physiological hypertrophy (exercise, pregnancy) enhances function reversibly, while pathological hypertrophy (hypertension, cardiomyopathy) progresses to dysfunction.
At the cellular level, mechanical sensors activate signaling pathways (mTOR, calcineurin) that regulate protein synthesis and gene expression. While beneficial in trained muscles, cardiac hypertrophy often signals disease progression requiring clinical intervention.
Key distinctions include reversibility, functional consequences, and molecular signatures. Understanding these differences helps clinicians manage conditions like hypertension and guides athletes in optimizing training adaptations.
Hypertrophy = Increased cell size | Physiological = Reversible/Adaptive | Pathological = Progressive/Dysfunctional
Answer these 5 questions to test your understanding
Your performance on the Hypertrophy Knowledge Test
Loading your results...