What is hypertrophy?

Hypertrophy Definition

Hypertrophy refers specifically to an increase in the size of individual cells, rather than an increase in cell number, and should be used only in the context of describing the status of individual cells (such as cardiac myocytes) rather than whole organs or tissues. 1

Proper Definition and Distinction

Hypertrophy represents a fundamental biological process where existing cells increase in size rather than in number. This distinction is critical for understanding tissue growth mechanisms:

• Hypertrophy: Increase in cell size without changing total cell number 1, 2
• Hyperplasia: Increase in cell number through proliferation 3, 4

The European Society of Cardiology position paper specifically addresses this distinction, proposing that the term "hypertrophy" should be restricted to describing the status of individual cells rather than whole organs 1. When referring to changes in entire organs, the term "remodeling" is more appropriate to describe the reorganization of different tissue components.

Types of Hypertrophy

Hypertrophy can be classified into two main categories:

1. Physiological hypertrophy:

   • Occurs in response to normal stimuli like exercise or pregnancy
   • Generally reversible
   • Associated with normal or supranormal function
   • Example: Athlete's heart 1, 5

2. Pathological hypertrophy:

   • Results from abnormal loading or disease states
   • Often irreversible
   • Associated with increased morbidity and mortality
   • Example: Cardiac hypertrophy due to hypertension or valve disease 1, 5

Cellular Mechanisms

At the cellular level, hypertrophy involves:

• Increased rate of protein synthesis exceeding the rate of protein degradation 2
• Enlargement of existing cells rather than formation of new cells 2, 4
• In cardiac muscle, increased myocyte fiber diameter 5
• In skeletal muscle, activation of specific signaling pathways (e.g., IGF-1 pathway) 6

Clinical Significance

Understanding hypertrophy has important clinical implications:

• In cardiac disease, excessive myocyte hypertrophy (fiber diameter >30μm) may predict poor outcomes after valve replacement 5
• In skeletal muscle, hypertrophy represents a positive adaptation to resistance training 2, 6
• The inability of certain organs (heart, brain, kidney) to undergo hyperplasia limits their regenerative capacity 4

Measurement and Assessment

When evaluating hypertrophy, particularly in cardiac tissue, multiple parameters should be assessed:

• Individual cell size measurements
• Functional assessment
• Histological examination
• Molecular characterization 1

Common Pitfalls

A major pitfall in discussing hypertrophy is using the term indiscriminately to describe any increase in organ size or mass. The European Society of Cardiology emphasizes that:

• Simple measurements of organ mass or volume are insufficient to characterize tissue changes
• Nine possible combinations of altered cardiac structure can occur with various changes in wall thickness and chamber size
• Functional, histological, and molecular characterization are necessary for proper assessment 1

Hypertrophy should not be confused with normal developmental growth, which represents a different biological process 1.