Atrophy versus Hypertrophy

Contributors

  • Susanne Ulm

Atrophy versus Hypertrophy

Heart growth is very common and everyone experiences it during lifetime. The heart compensates the increased work (workload) by increasing its size. The process is called cardiac hypertrophy which is the opposite of atrophy (the heart gets smaller due to extended resting periods). Hypertrophy is important because cardiomyocytes (heart cells) stop dividing after birth. Therefore after brith (of a child) the heart can only increase its size by hypertrophic growth of cardiomyocytes (= postnatal growth). This type of hypertrophy is called physiological hypertrophy and also occurs in pregnant women and active people (regular endurance training). This process is reversible. In contrast, pathological hypertrophy is only a 'one-way street' heart growth. The heart develops it in response to several pathological stresses such as hypertension, valvular diseases or following a heart attack. The heart shape can be further described as eccentric or concentric during hypertrophic growth.



Atrophy

The heart is smaller than the normal heart due to hemodynamic unloading which means the heart has to work less hard than usual. This happens in people with prolonged (bed) rest including people with a spinal cord injury, paralysis and even astronauts (being in space without gravity is too easy for the heart). Therefore, a strict and very controlled exercise regime is necessary that depends on the circumstances. For example, astronauts have to exercise in space to prevent atrophy whereas people following a spinal cord injury could not move for a while and need to increase the exercise gradually without exhausting the atrophic heart.

 

Cause:

  • Hemodynamic unloading due to prolonged bed rest (such as after spinal cord injury and paralysis)

 

Molecular/biological characteristics:

  • Heart size ↓
  • Heart function ↓
  • Cardiomyocyte (heart cell) size ↓
  • Apoptosis ↔ (none)

 

Symptoms:

  • Pale and cold extremities
  • Irregular respiration
  • Cough

 

Treatment:

  • Strict physical fitness guidelines to re-build cardiac muscle

Hypertrophy

Cardiomyocytes (heart cells) lose their ability to divide after birth. Therefore the heart must be able to increase its muscle mass without changing the number the cardiomyocytes. This process is called hypertrophy and involves changes in protein synthesis which finally leads to increased cardiomyocyte cell size. This process is triggered by hemodynamic overload which means the heart has to work harder than usual.

Depending on the cause (stimulus) and morphology (shape) 4 different forms of hypertrophy occur:

  • Physiological hypertrophy
  • Pathological hypertrophy
  • Eccentric hypertrophy
  • Concentric hypertrophy


Note:

There is a difference between the cardiac hypertrophy and cardiac hypertrophic remodelling.

Cardiac hypertrophy = growth of cardiomyocytes leading to increased heart size

Cardiac hypertrophic remodelling = hypertrophy and processes related to hypertrophy (for example development of fibrosis and apoptosis)

Physiological and pathological hypertrophy

Depending on the trigger (stimulus) 2 different forms of hypertrophy may develop: physiological or pathological hypertrophy



*Cardiomyopathy

Cardiomyopathy means ‘heart muscle disease’ and is often used to describe severe myocardial diseases that likely lead to heart failure. It is differentiated into extrinsic and intrinsic cardiomyopathy.

Extrinsic cardiomyopathy:

  • The primary source of the heart disease is outside of the myocardium and thus not due to abnormalities of cardiomyocytes.
  • For example: Ischemia (poor oxygen supply to the heart), substance abuse, diabetes

Intrinsic cardiomyopathy:

  • The heart muscle is weak because of heart cell abnormalities and not due to an external source.
  • For example: genetic/familial diseases, infections (that cause inflammation of the heart muscle)

 

**Fibrosis

Fibrosis consists of two types depended on its location within the heart muscle:

Vascular fibrosis:

  • It enables structural support of the heart around blood vessels.
  • This type of fibrosis is normal and can be found in a healthy heart.

Intercellular fibrosis (also: interstitial fibrosis):

  • It counterbalances the increased workload.
  • In response to stress stimuli cardiomyocytes and fibroblasts are both able to secrete fibrotic factors to stimulate synthesis of fibrosis.
  • Dead cardiomyocytes leave an empty space and fibrosis is 'produced' to connect the remaining heart cells and thereby prevents the heart from falling into pieces

 

***Metabolism

In the heart 60-80% of the energy is supplied by fatty acid oxidation for ATP production, whereas glucose, lactate and ketone provide substrates for the remaining 40-20%. The heart can switch easily between substrates depending on nutritional supply and hormonal status.

Pathological hypertrophy is characterised by a metabolic shift from fatty acid oxidation towards glucose metabolism. This adaptive response allows the heart to produce more ATP per molecule oxygen since ATP production from fatty acids consumes more oxygen than that from glucose.

Overview: Physiological and pathological hypertrophy



Concentric and eccentric hypertrophy

Depending on the morphological changes of the heart, hypertrophy is also differentiated into eccentric and concentric hypertrophy. In eccentric hypertrophy, serial organisation of new sarcomeres results in a bigger chamber volume. The heart wall thickness is not affected or thinner. Concentric hypertrophy shows parallel pattern of sarcomere organisation which leads to increased wall thickness without changing the heart chamber volume. 

 

Note:

Although these definitions are very clear, in nature pure forms of either eccentric or concentric hypertrophy do rarely exist. Often mixed heart types occur where one form is more dominant than the other one.



Literature

Bernardo BC, Weeks KL, Pretorius L, McMullen JR. Molecular distinction between physiological and pathological cardiac hypertrophy: experimental findings and therapeutic strategies. Pharmacology & therapeutics. 2010;128:191-227

Goldberg IJ, Trent CM, Schulze PC. Lipid metabolism and toxicity in the heart. Cell metabolism. 2012;15:805-12.

McMullen JR, Jennings GL. Differences between pathological and physiological cardiac hypertrophy: novel therapeutic strategies to treat heart failure. Clinical and experimental pharmacology & physiology. 2007;34:255-62.

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