27.13. What mechanism lay on the base of development of the heart’s hypertrophy?
During the prolonged loading on the heart develops its hyperfunction which in time causes the structural changes in the heart the hypertrophy of myocardium.
The most proved theory which can explain the mechanisms of the transferring the hyperfunction of heart into hepertrophy is the F. Meerson’s conception (scheme 121).
Scheme 121 the mechanism of compensatory hypertrophy of myocardium:
An injury the reducing of ATP formation
Loading: the increase of ATP using
Regulators of transcription
The increase of transcription and transmission
The increase of proteins biosynthesis
Hypertrophy
According to this concept the main chain which links the increase of cell’s function with the work of its genetic apparatus is the increase of
,
where [ATP], [P], [АТФ]
– are the concentrations of ADP inorganic phosphate and ATP in the
cytoplasm of cells.
AP normally increases in two cases:
a) during the intensified using of ATP – it is always observed during the increase of functional lading on cells (during their hyperfunction);
b) during the breaches of ATP forming which is characteristic for different types of cells’ injury.
The increase of ПР indicator causes the appearance of substances in cells – regulators of transcription which effecting on the genom of cell, increase the synthesis of information RNA on the matrix of genes which codify the structure of functionally important cell’s proteins including contractility proteins and ferments. The whole line of metabolites among which c-AMP, creatin, ions of Mg2+, polyamines (spermin, spermidin) and so on.
So, the development of hypertrophy of the heart can be described in such sequence of processes: the increase of loading on heart (hyperfunction)→ an increase of use of ATP which exeed’s the intensity of its resynthesis → the increase of phosphorilating potential → appearance or increase of concentration of substances (regulators of transcription) in cells → the increase of intensity of RNA’s synthesis and processes of transmission in ribosomes → the increase of structural, functional proteins and proteins-ferments’ biosynthesis → the increase of myocardium mass, its hypertrophy.
27.14. What phases can be distinguished in the process of development of compensatory hypertrophy of the heart? Give their characteristics.
According to dynamics of metabolism, the structures and functions of myocardium in the development of compensatory hypertrophy of heart there are main phases:
1. Damageable phase. It develops directly after the increasing of lading and characterized by combination of pathological changes in the myocardium (disappearance of glycogen, the reduction of creatinphosphate level, the reduction of intracellular potassium content and the increase of sodium content, activation of glycolysis, accumulation of lactate with mobilization reserves and the organism in whole. At this phase increase the lading per unite of muscles’ mass, intensity of structures’ functioning (ISF), undergoes quicker, during weeks, increase of heart’s mass because of the intensified protein’s synthesis and the thickening of muscular fibers.
2. The phase of finished hypertrophy and comparatively steady hyperfunction. At this phase the process of hypertrophy is finished, the mass of myocardium is increased to 100 – 120 % and does not increase any more, ISF became normal. Pathological changes in metabolism and structure of myocardium don’t show them-selves, the use of oxygen, the formation of energy, the content of макроэргических joining do not differ from normal. Hemodynamic breaches became normal. Hypertrophied heart adapted to new conditions of lading and compensates them during a long time.
3. The phase of gradual exhaustion and progressive cardiosclerosis. It is characterized by deep metabolic and structural changes which gradually accumulate elements which in form energy and contractivity elements of myocardium cells. The part of muscular fibers die and they are replaced by connective tissue, ISF again increases. The regulatory apparatus of the heart upsets. The progressive exhaustion of compensatory reserves leads to the appearance of chronic insufficiency of heart and later to circulation’s insufficiency.