Pathogenesis of hypotrophy

The pathogenesis of hypotrophy is complicated. In its basis, despite the diversity of etiological factors, there is a chronic stress reaction - one of the universal nonspecific pathophysiological reactions of the organism that arise in many diseases, as well as with the long-term action of various damaging factors.

The impact of stress factors causes complex changes and a complex reaction of all links of the neuroendocrine-immune system, leading to a cardinal change in metabolic processes and a change in the reactivity of the organism. The intensity of the basic metabolism increases sharply and the energy and plastic material requirements are significantly increased.

Increased protein and calorie needs for pathology in children)

Condition	Clinical manifestations	Need
		Energy,%	Protein,%
Healthy	None	100	100
Light stress	Anemia, fever, mild infection, minor surgical interventions	100-120	150-180
Moderate stress	Musculoskeletal trauma, exacerbation of a chronic disease	120-140	200-250
Significant stress	Sepsis, severe trauma, major surgical interventions	140-170	250-300
Expressed stress	Heavy burns, rapid rehabilitation with hypotrophy	170-200	300-400

The hormonal response to hypotrophy is of a combined nature, but the catabolic orientation of the processes prevails. Increased levels of catecholamines, glucagon and cortisol (powerful catabolic hormones) leads to increased lipolysis and protein degradation with the mobilization of amino acids (primarily from skeletal muscles), as well as the activation of hepatic gluconeogenesis. In addition, the activity of thyroid hormones increases, there is an increase in the level of antidiuretic hormone and development of hyperaldosteronism, which significantly changes the electrolyte balance in the body of a child with hypotrophy. In addition to catabolic, the production of anabolic hormones, in particular HGF, increases, but its concentration rises against the background of low levels of somatomedins and insulin-like growth factor, which completely neutralizes its activity. The level of another anabolic hormone - insulin - is usually reduced with hypotrophy, in addition, its activity is disturbed at the receptor and postreceptor level. Possible causes of insulin resistance in hypotrophy:

• a significant increase in the activity of the control of the hormones;
• high serum level of non-esterified fatty acids against activated lipolysis;
• Electrolyte imbalance in the form of reduced levels of chromium, potassium and zinc.

[1], [2], [3], [4], [5], [6], [7]

Water-electrolyte imbalance

Similar violations of neuroendocrine regulation in children with hypotrophy lead to pronounced changes in the internal environment of the body and body composition. The level of total hydration rises sharply: the water content in the body increases by 20-25% and reaches 89% of the total body weight, while in the norm in children this figure does not exceed 60-67%. The level of hydration is increased due to both intracellular and (to a greater extent) extracellular fluid. At the same time there is a redistribution of fluid in the body: basically the liquid concentrates in the interstitial space, and the bcc decreases sharply (to 50% of the normal level), which is probably due to the development of hypoalbuminemia and a decrease in the osmotic pressure of blood plasma in children with hypotrophy.

Reduction of BCC causes a decrease in renal plasma flow and filtration, which stimulates further increase in the production of antidiuretic hormone and aldosterone and the retention of sodium and water in the body, closing the vicious circle. Children with hypotrophy have a sharp excess of sodium in the body, even in the absence of edema, and sodium accumulates mainly in the intercellular space. The content of total body sodium during hypotrophy increases almost 8 times, while its serum level may remain within normal limits or be slightly elevated. The level of total potassium in the body is reduced to 25-30 mmol / kg, in a healthy child this figure is 45-50 mmol / kg. Reducing the total potassium content is directly related to the inhibition of protein synthesis and sodium retention in the body. At a hypotrophy level of other minerals also decreases: magnesium (on 20-30%), phosphorus, iron, zinc, copper. There is a deficit in most water- and fat-soluble vitamins.

Changes in protein metabolism

The protein metabolism undergoes the greatest changes in hypotrophy. The content of total protein in the body of a child with hypotrophy is reduced by 20-30%. There is a decrease in both muscular (by 50%) and visceral protein pool. The total level of albumin in the body is reduced by 50%, but the extravascular pool of albumin is actively mobilized and returned to circulation. The plasma concentration of most transport proteins decreases: transferrin, ceruloplasmin, retinol-binding protein. The level of fibrinogen and most factors of blood clotting decreases (II, VII, X, V). The amino acid composition of the protein changes: the level of essential amino acids decreases by 50%, the proportion of amino acids with a branched side chain decreases, the valine content decreases 8 times. Due to the inhibition of catabolism of lysine and histidine, their level remains practically unchanged. The content of alanine and other glycogen amino acids in the body is significantly increased due to the breakdown of muscle proteins and an increase in transaminase activity in muscle tissue.

The change in protein metabolism is gradual and adaptive. The body adapts to a significantly reduced flow of protein from the outside, and a child with hypotrophy notes the "conservation" of protein metabolism. In addition to the inhibition of synthesis, there is a retardation of albumin degradation by an average of 50%. The half-life of albumin is doubled. At a hypotrophy efficiency of reutilization of amino acids in an organism grows up to 90-95%, in norm this indicator does not exceed 75%. The enzymatic activity of the liver increases with simultaneous inhibition of production and excretion of urea (up to 65-37% of the normal level). To maintain an adequate level of whey and liver protein pool, muscle protein is actively used. In muscle tissue, inhibition of synthetic activity develops, urinary excretion of creatinine, hydroxyproline, 3-methylhistidine increases.

[8], [9], [10], [11]

Changes in fat metabolism

Due to increased lipolysis in children with hypotrophy, there is a threefold decrease in the volume of adipose tissue. Fats are actively used for the processes of gluconeogenesis, which leads to a decrease in the serum level of triglycerides, cholesterol and phospholipids. Lipoproteins of very low density in blood plasma are practically absent, and the concentration of low density lipoproteins is significantly reduced. Due to the deficiency of apoproteins, lack of lysine, choline and carnitine in the body, synthesis of lipoproteins is disrupted. There is a pronounced deficiency of essential fatty acids. Reduced lipoprotein lipase activity leads to a disruption in the utilization of triglycerides in tissues; overload with tri-glycerides (their content is increased by 40%) with insufficient quantity of low-density lipoproteins negatively affects liver function, which leads to the development of balloon and fatty degeneration of hepatocytes.

[12], [13], [14], [15], [16], [17], [18], [19],

Changes in the gastrointestinal tract

Dystrophic changes in the mucosa of the small intestine lead to atrophy of the villi and the disappearance of the brush border. The secretory function of the digestive glands is disrupted, the acidity of the gastric juice decreases, and the production and activity of digestive enzymes and biliary secretions develop. The barrier function of the intestinal mucosa suffers: the intercellular interaction of enterocytes is disrupted, the production of lysozyme and secretory immunoglobulin A. Is inhibited. As a result of degeneration of the muscular layers of the intestinal wall, intestinal motility is disrupted, general hypotension and dilatation develop with periodic waves of anti-peristalsis. Similar changes in the gastrointestinal tract lead to the development of maldigestion, malabsorption, ascending bacterial contamination of the small intestine, and aggravation of PEM.

[20], [21], [22], [23], [24], [25], [26], [27], [28], [29]

Changes in the cardiovascular system

From the side of the cardiovascular system in children with hypotrophy, there is a tendency to the development of blood circulation centralization, which appears against the background of hypovolemia and manifests itself as a hyperdynamic reaction of the myocardium, pulmonary hypertension, spastic condition of precapillary arterioles, microhemocirculation disturbance with signs of "slug syndrome" in microvessels. Hemodynamic disorders are pathogenetically associated with a chronic stress reaction. With grade I and II hypotrophy, increasing sympathicotonia and increasing activity of the central contour of regulation are noted, at the third degree - "disruption of adaptation", decentralization of regulation with transition to autonomous levels. In severe form of hypotrophy, negative chronotropic effect, tendency to hypotension, bradycardia and a high risk of hypovolemic shock are noted. However, infusion therapy should be used extremely cautiously, because due to high tissue hydration, changes in the microcirculatory bed and the development of sodium-potassium imbalance, the risk of rapid development of cardiovascular failure and sudden death syndrome due to asystole is great.

[30], [31], [32], [33], [34], [35], [36], [37],

Changes in the immune system

In children with hypotrophy, transient secondary immunodeficiency develops (metabolic immunodepression). As a pathogenetic link of the disturbances of immunological reactivity in hypotrophy, metabolic shifts are associated with a pronounced deficiency of plastic material (protein), the instability of carbohydrate metabolism with peaks of transient hyperglycemia, and the switching of metabolism mainly to lipid. Mark violations of both congenital and acquired immunity. Disturbances of congenital immune defense in hypotrophy are the most relevant for microcytic phagocytosis. Due to the impaired maturation of neutrophils and their mobilization from the bone marrow, the number of circulating neutrophils in hypotrophy decreases insignificantly, but their functional activity suffers significantly: the neutriphilic chemotactic and opsonizing activity is suppressed, their ability to lase phagocytic bacteria and fungi is impaired. The function of macrophages suffers insignificantly. Hypotrophy does not lead to significant violations of the complement system, however, when the infection stratifies, the latter is quickly depleted. A decrease in the number and lytic activity of NK cells is noted. On the part of the acquired immunity in hypotrophy, the cellular link of the immune defense is most damaged. Depression of both primary and secondary cellular immune response is noted. The absolute number of T cells decreases, especially CD4, the CD4 / CD8 ratio is disrupted. The level of immunoglobulins is usually unchanged, but these antibodies have low affinity and specificity.

[38], [39], [40], [41]

Kwashiorkor

Kvashiorkor is a special variant of hypotrophy, in its development an essential role is attached mainly to a carbohydrate diet with a sharp deficit of protein food and a layering of secondary infection against a background of malnutrition and disturbed adaptation, which causes a significant restructuring of metabolic processes in the body and, first of all, the protein-synthetic function of the liver . In the liver, the synthesis of visceral transport proteins (such as albumin, transferrin, lipoproteins) is blocked, and the production of acute phase proteins necessary to provide an inflammatory response of the body is activated. Against the backdrop of a deficiency in transport proteins, hypo-oncotic edema and fatty degeneration of the liver rapidly develop. Kwashiorkor, like other forms of hypotrophy, is a manifestation of the classical stress reaction, but its development is accelerated, therefore the homeostasis disorders described above are also valid for this form of hypotrophy, however they are more acute and intense.