Criteria and basic classification
Pathological weight loss is generally divided into two stages depending on severity. Wasting is diagnosed when the adipose tissue deficit is 20–25% or more, and the body mass index (BMI) drops below 18.5 kg/m². Cachexia is already a critical condition. In this state, the BMI drops below 17 kg/m², more than 50% of fat mass is lost, and pronounced loss of muscle and connective tissue begins.
Globally, these disorders are divided into exogenous (caused by a simple lack of food) and endogenous. Endogenous forms, in turn, are classified into primary (hypothalamic) and secondary (symptomatic), which develop against the background of other severe diseases.
Primary (centrogenic) wasting
Primary forms are associated with a failure in central neuroendocrine regulation — the so-called "adipocyte–hypothalamus" system (or lipostat system). The main regulator of energy balance here is neuropeptide Y, which is synthesized in the hypothalamus and normally stimulates appetite.
Causes of this failure can include traumatic brain injury, hypothalamic ischemia, CNS tumors, or severe prolonged psychogenic stress.
Pathogenesis develops through two main mechanisms:
- Suppression of neuropeptide Y synthesis. This often occurs due to excessive synthesis of leptin, which blocks the production of the peptide. No neuropeptide Y means no feeling of hunger.
- Hyposensitization. Peptide synthesis may remain normal, but target cells lose their sensitivity to it.
As a result, trans- and parahypophyseal activation of endocrine glands decreases, metabolism becomes inefficient, and fat accumulation in adipocytes is completely halted.
Secondary cachexia and the role of TNF-α
Secondary (symptomatic) wasting is a consequence of other pathologies: malabsorption syndrome, hypoinsulinemia (type 1 diabetes mellitus), glucocorticoid deficiency, somatostatin or glucagon hyperproduction, and insufficient influence of thymic hormones.
A special place is occupied by the cachectic (cytokine) variant, which is characteristic of oncology and chronic inflammation. A key role in it is played by tumor necrosis factor alpha (TNF-α), also called cachectin. It is produced by macrophages and adipocytes themselves, acting simultaneously in four directions:
- Central action: suppresses the synthesis of neuropeptide Y in the brain.
- Intracellular action: inhibits the activity of protein kinases, completely stopping the process of lipogenesis.
- Vascular action: decreases the activity of the enzyme lipoprotein lipase in the endothelium, preventing fatty acids from being transported into adipocytes.
- General metabolism: potently stimulates catabolic (breakdown) processes and suppresses anabolic reactions.
Anorectic and exogenous variants
The anorectic variant of pathogenesis is characteristic of neuropsychiatric disorders (anorexia nervosa). The risk group mainly includes adolescent girls (16–18 years old) with dysmorphophobia or dysmorphomania — a critical, distorted perception of their body as overweight. The triggering factor is repeated emotionally negative stress responses. They lead to excessive production of anorexigenic substances (serotonin, cholecystokinin), an increase in cachectin levels, and a decrease in the synthesis of neuropeptide Y. The result is prolonged episodes of food refusal.
Exogenous wasting develops with a physical food deficit (starvation). Two parallel processes are triggered in the body: depletion of fat stores (lipolysis) and general metabolic disorders. Insufficiency of biological oxidation occurs, plastic processes (synthesis of proteins and cellular structural components) are suppressed, which ultimately leads to severe multiple organ failure.
Briefly: answers to topical questions
What specific changes in protein metabolism and nitrogen balance are observed in cachexia?
In wasting and cachexia, the following changes in protein metabolism and nitrogen balance are described:
- Negative nitrogen balance — associated with increased catabolism of endogenous proteins and intensified proteolysis.
- Decreased protein assimilation — leads to hypoalbuminemia, a decrease in plasma oncotic pressure, and the formation of edema.
- Decreased plastic processes — manifested by insufficiency of tissue regeneration processes and slowed growth and development of the body.
- In cancer cachexia, an increase in the level of protein metabolism in the tumor tissue is noted; the tumor acts as a nutrient "trap", leading to starvation of the body.
What is the role of the hormone leptin in the physiological regulation of energy balance?
In the physiological regulation of energy balance, leptin reduces appetite and increases the body's energy expenditure.
Main functions of the hormone:
- Suppression of the feeling of hunger — leptin normally suppresses the formation of the appetite stimulant (neuropeptide Y).
- Activation of the satiety center — neurons in the ventromedial nucleus of the hypothalamus serve as a key target for the hormone's receptors.
- Stimulation of energy expenditure — increases overall energy expenditure.
- Growth factor function — stimulates angiogenesis, proliferation of hematopoietic cells and pancreatic beta cells.
The level of the circulating hormone, which is synthesized in adipocytes, is directly proportional to the amount of fat mass.
To remember the 4 effects of TNF-α (cachectin), use the "Four S" rule: Suppresses appetite (blocks neuropeptide Y in the brain), Stops lipogenesis (inside the cell), Sascular block (prevents fats from entering tissues), Spawns catabolism / burns reserves (general catabolism).
Class and exam questions
What is the difference between wasting and cachexia?
Wasting is a fat deficit from 20% and BMI < 18.5. Cachexia is the extreme stage: loss of more than 50% of fat, BMI < 17, and pronounced loss of muscle and connective tissue.
Which hormone suppresses neuropeptide Y synthesis in primary wasting?
Excessive leptin synthesis leads to the suppression of neuropeptide Y production in the hypothalamus. This deprives the patient of the feeling of hunger.
What endocrine pathologies cause secondary wasting?
These include hypoinsulinemia (type 1 diabetes mellitus), glucocorticoid deficiency (adrenal insufficiency), somatostatin hyperproduction, and increased glucagon synthesis.
What else to study on this topic
- Mechanisms of development of multiple organ failure in exogenous starvation.
- The role of serotonin and cholecystokinin in the pathogenesis of anorexia nervosa.
- The effect of thymic hormone deficiency on body weight regulation.
- Trans- and parahypophyseal regulation in hypothalamic wasting.
- Dysmorphomania as a triggering factor for eating disorders.
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