Water-Electrolyte Balance and Kidneys
The dynamics of water metabolism and renal function are strictly tied to the stages of the febrile response. Direct damage to renal tissue typically does not occur; all shifts are secondary and regulatory in nature.
- First stage (st. incrementi): Hypohydration develops. Due to the activation of sympathoadrenal influences, filtration pressure increases, which raises diuresis. Additionally, fluid is lost due to increased sweating. Ions such as $Na^+$, $Ca^{2+}$, and $Cl^-$ begin to accumulate in excess within tissues.
- Second stage (st. fastigii): Hyperhydration sets in—the total body water volume increases. The body retains water due to the enhanced synthesis and release of corticosteroids (primarily aldosterone) and antidiuretic hormone (ADH). These hormones activate water reabsorption in the renal tubules. Diuresis decreases, while excess tissue ions persist.
- Third stage (st. decrementi): Aldosterone and ADH levels decline. A massive excretion of accumulated ions and water occurs via sharply increased diuresis and profuse sweating.
Nervous and Endocrine Regulation
The endocrine system acts as a crucial component of adaptation mechanisms as well as a target for pathogenic influences. The synthesis of liberins, ACTH, TSH, and ADH increases. Blood concentrations of glucocorticoids, catecholamines, insulin, and thyroid hormones (triiodothyronine $T_3$ and tetraiodothyronine $T_4$) rise. The levels of local bioactive substances—kinins, prostaglandins (PGs), and leukotrienes—also change.
The nervous system reacts to most pyrogens (infectious, non-infectious, leukocytic cytokines) functionally; they do not exert a specific damaging effect on neural structures. Nonspecific clinical manifestations include:
- Headache, depressed mood, and irritability.
- Sleep disturbances (somnolence or, conversely, insomnia).
- Confusion, lethargy, and sometimes hallucinations.
- Increased sensitivity of the skin and mucous membranes (hyperesthesia), along with altered pain perception.
- Reflex abnormalities and the development of neuropathies.
Cardiovascular and Respiratory Systems
Hemodynamics and external respiration are restructured to meet new metabolic demands.
- Cardiovascular system: During the first stage and the beginning of the second stage, the effects of the sympathoadrenal, hypothalamic-pituitary-adrenal, and thyroid systems dominate. Tachycardia, hypertensive responses, and the centralization of blood flow occur. Arrhythmias are frequently recorded. In uncomplicated courses, these changes resolve by the end of the second stage (aggravating in complicated cases), and during the third stage, deviations gradually disappear.
- Respiration: Due to fluctuations in metabolic intensity, blood pressure deviations, and impaired blood oxygenation, pH drops (acidosis develops) and the partial pressure of carbon dioxide ($pCO_2$) rises. To compensate, alveolar ventilation volume increases significantly. Respiratory rate and depth may exhibit unidirectional or bidirectional deviations (e.g., increased depth with decreased rate). Gas exchange in the lungs is activated due to increased pulmonary blood perfusion against the background of blood flow centralization.
Digestive System
The digestive system is a target for pathogenic factors but does not participate directly in the mechanisms of fever development. Due to intoxication, the direct effect of high temperature, and sympathoadrenal activation, total functional suppression occurs:
- Appetite decreases (anorexia) and salivation drops, causing dry mouth.
- Secretory, motor, and digestive functions of the stomach and intestines are suppressed.
- Pancreatic enzyme production and bile secretion are inhibited.
The clinical consequences of this dysfunction include impaired food absorption and digestion, flatulence, constipation, and potential nausea and vomiting.