Pathogenesis of true fever
The initiation of the febrile response is triggered by pyrogens (most commonly infectious agents). Under their influence, activated leukocytes begin to release cytokines — interleukins (IL-1, IL-6) and tumor necrosis factor (TNF).
These molecules act as stimulators for the production of prostaglandin E2 (PGE2). It is PGE2 that acts on the hypothalamic thermoregulatory center, shifting its "set point" to a new, higher level. To achieve this goal, the body employs two mechanisms:
- Decreased heat loss: there is a sharp spasm of the peripheral vessels of the skin and subcutaneous tissue (vasoconstriction).
- Increased heat production: tissue metabolism is activated. In newborns and infants, non-shivering thermogenesis plays a crucial role here — the breakdown of brown adipose tissue, which accounts for up to 5% of their body weight.
Caution: neurogenic temperature elevation differs from true fever in that the shift in the "set point" occurs without the involvement of cytokines. It is associated with direct damage to hypothalamic neurons (e.g., in traumatic brain injury or ischemia).
Protective value and consequences of untreated fever
Temperature elevation is adaptive in nature. It serves as a marker of the pathological process and powerfully stimulates the immune response: the activity of polymorphonuclear leukocytes (neutrophils) increases, phagocytosis is enhanced, and the synthesis of endogenous interferon is stimulated. In addition, high temperature exerts a direct antimicrobial effect, creating an unfavorable environment for the survival of heat-sensitive pathogens.
However, intense hyperthermia (above 39 °C) sharply increases basal metabolism and tissue oxygen demand. In the absence of adequate therapy and with the progression of the process, dangerous complications develop:
- Initial stage: general weakness, fever, formation of painful indurations (infiltrates).
- Abscess formation: formation of a purulent cavity against the background of a temperature of 38–40 °C and pronounced sweating.
- Sepsis (generalization): massive systemic inflammation with recurrent chills and a critical deterioration in condition.
Clinical variants: "pink" and "pale" fever
Depending on the adequacy of vascular tone, two types of febrile response are distinguished.
"Pink" (red) fever is a favorable type of hyperthermic reaction. Here, a balance is maintained between heat production and heat loss. Peripheral vasodilation corresponds to the level of heat production, so the skin is warm, pink, and moderately moist. Tachycardia is proportional to the temperature, and physical cooling methods (sponge baths) have a good effect.
"Pale" fever (hyperthermic syndrome) is a dangerous state of uncoupling between heat production and heat loss. Due to marked spasm of peripheral vessels, heat loss drops sharply against the background of massive heat production. Centralization of blood circulation occurs, and tissue hypoxia and metabolic acidosis progress. Symptoms of "pale" fever: pale skin with a mottled pattern, muscle shivering, severe chills, cold hands and feet, acrocyanosis (bluish lips and nails).
Difference between fever and hyperthermia
It is important to differentiate fever from heat-related illnesses (hyperthermia). The main difference is that in hyperthermia, the hypothalamic "set point" remains normal.
Temperature rises due to a gross imbalance: either there is too much exogenous heat (heat stroke), thermoregulatory mechanisms are blocked (atropine poisoning), or there is endogenous hyperproduction of heat (hyperthyroidism). The thermoregulatory center attempts to lower the temperature, but physiological mechanisms cannot cope.
Note: physiological temperature fluctuations do not require correction. They are associated with a temporary acceleration of metabolism due to circadian rhythms, digestion of a heavy meal, or intense physical exercise.
"Pale means trouble, pink means we're working." Pale fever indicates vasospasm and hypoxia, while pink indicates normal heat dissipation.
Class and exam questions
Is it always necessary to bring down a high temperature?
No. Intensive antipyretic therapy is required only when hyperthermia begins to exert a damaging effect. Fever itself is adaptive and activates immunity.
How do infants increase heat production?
In early childhood, the most important mechanism is non-shivering thermogenesis. It is provided by the active metabolism of brown adipose tissue, which accounts for about 5% of body weight in infants.
Why are physical cooling methods ineffective in "pale" fever?
Due to peripheral vasospasm. Wiping with cold water will only increase skin vasoconstriction, reduce heat loss even further, and exacerbate internal organ overheating.
What else to study on this topic
- Malignant hyperthermia: mechanism of development during inhalation anesthesia
- Pathophysiology of febrile seizures in young children
- Specifics of neurogenic hyperthermia in neuroinfections and CNS trauma
- Differential diagnosis of causes of low-grade fever
- Mechanisms of tissue hypoxia in hyperthermic syndrome
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