Neurotransmitters acting at the installation point during fever
There are good reasons to assume that the prostaglandin is a neurochemical mediator that increases the temperature of the “set point” of the hypothalamic preoptic region when exposed to the endogenous pyrogen. Minimal doses of prostaglandins E1 and E2 when they are injected into the brain of laboratory animals quickly cause fever. Parenterally administered prostaglandins are typically pyrogenic only in large doses, possibly due to their inactivation in the lungs. However, febrile reactions were noted in patients after injections of prostaglandin E2; described severe pyrexia after intravaginal administration. An increase in prostaglandin concentration is found in the brain of laboratory animals during fever. Inhibition of prostaglandins synthetase of the CNS (acetylsalicylic acid or paracetamol) leads to a decrease in body temperature during fever, but does not affect the normal temperature.
This observation confirms the view that the value of prostaglandins in the preoptic region of the hypothalamus is limited by the temperature rise of the “set point” during fever, and in normal conditions they do not play a role. The significance of mediators such as cyclic AMP and monoamines is unclear.
The development of fever with increasing temperature “set point” of the preoptic region of the hypothalamus includes a complex series of effector steps. The metabolic activity increases and oxygen tension increases, primarily caused by an increase in muscle tone, which can sometimes turn into trembling. There is also a general increase in metabolic rate, regardless of the increase in skeletal muscle activity.
After the introduction of bacterial endotoxin, the increase in metabolic activity is the earliest thermogenic effect. Soon after, vasoconstriction of the skin vessels develops, which leads to a decrease in its temperature and a decrease in heat loss through radiation, conduction, and convection. This is especially noticeable in the limbs. Slowing down of the blood circulation also helps to reduce perspiration. A piloerest, which serves as a symbol for a modern person more than a method of preserving heat, is a rudimentary echo of the past, when hair was an effective thermal protection for a person. A decrease in skin temperature is subjectively perceived as a sensation of cold, and the patient tries to warm up, despite the rise in internal body temperature. The child curls up, which leads to a decrease in the area of the open surface of the body, and tightly pulls the blanket over himself. Cooling of the skin also includes sensory feedback to the preoptic region of the hypothalamus, which further causes an increase in heat production.
Often, the onset of fever, especially sudden, is accompanied by chills – a strong sensation of cold, combined with intense trembling. Although chills are considered typical of purulent infections and bacteremia, its diagnostic value was less than previously thought. Chills can occur with viral and bacterial infections, as well as with non-communicable diseases such as lymphoma. It is important to remember that antipyretic drugs can cause chills by reducing body temperature to normal levels. Such side effects of these drugs should not be confused with the chills caused by the underlying disease.
The body temperature rises until it reaches the reference temperature of the “set point”. At the same time, heat production comes to equilibrium with heat transfer, although at a higher temperature than normal. The patient feels a surge of heat, or at least no longer suffers from cold. The skin temperature increases, reflecting the high temperature of the “core” and the increased metabolic rate. The sharp increase in heat production of skeletal muscles located under the skin also contributes to a further increase in skin temperature. In a clinical examination, it was found that the skin was hot in 60% of children with fever.