by Alberto J. Muniagurria

Fever is the elevation of body temperature above the normal range of diurnal variations and induced disease. It occurs due to a rearrangement of the thermoregulatory center, which is located in the hypothalamus.

Other causes of elevation of body temperature have been described that do not have the same mechanism or meaning.

The hyperthermia would be caused by an increase in body temperature due to extracorporeal causes; in this case there are no variations in the thermoregulatory center, and in this sense the best example is the clinical picture known as "heat stroke". Some authors include the term hyperthermia as fever, but for a better understanding it is convenient to separate the two concepts.

The hypothalamic fever would be the result of traumatic injury, ischemic, neoplastic or an intrinsic alteration of the hypothalamus. In these cases, the clinical picture is accompanied by other hypothalamic disorders (diabetes insipidus, etc.).

Fever is linked to the presence of disease from 450 years before Christ, initially believed to have some relationship with typhoid epidemics.

In the normal individual the body temperature is kept in balance due to mechanisms of production and heat loss that are permanently under the control of physiological systems. The greater production of heat is generated fundamentally through muscular activity, to which are added the permanent combustion of nutritional substances and the metabolic activity of the different apparatuses and systems, and to a lesser extent by exogenous sources such as ambient temperature. Heat loss, in turn, is normally caused by radiation and water evaporation through the skin surface and the respiratory tract.

The central and peripheral factors involved in regulating body temperature are numerous and complex. In the normal individual, the temperature varies at different times of the day. The presence of a daily circadian rhythm or daily temperature variation that has no relation to the inhabited geographic region or to climatic changes has been reliably demonstrated through numerous studies.

The thermal movement is 0.6 ° C in the twenty-four hours, reaching the lowest level in the morning and the maximum point between 16 and 18 hours. This change is more marked in young women, and the difference between the highest and lowest temperatures recorded is most pronounced in children. The circadian rhythm is unique and characteristic of each individual, and difficult to modify. When fever occurs, this rhythm is altered, but when normal values ​​are restored, the variations that existed in the usual circadian rhythm are resumed. This always happens, but it can be modified in the event that there is a hypothalamic alteration that modifies the usual rhythm.

All of the above is important because, if the circadian rhythm of an individual is known, it is possible to recognize, in its absence, low-grade feverish states or to guide the diagnosis of feigned or patient-induced fever.

Increasing temperature can be beneficial on some occasions, such as in the treatment of rheumatoid arthritis. Thus, the patient with chronic brucellosis can benefit from the presence of fever.

On the other hand, the lack of fever can be a disadvantage, which can be observed in diabetic patients or infected elderly people. This is considered a sign of weakness despite the fact that the relationship between temperature rise and the body's defense mechanisms is not clearly known. When the temperature rises, the metabolism accelerates with the consequent increase in the consumption of oxygen, nitrogenous components, salt and water. During the feverish period the appetite is lost and the feeding is irregular due to the feeling of discomfort.


Animal studies show that there is a zone in the brain that controls body temperature, called the thermoregulatory center. It is located in the preoptic area of ​​the hypothalamus near the floor of the third ventricle and, like other minor brainstem centers, it contains a type of thermosensitive cells which, upon receiving a message from a stimulating or pyrogenic substance, would increase the concentration of monoamines and prostaglandins, especially series E.

Pyrogenic substances have been recognized as fever induction factors for years, and the most studied of these is a product of bacterial origin called endotoxin. This lipoprotein would be found in gram-negative bacteria. In turn, other fever-inducing substances are described, such as etiocholanolone, which is a metabolic derivative of androgens, and substances that are present in incompatible blood. All these substances are recognized as exogenous pyrogens, and do not share a common biological or chemical structure with each other. Furthermore, they do not act directly on the hypothalamus but through an endogenous pyrogen.

Endogenous pyrogen, also called leukocyte pyrogen, occurs in leukocytes, especially monocytes, and also in liver Kupffer cells, and in alveolar macrophages and sinusoidal spleen cells  , but not lymphocytes. The production of this substance in vitro by lymphoma cells, leukemia cells and renal carcinomas is described. It is a low molecular weight protein that acts at the level of the hypothalamic thermostat producing its rearrangement, in febrile patients it has not yet been detected. According to Woiff, this is due to its very low plasma concentration and its high lability in the blood. It occurs at the time of the stimulus, which would induce the synthesis of a new messenger RNA before the endogenous pyrogen is released into the circulation.

Normally the thermoregulatory center keeps the internal temperature controlled at 37 ° C. When fever occurs, the hypothalamic thermostat rearranges itself, according to Wolf, from 37 ° to 39 °. When this occurs, signals are emitted to the posterior hypothalamus and from it to the body to decrease peripheral losses and increase heat production. Peripheral loss is decreased or heat is conserved by reducing peripheral blood circulation due to cutaneous and subcutaneous cellular vasoconstriction; therefore the sensation of cold takes place, which induces the tremor or chill. These muscle contractures increase the production of heat, which raises the temperature of the blood to match that set by the thermostat. Blood is derived centrally and thus raises body temperature. There is an increase in metabolic activity during fever states; When the temperature returns to normal values, it does so by increasing the heat loss. This is achieved by increasing the circulation of the peripheral tissues by vasodilator and the consequent sweating, which allows heat to dissipate through the skin.

In children, when the temperature quickly reaches values ​​of 39° - 40° C, sometimes with the contribution of a caring mother who tries to clothe him, convulsive movements may occur. In these cases it is not yet defined if any injury should previously exist. cerebral. The patient who develops febrile seizures would lower their threshold for new episodes.

Fever as a reason for consultation

Normally, the axillary temperature ranges between 36 and 37 ° C, while the oral and rectal temperatures reach up to 37.5 ° C. Fever is a frequent reason for consultation and, as pain, especially at night, awakens anxiety in the patient and his family. The perception of elevated temperature varies significantly from person to person. There are individuals who can feel variations in body temperature of half a degree.

It is rarely the only manifestation of disease, since it is generally accompanied by other symptoms. The patient complains of hot or cold sensation, decay, headache, back pain, joint pain and generalized myalgia. The link between these sensations and the rise in temperature is not known for sure.

The patient should be questioned about the onset of fever, the type, the factors that precipitate or alleviate it (acetylsalicylic acid, due to its inhibitory action on prostaglandins, inhibits fever, but not the hyperthermia). The physician should ask about its duration and severity and about the existence of associated symptoms and signs such as sweats, chills, weight loss, appetite, gastrointestinal, genitourinary manifestations, edema, pain, skin lesions, changes in urine and fecal matter, etc.

Questions should be asked about predisposing factors and other triggers such as history of previous infections, trauma, medications (frequent cause of fever), toxics, alcohol, tobacco, family history of fever, diabetes, age, social status and residence must be taken into account.

The chill frequently accompanies fever. It is important to differentiate the chill or shivers, with marked trembling of the body and chattering of teeth, from the feeling of cold in the back with slight tremor. The first is a typical presentation of episodes of bacteremia, while the second is seen in viral charts. Fever can be accompanied by delusions, especially in the elderly or debilitated patients, and it is common for there to be restlessness or nervousness. In children, as noted above, rising temperatures can trigger seizures. This has been described in patients who have a family history of epilepsy.

When fever is present above 38 ° C for two or more weeks with no apparent cause on questioning, physical examination, and studies conducted after a week of evaluation in a full hospitalization regimen, prolonged fever of unknown origin.

Despite being well described and occasionally found, the types of fever listed below are not, by themselves, of general diagnostic value. The etiological causes can be superimposed on its presentation. Thus, for example, viral diseases can present with fever of the hepatic type.

Intermittent fever is referred to when the temperature drops to normal values ​​at any time of the day. When the variation between the peak and the descent is very fast, it is called hectic or septic fever .

Classically it was considered as the form of presentation of internal suppurations, lymphomas or miliary tuberculosis. The remitting fever is one that falls during some time of the day, but without returning to normal values, while the sustained fever is the one that persists without significant daily variations. Recurrent fever , in turn, is the name used when periods of fever appear between one or more days of normal temperature; malaria has this type of fever, called tertian or quartan. The fever Pel-Ebsiein, which can be seen in patients with Hodgkin's disease, is characterized by an increase in temperature of 4 to 10 days duration separated by periods of 4 to 10 asymptomatic days.

Differential diagnosis of fever

In the vast majority of patients, fever is secondary to infectious processes , often of viral origin. In these viral conditions, the process lasts a few days and there is not much that can be done from the diagnostic and therapeutic point of view, although lately conditions of carrying out in the laboratory diagnostic tests for specific viruses. Although infections are the most frequent cause of fever, many non-infectious diseases can present with temperature rises, for example major injuries , neoplastic diseases, hemolytic crisis; vascular accidents such as pulmonary embolisms, myocardial infarction and strokes, autoimmune diseases such as collagen or drug-induced diseases, and metabolic disorders such as gout, hypertriglyceridemia, and thyroid crisis.

Prolonged fever of unknown origin

One of the most complex problems in medical practice is feverish symptoms that last for weeks or months without a clear diagnosis. The list of processes that produce it is very large. In a study carried out by the author, an incidence of 51% of infections, 15.6% of neoplastic diseases and 4.4% of collagen diseases was found in 45 patients, with tuberculosis, bacterial endocarditis, and sepsis being more frequent. and respiratory, urinary, and abdominal infections.

Among the neoplasms most commonly associated with prolonged fever of unknown origin, Hodgkin's disease, lymphomas, hypernephromas, preleukemias, and atrial myxoma may be mentioned. Disorders of collagen include disseminated lupus erythema cough, rheumatoid arthritis, and temporal arteritis. Drugs can frequently induce these symptoms, as occurs, for example, with penicillin and alpha-methyldopa. type 1 hyperlipidemia.

Simulated fever, in turn, is seen in young women, hysterical and linked to the medical profession.

A habitual hyperthermia is also described, with prolonged fever ranging from 37.3 to 37.7% in young female patients who complain of tiredness, insomnia and general pain, and in such cases the diagnosis is by exclusion.

In the laboratory of cases of prolonged fever of unknown origin, it is common to find an elevation of the erythrosedimentation due to an increase in fibrinogen, haptoglobins and ceruloplasmines, which can be demonstrated by the elevation of alpha-2-globulins in the proteinogram by electrophoresis. On the blood count microcytic and hypochromic anemia may be found, perhaps associated with the low iron levels that accompany prolonged febrile processes. The white blood cell count may be elevated, with a predominance of neutrophils in bacterial infections, and decreased in some bacterial infections, such as tropical fever and viral processes.