A fever is an elevated body temperature above the normal range, typically caused by the body's response to an infection, illness, or other internal disturbances. Fever is part of the body's defense mechanism to combat infections. That is, fever is an immune response caused by the release of various mediators, or signaling molecules, by cells in response to infection or inflammation. These mediators can trigger a variety of reactions in the body that ultimately result in an elevation in body temperature. Here are some examples of mediators involved in fever:
1. Prostaglandins: Prostaglandins are lipid molecules produced by cells that have many effects on the body, including increasing the production of heat-producing hormones and causing vasoconstriction in the body, resulting in decreased heat loss. Prostaglandin E2 (PGE2) is one of the key players in fever pathophysiology. PGE2 is a type of lipid compound that has a wide range of effects on different cells and tissues in the body, including inducing fever. PGE2 is produced by glial cells in the brain, especially in the hypothalamus, which is the part of the brain that regulates body temperature. When PGE2 is produced in response to inflammation or infection, it triggers the hypothalamus to increase the temperature set point, which results in an increase in body temperature.
The exact mechanism by which PGE2 triggers the hypothalamus to increase the temperature set point is not fully understood, but it is believed to involve the activation of certain neurons in the hypothalamus that are responsible for regulating body temperature. This activation results in an increase in the production of heat-producing hormones, such as thyroid hormones, as well as an increase in the production of sweat.
Additionally, the immune system plays an important role in fever pathophysiology. When the body detects an infection or inflammation, immune cells, such as monocytes and lymphocytes, are activated. This activation results in the release of compounds, such as cytokines and eicosanoids, which have a range of effects on the body, including inducing fever.
2. Cytokines: Cytokines are signaling molecules produced by immune cells in response to infection. There are many different cytokines involved in fever, but IL-1, IL-6, and TNF-alpha are particularly important. These cytokines can trigger a variety of reactions in the body that ultimately result in an increase in body temperature.
3. Leukotrienes: Leukotrienes are lipid molecules involved in many different biological processes, including inflammation and tumor cell growth. They can also be involved in fever by causing vasoconstriction in the body and reducing heat loss.
4. Complement system: The complement system is part of the immune system that attacks and destroys foreign invaders such as bacteria and viruses. When activated, the complement system can release various proteins that can trigger a range of reactions in the body, including fever.
Common causes of fever:
1. Infections: Bacterial, viral, fungal, or parasitic infections are the leading causes of fever. Examples include the flu, common cold, urinary tract infections, pneumonia, and COVID-19.
2. Inflammatory Conditions:Conditions like rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus can lead to fever as part of their inflammatory response.
3. Heat-Related Illness:Exposure to high temperatures, heat stroke, or severe dehydration can result in fever.
4. Medications: Some medications may cause fever as a side effect. This is relatively rare but can occur.
5. Vaccinations:Fever is a common side effect of some vaccines, especially in the first 48 hours after vaccination.
6. Autoimmune Diseases:Conditions like lupus and vasculitis can cause fever as part of their autoimmune response.
7. Cancer: Some cancers, especially blood cancers like leukemia and lymphoma, can cause fever as a symptom.
8. Inflammatory Disorders:Conditions like Kawasaki disease in children or adult-onset Still's disease can cause persistent or recurrent fever.
9. Trauma or Tissue Injury: After surgery or a serious injury, a mild fever might occur as part of the body's natural healing process.
10. Unknown Causes:In some cases, the cause of fever might not be immediately apparent, and it may require further investigation.
MECHANISM OF FEVER
The mechanism of fever involves a complex physiological response by the body to pathogens or other factors that trigger the immune system's defense mechanisms. Here's a simplified explanation of the key steps involved:
1. Pathogen Detection:When the body is exposed to an infection, such as a virus or bacteria, immune cells (macrophages and white blood cells) detect the presence of these pathogens. They recognize specific molecules on the surface of these invaders, called antigens.
2. Release of Pyrogens:Immune cells respond to the pathogens by releasing signaling molecules known as pyrogens. Pyrogens include various cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF). These pyrogens travel to the hypothalamus in the brain.
3. Hypothalamic Response:The hypothalamus is the body's internal thermostat, controlling body temperature. When pyrogens reach the hypothalamus, they trigger it to reset the body's "set point" for temperature. The normal body temperature, which is around 98.6°F (37°C), is temporarily raised.
4. Generation of Prostaglandin E2 (PGE2): One of the key actions of pyrogens in the hypothalamus is to stimulate the production of prostaglandin E2 (PGE2). PGE2 is a lipid molecule that plays a central role in the fever response.
5. Elevation of Body Temperature: PGE2 acts on the hypothalamus, causing it to reduce heat loss mechanisms (vasoconstriction of blood vessels and shivering) and increase heat production (muscle contractions). These changes raise the body's temperature to the new "set point."
6. Fever: The result is an elevated body temperature, which we recognize as a fever. This increased body temperature is believed to help the immune system function more efficiently. It can inhibit the growth of some pathogens, increase the activity of immune cells, and enhance the overall immune response.
7. Resolution: As the infection is fought off and the immune response subsides, the production of PGE2 decreases, and the hypothalamus resets the body's temperature set point back to normal. This leads to a reduction in fever, often accompanied by sweating and a feeling of cooling down.
Fever can present in various patterns patterns:
1. Continuous Fever:In this pattern, the fever remains elevated without significant fluctuations, typically less than 1°C (1.8°F) change throughout the day.
2. Remittent Fever: With a remittent fever, the body temperature remains elevated, but it fluctuates more than 1°C (1.8°F) throughout the day. The temperature may decrease but doesn't return to normal.
3.Intermittent Fever: In this pattern, fever comes and goes, with alternating periods of elevated temperature and normal temperature. An example is the fever in malaria, which often follows a 48-hour or 72-hour cycle.
4. Pel-Ebstein Fever: A cyclical fever pattern seen in Hodgkin's lymphoma, where the fever recurs at regular intervals, typically every 1-2 weeks.
5. Sustained or Continuous Fevers: These fevers remain elevated over a more extended period and can be associated with various chronic infections or inflammatory conditions.
6. Relapsing Fevers: These fevers come and go, with relatively short fever-free intervals between episodes. Diseases like relapsing fever (caused by spirochete bacteria) exhibit this pattern.
7. Undulating Fevers: This pattern involves fluctuating fever with gradual increases and decreases in temperature over several days. Conditions like brucellosis can cause this type of fever.
8. Hectic Fever: Characterized by rapid and irregular temperature fluctuations, often associated with severe sepsis or endocarditis.
9. Step-Ladder Fever: In this pattern, the fever increases for several days, then plateaus for a period, followed by another increase. It may be seen in conditions like typhoid fever.
10. Pulsus Alternans: Not a fever pattern per se, but a physical finding where there is an alternating strong and weak pulse, sometimes associated with severe illnesses.
TEMPERATURE IN FEVER
Normal Body Temperature:Normal body temperature for adults is around 98.6°F (37°C).It can vary slightly between individuals but is generally within the range of 97°F to 99°F (36.1°C to 37.2°C).
Fever: A fever is often defined as a body temperature above 100.4°F (38°C).Fevers can be caused by various infections, inflammation, or other medical conditions.
Hyperpyrexia: Hyperpyrexia is an extremely high body temperature, often above 106°F (41.1°C).This is a medical emergency and requires immediate attention.
Hypothermia: Hypothermia occurs when the body temperature drops below 95°F (35°C).It can be life-threatening and requires prompt treatment.
CLASSIFICATION OF FEVER
Fever can be classified in several ways, depending on the criteria used for classification. Here are common classifications of fever:
1. By Duration:
- Acute Fever:Lasts for a short duration, typically less than seven days.
- Subacute Fever:Lasts for one to two weeks.
- Chronic Fever: Persists for more than two weeks, often with less intense temperature elevations.
2. By Temperature Pattern:
- Intermittent Fever: Comes and goes, with alternating periods of elevated temperature and normal temperature.
- Remittent Fever:The body temperature remains elevated but fluctuates more than 1°C (1.8°F) throughout the day.
- Continuous Fever:Fever remains elevated without significant fluctuations.
- Relapsing Fever: Fever episodes are interspersed with fever-free intervals.
- Undulating Fever:Involves fluctuating fever with gradual increases and decreases in temperature.
3. By Clinical Presentation:
- Low-Grade Fever: Characterized by a mild elevation in body temperature, usually not exceeding 100.4°F (38°C). It's often associated with chronic conditions or low-grade infections.
- High Fever: Refers to a fever with a significant temperature elevation, often above 103°F (39.4°C).
4. By Cause:
- Infectious Fever: Caused by infections, including bacterial, viral, fungal, or parasitic.
- Non-Infectious Fever: Caused by factors other than infections, such as inflammatory conditions or medication side effects.
5. By Fever Patterns in Specific Diseases:
- Some diseases have characteristic fever patterns, such as the cyclical fevers in malaria or the intermittent fever seen in certain types of tuberculosis.
6. By Clinical Manifestations:
- Some fevers are classified based on their clinical symptoms and manifestations, such as "hectic fever" associated with rapid and irregular temperature fluctuations.
7. By Origin or Location:
- Febrile states can be classified as "central" (fever originates in the brain's hypothalamus) or "peripheral" (fever results from processes outside the hypothalamus).
8. By Recurrence:
- Some conditions, like Familial Mediterranean Fever (FMF), are characterized by recurrent fever episodes.
Chanting pathology
"Pyrogens rise, hypothalamus fires,
Prostaglandins spark, setpoint higher.
Vasoconstrict, shivers start,
Heat is trapped, cold takes part.
Metabolic surge, proteins burn,
Leukocytes rush, microbes churn.
Cytokines flare, tissues inflame,
Toxin fights, chills remain.
Crisis turns, sweat breaks free,
Vessels relax, back to ease!"
(Collected information)