Fever - etiology, pathogenesis, beneficial and harmful effects, clinical manifestations.
Fever is a controlled elevation of body temperature above the normal set point (usually > 37.5–38°C), mediated by hypothalamic regulation in response to pyrogens.
Etiology (Causes)
- 1 Infectious causes
Bacteria (e.g., Staphylococcus aureus, E. coli).
Viruses (e.g., influenza, dengue).
Fungi (e.g., Candida infections).
Parasites (e.g., malaria).
- 2 Non-infectious causes
Autoimmune diseases (e.g., systemic lupus erythematosus).
Malignancies (e.g., lymphomas, renal cell carcinoma).
Drug reactions (e.g., drug fever from antibiotics).
Tissue necrosis (e.g., myocardial infarction, large hematoma).
Pathogenesis
- 1 Exogenous pyrogens
From pathogens (e.g., lipopolysaccharides [LPS] from Gram-negative bacteria).
Stimulate monocytes, macrophages, and endothelial cells to produce endogenous pyrogens.
- 2 Endogenous pyrogens (cytokines)
IL-1, TNF-α, IL-6, IFN-γ.
These cytokines circulate to the hypothalamus.
- 3 Hypothalamic response
Cytokines stimulate prostaglandin E2 (PGE2) synthesis in hypothalamic preoptic area.
PGE2 raises the hypothalamic set point for temperature regulation.
- 4 Heat conservation and production
Vasoconstriction → reduces heat loss → chills.
Increased muscle tone and shivering → increases heat production.
- 5 New steady-state
Body temperature rises to new set point → fever established.
Beneficial Effects
Enhances phagocytic activity of neutrophils and macrophages.
Inhibits growth of certain pathogens (many bacteria replicate less efficiently at higher temps).
Promotes lymphocyte proliferation and antibody production.
Increases acute-phase protein synthesis (e.g., CRP).
Harmful Effects
Increased metabolic demand (e.g., higher oxygen and energy consumption).
Risk of febrile seizures (especially in children).
Can worsen neurological damage in brain injuries.
In severe cases → delirium, dehydration, circulatory collapse.
Clinical Manifestations
General symptoms
Chills and shivering (during temperature rise).
Sweating (during defervescence).
Anorexia, myalgia, fatigue.
Headache.
Cardiovascular
- Tachycardia (approx. 10 beats/min increase per 1°C rise).
- Possible hypotension in prolonged high fevers.
Respiratory
- Increased respiratory rate.
Neurological
- Malaise, irritability, confusion (especially in elderly).