FEVER

Fever

PKGhatak, MD

Merriam Webster dictionary defines fever as the elevation of the body temperature above normal.

The question then - what a normal body temperature.

It may come as a surprise to many that a normal body temperature is not so easily defined or universally accepted. Human body temperature varies - it is highest at sundown, reaches 37.4C (99.3F) then slowly decreases and drops to 35.2C (95.6F) at sunrise. This is known as Diurnal Variation.

CDC (center for disease control, USA) defines normal body temperature 37C (98.6F) and fever 38C (100.4F). In 1868 Carl Wuderlich wanted to answer that question and studied one million fever charts. He concluded that a normal axillary (under the armpit) temperature was 37 (+ -) 0.9C and any temperature over 38C as fever. A similar study conducted by Mackowiak concluded that a normal oral temperature was 99.9F and above that was fever. Small and Clements reviewed over 120,000 ER visit charts and reported a temperature of 1.8F above the diurnal variation was fever.

Causes of fever.

These are several causes of fever and can be mentioned here very briefly under External and Internal causes.

External causes. -

Infection. Viruses, bacteria, fungi, inhalation of fungal spores, parasites.

Inflammation.  Damage to body tissue by sprains, bone fractures, childbirth, surgery, crush injuries,

Snakebite, insect bites, plant poison.

Autoimmune disease/condition.  Rheumatoid arthritis and other collagen vascular diseases. Crohn's disease, ulcerative colitis. Mismatched blood and blood product transfusion, rejection of organ transplants.

Allergy.  Hay fever.

Malignancy.  Lymphoma, sarcoma, acute leukemia.

Food and Drinks.   Uncooked shellfish, unpasteurized milk and milk products, poorly cooked meat and eggs.

Drugs.  Fever from drugs is due to the development of antibodies or direct action of the heat controlling center of the brain. Penicillin tops the list followed by cephalosporins, anti-TB drugs, quinidine, procainamide, methyldopa, phenytoin.

Hear stroke.  Exposure to high ambient temperature and humidity, working in the boiler room, steam engine locomotive. 

Post anesthetic malignant hyperthermia. Certain anesthetic drugs can precipitate uncontrollable high temperatures in people with a rare inherited disorder.

Internal factors from damage to temperature center.

Brain damage from strokes. Methamphetamine intoxication, Traumatic Brain Injury (TBI).

Malignant hyperthermia. When body temperature reaches 109F(43C), the temperature center breaks down and unless medical attention is given immediately death becomes imminent. Examples are Parkinson's hyperpyrexia syndrome, Serotonin syndrome.

FUO (fever of unknown origin).  FUO in the earlier days due to subacute bacterial endocarditis or lymphoma. Now it is highly unlikely that a fever will not have a discernable cause.

Physiology of Fever.

The Temperature Regulating Center (TCR) is located in the Hypothalamus of the brain. Hypothalamus is also the nerve center of the sympathetic nervous system. The TCR is connected with other centers of the brain and via the Hypothalamus - pituitary portal circulation with the Pituitary gland. Through these pathways, the hypothalamus controls the metabolic rate, heat generation and heat dissipation of the body. Regulation of heart rate, breathing, and hormone levels is under the autonomic nervous system.

The setpoint of Temperature.

The hypothalamic auto-regulatory mechanism sets the normal core body temperature.

Pathology of fever.

Chemicals secreted by the phagocytic WBCs, immunocytes are called Cytokines, Interleukins, Prostaglandins. These are the chemical messengers that can turn the TCR up or down. Cytokines and interleukins promote Prostaglandin E2(PGE2) secretion. PGE2 acts directly on TCR.

Some bacterial degradation products can directly act on TCR and cause fever(pyrogenic).

Effect of fever:

Higher body temperature enhances the phagocytic action (ability to engulf) of WBC.

Immunocytic activities increase - production of IL-1(interleukin 1) and IL-6 are promoters of inflammation.

Inhibition of Bacterial growth. Most human pathogenic bacteria grow best at a normal body temperature; fever slows down the bacterial growth rate.

Metabolic reset.  At a higher temperature, glucose utilization, glycogen breakdown and glucose generation from fat and amino acids are accelerated.

Generation of body heat or Thermogenesis is under the control of the hypothalamus:

Shivering is a common method of thermogenesis; the release of adrenaline and thyroxine are other ways.

Loss of heat is achieved through vasodilatation and increased sweat production via the sympathetic nervous system.

 

In the pre-antibiotic era, the study of fever was an important subject in medical school. Paying meticulous attention to the characteristics of the fever chart, a physician could guess the bacteria responsible for the infection.

The fever was categorized as- 

Continuous, remittent (the temperature remained above normal throughout the day but fluctuated more than 2 C in 24 hrs.), intermittent, quotidian (every day), tertian (every 2-day interval), quartan (every 3-day interval).

Typhoid fever was diagnosed on the basis of remittent fever, and a palpable spleen. Other examples of intermittent fever are Malaria, Kala-azar, TB, Rat bite fever, EB virus.

The post antibiotic era changed the enthusiasm for fever study. At present, antigen testing for pathogens includes viruses, bacteria and many fungal and parasitic diseases. Antibody tests are also widely available. Present day clinicians look at the fever cart but rely less on it to make a diagnosis.

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