Fever

Outline

Definition Mechanism Types Clinical causes

Fever

A regulated elevation of core temperature due to disease. Body temperature is above 37.20C in the morning or above 37.80C in the evening.

Cytokines

Mediators released by cells as a response to inflammation. Monokines (released by monocytes/ macrophages) Lymphokines (released by lymphocytes)

Cytokines (2)

Cytokines was found in 1940, at the site of bacterial invasion. IL-1 (Interleukin 1), TNF (Tumor Necrosis Factors), IFN- (Interferon-), and IL-6. Released by leucocytes to induce prostaglandin (PG) release by cells at the surrounding of hypothalamus responsible for the development of fever Endogenous Pyrogen (EP).

ORGANUM VASCULOSUM LAMINA TERMINALIS

Hypothalamic integration center interprets information about skin and core temperature from corresponding thermoreceptors Set the idealized or set-point temperature

As thermostat is set higher, posterior hypothalamus is activated

The Results of Activation of Posterior Hypothalamus:

Increase heat production

Shivering Feeding Increased voluntary activity Increased secretion of thyroxin and norepinephrine Cutaneous vasoconstriction Curling up Horripilation (goose flesh)

Decrease heat loss

The events occurred in fever

In the first stage, the subject feels cold since the temperature in the skin is lower than the set-point temperature in hypothalamus. The response of the body is to increase heat production (shivering, horripilation) and to decrease heat loss (cutaneous vasoconstriction, paleness), therefore body temperature increases.

The events occurred in fever (2)

The metabolic rate increases in fever in proportion to the increase in temperature. Approximately 13% increase in metabolic rate for every degree centigrade of temperature above the normal.

The events occurred in fever (3)

The metabolic rate increases in: Liver: increased liver transaminase & bilirubin. Skeletal muscles: increased protein breakdown, mioglobin (rhabdomiolisis) and release of K+ ion. Negative nitrogen balance as a greater excretion of nitrogen, urea, and creatinine.

The events occurred in fever (4)

As metabolic rate increases, O2 demand rises (20%). Thus, there are increases in pulmonary ventilation, tidal volume rises (9%), and insensible perspiration through respiratory tract. Cardiac output increases, also stroke volume and pulse rate. Blood pressure rises in the beginning but then it returns to the normal.

The events occurred in fever (5)

Fluid & electrolytes disturbance Fluid depletion, dehydration, plasma becomes concentrated Influx of Na+ & Cl-, efflux K+, P and N. Hyperkalemia (causes by potasium release by skeletal muscle and efflux from body tissues), which can cause cardiac arrest.

The events occurred in fever (6)

Low perfusion causes organ disturbances (especially kidneys) and tissue necrosis Damage of brain results in Cheyne-Stokes respiration, central fever, paralysis, brain edema, convulsion, coma. Febrile convulsion affects children who experience a rapid rise in body temperature.

The events occurred in fever (7)

If the fever recedes, there is muscular relaxation and abundant sweating. Heat loss then predominates over heat production and temperature falls.

Types of fever

Based on the pattern: Intermitten Remittent Relapsing Continue

Types of fever (2)

Intermitten fever Fever with large diurnal variation Hectic or Septic fever: if the variation is very large Quotidian fever: if hectic fever occurs in each day

Types of fever (3)

Remitten fever A marked variation in temperature level each day, but the low point is still above the normal day.

Types of fever (3)

Relapsing fever Short febrile periods interspersed by periods of one or more days of normal temperature. Tertian: if the febrile periods occur in the 1st & 3rd day Quartan: if the febrile periods occur in the 1st & 4th day.

Clinical causes of fever

Infections Typhoid & Paratyphoid fever: remittent fever with staircase rises for several days followed with a plateau for one to three weeks, then a step like return to normal temperature

Clinical causes of fever (2)

Murine thyphus fever Sudden elevation followed with remittent high fever for 10 days, then a fall by lysis, returning to normal about 14th 18th day Gonococcal endocarditis Double quotidian: two steplike rises & falls in each 24h period. Found also in Kala-azar and miliary tuberculosis

Clinical causes of fever (3)

Dengue fever A saddleback curve (pelana kuda) or biphasic pattern, meant that a fever rises rapidly, then declines somewhat during the succeeding two or three days, then it rises again to peak on about the sixth day, after which it subsides quickly.

Clinical causes of fever (4)

Malaria Fever occurs in the 1st & 3rd day (relapsing fever), as seen in Malaria Tertiana caused by Plasmodium vivax & P. ovale. Fever occurs in the 1st & 3rd day (relapsing fever), as seen in Malaria Tertiana caused by plasmodium vivax & ovale. Relapsing fever also occur in Borellia infection & ratbite.

Malaria Tertiana

Malaria Quartana

Clinical causes of fever (5)

Diseases of CNS Head injury (related with prognosis) Cerebral vascular accident (high fever relates to large hemorrhage) Neurogenic hyperthermia (surgical operation of pituitary fossa & the 3rd ventricle) Spinal cord injury (interruption of the tract to & from the hypothalamus)

Clinical causes of fever (6)

Neoplasms Malignant growths frequently cause fever Lymphomas: the first symptom

Hodgkins disease: relapsing fever known as Pel-Ebstein fever (7-10 days of normal temperature alternate with equal periods of fever)

Clinical causes of fever (7)

Blood disorder Acute leukemia, acute hemolytic anemia, hemorrhagic disorder (such as thrombocytopenic purpura, hemophilia, scurvy). Embolism & Thrombosis in a large artery/ vein is associated fever (tissue necrosis) Myocardial infarction: low fever is expected during the first few days, and elevation as high as 103-1040C.

Clinical causes of fever (8)

Disturbances in fluid balance Dehydration Diabetic acidosis

Clinical causes of fever (9)

Heart failure Related with diminished heat dissipation due to a slowing blood flow, and associated with complication (bronchopneumonia, pulmonary infarction, rheumatic fever, myocardial infarction, thrombophlebitis). Paroxysmal tachycardia Extra heat production (cardica muscle) & impaired circulation

Clinical causes of fever (10)

Thyroid disease Thyrotoxicosis: a slight temperature elevation due to excessive heat production (chemical heat regulation increased metabolism) Thyroid crisis (after surgery of thyroid): a rapid rise in temperature accompanied by tachycardia, thready pulse, restlessness & stupor.

Clinical causes of fever (11)

Liver diseases Liver abcess (amebic or bacterial): hectic fever Liver carcinoma; cirrhosis Hemorrhage peptic ulcer

Clinical causes of fever (12)

Serum sickness Trias: Fever, athralgia, urticaria. Occurs 5-10 days after administration of an animal serum to human. Allergy

Clinical causes of fever (13)

Heavy sedation Psychiatric therapy, barbiturate intoxication, patient with tetanus due to pulmonary complication

Clinical causes of fever (14)

Tissue trauma Crushing injuries, fractures of large bones, post-extensive surgical procedure (due to absorption of products of damaged tissue).

Clinical causes of fever (15)

Drug Sulfonamide, penicillin, iodides, bromides, barbiturates, atropine, belladona, and morphine. Dinitrophenol (weight reduction) Therapy of Syphilis

Ninth-day fever/ erythema (arsenic drug) Jarisch-Herxheimer reaction (penicillin) Trias: fever, malaise & pain (24 48h lasts)

Clinical causes of fever (16)

Others Cotton dust fever, (Aerobacter cloacae), metal fume fever (Zinc oxide), catheter fever (infected urethral tract), teething (in children), milk fever (in lactation mother), psychogenic fever. Malingering.

Hyperthermia

Occurs when body heats dissipation is failed. Happens in prolonged exposure to heat and high ambient humidity Rectal temperature is higher than 410C

Hyperthermia (2)

The ability to dissipate heat by radiation falls as the radiant temperature of nearby objects increases The ability to dissipate heat by convection falls as the ambient temperature increases

Hyperthermia (3)

When ambient temperature reaches the mid 300C, evaporation becomes the only effective avenue for heat dissipation. However, since the rate of evaporation is inversely related with relative humidity, the ability to dissipate heat by evaporation falls as the ambient humidity increases.

Hyperthermia (4)

The combine reduction of heat loss by these three pathways can markedly increase the rate of heat storage causing progressive hyperthermia.

Clinical causes of hyperthermia (5)

Malignant hyperthermia

caused by Anesthetic gas halothane

Heat cramp Heat stroke Heat exhaustion

Summary

Is fever physiologic or pathologic? Is fever a symptom or sign? Is fever always associated with infection or not?

Competences

To be able to differentiate between fever and hyperthermia To be understand clinical causes of fever and hyperthermia To be understand management of fever and hyperthermia

References

Boron, W.F. & Boulpaep, E.L. 2005. Medical

physiology.

Iwan Darmansyah & Suharti K. Suherman (Eds). 1981. Penatalaksanaan Demam. Isselbacher et al. (Eds). Harrisons Internal

Medicines.

McBryde (Ed). 1952. Signs and Symptoms:

Applied pathologic physiology and clinical interpretation. Philadelphia: J.B. Lippincott. Subowo. 1993. Imunologi. Bandung: Angkasa.
p187-205.