I.                 Historical Aspects-

A.     Fever was first recorded in ancient hieroglyphics several thousand years BC.

B.     Hippocrates had a humoral theory about fever being a sign of ill health.

C.    In 1868 Mr. Wunderlich developed the thermometer and established fever as one of the 4 vital signs.

D.    Around 1900, Sir Wm. Osler described the “Three Great Scourges” as fever, famine, and war.

II.               Determinates of Body Heat-

A.     Biochemical reactions- (cellular ox-phos… ADP<>ATP)  are only ~50% efficient, with the rest of the resultant energy forming heat.

B.     Body water-  Heat regulation is less efficient with dehydration.  Dehydration exacerbates fever, so hydrating a pt. won’t cure fever, but may bring it down some.

C.    Heat dissipation-  occurs in three ways:

1.     radiation- heat transfer by near and far infrared electromagnetic waves

2.     convection- heat transfer by  bulk movement of particles having different temperature

3.     conduction- heat transferred between objects in physical contact

D.    Voluntary control- choice of clothing and environment

E.     Cutaneous blood vessels- vasodilation = heat loss, and constriction = heat conservation

F.     Sweating and shivering- sweating = cooling, and shivering = increased heat production

III.              Thermogenesis-

A.     Temperature receptors- located in skin, upper spinal cord, and anterior hypothalamus.  This regulatory mechanism can be lost with a high transection of the S.C. or head trauma, producing “central fever”.

B.     Exogenous pyrogens- large molecular weight substances (microbes, endotoxin, androgenic steroids, incompatible blood) may begin a fever by causing the release of cytokines.  Exogenous pyrogens cannot cross the BBB.

C.    Endogenous pyrogens- Cytokines (IL1, IL 2, TNF [catchectin], interferons) released from host monocytes and macrophages (this takes ~90 minutes) can go through the BBB to reach the thermoregulatory center.

D.    Thermoregulatory Center-  thermostat in the anterior hypothalamus that controls the body’s “set point.”  The “set point” is regulated by locally by arachadonic acid metabolites (mostly cycloxygenase-derived prostaglandins, prostacyclins, and thromoxanes).

E.     Vasomotor center- in the posterior hypothalamus is connected to the thermoregulatory center through a nervous system relay.  The vasomotor center has heat loss/gain mechanisms that are activated via the sympathetic nervous system.

IV.             Fever vs. Hyperthermia-

A.     Fever- elevated hypothalamic set point

B.     Hyperthermia- normal set point, but failed peripheral regulatory mechanisms

V.               Peripheral Heat disorders- body is exposed to heat or cold but can’t adequately compensate.  Exercise and dehydration can exacerbate these problems.

A.     Muscle Cramps (heat exposure)-  due to subclinical hypovolemia and hypokalemia

B.     Heat Exhaustion- weakness and lightheadedness due to more important hypovolemia

C.    Heat Stroke- marked fluid and salt loss.  Hot dry skin, tachycardia, high temperature and confusion.  This pt. needs mechanical lowering of their body temp and administration of fluid and salts.

D.    Hypothermia- core temp reduced by long exposure to cool, damp conditions or by short (minutes) immersion in cold water.  Tx with hot fluids and calories.  Loss of consciousness = poor Px.

VI.             Biologic Effects of Fever- probably adaptive in both animals and humans, but there is little data to prove the value of fever in infectious diseases.

A.     Cold blooded animals with infections move towards a heat source to get a better outcome.

B.     Some microbes are killed by high temperatures.

C.    Immune function-

1.      T cell functions and phagocytosis are enhanced @ higher temps,.

2.     Serum Fe and zinc (which microbes need for propagation) are removed from tissues for utilization by cells of the RES.

3.     Not all immune systems are enhanced by fever.

VII.           Artificial lowering of Temperature- only really indicated in:

A.     Cardiovascular Dz- the high metabolic demands of maintaining fever increase cardiac demand

B.     Seizures- febrile seizures in infants and children

C.    Increased CNS pressure- as in intracerebral edema or brain lesions, because fever can elevate pressure further and cause herniation.

D.    Hyperthyroidism- thyroid storm- “thyrotoxicosis”

E.     Hyperpyrexia- risk of permanent brain damage.

  • >40 C = hyperpyrexia
  • >41 C= delirium
  • >42 C= unconsciousness
  • >43 C= death

VIII.          Fever patterns- Fever is often defined as >37.3 C (99.2 F), but this is debatable.  In lecture, he insisted that you don’t have fever until >100.00 F.   A few conditions show typical fever patterns.

A.     continuous or sustained fever- temp remains above normal, with <0.3 C (0.5 F) change.  Often seen with typhoid, G (-) pneumonia, CNS damage.

B.     remittent fever- fever goes up and down, but doesn’t reach normal.  *most common type with infectious Dz.  Malaria is a special case in which the fever tends to spike every other day.

C.    intermittent fever- temp varies daily, but returns to normal each day.

D.    hectic fever- wide swings in temp >1.4 C (2.5 F).  Most often seen with intraabdominal abscess, pyelonephritis, cholangitis, lymphoma, or drug fever.

IX.             Fever of Unknown Origin (FUO)-  defined by three characteristics.  Serious and often fatal.

A.     documented fever- (>100 F).  Make sure that your office has confirmed this.

B.     three weeks duration

C.    negative work-up- H&P, CBC, ESR, UA, CXR, serum protein electrophoresis, antibody titers, direct exam of body fluids, radionuclide scanning (Tc99m, 67^Ga), CT, MRI, Sonogram, bone marrow Bx, bronchoscopy, endoscopy, tissue Bx, laparotomy, etc.  This is very expensive…~ $20,000.

X.               Etiology of FUO-

A.     Infection- 30%  May be granulomatous Dz, an occult abscess, or infective endocarditis, etc.

B.     Neoplasia- 20%  May be a hematologic malignancy, or a variety of solid tumors.

C.    Collagen Vascular Dz- 15%  Such as SLE, temporal arteritis in postmenopausal women or junior rheumatoid arthritis (JRA- Still’s Dz) in kids.

D.    Misc., Identifiable- 15%  Such as drug fever, sarcoidosis,  or regional ileitis (Crohn’s Dz)

E.     Unsolved- 20%

XI.             Principles of FUO-

A.     Consider common diseases-  more often you will see uncommon manifestations of common Dz than uncommon Dz.  “Don’t look for zebras.”

B.     Continued observation may be needed. If  you don’t find anything, discharge the pt, do weekly follow up in clinic, and wait for the Dz to clarify itself.  Don’t repeat tests w/out good reason.

C.    Review intake of prescribed and social drugs, especially aldomet, isonazid, dilantin, coumadin, antibiotics, heroin, and cocaine.

D.    When do you do surgery?  When the pt is known to have abnormal tissue (nodes, liver, lung)… not just to find out what might be wrong in there.

E.     Empiric trials with drugs don’t work and may mask the Dz, so it’s better not to try this.

F.     Factitious Fever- self-induced disorders should be considered when the pt’s condition is unexplainable, especially if there is an unusual dermal lesion or bacteremia involving unusual organisms.  The pt may be injecting material intradermally or intravenously.  This can be a suicide attempt or a means of obtaining attention.  The pt is often medically educated (nurse, doctor, orderly, etc.)