CMU-ISUMedical Corner

FEVER

Sir. Joseph AppletonMedical intern

18 April 2010

Lecture objectives

o Definition of Fever

o Mechanism of Fever

o Causes of Fever

o Types and patterns of Fever

o Clinical Vignettes

What is Fever?o Fever or pyrexia is defined as the elevation of

core body temperature above normal; in normal adults, the average oral temperature is 37°C (98.6°F).

o Hyperpyrexia refers to extreme elevation in temp, above 41.1°C (106°F)

o Hypothermia refers to an abnormally low temp below 35 °C (95°F) rectally.

o Fever of an unknown origin (FUO) is defined as a febrile illness lasting more than 3 weeks, with temperatures exceeding 38.3°C on several occasions, and lacking a definitive diagnosis after 1 week of evaluation in the hospital.

o Oral temp, rectal temp, axillary temp, and eardrum temperature.

Rapidly resp rates tend to increase the discrepancy b/w oral and rectal temps. In these situations, rectal temps are more reliable.

Mechanism of Fever

The febrile response, of which fever is but one component, is a complex physiologic reaction to disease involving a cytokine-mediated rise in body temperature, generation of acute-phase reactants, and activation of numerous physiologic endocrinologic, and immunologic systems.

Body temperature depends on the balance b/w the production and dissipation of heat.

How does the body generate heat?

Which gland is responsible for thermoregulation in our body? How?

What is set-point in physiology?

o The hypothalamus (central to the process) Function: thermostat controlling

thermoregulatory mechanisms that balance heat production with heat loss

o Integral to the process are the heat-sensitive receptors located in the pre-optic area of the anterior hypothalamus.

sensitive to elevations in blood temperature, increase signal output as the temperature rises above a fixed thermal set point (37.1°C average) and decrease output when the temperature drops below the set point.

Exogenous pyrogens(infectious agents, toxins, tumors)

(+) Monocytes, macrophages, endothelial

cells, other immune cells(+)

Antipyretics(–)

PGE2NSAIDs

(+)Anterior hypothalamus

Elevated thermoregulatoryset-point

(+)(+)

Heat conservationHeat production

(vasoconstriction,(involuntary musclebehavior changes)

contractions)

FEVER

Cytokines

Non-Ab proteins acting as mediators between cellso Monokines: produced by mononuclear

phagocyteso Lymphokines: produced by activated

lymphocytes, especially Th cellso Interleukins: cytokines that act as mediators

between leukocytesIL and a number

Cytokine network

Complex system of interactions between cytokines wherein one cytokine can:o Induce or suppress its own synthesiso Induce or suppress synthesis of other

cytokineso Induce or suppress synthesis of cytokine

receptorso Antagonize or synergize with other cytokines

Properties of cytokines

Can have similar actions (redundant)oCan share receptors or receptor componentsoDefect in a unique component: little effectoDefect in shared component: profound effect

IL-2Rγ defect X-linked SCID

Genes encoding cytokines can produce variants through alternative splicingo Yield slightly different but biologically

significant bioactivities

Cytokine receptorsMost are formed as heterodimers.

Many can be grouped into families based on common structural featureso Type 1 (IL-2 or hematopoietin receptor family)o Type 2 (interferon receptor family)o TNF receptor familyo IL-1 receptor familyoChemokine receptor family

Mediators of innate immune response

o TNF-αo IL-1o IL-10o IL-12o Type 1 interferons (IFN-α, IFN-β)o IFN-γo chemokines

Tumor necrosis factor (TNF-α)o Produced by activated macrophageso Most important mediator of acute inflammation in

response to microbes (esp gram negative bacteria)o Mediates recruitment of neutrophils and

macrophages to site of inflammation by inducing ICAM, etc on endothelial cells

o Stimulates endothelial cells and macrophages to produce chemokines

o Acts on hypothalamus to produce fevero Promotes production of acute phase proteins

Interleukin 1 (IL-1)

o Produced by activated macrophages

o Effects similar to TNF-α

o Helps activate Ts

Interleukin 10 (IL-10)Produced by activated macrophages and Th2 cells

Function in both innate and adaptive immune response

Inhibitory cytokineo Inhibits production of IFN-γ by Th1 cells

Shifts balance to Th2o Inhibits cytokine production by activated macrophageso Inhibits expression of MHC class II and co-stimulatory

molecules on macrophages

Causes of Fevero Bacterial infectionso Viral infectionso Parasitic Feverso Traumao Malignancy o Blood disorders (acute hemolytic anemia)o Drug reactionso Immune disorders (Collagen Vascular disease)

Patterns of Fever

There exist specific fever patterns that can occasionally trace towards the diagnosis.

Continuous Fever : Body temperature in such instances remain above normal throughout the day and does not fluctuate more than 1 degree Celsius in 24 hrs. (Lobar pneumonia, typhoid, UTI, brucellosis)

Intermittent Fever: elevated temperature is present only for some hrs of the day and turns to normal for remaining hrs. ( Malaria, Kala-azar, Pyaemia, septicemia

Remittant Fever : temperature remains above normal throughout the day and fluctuates more than 1 degree Celsius in 24hrs, (infectious endocarditits).

Relapsing Fever: calls for another kind of everyday sort of illness, that reappears at times, in fact a number of times, during which it takes almost quite a few days for the body temperature to return back to normal.

A neutropenic Fever: also referred to as “ febrile neutropenia”, is a type of fever in the absence of normal immune system functionining.

Management of Fever

• Non-Pharmacologic approach

• Cold towel application method• Exercise?

• Pharmacologic approach• NSAIDs• Antipyretics

Case 1

CC: Fever, cough, and chest painHX/PE: A 32-year of man comes to the emergency room

with 5 days of fever, a cough that is sometimes productive of blood, and pleuritic chest pain. He is an active intravenous drug user and last used o the day before his presentation. He denies being HIV positive. Past medical history is significant for skin abscesses in the past, but he has been recently quite well. He uses no medications and has no allergies.

Tem: 39 degree Celsius (102F),

BP: 112/72mmHg

PR: 110/min.

He is thin, weak appearing man lying on his side on the stretcher. Examination of the head, eyes, ears, nose and throat shows petechiae in his mouth and in his conjunctivae. Eye grounds are normal. His chest is bilaterally clear to border. There is no radiation of the murmur. His abdomen is benign, and his extremities do not have clubbing, but thin red lines are visible under the fingernails in the distal one-third.

Differential Dx

o Pneumonia

o Endocarditis

o Sepsis

o Bronchiectasis

Initial Dx plan

o Blood cultures

o Chest x-ray

o Results: MRSA , Multiple nodular lesions visible bilaterally

Further Dx plan

o Echocardiogram

o Results: Vegetation visible on TV with tricuspid regurgitation

o Tx Plan?

Case 2Chief complaint: fever, chills, RUQ painHX/PE: A 78-year old woman is brought to the ER room

with fever, chills, and RUQ pain. She was in her usual state of health until 1 week ago, when she began to develop intermittent pain in the RUQ associated with with darker colored urine. This morning the patient noticed feeling feverish and having a shaking chill. She denies any Hx of wt loss, any back pain, nausea, or vomiting. Her PMHX is significant for HTN for which she takes a beta-blocker.

She is frail appearing and in mild discomfort.

Vital signs are:o Temp: 38.4 degree Celsius (101.1F).o BP: 90/60mmHgo PR: 100/min, RR: 16/min.o Sclera are icteric. Heart and lungs are normal.

Abd examination is remarkable for being soft, with some RUQ tenderness and mild rebound tenderness. There is a well-healed scar on the RUQ. No masses are palpable. Rectal examination shows light-colored and Guaia-negative stool.

Differential Dx

o Cholangitis

o Common bile duct stones

o Cholecystitis

o Pancreatitis

o Hepatitis

Initial Dx plan

o CBCo BUNo Cro Results: CBC, WBC 14,000, Bilirubin

4mg/dL,o Alkaline phospatase 300U/L, rest of LFT

are normal.

Further Dx plan

o Ultrasound of the RUQ

o Results: Dilated common bile duct with common bile duct stones. No masses are appreciated in the liver or pancreas

o TX plan? ERCP? Endoscopic retrograde cholangiopancreatograpy when stable.

Case 3An 8-year old boy is brought in to the physician’s office with a 3-day Hx of fever and a rash. He has also had a mild sore throat and felt somewhat fatigued. His mother is concerns that could have “scarlet fever”. The rash started on his face and then spread to his arms and legs. He has only been given acetaminophen for the fever. He takes no other medications, has no known allergies, has no significant medical Hx, and has had no contact with anyone known to be ill.

On Examination:

Temp: 37 degree Celsius, (99.8F)

Other vital signs: normal

His cheeks are notably red, almost as if they had been slapped. His pharynx is normal appearing, and the remainder of his head and neck exam is normal. On his extremities there is a fine, erythematous, maculopapular rash but no vesicles or petechiae. A rapid group A streptococcal Ag test done is the office negative.

Dx/Tx

o What virus is the likely cause of this illness?

o In which human cells does this virus cause lytic infection?