[04.27] Approach to Patients with Fever and Fever of Unknown Origin V2.2.pdf

Pyrexia

What is the clinical term for fever?

Elevation of the body temperature that exceeds the normal daily variation and occurs in conjunction with an increase in the hypothalamic set point

How is fever defined physiologically?

Resetting of the home thermostat to a higher level

What analogy describes the shift of the hypothalamic set point from hypothalamic set point

Resetting of the home thermostat to a higher level

What analogy describes the shift of the hypothalamic set point from normothermic to febrile levels?

38C (100.4F)

What core body temperature defines fever according to the WHO and CDC?

Infection

What is fever often a physiological response to?

Endogenous (internal) and exogenous (external) pyrogenic substances

What two categories of substances elicit fever?

Microbial products, microbial toxins (endotoxins), whole microorganisms (viruses, parasites, bacteria, or fungi)

List three examples of exogenous pyrogens.

IL-1, IL-6, TNF (Tumor necrosis factor), CNTF (Ciliary neurotrophic factor), IFN-\alpha (Interferon-alpha)

List five examples of endogenous pyrogens or pyrogenic cytokines.

38C

What oral temperature is considered febrile?

37.8C

What rectal temperature is considered febrile?

37.2C

What axillary temperature is considered febrile, noting they tend to be cooler?

38C

What tympanic membrane temperature is considered febrile?

38C

What forehead temperature, measured using infrared technology, is considered febrile?

Hyperpyrexia

What term is defined as a fever of >41.5C (106.7F)?

Severe infections

What infectious condition can lead to extraordinarily high fever (hyperpyrexia)?

Central nervous system (CNS) hemorrhages

What non-infectious condition is the most common cause of hyperpyrexia?

41.5C

Fever due to infectious diseases rarely exceeds what temperature in the pre-antibiotic era?

Neuropeptides functioning as central antipyretics

What is speculated to mediate the natural thermal ceiling of 41.5C?

36.6-37.9C

equivalent in celsius to 97.9-100.2 F

rectally

What is the defined range of normal body temperature fluctuation?

Early evening

When is the highest point of normal body temperature reached?

Morning

When is the lowest point of normal body temperature reached?

Resetting of the thermostatic set-point in anterior hypothalamus

What mechanism characterizes fever?

Initiation of heat-conserving mechanisms

What physiological response results from the hypothalamic set-point resetting until the internal temperature reaches the new level?

Elevation in body temperature that occurs in the absence of resetting of the hypothalamic thermoregulatory center

How is hyperthermia defined?

Hypothalamus

What part of the brain normally regulates body temperature?

Preoptic anterior hypothalamus and posterior hypothalamus

What two areas of the hypothalamus contain neurons that receive temperature signals?

Peripheral nerves and temperature of the blood bathing the region

What are the two sources of signals received by the hypothalamic neurons?

Rectal temperature

What surrogate temperature measurement is closest to the actual core temperature and is considered the most reliable?

Metabolic activity in the muscle and liver

From where is excess heat production derived?

Skin and lungs

What two areas are responsible for heat dissipation?

Slowing down the growth of most pathogens and boosting the effectiveness of a body’s immune response (both innate and adaptive)

List two ways fever effectively helps the body fight infections.

Neutrophils

Fever increases the recruitment of what immune cells?

Oxidative activity

Fever enhances the activity of neutrophils in what way?

Antigen-presenting cells

Fever increases the activity of what cells crucial for adaptive immunity?

Tissue repair

Increased metabolic rates during fever accelerate what process?

37C (98.6^{\circ}\text{F})

What narrow range does the hypothalamus keep the body’s temperature within?

Sweat production and vasodilation

What two instructions does the hypothalamus send to cool the body down when it is too hot?

Norepinephrine

What substance is released when temperature drops, directing the body to preserve and produce heat?

Increases heat production in brown adipose tissue and induces vasoconstriction to reduce heat loss

List two actions of norepinephrine in response to a temperature drop.

Acetylcholine

What substance stimulates muscles to shiver, converting stored chemical energy into heat?

Inflammatory cytokines

What substances are produced by immune cells upon detecting a pathogen, some of which are fever-inducers?

Prostaglandin E2 (PGE2)

What molecule is synthesized in the hypothalamus in response to pyrogenic cytokines, acting as the major fever inducer?

Thermally tricked into thinking the body is cold

What happens when PGE2 acts on thermoregulatory neurons to raise the body’s temperature set-point?

Suppressing PGE2 synthesis

How do fever-reducing medications (e.g., aspirin, ibuprofen) work?

Sweating and vasodilation

What cooling mechanisms are activated when the hypothalamic thermostat is set back to normal?

40.5C (105^{\circ}\text{F})

At what temperature should precaution be taken to prevent irreversible damage to the brain?

Confusion, seizures, and irreversible damage to the brain

List three consequences of body temperature running too high (>40.5C).

Extended exposure to extreme heat or heat stroke

What are two common causes of hyperthermia?

The body does not produce the extra heat

What distinguishes hyperthermia from fever regarding heat production?

Cooling system is simply exhausted and fails to compensate for the excessive external heating

What fails in the body during hyperthermia, allowing temperature to rise uncontrolled?

No effect

What effect do fever-reducing medications have on hyperthermia?

36.8 \pm 0.4C

What is the mean oral temperature range for persons 18-40 years old?

37.2C

What is the maximum normal oral temperature at 6 AM (coolest)?

37.7C

What is the maximum normal oral temperature at 4-6 PM (hottest)?

0.5C or 0.9^{\circ}\text{F}

What is the typical normal daily temperature variation?

Morning temperature >37.2C or afternoon temperature >37.7C

What morning and afternoon temperatures define fever?

Elderly individuals

What patient population can have a reduced ability to develop fever, even in severe infections?

Rectal temperatures

What temperature measure is generally 0.4C higher than oral readings and is the best measure of core temperature?

Mouth breathing or ingestion of cold/hot liquids

List two factors that can lower oral temperature readings.

Axillary measures

What temperature measure is the least reliable, being lower by 0.5C from oral and 1C from rectal temperatures?

Lower esophageal temperatures

What measure closely reflects core temperature and is used to confirm hypothalamic function?

Tympanic membrane

What temperature measure is the most convenient, non-invasive, and widely available?

0.8C or 1.6^{\circ}\text{F} lower than rectal temperatures

How much lower are tympanic membrane readings in the unadjusted mode compared to rectal temperatures?

Hypothermia

What term seems to be an error in the source, where hyperthermia was meant to be discussed?

Rapid in onset and >40.5C

What two characteristics describe fever and hyperpyrexia in systemic sepsis?

Heat exposure or treatment with drugs that interfere with thermoregulation

What two preceding events characterize the diagnosis of hyperthermia?

Brain hemorrhage

What non-infectious cause is the most common cause of hyperpyrexia?

Hypothalamus

What part of the body, when affected (e.g., CNS hemorrhage), can cause hyperpyrexia?

Ovulation until menses

During what period does the morning temperature in menstruating women rise by around 0.6C and remain elevated?

IL-1, IL-6, TNF, IFN-\alpha

What endogenous pyrogens (cytokines) are secreted in the system when there is cytokine storm, leading to fever?

Lipopolysaccharide (LPS) from Gram-negative bacteria, fungi, or other pathogens

List three examples of exogenous pyrogens.

Hypothalamic set-point is raised

What happens after the hypothalamus receives signals from pyrogens?

Heat conservation and heat production

What two general mechanisms does the body use to increase core temperature to meet the new set-point?

Shunting of the blood away from the skin and into the vital organs

What is the heat conservation mechanism that makes the extremities cold and clammy in fever?

Shivering mechanism (through muscles) and raising metabolic rates in the liver (non-shivering mechanism)

List two mechanisms of heat production.

Skin is hot and dry

What characteristic of the skin distinguishes hyperthermia from fever, where the skin is cold and clammy?

Increased myocyte metabolic activity and altered hypothalamic regulation

What are the two general mechanisms leading to hyperthermia?

Exertion hyperthermia, thyrotoxicosis, pheochromocytoma, cocaine, delirium tremens, malignant hyperthermia

List six associated conditions characterized by excessive heat production leading to hyperthermia.

Heat stroke and autonomic dysfunction

List two associated conditions characterized by disorders of heat dissipation leading to hyperthermia.

Neuroleptic malignant syndrome (NMS), coronary vascular accident (CVA), trauma

List three associated conditions characterized by disorders of hypothalamic function leading to hyperthermia.

Elderly

What patient population is heat stroke common among due to problems with heat loss and generating thirst?

Inheritable sarcoplasmic reticulum malignancy in the muscles

What is the nature of malignant hyperthermia?

Halothane (anesthesia)

Malignant hyperthermia is triggered by what drug, causing muscles to become spastic and form heat?

Adverse reaction to neuroleptic or antipsychotic drug

What causes Neuroleptic Malignant Syndrome (NMS)?

Clinical characteristics of fever

What provides more useful information than fever pattern in diagnosis?

Illnesses presenting with more than one fever pattern, or instances of co-infections

List two reasons why fever pattern is less helpful in diagnosis.

Prolonged Fever

What fever pattern describes a single illness where the duration of fever exceeds what is expected for the clinical diagnosis (e.g., >14 days for URTIs)?

Adenoviral infections or respiratory syncytial virus

List two etiologies that can result in prolonged fevers lasting more than 10-14 days, which is unusual for URTIs.

Recurrent Fever

What fever pattern describes a single illness in which fever and other signs and symptoms wax and wane (fever cycle spans \sima week)?

Ascending cholangitis, dengue, malaria, relapsing fever (Borrelia recurrentis), yellow fever, brucellosis

List six potential causes of recurrent fever.

Single-Spike Fever

What fever pattern describes one fever episode, usually from a non-infectious cause?

Manipulation of infected/colonized mucosal surface, infection from non-sterile catheterization, blood transfusion, infusion-related sepsis, temperature error

List five causes of single-spike fever.

Double Quotidian Fever

What specific pattern is associated with two fever spikes in a day and is associated with few diseases?

Adult Still’s disease, visceral leishmaniasis, miliary TB, mixed malarial infections, right-sided gonococcal endocarditis

List five causes of double quotidian fever.

Sustained or Continuous Fever

What fever pattern describes prolonged fever with little or no change in temperature over the course of a day (fever never goes down throughout the day)?

Central fever (possible problem in the hypothalamus), roseola infantum, brucellosis, Kawasaki disease, scarlet fever, typhoid fever

List six causes of sustained or continuous fever.

Remittent Fever

What fever pattern describes the temperature going up and down in spikes with differences  0.6-1C but does not return to normal?

Viral upper respiratory tract infection, Legionella, tuberculosis, P. falciparum, acute rheumatic fever, Mycoplasma, subacute infective endocarditis (Viridans streptococci)

List five causes of remittent fever.