Fever

Question 1

Define

Normal temp

Fever

Hyperthermia

hyperpyrexia

Answer 1

NORMAL TEMPERATURE varies throughout the day and typically 36.8 ±0.8 ℃ FEVER is regulated by the hypothalamus in response to pyrogens, resulting in a rise in core temperature ≥37.8℃

HYPERTHERMIA is not regulated by the hypothalamus and is an uncontrolled body temperature rise

HYPERPYREXIA is an extraordinarily high fever (≥41.5℃) and type of hyperthermia

Question 2

Thermoregulation

where is heat generated from?

how is heat distributed?

How is heat lost?

what part of the body is trying to be controlled in thermoregulation?

What areas are involved in neurological thermoregulation?

Answer 2

NORMAL TEMPERATURE varies throughout the day

and typically 36.8 ± 0.8°C

• Heat is generated from metabolically active cells
• Heat is both local and distributed by the circulatory

system

• Heat is lost to the environment (conduction, convection, radiation and evaporation)
• Temperature of the shell and of the core
• Temperature remains under tight regulation at a

neurological level and a “thermal setpoint” theory

Neurological thermoregulation

•Rostral hypothalamus

(pre-optic area)

• Limbic system, brain stem
• Afferent signals from spinal cord, brainstem
• Efferent signals via the spinal cord,sympathetic system

Question 3

what is a fever?

Answer 3

A state of elevated core temperature, which is often, but not necessarily, part of the defensive responses of multicellular organisms (host) to the invasion of live (microorganisms) or inanimate matter recognized as pathogenic or alien by the host” “An elevation in core body temperature above the daily range for an individual”

Body temperature fluctuates throughout the day

Mackowiak et al JAMA 1992:

Normal temperature = 36.8±0.8°C

Abnormal → Temperature ≥37.3°C in the early morning

Abnormal → Temperature ≥37.8°C overall

Question 4

what are causes of hyperthermia

Answer 4

Hyperthermia is not regulated by the hypothalamus and uncontrolled body temperature

Excessive heat for thermoreg control - hypothalamic setpoint normal

Heat stroke syndromes

Metabolic disease - thyrotoxic storm, phaeochromocytoma, diabetic ketoacidosis.

Pharmacological agents - atropine, certain anaesthetics, neuroepiletic malignant syndrome(antipsychotics, autonomic dysfunction)

serotonin syndrome - cocaine, NMDA(ectasy), amphetamines, TCAs, SSRIs, MAOI, lithium

Neurological injury -brain haemorrhage, hypothalamic stroke, status epilepticus

Question 5

Pyrogens cause fevers

What is the difference between exogenous and endogenous pyrogens?

Answer 5

EXOGENOUS PYROGENS -

are derived from outside of the host and mainly microbes and their products

ENODENOUS PYROGENS

are host-derived biologically active proteins (pyrogenic cytokines)

Question 6

EXOGENOUS PYROGENS are derived from outside of the host and mainly microbes and their products

Answer 6

Bacterial infection and the production of bacterial endotoxins

• Lipopolysaccharide - (LPS) on gram-negative Enterobacteriaceae

Viral infection and non-human genetic material

• Influenza
• RSV and others

Bacterial exotoxins

Bacterial endotoxins

Viral genetic material

Fungal elements

→ Act as TLR ligands and activation of innate

immunity

→ Production of host

pyrogenic cytokines

Question 7

What are examples of endogenous pyrogenes?

ENODENOUS PYROGENS

are host

-

derived

biologically active

proteins (pyrogenic

cytokines

Answer 7

Produced on activation

of TLRs

Over 70 cytokines

•

IL

-

1, IL -6 and TNF

Stimulate lymphocyte proliferation, granulocytosisin the bone marrow

Question 8

PGE2

and thermostat control

Answer 8

PGE2 = Prostaglandin E2

• During fever [PGE2]↑↑ in hypothalamic tissue and

3rd cerebral ventricle (hypothalamic regulatory

centres)

• PGE2 is not a neurotransmitter but cAMP is
• Destruction of these tissues reduces the ability of

pyrogens to cause fever

• Animal studies suggest pyrogens do not cross the

blood - brain barrier

Question 9

How does infectious agents lead to a fever?

Answer 9

Question 10

What can cause problem with TLR ligans for dendritic cells and macrophages (and others)

Answer 10

Host genetic deficiencies

Treatment of autoimmune disease

•Glucocorticoids

Question 11

Production of pyrogenic cytokines get out of control examples which can lead to fevers

Answer 11

Cytokine disease and non

-

infection fever

Malignancies

• Lymphoma and leukaemia

Systemic vasculitis

• Eosinophilic granulomatosis

with polyangiitis

• Granulomatosis with polyangiitis

Other autoimmune diseases

• Still’s disease (a disorder featuring inflammation, is characterized by high spiking fevers, salmon-colored rash that comes and goes, and arthritis. Still’s disease is also referred to as systemic-onset juvenile idiopathic arthritis.)
• Familial Mediterranean fever (Familial Mediterranean Fever (FMF) is a genetic disorder that causes recurrent episodes of fever that are typically accompanied by pain in the abdomen, chest, or joints. It most often occurs in individuals of Mediterranean and Middle Eastern descent, and the first episodes typically begin in childhood.)

Question 12

Biologic agents and possible infection without fever

Answer 12

Treatment of

autoimmune disease

• Anti - IL1 (anakinra)
• Anti-TNF (infliximab)and ↑risk of TB reactivation

Question 13

What can dampen or mess up fever response preventing the endothalamic reticulum in the brain working

Answer 13

Brain injury

• Hypothalamic stroke
• Haemhorrage
• Status epilepticus

Use of anti-pyrexics

• Paracetamol
• Aspirin
• NSAIDs

Question 14

Pyrexia of unknown origin

3 criteria

3 general classifications are?

Answer 14

The PUO aetiology has

The PUO definition has

3 criteria:

• Fever ≥37.8 °C on several occasions
• Duration of fever ≥21 days
• Uncertain diagnosis after one week of investigation

in hospital

3 general classifications:

• Infections
• Malignancies
• Systemic rheumatic diseases

Question 15

Answer 15

Question 16

Answer 16

Question 17

Answer 17

Question 18

Answer 18

Question 19

falciparum malaria

Answer 19

is a medical emergency.

non falciparum malaria -> more than 6 months