Fever

Question 1

What is the normal range of temperature?

Answer 1

36-37.5°

Question 2

What is the difference between hyperthermia & hyperpyrexia?

Answer 2

Thermia - ≥37.8°

Pyrexia - ≥41.5°

Question 3

How is body temperature thermoregulated neurologically?

Answer 3

• rostral hypothalamus (pre-optic)
• limbic system, BS
• afferents from SC, BS
• efferent via SC, SNS

Question 4

Define ‘fever’.

Answer 4

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

Question 5

Causes of hyperthermia

Answer 5

Normal hypothalamic set point but excessive heat for thermoreg control = NOT regulated by hypothalamus (rapidly fatal)
- heat stroke syndrome
- metabolic disease (thyrotoxic storm, phaeochromocytoma, DKA)
- pharm agents (atropine, anaesthetics, NMS, serotonin syndrome)
- neuro injury (brain haemorrhage, hypothalamic stroke, status epilepticus)

Question 6

What is neuroleptic malignant syndrome? (NMS)

Answer 6

hyperthermia caused by:
- antipsychotics
- autonomic dysfunction

Question 7

What is serotonin syndrome?

Answer 7

Hyperthermia caused by:
- cocaine, NMDA, amphetamines
- TCAs, SSRIs, MAOIs, Li

Question 8

Give examples of exogenous pyrogens

Answer 8

Bacterial infection & bacterial exotoxins;
- TSST-1 toxin (staph aureus & toxic shock syndrome)
- Shiga toxin (shigella, dysentery)
- LPS (Gm-ve enterobact.)
Viral
- influenza, RSV
Other
- TLR-ligands (innate immunity), host pyrogenic cytokines

Question 9

Give examples of endogenous pyrogens

Answer 9

(TLR activation)
- cytokines (IL-1, IL-6, TNF etc)
= lymphocyte proliferation, granulocytosis in marrow

Question 10

How does destruction of hypothalamic & 3rd ventricle tissue impair the mechanism of pyrogens causing fever?

Answer 10

Cannot raise PGE2 via cAMP neurotransmitter & vasomotor centre
- pyrogens do not cross BBB

= cytokines with no systemic effect

Question 11

Which cytokine diseases cause a non-infection fever?

Answer 11

Malignancy - lymphoma, leukaemia
Systemic vasculitis - eosinophilic granulomatosis w/ polyangitis (EGP, GP)
AIDs - Still’s disease, familial Mediterranean fever (FMF)

Question 12

Which biological agents reduce the presentation of fever? (And hence must be monitored for apyrexic infection)

Answer 12

Anakinra (anti-IL1)
infliximab (anti-TNF), TB risk
Paracetamol, aspirin, NSAIDs

Question 13

What are the three PUO criteria?

Answer 13

• fever ≥37.8° on several occasions
• fever ≥21 days
• uncertain diagnosis after 1w investigation (hospital)