Fever Flashcards
What is fever?
Elevated core temperature often as part of a defensive mechanism against invasion of microorganisms recognised as pathogenic by the host
What % of paediatric admissions are due to fever?
30%
How does termperature regulation work?
Heat sensitive receptors in skin and within hypothalamus are sensitive to changes inblood temperature
Signal frequency is increased if temperature increases above 37.1, increasing the signal which inhibits sympathetic stimulation causing sweating and vasodilation
Signal frequency is decreased if temperature drops below 37.1, preventing inhibition of the SNS and causing vasoconstriction, piloerection, shivering, behavioural changes.
Effects of a drop in blood temperature?
Decreased inhibition of the SNS:
- piloerection
- shivering
- vasoconstriction
- behavioural changes
- NA release
- TSH release
Pathophysiology of fever?
Exogenous pyrogen e.g. LPS
Stimulates release of endogenous pyrogens by MACROPHAGES and neutrophils, such as IL-1, IL-6, IFN-Y, TNF-alpha
As well as initiating inflammation, these cross the BBB and cause upregulation of COX2 enzyme which increases PGE2 via the arachidonic acid pathway.
PGE2 acts at the PGER3 in the preoptic area of the hypothalamus raising cAMP and causing sympathetic output.
PGE2 raises the set temperature until PGE2 is no longer present
How do NSAIDs work and how do they cause stomach ulcers?
Inhibit COX2 to reduce the inflammatory effects of PGE2 and to reduce the raising of the hypothalamic set temperature
Also inhibit COX1 which reduces basal PGE2 production which usually has a protective effect
What is the primary cytokine to best correlate with fever?
IL-6
What cytokine is an endogenous antipyretic factor?
IL-10
Which other endogenous antipyretic facotrs are there?
glucocorticoids e.g. cortisol
What resets the thermostat?
PGE2 (and cAMP)
How does malignancy cause fever?
Direct production of TNF-a, IL-1 and IL-6 by the tumour
or
Macrophage production of TNF-a, IL-1, IL-6, in response to the tumour
Describe the APR
Endogenous pyrogens are produced by macrophages and neutrophils in response to injury or infection (IL-1, IL-6, IFN-y, TNF-a)
These cause the liver to produce CRP, SAA, fibrinogen, complement factor (up to several hundred times their basal concentration)
CRP = opsonin activation SAA = attracts leukocytes to site fibrinogen = coagulation factor aids in trapping microbes in blood clots CF = complement activation
What is raised ESR and what causes it?
Erythrocyte sedimentation rate; RBCs fall faster
Due to rouleaux formation
Due to fibrinogen (acute phase response)
What stimulates leukocytosis, and what is it?
IL-1 and TNF-a
First mechanism = release of cells from post-mitotic reserve pool in bone marrow = more immature cells (left shift)
Second = CSFs stimulate proliferation of precursor cells in bone marrow e.g. macrophage CSF
Why is fever potentially good?
IL-1 is critical for initation of innate immune system
Its evolutionarily conserved
It interfers with growth and virlence of pathogens (which grow best at normal body temp)
Small temperature elevations enhance immune function
What are the four types of fever and their example causes?
Remittent - Endocarditis, typhoid
Intermittent - malaria
Sustained - Pneumonia, UTI
Relapsing - tick-borne
What causes a fever which is always elevated but keeps spiking, and what type of fever is it?
Remittent fever
Endocarditis, typhoid fever
What causes a normal temp to keep spiking intermittently, within hours?
Intermittent fever
Malaria
Fever is always high, what’s it called and examples?
Sustained
UTI, pneumonia
Fever is low for a few days then spikes a while then low a few days
Relapsing
Tick borne disease
What are the four phases of fever?
Prodromal: “flu-like symptoms”, non specific
Chill: feeling cold, shivering etc as temperature is rising toward new set point e.g. vasoconstriction, piloerection, shivering, goose bumps, behavioural changes, feeling warm and shivering then stops.
Flush: cutaneous vasodilation causes red, warm and dry skin
Defervescence: sweating
What are rigors, and common cause?
Shivering to try to increase temperature
UTI
Night sweats common causee
Lymphoma, TB
Headache is due to? Red flag for? Also though?
Vasodilatation of cerebral vessels
Red flag for meningitis
Also common in non-specific fevers though
Delirium
Temporary mental confusion
Who is delirium common in?
Children and elderly
Myalgia and athralgia
Viruses ++ e.g. flu
Bacteraemia ++ e.g. meningococcal disease
Management of sepsis?
ABCDE Oxygen IV fluids ABx Blood cultures Serial lactates Hourly fluid output
Four conditions not to give antibiotics in?
Acute otitis media
Acute conjunctivitis
Acute URTI
Acute sinusitis
When shoudl you give ABx for sinusitis?
Double acute sinusitis - typical bacterial
What is hyperthermia?
Raised core temperature without a change in set hypothalamic point
Raised core temperature without sweating
What does hyperthermia look like?
Tachycardia / tachypnoea
NO SWEATING
Hypothermia
Collapse/LOC/seizures
Which drugs have no effect in hyperthermia?
Antipyretics
What is malignant hyperthermia?
Autosomal dominant condition
Triggered by exposure to halogenated anaestetic agents in GA or succinylcholine
Drastic increase in oxidative metabolism of skeletal muscle causing muscle contraction and overwhelms bodys ability to produce O2 and remove CO2 - rapid t increase to 43… fast death
What is drug fever.?
Fever coinciding with drug administration and ending when drug is stopped
How do antihistamines and TCAs cause drug fever?
Impaired heat dissipation
How does cimetidine cause drug fever?
Direct blocking of hypothalamic receptors
How do anticancer drugs cause drug fever?
Direct pyrogens
What is neuroleptic malignant syndrome and what might cause it?
Rare but life threatening reaction to DA antagonist neuroleptic medications such as haloperidol and chlorpromazine.
How does NMS present?
Central dopamine blockae in the hypothalamus leads to increased mucular rigitiy, EPS and hyperthermia
Onset 4-14d after start of therapy
How to treat NMS?
Discontinue the drugs
May need to treat complication e.g. ITU
How does thyrotoxicosis cause hyperthermia?
Raised T3/T4 = raised BMR
Acute exacerbation of chronic bronchitis?
Amoxicillin
Low severity CAP
Amoxicillin PO
Moderate severity CAP
Amoxicillin PO and clarithroymycin PO
Doxycyline if allergy to one
High severity CAP
Benpen + clarithromycin IV or co-amoxiclav + clarithromycin IV
HAP
Co-amoxiclav (broadspectrum)
Tazocin (anti-pseudomonal)
Ceftazidime (broad-spectrum ceph)
Gastroenteritis
Usually nothing as viral or self-limiting
Campylobacter
Clarithromycin if severe or immunocomprimised
Salmonella
Ciprofloxacin if severe
Shigellosis
Ciprofloxacin if severe
C diff
Oral metronidazole / vancomycin
Typhoid
cefotaxime
Pre-hospital meningitis tx
Benzylpenicillin as soon as possible
Cefotaxime if pen allergic
Hospital meningitis tx
After initial dose of benpen/cefotaxime
Cefotaxime up to 50y
Add amoxicillin if >50y
Lower UTI
Trimethoprim or nitrofurantoin (quinolone)
Lower UTI in pregnancy
Cefalexin
Sepsis
Tazocin or timentin (broad-spectrum anti-pseudomonal)
or
Cefuroxime (broad-spectrum cephalosporin)
Add vanc if suspected MRSA
Add metronidazole if suspected GIT origin (anaerobe)
Purulent conjunctivitis
Chloramphenicol
Periodontitis
Metronidazole
Otitis externa
Flucloxacillin
Clari if pen allergic
Otitis media
Nothing as usually caused by viruses
If systemically unwell or high risk of complications e.g. immunosuppression, amoxicilin or clarithro
Throat infections
Pen V
but URTI usually self limiting