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
Cellulitis
Flucloxacillin
Biliary / gut
Cefuroxime + metronidazole
Malaria
Quinine + doxycycline
TB
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
What is lysozyme?
Attaches onto PG layer of gram-positives
What is the definition of PUO?
> 38.3 for 3 weeks
3 days inpatient
3 outpatient consultations
Signs & symptoms of meningitis?
Unwell/drowsy STIFF NECK Purpuric haemorrhagic non blanching rash Bulging fontanelle Decreased consciousness Fever
Investigations of meningitis?
Bloods
BLood cultures
LP
CSF culture
Treatment of meningitis in neonate?
Gentamicin
Viral infections signs and symptoms?
Prodromal symptoms
Cough
Signs and symptoms of roseola infantum?
Sixth disease
High fever > generalised macular rash starting on trunk then face > FEVER SUBSIDES VERY QUICKLY ONCE RASH APPEARS and child becomes better
Complications of sixth disease?
Febrile convulsions, aseptic meningitis / encephalitis
Most common time for sixth disease?
9-12m
Pathophysiology of 6th disease?
HHV-6 infects CD4+ lymphocytes - remains latent
Can affect many organs and CNS early
Treatment of 6th disease?
SUpportive
Antivirals (ganciclovir) in immunocomprimised
Most common cause of seizures in childhood?
Febrile convulsions
What characterises simple febrile convulsons?
Up to 15m
Tonic clonic
Once in 24h
Full recovery in 1h
What characterises complex febrile convulsons?
Usually tonic clonic Above 15m Partial seizure More thn 1 in 24h No full recovery in 1h
Risk of recurrence of febrile convulsions?
30-50%
Initial investigations for febrile convulsions?
Rule out meningitis / encepahlitis with LUMBAR PUNCTURE
Glucose (hypoglycaemia = seizures)
Ca/Mg (low = seizures)
If all tests negative… maybe febrile convulsions
Symptomatic treatment of febrile convulsions
Rectal diazepam if above 5 minutes
Antipyretics
S&S Elderly patient with UTI
Dysuria Haematuria Lower abdo pain Fever CLEAR CHEST
Ix Elderly patient with UTI
Bloods
Urinalysis
MCU (MC&S)
Infective endocarditis S&S
Heart murmur Night sweats Weight loss Myalgia Arthralgia Fever
Infective endocarditis investigations
Bloods
Cultures
CXR
Echo
Sepsis
Rigors Hypotension Tachycardia Headache Fever Oliguria
Sepsis ix
Bloods Cultures CXR Urinalysis Sputum
Pneumonia ix
CXR
Bloods
Sputum
Urine
Meningitis signs
Headache Confusion NECK STIFFNESS Non blanching rash Fever
Meningitis ix
Bloods
LUMBAR PUNCTURE + CSF culture
Most common cause of UTI?
E coli and other “coliforms”
Proteus mirabilis
Klebsiella
Risk factors for UTI?
Elderly because LOW FLOW AND INEFFECTIVE EMPTYING
What is a simple UTI versus complicatied?
Simple = just in bladder COmplicated = tracking up
Treatment of simple UTI?
3 days trimethoprim
Diagnosis of UTI?
MSU sample
Waht do you do with an existing catheter in a UTI?
REPLACE IT
Wide-ranging non-focussed line of quiestioning - searhing for a positive response. Gets a comprehensive but time consuming history
Inductive
Initial differential diagnosis formed from initial info and then specific lines of focussed questioning
Hypothetico-deductive
Experienced clinical recognises key symptoms and links them quickly
Pattern recognition process
Pattern recognition process strength and weakness?
Fast decision making but mental short cuts may lead to errors
Adverse effects of macrolides?
N&V
Diarrhoea
Prolonged QT
Increased risk of statin-induced myopathy: withhold statin during treatment
Which class would you withhold statins during treatment for?
Macrolides
Which macrolide is particularly bad for causing diarrhoea?
Erythromycin (pro-motility)
Aminoglycosides A/Es?
Lots - dangerous (narrow window)
- Nephrotoxicity > renal failure
- Ototoxicity (irreversible damage to vestibular nerve)
- NMJ breakdown
- Headache, fever, dizziness
What drugs would you monitor serum levels of and why?
Aminoglycosides - narrow therapeutic window (monitor for accumulation)
Quinolones A/Es
Reduce seizure threshold
Tendon damage
Tetracyclines A/Es
Irritation of gastric mucosa - take with food but not milk (chelation)
Phototoxicity reactions (like severe sunburn)
DISCOLOURATION OF TEETH AND TEMPORARY GROWTH STUNTING DUE TO INCORPORATION INTO BONES - contraindicated in children and pregnancy/breast feeding
Trimethoprim A/Es
Rare
Rarely causes depression of haematopoesis
Sulfamethoxazole AEs
Rare but serious side effects e.g. bone marrow depression
Used rarely e.g. PJP pneumonia and other immunocompromised patients, and toxoplasmosis
Toxoplasmosis
Sulfamethoxazole
Metronidazole A/Es
Metallic taste Rashes Disulfram reaction with alcohol Dark urine Hepatitis/pancreatitis
Glycopeptides A/Es
Red man syndrome if infused too rapidly Phlebitis if not diluted sufficiently Nephrotoxicity (elderly++) Ototoxicity (elderly ++) Neutropenia after 1w or 25g
Monitor serum levels of..
Aminoglycosides
Vancomycin (after 3-4 doses; less in renal impairment)
Rifampicin A/Es
Stain body secretions orange
Monitor what during rifampicin tx?
LFTs
Oxazolidinones A/Es
HAEMATOPOETIC DISORDERS e.g. thrombocytopenia, anaemia, leukopaenia, pancytopenia
OPTIC NEUROPATHY (28d +++++)
Oxazolidonones monitoring?
FBC weekly
Oxazolidonones interactions?
MAOI so no tyramine rich foods, SSRIs, TCAs
Max course length linezolid?
28d
Penicillins AEs?
Few
Hypersensitivity 10%/true = 0.2%
Cholestatic jaundice
Which causes cholestatic jaundice?
Flucloxacillin
One of least toxic penicillins?
Benpen (pen G)
Cephalosporins A/Es
Hypersensitibity (about 10% of those pen allergic)
1st gen ceph use?
Skin / soft tissue (gram +ve)
2nd gen ceph use?
G-ve
3rd gen
G-ve … bad for g +ve
Good CSF for ceftriaxone so meninitis
Ceftazidime for pseudomonas
Which bacteria are intracellular?
Legionella
Listeria
Chlamydia
Mycobacterium
Lets Live inside Cosy Membranes
Which antibiotics pass into mammalian cells?
Glycopeptides
Macrolides
Quinolones
Tetracyclines
Quick, There! Get Me in!
Which drugs are cautioned in liver diseae?
Rifampicin (liver elimination)
Flucoxacillin (toxicity)
Co-amoxiclav (toxicity)
Which antibiotics impair CYP enzymes?
Macrolides
Which drug wouldn’t you use for UTI in renal impairment?
Nitrofurantoin
Excretion insufficient to raise level in urinary tract enough
Mycoplasma / legionella treatment?
Macrolides
Tetracyclines
Quinolones
(Quick, There, Get Me in!)
Which antibiotic would you give family planning advice with, to a fertile female?
Rifampicin
CYP enzyme induction = OCP level not high enough
Which antibiotic is highest linkage to peudomembranous colitis?
Clindamycin
Which type of antibiotics are most likely to cause c diff?
Broad spectrum
e.g. quinolones, 2nd/3rd gen cephs
If a patient is on methotrexate with a UTI, which drug would be given / not given?
Not trimethoprim as MTX toxicity likely as both reduce folate metabolism: liver toxicity, bone marrow suppression, neutropenia, ifnections
NITROFURANTOIN?
Give these on an empty stomach
Erythromycin / azithromycin
Penicillins
Note clarithromycin should be with food
Which macrolide is OD?
Azithromycin
Which macrolide causes particularly bad N&V/diarrhoea
Erythromycin
- increased gastric motility (used in gastroparesis)
What is the MOA of aminoglycosides?
Enter bacterial cell via O2-dependent transport system
Then bind to 30s…
Which bacteria is gentamicin NOT active against?
Anaerobes
- no o2-carrier system!
- hence no use for abscesses, CSF
Which is the only currently available oral anti-pseudomonals?
Quinolones
- ciprofloxacin
VERY GOOD BIOAVAILABILITY! Good for serious infections with oral dosing.
Which drug class shouldn’t be given with Ca/Al/Mg?
Quinolones
CYP inhibitor
SICKFACES.COM
Sodium Valproate
Isoniazid
Cimetidine
Ketoconazole & fluconazole
Fluoxetine Alcohol - acute consumption & cigarettes Cardiac failure and liver failure Erythromycin & clarithromycin Sulphonamides . Ciprofloxacin Omeprazole Metronidazole
Acne treatment
Tetracyclines
PJP w/ AIDS
Toxoplasmosis
Immunocompromised patients
Cotrimoxazole
-Rare but serious side effects so rarely used
Aspiration pneumonia AB
Metronidazole
Caution in 1st trimester++ of pregnancy due to mutagenic activity
Metronidazole
Glycopeptide used once daily
Teicoplanin due to long half life - 50h
Glycopeptide given intraventricularly
Vanc - directly into CSF
Elimination of nasal carriage of neisseria meningiditis
Rifampicin
Not licensed for under18s
Linezolid
Which unusual bacteria aren’t sensitive to penicillins, and why?
Mycoplasma - no cell wall
Which drugs are given with aminoglycosides?
Penicillins - synergism
Cephalosporins names and generations
1st gen… A
- CephALOthin
- CefAZOlin
- CefADROxil
2nd gen… F
- CeFURoxime
- CeFOXitin
- CeFAClor *
3rd gen... T - CefoTAXIme - CefTIZOXIme - CefTAZIDIme Note also the "me"'s - CefTRIAXONE
4th gen… EPIc QUEEN of PI&ROME
- CefEPIme
- CefQUINOme
- CefPIROME
Which drugs don’t cephs have action against?
LAME
Listeria
Atypicals (mycoplasma/chalmydia)
MRSA (except 5th)
Enterococci