2. OVERVIEW
Introduction
Thermoregulation
Pathophysiology of fever
Aetiology /Differential diagnosis of fever
Types of fever
Pyrexia of Unknown origin(PUO)
Factitious fever
History taking in a febrile patient
3. INTRODUCTION
FEVER(Pyrexia)
Is an elevation of body temperature above the normal
circadian range (daily variation) as a result of a change
in the thermoregulatory center located in the anterior
hypothalamus and pre-optic area (i.e. an increase in
the hypothalamic set point of 37 C) due to infection,
metabolic derangements or increased cell destruction.
4. THERMOREGULATION
Body temperature is controlled in the hypothalamus,
which is directly sensitive to changes in core
temperature
The normal 'set-point' of core temperature is tightly
regulated within 37 ± 0.5°C, as required to preserve
normal function of many enzymes and other
metabolic processes.
5. THERMOREGULATION
In a hot environment
sweating is the main mechanism for increasing heat
loss.
This usually occurs when the ambient temperature
rises above 32.5°C or during exercise
6. PATHOPHYSIOLOGY OF FEVER
The initiation of fever begins:
when exogenous or endogenous stimuli are presented
to specialized host cells, principally monocytes and
macrophages ,they will then stimulate the synthesis
and release of various pyrogenic cytokines including :
1)interleukin-1, interleukin-6
2)TNF-α, and
3)IFN-γ.
7. PATHOPHYSIOLOGY OF FEVER
Exogenous pyrogens: stimuli from outside the host
like : microorganism, their products, or toxins and it is
called Endotoxin
Endotoxin : lipopolysaccharide ( LPS)
LPS: is found in the outer membrane of all gram
negative organisms
Action :
1) through stimulation of monocytes and macrophages
2) direct on endothelial cell of the brain to produce
fever
8. PATHOPHYSIOLOGY OF FEVER
Endogenous pyrogens:
polypeptides that are produced by the body ( by
monocytes and macrophages ) in response to stimuli
that is usually triggered by infection or inflammation
stimuli
9. PATHOPHYSIOLOGY OF FEVER
Pyrogens:
Substances that cause fever are called pyrogens
Cytokines :
Cytokines are regulatory polypeptides that are
produced by
1) monocytes / macrophages
2) lymphocytes
3) endothelial and epithelial cell and hepatocytes
10. PATHOPHYSIOLOGY OF FEVER
The most important cytokines are :
Interleukin 1 and 1 (The most pyrogenic)
Tumor necrosis factor
Interferon gamma
Interleukin 6 (The least pyrogenic)
cytokines>fever develop within 1hr of infection
11. PATHOPHYSIOLOGY OF FEVER
Cytokine-receptor interactions in the pre-optic region of
the anterior hypothalamus activate phospholipase A.
This enzyme liberates plasma membrane arachidonic acid
as substrate for the cyclo-oxygenase pathway. The resulting
mediator, prostaglandin E2, then modifies the
responsiveness of thermosensitive neurons in the
thermoregulatory centre.
The PGE2 in the brain then stimulates the rapid release of
cAMP from glial cells, this release then induces the release
of neurotransmitters that raises the thermoregulatory set
point in the hypothalamus.
These events then lead to increased body heat content and
fever.
12. nfection, microbial toxins,
mediators of inflammation,
immune reactions
Microbial toxins
FEVER
nocytes/macrophages,
dothelial cells, others
genic cytokines IL-1, IL-
6, TNF, IFN
Cyclic
AMP
PGE₂
Hypothalamic
endothelium
Elevated
thermoregulatory set
point
Heat conservation,
heat production
Circulation
26
13. Human Physiology 5th edition 1990
INFECTION
Monocytes, macrophages
Hypothalamus: ↑ temperature setpoint
Skeletal muscle Skin arterioles
↑ vasoconstriction
↑ heat production ↓ heat loss
Heat production > Heat loss
Heat retention
↑ Body temperature
Endogenous pyrogens (IL-1,TNF, IL-6)
shivering Curl up/add clothes
15. TYPES OF FEVER
The pattern of temperature changes may occasionally hint at the diagnosis:
Continuous fever: Temperature remains above normal throughout the day
and does not fluctuate more than 1 °C in 24 hours, e.g. lobar pneumonia,
typhoid fever, urinary tract infection, brucellosis
Intermittent fever: The temperature elevation is present only for a certain
period, later cycling back to normal(i.e. Normal temp. between fever episodes),
e.g. malaria, pyaemia, or septicemia.
Following are its types
Quotidian fever, with a periodicity of 24 hours, typical of Plasmodium
falciparum malaria
Tertian fever (48 hour periodicity), typical of Plasmodium vivax or Plasmodium
ovale malaria
Quartan fever (72 hour periodicity), typical of Plasmodium malariae malaria.
16. TYPES OF FEVER
Remittent fever: Temperature remains above normal
throughout the day and fluctuates more than 1 °C in 24
hours, e.g., infective endocarditis.
Pel-Ebstein fever: A specific kind of fever associated
with Hodgkin's lymphoma, being high for one week
and low for the next week and so on. However, there is
some debate as to whether this pattern truly exists.
17. PYREXIA OF UNKNOWN ORIGIN (PUO)
A common presenting problem.
Defined as a consistently elevated body temperature of
more than 37.5 C persisting for more than 2 weeks
with no diagnosis despite one week of initial
investigations.
The commonest cause of PUO is a common disease
presenting atypically.
As the duration of fever increases the likelihood of an
infectious cause decreases.
Among children, infections are the most common
causes.
18. Aetiology and Epidemiology of
PUO in developed countries
Infections (30%)
Sepsis- Abscess at any site; Cholecystitis/ Cholangitis
Urinary tract infection
Dental and sinus infection
Bone and joint infections
Imported infections, e.g. Malaria, Dengue, Brucellosis
Enteric or Typhoid fever
Infective endocarditis
Tuberculosis (particularly extrapulmonary)
Viral infections (cytomegalovirus-CMV, Ebstein-Barr virus-EBV, human
immunodeficiency virus-HIV), Hepatitis A and B and toxoplasmosis
Fungal infections
Malignancy (20%)
Lymphoma and myeloma
Leukaemia
Solid tumours (renal, liver, colon, stomach, pancreas)
20. FACTITIOUS FEVER
This is defined as fever engineered by the patient by
manipulating the thermometer and/or temperature
chart apparently to obtain medical care.
uncommon and typically presents in young women
with a medical and nursing background.
Examples include The dipping of thermometers into
hot drinks to fake a fever.
The factitious disorder is usually medical but may
relate to a psychiatric illness with reports of
depressive illness.
21. FACTITIOUS FEVER
CLUES TO THE DIAGNOSIS OF FACTITIOUS FEVER
A patient who looks well
Absence of temperature-related changes in pulse rate
Temperature > 41°C
Absence of sweating during the period of fever
Normal ESR and CRP despite high fever
Useful methods for the detection of factitious fever
include
1) Supervised (observed) temperature measurement
2) Measuring the temperature of freshly voided urine
22. HISTORY TAKING IN FEBRILE
PATIENTS
Using the Calgary Cambridge guide as a framework to
interviewing patients.
The most important step is taking a meticulous detailed history
to explore the patients problems from three perspectives.
Biomedical perspective- to understand the chronology of
symptoms, analyse each symptom and review each system to
localize the source of the fever.
Contextual history- very important
Patients perspective- to understand the patients interpretation
of the illness.
Systems review- This is a guide not to miss anything. Any
significant finding should be moved to HPC or PMH depending
upon where you think it belongs.
23. exploration of the patient’s problems to discover the:
biomedical perspective the patient’s perspective
background information - context
providing the correct type and amount of information
aiding accurate recall and understanding
achieving a shared understanding: incorporating the
patient’s illness framework
planning: shared decision making
Initiating the session
Gathering information
Physical examination
Explanation and planning
Closing the session
Providing
structure
Building the
relationship
preparation
establishing initial rapport
identifying the reasons for the consultation
making
organisation
overt
attending to
flow
using
appropriate
non-verbal
behaviour
developing
rapport
involving
the patient
ensuring appropriate point of closure
forward planning
a
24. The content of the medical interview
Patient’s problem list
1.
2.
3.
Exploration of patient’s problems:
Biomedical perspective
sequence of events, symptom analysis, relevant systems review
Patient’s perspective
ideas, concerns, expectations, effects on life, feelings ICE
Background information - context
Past medical history
Family history
Personal and social history
Drug and allergy history
Systems review
b
25. BIOMEDICAL PERSPECTIVE
Presenting complaints of a patient with fever
Feeling hot
A feeling of heat does not necessarily imply fever
Rigors.
profound chills accompanied by chattering of the teeth
and severe shivering, implies a rapid rise in body
temperature. Can be produced by :
1) brucellosis and malaria
2) sepsis with abscess
3) lymphoma
Excessive sweating.
Night sweats are characteristic of tuberculosis, but
sweating from any cause is usually worse at night.
26. BIOMEDICAL PERSPECTIVE
Recurrent fever.
Source is often a focus of bacterial infection such as
cholecystitis or cholangitis or urinary tract infection
especially associated with an obstruction or calculi.
Headache.
Fever from any cause may provoke headache.
Severe headache and photophobia, may suggests
meningitis.
Delirium.
Mental confusion during fever is well described and
relatively more common in young children and in old age.
Muscle pain. Myalgia is characteristic of viral infections
such as influenza, Malaria and brucellosis.
27. BIOMEDICAL PERSPECTIVE
Symptom analysis for fever
Verify presence of fever- True or factitious fever
Duration- Acute or chronic
Mode of onset- Abrupt or gradual
Progression- Continuous or intermittent. If intermittent
ask about frequency to determine the pattern.
Severity- how it affects daily work/physical activities.
Relieving and aggravating factors
Treatment received or/and outcome
Associated symptoms- Localizing symptoms may
indicate the source of fever.
28. BIOMEDICAL PERSPECTIVE
Respiratory tract symptoms:
1) Sore throat, nasal discharge, sneezing-URTI
2) Sinus pain and headache-suggests sinusitis
3) cough, sputum, wheeze or breathlessness-suggests a LRTI
Genitourinary symptoms:
1) Frequency of micturition, dysuria, loin pain, and vaginal or
urethral discharge-suggesting
a) Urinary tract infection,
b) Pelvic inflammatory disease and
c) Sexually transmitted infection (STI)
29. BIOMEDICAL PERSPECTIVE
Abdominal symptoms: diarrhea, with or without blood, weight loss and
abdominal pain -suggesting
a) Gastroenteritis,
b) Intra-abdominal sepsis,
c) Inflammatory bowel disease,
d) Malignancy
Skin rash: enquire about appearance and distribution as it may provide clues
to the diagnosis-
1) Macular- Measles,Rubella,toxoplasmosis
2) Haemorrhagic- Meningococcal infections, viral haemorrhagic fever.
3) Vesicular- Chickenpox, Shingles, herpes simplex
4) Nodular- Erythema nodosum( TB and Leprosy)
5) Erythematous- Drug rashes, Dengue fever
30. BIOMEDICAL PERSPECTIVE
Joint symptoms: joint pain, swelling or limitation of
movement is suggestive of active arthritis.
A) distribution : mono , oligo or poly arthritis
B) appearance : fleeting
1) infective arthritis- oligoarthritis
2) collagen vascular disease-fleeting
3) reactive arthritis
32. CONTEXTUAL HISTORY
Past Medical /Surgical History
Start by asking the patient if they have any medical
problems
IHD/DM/Asthma/HT/RHD, TB/Jaundice/Fits e.g. if diabetic- mention time of
diagnosis/current medication/clinic check up
Past surgical/operation history
E.g. time/place/ what type of operation.
Note any blood transfusion / blood grouping.
H/O dental extractions/circumcision & any excessive bleeding during these
procedures.
Patient known to have rheumatic heart disease is at risk to develop infective
endocarditis if not given prophylaxis
Any minor operations or procedures including endoscopies, dental
interventions, biopsies.
History of trauma/accidents
E.g. time/place/ and what type of accident
History of tattoo piercing
33. CONTEXTUAL HISTORY
Drug and allergy History
dosage, timing &how long.
Drug fever is uncommon and therefore easily missed-The
culprits include :
penicillin and
cephalosporin
sulphonamide
anti tuberculous agents
anticonvulsants particularly phenytoin
OCT/Vitamins/Traditional /Herbal medicine & alternative
medicine such as acupuncture.
Blood transfusion.
Immunization against Hepatitis A &B, Typhoid fever.
Malaria prophylaxis
34. CONTEXTUAL HISTORY
Family History
Any familial disease/running in families e.g. breast
cancer, IHD, DM, Asthma, Arthritis
Infections running in families as TB, Leprosy.
Cholera, typhoid in case of epidemics.
35. CONTEXTUAL HISTORY
Personal and Social History
Smoking history - amount, duration & type- strong risk factor for IHD
Alcohol history - amount, duration & type-Unhealthy alcohol use is
associated with cardiomyopathy, CVA, liver cirrhosis, alcoholic
hepatitis, hepatocellular carcinoma.
Occupation, social & education background, family social support&
financial situation, Social class.
Home conditions-Water supply, Sanitation status in his home &
surrounding, Geographic area of living, fresh-water swimming.
Animals / birds in his/her house- exposure to birds (psittacosis) or
animals (toxoplasmosis, brucellosis, leptospirosis)
Consumption of unpasteurized milk or milk products (tuberculosis,
brucellosis and Q fever).
Sexual History- Unprotected exposure to sexual partner with STI, HIV
Illicit drug usage- injections and sharing of needles (HIV, hepatitis B
&C, infective endocarditis), site of injection (e.g Femoral vein-septic
arthritis, ilio-psoas abscess)
36. CONTEXTUAL HISTORY
Travel History
Travel to an area known to be endemic for certain disease:
Name of the area, duration of stay
Onset of illness- (incubation period)
1 –10 Days- Malaria, Dengue, Salmonella
10 –21Days-Malaria,Typhoid,Brucella,HepatitisA
Weeks-Months- Amoebiasis, HIV, Hepatitis
Vital questions-(Always ask about foreign travel).
a) Where have you been? …Endemic area or not ?
b) What have you done?
C) How long were you there?
d) Did you have insect bites or contact with animals?
e) Did you take precautions/prophylaxis against malaria?
If the patient has been in an endemic area
The most common diagnoses :Malaria, Typhoid fever, Viral hepatitis,
Dengue fever
Malaria must be excluded whatever the presenting symptoms
37. PATIENTS PERSPECTIVE
Always ask the patient how he/she feels/thinks about
the illness by analysing
Ideas
Concerns
Feelings
Expectations
Effects on daily living
38. SYSTEMS REVIEW
General
• Weakness
• Fatigue
• Anorexia
• Change of weight
• Fever/chills
• Lumps
• Night sweats
39. SYSTEMS REVIEW
Cardiovascular
• Chest pain
• Paroxysmal Nocturnal Dyspnoea
• Orthopnoea
• Short Of Breath(SOB)
• Cough/sputum (pinkish/frank blood)
• Swelling of ankle(SOA)
• Palpitations
• Cyanosis
42. SYSTEMS REVIEW
Urinary System
• Frequency
• Dysuria
• Urgency
• Hesitancy
• Terminal dribbling
• Nocturia
• Back/loin pain
• Incontinence
• Character of urine: color/ amount (polyuria) & timing
• Fever
43. SYSTEMS REVIEW
Nervous System
• Visual/Smell/Taste/Hearing/Speech problem
• Head ache
• Fits/Faints/Black outs/loss of consciousness(LOC)
• Muscle weakness/numbness/paralysis
• Abnormal sensation
• Tremor
• Change of behaviour or psyche.
• Paresis.
44. SYSTEMS REVIEW
Genital system
• Pain/ discomfort/ itching
• Discharge
• Unusual bleeding
• Sexual history
• Menstrual history – menarche/ LMP/ duration &
amount of cycle/ Contraception
• Obstetric history – Para/ gravida/abortion
46. THE END: REFERENCES
Guyton's Textbook of Medical Physiology
Davidson's Principles & Practice of Medicine
Hutchinson's Clinical Methods
Harrison’s Principles of Internal Medicine
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