2FEVERIs an elevation of body temperature above the normal circadian range as the result of a change in the thermoregulatory center located in the anterior hypothalamus andpre-optic area
3thermoregulation Body heat is Generated by a) basal metabolic activity andb) muscle movementand lost byConductionConvection (which is increased by wind or fanning)Evaporation which is increased by sweating
4Body temperature is controlled in the hypothalamus, which is directly sensitive to changes in core temperatureThe 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.
5In 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
6FEBRILE RESPONSE The initiation of fever begins when exogenous or endogenous stimuli are presented to specialized host cells, principally monocytes and macrophages ,they will stimulates the synthesis and release of various pyrogenic cytokines including :1)interleukin-1, interleukin-62)TNF-α, and3)IFN-γ.
71) Exogenous : stimuli from out side the host Like : microorganism, their products, or toxins and it is called EndotoxinEndotoxin : lipopolysaccharide ( LPS)LPS: is found in the outer membrane of all gram negative organismAction :1) through stimulation of monocytes and macrophages2) direct on endothelial cell of the brain to produce fever
82) 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
9Pyrogens:Substances that cause fever are called pyrogensWhat are these pyrogens:Cytokines :Definition :Cytokines are regulatory polypeptides that are produced by1) monocytes / macrophages2) lymphocytes3) endothelial and epithelial cell and hepatocytes
10The most important ones are : Interleukin 1 and 1 - :The most pyrogenicTumor necrosis factor InterferonInterleukin 6 ……………The least pyrogeniccytokines>fever develop within 1h of injection
11Mechanism of actionCytokine-receptor interactions in the pre-optic region of the anterior hypothalamusactivate 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.
12Diurnal variation6 am : 37.2………4pm : 37.7Rectal temperature>0.6o C oral temperatureFever: Morning : AM >37.2o CEvening : PM >37.7o C
13PRESENTATION OF FEVER Feeling hot A feeling of heat does not necessarily imply feverRigors.profound chills accompanied by chattering of the teeth and severe shivering and implies a rapid rise in body temperature. Can be produced by :1) brucellosis and malaria2) sepsis with abscess3) lymphomaExcessive sweating.Night sweats are characteristic of tuberculosis, but sweating from any cause is usually worse at night.
14Definition of fever Headache. Fever from any cause may provoke headache.Severe headache and photophobia, may suggests meningitisDelirium.Mental confusion during fever is well described and relatively more common in young children and in old age.Muscle pain. Myalgia is characteristic ofViral infections such as influenzaMalaria and brucellosis
15HyperthermiaIs an elevation of core temperature without elevation of the hypothalamic set point.Cause : inadequate heat lossExamples:1) Heat stroke2) Drug induced such as tricyclic antidepressant3) Malignant hyperthermia. associated with psychiatric drugs
16Why fever Elevation of body temperature increases chance for survival Temperatures appear to increase1) The phagocytic and Bactericidal activity of neurtrophils and3) The cytotoxic effects of lymphocytes …..soThe growth and virulence of several bacterial species are impaired at high temperature .
18Intermittent fever : exaggeration of the normal circadian rhythm…and when the variation is large it is called hecticcause :a) Deep seated infectionb) Malignancyc) Drug feverQuotidian fever : hectic fever that occur daily .Remittent fever :Temperature falls daily but not to normal .Causes : a) tuberculosisB) viral infectionC) many bacterial infections
19Relapsing fever :febrile episodes are separated by intervals of normal temperature a) Malaria fever every 3days (tertian).plasm. falciparamor every 4 days (quartan) ..plasm .vivaxb) Borrelia ..Days of fever followed by days of no fever .
20Fever patternPel-Ebstein fever : fever for 3 to 10 days followed by no fever for 3 to 10 daysCauses : a) Hodgkin lymphomab) Tuberculosis
21Fever PatternFever pattern cannot be considered diagnostic for a particular infection or disease and the typical pattern is not usually seen because of use of :1) Antipyretics2) Steroids3) Antibiotics
22impTemperature – pulse dissociation ( Relative bradicardia )is seen inA) Typhoid feverB) BrucellosisC) leptospirosisD) factitious feverE) acute rheumatic fever with cardiac conduction abnormalityF) Viral myocarditisG) Endocarditis with valve ring abscess affecting conduction .
23Fever Patterns..Degree Fever with extreme degree: gram-negative bacteremia,Legionnaires‘ disease, andbacteremic pyelonephritisNoninfectious cause of extreme pyrexia:heat stroke, intracerebral hemorrhage
24Physical examination Fever may sometimes be absent: seriously ill newbornselderly patients,uremic patient,significantly malnourished individuals,receiving corticosteroids orcontineous treatment with anti-inflammatory or antipyretic agents
25Approach to the febrile patient The most important step isMeticulous detailed history
26Approach to fever Detailed complain of the patient with the Rule out common infectionCareful history:1) chronology of symptomsDetailed complain of the patient with thesymotoms arranged chronologically
272) Use of drugsDrug fever is uncommon and therefore easily missed.The culprits include :penicillin andcephalosporinsulphonamideanti tuberculous agentsanticonvulsants particularly phenytoin
28prosthatic valve replacment 3)Surgical or dental procedurePatient known to have rheumatic heart disease is at risk to develop infective endocarditis if not given prophylaxis4)Nature of any prosthetic material or implanted devicesprosthesis implant for : the knee jointprosthatic valve replacment
295). occupational history including Exposure to animals : brocellosis infected person at home ..tuberculosis or infleunza6) Geographic area of living..
304) Travel historyAlways ask about foreign travel.a) Where have you been? …Endemic area or not ?b) What have you done?C) How long where you there?d) Did you have insect bites or contact with animals?e) Did you take precautions/prophylaxis against malaria
31If the patient has been in an endemic area The most common final diagnoses:Malaria,Typhoid fever,Viral hepatitis andDengue feverMalaria must be excluded whatever the presenting symptoms
325) Household pits6) Ingestion of unpasteurized milk or cheeses7) Sexual practice8) Iv drug abuse9) Alcohol intake10) Prior transfusion or immunization11) Drug allergy
33HISTORY-TAKING IN FEBRILE PATIENTS Symptoms of common respiratory infections.1) Sore throat, nasal discharge, sneezing …URTI (VIRAL )2) Sinus pain and headache. ….suggesting A sinusitis3) Elicit symptoms of lower respiratory tract infectioncough, sputum, wheeze or breathlessness
34Genitourinary symptoms. Ask specifically about :frequency of micturition, dysuria, loin pain, and vaginal or urethral discharge ….suggestinga) Urinary tract infection,b) Pelvic inflammatory disease andc) Sexually transmitted infection (STI)
35Abdominal symptoms.Ask about diarrhea, with or without blood, weight loss and abdominal pain ..suggesting :a) Gastroenteritis,b) Intra-abdominal sepsis,c) Inflammatory bowel disease,d) Malignancy
36Joint symptoms.joint pain, swelling or limitation of movement . If present ask aboutA) distribution : mono , oligo or poly arthritisB) appearance : fleeting or additiveIt suggest 1) infective arthritis…oligo2) collagen vascular disease…..fleeting3) reactive arthritis
37Travel history Always ask about foreign travel. If the patient has been in an endemic areaThe most common final diagnoses:Malaria,Typhoid fever,Viral hepatitis andDengue feverMalaria must be excluded whatever the presenting symptoms
38Drug history. Drug fever is uncommon and therefore easily missed. The culprits include :penicillin andcephalosporinsulphonamideanti tuberculous agentsanticonvulsants particularly phenytoin
39Alcoholic hepatitis, Alcohol consumption. hepatocellular carcinoma are all recognized causes of fever.
40Family history OFTuberculosisArthritisOther infectious diseasesAny one with symptomatology ofPolyserositis or bone pain
41Turks , Arabs , Armenians likely to have Ethnic origin of the patientis important. .Example:Turks , Arabs , Armenians likely to haveFamilial Mediterranean fever
422. Physical examinationRepeated meticulous examination on a regular basis until diagnosis is made .Temperature should be taken1) Orally ..or2) Rectally ….Axillary temperature is notoriously unreliable .
43Cautions while taking oral temperature 1) Recent consumption of hot or cold drinks2) Smoking3) Hyperventilation
44EXAMINATION 1) Document the presence of fever …and Do not miss FACTITIOUS FEVER
45FACTITIOUS FEVERThis 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 who work in paramedical professions.
46Examples includeThe dipping of thermometers into hot drinks to fake a fever,The factitious disorder is usually medicalbut may relate to a psychiatric illness with reports of depressive illness.
47FACTITIOUS FEVER CLUES TO THE DIAGNOSIS OF FACTITIOUS FEVER A patient who looks wellAbsence of temperature-related changes in pulse rateTemperature > 41°CAbsence of sweating during defervescenceNormal ESR and CRP despite high feverUseful methods for the detection of factitious fever include1) Supervised (observed) temperature measurement2) Measuring the temperature of freshly voided urine
48A careful examination is vital and must be repeated regularly Particular attention should be paid to :The skin ………….for skin rashThroat…………….for pharyngitisEyes………………for jaundice , scleritis.Nail bed ………….for clubbing, splinter hemorrhage.lymph nodes…….. for enlargmantabdomen …………for ascitis or sign of peritonitisheart ……………...for murmurs indicating endocarditis.
492) Look for RASHa) Erythmatous rash ( rash that blanch on pressure )Causes :1) Meseals : often accompanied byupper respiratory tract symptomsand conjunctivitis2) other viral infection like : rubella , scarlet fever
55Axillary lymph node enlargment :..may suggests: 1) Sepsis2)leukemia3) lymphomaJoints ( any joing but commonly the knee and ankle )Look for swelling , redness,hest and effusion …suggest active arthritis ..?infective
56Factitious fever Neck ..look for stiffness..may suggest meningitis Abdomen :Look for : Tenderness especially in the RIF…acute appendicitisChest and heartSign of consolidationPleural effeusionPericardial rubCardiac murmur………Endocarditis or acute rheumatic fever
5920 years male who is heroin drug abuser for long time came to ER c/o: of left thigh pain and fever .Look at the picture and guess what is his problem
60The answer :Hip flexor spasm due to psoas abscessSecondary to staphylococcus septicemia with seeding into the muscle
61Laboratory tests Laboratory investigation is indicated if presentation suggests more thanSimple viral infection oracute phartngitis in children,Lab test can be focused if the history is suggesting certain diagnosis
621) complete blood count with deifferential , 1) invetigations:1) complete blood count with deifferential ,** band forms and toxic granulation ..suggest bacterial infection** Neutropenia : may be seen with :Infection : Typhoid,brucellosis ,viral infectionvasculitis : systemic lupus erythromatosis
63** lymphocytosis : may be seen in : Tuberculosis , brucellosis , Viral disease.** Monocytosis : is seen withTuberculosis , typhoid and brucellosislymphoma**Eosinophilia is seen in :Hypersensitivity drug syndromHodgkin diseaseAdrenal insufficiency
64blood films to exclude Malaria UrinalnalysisSample any fluid and examine : pleural, peritoneal or jointBone marrow biopsy for histopathology study if :an infiltrative disease is suspectedStool inspection for occult blood
652) chemistry : electrolytes ,glucose, urea , and liver function 3) microbiologySamples from : sputum , urethra and other sites like joint, pleural fluid , ascetic fluid ..and send forsmears and cultureSputum evaluation :a) gram stainingb) Z-N staining for asid fast bacilliCulture for :blood, abnormal fluid collection and urineCSF: if meningitis is suspected ..gram stain and culture
66SPECIAL BLOOD TEST :HIV screening for patient who has risk factor :1)Recent travel with sexual exposure2) injection drug user3) sex workers4) blood transfusion recipientRadilologychest x ray is indicated for any patient with significant febrile illness.
67Outcome of diagnostic efforts 1) patient recover spontaneouslysuggesting : viral illness or some of the spontaneously recovering bacterial infection : mainly intracellular organism like typhoid or brucellosis2) diagnosis is reached3)If fever persist for more than 2-3 weeks with no diagnosis is reached by : a) repeated physical examinationb) laboratory test ….thenIt is pyrexia of unknown origin
68Treatment of fever Is it fever or hyperthermia Hyperthermia 1.Heat strokeClassic heat stroke2.Drug-induced hyperthermia3.Malignant hyperthermia
69Heat strokeThermoregulatory failure in association with a worm environment1) Exertional : young person exercising at ambient temperature and or humidities that are higher than normal .2)non Exertional :typically occur in elderly.
70Hyperpyrexia : more than 40 should be treated by : anti pyretics and physical cooling While resetting the hypothalamic set point with antipyretic will speed the process.Antipyretics also help for :Headache , myalgia , chills .
71Low grade or moderate fever is not harmful ; So no antipyretics use except for1)pregnant women2) child with febrile seizures .
72Why no antipyretics for mild fever Obscure the natural history of the patient disease or syndrome.Gives false feeling of well being ..may miss meningitis …Imminently life- threatening
73Antibiotics use In ER Pathogens Infection focus host factors (Immune factors)Common infection in ER1. UTI2. Respiratory tract infection3. CNS infection4. Cellulitis
74Antibiotics use in-UTI Upper urinary tract infectionSymptomes : Fever , flank pain, dysurialab test : Pyuria , bacturiaTreatment : cotrimoxasole , Cephalosporin oraminoglycoside …….duration: 7-10 days
75Antibiotics use In-Respiratory tract infection Pneumonia1. Cough, fever, sputum or notclinical manifestations: consolidationCXR : .opacity with air bronchograminterstitial infiltratesputum : gram‘s stainTreatment :3rd generation cephalsporine and macrolides
76Antibiotic use in-respiratory tract infection Nosocomial feverFever aquired after 48 hours of admittion to the hospital1) pneumonia2) catheter related infection3) UTIConsider hospital pathogen while selecting antibiotics
77Antibiotics use in-CNS infection Bacterial meningitis1. Aggressive antibiotics-due toprognosis and sequence2. cephalosporinVancomycinViral meningitis1. Observation, s/s Tx2. Herpes meningitis- acyclovircontinuing