Transcript Pathophysiology of Fever

An Approach to a Patient with
Fever
MPPRC- IIB Group 1
General Objective
Integrate and apply knowledge acquired in
the subjects of Medicine I, Pathology,
Pharmacology and Radiology in the
management of a patient with fever
Specific Objectives
1. Identify significant signs and symptoms and
correlate with fever.
2. Define and explain the etiology and
pathophysiology of fever.
3. To identify the necessary ancillary procedures that
can help in the diagnosis of a patient with fever
4. To formulate an effective pharmacologic and nonpharmacologic management for a patient with
fever.
General Data
PP, 56 years old, female, married, market vendor from
Sampaloc, Manila
Missing Data:
• Date & time of interview
• Source & % reliability
• Interviewer & role
• Race
• Religion
• Birthday
• Place of birth
Chief Complaint : Fever
History of Present Illness:
3 weeks
2 weeks
Day of
consultation
and admission
• Fever
• Persistence of fever
• Self medication with Paracetamol,
Ibuprofen, and Amoxicillin
• Persistence of fever
• How was the temperature taken? How often?
• Impact on the patient’s lifestyle?
• Persons the patient had contact with who
manifested the same signs and symptoms.
• Associated symptoms
Past Medical History
• No other medical or surgical illness requiring
hospitalization
• No history of blood transfusion
• No history of illicit drug use
• No history of tattoo piercing
• No history of wading in flood waters
Past Medical History
• Childhood illness?
– Measles? Mumps? Chickenpox? Scarlet fever? Acute
rheumatic fever?
• Major Adult illness?
– Hepatitis? Myocardial infarction? Parasitic disease? Other
infections?
• Immunizations?
– Influenza? Cholera? Typhus? Hepatitis B? BCG? Typhoid?
• Past medications?
• Allergies?
• Recent health examination?
Obstetric & Gynecologic History
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G5P5 (2005)
Menarche- 13 years old
Menopause- 50 years old
Any complications in pregnancy or labor,
postpartum or with the infant?
• Multiple sex partners?
• Date of most recent Pap smear and result?
• Hormone therapy? Dose and duration?
Family History
• No family history of hypertension, diabetes
mellitus, cancer, pulmonary tuberculosis
• Autoimmune disease, blood disorders?
Personal and Social History
•Sampaloc, Manila
•Market vendor
•Non smoker, non passive smoker
•Non alcoholic beverage drinker
•Fond of eating street foods
•No travel to endemic areas
Missing Data:
1.
2.
3.
4.
5.
What is the patient’s usual diet? Preferred foods?
Food preparation?
Source of drinking water?
How is the patient’s home condition?
Any household pets?
Review of systems
General
• No sign of weight loss
• Body malaise, fatigability, night sweats?
Skin, hair, nails
• No rashes
• Bruising, lesions, dryness, pruritus?
Head and Neck
• No headache
• Dizziness, syncope, trauma?
Eyes
• No blurring of vision
• Discharge?
Ears
• No ear discharge, tinitus
• Otalgia?
Review of systems
Nose
• No data given
• Nasal discharge?
Breast
• No data given
• Lumps, nodules, pain?
Chest and Lungs
• No cough, difficulty of breathing
• Dyspnea, sputum, hemoptysis?
Cardiac
• No chest pain, palpitation
Gastrointestinal
• No diarrhea, constipation, melena, hematochezia
• Dysphagia, hematemesis, flatulence ?
Review of Systems
Genitourinary
• No dysuria, frequency, urgency, pollakuria, polyuria
• Pain, hematuria, changes in urine?
• Lesions, discharges, pain?
Lymph node
• No given data
• Enlargement, pain?
Musculoskeletal
• No joint pains
• Joint stiffness, restriction of motion, swelling?
Endocrine
• No heat or cold intolerance, polydipsia, polyphagia
Physical Examination
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•
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Conscious, coherent, obese, oriented as to time, place and person
BP = 110/80
CR = 80 bpm regular
PR = 80 bpm regular
RR = 22 per minute
Temperature = 39.5C
Height = 1.5m
Weight = 70kg
BMI = 31
No skin rashes
Pink palpebral conjunctiva
Anicteric sclera
Hepatospenomegaly
Physical Examination
• Pulse rhythm, amplitude, contour
• Respiration regularity, rhythm, depth, breath
sounds
• Heart sounds
• Abdominal tenderness
• Inspection and palpation of lymph nodes
• Pelvic examination
Salient Features
Subjective Data
• PP, 56 years old, female,
married, market vendor
from Sampaloc, Manila
• Prolonged intermittent, low
to moderate fever lysed by
ibuprofen and paracetamol
• Fond of eating street foods
• No travel to endemic areas
Objective Data
• Pulse temperature
disproportion
(PR=80bpm;Temp=39.5C)
• RR= 22/ min
• No skin rashes
• Pink palpebral conjunctiva
• Anicteric sclera
• Hepatosplenomegaly
• Unremarkable head, neck,
ear, nose, throat, eyes,
chest and lungs, heart and
blood vessels, breast and
axilla, GI, GU,
musculoskeletal.
• Based on the Medical history and physical
examination, the patient manifests with
prolonged fever secondary to infection.
Chief complaint: FEVER
“Is an elevation of body temperature that exceeds the normal daily variation
and occurs in conjunction with an increase in the hypothalamic set point.”
Harrison’s Principles of Internal Medicine, 17th edition
Fever classification
Grade
oC
low grade
38–39
moderate
39–40
high-grade
40–42
hyperpyrexia
>42
oF
100.4–102.2
102.2–104.0
104.0–107.6
>107.6
FEVER PATTERNS
Intermittent
40
39.5
39
38.5
38
37.5
37
36.5
36
35.5
D1
D2
D3
D4
Intermittent: marked by a daily temperature drop into the normal
range and then a rise back to above normal
Remittent
40.5
40
39.5
39
38.5
38
37.5
37
36.5
D1
D2
D3
D4
Remittent: A fever with diurnal variation of more than 1.1 0C but
with no normal readings
Continuous
39.6
39.5
39.4
39.3
39.2
39.1
39
38.9
38.8
38.7
38.6
D1
D2
D3
D4
Continuous: A fever with a diurnal variation of 0.5 to 10C
Relapsing
39.5
39
38.5
38
37.5
37
36.5
36
D1
D2
D3
D4
Relapsing: Febrile episodes are separated by intervals of normal
temperature; bouts of fever occurring every five to seven
days
Septic
40
39.5
39
38.5
38
37.5
37
36.5
36
35.5
D1
D2
D3
D4
Septic: An intermittent fever that fluctuates widely, typically producing
chills and sweating
Pathophysiology of Fever
• Pyrogen
– the term is used to describe any substance that
causes fever
Source: Harrison’s Principles of Internal Medicine (16th Edition), p. 106
Pathophysiology of Fever
• Cytokines
– small proteins (molecular mass,10,000 to 20,000
Da) that regulate immune, inflammatory, and
hematopoietic processes
• Pyrogenic cytokines:
– IL-1, IL-6, tumor necrosis factor (TNF), ciliary
.
neurotropic factor (CNTF), and interferon (IFN)
Source: Harrison’s Principles of Internal Medicine (16th Edition), p. 106
Pathophysiology of Fever
• The synthesis and release of endogenous
pyrogenic cytokines are induced by a wide
spectrum of exogenous pyrogens (bacterial,
fungal or viral sources)
Source: Harrison’s Principles of Internal Medicine (16th Edition), p. 106
Pathophysiology of Fever
• Cellular sources of pyrogenic cytokines
include: monocytes, neutrophils, and
lymphocytes
Source: Harrison’s Principles of Internal Medicine (16th Edition), p. 106
INDUCTION OF FEVER
Infection, microbial
toxins, mediators of
Inflammation, immune
reactions
Microbial toxins
Cyclic
AMP
Monocytes / macrophages,
endothelial cells, others
Pyrogenic cytokines IL-1,
IL-6, TNF, IFN, ciliary
neurotrophic factors
PGE2
Hypothalamic
endothelium
Fever
Heat conservation,
heat production
Elevated
thermoregulatory
set point
Circulation
Harrison’s Principle of Internal Medicine 17 th edition
Pathophysiology of Fever
• Tachycardia usually accompanies fever
PULSE RATE is PROPORTIONAL to
TEMPERATURE
Source: DeGowin’s Diagnostic Examination (8th Edition), p. 61-62
Pathophysiology of Fever
“For every 0 rise in temperature, pulse increases
by 10. Pulse temperature dissociation
is seen in typhoid, brucellosis, leptospirosis,
viral myocarditis, diphtheria, rheumatic
carditis, bacterial endocarditis, etc. “
www.rationalmedicine.com
-allergic reactions
-stimulation of the body's
immune response
-autoimmune diseases
- cancer
- drug reactions
- hormonal disorder
- hypothalamic tumors
-too much exposure to the sun
autoimmune diseases
allergic reactions
cancer
drug reactions
hormonal disorder
hypothalamic tumors
Non - infectious
No joint pains
No skin rashes
autoimmune diseases
allergic reactions
cancer
drug reactions
hormonal disorder
hypothalamic tumors
Non - infectious
No difficulty breathing
No skin rashes
allergic reaction
cancer
drug reactions
hormonal disorder
hypothalamic tumors
Non - infectious
No significant weight loss
No family history of
cancer
cancer
drug reactions
hormonal disorder
hypothalamic tumors
Non - infectious
drug reactions
No illicit drug use
No skin rashes
hormonal disorder
hypothalamic tumors
Non - infectious
No heat or cold
intolerance
No significant weight loss
hormonal disorder
hypothalamic tumors
Non - infectious
No heat or cold
intolerance
No significant weight loss
hypothalamic
tumors
Non - infectious
Non - infectious
Prolonged fever with
hepatosplenomegaly
Infectious origin
Tuberculosis
Brucellosis
Typhoid Fever
Pulse fever
disproportion
Prolonged fever with
hepatosplenomegaly
Infectious origin
Tuberculosis
Brucellosis
Typhoid Fever
Enteric (Typhoid)
Fever
Is a systemic disease characterized by
fever and abdominal pain and caused
by dissemination of S. Typhi or S.
Paratyphi.
Harrison’s Principles of Internal Medicine, 17th edition
Dissemination of the bacteria through the
macrophages via the lymphatics and colonize
reticuloendothelial tissue.
Hepatosplenomegaly
Use of antibiotic
before seeking
medical help
Pulse Fever
disproportion
Prolonged fever
Typhoid Fever
Incubation period of the agent
THE CAUSATIVE AGENT
Salmonella is a genus
in
the
family
Enterobacteriaceae that
has more than 2300
serotypes
previously
described
in
the
Kauffman-White schema
•Introduction to Diagnostic Microbiology by Danessa Delost
•Clinical immunology and Serology by Dorresteyn Stevens
S typhi has O and H antigens, an envelope
(K) antigen, and a lipopolysaccharide
macromolecular
complex,
called
endotoxin, that forms the outer portion
of the cell wall.
Salmonellae are grouped based on the
somatic O antigen and further divided
into serotypes based on flagellar H and
surface Vi (virulence) antigens
•Introduction to Diagnostic Microbiology by Danessa Delost
•Clinical immunology and Serology by Dorresteyn Stevens
S typhi is similar to other salmonellae in that it is:
• Gram-negative,
• Flagellate,
• Non-encapsulated,
• Non-sporulating,
• Facultative anaerobic bacillus,
• Ferments glucose,
• Reduces nitrate to nitrite,
• Synthesizes peritrichous flagella when motile.
•Introduction to Diagnostic Microbiology by Danessa Delost
•Clinical immunology and Serology by Dorresteyn Stevens
LABORATORY PROCEDURES
Complete Blood Count (CBC)
A complete blood count will normally include:
Red cell count
White cell count
Hemoglobin
Hematocrit
Differential Count:
Neutrophils: 55%–70%
Band neutrophils:0%–3%
Lymphocytes:20%–40%
Monocytes: 2%–8%
Eosinophils: 1%–4%
Basophils: 0.5%–1%
Complete Blood Count (CBC)
• Neutropenia
– May be present with some viral infections, drug
reactions
– Systemic Lupus Erythematosus
– Typhoid
– Brucellosis
– Lymphoma
– Tuberculosis
Complete Blood Count (CBC)
• Lymphocytosis
– Typhoid
– Brucellosis
– Tuberculosis
– Viral disease
Complete Blood Count (CBC)
• Monocytosis
– Typhoid
– Brucellosis
– Tuberculosis
– Lymphoma
Complete Blood Count (CBC)
• Monocytosis
– Typhoid
– Brucellosis
– Tuberculosis
– Lymphoma
IDENTIFICATION / LABORATORY DIAGNOSIS
• Gold Standard: Culture and Sensitivity
• Widal Test
• TyphiDot Test
• PCR and Molecular Studies
•
•
Introduction to Diagnostic Microbiology by Danessa Delost
Clinical immunology and Serology by Dorresteyn Stevens
CULTURE AND SENSITIVITY
• The organism is non-fastidious
• Can be cultured on Laboratory Culture Media
– Hektoin Enteric Agar
– Sheep Blood Agar
– Salmonella-Shigella Agar
– Mackonkey Agar
– TSI, LIA, SSA, Motility Agar, Urea Broth and other
Biochemical Test Agar Media
Black Raised Colonies in HEA
medinfo.ufl.edu/.../bms5300/images/d7047.jpg
The presence of any black colored area indicates the
deposition of hydrogen sulfide, (H2S) under alkaline conditions in
SSA
medinfo.ufl.edu/.../bms5300/images/d7047.jpg
Salmonella typhi in BSA
medinfo.ufl.edu/.../bms5300/images/d7047.jpg
THE WIDAL TEST
Accurate Serological Study
SEROLOGICAL STUDIES
• Employs the Widal Test (pronounced VIDAL
TEST)
• This test involves the agglutination of reagent
typhoid bacilli parts when mixed with serum
containing typhoid antibodies from an
individual having typhoid fever.
• This test differentiates typhoid fever and
paratyphoid fever.
•
•
Introduction to Diagnostic Microbiology by Danessa Delost
Clinical immunology and Serology by Dorresteyn Stevens
THE WIDAL TEST
• This test is Specific for the detection of typhoid fever.
• It measures the pressence of anti-”O” and anti-”H”
antibodies
• Uses bacterial suspension of killed S. typhi and S.
paratyphi. (Salmonella “O” antigens of groups A,B,C,D and
Salmonella “H” antigens groups a,b,c,d
• Antibodies formed against the “O” antigen are generally
of the IgM type and the Anti-H antibodies are generally
IgG type.
•
•
Introduction to Diagnostic Microbiology by Danessa Delost
Clinical immunology and Serology by Dorresteyn Stevens
TYPHI DOT TEST
• Employs Immunochrom Procedure
• Uses prepared antigen and patient’s serum
with antibody
• Sensitive and fast
• Expensive
•
•
Introduction to Diagnostic Microbiology by Danessa Delost
Clinical immunology and Serology by Dorresteyn Stevens
RADIOLOGY
• Chest X-ray
• Abdominal X-ray
• Ultrasound Imaging
CHEST X-RAY
• Not a reliable
procedure to
diagnose
• To rule out the
possibility of
tuberculosis
Abnormal Chest X-ray
• Fluffy infiltrate with
patchy areas of
consolidation involving
the upper and lower
parts of the right lower
and right upper lobes
respectively
Plain Films
• Determination of hepatomegaly on plain films
is generally unreliable and can be made with
certainty only when the liver is massively
enlarged.
• May show liver calcifications and air within
the biliary tree or abscesses
• Don’t show soft-tissue abnormalities such as
fluid-filled cysts, liver tumors, and dilated bile
ducts.
ULTRASOUND IMAGING
• To evaluate size, shape, and position of the liver.
• To evaluate problems of the liver, including liver
masses, cirrhosis, fat deposits
• To determine the size of the enlarged spleen and
look for damage or disease.
• To determine whether a mass in any of the
abdominal organs (such as the liver) is a solid tumor
or a simple fluid-filled cyst.
Pharmacotherapy
Pharmacotherapy
Problem
Goal
Solutions
• Decrease fever
•Antipyretics
• Find cause of
fever and eliminate
Typhoid Infection •Eliminate infective •antibiotics
agent
with broader
range
Persistent fever
despite of
medication
How to decrease Fever?
Antipyretics
• drugs that reduce body temperature
• cause the hypothalamus to override an
interleukin-induced increase in temperature
– Aspirin and paracetamol
Antipyretics
Aspirin
• Anti-inflammatory, antipyretic, analgesic, anticlotting drug
• suppressed the production of prostaglandins and
thromboxanes
– irreversible inactivation of the cyclooxygenase (COX)
enzyme
• acts as an acetylating agent where an acetyl group is
covalently attached to a serine residue in the active
site of the COX enzyme
Antipyretics
Paracetamol
• widely-used analgesic and antipyretic
• reduces the production of prostaglandins
– inhibit the cyclooxygenase (COX) family of
enzymes
• has no direct effect at the site of inflammation
but instead acts in the CNS to reduce
temperature
Antipyretics
Febrifuges
– herbal remedies with a fever-reducing effect
• catnip
• chamomile
• sage
• wormwood
• yarrow
How to decrease Fever?
•
•
•
•
Non pharmacologic approach
maintenance of adequate hydration
Maintenance of adequate fluid intake
External cooling
– use of cooling blankets
– alcohol sponges
How to eliminate Food-borne infection?
Drug of choice:
Ciprofloxacin
• oral tablets (250, 500, 750, and 1000 mg)
• ready-made infusion bottles (200 and 400 mg)
• BID
How to eliminate Food-borne infection ?
• Alternative choices:
3rd generation antibiotics
Ceftriaxone
• starting dose is 1 gram IV daily
• Doses range from 1–2 grams IV or IM every 12–24
hours, depending on the type and severity or the
infection, up to 4 grams daily
How to eliminate Food-borne
infection
Alternative choices:
4th generation antibiotics
Cefepime
Mild to moderate: 500 mg to 1 gram IV q12h.
Moderate to severe: 1-2 grams IV q12h.
http://www.globalrph.com/cefepime_renal.htm
How to eliminate Food-borne infection ?
Alternative choices:
Antibiotic combinations
Co-amoxiclav
Standard adult dosage:
co-amoxiclav 250/125 (one tablet Augmentin 250)
taken every 8 hours
How to eliminate Food-borne infection ?
Lt Gen SP Kalra AVSM Bar*, Lt Col N Naithani+, Col SR Mehta VSM#, Sqn Ldr AJ Swamy**. Current Trends in the Management of Typhoid Fever
http://medind.nic.in/maa/t03/i2/maat03i2p130.pdf
Thank you!!!