JC95 (Medicine) - Fever Flashcards
Define normal oral, rectal, tympanic and axillary temp
Oral: 33.2-38.2
Rectal: 34.4-37.8
Tympanic: 34.4-37.8
Axillary: 35.5-37.0
Determinants of basal body temperature
Age, sex, time of measurement (diurnal pattern and ovulation pattern), activity level, illnesses
Describe the physiological responses to increase body temperature
Increase temperature detected by temperature-sensitive receptors in skin and hypothalamus
Increase voluntary responses:
- Reduce activity
- Loose clothing
- Expose body to cold environment
- Cooking drink
Hypothalamus activates cooling mechanisms:
- Increase parasympathetic nervous system - Increase sweating
- Decrease sympathetic nervous system - increase vasodilation and decrease basal metabolic rate
Describe physiological responses to hypothermia
Voluntary responses:
- Eat
- Seek heat source
- Increase muscle activity
- Warm clothing
Hypothalamic response:
- Increase thyroid hormone - increase BMR
- Increase sympathetic nervous system: Vasoconstriction, Increase BMR, Piloerection
- Increase shivering
Physiological mechanism of pyrexia at the hypothalamus
1 .Infections releases LPS and causes Monocyte activation/ LPS directly enters hypothalamus/ Inflammation triggers monocyte reaction
- Monocytes Release pyrogenic cytokines e.g. IL-1, TNFa, IL-6 into blood stream
- Pyrogenic cytokines stimulate endothelium of hypothalamus to release PGE2
- PGE2 activates EP3 receptors and downstream neurotransmitters, cAMP at Hypothalamic thermoregulatory center
- Increase thermoregulatory set point and activate peripheral heat response (e.g. chills, rigor)
- Fever
Define oral, rectal, tympanic and axillary temperatures limits for fever
Define hyper-pyrexia
Hyper-pyrexia = >40
Compare fever with hyperthermia
- Physiology
- Temperature pattern
- Causes of hyperthermia
Fever:
- Change in hypothalamic set-point by pyogenic cytokines
- Preserve diurnal variation
Hyperthermia
- Failure in thermoregulation
- No diurnal variation
Causes:
Heatstroke, Malignant neuroleptic syndrome (neuroleptic, antipsychotics), Serotonin syndrome, thyroid storm
Causes of these fever patterns
A, B - Continuous fever
- Pyogenic infections
- Dengue fever
- Fungal infections
C - Remittent fever
- Infective endocarditis
- Brucellosis
- Typhoid fever
D - Intermittent fever
- Malaria
- Tuberculosis
- Lyme disease
- Borreliosis
- EBV
Ddx major causes of fever
Infections: viral, bacterial, fungal, parasitic
Autoimmune diseases: e.g. Sarcoidosis, SLE, Giant cell arteritis…
Malignancies: Lymphoma, Leukaemia, RCC…
Tissue destruction: Massive infarct, Massive hemolysis, Rhabdomyolysis
Metabolic disorders: Gout attack, Porphyria
Drugs: Antibiotics, Anticonvulsants (cf hyperthermia in antipsychotics)
Pyrexia of unknown origin
Clinical definition
Fever >38.3 on several occasion
Over duration of 3 weeks
Unable to reach diagnosis despite 1 week of inpatient investigation
Most common causes of Pyrexia of Unknown Origin
Most common: Non-infectious inflammatory disorders
Infection:
- Mycobacterial
- Abdominal abscess
- Endocarditis
Malignancies
- Solid organ
- Lymphoma
Autoimmune:
- Vasculitis
- Adult Still’s disease
- SLE
Drug fever
4 types of hypersensitivity reactions
- IgE mediated HS
- IgG mediated cytotoxic HS
- Immune complex-mediated HS
- Cell-mediated HS
Type 1 Hypersensitivity reaction
Pathophysiology
IgE mediated HS
- IgE bind to mast cells via Fc portion, allergen cross links IgE and causes degranulation
- Causes localized and systemic anaphylaxis
E.g. seasonal allergies, food allergies
Type 2 Hypersensitivity reaction
- Pathophysiology
- example
IgG-mediated Cytotoxic HS
IgG tags onto target cell for:
Cytotoxic T cell recognizes Fc region of IgG and initiates cell killing (ADCC)
Complement activation
e.g. ABO mismatch, erythroblastosis fetalis
Type III hypersensitivity reaction
- Pathophysiology
- Examples
Immune complex mediated HS
Antigen-Ab complex deposit in tissue can activate complements, chemotaxis draws neutrophils to site of infection
Examples: Glomerulonephritis, RA, SLE
Type IV hypersensitivity reaction
- Pathophysiology
- Examples
Cell-mediated HS
Th1 cells secrete cytokines
Activate MQ and cytotoxic T cells to site of infection
Examples:
Contact dermatitis
Tuberculin reaction
Autoimmune diseases: Type 1 DM, Multiple sclerosis, RA
Drug fever
3 pathophysiological mechanisms and examples of each mechanism
Hypersensitivity reaction
Altered thermoregulatory mechanism
- Exogenous thyroid hormone
- Anti-cholinergic drugs
- Sympathomimetic drugs (e.g. ecstasy, amphetamine)
Idiosyncratic reaction (Antipsychotics and antidepressants)
- Serotonin syndrome (SSRI, Tramadol)
- Neuroleptic malignant syndrome
- Malignant hyperthermia
Outline history taking for PUO
Localizing symptoms: infection, malignancy, autoimmune
Drug history
- Exogenous thyroid hormone
- Anti-cholinergics
- Sympathomimetics
- Antipsychotics and antidepressants
Travel history and exposure history
Immunosuppression conditions
2 acute phase reactants
Erythrocyte sedimentation rate - long-term inflammation
C-reactive protein - acute inflammation
ESR
Confounding factors that increase and decrease ESR levels
Increase ESR: Age Female sex Pregnancy Anaemia Renal disease
Decrease ESR:
Red cell abnormalities
Extreme leukocytosis
Hyper-viscosity (e.g. MM)
Explain why albumin is low in acute inflammatory response (check)
Rouleaux formation increases during acute inflammatory response due to acute phase reactants and immunoglobulin in blood
Albumin acts to decrease the rate of rouleaux formation and becomes depleted
C reactive protein
Physiological process of production
Function of CRP
Infection or inflammation activates monocytes to release IL6, IL1B
Inflammatory cytokines bind to hepatocytes and activate NFkB pathway for transcription and translation of plasma CRP
Plasma CRP increases complement C1q binding to bacterium
Plasma CRP binds to apoptotic cells for phagocytosis
Plasma CRP binds to inflamed tissue and activates neutrophil, monocytes
Procalcitonin
Normal physiological production
Normal:
Only thyroid and lung produces pro-calcitonin
Thyroid C-cells produces most of pro-calcitonin and calcitonin
Procalcitonin
- Production during inflammation
Inflammation: All organs produce procalcitonin (c.f. only lung and thyroid normally)
Pathway:
LPS activates monocytes to release pro-inflammatory cytokines IL-1B and TNF-a
Pro-inflammatory cytokines active Calcitonin gene transcription in ADIPOCYTES (in any organ)
Calcitonin mRNA»_space; Pro-calcitonin production
Procalcitonin directly released through vesicles from Golgi apparatus
Compare the time of onset and concentration response of Pro-calcitonin to treatment
Procalcitonin level drops rapidly and rises rapidly in comparison to CRP > good for early identification of sepsis
Procalcitonin levels drop after effective treatment
Modalities of imaging for PUO
CT, MRI
Gallium scan
PET-CT
