Fever and hyperthermia

Eva Lovsov 2010

Skin : less than core

warmer core 37oC

Outside: -20 to + 40 But also -60 and +100 (Antarctis/sauna)

perpheral (skin) thermoreceptors

central thermoreceptors hypotalamus, spinal cord

centre of thermoregulation hypotalamus

TSH-RH TSH T3, T4

ANS - sympathicus

somatomotor NS

metabolism brown adipose tissue muscle shivering muscle activity

sweat glands

vasomotor activity

Mechanisms of heat production

metabolism skeletal muscle tone muscle shivering chemical thermogenesis in brown adipose tissue And helping vasoconstriction heat saving voluntary mechanisms - behaviour

Mechanisms of heat loss

radiation Conduction, convection evaporation And helping vasodilatation
radiation convection evaporation

20oC 30oC 36oC 61% 26% 13% 46% 27% 0% 0%

27% 100%

Fever
stages prodromal stage stadium incrementi - temperature raise stadium acme culmination of fever stadium decrementi decrease of temperature

Fever prodromal stage

exogenous pyrogens lipopolysaccharides endogenous pyrogens IL-1, IL-6, TNF
hypotalamic thermostat

arachidonic acid
cyclooxygenase

ASA ibuprofen

PGE2 increased set point

Stadium incrementi
increase of heat production and saving of heat vasoconstriction white, cold skin higher muscle tone muscle shivering behaviour warm dress, warm covers

Stadium acme
body temperature is maintained at the new level until the fever breaks. endogenous antipytetics arginine vasopressin melanocyte-stimulationg hormone ACTH-RH exogenous antipyretics acetylsalicylic acid

return the set point to normal

Stadium decrementi
decrease of heat production and heat loss vasodilatation sweating

Difference between fever and hyperthermia

39

Hyperthermia real temperature

38

37

set point thermoregulation failure

Difference between fever and hyperthermia

39

Fever real temperature

38

37

set point
thermoregulation failure

NO! normal thermoregulation

Classification of fever
Intensity subfebrility + 0,5oC middle fever + 2oC high fever + 3oC very high fever + > 3oC

Classification of fever
Type febris continua 1oC febris remittens 1,5 - 2oC februs intermittens - alternation of febrile and nonfebrile periods febris recurrens - return of fever (malaria) febris atypica - (typhus abdominalis)

Classification of fever
Length febris ephemera febris acuta febris chronica 1 day

Benefits of fever
kills thermolabile microorganisms it has adverse effects on growth and replication of some microorganisms decrease of serum level concentration of iron, zinc, copper which are needed for some microorganism lysosomal breakdown effect on phagocytosis production of antiviral interferon

Malignant hyperthermia (hyperpyrexia)

malignant hyperthermia syndrome malignant hyperpyrexia rare life-threatening condition that is triggered by exposure to certain drugs used for general anaesthesia (specifically volatile anesthetics - Halothane), and the neuromuscular blocking agent succinylcholine Hereditary

the syndrome firstly recognized in Australia in 1962 the efficacy of dantrolene as a treatment was discovered by South African anesthesiologist Gaisford Harrison in 1975 incidence: between 1:4 500 to 1:60 000 general anaesthesias Cause mutation in the ryanodine receptor, inherited autosomal dominant at least 70 mutations gene on the long arm of the 19th chromosome (19q13.1) these mutations tend to cluster in one of three domains within the protein, designated MH1-3. MH1 and MH2 are located in the N-terminus of the protein, which interacts with L-type calcium channels and Ca2+. MH3 is located in the transmembrane forming C-terminus. This region is important for allowing Ca2+ passage through the protein following opening.

Pathomechanism
50-70% of cases mutation of ryanodine receptor (RYR) located on the sarcoplasmatic reticulum (SR) RYR opens in response to increases in intracellular Ca2+ level mediated by Ltype calcium channels drastic increase in intracellular calcium levels muscle contraction. The process of reabsorbing this excess Ca2+ consumes large amounts of ATP, and generates the excessive heat (hyperthermia). The muscle cell is damaged by the depletion of ATP, the high temperatures, and the leak of potassium, myoglobin, creaite...from the cells. mutation of CACNA1S gene, which encodes L-type voltage-gated calcium channel other mutations

Signs and symptoms

muscular rigidity hypermetabolic state with increased oxygen consumption and hypercapnia tachycrdia hypertermia - ~2C per hour, > 38C, up to 42C rhabdomyolysis red-brown decoloration of the urine cardiological signs - evidence of electrolyte disturbances tachycardia, ventricullar fibrilation respiratory acidosis metabolic acidosis high blood concentration of creatine kinase, pottasium, myoglobin The symptoms usually develop within one hour after exposure to trigger substances, but may even occur several hours later in rare instances.

Treatment
Dantrolene (Dantrolene sodium) intravenously Dantrolene - a muscle relaxant - work directly on the ryanodine receptor to prevent the release of calcium. After the widespread introduction of treatment with dantrolene the mortality of malignant hyperthermia fell from 80% in the 1960s to less than 10%.