Ridha Ramdani Rahmah 130110110108 F1

THERMOREGULATION

The internal core temperature is homeostatically maintained at 100
0
F (37.8
0
C). The normal body temperature varies among individuals
and varies throughout the day, ranging from 35.5
0
C in the morning to 37.7
0
C in the evening.
Thermoregulatory concept (!) : Internal core (organs, CNS, and muscles) and outer shell (skin and subcutaneous fat)
The temperature within the internal core is subject to precise regulation maintain its homeostatic constancy --> 37.8
0
C. In contrast, the
temperature in outher shell is cooler, and it helps to maintain the cores thermal constancy.
Heat input to the body must balance heat output to maintain a constant total heat content and thus a stable core temperature.

The hypothalamus is the bodys thermostat.

The core temperature is monitored by central thermoreceptors,
while the outer shell temperature is monitored by peripheral
thermoreceptors.
The posterior region of hypothalamus is activated by cold, triggers
reflexes that mediate heat production and conversion
The anterior region is activated by warmth, initiate reflexes that
mediate heat loss
Non-shivering thermogenesis is mediated by epinephrine and
thyroid hormone, both of which increase heat production by
stimulating fat metabolism

Temperature-decreasing mechanisms Temperature-increasing mechanisms
Vasodilation of skin blood vessels Vasoconstriction of skin blood vessels
Sweating. An additional 1
o
C increase in body temperature causes
enough sweating to remove 10 times the basal rate of body to
produce heat
Piloerection, sympathetic stimulation causes the arrector pili
muscles attached to the hair follicles to contract , which
brings the hairs to an upright stance
Decreases in heat production, shivering and thermogenesis are
inhibited
Increases in thermogenesis, by promoting shivering,
sympathetic excitation, and thyroxine secretion






FEVER

Definition
Ridha Ramdani Rahmah 130110110108 F1
The term fever refers to an elevation in body temperature that is caused by infection or inflammation (Sherwood). Fever, which means a
body temperature above the usual range of normal, can be caused by abnormalities in the brain itself or by toxic substances that affect the
temperature-regulating centers (Guyton). Fever is defined as a rectal temperature 38
0
C and a value 40
0
C is called hyperpyrexia.

Pyrogen
The term pyrogen is used to describe the substance that causes fever. There are two types of pyrogen, exogenous and endogenous. IL-1
released from neutrophils and macrophages (fever-causing cytokines) are known as endogenous pyrogens to differentiate them from
pathogen-produced exogenous pyrogens.
Pyrogens act directly on the hypothalamus, the portion of the brain that controls the bodys thermostat. The release of endogenous
pyrogens by inflammatory cells occurs after phagocytosis, after exposure to bacterial endotoxin, or after exposure to antigen-antibody
complexes.

Endogenous Exogenous
Cytokines : IL-1, IL-6, TNF-, and IFN-
, IFN-
Infectious pathogens : microbes,
microbial toxins, or other product of
microbes
Stimulated leukocytes Drugs : vancomycin, amphotericin B,
and allopurinol
Cells that produce lipid (PGE
2
)
Antigen-antibody complexes in the
presence of complement, lymphocyte,
bile acids, and androgenic steroids
capable for stimulating endogenous

Malignancy can produce them
Inflammatory diseases can produce
them


Etiology
1. Infectious : bacteria, virus, protozoa, parasites
2. Non-infectious
a. Inflammatory
b. Neoplastic
c. Miscellanous : AMI, pulmonary embolism, phlebitis, dry gangrene, cerebrovascular accidents, acute pancreatitis, pulmonary
hemorrhage, acute respiratory distress syndrome, noninfectious diarrhea, pleural effusions, renal infarcts, C. difficile di arrhea
d. Immunological rheumatological disorder
e. Drugs
f. Metabolic and endocrine disorder
g. Tissue injury

Clinical Phase
1. Prodormal phase : nonspecific complaints, such as mild headache and fatigue, general malaise, and fleeting aches
2. Cold or chill phase : shivering (heat production), although the temperature is higher, vasoconstriction, and piloerection, the skin is pale
and is covered with goose flesh, feeling of being cold, put to curl up in position
3. Fever phase : cutaneous vasodilation, skin becomes warm and flushed
4. Defervescence phase : initiation of sweating

Type
Type Description Diseases
Intermittent An exaggerated circadian rhytm that includes a period of
normal temperatures on most days; extremely wide
fluctuations may be termed septic or hectic fever
Abscesses, malaria falciparum, miliary TB,
peritonitis, gram-negative sepsis,
endocarditis, Kawasaki disease, toxic shock
syndrome
Remittent Persistent and varies by more than 0.5
0
C/day TBC, p. falciparum malaria, viral URTI, ARF,
legionella, mycoplasma
Relapsing It is characterized by febrile periods that are separated
by intervals of normal temperature
Relapsing fever, dengue, malaria, smallpox,
yellow fever, brucellosis
Biphasic A single illness with 2 distinct periods (camelback fever
pattern)
Leptospirosis, dengue fever, colorado thick
fever, smallpox, yellow fever, poliomyelitis,
chikungunya fever
Continuous Persistent and does not varies by more than 0.5
0
C/day Typhoid fever, scarlet fever, brucellosis, drug
fever, fastitious fever

Pathogenesis
Certain disease states, through the elaboration of exogenous pyrogens, stimulate monocytes and macrophages to produce endogenous
pyrogens such as IL-1, IL-6, TNF-, and interferon-. These pyrogenic cytokines act at the endothelial surface of the circumventricular
organ of the preoptic area of the anterior hypothalamus (PO/AH) to induce the production of PGE2, which elevates the bodys thermal
set point.
Ridha Ramdani Rahmah 130110110108 F1
Physiologic and behavioral responses may be invoked to raise body temperature to a new set point. This febrile response must be
considered in the context of an overlapping acute-phase response as a global nonspecific response to the original insult. Intrinsic
central antipyretics and systemic antipyretics exert their effects by decreasing levels of PGE2, decreasing the set point and lowering
body temperature.
Endogenous cryogens or antipyretics : arginine vasopressin (AVP), -melanocyte-stimulating-hormone (-MSH), and corticotropin-
releasing factor are released from the brain, and systemic anti-inflammatory cytokines

Benefits
A raised body temperature kills many microorganisms and has
adverse effects on the growth and replication of others.
It decreases serum levels of iron, zinc, and copper, all of which are
needed for bacterial replication.
The body switches from burning glucose to a metabolism based on
lipolysis and proteolysis, thereby depriving bacteria of a food source.
Anorexia and somnolence reduce the demand for muscle glucose.
It also causes lysosomal breakdown and autodestruction of cells,
thus preventing viral replication in infected cells.
Heat increases lymphocytic transformation and motility of
polymorphonuclear neutrophils, thus facilitating the immune
response.

Notes
A temperature increase of normally 1
0
F is accompanied by an
appropriate pulse increase of 10 beats/min

References
1. Sherwood, Lauralee. 2010. Human Physiology, 7
th
ed.
2. Arthur C. Guyton, and John E. Hall. 2006. Textbook of Medical
Physiology, 11
th
ed.
3. Kathyrn L. McCance et al. 2010. Pathophysiology : The Biologic Basis
for Disease in Adults and Children, 6
th
ed. Mosby Elsevier.
4. Kliegman, et al. 2011. Nelson Textbook of Pediatrics, 19
th
ed. Elsevier.
5. Braunwald et al. 2005. Harrisons Principles of Internal Medicine, 16
th

ed.
6. Burke A. Cunha. 2006. Infectious Diseases in Critical Care
Medicine, 2
nd
ed.