Dr David McGrath

Spine Physician

MB BS (Hons) FAFOM, RACP, FAFMM
Master of Pain Medicine

Temperature Regulation (and Fever)

Bottom Line: An important aspect of Homeostasis and component of microbial defence

1.Body temperature is tightly controlled in a small range.(36.5-37.5). Within this range our enzymes and other chemical processses work at optimal efficiency. This type of animal organisation is termed homoio/thermic (contrasting with poikiol/thermic ). Large increases from normal, leads to muscle "meltdown" known as rhabdo/myolysis and/or death.
2. Fever arises during a number of illnesses. Fever is usually part of a divergent response with associated, Sweating,Perception of Cold,Chills. (a missing component implies serious illness)
3.Heat arises through Thermogenesis. Thyroid hormone stimulates (Na-K )ATPase in cytoplasmic membranes (outer boundary of cells) leading to ADP ,phosphate and heat. (54kJ/mol)
4. The largest produces of heat in the body are Skeletal muscles,liver,splanchic organs and brain.
5. Exercise creates heat from muscles
6. Digestion produces heat from GIT
7. The nervous system regulates the balance between heat loss and metabolism.The hypothalamus is pivotal area of brain. (temperature sensing, motor output to hormonal system, vascular system, sweat glands) A high level, leads to greater heat loss mechanisms. A low level, leads to greater heat conserving mechanisms.
8. Heat loss, occurs through conduction, radiation and evaporative loss.(lungs and skin)
9. Heat re-distribution is achieved by the circulation. Heat delivered to the skin, is transfered into sweat losses. (in addition to conduction, radiation)
10. Diurnal variation. We cool during the night and heat during the day. Lowest temperature is around 2-4 am and highest 6-10pm. When a fever exists, it is superimposed upon the daily cycle.The temperature cycle is also invarient to night work-day sleep cycle reversal.
11. Younger individuals have a larger dynamic core temperature range. (lose less heat when it is cold, and more heat when it is hot)
12. Children are able to obtain more heat by splitting tia/acyl/glycerides into glycerol and FFA (free fatty acids) from their BROWN fat. (adults have very little of this type of fat)
13. Fever, is temperature >37.2 with sweating,hyperventilation,vasodilation in skin. Early phases may have muscle shivering,vasoconstriction,piloerection (hairs on end) (CHILLS). This reduces heat loss, which accompanied by an increase in metabolism (thyroid action ) leads to a heat accumulation and fever.
14.Fevers can be produced by micro-organisms and viruses. This provokes a defensive cascade, leading to local hormone release (cytokines). IL1,IL-6 and TNF-alpha are the principle PYROGENS.
They are produced by macrophages (monocytes), endothelial cells and astrocytes (brain cells). Some interferons also are pyrogenic. They also act through an intermediate activation of the COX prostaglandin pathways, to PGE2. Hence anti-inflammatories, through COX inhibitors (asprin, non steroidal drugs) block fever. (but not other actions of IL-1,TNF-alpha )
15. Pyrogens act on cells within the hypothalamus, allowing an increase in the temperature SET.Temperature rises until a new equilibrium is established within those brain cells. (receiving thermal input from from the circulation)

Mathematical we have:
Chemical Pyrogens-Core Temperature+Other=0
Core Temp=Positive (heat production,exothermic) + Negative (heat loss factors)
Pyrogens= Exogenous + Endogenous
Thus if we have an infection, core temperature goes UP

The main Endogenous Pyrogens in the body are IL-1 and TNF-alpha. Their effects are multiple.

Cellular Movements	Cellular Function
Myelopoesis (white cell numbers) and Bone Marrow release of Neutrophils (better defence)	Activate T cells (better defence)
Induce Fibroblasts numbers (ready for healing/scarring)	Decrease appetite (no energy needed for digestion)
Induce B cell numbers (better defence)	Activate Osteoclasts (break down bone)
Cellular Function
Mobilize Lipids from Adipocytes (More energy)	Induce Collagenase from Chondrocytes (break down cartilage)
Proteo/synthesis From Liver (Important proteins in defence)	Sleep activity in brain (be less active)
Glycogenolysis in Liver (Glucose release into blood)	Induce ACTH,Growth Hormone,ADH release from Pituitary (Hormone response for defence)
Glycogenolysis in Muscles (Glucose for Energy)	Increase release of Insulin,Cortisol,Adrenalin (more glucose absorption)
Beta Endorphins Increase (Signal control in NS)	Increase production of PAF (Platelet activating factor) (More clotting potential)

1. General effect is protective and catabolic (mobilisation of resources)
2. The optimal temperature for some of these processes is 39.5 C
3. Activates immune system, improves cellular nutrition,controls neural input

(to be continued)