regulation of blood glucose described above is a classic example of negative feedback; here two antagonistic hormones are constraining a variable within its normal range by minimising any deviations from the physiological set point.
If a variable remains consistently outside of its normal physiological range then pathological (disease) states usually occur. In the case study at the start of the chapter, Ian’s blood glucose was recorded at 24.5 mmol/l, which is greatly outside its normal range of 4–6 mmol/l. As a patient with type II diabetes, over time Ian had become progressively resistant to the effects of his own insulin. Without an effective insulin response to reduce his blood glucose, Ian arrived at his GP surgery with pronounced hyperglycaemia (see next section).
In some patients with type II diabetes insulin injections are also prescribed to help lower their blood glucose. Occasionally, particularly when the patient has not eaten enough carbohydrate, insulin injections can lead to blood glucose dropping below its normal range; this is referred to as hypoglycaemia. Hypoglycaemia is extremely dangerous and can potentially lead to coma and death unless treated quickly. Fortunately, most patients who use insulin learn to become aware of the early warning signs of hypoglycaemia (e.g. feeling shaky and disorientated) and carry something sweet such as a bar of chocolate or some biscuits to quickly boost their blood glucose.
Hyper and hypo prefixes
In clinical practice, the terms hyper (meaning high) and hypo (meaning low) are commonly used as prefixes when a named variable is outside of its normal range. In Ian’s case the term hyperglycaemia literally means: hyper (high) glyc (sugar/glucose) aemia (in blood), so hyperglycaemia is the medical term for high blood sugar. Similarly, if a patient injects too much insulin, this results in hypoglycaemia, which means hypo (low) glyc (sugar/glucose) aemia (in blood) or low blood sugar.
Now that you have been introduced to the prefixes hyper and hypo, attempt Activity 2.1 to reinforce your understanding.
Activity 2.1 Evidence-based practice and research
Write down the medical terms for the following pathological states. Hint: you will need to know the chemical symbols for each of the electrolytes below.
High blood calcium and low blood calcium
High blood sodium and low blood sodium
High blood potassium and low blood potassium
There are some possible answers to all activities at the end of the chapter, unless otherwise indicated.
Activity 2.1 reveals the importance of learning medical terminology since all of the pathological states highlighted in the activity will be routinely encountered in clinical practice. We will now develop your understanding of negative feedback by examining how a stable body temperature is maintained.
Regulation of body temperature: thermoregulation
Most of the cellular enzymes that drive the biochemical reactions necessary for life have an optimal temperature which is usually close to that of the core temperature of the body. In health, core temperature is maintained close to 37°C and this can be regarded as the physiological set point.
The normal range for core temperature is extremely narrow at between 36.1°C and 37.2°C (Figure 2.2). To ensure core temperature is maintained close to 37°C, the human body has some very elaborate and highly coordinated physiological responses.
Figure 2.2 Homeostatic control of body temperature
Increased body temperature (hyperthermia)
As core temperature begins to rise (e.g. following a bout of intense exercise) temperature sensors (thermoreceptors) detect this rise and feed information to the hypothalamus. This region of the brain functions as the thermoregulatory control centre initiating the physiological changes that will lower core temperature towards the set point of 37°C. When the core temperature is high, the hypothalamus increases blood flow to the skin by initiating the vasodilation of blood vessels in the dermis. Since the skin has a large surface area of over 1.5–2 square metres, this allows rapid heat loss through conduction, convection and radiation. If the core temperature remains high then eccrine sweat glands in the skin can be activated. These produce a thin watery sweat that will evaporate at the skin’s surface to allow rapid cooling; however, if water intake is not maintained then prolonged sweating can lead to dehydration (Chapter 1).
If the core temperature cannot be reduced, this can lead to hyperthermia (remember, hyper means high), and this is commonly seen in heatstroke, for example in endurance athletes. Heatstroke is a life-threatening medical emergency since having a persistently high core temperature reduces the activity of the enzymes essential for cellular metabolism and energy release. It is treated initially by cooling the body by whatever means are available; initially this will involve removing layers of clothing and immersing the body in cool water or using ice packs.
Low body temperature (hypothermia)
Unlike many animals, humans do not have a layer of fur to minimise heat losses. The thin layer of hair that we possess can only trap a small amount of warm air close to the skin, which leaves the human body very vulnerable to heat loss. Without adequate shelter and heat, in cold environments the core temperature can rapidly drop, slowing the rate at which cellular enzymes can function. As the core temperature drops, thermoreceptors relay information to the hypothalamic thermoregulatory control centre, which responds by switching off the production of sweat and reducing blood flow to the skin by initiating vasoconstriction in the dermis.
This minimises heat loss at the skin surface and typically results in the skin taking on a pallid and sometimes bluish appearance (think of how your fingers look when making a snowball).
If this is not sufficient to raise the core temperature towards the set point quickly enough, shivering is initiated where the major skeletal muscle groups contract in spasmodic movements to generate extra heat. If an individual remains in a cold environment for extended periods of time, hormonal adaptations occur such as enhanced release of adrenaline and the thyroid hormones (T3 and T4). This increases the metabolic rate in the longer term (Figure 2.2), generating further internal heat via metabolic thermogenesis. These hormonal adaptations allow the body to adapt to living in a colder environment.
Beneath the dermis of skin is a layer of subcutaneous fat called the hypodermis. This acts as a layer of insulation helping prevent heat loss by holding the heat generated through metabolism within the core of the body. Individuals that are overweight or obese often find it difficult to lose heat because their subcutaneous layers are thicker and this can put them at greater risk of heatstroke, particularly when exercising on hot days. Conversely, older individuals often lose a significant amount of subcutaneous fat as they age and consequently find it harder to retain heat and maintain their core temperature.
Older people also tend to have a lower metabolic rate and a reduced shivering response which places them at increased risk of hypothermia. Hypothermia (remember, hypo means low) is defined as a core temperature of 35°C or lower. At these temperatures cellular enzymatic activity will have slowed significantly and the patient will initially show increased shivering and progressive mental confusion. As hypothermia progresses, the shivering response may be lost, allowing the
