A Level Biology: Homeostasis



Homeostasis literally means “standing still” and it refers to the process of keeping the internal body environment in a steady state. The importance of this cannot be over-stated since a great deal of the hormone system and autonomic nervous system is dedicated to homeostasis.


Factors that are controlled by homeostasis include: -


Body temperature – to keep enzymes working near their optimum temperature and stop them denaturing


Blood pH – to keep enzymes working near their optimum pH


Blood (sugar) glucose concentration – to ensure there is enough glucose available for cellular respiration, but not enough to lower the blood water potential and dehydrate cells


Blood water potential – to prevent loss or gain of water from cells by osmosis


You’ll need to know two examples of homeostasis in detail: temperature and blood glucose (but be aware that you may have to apply knowledge of homeostatic mechanisms to the others too!)


Negative and positive feedback


All homeostatic mechanisms use “Negative Feedback” to maintain a constant value (known as the set point).


Negative feedback means that whenever a “change” occurs in a system, the change automatically causes a corrective mechanism to start. This corrective course of action reverses the “change” and brings the system back to normal (i.e. back to its set point). 


[insert negative feedback graph]


So, in a system controlled by negative feedback the level is never maintained perfectly, but constantly oscillates about the set point. An efficient homeostatic system minimises the size of the oscillations.


Temperature Homeostasis (Thermoregulation)

One of the most important examples of homeostasis is the regulation of body temperature. There are basically two ways of doing this: mammals and birds can generate their own heat and are called endotherms; while all other animals rely on gaining heat from their surroundings, so are called ectotherms.


Temperature Homeostasis in Endotherms

Endotherms (mammals and birds) can generate heat internally, have thermal insulation, and can usually maintain a remarkably constant body temperature. Humans and most other mammals maintain a set point of 37.5 ± 0.5 °C, while birds usually have set points of 40-42°C. Endotherms are sometimes called warmblooded animals, but this term isn’t very scientific, partly because endotherms can get quite cold (e.g. during hibernation). Endotherms don’t keep their whole body at the same temperature: they maintain a constant core temperature; while allowing the peripheral temperature to be colder, especially the surface, which is in contact with the surroundings.


The advantage of being endothermic is that animals can survive in a wide range of environmental temperatures, and so can colonise almost any habitat, and remain active at night and in cold weather. 


This gives endothermic predators an obvious advantage over ectothermic prey. The disadvantage is that it requires a lot of energy, so endotherms need to eat far more than ectoderms.


In humans temperature homeostasis is controlled by two thermoregulatory centres in the hypothalamus.


The thermoregulatory centres receive input from two sets of thermoreceptors: receptors in the hypothalamus itself monitor the temperature of the blood as it passes through the brain (the core temperature), and receptors in the skin monitor the external temperature. Both pieces of information are needed so that the body can make appropriate adjustments.


One of the thermoregulatory centres – the heat loss centre – is activated when the core temperature rises. It sends impulses to several different effectors in the body to reduce the core temperature.


The other thermoregulatory centre – the heat gain centre – is activated when the core temperature falls. It sends impulses to several different effectors in the body to increase the core temperature.


The thermoregulatory centre is part of the autonomic nervous system, so the various responses are all involuntary. The exact responses to high and low temperatures are described in the table below:


[insert table]


Note that some of the responses to low temperature actually generate heat (thermogenesis), while others just conserve heat.


Similarly some of the responses to cold actively cool the body down, while others just reduce heat production or transfer heat to the surface.


Therefore, the body has a range of responses available, depending on the internal and external temperatures.

[insert diagram of thermoregulatory centres]


Mammals can alter their set point in special circumstances:


Fever. Chemicals called pyrogens released by white blood cells raise the set point of the thermoregulatory centre causing the whole body temperature to increase by 2-3 °C. This helps to kill bacteria and explains why you shiver even though you are hot.


Hibernation. Some mammals release hormones that reduce their set point to around 5°C while they hibernate. This drastically reduces their metabolic rate and so conserves their food reserves.


Torpor. Bats and hummingbirds reduce their set point every day while they are inactive. They have a high surface area: volume ratio, so this reduces heat loss.


Failure of temperature homeostasis


Hypothermia occurs when heat loss exceeds heat generation, due to prolonged exposure to cold temperatures. As the core temperature decreases the metabolic rate also decreases, leading to less thermogenesis. If the core temperature drops below 32°C shivering stops so the core temperature drops even further. If the core temperature falls below 30°C hypothermia is usually fatal.


Hyperthermia occurs when heat gain exceeds heat loss, usually due to prolonged exposure to high temperatures. This situation is often associated with dehydration, which reduces sweating, the only effective way to cool down. A rise in core temperature increases the metabolic rate, fuelling a further increase in temperature. If the core temperature rises above 40°C hyperthermia is usually fatal.


Both hypothermia and hyperthermia are examples of the dangers of positive feedback.


Positive feedback occurs when the change stimulates a further change in the same direction. Positive feedback is potentially dangerous and is usually associated with a breakdown in the normal control mechanism.


[insert positive feedback graph]


Temperature Control in Ectotherms (link to evolution adaptations)


Ectotherms (all animals except mammals and birds) rely on external heat sources to warm up; do not have thermal insulation; and their body temperature varies with the environmental temperature. 


Ectotherms are sometimes called cold-blooded animals, but this term isn’t very scientific, because ectoderms can get very warm. Reptiles, such as lizards, iguanas and crocodiles are classic ectotherms. They cannot warm up by shivering because, if their temperature is low, they cannot respire fast enough to make ATP for rapid muscle contraction. Instead, reptiles regulate their body temperature by thermoregulatory behaviour e.g: -


Iguanas start every day by basking on rocks in the sun until their metabolic rate is fast enough for them to become active.


Lizards lie down on warm ground to gain heat, and raise themselves off the ground if they get too hot.


To prevent overheating in the midday sun lizards take shelter under rocks or vegetation.


Some lizards can adjust the amount of heat they gain by changing their angle to the sun. Turning their backs to the sun presents the maximum surface area, while pointing towards the sun presents the minimum surface area.


Crocodiles can move between the land and the water during the day to maintain a constant temperature.


At night, lizards shelter in burrows, which provide insulation to reduce heat loss (and hide them from predators).


The advantage of being ectothermic is that animals use far less energy than endoderms. At rest the metabolic rate of a reptile is only 10% of that of a mammal of similar size. At night, when the core temperature of ectotherms drops with the temperature of the surroundings, their metabolic rate drops still further. This means ectothermic animals need to eat far less than endotherms, and can often survive for weeks without eating. The disadvantages are that, at certain times of the day, ectotherms can only move slowly and have slow reactions. This makes them easy prey and poor predators.



Blood Glucose Homeostasis

Glucose is the transport carbohydrate in animals, and its concentration in the blood affects every cell in the body. The brain in particular can only respire glucose (not lipids) but it doesn’t store glycogen. Very low concentrations of glucose (hypoglycaemia) will cause brain cells to die and very high concentrations (hyperglycaemia) will lower the blood water potential and kill cells by dehydration. The concentration of glucose in the blood is therefore strictly controlled within the range 80-100 mg 100cm-3. 


[insert diagram shows the main sources and fates of blood glucose]


The main source of blood glucose is the digestion and absorption of dietary carbohydrate (mostly starch). Blood from the intestine goes directly to the liver in the hepatic portal vein before being carried to the rest of the body.


Glucose is mainly used for respiration in all cells. It can also be used to synthesise amino acids, nucleotides, etc.


For storage glucose can be converted to the polysaccharide glycogen in liver and muscle cells (glycogenesis). This is reversible, and when glucose is needed the glycogen can be broken down again (glycogenolysis).


Excess glucose can also be converted to triglycerides in the liver (lipogenesis) then transported as lipoproteins to adipose tissue for storage. This process is irreversible: triglycerides can be used in aerobic respiration but cannot be used to make glucose.


Animals don’t normally synthesise glucose, but when dietary glucose is scarce proteins and nucleic acids can be used to synthesise glucose (gluconeogenesis).


Control of blood glucose concentration


Blood glucose concentration is unusual in that it is not controlled by the CNS, but by the pancreas, which is both an exocrine and an endocrine organ. Regions of the pancreas, called the islets of Langerhans, serve as both glucose receptors and as endocrine cells, releasing hormones to effect the control of glucose.


There are two kinds of islet cells, called alpha and beta cells. Both cells have glucose receptors, but the alpha cells detect low glucose concentrations and respond by secreting glucagon, while the beta cells detect high glucose concentrations and respond by secreting insulin. 


These two hormones are antagonistic, which means that they have opposite effects on blood glucose.


[insert glucose feedback diagram]


After a meal, glucose is absorbed from the gut into the bloodstream, increasing the blood glucose concentration. This increase is detected by the pancreas, which secretes insulin from its beta cells in response.


Insulin causes glucose to be taken up by the liver and converted to glycogen. This reduces blood glucose, which is detected by the pancreas, which stops secreting insulin. If the glucose level falls too far, the pancreas detects this and releases glucagon from its a cells. Glucagon causes the liver to break down some of its glycogen store to glucose, which diffuses into the blood. This increases blood glucose, which causes the pancreas to stop producing glucagon. These negative feedback loops continue all day, as shown in this graph:


[insert graph]


The mechanism of glucose homeostasis hormone action


[insert diagram] 


This diagram summarises how the hormones insulin and glucagon exert their effects. It also includes the hormone adrenaline, which is the “fight or flight” hormone released by the adrenal glands. Amongst many other effects, adrenaline also stimulates the release of glucose from the liver, to provide more energy for muscle contraction.


1. Insulin molecules bind to an insulin receptor protein in the cell membrane. This binding activates an enzyme active site on the inner surface of the same membrane protein, which catalyses a reaction activating a molecule called insulin receptor substrate (IRS). IRS is the second messenger for insulin.


2. IRS has two separate effects in the cell. Firstly it increases the rate of glucose uptake by recruiting more glucose transporters to the cell membrane. These receptors are stored in cytoplasmic vesicles, and IRS causes these vesicles to fuse with the cell membrane.


3. Secondly, IRS actives the enzyme glycogen synthase, which synthesises glycogen from cytoplasmic glucose. In fact there are several steps here: IRS activates one enzyme, which activates another, which activates another, which activates glycogen synthase. This cascade amplifies the effect, so each molecule of insulin can activate thousands of molecules of glycogen synthase.


4. If present in the blood, glucagon and adrenaline each bind to their specific membrane receptor proteins.


5. These hormone-receptor complexes now activate a membrane-bound enzyme called adenylate cyclase, which catalyses the conversion of ATP to cAMP (cyclic adenosine monophosphate), which is the second messenger for these hormones.


6. cAMP activates the enzyme glycogen phosphorylase, which catalyses the breakdown of glycogen to glucose. This process involves another multi-step cascade amplification.


These hormones demonstrate two advantages of the second messenger system: one hormone (insulin in this case) can have two completely different effects in a cell; while two different hormones (glucagon and adrenaline in this case) can have the same effect in a cell. Each hormone can have different effect in different cell types too.

Diabetes Mellitus

Diabetes is a disease caused by a failure of glucose homeostasis. 


There are two forms of the disease. 


In insulin-dependent diabetes (also known as IDDM, type 1 or early-onset diabetes) there is a severe insulin deficiency due to autoimmune killing of b cells (possibly due to a virus). This type usually appears in childhood.


In non insulin-dependent diabetes (also known as NIDDM, type 2 or late-onset diabetes) insulin is produced, but the insulin receptors in the target cells don’t work, so insulin has no effect. This type tends to appear in overweight people at around age 40, and it accounts for 90% of diabetes cases in the industrialised world.


In both cases there is a very high blood glucose concentration after a meal, so the kidney can’t reabsorb it all back into the blood, so much of the glucose is excreted in excess urine (diabetes mellitus means “sweet fountain”). This leads to the symptoms of diabetes:


• high thirst due to osmosis of water from cells to the blood, which has a low water potential.

• copious urine production due to excess water in blood.

• poor vision due to osmotic loss of water from the eye lens.

• tiredness due to loss of glucose in urine and poor uptake of glucose by liver and muscle cells, so no glycogen stores.

• muscle wasting due to gluconeogenesis caused by increased glucagon.


Until the discovery of insulin in 1922 by Banting and Best, diabetes was an untreatable, fatal disease. Today diabetes can be treated by injections with insulin or by careful diet. Insulin can be extracted from the pancreas tissue of cattle and pigs, or it can be made in fermenters by genetically-engineered bacteria (pxx).


Treatment is improving all the time, with the development of fast-acting and slow-acting insulin preparations; simpler injection pens; oral insulin preparations (insulin, a protein hormone, is normally digested in the intestine); portable insulin infusion pumps; and even the possibility of islets of Langerhans transplants.

Control of the Mammalian Oestrous Cycle

Female mammals produce eggs and become receptive to mating in a regular cycle, called the oestrus cycle.


The oestrus cycle can vary in length from five days in mice to one year for red deer. Oestrus itself refers to the period of the cycle when the female is sexually receptive, or “on heat”. For example dogs usually come into heat twice a year. In humans the oestrus cycle is also known as the menstrual cycle because it is one month long (from the Latin mens, month). Humans (and other primates) are unusual in that the females are sexually receptive throughout the year, and the uterine lining (the endometrium) is shed each month through the vagina in the process of menstruation (the “period”).


The menstrual cycle in humans is controlled by four hormones secreted by two glands.

• The pituitary gland, below the hypothalamus in the brain, secretes the hormones follicle stimulating hormone (FSH) and luteinising hormone (LH), which target the ovaries.

• The ovaries are endocrine organs as well as creating and releasing ova. They secrete the hormones oestrogen and progesterone, which target the pituitary gland and the uterus.

The effects of these four hormones are shown in this diagram.


[insert diagram]


Each hormone affects the release of other hormones by negative and positive feedback loops, so each hormone is produced in sequence. This chart shows how the concentration of each hormone in the blood changes throughout a 28-day cycle.


[insert graph]


1. FSH is secreted by the pituitary glands, and stimulates the development of a Graafian follicle in one of the ovaries. This follicle contains a single ovum cell surrounded by other calls.


2. The follicle secretes oestrogen, which stimulates the uterus to rebuild the endometrium wall that has been shed during menstruation. Oestrogen also affects the pituitary gland, initially inhibiting the release of FSH. However, as the follicle gradually develops, the concentration of oestrogen in the blood rises, and it starts to stimulate the release of FSH and LH by the pituitary gland.


3. The sudden surge of LH at about day 14 causes the fully developed follicle to burst, release the ovum in the oviduct – ovulation. LH also stimulates the follicle to develop into a body called the corpus luteum, which secretes progesterone.


4. Progesterone stimulates the uterus to complete the development of the endometrium wall, which is now ready to receive an embryo. Progesterone also inhibits the release of LH and FSH by the pituitary gland, which in turn stops the release of oestrogen and progesterone by the ovaries.


5. The corpus luteum degenerates over the next 10 days, due to prostaglandins produces by the ovary, so less progesterone is secreted. When the concentration of progesterone drops low enough, menstruation is triggered. The inhibition of the pituitary gland is also removed, so FSH starts to be released and the cycle starts again.


If an egg is fertilised and the embryo implants in the uterus, the embryo secretes a hormone called human chorionic gonadotrophin (HCG). HCG stops the corpus luteum degenerating, so progesterone continues to be produced and there is no menstruation. Progesterone also stops the pituitary releasing FSH, so no more ova are matured during pregnancy. Pregnancy test kits test for the presence of small amounts of HCG in the urine.