Homeostasis questions

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In what way do plasma proteins act as buffers? Will a deficiency in plasma proteins produce alterations of acid base balance?

How long ago was nitric oxide discovered? Is it a substance that has been re-discovered and likely to be used as a form of treatment? If so for what forms of disease?

How do the skeletal, muscle and integumentary systems interact to preserve homeostasis in the human body?

What is the importance of homeostasis to living organisms?

How are the cardiovascular and respiratory systems affected by the environment?

What are two examples of homeostasis?

What are the advantages and disadvantages of homeostasis?

What is the influence of smiling on the physiology and chemistry of the body, and why is it good for our health to smile?

How does the immune system contribute to homeostasis?

We have been given an assignment to discuss regulatory mechanism in the cardiovascular and integumentary systems that maintain homeostatic balance. I am finding it very difficult to obtain much information on the subject and I would be very grateful of any information that you may be able to send me.

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In what way do plasma proteins act as buffers? Will a deficiency in plasma proteins produce alterations of acid base balance?

Recall that a protein is built up from a sequence of amino acids. Some of the amino acids - for example histidine - are able to carry out a buffering function and ‘mop up’ or release hydrogen ions according to circumstances and help to stabilise pH at an optimal level. (These amino acids have acidic radicals that can dissociate to form weak bases plus hydrogen ions that can function as a buffering system. In case you are not familiar with the term ‘buffer’, it means a chemical system which helps to maintain the level of acidity/alkalinity of a solution at an acceptable and relatively constant level.)

Proteins are very plentiful inside cells and in various extracellular fluids, and they provide an important and rapid buffering action. In plasma there are three main classes of proteins: albumin, globulin, and fibrinogen, most of which are produced in the liver and lymphoid tissue, and all of which can contribute to the maintenance of acid-base balance. However, they are helped in this vital homeostatic role by other buffering systems:

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bicarbonate and phosphate buffers in the blood and tissue fluid act within seconds or fractions of seconds, like the proteins

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modulation of the rate of carbon dioxide removal from the blood by the respiratory system helps maintain an appropriate pH, but acts more slowly over minutes rather than seconds

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excretion of acids and alkalis by the kidneys has a powerful influence on acid-base balance but takes longer - hours and days

With regard to the effects of a deficiency of plasma proteins - this would depend to some extent on the reason for the deficiency. For example, in nephrosis (a kidney disease) the plasma proteins are lost into the urine, and together with loss of normal kidney buffering functions this would threaten acid-base homeostasis. On the other hand, if the reduction in plasma proteins is the result of under-production of the proteins by the liver, it is possible that the other buffering systems could compensate at least for a time. However, we should also remember the other roles of plasma proteins in producing colloid osmotic pressure, immune reactions, and blood coagulation when considering the effects of a deficiency.

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How long ago was nitric oxide discovered? Is it a substance that has been re-discovered and likely to be used as a form of treatment? If so for what forms of disease?

"Few science watchers will not be aware of the biological importance of nitric oxide. The speed of the unfolding of this story is breathtaking. As recently as 1978 it was conclusively proved that nitric oxide was produced by living systems; since then the ramifications of the observation have had major implications in the control of at least three systems - cardiovascular, immunological, and nervous." Breckenridge (1995)

Although nitric oxide has been known about for a long time, its biological significance was discovered only recently. By 1987 it was shown that nitric oxide is released by the endothelial cells lining blood vessels (Palmer et al, 1987). From here the nitric oxide diffuses to adjacent smooth muscle cells in the vessel wall and causes them to relax, allowing vasodilation. Nitric oxide is now regarded as a key determinant of blood pressure and local blood flow.

To many people’s surprise, nitric oxide has since been found to have significant controlling effects on at least three other major systems: the immune system, nervous system, and locomotor system. In the immune system, nitric oxide is involved in the killing of bacteria and tumour cells. In the nervous system, nitric oxide has several roles. During development, it halts the cell cycle of developing neurons and causes them to begin their final differentiation. It also influences axonal growth. In the adult nervous system, nitric oxide is involved in memory by providing a feedback loop between postsynaptic and presynaptic neurons that modifies the properties of the synapses. It is involved in olfactory sensation. Nitric oxide is also active in brain areas concerned with sexual and emotion-linked behaviours. It is involved in autonomic functions such as penile erection and peristalsis. In the locomotor system, nitric oxide appears to have a similar relaxing effect on skeletal muscle to that on vascular smooth muscle.

With regard to the possible clinical applications of this knowledge, there appear to be two main therapeutic strategies - either deliver more nitric oxide to sites where it is needed, or inhibit nitric oxide formation where it is in excess. Here are some examples of the therapeutic applications currently being investigated:

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cardiovascular function: in atherosclerosis, the endothelium has a reduced capacity to produce nitric oxide. The widely used anti-angina drug nitroglycerine (glyceryl trinitrate) is now known to enhance the production of nitric oxide, and research is in progress to find other drugs that have a similar effect

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immune reactions: nitric oxide is released in large quantities by macrophages when engulfing and killing bacteria. On occasion, however, this produces a severe drop in blood pressure as blood vessels dilate in response to the nitric oxide, and this can lead to circulatory shock and unconsciousness. In this life-threatening situation, inhibitors of nitric oxide synthesis may be useful. In the context of cancer, methods are being sought to enhance the cytotoxic ability of lymphocytes and to encourage cancer cells to undergo apoptosis by producing endogenous nitric oxide

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nervous system: excess nitric oxide seems to be involved in the acute damage caused by a stroke and in the longer term brain damage in Parkinson’s disease, Huntington’s disease, and Alzheimer’s disease. Inhbitors of nitric oxide are being developed as treatments for these diseases

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pregnancy: during a normal pregnancy, increased production of nitric oxide helps to keep blood vessels functioning well with the increased maternal blood volume. However, in pre-eclampsia nitric oxide regulation is inadequate and blood pressure rises, endangering both mother and unborn baby. A nitrate-releasing skin patch is being evaluated as a potential treatment for this condition

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lungs: nitric oxide gas has been used to reduce dangerously high blood pressure in the lungs of infants. The dosage is critical, since the gas can be toxic at high concentrations

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impotence: nitric oxide can initiate erection by dilating the blood vessels supplying the penis. This knowledge has already led to the development of new drugs against impotence

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artificial blood: haemoglobin has a high affinity for nitric oxide, and plays a key role in nitric oxide homeostasis - it has the ability to mop up free nitric oxide and also to release it when required. This property of haemoglobin will need to be emulated by artificial replacements for blood

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diagnosis: inflammatory diseases can be identified by analysing the production of nitric oxide by tissues such as the lungs and intestines. This is used for diagnosing asthma, colitis, and other diseases.

To mark the significance of their work on nitric oxide, the 1998 Nobel Prize for physiology or medicine was awarded to Furchgott, Ignarro, and Murad.

Reference

Breckenridge, A. (1995) British Medical Journal310, 377-380 (11th. Feb).

Palmer, R.M.J., Ferrige, A.G., and Moncada, S. (1987) Nature327, 524-526.

Snyder, S. (1994) More jobs for that molecule. Nature372, 504-505.

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How do the skeletal, muscle and integumentary systems interact to preserve homeostasis in the human body?

All the body systems contribute to homeostasis through a complex web of interactions with each other, and it is difficult to disentangle three systems for consideration as if in isolation. However, here are examples of homeostatic links between the skeletal, muscular and integumentary systems.

The skin interacts indirectly with the skeletal system by being one of the sources of vitamin D. Within skin exposed to sunlight, vitamin D is synthesised from a precursor molecule and transported to the digestive tract where it is needed. Vitamin D enables the uptake of calcium from our diet, and of course calcium is a key constituent of bone. The mineral component of bone matrix contains a modified form of calcium phosphate known as calcium hydroxyapatite, and if there is insufficient uptake of calcium then bone formation will be adversely affected. (Vitamin D is also present in some food materials, and this can compensate for a potential deficiency in climates where sunshine is scarce.) So the skin contributes to calcium homeostasis and skeletal health.

Because of its composition, bone acts as a calcium reserve, and there are times when calcium must be mobilised from bone tissue for use by other systems. For example, it is very important for normal muscle function that there is the correct level of calcium ions in the blood and tissue fluids - too much or too little calcium can compromise muscle activity. Therefore, the skeletal system also contributes to calcium homeostasis.

Muscular activity requires a source of energy and this comes predominantly from glucose delivered via the blood stream and glycogen stored within the muscle cells. When muscles are working aerobically, there are several by-products: heat, carbon dioxide, and water. The heat produced by active muscles helps to maintain body temperature, so muscle is contributing to heat homeostasis. However, if more heat is being produced than is needed, as for example during vigorous exercise, the excess heat has to be lost from the body to prevent a harmful rise in body temperature and the potential development of heat stroke.

This is where the integumentary system can help - the large surface area of the skin makes it ideal for temperature regulation, and excess heat can be dissipated by radiation, conduction, and convection. The rate of heat loss can be modulated by increasing or decreasing the amount of blood flowing through blood vessels in the dermis close to the surface of the skin. Skin blood flow is regulated by the temperature-regulating centre in the hypothalamus, which directly influences sympathetic tone in dermal blood vessels. When the body temperature rises, as for example during exercise, sympathetic tone is reduced and this brings about dilatation of the blood vessels supplying the skin. The increase in skin blood flow allows heat to be lost more rapidly so that body temperature does not rise above the normal homeostatic range. The rate of heat loss can also be boosted by the production of sweat, which takes up additional heat as it evaporates. Conversely, if heat production is less than required, the dermal vessels constrict, sweating stops, and heat is conserved by the body. So the skin contributing to heat homeostasis.

From these two examples - heat and calcium - it can be seen that the skeletal, muscular, and integumentary systems work together to maintain homeostasis.

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What is the importance of homeostasis to living organisms?

The larger living organisms are composed of communities of cells. Each cell is alive and interacts with its immediate surroundings. To remain alive and functioning normally, cells need a relatively constant environment from which they can obtain the materials they need to carry out the metabolic processes within them, and be able to dispose of their waste materials into the environment without them accumulating and becoming toxic. Many of the functions that cells perform depend on specialised macromolecules such as proteins, and these large molecules are extremely sensitive to temperature and other qualities of their surroundings. They can quickly become disrupted if they are exposed to fluctuating conditions.

Homeostasis is the name given to the dynamic processes that enable optimum conditions to be maintained for constituent cells, in spite of continual changes taking place both internally and externally. All the systems of the human body are involved, with particular contributions by the endocrine, nervous, respiratory, and renal systems. Whenever an imbalance occurs, regulatory systems become active to restore the optimum conditions, usually by a process known as negative feedback in which a deviation from the normal level is detected and initiates changes which bring the level back to where it should be.

The concept of a constant internal environment was first discussed by the French physiologist Claude Bernard in the middle of the nineteenth century. In 1932 Cannon introduced the term 'homeostasis' and defined it as - 'a condition which may vary, but remains relatively constant' (Clancy and McVicar, 1995).

Reference

Clancy, J., and McVicar, A. (1995) Physiology & anatomy: a homeostatic approach. London: Edward Arnold (Introduction to homeostasis, pp 2-7).

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How are the cardiovascular and respiratory systems affected by the environment?

We are open systems, constantly interacting with the changing environment that surrounds us and engaged in a wide range of activities. To ensure our survival, the systems of the body have to adapt continuously to these changing circumstances. We have to satisfy our basic needs for food, water, and oxygen and at the same time be able to rid ourselves of waste materials such as carbon dioxide, faeces, and urea. Linking these inputs and outputs are the complex metabolic, behavioural, and psychological processes which make us what we are. In the midst of all these dynamic activities, the internal environment of the body has to be kept within certain quite narrow limits for the sake of the delicate cells from which the body is made. This is the process called homeostasis, and the cardiovascular and respiratory systems have important roles in this - in order to maintain homeostasis all the bodily systems have to work together in co-ordination.

cardiovascular system

Think of the heart, blood vessels, and blood as a transport system delivering oxygen, nutrients and hormones to the cells of the body and removing metabolic waste products. Changes in the activities of the cardiovascular system are often a result of changes in the activities of other systems such as the musculoskeletal system (eg: during exercise), or the nervous system (eg: during stressful experiences). Here are some of the physical and psychological influences on the cardiovascular system set in motion by environmental events:

physical

The heart rate, cardiac output, peripheral resistance and blood pressure respond to different degrees of bodily activity, and sometimes our level of activity is dictated by environmental factors. At rest - when demands on bodily systems are less and we are in a secure and non-threatening environment- the heart rate slows and cardiac output falls. During exercise the heart rate speeds up and the cardiac output increases. The degree by which these changes occur will be dependent upon the activity which is undertaken and the level of control that we have over them. Walking briskly to the shops to obtain food clearly uses more energy than driving there, or sitting and resting after the food has been consumed! Lifestyle factors such as dietary habits and exercise have profound effects on the cardiovascular system, and although there is an element of personal choice in this, there are also powerful environmental influences on us to behave in particular ways. A diet that is low in animal fat, salt, and refined sugar is thought to be beneficial to the cardiovascular system. However, many of the processed foods that are heavily advertised contain high proportions of fat, salt, and sugar, and a dietary dependence on these products will lead to and increased risk of cardiovascular problems. Aerobic exercise brings undoubted benefits, while a lifestyle that avoids stressing the cardiovascular system on a regular basis is thought to be detrimental. Cigarette smoking has a profound effect on cardiovascular function due to the damage that nicotine has the endothelial lining of blood vessels, accelerating atherosclerotic changes and increasing the risk of premature death.

psychological

Our emotional state can be modified by environmental events and stimuli, and these changes can in turn influence heart rate, blood pressure, and patterns of blood distribution. Love, anger, and sexual excitement are examples of emotional feelings that can be triggered environmentally and result in a temporary increase in sympathetic nervous system activity, increasing heart rate and blood pressure. (There are times when an acute stress can produce the opposite effect: for example, the sight of blood may cause a sudden fall in peripheral resistance, a fall in blood pressure, and fainting.) Prolonged exposure to stress, for example during conflict and war, can drain the ability of the body to adapt, leading eventually to exhaustion and even death. Embarrassing situations can cause blushing and increased heart rate. On the other hand, listening to soothing music can reduce the heart rate and lower blood pressure.

respiratory system

Breathing is essential to life: it allows oxygen to be taken in, carbon dioxide to be given off, and the pH of the blood to be regulated. The metabolic processing food within cells in order to obtain the energy needed for a whole range of cellular activities is dependent on a continuous supply of oxygen to the cells. Here are some of the environmentally-derived factors that can influence respiratory function:

physical

Any significant changes in the availability of oxygen can lead to a state of hypoxia (low oxygen levels in the blood) and endanger cells that have a continuous oxygen requirement. For example, an ascent to high altitude has a profound effect on respiratory function, and when the adaptive changes are exhausted the climber will experience altitude sickness. Problems can also arise when diving to great depths in the ocean. Prolonged exposure to air contaminated with harmful substances such as coal dust, silica dust, and asbestos can lead to severe pulmonary fibrosis, producing pneumoconiosis, silicosis, or asbestosis respectively. Chronic exposure of the bronchial epithelium to the tar and nicotine contained in cigarettes significantly increases the risk of lung cancer. Bacteria, viruses and protozoa can invade the respiratory system and produce inflammatory responses within the walls of the bronchial tree. The transfer of gases then becomes impaired as a result of the oedema that accompanies the inflammatory response to infection. In spite of vaccination programmes, infectious diseases such as pulmonary tuberculosis are still of major public health concern.

psychological.

Our emotional state can have an effect on the respiratory rate, as we saw in the context of the cardiovascular system. When we are calm and at rest, the respiratory rate slows and breathing is more shallow as opposed to the increase in rate and depth (hyperventilation) that can occur when stress is experienced. When we are very anxious we can become aware that our breathing is much more rapid than usual.

Reading

Clancy, J., and McVicar, A.J. (1995) Physiology & Anatomy: a homeostatic approach. London: Edward Arnold (Stress, Chapter 22, p 656).

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What are two examples of homeostasis?

Homeostasis is the maintenance of a relatively stable and optimal internal environment in the face of changing patterns of activity and a changing external environment. External factors impinging on the organism include changes in temperature, the presence or absence of sunlight, the presence or absence of specific chemicals, the availability of nutrients and water, and the presence of potentially infectious organisms and parasites. Living organisms achieve homeostasis by monitoring and regulating a variety of internal parameters and by behavioural changes.

For example, the regulation of temperature in warm-blooded animals occurs through several negative feedback mechanisms that balance the amount of heat being gained with the amount of heat being lost from the body. Thus, if the organism’s body temperature begins to rise, either because of a rise in ambient temperature or increased production of metabolic heat, changes are initiated which prevent overheating. These include sweating, which cools the surface of the skin by means of evaporation of moisture from its surface, and dilatation of blood vessels close to the body surface to allow for greater heat loss. A fall in body temperature causes constriction of peripheral vessels to conserve heat and the initiation of shivering (muscle contractions) to generate more heat metabolically.

The regulation of salt and water balance is another example of homeostasis. The kidneys play an important role in maintaining the correct water content of the body and the correct salt composition of extracellular fluids. External changes which lead to excessive fluid loss initiate feedback mechanisms which act to maintain the body’s fluid content and the kidneys act to limit water loss via excretion.

Reference

Purves, W.K., Orians, G.H., Heller, H.C., and Sadova, D. (1995) Life: the science of biology (5thedition). USA: W.H. Freeman & Co.

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What are the advantages and disadvantages of homeostasis?

Homeostasis is the maintenance by living organisms of a relatively stable internal environment even though changes are occurring in activity levels and in the external environment. The advantage of homeostasis is that the organism can adjust to changes, for example in temperature and water availability, without its component cells being adversely affected since they are having all their needs met by the controlled internal environment. Warm blooded animals are capable of living in a range of different habitats from cold polar regions to hot tropical regions because of the effectiveness of their mechanisms for temperature control. On the other hand, cold-blooded animals are more restricted in the range of habitats in which they can flourish due to their lack of homeostatic control.

A constant internal environment makes it possible for cells to become more specialised and efficient at a particular task. Thus some cells can become organised into tissues specialised to maintain the ionic composition of the internal environment (eg: the kidneys), and others maintain optimum levels of O2and CO2 (eg: the lungs).

A possible disadvantage of homeostasis is that it requires the organism to invest effort into maintaining internal stability. For example, additional energy will be required to maintain a warm body temperature in a cooler external environment. This could be a problem if food is scarce. Also, on occasion the complex web of homeostatic regulations and controls may break down, giving rise to illness. If systems, organs, tissues, and cells that are normally concerned in maintaining internal balances become damaged or diseased, the survival of the whole organism can be put at risk.

Reference

Purves, W.K., Orians, G.H., Heller, H.C., and Sadova, D. (1995) Life: the science of biology (5thedition). USA: W.H. Freeman & Co.

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What is the influence of smiling on the physiology and chemistry of the body, and why is it good for our health to smile?

It is often said that smiling is good for you, and that 'humour is the best medicine'. Presumably, the mental states that result in smiling and laughing are better for one's health than states of anxiety or aggression, which tend to be linked with stress responses within the body such as the release of the hormones adrenaline and cortisol. Stress responses are quite costly for the body, using up reserves of energy and psychological well-being, so perhaps smiling helps us to feel more relaxed and allows the body to restore its physiological balances and reserves (homeostatic balance).

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How does the immune system contribute to homeostasis?

This is an interesting question, and the answer that you develop in your project will be influenced by the stage you have reached in your understanding of the body. We don't want to do the project for you, so here are some ideas for you to select from and develop.

The most natural starting point is to remember that the immune system defends the internal environment of the body from invading micro-organisms and viruses, and also looks out for and deals with cells in the body that are beginning to become transformed into cancer cells. These are direct contributions to homeostasis - free of the damaging effects of infection and cancer, the normal processes of homeostasis can take place. So it will be worthwhile for you to review the non-specific and specific immune processes and see how this protective role is achieved.

The immune system is complex and potent, and although usually it works very effectively, it can occasionally cause problems within the body by turning against normal cells within the body - autoimmune disease. So as well as considering the ways in which the immune system contributes to homeostasis, you might also want to look at the ways in which the immune system itself is kept in balance (Van Parijs and Abbas, 1998).

At a more detailed level, people are finding that the immune system contributes to homeostasis in a large number of subtle ways. Recent research is showing that molecules generated by the immune system are involved in nutrient transport, receptor regulation, and other physiological effects. For example, immunoglobulins transport nutrients from the intestinal lumen to body tissues for absorption, and also transport breakdown products of internal metabolism to other tissues where they can be recycled or excreted (Humphrey and Klasing, 2004). Immunoglobulins influence the response of target organs throughout the body to neurotransmitters and hormones - they regulate cell receptors for insulin, thyroid hormones, acetylcholine, parathyroid hormones, serotonin, and dopamine. Bone homeostasis is mainly regulated by the balance between bone formation and resorption, and involves the coordinated action of osteoblasts and osteoclasts. Osteoblasts are bone-forming cells, and osteoclasts resorb bone matrix. Although the activities of these cells are regulated by the local microenvironment, it has recently been shown that bone homeostasis is greatly influenced by components of the immune system (Rho, Takami, and Choi, 2004). So we are developing a better understanding of the wide-ranging effects that the immune system has on homeostasis.

References

Humphrey, B.D., and Klasing, K.C. (2004) Modulation of nutrient metabolism and homeostasis by the immune system. World's Poultry Science Journal, 60(1), 90-100 (March).

Rho, J., Takami, M., and Choi, Y. (2004) Osteoimmunology: interactions of the immune and skeletal systems. Molecules and Cells, 17(1), 1-9 (Feb 29).

Van Parijs, L., and Abbas, A.K. (1998) Homeostasis and self-tolerance in the immune system: turning lymphocytes off. Science, 280(5361), 243-248 (Apr 10).

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We have been given an assignment to discuss regulatory mechanism in the cardiovascular and integumentary systems that maintain homeostatic balance. I am finding it very difficult to obtain much information on the subject and I would be very grateful of any information that you may be able to send me.

I think the best way to approach an assignment like this is to begin to gather bits and pieces of evidence that later you can build into your answer. For example, you will need to be clear about the main functions of the cardiovascular system and the integumentary system. Then you will need to have a general insight into homeostasis – the processes by which an appropriate internal environment is maintained so that the cells of the body can be healthy and do their jobs. There are many, many homeostatic processes going on inside the body, and it can all be a bit bewildering when you first study the subject – maintenance of body temperature, pH, electrolyte balance, blood pressure and so on, the list seems endless. What you can do though is extract from all of these a generalised model of how a homeostatic control system works, with an output of some kind, a sensor measuring that variable, a preset level somewhere (probably in the brain) for comparison, and then a way of increasing the output if it drops too low, and a way of reducing the output if it rises too high. This is called a negative feedback loop, and is a control system designed to keep variables in balance. It is a central concept in the whole subject of homeostasis. You can find diagrams that illustrate this concept in most books on human anatomy and physiology. Which textbook do you use? I find that ‘Human anatomy and physiology’, 6th edition, by Marieb, is very good, but there are many other excellent books. Have a search in the one you normally use and see if it has a suitable diagram.

The assignment question says ‘Discuss...’, so this means that you will need to do a bit more than just give descriptions of each thing. ‘Discuss’ usually means weighing things up, one against another. So, you could point out that although each of the body systems has certain primary roles to carry out – the cardiovascular system as a transport system let’s say, and the skin as a protective boundary – at the same time they have to contribute to homeostasis by working together co-operatively. You could then explain how the cardiovascular system and skin work together to help to maintain a relatively constant body temperature. Blood circulation through superficial blood vessels in the skin can be increased or reduced in order to control how much heat is lost through the skin. The skin also contains sweat glands, which help in temperature regulation too. So that would be a nice example of systems working together to achieve homeostatic balance. You could describe the temperature regulation system of the body, and the roles of the two named systems, in terms of the negative feedback model mentioned earlier.

These are just a few ideas to get you started – I hope this helps a bit. Try not to get too bogged down in detail. One or two well-chosen examples will be able to meet the requirements of the question and show that you have a good understanding of these key concepts.

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