Chapter 15

The enzyme controlled reactions of life can only take place if the conditions are right, the concentration of chemicals must be maintained as must the balance of water and fluids in the body along with the core body temperature. Organisms use both chemicla and electrical systems to monitor and respond to changes to maintain a dynamic equilibrium. Homeostasis is defined as a balance of inputs and outputs with smal fluctuations over a narrow range to maintain a constant internal environment. Receptors and effectors are vital for the body to maintain this dynamic equilibrium, as in homeostasis it is essential to monitor changes in the internal environment such as blood pH, core body temperature, and concentrations of sodium ions and urea in the blood. Information sent from sensory receptors is transmitted to the brain and impulses are sent along motor neurones to the effectors which bring about changes to restore the equilibirum of the body. Effectors are the muscles or glands that bring about a change in response to a stimulus.

Homeostasis depends on sensory receptors detecting small changes in the body and effectors working to restore the stayus quo, these precise control mechanisms in the body are based on feedback systems that enable the maintenance of a relatively steady syate around a narrow range of conditions.

Most of the feedback systems in the body involve negative feedback. A small change in one direction is detected by sensory receptors and as a result effectors work to reverse the change and restore conditions to their base level. Negative feedbakc systems work in reverse to the intial stimulus. They are important in the maintenance of blood glucose concentration, temperature control and the water balance of the body.

There are relatively few positive feedback systems in the body. In a positive feedback system, a change in the internal environment of the body is detected by sensory receptors, and effectors are stimulated to reinforce that change and increase the response. One example occurs in the blood clotting cascade. When a blood vessel is damagef platelets stick to the damaged region and they release factors that initiate clotting and attract more platelets. These platelets also add to the positive feedback cycle and it continues until the clot is formed.

An important part of homeostaasis is the maintenance of a relatively constant core body temperature to maintain optimum enzyme activity. This process is known as thermoregulation. Organisms are constantly heating up and cooling down as a result of their surroundings, these changes depend on a number of physical processes which include:

• Exothermic chemical reactions
• Latent heat of evapouration - objects cool down as water evapourates from a surface.
• Radiation - the transmission of electromagnetic waves to and from the air, water and ground.
• Convection - the heating and cooling by currents of air or water, as warm water/air rises and cooler water/air sinks, setting up convection currents around an organism.
• Conduction - heating a result of collision of molecules, such as the ground and water.

In many cases the balance between heating and cooling determines the core temperature of an organism. Animals can be classified as endotherms or ectotherms depending on how they maintain and control their body temperature.

Most animals are ectotherms and use their surroundings to warm their bodies, and their core temperature is heavily dependant on their environment. ectotherms include all invertebrates, fish, amphibians and reptiles. Many ecotherms living in water don't need to thermoregulate as water has a high heat capacity, mreaning that their envonrment does not change temperature much. Ectotherms that live on land have a much bigger problem with temperature regulation. The temperature of the air can vary dramatically between the seasons and even over a 24 hour period, so terrestrial ectotherms have evolved a range of strategirs and adaptations so that enable them to heat up or cool down.

Mammals and birds are endotherms. They rely on their metabolic processes to warm up and they usually maintain a very stable core temperature regardless of the temperature of their environment. They have adaptations which enable them to maintain their body temperature and to take advantage of warmth from the environment. As a result endothrms survive in a wide range of environments. Keeping warm in cold conditions and cooling down in hot conditions are both active processes. Therefore the metabolic rate of endotherms is around 5 times higher than ectotherms, so they need to consume more food to meet their metabolic needs compared to ecotherms of a similar size.

Behavioural responses:

Ectotherms display a number of behaviours which increase or reduce the radiation they absorb from the Sun. Sometimes they need to warm up to reach at temperature at which their metabolic reactions happen fast enough for them to be active. They may bask in the sun, orientate their bodies so maximum surface area is exposed to the Sun ot even extend areas of their body to increase surface area. For example lizards often bask for long periods to get warm enough to move fast and hunt their prey. Ectotherms can also increase their body temperature through conduction by pressing thier bodies against the warm ground, or as a result of exothermic metabolic reactions, for example iguanas contract their muscles and vibrate to increase cellular metabolism to raise their body temperature. 

Ectotherms sometimes need to cool down to prevent their core temperature reaching a point where enzymes will begin to denature. To cool down many of the warming processes are reversed. ectotherms shelter from the sun and seek shade, or press their bodies against cool earth or rock, along with orientationg their bodies so that the minimum surface area is exposed to the sun, and minimise their movements to reduce the metabolic heat generated.

Phsyiological responses:

Much of the thermoregulation by ectotherms is the result of behavioural responses but some of them has physiological responses as well. Dark colours absorb more radiation than light colours. Lizards living in cold climates tend to be darker coloured than those living in hotter countries so they get warmer. Some ectotherms are also able to alter their heart rate to increase or decrease the metabolic rate and sometomes to affect the warming or cooling across body surfaces. Ectotherms are always more vuneravle to fluctuations in the environment than endotherms so need a variety of strategies to maintain a stable core temperature. They need less food than endotherms as they use less energy regulating their temperatures, so thet can survive in some very harsh environments where food is scarce.

The Namaqua chameleon lives in the Namib desert which is one of the most inhospitable hot and waterless environments on Earth, so it is an extremely adapted ectotherm: It is black in the morning and orientates its body sideways to the sun, it has an increases heart rate early in the morning when basking along with inflating its body and pressing its body to the sand, and as the day progresses it becomes pale, deflates, slows its heart rate, holds itself away from the desert surface and pants in the middle of the day.

In any homeostatic system receptors are needed to detect change in the internal environment. The peripheral temperature receptors are in the skin and detect changes in the surface temperature. Temperature receptors in the hypothalamus detect the temperature of the blood deep within the body. The temperature of the skin is much more likley to be affected by external conditions than the temperature of the hypthalamus. The combination of both gives the body great sensitivity and allows it to pre-empt possible problems that might result from changes in the external environment.

Endotherms use their internal exothermic metabolic activites to keep them warm, and energy requiring physiological repsonses to cool down. They also have passive ways of heating up and cooling down, to reduce the energy demands of the body. Like ectotherms endotherms have a range of behavioural responses, some animals can even become dormant through the coldest weather (hibernation) or through the hottest weather (aestivation) to avoid heat stress. In spite of these behavioural responses endotherms mainly rely of physiological adaptations to maintain a stable core body temperature, regardless of the environmental conditions or the amount of exercise being done. These adaptaions include the peripheral temperature receptors, the thermoregulatory centres in the hyopthalamus, the skin, and muscles.

Vasodilation: The arterioles near the surface of the skin dilate when the temperature rises, the vessels that provide a direct connection between the arterioles and the venules constrict, forcing blood through the capillary network close to the surface of the skin, the skin flushes and cools as a result of increases radiation, or the skin can be pressed againt a cool surface cooling can result from conduction.

Increased sweating: As the core temperature starts to increase, rates of sweating also increase. The sweat spreads out across the surface of the skin, in some mammals there are sweat glands all over the body. As sweat evapourates from the surface of the skin, heat is lost, cooling the blood below the surface. In some animals the sweat glands are restricted to less hairy areas, these animals often open up their mouths and pant when they are hot.

Reducing the insulating effect: As the body temperature begins to increase the erector pili muscles in the skin relax, as a result the hair or feathers of the animal relax and lie flat to the skin, this avoids trapping an insulating layer of air, this has little effect in humans. Endotherms that live in hot climates often have anatomical adaptations as well to increase the animals ability to cool down , such as an increased SA:V ratio such as large ears, to maximise cooling, or pale fur or feathers to reflect radiation.

Vasoconstriction: The arterioles near the surface of the blood constrict, the arteriovenous shunt vessels dilate, so very little blood flows through the capillary network close to the surface of the skin, so little radiation leaves and the warm blood is kept below the surface.

Decreased sweating: As the core temperature falls, tates of sweating decrease and sweat production will stop entirely, which greatly reduces cooling by the evapouration of water from the surface of the skin, although some evapouration from the lungs still continues.

Increasing the insulating effect: As the body temperature falls the erector pili muscles in the skin contract pulling the hair or feathers of the animla erect, trapping an insulating layer of air so reducing cooling through the skin, and be very effective in many animals.

Shivering: As the core temperature falls the body may begin to shiver, which is the rapid, involuntary contracting and relaxing of the large voluntary muscles in the body, the metabolic heat from the exothermic reactions warm up of the body instead of moving it and it is very effective. 

Endotherms living in cold climates have additional anatomical adaptations to help them keep warm. Many have adaptations that minimise their SA:V ratio to reduce cooling. Another commone example is a thick isulating layer of fat underneath the skin, for example blubber in whales. Some animals hibernate where they build up fat stores, build a well insulated shelter and lower their metabolic rate so they pass the worst of the cold water in a deep sleep. Polar bears demonstrate many of the ways in which endotherms can survive in extremely cold conditions. They have small ears and fur on their feet to insulate them from ice. The hairs are hollow so trap a permanent layer of insulating hairm the skin underneath is black, so it absorbs warming radiation. They have a thick layer of fat under the skin and polar bears are so well insulated that their external temperatures are similar in temperature to the snow and ice on which they live. Feamles dig dens in the snow and reamin in them while they give birth to cubs and only emerge when the cubs are large enough to survive the cold. They are so adapted to life in temperatures down to -50°C that they can overheat at temperatures over 10°C.

The physiological responses of endotherms to changes in the core temperature are the result of complex homeostatic mechanis,s involving negative feedback control from the hypthalamus. There are two control centres:

• The heat loss centre - this is activated when the temperature of the blood flowing through the hypthalamus increases. It sends impulses through autonomic motor neurones to effectors in the skin and muscles, triggering responses that act to lower the core temperature.
• The heat gain centre - this is activated when the temperature of the blood flowing through the hypthalamus decreases. It sends impules through the autonomic nervous system to effectors in the skin and muscles, triggering responses that act to raise the core temperature. 

The interaction of the sensory receptors, the autonomic nervous system, and the effectors in a sophisticated negative feedback system enables endotherms to maintain a very stable core body temperature regardless of environmental conditions or activity levels.

Many of the chemical reactions of metabolism that takes place in the cells of the body produce waste products that are toxic if they are allowed to build up. Excretion is the removal of the waste products of metabolims from the body, the amin metabolic waste products in mammals are:

• Carbon dioxide - one of the waste products of cellular respiration which is excreted from the lungs.
• Bile pigments - formed fromthe breakdown of haemoglobin from old red blood cells in the liver. They are excreted in the bile from the liver into the small intestine via the gall bladder and bile duct. They colour the faeces.
• Nitrogenous waste products (urea) - formed from the breakdown of excess amino acids by the liver. All mammals produce urea as their nitrogeneous waste. Fish produce ammonia while birds and insects produce uric acid. Urea is excreted by the kidneys in the urine.

The liver is one of the major body organs involved in homeostasis and is the largest internal organ of the body. The liver has a rich blood supply, oxygenated blood is supplied by the hepatic artery and removed from the liver and returned to the heart in the hepatic vein. The liver is also supplied with blood by a second vessel, the heaptic portal vein. This carries blood loaded with the products of digestion comes straight from the intestines and this is the starting point for many of the metabolic activites of the liver. Liver cells, or hepatocytes have large nuclei, prominent Golgi apparatus and lots of mitochondria. The blood from the hepatic arterty and the hepatic portal vein is mixed in spaces called sinusoids which are surrounded by hepatocytes. This mixing increases the oxygen content of the blood from the hepatic portal vein, supplying the hepatocytes with enough oxygen for their needs. The sinusoids contain Kupffer cells, which act as the resident macrophages of the liver, ingesting foreign particles and helping to protect against disease. The hepatocytes secrete bile from the breakdown of the blood into spaces called canaliculi, and from there the bile drains into the bile ductules which take it to the gall bladder.

Carbohydrate metabolism: Hepatocytes are closely involved in homeostatic control of glucose levels in the blood by their interactio with insulin and glucagon. When blood levels rise, insulin levels rise and stimultae hepatocytes to convert glucose to the storage carbohydrate glycogen. Similarily when blood glucose concentration starts to fall the hepatocytes are stimulated to convert the glycogen back to glucose under the influence of the hormone glucagon.

Deamination of excess amino acids: The liver plays a vital role in protein metabolism where hepatocytes synthesise most of the plasma proteins. Hepatocytes also carry out transamination - the conversion of one amino acid into another. This is important because the diet does not always contain the required balance of amino acids but transamination can overcome this. The most important role of the liver in protein metabolism is deamination - the removal of an amine group from a molecule. The body cannot store either proteins or amino acids, any excess protein would be excreted and therefore wasted if not for the action of hepatocytes. They deaminate the amino acids, removing the amino group and converting it first into ammonia which is very toxic and then to urea, which is toxic in high concentrations but not in the concentrations found in the blood. The remainder of the amino acid can then be fed into cellular respiration or converted into lipids for storage. The ammonia produced is converted into urea in a set of enzyme controlled reactions known as the orinthe cycle which involved hydrations, dehydrations and carboxylation.

Detoxification: The level of toxins in the body always tends to increase. Apart from urea many metabolic pathways produce potentially toxic substances. We also take in a wide variety of toxins by choice in the form of alcohol and drugs and the liver is where most of these substances are detoxified. One example is the breakdown of hydrogen peroxide. Hepatocytes contain the enzyme catalase, one of the most active known enzymes which splits the hydrogen peroxide into oxygen and water. Another example is the way in which the liver detoxifies ethanol, hepatocytes contain the enzyme alcohol dehydrogenase that breaks down the ethanol into ethanal, which is then converted to ethanoate which may be used to build up fatty acids or used in cellular respiration.

Cirrhosis of the liver: Cirrhosis is a disease where the normal liver tissue is replaced by fibrous scar tissue, and the most common cause is the excessive drinking of alcohol. In fatty liver, big fat filled vesicles displace the nuclei of the hepatocytes and the liver gets larger. In alcoholic hepatitis the patient will have fatty liver along with damaged sinusiods and the narrowing of the hepatic veins. In alcoholic cirrhosis the liver tissue is irreversibly damaged. many of the hepatocytes die and are replaced with fibrous tissue. The hepatocytes cam no longer divide and replace themselves so the liver shrinks and its ability to deal with toxins in the body decreases.

Human kidneys are typical of all mammalian kidneys, they are a pair of organs attached to the back of the abdominal cavity. They are surrounded by a thick protective layer of fat and of fibrous connective tissue. The kidneys are important in osmoregulation and excretion - they filter nitrogeneous waste products out of the blood like urea and help maintain the water balance and pH of the blood. The kidneys are supplied with blood at arterial pressure by the renal arteries that branch off from the abdominal aorta  through the kidneys. Blood that has circulated is removed by the renal vein which drains into the inferior vena cava. The kidneys are made up of millions of structures called nephrons that act as filtering units. The liquid produced by the kidney tubules is urine, which passes out of the kidneys down tubes called ureters and collected into the bladder, which, once full causes the sphincters at the exit of the bladder to open and the urine passes out down the ureathra. There are 3 main areas of the kidney, the cortex, medula and pelvis:

• The cortex is the dark outer layer and is where the filtering of the blood takes place, it has a dense network of capillary tubes carrying blood from the renal artery to the nephrons.
• The medulla is lighter in colour and contains the tubules of the nephrons that form the pyramids of the kidney collecting ducts.
• The pelvis is the central chamber where the urine collects before passing out down the ureter

In the nephrons the blood is filtered and then the majority of the filtered material is returned to the blood, removing nitrogeneous waste and balancing the mineral ions and water. There are around 1.5 million nephrons in each kidney, providing the body kilometres of tubules for reabsportion of glucose, minerals salts and water. The main structrue and functions are:

• Bowman's capsule - cut shaped structure that contains the glomerulus, a bundle of capillaries, more blood enters than leaves due to the ultrafiltration process.
• Proximal convoluted tubule (PCT) - this is the first coiled region of the tubule after the Bowman's capsule and is found in the cortex of the kidney. This is where many of the substances needed by the body are reabsorbed into the blood.
• Loop of Henle - a long loop of tubule that creates a region of very high solute concentration in the tissue fluid deep in the medulla. The descending loop runs down the cortex through the medulla to a hairpin bend at the bottom of the loop. The ascdending loop travles back up through the medulla to the cortex.
• Distal convoluted hormone (DCT) -  a second twisted tubule where the fine tuning of the water balance is controlled through varying wall permeability is determined by the levels of ADH in the blood, further ion and pH balance also takes place in this tubule.

• Collecting duct - the urine passes down the collecting duct throigh the medulla to the pelvis. More fine tuning of water balance tkes place as the walls of this part of the tubule are also sensitive to the concentration of antidiuretic hormone.

The nephron has a network of capillaries around it which finally lead into a venule and then to the renal vein. The blood that leaves the kidney has greatly reduced levels of urea, but the levels of glucose and other substances such as amino acids needed by the body are almost the same as when the blood enters the kidneys (may be slightly less as some glucose will have been used for selective reabsorption), and the mineral ion concentration in the blood has also be restored to ideal levels.

The first stage of in the removal of nitrogenous waste and osmoregulation of the blood is ultrafiltration, which in the kidneys is a specialised form of the proces that results in the formation of the tissue fluid in the capillary beds of the body and is the result of the structure of the glomerulus and the cells lining the Bowman's capsule. The glomerulus is supplied by blood from a relatively wide afferent (incoming) arteriole from the renal artery. \the blood leaves through a narrowwer efferent (outward) arteriole and as a result there is a considerable pressure in the capillaries of the glomerulus. This forces the blood out through the capillary wall, so it acts like  sieve. The the fluid passes through the basement membrane which is made of a network of collagen fibres and other proteins that make a second sieve. Most of the plasma contents can pass through the basement membrane but the blood cells and many of the proteins are retained in the capillary because of their size. The wall of the Bowman's capusule also involves special cells called podocytes that act as an additional filter. They have extensions callled pedicels that wrap around the capillaries forming slits that make sure any cells, platelets, or large plasma proteins that have managed to get through the epithelial cells and the basement membrane do not get into the tubule itself. The filtrate which enters the capsule contains glucose, salt, urea and other substances in the same concentrations as they are in the blood. The process is so efficient that 20% of the water and solutes are removed from the blood plasma as it passes through the glomerulus. The volume of blood filtered is knwona s the glomerular fitration rate.

Ultrafiltration removes urea, the waste product of protein breakdown, from the blood but it also removes a lot of water along eith the glucose salt and other substances which are present in the plasma, any of these substances are needed by the body. The ultrafiltrate is also hypotonic (less concentrated than) the blood plasma. The main function of the nephron after the Bowman's capsule is to return most of the filtered substances back into the blood. 

In the proximal covoluted tubule all of the glucose, amino acids, vitamins and hormones are moved from the filtrate back into the blood by active transport. Around 85%  of the NaCl and water is reabsorbed as well - the sodium ions are moved by active transport while the chloride ions and water follow passively down concentration gradients. The cell lining in the PCT have clear adaptations as they are covered with microvilli, greatly increasing the surface area over which substances can be reabsorbed and have many mitochondria to provide the ATP needed in active transport systems. Once the substances have been removed from the nephron they diffuse into the extensive capillary network which surrounds the tubules down steep concentration gradients maintained by a constant flow of blood. The filtrate reaching the loop of Henle is isotonic (same concentration) with the tissue fluid surrounding the tubule and the blood. At this stage over 80% of the glomerular filtrate has been reabsorbed into the blood, regardeless of the conditions of the body.

The loop of Henle is the section of kidney tubule that enables mammals to produce urine more concentrated than their own blood. Different areas of the loop have different permeabilites to water and this is central to its function, as it acts as a countercurrent multiplier using energy to produce concentration gradients that result in the movement of substances such as water from one area to another. Cells use ATP to transport ions using active transport and this produces a diffusion gradient in the medulla. The changes that take place in the loop of descending limb of the loop of Henle depend on the high concentrations of NaCl ions in the tissye fkuid if the medulla that are the result of the events in the ascending limb of the loop.

• The descending limb leads from the PCT and is the region where water moves out of the filtrate down a concentration gradient, The upper part is impermeable to warer but the lower part which runs into the medulla is permeable to water and runs down into the medulla. The concentration of sodium and chloride ions in the tissue fluid of the medulla gets higher and higher moving through through from the cortex to the pyramidsm , as a result of the ascending limb of the loop of Henle. The fitrate entering the descending limb of the loop is isotinic with the blood, as it travels down the limb water passes out of the limb into the tissue fluid by osmosis down a conentration gradient.

• The water then moves down a concentration gradient into the blood of surrounding capillaries (the vasa recta). The descending limb is not permeable to sodium and chloride ions and no active transport takes place in the descending limb. The fluid that reaches the hairpin bend is very concentrated and hypertonic to the blood in the capillaries.
• The first section of the ascending limb of the loop is very permeable to sodium and chloride ions and they move out of a concentrated solution by diffusion. In the second part of the ascending limb sodium and chlroide ios are actively pumped out into the medulla tissue fluid. Importantly the ascending limb of the loop is impermeable to water so water cannot follow the chloride and sodium ions down a concnetration gradient, meaning the fluid left in the ascending loop becomes increasingly dilute whilst the tissue fluid of the medulla develops the very high concentration of ions that is essential for the kidney to produce urine that is more concentrated than the blood as it sets up the countercurrent multiplier system.

By the tome the dilute fluid has reached the top of the ascending limb it is hyoptonic to the blood and then enters the distal convoluted tubule and collecting duct.

Balancing the water needs of the body takes place in the DCT and collecting duct. These are the areas where the permeability of the walls of the tubules caries with the levels of ADH. The cells lining the DCT have manny mitochondria so are adapted to carry out active transport. If the body lacks salt sodium ions will be actively transported out of the DCT with the chloride ions following down an electrochemical gradient. Water can also leave the DCT if the walls are permeable as a response to ADH. The DCT also plays a role in balancing the pH of the blood.

The collecting duct passes through the concentrated tissue of the renal medulla, which is the main site where the concentration and volume of urine produced is determined. Water moves out of the collecting duct by diffusion down a concentration gradient as it passes through the renal medulla. As a result the urine becomes more concentrated. The level of sodium ions in the surrounding fluid increases through the medulla from the cortex to the pelvus, This means can water can be removed form the collecting duct all the way along its length, producing very hypertonic urine when the body needs to conserve water. The permeability of the collecting duct is determined by the level of ADH.

The kidney plays an important homeostatic role as it is the main organ of osmoregulation which involves controlling the water potential of the blood within very narrow boundaries, and the water potential of the body has to be maintained regardless of the solutes you intake when you eat and drink, and changing the concentration of the urine is crucial in this dynamic equilibrium. The amount of water lost in the urine is controlled by ADH in a negative feedback system.

ADH is produced by the hypothalamus and secreted into the posterior pituitary gland where it is stored. ADH increases the permeability of the collecting duct to water. ADH is released from the pituitary gland and carried in the blood to the cells of the collecting duct where it has its effect. The hormone does not cross the membrane of the tubule cells but binds to receptors on the cell membrane and triggers the formation of cAMP which causes a cascade of events:

• Vesicles in the cells lining the collecting duct fuse with the cell surface mmebranes on the side of the cell in contact with the tissue fluid of the medulla.
• The membranes of these vesicles contain protein-based water channels (aquaporins) and when they are inserted into the cell surface membrane they makae it permeable to water.
• This provides a route for water to move out of the tubule cells into the tissue fluid of the medulla and the blood capillaries by osmosis.

The more ADH that is released the more water channels are inserted into the membranes of the tubule cells. This makes it easy for more water to leave the tubules by diffusion, resulting the formation of a small amount of very concentrated urine. Water is returned to the capillaries, maintaing the water potential of the blood and therefore the tissue fluid of the body. When ADH levels fall the reverse happens. Levels of cAMP fall, then the water channels are removed from the tubule cell membranes and enclosed in vesicles again. The collecting duct becomes impermeable to water resulting in the production of large amounts of very dilute urine being produced. The the permeability of the collecting duct is controlled to match th water requirements of the body. This is brought about by a negative feedbakc system involving osmoreceptors in the hypothalamus of the brain, which are sensitive to the concentration of inorganic ions in the blood and are linked to the release of ADH.

When water is in short supply the concentration of inorganic ions in the blood rises and the water potential of the blood becomes more negative, which is detected by receptors in the hypothalamus which sends impulses to the posterior pituitary gland which is released into the blood. The ADH is picked up by receptors in the cells of the collecting duct and increases permeability to water. Water leaves the filtrate in the tubules and passes into the blood of the surrounding capillary netowork and a small volume of concentrated urine is produced.

When large amountsof liquid are taken in the blood becomes re dilute and its water potential becomes less negative. This change is detected by the osmorecptors if the hypothalamus and nerve impulses to the posterior pitiuitary are reduced or stopped and so the release of ADH from the pituitary is inhibited. Very little reabsorption of water can take place because the walls of the collecting duct remain impermeable to water. In this way the concentration of the blood is maintained and large amounts of dilute urine are produced. 

The osmorecpetors in the hypothalamus are not the only sensory receptors that exert control over the release of ADH. It is also stimulated or inhibited by changes in the blood pressure detected by baroreceptors in the cariotid and aortic arteries. A rise in blood pressure can often be caused by a rise in blood volume, which is detected by baroreceptors and in turn they prevent the release of ADH, increasing the volume of water lost in the urine and so decreasing the blood pressure. If the blood pressure falls it can be a signal that the blood pressure has fallen so if barorecpetors detect a fall in blood pressure there is an increase in the release of ADH from the pituitary, so the kidneys respond to reduce water loss from the body. Water is returned to the blood increasing pressure and a small amount of concentrated urine is produced.

Urine contains water, urine, salts and the breakdown chemicals of a huge range of chemicals, including toxins and hormones, and a number of different types of disease will lead to new substances showing up in your urine, eg creatine as a result of muscle damage. The human embryo implants in the uterus around 6 days after conception, the site of the developing placenta begins to produce a chemical called human chorionic gonadotrophin (hCG). Some of this hormone will be found in the blood and the urine of the mother. Modern pregnancy tests test for hCG in the urine using monoclonal antibodies. Monoclonal antibodies are antibodies from single clone of cells that are produced to target particular cells in or chemicals in the body. A mouse is injected with hCG so it makes the appropriate antibody. The B-cells that make the required antibody are removed from the spleen and fused with a myeloma, a type of cancer cell which divides very rapidly. This knew cell is called a hybridoma, each of which reproduces rapidly resulting in a clone of millions of cells making the desired antibody, which are collected, purified. The main stages are:

• The wick of the rest is soaked in the first urine passed in the morning which will have the highest level of hCG.
• The test contains mobile monoclonal antibodies that have small coloured beads attached to them, which will only bind to hCG to form a hCG-antibody complex.

• The urine carries on along the rest structure until it reaches the window. Here there are immobilised monoclonal antibodies arranged in a line or pattern that only bind to the hCG-antibody complex. If the woman is pregnant a coloured line appears in the first window.
• The urine continue up through the test to a second window. Here there is usually a line of immobilised monoclonal antibodies that bind only to the monoclonal antibodies, regardless of whether they are bound to hCG or not. This colourled line formes regardless of whether the woman is pregnant and simply indicates that the test is working.

Urine and anabolic steroids: Atheletes and body builders may try and cheat by using anabolic steroids which are hormones which mimic the action of testosterone and stimulate the growth of muscles. However they are excreted in the urine so by testing the urine using gas chromatography scientists can show whether an individual has been using drugs which are banned. 

Urine and drug testing: Urine can also be tested for the presence of many different drugs as the metabolites are filtered through the kidneys and stored in the bladder. A urine sample is divided into two and the first will be tested using monoclonal antibodies to bind to the drug's breakdown product. If this test is positive the second sample will be run through a gas chromatogram to confirm the presence of a drug.

The kidneys play a vital role in homeostasis, if they are damaged and become less efficient or stop working, the effects may be fatal. There are a number of reasons why the kidneys might fail, they include kidney infections where the sturucture of the podocytes and tubules themselves may be damaged or destroyed, raised blood pressure that can damage the structure of epithelial cells and basement membrane of the Bowman's capsule, and genetic conditions such as polycystic kidney disease where the healthy kidney tissue is replaced by fluid filled cysts or damaged by pressure from cysts. If the kidneys are infected or effected by high blood pressure this may cause:

• Protein in the urine - if the basement membrane or podocytes of the Bowman's capsule are damaged, they no longer act as filters and large plasma proteins can pass into the filtrate and are passed out into the urine.
• Blood in the urine - another symptom that the filtering process is no longer working.

If the kidneys fail completely, the concentrations of urea and mineral ions build up in the body, the effects include:

• Loss of electrolyte balance - if the kidneys fail the body cannot excrete excess potassium, sodium and chloride ions. This causes osmotic imbalances and eventual death.

• Build up of toxic urea in the blood - if the kidneys fail the body cannot get rid of urea and it can poison the cells.
• High blood pressure - the kidneys play an important role in controlling the blood pressure by maintaining the water balance of the blood. If the kidneys fail the blood pressure increases which can lead to a number of problems including heart problems and strokes.
• Weakend bones as the calcium/phosphorous balance in the blood is lost.
• Pain and stiffness in joints as abnormal proteins build up in the blood.
• Anaemia - the kidneys are involved in the production of a hormone called erythropoietin that stimulates the formation of red blood cells causing tiredness and lethargy.

Kidney problems alwats affect the rate at which blood is filtered in the Bowman's capsules of the nephrons. The glomerular filtration rate (GFR) is widely used as a measure to indicate kidneys diseases. The rate of filtration is not measured directly but a blood test is taken to measure the levels of creatine which is a breakdown product of muscles and is used to give an estimate of the GFR, as if creatine levels go up it is a signal that the kidneys are not working properly along with taking into account that GFR steadily decreases with age and that man usually have more muscle mass and therfore more creatine than women.

There are two main ways in which kidney failure is treated, through dialysis or a transplant. In renal dialysis the function of the kidney is carried out artificially. In a transplant a new healthy kidney is put into the body to replace the functions of the failed kidney. There are two types of dialysis:

Haemodialysis involves using a dialysis machine and is usually carried out in the hospital. Blood leaves the patient's body from an artery and flows into the dialysis machine where it flows between partially permeable dialysis membranes which mimic the basement membrane of the Bowman's capsule. On the other side of the membranes is the dialysis fluid. During dialysis it is vital that the patient loses the excess urea and mineral ions that have built up in the blood, but is equally important that they do not lose useful substances such as glucose and some mineral ions. The loss of these substances is prevented by careful control of the dialysis fluid which contains normal plasma levels of glucose to ensure there is no net movement of glucose out of the blood. The dialysis fluid also contains normal levels of mineral ions so any excess mineral ions in the blood move out by diffusion down a concentration gradient into the dialysis fluid, thus restoring the correct electrolyte balance of the blood. The dialysis fluid contains no urea meaning there is a vey steep concentration gradient from the blood to the fluid, so much urea leaves the blood. The blood and the dialysis fluid flow in opposite directions to maintai a countercurrent exchange system to maximise the exchange that takes place.

Haemodialysis depens on diffusion down concentration gradients and there is no active transport. It takes about 8 hours and has to be repeated regularily. Patients with kidney failure who rely on hameodialysis have to remain attached to a dialysis machine several times a week for many hours, and also need to manage their diets carefully eating little protein, salt and monitoring their fluid intake to keep their blood chemistry as stable as possible.

Peritonal dialysis is done inside the body - it makes use of the natural dialysis membranes formed by the lining of the abdomen called the peritoneiu,. It is usually done at home and the patient can carry on with their normal life while it takes place. The dialysis fluid is introduced into the abdomen using a catheter. It is left for several hours for dialysis to take place across the peritonal membranes, so that excess ions and urea pass out of the capillaries, into the tissue fluid and out across the peritonal membrane into the dialysis fluid. The fluid is then drained off leabinf the blood balanced again and the urea and excess mineral ions removed.

Long term dialysis can have some serious side effects, so the best solution for patients is a kidney transplant where a single healthy kidney from a donor is placed within the body. The blood vessles are joined and the ureter of the new kidney is inserted into the bladder. If the transplant is successful the kidney will function normally for many years. The main problem with transplanted organs is the risk of rejections. The anitgens on the donor organ differ from the antigens on the cells of the recipient and the immune system is likely to recognise this, which can result in the rejection and destruction of the new kidney. There are a number of ways to reduce the risk of rejection. The match between the donor and recipient's antigens is made as close as possible. The recipient is given immunosuppresant drugs for th rest of their lives to help prevent rejection of the new organ. Immunosuppressant drugs are impriving all the time and the need for a very close tissue match is becoming less important. The disadvantage of taking immunosuppresant drugs is that they can prevent the patients from responding effectively to pathogens and have to take great care if they become ill.

Dialysis is much more readily available than donoir organs and it enables the patient to lead a relatively normal life, but patients do need to regularily monitor their diet. Long term dialysis is much more expensive than transplant and can eventally cause damage to the body. If the patient recieves a kidney transplant thet are free from the restrictions which come with regular dialysis. The main soruce of donor kidneys is from people who die suddenly, often from road accidents, strokes or heart attacks. Unfortunately for people needing a transplant there is a shortage of donor kidneys as cars are safer and not all people register for organ donation. The development of stem cell therapy is promising, as it is possible to to grow functioning embryonic kidney tissue from stem cells.