Homeostasis in Mammals PDF

# Homeostasis ## 14.1 Homeostasis in Mammals - Discuss the importance of homeostasis in mammals - Explain the principles of homeostasis in terms of internal and external stimuli, receptors, central control, coordination systems, effectors (muscles and glands) - Define the term 'negative feedback' an...

# Homeostasis ## 14.1 Homeostasis in Mammals - Discuss the importance of homeostasis in mammals - Explain the principles of homeostasis in terms of internal and external stimuli, receptors, central control, coordination systems, effectors (muscles and glands) - Define the term 'negative feedback' and explain how it is involved in homeostatic mechanisms - Outline the roles of the endocrine system in coordinating homeostatic mechanisms ### Importance of Homeostasis: Homeostasis is essential for the proper functioning of organisms because: * Enzymes that control biochemical reactions within cells, and other proteins such as membrane channel proteins, are sensitive to changes in pH and temperature. Any change to these factors reduces the efficiency of enzymes or may even prevent them working altogether, e.g. may denature them. Changes to membrane proteins may mean that substances cannot be transported into or out of cells. * Changes to water potential of the blood and tissue fluids may cause cells to shrink and expand, even to bursting point, owing to water leaving or entering by osmosis. In both situations the cells cannot operate normally. ### The Importance of Homeostasis * Enzymes are optimal for the biochemical reactions within cells, and other proteins such as membrane channel proteins, are sensitive to changes in pH and temperature. Any change to these factors reduces the efficiency of enzymes or may even prevent them working altogether, e.g. may denature them. Changes to membrane proteins may mean that substances cannot be transported into or out of cells. * Changes to the water potential of the blood and tissue fluids may cause cells to shrink and expand (even to bursting point) owing to water leaving or entering by osmosis. In both situations the cells cannot operate normally. ### What is Homeostasis? Homeostasis is the maintenance of a constant state. More specifically, it refers to the internal environment of organisms and involves maintaining the chemical make-up, volume and other features of blood and tissue fluid within narrow limits, sometimes called normal ranges. Homeostasis ensures that the cells of the body are in an environment that meets their needs and allows them to function normally despite external changes. This does not mean that there are no changes - on the contrary, there are continuous fluctuations brought about by variations in internal and external conditions. These changes, however, occur around a set point. Homeostasis is the ability to return to that set point and so maintain organisms in a balanced equilibrium. ## 14.2 Excretion and Kidney Structure - Describe the deamination of amino acids and outline the formation of urea in the urea cycle - Describe the gross structure of the kidney ### Excretion Excretion is the removal of the waste products of metabolism from the body. This is distinct from elimination (egestion), which is the removal of substances such as dietary fibre that have never been involved in the metabolic activities of cells. ### Excretory Substances: - An adult human produces about 500 dm³ of carbon dioxide and 400 cm³ of water each day as a result of respiration. - Other excretory products include bile pigments and mineral salts as well as the nitrogenous excretory product urea CO(NH2)2. ### Urea: Urea is used as the nitrogenous excretory product of organisms that have some access to water, but not in large volumes, e.g. animals living on land, such as mammals. Urea is produced in the liver from excess amino acids in three stages: * **Deamination:** Amino groups (NH2) are removed from the amino acids in a process called deamination and made into ammonia. * **Respiration:** The remainder of the amino acid can be respired to give ATP. * **Ornithine Cycle:** The ammonia is converted to urea by the addition of carbon dioxide in a pathway called the ornithine cycle. ATP is required for this process. ### Structure of the Kidney: In mammals there are two kidneys found at the back of the abdominal cavity, one on each side of the spinal cord. Weighing only 150g each, they filter your blood plasma every 22 minutes of your life. A section through the kidney shows it is made up of the: - **Fibrous Capsule:** An outer membrane that protects the kidney - **Cortex:** A lighter coloured outer region made up of renal (Bowman's) capsules, convoluted tubules, and blood vessels. - **Medulla:** A darker coloured inner region made up of loops of Henlé, collecting ducts, and blood vessels. - **Renal Pelvis:** Funnel-shaped cavity that collects urine into the ureter. - **Ureter:** Tube that carries urine to the bladder. - **Renal Artery:** Supplies the kidney with blood from the heart via the aorta. - **Renal Vein:** Returns blood to the heart via the vena cava. A microscopic examination of the cortex and medulla reveals around one million tiny tubular structures in each kidney. These are the basic structural and functional units of the kidney - the **nephrons**. ## 14.3 The Structure of the Nephron - Describe the detailed structure of the nephron with its associated blood vessels using photomicrographs and electron micrographs. - Describe the gross structure of the kidney. ### The Nephron: The nephron is the functional unit of the kidney. It is a narrow tube, closed at one end, with two twisted regions separated by a long hairpin loop. Each nephron is made up of the: - **Renal (Bowman's) Capsule:** The closed end at the start of the nephron. It is cup-shaped and contains within it a mass of blood capillaries known as the glomerulus. Its inner layer is made up of specialised cells called podocytes. - **Proximal (First) Convoluted Tubule:** A series of loops surrounded by blood capillaries. Its walls are made of cuboidal epithelial cells with microvilli. - **Loop of Henle:** A long, hairpin loop that extends from the cortex into the medulla of the kidney and back again. It is surrounded by blood capillaries. - **Distal (Second) Convoluted Tubule:** A series of loops surrounded by blood capillaries. Its walls are made of cuboidal epithelial cells, but it is surrounded by fewer capillaries than the proximal tubule. - **Collecting Duct:** A tube into which a number of distal convoluted tubules empty. It is lined by cuboidal epithelial cells and becomes increasingly wide as it empties into the pelvis of the kidney. ### Associated Blood Vessels: Associated with each nephron are a number of blood vessels: - **Afferent Arteriole:** A tiny vessel that is a branch of the renal artery and supplies the nephron with blood. The afferent arteriole enters the renal capsule of the nephron where it forms the - **Glomerulus:** A many-branched knot of capillaries from which fluid is forced out of the blood. - **Efferent Arteriole:** A tiny vessel that leaves the renal capsule. It has a smaller diameter than the afferent arteriole, which causes an increase in blood pressure within the glomerulus. The efferent arteriole carries blood away from the renal capsule and later branches to form the - **Peritubular Capillaries:** A concentrated network of capillaries that surrounds the proximal convoluted tubule, the loop of Henlé and the distal convoluted tubule and from where they reabsorb mineral salts, glucose and water. The peritubular capillaries merge together into venules (tiny veins) that in turn merge together to form the renal vein. ## 14.4 Kidney Function - Ultrafiltration and Selective Reabsorption - Describe how the processes of ultrafiltration and selective reabsorption are involved with the formation of urine in the nephron ### Functions of the Kidney: The functions of the kidney are listed in Table 1. The main one, that of regulating the composition of blood, is carried out by the nephrons in a series of stages: ultrafiltration, selective reabsorption, and the reabsorption of water and minerals. | **Regulating the Composition of the Blood and Maintaining a Constant Water Potential by:** | |---|---| | - Maintaining a Constant Volume of Water | | - Removing Wastes such as Urea | | - Maintaining the Concentrations of Mineral Ions and Other Substances Constant | | - Regulating Blood Pressure | | - Maintaining the Body's Calcium Level | | - Stimulating the Production of Red Blood Cells | ### Ultrafiltration: Blood enters the kidney through the renal artery, which branches frequently to give around one million tiny arterioles, each of which enters a renal (Bowman's) capsule of a nephron. This is called the afferent arteriole and it divides to give a complex of capillaries known as the glomerulus. The glomerular capillaries later merge to form the efferent arteriole, which then sub-divides again into capillaries (the peritubular capillaries), which wind their way around the various tubules of the nephron before combining to form the renal vein. The walls of the glomerular capillaries are made up of endothelial cells with pores between. As the diameter of the afferent arteriole is greater than that of the efferent arteriole, there is a build up of hydrostatic pressure within the glomerulus. As a result, water, glucose, mineral ions and other substances up to a relative molecular mass of up to 68000 are squeezed out of the capillary to form the glomerular filtrate. The movement of this filtrate out of the glomerulus is resisted by the: - **Capillary endothelium** - **Basement membrane of the epithelial layer of the renal (Bowman's) capsule** - **Epithelial cells of the renal (Bowman's) capsule** - **The hydrostatic pressure of the fluid in the renal capsule space (the intracapsular pressure)** - **The low water potential of the blood in the glomerulus** This total resistance would be sufficient to prevent filtrate leaving the glomerular capillaries, but there are some modifications to reduce this barrier to the flow of filtrate: * The inner layer of the renal (Bowman’s) capsule is made up of highly specialised cells called podocytes. These cells allow filtrate to pass beneath them and through gaps between their branches. Filtrate passes between these cells rather than through them. * The endothelium of the glomerular capillaries has spaces up to 100 nm wide between its cells. Again, fluid can therefore pass between, rather than through, these cells. As a result, the hydrostatic pressure of the blood in the glomerulus is high enough to overcome the resistance, and so filtrate passes from the blood into the renal capsule. This filtration under pressure is known as **ultrafiltration**. The filtrate has much the same composition as blood plasma, with the exception of the plasma proteins which are too large to pass across the basement membrane. Many of the substances in the 125 cm³ of filtrate passing out of blood each minute are extremely useful to the body and need to be reabsorbed. ### The Glomerulus - A Unique Capillary Bed: In mammals, the glomerulus is the only capillary bed in which an arteriole (the afferent arteriole) supplies it with blood and an arteriole (the efferent arteriole) also drains blood away. In all other mammalian capillary beds it is a venule that drains away the blood. The glomerular capillaries need to merge into an efferent arteriole because this increases the hydrostatic pressure within the glomerulus and allow ultrafiltration to occur. ### Selective Reabsorption: In the proximal convoluted tubule nearly 85% of the filtrate is reabsorbed back into the blood. Why then, you may ask, allow it to leave the blood in the first place? Ultrafiltration operates on the basis of size of molecule: all below 68000 relative molecular mass are removed. Some are wastes, but most are useful. About 180 dm³ of water enters the nephrons each day. Of this volume, only about 1 dm³ leaves the body as urine. Eighty-five per cent of the reabsorption of water occurs in the proximal convoluted tubule. ## 14.5 Kidney Function - Loop of Henle and Reabsorption of Water: - Describe the counter current multiplier - Describe how the loop of Henlé generates a concentration gradient in the medulla - Describe the effects of ADH on the collecting ducts. ### The Loop of Henle: The loop of Henle is a hairpin-shaped tubule that extends into the medulla of the kidney. It is responsible for creating the conditions in the surrounding interstitial fluid that lead to the reabsorption of water from the distal convoluted tubule and the collecting duct. This results in concentrating the urine so that it has a lower water potential than the blood. The concentration of the urine produced is directly related to the length of the loop of Henle. It is short in mammals whose habitats are in or by water (e.g. beavers) and long in those whose habitats are dry regions (e.g. kangaroo rat). #### Counter-Current Multiplier: The loop of Henle acts as a counter-current multiplier. To understand how this works it is necessary to consider the following sequence of events: 1. **Sodium and chloride ions are actively pumped out of the ascending limb of the loop of Henle using ATP provided by the many mitochondria in the cells of its wall.** This creates a low water potential (high ion concentration) in the region of the medulla between the two limbs (called the interstitial region). In normal circumstances water would pass out of the ascending limb by osmosis. However, the thick walls are almost impermeable to water and so very little, if any, escapes. 2. **The walls of the descending limb are, however, very permeable to water and as the cells have many membrane protein channels known as aquaporins, it passes out of the filtrate by osmosis into the interstitial space.** This water enters the blood capillaries in this region by osmosis and is carried away. 3. **The filtrate progressively loses water in this way as it moves down the descending limb, lowering its water potential. It reaches its minimum water potential at the tip of the hairpin.** 4. **At the base of the ascending limb, sodium and chloride ions diffuse out of the filtrate and as it moves up the ascending limb, these ions are also actively pumped out.** Therefore, the filtrate develops a progressively higher water potential. 5. **In the interstitial space between the ascending limb and the collecting duct there is a gradient of water potential with the highest water potential in the cortex and an increasingly lower water potential the further into the medulla one goes.** 6. **The collecting duct is permeable to water and so, as the filtrate moves down it, water passes out of it by osmosis.** This water passes by osmosis into the blood vessels that occupy this space and is carried away. 7. **As water passes out of the filtrate, its water potential is lowered. However, the water potential is also lowered in the interstitial space and so water continues to move out by osmosis down the whole length of the collecting duct.** The counter-current multiplier ensures that there is always a water potential gradient drawing water out of the tubule. 8. **The water that passes out of the collecting duct by osmosis does so through aquaporins (water channels). The hormone ADH can alter the number of these channels and so control water loss.** By the time the filtrate, now called urine, leaves the collecting duct on its way to the bladder, it has lost most of its water and so it has a lower water potential than the blood. ### The Distal (Second) Convoluted Tubule: The cells that make up the walls of the distal (second) convoluted tubule have microvilli and many mitochondria that allow them to reabsorb material rapidly from the filtrate, by either diffusion or active transport. The main role of the distal tubule is to make final adjustments to the water and salts that are reabsorbed and to control the pH of the blood by selecting which ions to reabsorb. To achieve this, the permeability of its walls becomes altered under the influence of various hormones. A summary of the processes taking place in the nephron is given in Figure 2. ### Counter-Current Multiplier: When two liquids flow in opposite directions past one another, the exchange of substances (or heat) between them is greater than if they flowed in the same direction next to each other. In the case of the loop of Henle, the counter-current flow means that the filtrate in the collecting duct with a lower water potential meets interstitial fluid that has an even lower water potential. This means that, although the water potential gradient between the collecting duct and interstitial fluid is small, it exists for the whole length of the collecting duct. There is therefore a steady flow of water into the interstitial fluid, so that around 80% of the water enters the interstitial fluid and hence the blood. If the two flows were in the same direction (parallel) less of the water would enter the blood. ## 14.6 Control of Water and Solute Concentration of the Blood - Describe the roles of the hypothalamus, posterior pituitary, ADH and collecting ducts in osmoregulation - Describe the effects of ADH on the collecting ducts The quantity of water and salts we take in varies from day to day, as does the quantity we lose. Table 1 shows the daily balance between loss and gain of salts and water for a typical human. The blood, however, needs to have a constant volume of water and concentration of salts to avoid osmotic disruption to cells. The homeostatic control of water and solute concentrations in the blood is achieved by hormones that act on the distal (second) convoluted tubule and the collecting duct. | **Volume of Water/cm³ day-1** | |---|---| | **Water Gain** | **Water Loss**| | - Diet: 2300 | - Urine: 1500 | | - Metabolism, e.g. respiration: 200| - Expired Air: 400 | | - Evaporation from skin: 350 | | - Faeces: 150 | | - Sweat: 100 | | **TOTAL: 2500** |**TOTAL: 2500** | | **Mass of Salt/g day-1** | |---|---| | **Salt Gain** | **Salt Loss** | | - Diet: 10.50 | - Urine: 10.00 | | - Faeces: 0.25 | | - Sweat: 0.25 | | **TOTAL: 10.50** | **TOTAL: 10.50** | As a result of facilitated diffusion and active transport by cells in the ascending limb of the loop of Henle, sodium and chloride ions are concentrated in the interstitial fluid surrounding the distal convoluted tubule and the collecting duct. There is a gradient of water potential within this interstitial region, with the highest water potential in the cortex and the lowest in the medulla region closest to the renal pelvis. Some urea passes out of the filtrate in the collecting duct into the interstitial region, so further increasing the concentration of solutes and decreasing the water potential. At all points, the interstitial region has a lower water potential than the filtrate passing down the collecting duct. ### The Naming of Antidiuretic Hormone: The name *antidiuretic hormone (ADH)* may, at first, seem unusual. However, it describes its function precisely. *Diuresis* is the production of large volumes of dilute urine. It is a symptom of a disease called *diabetes insipidus* (so called because the urine from sufferers did not taste sweet!). The disease was successfully treated with pituitary extract. Therefore, it was suggested that a hormone existed that was given the name 'antidiuretic hormone'. As the effect of ADH is to increase the permeability of collecting ducts so that more water is reabsorbed into the blood, it causes the production of small volumes of concentrated urine. This is the opposite of diuresis - hence the name *antidiuretic hormone*. ### Regulation of the Water Potential of the Blood: The water potential of the blood is determined by the balance of water and salts within it. A rise in solute concentration lowers its water potential. This may be caused by: - Too little water being consumed. - Much sweating occurring. - Large amounts of salt being taken in (ingested). The body responds to this decrease in water potential as follows: 1. **Sensory cells called osmoreceptors in the hypothalamus of the brain detect the decrease in water potential.** 2. It is thought that, when the water potential of the blood is low, water is lost from these osmoreceptor cells by osmosis. 3. Owing to this water loss, the osmoreceptor cells shrink, a change that stimulates the neurosecretory cells in the hypothalamus to produce a hormone called *antidiuretic hormone (ADH)*. 4. ADH passes along the neurones (nerve cells) to the posterior pituitary gland, from where it is secreted into the capillaries. 5. ADH passes in the blood to the kidney, where it increases the permeability to water of the cell surface membrane of the cells that make up the walls of the distal (second) convoluted tubule and the collecting duct. 6. Receptors on the cell surface membrane of these cells bind to ADH molecules, activating a second messenger system within the cell. This results in the activation of a protein kinase, an enzyme that adds phosphate groups to other proteins to activate them. 7. The action of protein kinase causes vesicles within the cell to move to, and fuse with, its cell surface membrane. (ADH binding also leads to an increase in transcription of the gene coding for the aquaporin protein, increasing the number of available aquaporins.) 8. When the vesicles fuse with the cell surface membrane, the number of aquaporins in the membrane increases greatly, making the cell surface membrane much more permeable to water. 9. As it is a small molecule, some urea can cross the phospholipid bilayer of the membrane. ADH binding also leads to an increase in membrane transport proteins for urea, so that the collecting duct becomes more permeable to urea and some will leave the filtrate to further decreases the water potential of the interstitial region. 10. The combined effect is that more water leaves the collecting duct by osmosis down a water potential gradient and re-enters the blood. 11. As the reabsorbed water came from the blood in the first place, this will not, in itself, increase the water potential of the blood, but merely prevent it from decreasing any further. Therefore, the osmoreceptors also stimulate the thirst centre of the brain, to encourage the individual to seek out and drink more water. 12. The osmoreceptors in the hypothalamus detect the increase in water potential and ADH secretion from the posterior pituitary is reduced. 13. The decrease in ADH concentration in the blood will lead to a decreased permeability of the collecting duct to water and urea so that the permeability returns to its former state. This is an example of homeostasis and the principle of negative feedback. ## 14.7 Hormones and the Endocrine Glands - Outline the role of cyclic AMP as a second messenger with reference to the stimulation of liver cells by adrenaline and glucagon. - Describe the three main stages of cell signalling in the control of blood glucose by adrenaline as follows: 1. hormone-receptor interaction at the cell surface 2. formation of cyclic AMP, which binds to kinase proteins 3. an enzyme cascade involving activation of enzymes by phosphorylation to amplify the signal Mammals possess two main coordinating systems - the nervous system that communicates rapidly, and the endocrine system that usually does so more slowly. Both systems interact in order to maintain a constant internal environment, at the same time being responsive to a varying external environment. Both systems also use chemical messengers - the endocrine system exclusively so, and the nervous system through the use of neurotransmitters in chemical synapses. The chemical messenger adrenaline may act both as a hormone and a neurotransmitter. ### Hormones A hormone is a regulating chemical produced and secreted by an endocrine gland and is carried in the blood to the cells, tissues or organ on which it acts - known as the target cell (target tissue, target organ) - that have complementary receptors on their cell surface membranes or their internal membranes. Hormones may differ chemically from one another, but they share many common characteristics. Some hormones have their action at the cell surface, and other hormones are able to enter the cell to have an effect. #### Characteristics of Hormones: * Effective in very small quantities, but often have widespread and permanent effects. * Normally relatively small molecules. * Often proteins or polypeptides, although some are steroids. * Transported by the blood system. * Produced by endocrine glands. ### Mechanisms of Hormone Action One mechanism of hormone action is called the *cyclic AMP second messenger system*. An example of this system occurs in stimulation of liver cells by the hormones adrenaline and glucagon, leading to the conversion of glycogen to glucose. The process involving adrenaline, shown in Figure 1, has three stages: 1. **Adrenaline binds to its complementary receptor on the cell surface membrane of a liver cell.** Binding activates a membrane protein, termed a G protein. 2. **The G protein activates another membrane protein, an enzyme called adenylate cyclase.** The activated enzyme converts ATP to cyclic AMP (the second messenger). Cyclic AMP binds to and activates a kinase protein. 3. **There follows an enzyme cascade in which enzymes are activated by phosphorylation.** This amplifies the first signal as one enzyme molecule can catalyse the phosphorylation of many other enzyme molecules. The last enzyme in the chain catalyses the breakdown of glycogen to glucose. The glucose diffuses out of the liver cell and into the blood, through protein carriers called transporter proteins. ## 14.8 Control of Blood Glucose Concentration - Describe the roles of the pancreas, insulin and glucagon and describe the role of the liver in regulating glucose concentration. ### The Pancreas The pancreas is a dual-purpose gland; it is involved in both the digestive and the endocrine systems (Topic 12.6). The endocrine part of the pancreas is composed of groups of cells called islets of Langerhans that are scattered throughout the gland. These contain several different types of cells that release hormones. ### Hormones of the Pancreas: The main hormones produced by the pancreas, which are involved in the regulation of blood glucose concentration, are: * **Insulin:** Produced by β cells. It is secreted into the bloodstream when blood glucose concentration is high. * **Glucagon:** Produced by α cells. It is secreted into the bloodstream when blood glucose concentration is low. ### Insulin: Insulin lowers blood glucose concentration by: * **Increasing the uptake of glucose by cells:** Insulin binds to its receptor on the cell surface membrane. This actives a cascade of reactions that leads to the phosphorylation of glucose transporter proteins (GLUT4). This causes them to move from the cytoplasm to the cell surface membrane where they act as channels for glucose to diffuse into the cell. * **Increasing the conversion of glucose into glycogen:** Insulin activates enzymes that promote the conversion of glucose in the liver and muscle cells to glycogen. This is called glycogenesis. * **Suppressing the release of glucose from the liver cells:** Insulin suppresses the breakdown of glycogen to glucose (glycogenolysis) and inhibits the synthesis of glucose from non-carbohydrate sources (gluconeogenesis) in the liver. ### Glucagon: Glucagon raises the blood glucose concentration by: * **Increasing the breakdown of glycogen in the liver:** Glucagon acts on liver cells and activates enzymes that convert glycogen, which is stored in the liver, to glucose (glycogenolysis). The glucose is then released into the bloodstream. * **Increasing gluconeogenesis in the liver:** Glucagon stimulates the liver to produce glucose from other sources including glycerol and amino acids (gluconeogenesis). ### The Liver: The liver plays an important role in regulating blood glucose concentration because: * **It stores excess glucose as glycogen:** When blood glucose level is high, the liver cells take up glucose from the blood and store it as glycogen. * **It converts non-carbohydrate sources into glucose:** When blood glucose level is low, the liver uses non-carbohydrate sources such as amino acids and glycerol to produce glucose. ### Control of Blood Glucose: The control of blood glucose is an example of negative feedback. When blood glucose concentration rises, it stimulates the release of insulin and inhibits the release of glucagon. The actions of insulin lower blood glucose concentration. When blood glucose concentration falls, it stimulates the release of glucagon and inhibits the release of insulin. The actions of glucagon raise blood glucose back to normal. ## 14.9 Diabetes - Distinguish between Type 1 and Type 2 diabetes. - Explain the effects of diabetes on blood glucose concentration. ### Diabetes: Diabetes is a common condition in which the body can no longer regulate blood glucose levels effectively. There are two main types of diabetes: #### Type 1 Diabetes: Also known as *juvenile diabetes* or *insulin-dependent diabetes*. It is an autoimmune disease where the body's immune system mistakenly destroys the β cells in the islets of Langerhans in the pancreas. This prevents the pancreas from producing insulin. People with Type 1 diabetes cannot produce insulin and so they need to inject insulin every day to maintain their blood glucose concentration within the normal range. #### Type 2 Diabetes: Also known as *adult-onset diabetes* or *non-insulin-dependent diabetes* is more common than Type 1. It is caused by a combination of factors including genetic predisposition, obesity, lack of exercise, a diet that is high in saturated fats and cholesterol, and ageing. People with Type 2 diabetes produce insulin but either their body cells do not respond to it properly (insulin resistance) or their pancreas cannot produce enough insulin to meet the body's needs. Those with Type 2 diabetes may need to take tablets or insulin injections to maintain their blood glucose concentration within the normal range. ### Effects of Diabetes: Diabetes causes a number of serious health problems: * **High blood glucose concentration:** In the absence of insulin or if the cells are resistant to insulin, the blood glucose concentration remains high. * **Hyperglycaemia:** In severe cases, the high concentration of glucose in the blood can cause complications such as loss of consciousness. * **Dehydration:** High glucose concentration in the blood reduces the water potential of the blood. This, in turn, reduces the water potential of the cells, causing water to move out of the cells by osmosis. Dehydration can be serious and can affect the functioning of all body systems. * **Ketoacidosis:** When the body runs out of glucose, it starts to break down fats for energy. The breakdown of fats produces ketone bodies, which are acidic. The build-up of ketone bodies in the blood can make it acidic, resulting in a condition called ketoacidosis. Ketoacidosis is life-threatening. * **Long-term complications:** Diabetes can damage blood vessels in the eyes, kidneys, and nerves. This can eventually lead to blindness, kidney failure and peripheral neuropathy.