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  1. 1. Biology – Communication, Homeostasis and EnergyModule 2 – Excretion 1) EXCRETIONExcretion is the removal of metabolic waste from the body, i.e. the removal of by-products or unwanted substances from normal cell processes.Almost any cell product formed in excess by the metabolic processes occurring mustbe excreted. The main excretory products are carbon dioxide, a waste product ofrespiration, and nitrogen-containing compounds, such as urea, which isproduced in the liver from excess amino acids.How?Carbon dioxide diffuses out of respiring cells into the surrounding tissue fluid andeventually into the bloodstream. It travels in the blood (mostly in the form ofhydrogencarbonate ions) to the lungs, where it diffuses through the alveoli walls andis expired.Urea is formed when amino acids are deaminated in the liver. Deamination is theremoval of an amine group from an amino acid to produce ammonia. The ureatravels in the bloodstream to the kidneys (dissolved in the plasma), where it isremoved from the blood to form part of urine. It is then stored as urine in the bladder,until it passes out of the body via the urethra.Why?Carbon dioxide in excess is toxic. A high level of carbon dioxide in the body hasthree main negative effects: 1) A high proportion of carbon dioxide is carried in the blood as hydrogencarbonate ions, which can form hydrogen ions. These hydrogen ions compete with oxygen for haemoglobin, so too much carbon dioxide in the blood leads to insufficient oxygen transport to respiring cells. 2) When carbon dioxide binds directly to haemoglobin (forming carbaminohaemoglobin), it creates a molecule that has a lower affinity for oxygen than haemoglobin itself. 3) Carbon dioxide in the blood plasma can combine with water to produce carbonic acid, which then dissociates to produce hydrogen ions. Hydrogen ions lower the pH of the blood, making it more acidic. If the blood pH falls below 7.35, the results are slowed or difficult breathing, headache,
  2. 2. drowsiness, restlessness, tremor and confusion. This is known as respiratory acidosis.The body cannot store excess amino acids, however, it does not allow them to goto waste. In the liver, amino acids are deaminated to form a keto acid and a highlytoxic compound, ammonia. The keto acid can be directly respired by cells underaerobic conditions, or stored as a carbohydrate or fat after conversion. Theammonia, on the other hand, being toxic, must be converted to a less toxicsubstance, urea, which can be transported to the kidneys for excretion. 2) THE LIVERLiver cells, or hepatocytes, carry out several hundred metabolic processes and theorgan itself plays an important role in maintaining homeostasis. It must have a veryrich supply of blood because of this, so the structure of the liver is arranged to allowthis.The liver is supplied with blood from two sources: - Oxygenated blood from the heart travels via the aorta to the hepatic artery, then into the liver. This supplies the liver cells with much oxygen necessary for aerobic respiration. Liver cells are very active, so require a lot of ATP formed from aerobic respiration. - Deoxygenated blood from the digestive system enters the liver via the hepatic portal vein, which carries blood rich in digestive products. Since the concentration of these products is uncontrolled thus far, the blood may contain toxic compounds that have been absorbed by the intestine. All blood leaves the liver via the hepatic vein, which joins the vena cava eventually.The fourth vessel is not a blood vessel, but a bile duct, which carries bile (asecretion from the liver) to the gall bladder, where it is stored until required to aid thedigestion of fats in the small intestine.How are the cells arranged?The liver is divided into lobes, which are further divided into cylindrical lobules. Thecells, blood vessels and chambers in the liver are all arranged to ensure the bestexchange of substances from and into the blood possible.The hepatic artery and hepatic portal vein split into smaller and smaller vessels asthe run between, and parallel to, the lobules. They are known as inter-lobularvessels. At intervals, branches from the hepatic artery and hepatic portal vein enterthe lobules, converging to form a sinusoid, which is lined by liver cells. The livercells are therefore able to remove molecules from the blood and pass molecules into
  3. 3. the blood. The sinusoids then empty into a branch of the hepatic vein, the intra-lobular vessel. The branches of the hepatic vein from different lobules converge toform the hepatic vein.Bile is formed by the liver cells, and this is secreted into the bile canaliculus. Theseconverge to form the bile duct, which transports the bile to the gall bladder.Kupffer cells are specialised macrophages that move around the sinusoids. Theyare involved in the breakdown of aged red blood cells. One of the products ofhaemoglobin breakdown is billirubin, which is excreted as part of the bile and infaeces. 3) FUNCTIONS OF THE LIVERThe liver is involved in many metabolic functions, including: - Control of: blood glucose levels, amino acid levels, lipid levels - Synthesis of: red blood cells in fetus, bile, plasma proteins, cholesterol - Storage of: vitamins A, D and B12, iron, glycogen - Detoxification of: alcohol and drugs - Breakdown of hormones - Destruction of red blood cellsForming UreaWe usually eat more than our required amount of protein, so, as it cannot be stored,it must be excreted, as the amine groups are toxic. Proteins are deaminated whichproduces ammonia, a highly toxic compound. It also produces a keto acid, which canbe directly respired or stored.The ornithine cycle – ammonia must be converted to a less toxic form as quickly aspossible, so it is combined with carbon dioxide to produce urea. Urea is less toxicthan ammonia, and is passed back in the blood to travel to the kidneys.Ammonia + Carbon Dioxide  Urea + Water
  4. 4. DetoxificationThe liver is able to detoxify many compounds, some produced in the body (such ashydrogen peroxide) and some consumed (such as alcohol). Toxins can be renderedharmless by reduction, oxidation, methylation or combination with another molecule.Since the liver is involved in detoxification, its cells contain many enzymes involvedin the detoxification of substances. Catalase is one such enzyme, which breakshydrogen peroxide down to harmless oxygen and carbon dioxide.Detoxification of AlcoholAlcohol, or ethanol, is an intoxicating drug that suppresses nervous activity.However, it also contains chemical potential energy, which can be used inrespiration. It is broken down in the hepatocytes by the action of the enzyme ethanoldehydrogenase. The resultant is ethanal, which is further dehydrogenated by theenzyme ethanal dehydrogenase. The final compound is ethanoate (acetate), whichis combined with CoA to form acetyl CoA, which enters the Krebs cycle. In addition,the hydrogen atoms released by the dehydrogenation reactions are used to reduceNAD and FAD used in oxidative phosphorylation.NAD is also required to oxidise and break down fatty acids, so if too much is beingused in the detoxification of alcohol, then the fatty acids are converted back to lipidsand stored in the liver cells, causing an enlarged liver. This can lead to alcohol-related hepatitis or to cirrhosis. 4) THE KIDNEYMost people have two kidneys, positioned both sides of the spine and just under thelowest rib. Each kidney is supplied with blood from the renal artery and is drained bya renal vein. The kidney removes waste products from the blood and producesurine, which passes out of the kidney down the ureter to the bladder.The kidney can be described as consisting of three regions, enclosed within a toughcapsule: - The outer region, known as the cortex - The inner region, known as the medulla - The pelvis of the kidney, leading to the ureter.Each kidney actually consists of tiny tubules, known as nephrons, which areabundant and are associated with tiny capillaries. Each nephron begins in the cortex,where they form a knot known as the glomerulus. This is surrounded by a cup-shaped structure known as the Bowman’s capsule. The afferent arteriole carriesblood to the glomerular capillary, where it is pushed into the Bowman’s capsule
  5. 5. through the process of ultrafiltration. The capsule leads into the nephron, which isdivided into four parts: - Proximal convoluted tube - Loop of Henle - Distal convoluted tube - Collecting ductAs the fluid moves along the nephron, its composition is altered; achieved byselective reabsorbtion of salts, water, etc. These substances are absorbed backinto the tissue fluid and blood capillaries surrounding the nephron tubule. The finalproduct in the collecting duct is urine.How does the composition of the fluid change? - In the proximal convolution, the fluid is altered by the reabsorbtion of all sugars, most salts and some water. In total, around 85% of the fluid is reabsorbed here. - In the descending limb of the loop of Henle, the fluid’s water potential is decreased by the addition of salts and the removal of water. - In the ascending limb of the loop of Henle, the water potential is increased as salts are removed by active transport. - In the collecting duct, the water potential is decreased again by the removal of water. This ensures that urine has a low water potential, so it has a higher concentration of solutes than the blood or tissue fluid. 5) FORMATION OF URINEThe barrier between the blood in the capillary and the lumen of the Bowman’scapsule consists of only three layers of cells: - The capillary endothelium - A basement membrane - The Bowman’s capsule epithelial cellsThe endothelium of the capillaries has narrow gaps between its cells to allowultrafiltration. They allow the blood plasma (and whatever is in solution in it) to passthrough. The basement membrane is a fine mesh of collagen fibres andglycoproteins. These act as a filter, only allowing molecules with a relative molecularmass of less than 69,000 to pass through. Thus, blood cells and proteins are held inthe capillaries. Finally, the epithelial cells of the Bowman’s capsule (known aspodocytes) have finger-like projections called major processes. These ensure thatthere are gaps between cells, so that fluid from the blood in the glomerulus can passinto the lumen of the Bowman’s capsule.
  6. 6. What is filtered? - Water - Amino acids - Glucose - Urea - Inorganic ions (such as potassium, sodium and calcium).This means that only blood cells and proteins are left in the capillary, and this causesa very negative water potential. This low water potential enables the blood toreabsorb water at a later stage.The cells lining the proximal convolution are adapted to allow 85% of the filtrate to bereabsorbed: - Microvilli, formed by folding the cell surface membrane, increase the surface area for reabsorbtion. - The cell surface membrane also contains co-transporter proteins, which transport glucose, amino acids and sodium ions out of the filtrate by facilitated diffusion. - The opposite membrane of the cell contains sodium-potassium ion pumps that pump sodium ions out and potassium ions in. It is also folded to increase its surface area. - As much ATP is required, the cells lining the proximal convolution have many mitochondria.How? - The sodium-potassium ion pumps remove sodium from the cells and thus reduce the concentration of sodium ions in the cell cytoplasm. - Glucose and amino acids are transported into the cello by facilitated diffusion, which means that the concentrations of these substances rise inside the cell. - The cell’s cytoplasm, because it now contains many solutes, has a lower water potential than the filtrate in the tubule, so water diffuses into the cells by osmosis. - The water potential and concentrations of salts, glucose and amino acids are lower in the tissue fluid surrounding the cells of the proximal convolution, so the salts, glucose and amino acids diffuse into the tissue fluid by facilitated diffusion, and water diffuses into the tissue fluid by osmosis. - Larger molecules may be reabsorbed by endocytosis.
  7. 7. 6) WATER REABSORBTIONWhen the filtrate reaches the loop of Henle, there is about remaining. Therole of the loop of Henle is to create a low water potential in the tissue of themedulla. This ensures that even more water can be reabsorbed from the filtrate inthe collecting duct. The loop of Henle consists of a descending limb that descends into the medullaand an ascending limb that ascends back out to the cortex. This arrangementallows salts to be transferred from the ascending limb into the descending limb. Theoverall effect is to increase the concentration of salts in the tubule fluid andconsequently they diffuse out into the surrounding medulla tissue fluid, giving it avery low water potential.As the tubule descends deeper into the medulla, its water potential begins to fall, dueto the loss of water by osmosis to the surrounding tissue fluid, and also the diffusionof sodium and chloride ions into the tubule from the surrounding tissue fluid.As the tubule ascends up the cortex, its water potential begins to rise, because: - At the base of the tubule, sodium and chloride ions diffuse out of the tubule into the tissue fluid. - Higher up the tubule, sodium and chloride ions are actively transported out into the tissue fluid. - The wall of the ascending limb is impermeable to water, so water cannot leave the tubule.
  8. 8. - The fluid loses salts, therefore, and no water as it moves up the ascending limb.The movement of salts from the ascending limb into the medulla creates a high saltconcentration in the tissue fluid of the medulla, so there is a very negative waterpotential. This allows water to be reabsorbed in the distal convolution and thecollecting duct. The amount of water reabsorbed depends on the needs of thebody. 7) OSMOREGULATIONOsmoregulation is the control of water and salt levels in the body. To maintain anosmotic balance for efficient cellular processes, the correct water potential must bemaintained between cells and surrounding tissue fluids.Water is gained from food, drink and respiration.Water is lost through urinating, sweating, exhaling water vapour, and in faeces.Controlling the loss of water in the urine involves making the walls of the collectingduct more or less permeable, depending on the body’s need. When less water needsto be conserved, the walls of the collecting duct are less permeable, and vice versa.The permeability of the collecting duct walls is influenced by the level of antidiuretichormone (ADH) in the blood stream. The cell surface membranes of the cells in thewall contain receptors specific to ADH.When ADH binds to these receptors, it activates a second messenger inside the cell,which causes a chain of enzyme-catalysed reactions. The effect of these reactions isto insert aquaporins (water-permeable protein channels) into the plasmamembrane. This makes the walls of the collecting duct more permeable to water,thus allowing more to be reabsorbed and less to be passed out in urine.Controlling the concentrations of ADH in the bloodLike many of the homeostatic functions, the hypothalamus controls the secretion ofADH: - Osmoreceptors in the hypothalamus respond to the effects of osmosis. When the water potential is low, the osmoreceptors lose water by osmosis, causing them to shrink. - The shrinking of the receptors causes stimulation of neurosecretory cells, which produce and secrete ADH. The ADH is manufactured in the cell body of these cells, which lies in the hypothalamus. The ADH flows down to the terminal bulb in the posterior pituitary gland, where it is stored until needed.
  9. 9. - When the neurosecretory cells are stimulated, they send action potentials down their axons, which causes the secretion of ADH.In order to ensure that ADH does not have a constant effect, it has a half-life of 20minutes, so it is gradually broken down in the blood, slowing its effect on thecollecting duct’s walls. 8) KIDNEY FAILUREKidney failure occurs mostly due to diabetes mellitus, hypertension and infection.TreatmentDialysis is the most common treatment for kidney failure, and essentially bypassesthe kidney by removing wastes, excess fluid and salt from the blood by passing itover a dialysis membrane. It is a partially permeable membrane that allows theexchange of substances between the blood and the dialysis fluid. The fluid containsthe correct concentrations of salt, urea, water and other substances in the bloodplasma, so any substances in excess will diffuse across the membrane into thedialysis fluid.In haemodialysis, blood from a vein is passed through a dialysis machine thatcontains a dialysis membrane. It is usually performed at a clinic three times a weekfor several hours, however, it can be carried out at home.In peritoneal dialysis, the filter is the body’s own abdominal membrane. A surgeonmust implant a tube in the abdomen into which dialysis solution is poured. Afterseveral hours, the solution is drained from the abdomen. PD is performed severaltimes a day at home or work.A kidney transplant is a less common treatment for kidney failure. A donor, usuallya family member, can donate one of their healthy kidneys to a patient in need of akidney transplant. A surgeon implants the new organ into the lower abdomen andattaches it to the blood supplies and ureter. However, a patient’s body can see thekidney as a foreign body and initiate an immune response against it. Because of this,for the life of the organ, the patient must take immunosuppressant drugs.