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A2 - Unit 4 - Module 2 - OCR - Excretion - All Notes Final

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Slides specifically for OCR syallbus during A-Levels, this is for A2 - Unit 4 - Module 2 - 1.2.1 - 1.2.8. I have made these for my students and they have found them very useful.

Includes Summary Questions, Further Application questions and key definitions at the end of the slides

Slides aimed for teachers, but can be used as revision slides for students also.

More than welcome to download, good luck with exams!

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A2 - Unit 4 - Module 2 - OCR - Excretion - All Notes Final

  1. 1. A2 – Module 1 – Unit 2 - Excretion 5/17/2015 1
  2. 2. 1.2.1 Excretion 5/17/2015 2
  3. 3. What is excretion?  Excretion = the removal of metabolic waste from the body  Metabolic waste = consists of waste substances that may be toxic or are produced in excess by the reactions inside cells.  There are 2 substances that are produced in very large amounts:  Carbon dioxide  Nitrogen containing compounds such as urea  Note: EGESTION is when your body removes undigested food by the process of defecation. EXCRETION is when your body removes metabolic waste which has entered your cells. 5/17/2015 3
  4. 4. Where are these substances excreted?  Carbon dioxide is passed from the cells of respiring tissues into the bloodstream. It is transported in the blood (mostly in the form of hydrogencarbonate ions) to the lungs. In the lungs the carbon dioxide diffuses into the alveoli to be excreted as we breathe.  Urea is made from the break down of excess amino acids in the liver. This process is called deamination. Urea is passed into the bloodstream to be transported to the kidneys.  it is transported in solution (dissolved in plasma)  In the kidneys, urea is removed from the blood to become a part of urine.  Urine is stored in the bladder before being excreted via the urethra. 5/17/2015 4
  5. 5. Why must these substances be remove? Part I Carbon dioxide:  Excess carbon dioxide can lead to toxicity via three main effects: 1. Carbon dioxide is transported in the blood as hydrogencarbonate ions. This occurs inside the red blood cells under the influence of carbonic anhydrase H2CO3  H+ + HCO3 - The hydrogen ions combine with haemoglobin. They compete with oxygen for space on the haemoglobin. If there is too much carbon dioxide in the blood it will reduce oxygen transport 2. Carbon dioxide when bound to haem forms carbaminohaemoglobin. (Carbon dioxide has a higher affinity for haem, when the compound is formed carbaminohaemoglobin will have a lower affinity for oxygen than normal haem) Therefore it becomes difficult for oxygen to attach onto haem as carbon dioxide is strongly associated with haem. 5/17/2015 5
  6. 6. Why must these substances be removed? Part II 3. Excess carbon dioxide can cause respiratory acidosis. The carbon dioxide dissolves in the blood plasma. Once dissolved it can combine with water to produce carbonic acid: CO2 + H2O  H2CO3 The carbonic acid dissociates to release hydrogen ions H2CO3  H+ + HCO3 -  The hydrogen ions lower the pH  acidity within the blood circulation. Proteins in the blood act as buffers to resist the change in pH.  If the pH change is small the extra H+ ions are detected by the respiratory centre in the medulla oblongata of the brain resulting in  Increased breathing rate removing excess carbon dioxide 5/17/2015 6
  7. 7. Why must these substances be removed? Part III   If the pH drops below 7.3 it results in  slowed or difficult breathing, headache, drowsiness, restlessness, tremor and confusion.  May also be a rapid heart rate and changes in blood pressure.  THIS IS RESPIRATORY ACIDOSIS (A MEDICAL EMERGENCY, NEEDS TREATMENT IMMEDIATELY) Respiratory acidosis can also be caused by diseases or conditions that affect the lungs themselves due to blockage of airway leading to increase in carbon dioxide. These diseases include; emphysema, chronic bronchitis, asthma or severe pneumonia. Conditions such as swelling, a foreign object or vomit in the airways are also causative. 5/17/2015 7
  8. 8. Why must these substances be removed? Part IV  Nitrogenous Compounds:  The body cannot store proteins or amino acids(aa). However, aa contain as much energy as carbohydrates, therefore we do not want to waste this energy source. AA are transported to the liver and the potentially toxic amino group is removed (deamination).  Step 1 -The amino group initially forms a very soluble and highly toxic compound = ammonia  Amino acid + oxygen  keto acid + ammonia  Step 2 - Ammonia is converted to a less soluble and less toxic compound = urea  Ammonia + carbon dioxide  urea + water 2NH3 + CO2  CO(NH2)2 + H2O  Urea is then transported to the kidneys for excretion. The remaining keto acid can be used directly in respiration to release its energy or it may be converted to a carbohydrate or fat for storage. 5/17/2015 8
  9. 9. 1.2.2 The Liver 5/17/2015 9
  10. 10. The structure of the liver  The liver cells namely the hepatocytes carry hundreds of metabolic processes and has an important role in homeostasis. Therefore it is essential for a continuous supply of blood. The internal structure of the liver is arranged to ensure that as much blood flows past as many liver cells as possible 5/17/2015 10
  11. 11. Blood flow to the liver  TO:  The liver has two blood supplies  Oxygenated blood from the heart. Blood travels from the aorta via the HEPATIC ARTERY INTO THE LIVER.  This supplies the oxygen essential for aerobic respiratory. Hepatocytes are very active and require energy in the form of ATP so it is essential there is a good oxygen supply.  Deoxygenated blood from the digestive system. This enters the liver via the HEPATIC PORTAL VEIN. This blood is rich in the products of digestion. The concentration of the various compounds will be uncontrolled and the blood may contain toxic compounds that have been absorbed by the intestine. 5/17/2015 11
  12. 12. Blood flow from the liver  FROM:  Blood leaves the liver via the HEPATIC VEIN. This re-joins the vena cava and the blood returns to normal circulation  A Fourth vessel connected to the liver is not a blood vessel. It is the bile duct. Bile is a secretion from the liver. It has both a digestive function and an excretory function. The bile duct carries bile from the LIVER TO THE GALLBLADDER where it is stored until required to aid the digestion of fats in the small intestine. 5/17/2015 12
  13. 13. The arrangement of cells inside the liver  The liver is divided into lobes and further divided into cylindrical lobules.  As the hepatic artery and hepatic portal vein enter the liver, they split into smaller and smaller vessels which run parallel or between the lobules and are known as inter- lobular vessels.  The blood from two blood vessels are mixed and passed through a special chamber called sinusoid which furthermore empty into the intra-lobular vessels a branch of the hepatic vein.  The branches of the hepatic vein from different lobules join together to form the hepatic vein draining blood from the liver.  As blood moves along the sinusoid it is in very close contact with the liver cells. They are able to remove molecules from the blood and pass molecules into the blood.  One of the many functions of the liver cells is to manufacture bile. This is released into the bile canaliculi (small canals). These join together to form the bile duct, which transports the bile to the gall bladder. 5/17/2015 13
  14. 14. Liver Cells  Hepatocytes are unspecialised simple cuboidal shaped cells which have many microvilli on their surface  They are however involved in many metabolic functions including;  Protein synthesis  Transformation  Storage of carbohydrates  Synthesis of cholesterol and bile salts  Detoxification and other processes  This means that their cytoplasm must be very dense and is specialised in the amounts of certain organelles that it contains 5/17/2015 14
  15. 15. Kupffer cells  Kupffer cells are specialised macrophages moving about in the sinusoids involved in the breakdown and recycling of red blood cells. A product it produces during breakdown is bilirubin which is excreted as part of the bile and in faces. Bilirubin is the brown pigment is faeces.  Application Scenario:  A common condition in newborns, jaundice refers to the yellow color of the skin and whites of the eyes caused by excess bilirubin in the blood.  It is also seen in adults where an excess chronic consumption of alcohol can have damaging effects on your liver meaning that you are not removing bilirubin from your liver and bile ducts quickly enough, as it builds up in the blood it is deposited in the skin… The resulting is jaundice. 5/17/2015 15
  16. 16. 1.2.3 – Functions of the liver 5/17/2015 16
  17. 17. Wide Range of functions of the liver  Control of:  Blood glucose levels, amino acid levels, lipid levels  Synthesis of:  RBC in the fetus, bile, plasma proteins, cholesterol  Storage of:  Vitamins A, D and B12 , iron, glycogen  Detoxification of:  Alcohol and drugs  Breakdown of hormones  Destruction of RBCs 5/17/2015 17
  18. 18. Formation of Urea  Daily requirement is 40-60g of protein, but daily consumption is far more greater therefore, breakdown of amino acids are needed as accumulation leads to toxicity.  Two step process occurs in the liver before the amino acid component is excreted  DEAMINATION  ORNITHINE CYCLE 5/17/2015 18
  19. 19. Formation of Urea  DEAMINATION:  Removal of NH3 group fro the amino acid with oxygen forming a keto acid (-RCOCOOH) and Ammonia (NH3)  Ammonia is highly toxic and very soluble therefore should not be allowed to accumulate in the blood circulation.  On removal of NH3 group energy is released.  THE ORNITHINE CYCLE:  Ammonia is converted into a less soluble and less toxic substance when combined with CO2 forming Urea.  Urea is further passed into the blood circulation and into the kidneys where it is filtered out of the blood circulation and is concentrated in the urine.  5/17/2015 19
  20. 20. Detoxification  The liver detoxifies alcohol and drugs. Toxins can also be rendered harmless by oxidation, reduction, methylation or a combination with another molecule.  Liver cells contain many enzymes that enable rendering of toxic molecules  less toxic form.  This includes catalase which converts H2O2 to oxygen and water  DETOXIFICATION OF ALCOHOL:  Alcohol is a CNS depressant; contains a lot of energy that can be used for respiration.  STEP 1: Ethanol  Ethanol dehydrogenase  Ethanal (occurs in the hepatocytes)  STEP 2: Ethanal  Ethanal dehydrogenase  Ethanoic acid  STEP 3: Ethanoic acid  Ethanoate + CoA  Acetyl CoA  The hydrogens release in the steps above are combined with NAD  NADH  NAD is required to oxidise and breakdown fatty acids for use in respiration 5/17/2015 20
  21. 21. Future Possible Complications  If the liver has to detoxify too much alcohol it has insufficient NAD to deal with the fatty acids.  These fatty acids are converted back to lipids and are stored in the hepatocytes, causing the liver to become enlarged  Causes a condition known as fatty liver  alcohol-related hepatitis or cirrhosis. 5/17/2015 21
  22. 22. Stretching Your Knowledge Scenario:  Liver cells contain a large group of enzymes called the cytochrome P450 enzymes. These are responsible for the breakdown of some toxic molecules, such as cocaine and other drugs (recreational and medicinal). The P450s are most concentrated in the endoplasmic reticulum of liver cells. As a result of variation these enzymes can be more effective in some people than in others (Caucasian population compared to Afro-Caribean population)  Many drugs can be more effective in some people than in others and may also cause variable side effects Task: 1. Suggest why the P450s are most concentrated in the endoplasmic reticulum? 2. Suggest why many medicinal drugs have different side effects in different people 3. Explain why the P450s are not identical in every person. 5/17/2015 22 The P450s are proteins; these are manufactured by the ribosomes that are attached to the endoplasmic reticulum – they can be packaged in vesicles and transported to where they are needed Each person may have slightly different enzymes (evolution). These may break the drugs down in a slightly different way producing different by-products (SEs) Genetic variation means that different people will have different alleles – these will produce slightly different enzymes.
  23. 23. Questions: 1. Why must ammonia be converted to urea? 2. Explain why excess amino acids and alcohol should not be excreted? 3. Suggest why the liver cells have large number of mitochondria and ribosomes 5/17/2015 23 Ammonia is highly soluble and very toxic; urea is less soluble and less toxic They contain valuable energy that can be converted to useable forms. Some amino acids can be converted into other amino acids The mitochondria provide ATP (metabolic energy) for the active or energy- requiring processes, e.g. protein synthesis, mitosis, active transport, endo and exocytosis. The ribosomes manufacture the many enzymes that are needed in liver cells.
  24. 24. 1.2.4 The Kidney 5/17/2015 24
  25. 25. The structure of the kidney  Positioned at each side of the spine just below the lowest rib  Supplied with blood from a renal artery and is drained by a renal vein  JOB: - remove waste products from the blood and to produce urine.  Urine passes out of the kidney down the ureter to the bladder where it can be stored before release 5/17/2015 25
  26. 26. The Nephron - Part I  The bulk of each kidney consists of tiny tubules called nephrons.  They are closely associated with tiny blood capillaries  Each nephron starts in the cortex  In the cortex the capillaries form a knot called the glomerulus  This is surrounded by a cup-shaped structure called the Bowman’s Capsule  Fluid from the blood is pushed into the Bowman’s capsule by the process of ultrafiltration 5/17/2015 26
  27. 27. The Nephron - Part II  The capsule leads into the nephron which is divided into 4 parts:  The proximal convoluted tubule  Loop of Henle (Descending and Ascending Limb)  Distal convoluted tubule  Collecting duct  As fluid moves along the nephron its composition is altered. This is achieved by selective reabsorption. Substances are reabsorbed back into the tissue fluid and blood capillaries surrounding the nephron tubule.  The final product in the collecting duct is urine, passed into the pelvis  ureter  bladder. 5/17/2015 27
  28. 28. How does the composition of the fluid change?  In the PCT the fluid is altered by the reabsorption of all the sugars, most salts and some water  In total about 85% of the fluid is reabsorbed here  In the DL of the Loop of Henle, the water potential of the fluid is decreased by the addition of salts and removal of water  In the AL of the Loop of Henle, the water potential of the fluid 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 the final product (urine) has a low water potential.  Urine has a higher concentration of solutes than is found in the blood and tissue fluid. 5/17/2015 28
  29. 29. Questions: 1. Suggest why the nephrons are convoluted 2. Why are there many capillaries around each nephron? 3. Explain why reabsorption from the nephron must be selective 5/17/2015 29 The fact that the nephrons are convoluted allows there to be an increase the length for greater surface area for absorption or filtration. This ensures accuracy and minimizes loss in terms of absorption of useful molecules required for the body. Materials reabsorbed from the fluid in the tubule can re-enter the blood circulation Some of the molecules in the nephron are waste and must be left in the fluid to be excreted. Other molecules are useful to the body and must be reabsorbed.
  30. 30. Practice Exam Questions: 1. What is meant by the term excretion? [2 marks] 2. Name the two excretory products produced in mammals [2 marks] 3. Name the two organs that remove these products from the body [2 marks] 4. Name the blood vessels that carry blood to the liver [2 marks] 5. What is a sinusoid and where is it found? [2 marks] 6. What is a hepatocyte? [1 marks] 7. What is meant by the term deamination? [2 marks] 8. What occurs during the ornithine cycle? [2 marks] 9. Name the three sections of the kidney as seen in longitudinal section [3 marks] 10. Name the tubules found in the kidney [2 marks] 5/17/2015 30
  31. 31. Practice Exam Question: ANSWERS 1. The removal of waste products from cell metabolism 2. Carbon dioxide and urea 3. The lungs and the kidneys 4. The hepatic artery( oxygenated blood) and hepatic portal vein (deoxygenated blood) 5. A sinusoid is a channel between the liver cells; they are found in the liver lobules 6. A liver cell 7. The removal of the amino group from an amino acid forming ammonia and leaving a ketose residue 8. The conversion of ammonia to urea by the addition of carbon dioxide 9. Cortex, medulla and pelvis 10. Nephrons 5/17/2015 31
  32. 32. 1.2.5 – Formation of Urine 5/17/2015 32
  33. 33. Overview Videos:   5/17/2015 33
  34. 34. Ultrafiltration - PART I  Blood flows through the afferent arteriole into the glomerulus and blood leaves through the efferent arteriole  Afferent arteriole is wider in diameter than the efferent arteriole  Efferent arteriole is an arteriole – which is muscular and can constrict to raise the blood pressure in the glomerulus. In most organs a venule carries away blood away  This difference ensures the glomerulus is higher in pressure in comparison to the pressure in the Bowman’s capsule  This pressure differences pushes the fluid from the blood into the Bowman’s capsule 5/17/2015 34
  35. 35. Ultrafiltration - PART II  The barrier between the blood in the capillary and the lumen of the Bowman’s capsule consists of three layers:  Endothelium of the capillary  A basement membrane  The epithelial cells of the Bowman’s capsule (podocytes) 5/17/2015 35
  36. 36. Ultrafiltration - PART III  Each structure is adapted to allow ultrafiltration:  Fenestrated Endothelium – narrow gaps between each endothelium cells – blood plasma and substances dissolved in blood plasma can pass through these narrow gaps  Basement membrane – fine mesh of collagen fibres and glycoprotein  This filter prevent the passage of molecules with a relatively high molecular mass. All proteins (and all blood cells) are held in the capillaries of the glomerulus  Epithelial cells of the Bowman’s capsule are called PODOCYTES which have a specialized shape.  Podocytes have finger-like projections called major processes. Ensuring that gaps are present in between cells.  The fluid from the blood in the glomerulus can pass between these cells into the lumen of the Bowman’s capsule 5/17/2015 36
  37. 37. What is filtered out of the blood?  Blood plasma containing dissolved substances is pushed under pressure from the capillary into the lumen of the Bowmans capsule. This includes the following substances:  Water  Amino acids  Glucose  Urea  Inorganic ions (Na+, Cl-, K+) 5/17/2015 37
  38. 38. What is left in the capillary?  The blood cells and proteins are left in the capillary  Presence of the proteins means that the blood has a very low (very negative) water potential  Due to this low water potential it ensures that some of the fluid is retained in the blood, and this contains some of the water and dissolved substances listed above  The very low water potential of the blood in the capillaries is important to help reabsorb water at a later stage. 5/17/2015 38
  39. 39. Stretching Your Knowledge Scenario:  High Blood pressure can damage the capillaries of the glomerulus and the epithelium of Bowman’s capsule. Task:  Explain why the presence of protein in urine can be a sign of hypertension? 5/17/2015 39 Proteins are normally filtered by the basement membrane. If this has been damaged by high blood pressure then proteins can enter bowmans capsule from the blood and pass into the urine presenting as proteinuria
  40. 40. Selective Reabsorption - PART I  Reabsorption is achieved by a combination of processes described below. The cells lining the proximal convoluted tubule are specialized to achieve this reabsorption:  PCT cells are highly folded forming microvilli for increase surface area for reabsorption  PCT cells also have special co-transporter proteins transporting glucose or amino acids, in association with sodium ions from the tubule into the cell  facilitated diffusion  Molecules are moving from a high water potential to a low water potential (no ATP is required)  PCT cells lined towards the capillaries are also highly folded forming microvilli for increased surface area. This membrane contains sodium-potassium pumps that pump sodium ions out of the cell and potassium ions into the cell.  These pumps require ATP, so have high amounts of mitochondria surrounding  Large molecules, such as small proteins that may have entered the tubule, will be reabsorbed by endocytosis. 5/17/2015 40
  41. 41. Selective Reabsorption - PART I 5/17/2015 41PCT cells lining towards the capillaries PCT cells lining
  42. 42. 5/17/2015 42
  43. 43. Questions: 1. Explain what is meant by ultrafiltration? 2. Suggest what might happen if water is not reabsorbed from the nephron 3. Explain why the concentrations of glucose and amino acids are the same in the glomerular filtrate as in the blood plasma 5/17/2015 43 Filtering on a molecular scale. Small molecules pass through the basement membrane, which acts as a filter, while larger molecules are held in the blood A large volume of very dilute urine would be produced and dehydration would occur Because the amino acids and glucose have been passed from the blood plasma to the glomerular filtrate by ultrafiltration in the glomerulus
  44. 44. 1.2.6 – Water reabsorption OCR – A2 – Module 2 5/17/2015 44
  45. 45. Reabsorption of Water  Each minute 125cm3 of fluid is filtered from the blood and enters the nephron tubules  After selective reabsorption in the proximal convoluted tubules about 45cm3 is left  The role of the loop of henle is to create a low (very negative) water potential in the tissue of the medulla  ensures that more water can be reabsorbed from the fluid in the collecting duct 5/17/2015 45
  46. 46. The Loop of Henle - Part I  Consists of a descending limb which descends into the medulla and an ascending limb that ascends back out to the cortex.  The overall effect of the loop of henle:  Filter the fluid entering the descending limb which is slightly concentrated.  Osmotically removing water from the descending limb into the Vasa Recta  Water potential decreases and is highly concentrated as you enter the ascending limb  Here Na+ and Cl- ions are actively removed from the ascending limb into the Vasa Recta  The ascending limb is impermeable to water, so cannot leave the tubule.  The ascending limb increases in water potential as it enters the DCT  = COUNTERCURRENT MULTIPLIER 5/17/2015 46
  47. 47. The Loop of Henle - Part II  Vasa Recta surrounds the loop of henle in an opposing fashion;  As you go down the descending limb in the loop of henle you are ascending in the Vasa Recta, as you go up the ascending limb in the loop of henle you are descending in the Vasa Recta  The top of the ascending limb urine is highly dilute (watery) therefore as you continue from the DCT and CT water is reabsorbed leaving a concentrated fluid which is excreted  The amount of water reabsorbed depends on the needs of the body and so the kidney is also an organ of osmoregulation. 5/17/2015 47
  48. 48. The Collecting Duct  At the top of the ascending limb it connects to the DCT which is very short in comparison to your PCT, active transport is used to reabsorb water from your DCT into your surrounding tissue fluid  From the DCT  CD water has a high water potential therefore the CD carries on removing water leaving as it descends from the medulla into your pelvis.  The remaining solute left becomes highly concentrated and is excreted. 5/17/2015 48
  49. 49. Stretching Your Knowledge Scenario:  Question: Why do camels have humps? Answer: It was a myth that the hump was due to a long loop of henle. However current research shows that the hump stores fat which can be metabolized to release energy and water. But why do camels need an extra long loop of Henle? All mammals adapted to living in arid regions share this feature. It provides them with a longer countercurrent mechanism that can increase the salt concentration in the medulla more than in other mammals. Task:  Explain why it is beneficial to mammals living in arid regions to have higher salt concentrations in their medullas? 5/17/2015 49 A higher salt concentration in the medulla means that a greater water potential gradient can be achieved between the urine in the CD and the medulla. This means that more water can be reabsorbed from the CD and then pass into blood capillaries and the urine is made more concentrated. There will be less urine produced and less water lost.
  50. 50. Stretching Your Knowledge Scenario:  The tissue fluid in the medulla has a low water potential, so how can water pass from the tissue fluid into the blood plasma by osmosis? Task:  Explain an arrangement of the blood vessels that could create blood plasma with an even lower water potential than the tissue fluid. 5/17/2015 50 A higher salt concentration in the medulla means that a greater water potential gradient can be achieved between the urine in the CD and the medulla. This means that more water can be reabsorbed from the CD and then pass into blood capillaries and the urine is made more concentrated. There will be less urine produced and less water lost.
  51. 51. Questions: 1. Why must the collecting duct pass back through a region of low water potential? 1. Why is it important for terrestrial mammals to reabsorb as much water as possible? 2. Suggest why beavers have short loops of Henle 5/17/2015 51 This arrangement allow water to be reabsorbed from the collecting ducts back into the tissue fluid of the medulla. This concentrates the urine. Terrestrial mammals gain water by eating and drinking. They lose water through sweat, exhaling, excretion and egestion. It is important not to lose more water than necessary, as it may not be readily available. Beavers live beside or in water. Water is readily available and they do not need to conserve it as much.
  52. 52. 1.2.7 - Osmoregulation 5/17/2015 52
  53. 53. Osmoregulation  Osmoregulation = control of water levels and salt levels in the body.  Water is gained from: Food, drink, metabolism  Water is lost in: urine, sweat, water vapor in exhaled air, faeces  When drinking plentiful fluid you will produce a large volume of dilute urine  When drinking a less amount of fluid you will produce smaller volumes of more concentrated urine  The walls of the collecting duct can be made more or less permeable according to the needs of the body  On a cool day your requirement of water is lower therefore the walls of the collecting duct are less permeable and less water is reabsorbed therefore producing more urine  On a warmer day you requirement of water is much more greater therefore the walls of the collecting duct are more permeable and more water is reabsorbed therefore producing a smaller volume of urine. 5/17/2015 53
  54. 54. Altering the permeability of the CD - PART I  The walls of the collecting duct respond to Antidiuretic hormone (ADH) in the blood.  ADH has an antidiuretic action that prevents the production of dilute urine (and so is called an antidiuretic)  Cells in the wall have membrane-bound receptors for ADH.  The ADH binds to these receptors and causes a chain of enzyme-controlled reactions inside the cell. 5/17/2015 54
  55. 55. Altering the permeability of the CD - PART II  If there is more ADH in the blood then vesicles containing water-permeable channels (aquaporins) will fuse into the cell surface membrane  Therefore, the walls more permeable to water. More ADH = More permeable channels inserted  more water reabsorbed by osmosis  More concentrated urine  If there is less ADH in the blood then the cell surface membrane folds inwards to create new vesicles that remove water- permeable channels from the membrane  Therefore, the walls less permeable to water  less water is reabsorbed via osmosis into the blood  more water passes out into the (dilute) urine. 5/17/2015 55
  56. 56. Normal Effect: 5/17/2015 56
  57. 57. Too Much Water: 57
  58. 58. Too Little Water: 5/17/2015 58
  59. 59. Adjusting the concn of ADH in the blood - PART I  The Water potential of the blood is monitored by osmoreceptors in the hypothalamus of the brain  When water potential of the blood is low the osmoreceptor cells lose water by osmosis causing them to shrink  stimulates neurosecretory cells in the hypothalamus  The neurosecretory cells are specialized neurons (nerve cells) that produce and release ADH.  ADH releasing cell bodies are found to lie in the hypothalamus  ADH flows down the axon to the terminal bulb in the posterior pituitary gland and stored until needed 5/17/2015 59
  60. 60. Adjusting the concn of ADH in the blood - PART II  When the neurosecretory cells are stimulated they send an AP down their axons and cause the release of ADH  ADH enters blood capillaries running through the posterior pituitary gland  around the body  acts on the cells of the collecting ducts  Once water potential rises, less ADH is released  ADH is slowly broken down and collecting ducts will receive less stimulation – half-life of about 20minutes  Half-life of a substance is the time taken for it’s concentration to drop to half it’s original value. 5/17/2015 60
  61. 61. 5/17/2015 61
  62. 62. Control of water potential in the blood by negative feedback 5/17/2015 62 Increase in water potential of blood Detected by osmoreceptors in hypothalamus Less ADH released from the posterior hypothalamus Collecting duct walls less permeable Less water reabsorbed into blood; more urine produced Decrease in water potential of blood Normal water potential of blood Decrease in water potential of blood Detected by osmoreceptors in hypothalamus More ADH released from the posterior hypothalamus Collecting duct walls more permeable More water reabsorbed into blood; less urine produced Decrease in water potential of blood
  63. 63. Stretching Your Knowledge Scenario: A number of drugs have an effect on urine production. Some have effects that are unwanted or may be a nuisance. Alcohol inhibits the production of ADH, and certain antibiotics, such as tetracycline, can cause renal failure through a variety of mechanisms including direct toxicity to the nephron tubules. Other drugs have effects that may be useful. Diuretic drugs increase urine production and antidiuretic drugs do the opposite by increasing the reabsorption of water at the distal tubule and collecting ducts without significantly modifying the rate of glomerular filtration. Task:  Explain why drinking too much alcohol can cause a hangover?  Suggest what symptoms may be relieved by the use of (i) Diuretics and (ii) antidiuretics 63 Alcohol inhibits the release of ADH therefore the collecting ducts are not very permeable and less water is reabsorbed. This means that more water is lost in urine and dehydration occurs. The ethanal produced form the metabolism of ethanol also contributes to the headache (i) – Diuretic drugs can be used to relieve water retention, which can cause swelling and high blood pressure. (ii) Antidiuretic drugs can be used to relieve diabetes insipidus (a form of diabetes caused by a lack of ADH, resulting in very large amounts of watery urine) and bed wetting.
  64. 64. Questions: 1. How do neurosecretory cells differ from normal nerve cells? 1. Explain what is meant by negative feedback? 2. Why is it important that ADH is broken down? 5/17/2015 64 Neurosecretory cells manufacture a hormone in their cell body; this is transferred down the axon. When it is released it goes straight into the blood rather than to another nerve cell Negative feedback occurs when a change in the internal conditions stimulates a reversal of that change – so the conditions are kept constant ADH must be broken down so that it is not continually acting on the walls of the collecting ducts
  65. 65. 1.2.8 – Kidney Failure 5/17/2015 65
  66. 66. Kidney Failure  Most common causes are:  Diabetes mellitus (both type I and type II sugar diabetes)  Hypertension  Infection  Once the kidneys fail completely the body is unable to remove excess water and certain waste products from the blood  This includes urea and excess salts.  It is also unable to regulate the levels of water and salts in the body  rapid death 5/17/2015 66
  67. 67. Treatment of Kidney Failure - PART I  Two main treatments for CKD:  Dialysis (2 subtypes):  most common treatment removing waste, excess fluid from blood by passing the blood over a dialysis membrane. The membrane is a partially permeable membrane that allows the exchange of substances between the blood and dialysis fluid.  This fluid contains the correct concentrations of salts, urea, water and other substances in blood plasma  Any substances in excess in the blood diffuse across the membrane into the dialysis fluid  Any substances that are too low in concentration diffuse into the blood from the dialysis fluid.  Dialysis must be combined with a carefully monitored diet. 5/17/2015 67
  68. 68. Treatment of Kidney Failure - PART II  Hemodialysis  Blood from a vein is passed into a machine that contains an artificial dialysis membrane. Heparin is added to avoid blood clotting and any bubbles are removed before the blood returns to the body  Hemodialysis is usually performed at a clinic 3 times a week for several hours at each sessions, but some patients learn to carry it out at home 5/17/2015 68
  69. 69. Treatment of Kidney Failure - PART III  Peritoneal Dialysis  The filter is the body’s own abdominal membrane (peritoneum).  First a surgeon implants a permanent tube in the abdomen.  Dialysis solution is poured through the tube and fills the space between the abdominal walls and organs  After several hours, the used solution is drained from the abdomen.  PD is usually performed in several consecutive sessions daily at home or work.  As the patient can walk around having dialysis, the method is sometimes called ambulatory PD 5/17/2015 69
  70. 70. Treatment of Kidney Failure - PART IV  Kidney Transplant  In a kidney transplant the old kidneys are left in place unless they are likely to cause infection or are cancerous. The donor kidney can be from a living relative who is willing to donate one of their healthy kidneys or from someone who has died  A kidney transplant is major surgery. While the patient is under anesthesia, the surgeon implants the new organ into the lower abdomen and attaches it to the blood supply and the bladder  Many patients feel much better immediately after the transplant, which is the best life-extending treatment for kidney failure.  However, the patient’s immune system will recognize the new organ as a foreign object and produce a reaction  Patients are given immunosuppressant drugs to help prevent rejection 5/17/2015 70
  71. 71. Advantages and Disadvantages of Kidney Transplant 5/17/2015 71 Advantages Disadvantages Freedom from time-consuming dialysis Need immunosuppressant's for the life of the kidney Diet is less limited Need major surgery under a general anesthetic Feeling better physically Risks of surgery include infection, bleeding and damage to surrounding organs A better quality of life i.e. able to travel Frequent checks for signs of organ rejection No longer seeing oneself as chronically ill Side effects: anti-rejection medicines cause fluid retention and high blood pressure; immunosuppressant's increase susceptibility to infections
  72. 72. Testing Urine Samples - PART I  Substances or molecules with a relative molecular mass of less than 69,000 can enter the nephron. This means that any metabolic product or other substance that is in the blood can be passed into the urine – as long as it is small enough.  If these substances are not reabsorbed further down the nephron they can be detected in urine  Pregnancy Testing:  Once implanted in the uterine lining, a human embryo starts secreting a pregnancy hormone called human chorionic gonadotrophins (hCG) (Mr. = 36,700)  It can be found in urine as early as 6 days after conception. The pregnancy tests on the market today are manufactured with monoclonal antibodies.  Antibody is specific, it will only bind to hCG, not to other hormones. 5/17/2015 72
  73. 73. Testing Urine Samples - PART II  When someone takes a home pregnancy test, she soaks a portion of the test strip in her urine.  Any hCG in the urine attaches to an antibody that is tagged with a blue bead  This hCG-antibody complex moves up the strip until it sticks to a band of immobilized antibodies  As a result all the antibodies carrying a blue bead and attached to hCG are held in one place forming a blue line  There is always one control blue line to use for comparison; a second blue line indicates pregnancy 5/17/2015 73
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  75. 75. Testing Urine Samples - PART III  Testing for anabolic steroids:  Anabolic Steroids – increase protein synthesis within cells  build-up of cell tissues especially in the muscles  Non-medical uses for anabolic steroids are controversial because they can give advantage in competitive sports and they have dangerous side effects (use in sports is now banned)  Half-life of about 16 hours and remain in the blood for many days.  Relatively small molecules and enter the nephron easily 5/17/2015 75
  76. 76. Testing Urine Samples - PART IV  Testing for anabolic steroids involves analyzing a urine sample in a laboratory using gas chromatography or mass spectrometry  In a gas chromatography the sample is vaporized in the presence of a gaseous solvent and passed down a long tube lined by the absorption agent  Each substances dissolves differently in the gas and stays there for a unique, specific time, the retention time.  Eventually the substances comes out of the gas and is absorbed onto the lining  detector  creates a chromatogram  Standard samples of drugs, as well as the urine samples are run so that the drugs can be identified and quantified in the chromatograms 5/17/2015 76
  77. 77. Questions: 1. What components of the diet must be carefully monitored in someone who undergoes dialysis 2. Explain why hemodialysis fluid has to be sterile and at 37oC 3. Create a table of advantages and disadvantages of dialysis as a treatment for kidney failure 4. Explain why standard samples of drugs must be run alongside a urine sample in gas chromatography 5/17/2015 77
  78. 78. Module Summary: 5/17/2015 78
  79. 79. Module Summary:  1.2.1 – Excretion  Key Definitions:  Excretion  removal of metabolic waste form the body  Metabolic waste  consists of waste substances that may be toxic or are produced in excess by the reactions inside cells  Deamination  removal of an amine group from an amino acid to produce ammonia 5/17/2015 79
  80. 80. Module Summary:  1.2.2 – The Liver  Key Definitions:  Hepatic Portal Vein  unusual blood vessel that has capillaries at both ends – it carries blood from the digestive system to the liver  Function of Kupffer cells  appears to be the breakdown and recycling of old red blood cells. Bilirubin is ne of the waste products from the breakdown of hemoglobin 5/17/2015 80
  81. 81. Module Summary 5/17/2015 81  1.2.3 – Functions of the Liver  Key Definitions:  Urea  excretory product formed from the breakdown of excess amino acids  Ornithine cycle  the process in which ammonia is converted to urea. It occurs partly in the cytosol and partly in the mitochondria, as ATP is used  Detoxification – conversion of toxic molecules to less toxic or non-toxic molecules
  82. 82. Module Summary:  1.2.4 – The Kidney  Key Definitions:  Nephron the functional unit of the kidney. Microscopic tubule that receives fluid from the blood capillaries in the cortex and converts this to urine, which drains into the ureter  Glomerulus  fine network of capillaries that increases the local blood pressure to squeeze fluid out of the blood. It is surrounded by a cup-or funnel-shaped capsule which collects the fluid and leads into the nephron  In selective reabsorption useful substances are reabsorbed form the nephron into the bloodstream while other excretory substances remain in the nephron  The PCT is the closest to the Glomerulus / The DCT is the furthest from the glomerulus 5/17/2015 82
  83. 83. Module Summary:  1.2.5 – Formation of Urine  All organs have afferent vessels – they bring blood into the organ. Similarly, efferent vessels carry blood away from the organ. In a glomerulus the efferent vessels is an arteriole – which is muscular and can constrict to raise the blood pressure in the glomerulus. In most organs a venule carries blood away  Ultrafiltration is filtration at a molecular level – as in the glomerulus where large molecules and cells are left in the blood and smaller molecules pass into the Bowman’s capsule  Podocytes are specialized cells that make up the lining of the Bowman’s capsule  TIP: the endothelium of the capillary and the epithelium of Bowman’s capsule contains gaps or pores. These two layers of cells do little to filter out larger molecules. IT is the basement membrane that is actually involved in ultrafiltration  Key Definitions:  Microvilli are microscopic folds of the cell surface membrane that increase the surface area of the cell  Co-transporter proteins are proteins in the cell surface membrane that allow the facilitated diffusion of simple ions to be accompanied by transport of a larger molecule such as glucose  Facilitated diffusion is diffusion that is enhanced by the action of proteins in the cell membrane  Sodium-Potassium pumps are special proteins in the cell surface membrane that actively transports sodium and potassium ions against their concentration gradient 5/17/2015 83
  84. 84. Module Summary:  1.5.6 – Water reabsorption  Key definitions:  A hairpin countercurrent multiplier is the arrangement of a tubule in a sharp hairpin so that one part of the tubules passes close to another part of the tubule with the fluid flowing in opposite directions. This allows exchange between the contents and can be used to create a very high concentration of solutes  Osmoregulation is the control and regulation of water potential of the blood and body fluids. In humans the kidney controls the water potential of the blood  The distal convoluted tubule is the coiled portion of the nephron between the loop of henle and the collecting duct. 5/17/2015 84
  85. 85. Module Summary:  1.5.7 – Osmoregulation  Key definitions:  Antidiuretic Hormone (ADH) is released from the pituitary gland and acts on the collecting ducts in the kidneys to increase their reabsorption of water  Osmoreceptor are receptor cells that monitor the water potential of the blood. IF the blood has a low water potential then water is moved out of the osmoreceptor cells by osmosis, causing them to shrink. This causes stimulation of the neurosecretory cells  Hypothalamus is part of the brain that contains neurosecretory cells and various receptors that monitor the blood  Neurosecretory cells are specialized cells that act like nerve cells but release a hormone into the blood. ADH is manufactured in the cell body and passes down the axon to be stored in the terminal bulb. If an action potential passes down the axon then ADH is released from the terminal bulb  Posterior pituitary gland is the hind part of the pituitary gland, which releases ADH. 5/17/2015 85
  86. 86. Module Summary:  1.5.8 – Kidney Failure  Key Definitions:  Human chorionic gonadotrophins (hCG) is a hormone released by human embryos; it’s presence in the mothers urine confirms pregnancy  Monoclonal antibodies are identical because they have been produced by cells that are clones of the original cell  Anabolic steroids are drugs that mimic the action of steroid hormones that increase muscle growth  Gas chromatography is a technique used to separate substances in a gaseous state. A Chromatogram is a chart produced when substances are separated by movement of a solvent along a permeable material such as paper or gel 5/17/2015 86
  87. 87. Thank you, feel free to ask for any help. By Piril Erel 5/17/2015 87