1. UNDERSTANDING THE GLOMERULUS A TUTORIAL To run the tutorial select Slide-Show mode of Powerpoint (Version 4 or higher) by John Bradfield previously Professor of Histopathology University of Bristol England UK When you have done this - left click mouse to proceed

2. How to find your way around Make sure you are in Slide Show mode To escape from the tutorial at any time - right click the mouse and select End Show left click mouse to proceed Instructions are in RED ITALICS Left click mouse to proceed

3. Date created April 2001 Copyright Bristol Biomedical Image Archive University of Bristol UK Institute of Work Department of Pathology & Microbiology University of Bristol UK left click mouse to proceed

4. After you have worked through it, you will understand: This tutorial is about the normal glomerulus left click to proceed the functional histology of the human glomerulus the things that can go wrong with the glomerular filter How this acts as a necessary introduction to the subject of Glomerulonephritis

5. This tutorial can be used at two levels: Is this for you? It is also useful for clinical students as an introduction to the family of diseases of the glomerulus known as glomerulonephritis Previous knowledge requirements = By first year health workers including medical students and nurses as an introduction to the glomerulus of the kidney left click mouse to proceed basic biology only

6. Before the main part of the tutorial there is a short preview of The main components of the human nephron If you wish to do this, press this button The main tutorial is about, The structure and function of the human glomerulus, If you wish to do this, press this button After the main part of the tutorial there is a short review of What happens in glomerular disease If you wish to see this, press this button use mouse to press one button to select otherwise right click to exit the show

7. On the previous slide you used the mouse left click instead of using the mouse to point and click on one of the option buttons Please now left click to return to previous slide

8. Before the main part of the tutorial there is a short preview of The main components of the human nephron If you wish to do this, press this button The main tutorial is about, The structure and function of the human glomerulus, If you wish to do this, press this button After the main part of the tutorial there is a short review of What happens in glomerular disease If you wish to see this, press this button use mouse to press one button to select otherwise right click to exit the show

9. On the previous slide you used the mouse left click instead of using the mouse to point and click on one of the option buttons Please now left click to return to previous slide

10. Before the main part of the tutorial there is a short preview of The main components of the human nephron If you wish to do this, press this button The main tutorial is about, The structure and function of the human glomerulus, If you wish to do this, press this button After the main part of the tutorial there is a short review of What happens in glomerular disease If you wish to see this, press this button use mouse to press one button to select otherwise right click to exit the show

11. So - we need to start with the nephron left click mouse to proceed A short preview of The main components of the human nephron The overall function of the kidneys depends on functional units called nephrons There are supposed to be 1 million nephron in each kidney (I often wonder who counted)

12. The structures of the nephron Can you name the components of the nephron ? left click mouse to proceed

13. The structures of the nephron How to play the game: 1. Click to make an arrow point to each component in turn 2. Decide on the name 3. Then click to see the answer left click mouse to start

14. The structures of the nephron What is this? to see - left click mouse

15. The structures of the nephron This is the afferent arteriole that brings the blood under arterial pressure to drive the glomerular filter for next - left click mouse

16. The structures of the nephron What is this? to see - left click mouse

17. The structures of the nephron This is the capillary Actually a whole tuft of capillaries The basement of the capillaries act as the filter itself for next - left click mouse

18. The structures of the nephron What is this? to see - left click mouse

19. The structures of the nephron This is the efferent arteriole that drains the blood Arteriolar muscle tone helps control the capillary pressure for next - left click mouse

20. The structures of the nephron What is this? to see - left click mouse

21. The structures of the nephron This is the capsule of the glomerular sac It contains filtrate in a space called Bowmans space for next - left click mouse

22. The structures of the nephron What is this? to see - left click mouse

23. The structures of the nephron This is the proximal convoluted tubule for next - left click mouse

24. The structures of the nephron What is this? to see - left click mouse

25. The structures of the nephron This is loop of Henle for next - left click mouse

26. The structures of the nephron What is this? to see - left click mouse

27. The structures of the nephron This is the distal convoluted tubule for next - left click mouse

28. The structures of the nephron What is this? to see - left click mouse

29. The structures of the nephron This is the collecting duct for last- left click mouse

30. 1. Afferent arteriole 3. Efferent arteriole 4. Capsule of glomerular sac 2. Glomerular capillaries 5. Proximal convoluted tubule 6. Loop of Henle 7. Distal convoluted tubule 8. Collecting Duct Well done You now know the eight essential structures of the nephron left click to proceed

31. Click this button to re-do the preview Click this button to start the main tutorial Click this button to go to the clinical relevance use mouse to press one button to select otherwise right click to exit the show That completes our preview of the most important structures of the human nephron

32. left click the mouse to start This main tutorial is about The structure and function of the human glomerulus First we will look at the non-cellular structures and then we will look at the cells

33. The structure and function of the human glomerulus The story starts with the arrival of the blood in the arteriole To start - left click the mouse

34. Lets look at how the glomerulus develops Here is a histological section showing an arteriole running next to the beginning of the tubular system Afferent arteriole left click to continue Efferent arteriole left click to animate each stage

35. Now watch as a tuft of capillaries sprouts out from the arteriole and invaginates the top of the tubule: to start the show - left click the mouse How the glomerulus develops

36. Wow! left click to proceed

37. Wow! Now lets see what all those cartoon capillaries would really look like down the microscope left click when you are ready

38. When you have looked - left click to remove our cartoon capillaries

39. And here you have it The histological structure of the capillary tuft left click for some more drama

40. More drama Now we can watch the blood flow through the real capillary spaces left click to activate left click to proceed

41. The glomerulus acts as a filter And within the glomerulus, the actual filter membrane is the basement membrane of the blood capillaries left click to import the basement membranes into the diagram This is the most important structure in the glomerulus left click to proceed

42. Make a list then - to see answer - left click The blood pressure within the capillaries forces water and electrolytes and small molecular substances through the basement membrane filter What is held back by the basement membrane? 1. Cells (red cells, white cells and platelets) 2. Large plasma proteins (albumin and larger) click to proceed larger not lager!!!

43. Click for next Filtrate (water and electrolytes and small molecular substances) appears on the downstream side of the basement membrane The filtrate collects in Bowmans space

44. Here is Bowmans space Bowmans space accepts the filtrate Click to watch this happen. Click for next left click to see blood flow through the capillaries and the filtrate appear in Bowmans space left click again to see the filtrate flow onwards through the tubules left click to proceed

45. Click to watch this sequence again Click for next

46. The last structural component of the glomerulus is the loose supporting connective tissue that is given the name of the mesangium When you are ready to insert the mesangial matrix into the diagram - left click to show left click to move on

47. This is the normal human glomerulus as seen down the light microscope We have looked at all of the non-cellular structures Now it is time to look at the cells left click to proceed

48. This is the normal human glomerulus as seen down the light microscope There are three types of cell that live in the normal glomerulus left click to look at the three cell types

49. left click to zoom. These three cell types are designated by where they lie in relation to the basement membrane At this magnification we can only just make out the cell nuclei To see better we need to zoom in Lets zoom in on the area shown

50. first left click to define area for zoom Three types of cell live in the normal glomerulus This is all hopelessly blurred To see things properly, we need to zoom in even further - using an electron microscope

51. left click again when ready to zoom Three types of cell live in the normal glomerulus

52. left click for next Thats better - now we can see individual red blood cells passing through the glomerular capillaries Three types of cell under the electron microscope left click to proceed As usual, the basement membranes are shown in black At last we are ready to define our resident glomerular cells

53. left click for next Here is the first of the three types of cell found in the normal human glomerulus Some cells lie within the basement membranes and line the capillaries These are nuclei of endothelial cells

54. left click for next Some lie the outside the basement membrane This is the nucleus of an epithelial cell Here is the second of the three types of cell found in the normal human glomerulus

55. left click for next Lastly, some lie in the mesangial matrix of the stalk - (= mesangium) These are nuclei of mesangial cells Here is the third of the three types of cell found in the normal human glomerulus

56. left click for next Summary The five components of the normal human glomerulus Cells Endothelial cells - lining the capillaries Epithelial cells - downstream of the basement membranes Mesangial cells - controlling cells in the supporting stalk Non-cellular components Capillary Basement Membranes - this is the actual filter Mesangium - the supporting stalk

57. Click this button to re-do the preview Click this button to re-do start the main tutorial Click this button to go to the clinical relevance use mouse to press one button to select otherwise right click to exit the show That completes our main tutorial on The structure and function of the human glomerulus

58. On the previous slide you used the mouse left click instead of using the mouse to point and click on one of the option buttons Please now left click to return to previous slide

59. Click this button to re-do the preview Click this button to re-do start the main tutorial Click this button to go to the clinical relevance use mouse to press one button to select otherwise right click to exit the show That completes our main tutorial on The structure and function of the human glomerulus

60. On the previous slide you used the mouse left click instead of using the mouse to point and click on one of the option buttons Please now left click to return to previous slide

61. Click this button to re-do the preview Click this button to re-do start the main tutorial Click this button to go to the clinical relevance use mouse to press one button to select otherwise right click to exit the show That completes our main tutorial on The structure and function of the human glomerulus

62. The secret to our understanding lies in what we have already learned about the glomerulus 1. The filter needs an adequate blood supply under adequate pressure 2. The filter must not leak left click for next Clinical applications This last part of the tutorial on the human glomerulus is a short review of what can go wrong during human glomerular disease

63. 1. The filter needs an adequate blood supply under adequate pressure If the filter stops filtering: This is renal failure (acute or chronic) 2. The filter must not leak If it leaks red cells: This is haematuria (blood in the urine) If it leaks protein: This is proteinuria (protein in the urine) left click for summary slide of clinical part of our tutorial Clinical manifestations of glomerular disease

64. 1. Haematuria 2. Proteinuria 3. Renal failure 4. Any combination of these left click for next Summary Clinical manifestations of glomerular disease

65. Click this button to re-do the preview Click this button to re-do the main tutorial Click this button to re-do the clinical relevance Click the yellow button for short revision test This ends this three-part tutorial on THE HUMAN GLOMERULUS otherwise right click to exit the show Well done for reaching the end

66. On the previous slide you used the mouse left click instead of using the mouse to point and click on one of the option buttons Please now left click to return to previous slide

67. Click this button to re-do the preview Click this button to re-do the main tutorial Click this button to re-do the clinical relevance Click the yellow button for short revision test This ends this three-part tutorial on THE HUMAN GLOMERULUS otherwise right click to exit the show Well done for reaching the end

68. On the previous slide you used the mouse left click instead of using the mouse to point and click on one of the option buttons Please now left click to return to previous slide

69. Click this button to re-do the preview Click this button to re-do the main tutorial Click this button to re-do the clinical relevance Click the yellow button for short revision test This ends this three-part tutorial on THE HUMAN GLOMERULUS otherwise right click to exit the show Well done for reaching the end

70. Revision Test: The structures of the nephron Can you name these eight components of the nephron? Write down the 8 answers before you proceed Then left click to see all the answers 1. 2. 5. 3. 8. 7. 4. 6.

71. Revision Test: The structures of the nephron 1. 2. 5. 3. 8. 7. 4. 6. Dont cheat Theres no point You are only cheating yourself left click to see all the answers

72. 1. Afferent arteriole 3. Efferent arteriole 4. Capsule of glomerular sac 2. Glomerular capillaries 5. Proximal convoluted tubule 6. Loop of Henle 7. Distal convoluted tubule 8. Collecting Duct Revision Test: The structures of the nephron left click to continue revision quiz

73. left click for all of the answers Revision Test of main part of tutorial Can you list? The five important components of the normal human glomerulus Cells 1. ??? lining the capillaries 2. ??? downstream of the basement membranes 3. ??? controlling cells in the supporting stalk Non-cellular components 4. ??? this is the actual filter 5. ??? the supporting stalk

74. left click for next Revision Test of main part of tutorial The five important components of the normal human glomerulus Cells 1. Endothelial cells - lining the capillaries 2. Epithelial cells - downstream of the basement membranes 3. Mesangial cells - in the mesangial stalk Non-cellular components 4. Capillary Basement Membranes - this is the actual filter 5. Mesangium - the supporting stalk

75. 1. 2. 3. 4. left click for all of the answers Revision Test Can you list the clinical manifestations of glomerular disease = Glomerulonephritis?

76. 1. Haematuria 2. Proteinuria 3. Renal failure 4. Any combination of these left click for next Revision Test The clinical manifestations of glomerular disease = Glomerulonephritis?

77. Click this button to re-do the preview Click this button to re-do the main tutorial Click this button to re-do the clinical relevance Click the yellow button for short revision test This ends the three Revision Tests on THE HUMAN GLOMERULUS otherwise please left click before you leave Well done for doing the revision tests

78. On the previous slide you used the mouse left click instead of using the mouse to point and click on one of the option buttons Please now left click to return to previous slide

79. Click this button to re-do the preview Click this button to re-do the main tutorial Click this button to re-do the clinical relevance Click the yellow button for short revision test This ends the three Revision Tests on THE HUMAN GLOMERULUS otherwise please left click before you leave Well done for doing the revision tests

80. On the previous slide you used the mouse left click instead of using the mouse to point and click on one of the option buttons Please now left click to return to previous slide

81. Click this button to re-do the preview Click this button to re-do the main tutorial Click this button to re-do the clinical relevance Click the yellow button for short revision test This ends the three Revision Tests on THE HUMAN GLOMERULUS otherwise please left click before you leave Well done for doing the revision tests

82. I suggest that you visit the appropriate site within The virtual Hospital on www.vh.org/Providers/Textbooks/GN/GNHP.html The virtual Hospital on www.vh.org/ is an excellent site for all sorts of things If you want to know more about the pathology of Glomerulonephritis: left click for the last page

83. If you would like to: comment praise make suggestions for improvement suggest any other topics for similar tutorials then please email - brisbio-info@bristol.ac.uk or - John.Bradfield@bristol.ac.uk Goodbye and thank you for doing this tutorial I hope that it was informative and enjoyable right click to end show