UNDERSTANDING THE GLOMERULUS A TUTORIAL To run the tutorial select Slide-Show mode of Powerpoint (Version 4 or higher) by John Bradfield previously Professor

UNDERSTANDING THE GLOMERULUS

A TUTORIAL

To run the tutorial select

“Slide-Show” mode of Powerpoint (Version 4 or higher)

byJohn Bradfield

previously Professor of HistopathologyUniversity of Bristol

EnglandUK

When you have done this - left click mouse to proceed

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

Date created

April 2001

Copyright

Bristol Biomedical

Image ArchiveUniversity of Bristol

UK

Institute of Work

Department ofPathology & Microbiology

University of Bristol

UK


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

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


basic biology only

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,


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

On the previous slide

you used the mouse left click

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So - we need to start with

the nephron


A short preview of


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)

The structures of the nephron

Can you name the components 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


What is this?

to see -

left click mouse


This is the

afferent arteriole

that brings the blood under arterial pressure to drive the glomerular filter

for next -

left click mouse


What is this?

to see -

left click mouse


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


What is this?

to see -

left click mouse


This is the

efferent arteriolethat drains the blood

Arteriolar muscle tone helps control the capillary pressure

for next -

left click mouse


What is this?

to see -

left click mouse


This is the

capsule of the glomerular sac

It contains filtrate in a space called Bowman’s space

for next -

left click mouse


What is this?

to see -

left click mouse


This is

the proximal convoluted tubule

for next -

left click mouse


What is this?

to see -

left click mouse


This is

loop of Henle

for next -

left click mouse


What is this?

to see -

left click mouse


This is

the distal convoluted tubule

for next -

left click mouse


What is this?

to see -

left click mouse


This is

the collecting duct

for last-

left click mouse

1. Afferent arteriole

3. Efferent arteriole

4. Capsule of glomerular sac

2. Glomerular capillaries

5. Proximal convoluted tubule

6. Loop of Henle

7. Distalconvolutedtubule

8. CollectingDuct

Well done

You now know the eight essential structures of the nephron


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



That completes our preview of the most important structures of the human nephron

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

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

Let’s 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

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

Wow!


Wow!

Now let’s see what all those cartoon capillaries would really look like down the microscope

left click when you are ready

When you have looked -

left click to remove our cartoon capillaries

And here you have it

The histological structure of the capillary tuft

left click for some more drama

More drama

Now we can watch the blood flow through the real capillary spaces

left click to activate


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


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!!!

Click for next

Filtrate

(water and electrolytes and small molecular substances) appears on the downstream side

of the basement membrane

The filtrate collects in Bowman’s space

Here is Bowman’s space

Bowman’s 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 Bowman’s space

left click again to see the filtrate flow onwards through the tubules


Click to watch this sequence again

Click for next

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

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


This is the normal human glomerulus as seen down the light microscope

There arethree types of cell

that live in the normal glomerulus

left click to look at the three cell types

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

Let’s zoom in on the area shown

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

left click again when ready to zoom

Three types of cell

live in the normal glomerulus

left click for next

That’s better - now we can see individual red blood cells passing through the glomerular capillaries

Three types of cell

under the electron microscope



As usual, the basement membranes are shown in black

At last we are ready to define our resident glomerular cells

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 ofendothelial cells

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


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


left click for next

Summary

The five components of the normal human glomerulus

Cells

Endothelial cells -

lining the capillaries

Epithelial cells -downstream of thebasement membranes

Mesangial cells -

controlling cellsin the supporting stalk

Non-cellular components

CapillaryBasement Membranes -this is the actual filter

Mesangium -

the supporting stalk


Click this button to re-do start the main tutorial




That completes our main tutorial on




instead of

using the mouse to

point and click












instead of

using the mouse to

point and click










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

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

1. Haematuria

2. Proteinuria

3. Renal failure

4. Any combination of these

left click for next

Summary

Clinical manifestations of glomerular disease


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


Well done for reaching the end



instead of

using the mouse to

point and click













instead of

using the mouse to

point and click











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.


1.

2.

5.

3.

8.

7.

4.

6.

Don’t cheat

There’s no point

You are only cheating yourself

left click to see all the answers

1. Afferent arteriole

3. Efferent arteriole

4. Capsule of glomerular sac

2. Glomerular capillaries

5. Proximal convoluted tubule

6. Loop of Henle

7. Distalconvolutedtubule

8. CollectingDuct


left click to continue revision quiz

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 capillaries2. ???downstream of thebasement membranes

3. ???

controlling cellsin the supporting stalk


4. ???

this is the actual filter

5. ???


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


4. Capillary Basement Membranes - this is the actual filter

5. Mesangium -


1.

2.

3.

4.

left click for all of the answers

Revision Test

Can you list the clinical manifestations of

glomerular disease = Glomerulonephritis?

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?





This ends the three Revision Tests on


otherwise please left click before you leave

Well done for doing the revision tests



instead of

using the mouse to

point and click













instead of

using the mouse to

point and click











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

If you would like to:

• comment

• praise

• make suggestions for improvement

• suggest any other topics for similar tutorials

then please email - [email protected]

or - [email protected]

Goodbye and thank you for doing this tutorial

I hope that it was informative and enjoyable

right click to end show

Documents

UNDERSTANDING THE GLOMERULUS A TUTORIAL To run the tutorial select Slide-Show mode of Powerpoint (Version 4 or higher) by John Bradfield previously Professor