Then - left click mouse anywhere to proceed.

Then - left click mouse anywhere to proceed.
The Pathology of GLOMERULONEPHRITIS A Tutorial. by John Bradfield previously Professor of Histopathology University of Bristol England UK To run the tutorial If you are in Powerpoint use mouse pointer to select “Slide-Show” mode If you are in Outlook Express or Netscape - right click mouse and select “Full Screen” Then - left click mouse anywhere to proceed.

left click mouse anywhere to proceed
Date created October 2001 Institute of Work Department of Pathology & Microbiology University of Bristol UK Copyright Bristol BioMedical Image Archive University of Bristol UK left click mouse anywhere to proceed

How to find your way around 1.
Make sure you are in “Slide Show” mode. Instructions are in red italics - as at the bottom of this slide To escape from the Tutorial at any time Press “End” key on keyboard for instructions for exit “left click mouse to proceed” means: left click mouse anywhere on the slide. If asked to “click on a button” or a text box, you need to rather precise The next slide illustrates this. left click mouse to proceed

This slide is about what to do if instruction is “click on a button”. The important thing is to put the arrow over the button but DO NOT CLICK UNTIL THE ARROW CHANGES TO A HAND. Because this is Powerpoint and not a web site: If you click anywhere else, the tutorial will mistakenly go to the next slide in the sequence instead of where you want to go. This is so important that we need to practice the habit NOW: Put arrow > hand over the button and left click mouse. Please do this now. left click mouse to proceed

DO NOT CLICK UNTIL THE ARROW CHANGES TO A HAND
How to find your way around 3. Whoops. You have arrived here by mistake. This is because you clicked on the background and not on the button. DO NOT CLICK UNTIL THE ARROW CHANGES TO A HAND To go back and try again:- Put arrow > hand over the button and left click mouse. Please do this now.

Well Done. It might seem simple but this is a Powerpoint program and not the Web, so we have to be extra careful to obey the rules or it all goes wrong. Good Luck and Bon Voyage To enter the tutorial left click mouse anywhere

left click mouse to proceed
Glomerulonephritis If this is your first visit to this tutorial I strongly recommend that you press within this button If you have visited before, or are here for revision, you might like to go directly to the main part of the tutorial in which case you should press within this button left click mouse to proceed

You have arrived here by mistake. This is because you clicked on the background and not on the button. Please go back and try again. DO NOT CLICK UNTIL THE ARROW CHANGES TO A HAND Put arrow > hand over the button and left click mouse. Please do this now.

left click mouse to proceed
Glomerulonephritis Why did I write this tutorial?…………………………………………………... Because so many beginners find the subject both difficult and confusing. Why is this?……………………………………………….…. Usually, because they were taught badly first time round. If that includes you Don’t worry Help is at hand Left click to accept help left click mouse to proceed

After you have worked through this tutorial
GLOMERULONEPHRITIS Help is at hand After you have worked through this tutorial You will not only understand: the descriptive words used in the classification the pathology the causes and mechanisms But you will also be able to: read about glomerulonephritis with interest left click to proceed left click to find out left click to find out

Otherwise - left click mouse to proceed to tutorial.
Previous knowledge requirements You need to know a bit about the normal histology of the human glomerulus. If in doubt Press this button to try a short test Otherwise - left click mouse to proceed to tutorial.

left click anywhere to proceed.
Previous knowledge requirements Done the test and ready to go? left click anywhere to proceed.

How to use this tutorial
Is your first time? Choose Part 1 = Introduction to the Basic Vocabulary of Glomerulonephritis in general. (A very short section.) If you have visited before You may prefer to go straight to Part 2 = Main tutorial on Pathology of Glomerulonephritis To choose - place arrow>hand over button and left click..

BASIC VOCABULARY

left click to proceed GLOMERULONEPHRITIS Welcome to Part 1
Basic Vocabulary left click to proceed

Let’s start by spending some time on
How to use the words left click to proceed

Renal diseases in which the main abnormality lies in the glomerulus.
What is GLOMERULONEPHRITIS? Definition: Glomerulonephritis is the name given to: Renal diseases in which the main abnormality lies in the glomerulus. Write down your Definition before you proceed left click to proceed

left click to proceed Glomerulonephritis versus Glomerular diseases
In spite of the name, “Glomerulonephritis” is often applied to all glomerular diseases, not just those in which there is inflammation (- itis). However, when the main feature is deposition of materials in the glomerulus, then these diseases are not traditionally included as glomerulonephritis. Amyloid Diabetic glomerular disease Examples ? left click to proceed

left click to proceed Primary versus Secondary Glomerulonephritis
To be honest, which disease falls into which group is more governed by historical precedent than by biological sense. What to do? Only use the terms in the following way Secondary glomerulonephritis is where the glomerular damage is secondary to an ongoing systemic disease in the rest of the body Systemic Lupus Erythematosus Henoch Schonlein Purpura Diabetes Mellitus Examples ? left click to proceed

This section is now finished.
GLOMERULONEPHRITIS Part 1 Basic Vocabulary This section is now finished. Click on this button to return to Index Page to choose next Part

MAIN TUTORIAL

left click to proceed Part 2 = Main Tutorial Pathology of
Glomerulonephritis left click to proceed

The KEY to understanding THE CLASSIFICATION OF GLOMERULONEPHRITIS lies in appreciating that :
Each name may call on any of these components Clinical Features Pathology Causes and Mechanisms Eponymous left click to proceed

The KEY to understanding GLOMERULONEPHRITIS lies in appreciating that each type is defined using these components. Each name may call on any of these components Clinical Features Pathology Causes and Mechanisms Eponymous Because of this the next two slides will comprise a short detour into Clinical Things and Causes and Mechanisms left click to proceed

One slide on Important clinical things in glomerular disease
Age Acute versus Chronic Clinical patterns Proteinuria - Symptomless (revealed only on tests) - Nephrotic syndrome Haematuria - Symptomless (revealed only on tests) Patient may notice Renal failure - (acute or chronic) Acute Nephritic Syndrome Secondary to other disease left click to proceed

One slide on: Causes and mechanisms in glomerular disease
Primary glomerular disease (Glomerulonephritis) mostly immunological Glomerulus is innocent bystander = Immune complex disease Antibodies directed against glomerular components = Anti-basement membrane disease Don’t know = Immunological mechanisms involved but mechanisms not known Secondary glomerular disease (Glomerulonephritis and others) variety of mechanisms, some immunological left click to proceed

left click to proceed That ends our various detours and distractions
Now - at last - THE PATHOLOGY left click to proceed

Pathology of Glomerular Disease
There are several things to explore under this heading. You can choose from this list. 1. Patterns of damage 2. Light microscopy = histology 3. Electron microscopy 4. Immunological 5. Clinical indications for a renal biopsy 6. How a renal biopsy is handled in the laboratory 7. Exit tutorial Use the arrow/hand to click on your choice

PATTERNS OF CHANGE

Biopsy Pathology of Glomerular Disease Patterns of glomerular damage
Welcome to a mini-unit on Patterns of glomerular damage Left click to enter

Left click to proceed Pathological features of glomerulonephritis
Descriptive Terms Patterns of Damage - 1 One Glomerulus compared with another All glomeruli normal = No glomerulonephritis All glomeruli abnormal = diffuse glomerulonephritis Some glomeruli abnormal = focal glomerulonephritis (often secondary to systemic disease) Left click to proceed

Pathological features of glomerulonephritis Within a single glomerulus
Descriptive Terms Patterns of Damage - 2 Within a single glomerulus Normal = No glomerulonephritis Damage to part of glomerulus only = segmental glomerulonephritis Damage to all parts = global glomerulonephritis Left click to proceed

Pathological features of glomerulonephritis Within a single glomerulus
Descriptive Terms Patterns of Damage - 2 Within a single glomerulus There is one further pattern of damage within a single glomerulus that is important because it: 1. Signifies very bad news 2. Picks out a particular group of patients under the collective title of Left click to reveal

Pathological features of glomerulonephritis Descriptive Terms
Patterns of Damage - 2 Within a single glomerulus There is one further pattern of damage within a single glomerulus that is important because it: 1. Signifies very bad news 2. Picks out a particular group of patients under the collective title of Rapidly Progressive Glomerulonephritis Rapidly Progressive Glomerulonephritis is uncommon but very serious. Click here to learn more about it Otherwise left click in here

Press here for one slide about Goodpasture’s disease
Pathological features of glomerulonephritis Descriptive Terms Rapidly Progressive Glomerulonephritis Causes: 1. Bad end of the spectrum of many mechanism but especially - Anti-basement membrane disease inluding Goodpasture’s disease Press here for one slide about Goodpasture’s disease Otherwise left click in here

Left click to proceed Goodpasture’s Disease Clinical features:
1. Rapidly Progressive Renal Failure 2. Haematuria 3. Haemoptysis Pathological features: 1. (Cresentic Glomerulonephritis) 2. Deposition of linear IgG and IgM along basement membranes. Cause: Specific auto immune immunoglobulin attack on basement membrane’s of 1. Capillaries of the glomeruli in the kidneys and 2. Capillaries in the lung. Left click to proceed

That ends this mini-unit on Patterns of glomerular damage left click in here to return to “Pathology” page

LIGHT MICROSCOPY

Welcome to a mini-unit on Light microscopy This section describes the central basis for the pathological classification of Glomerulonephritis The way in is to start with the normal components of the Human Glomerulus Left click to enter Left click to proceed Left click to proceed

Normal Components of the Human Glomerulus
Stuff = non-cellular material Cells Normally present Normally present Glomerular Basement Membrane Endothelial cells Epithelial cells Mesangial cells Click anywhere to see a picture of a normal human glomerulus against which to compare the various diseases.

Left click anywhere to proceed
A picture of a normal human glomerulus against which to compare the various diseases. Tufts of capillaries Tufts of capillaries Bowman’s Space Thin basement membranes Afferent arteriole Nuclei of glomerular cells Left click anywhere to proceed

What can change in disease ? Too many cells = proliferation
Stuff (= non-cellular material) Normally present Normally present Endothelial cells Capillary Basement Membrane Epithelial cells Mesangium = stalk Thickening of the basement membrane Too many cells = proliferation Mesangial cells First let’s look at changes the previously normal components. Now click to see changes in normal non-cellular stuff. Left click to proceed. Click to see changes in resident normal cells

Stuff (= non-cellular material) Normally present Normally present Endothelial cells Capillary Basement Membrane Epithelial cells Mesangium = stalk Thickening of the basement membrane Too many cells = proliferation Mesangial cells Now we will look at abnormal components that can appear in disease. Click when you are ready.

Stuff (= non-cellular material) Normally present Normally present Endothelial cells Capillary Basement Membrane Epithelial cells Mesangium = stalk Thickening of the basement membranes Too many cells = proliferation Mesangial cells Only present when abnormal Amyloid Collagen scars (glomerulosclerosis) Myeloma protein Diabetic deposits Deposits Fibrin Inflammatory cells Too many cells = inflammation. But still called “proliferation” Now left click to see abnormal non-cellular stuff. Left click to see how this slide provides the key to the histological classification of glomerulonephritis. Left first click to see abnormal cells.

HISTOLOGICAL CLASSIFICATION OF GLOMERULAR DISEASE
Some important things It is more important to know how the nomenclature and classification works rather than knowing a great deal about every type of glomerulonephritis. The following pictures are for illustration and interest. You do not need to learn the skill of recognising the diagnosis from the histology. (that important skill is for the renal pathologists alone, and very difficult it often is). Many facts are introduced as questions. If this is your first visit, do not worry if you cannot answer the questions. If you could - you would not need the tutorial. Click anwhere to proceed

HISTOLOGICAL NAMES USED IN GLOMERULONEPHRITIS
What is this called? Proliferative glomerulonephritis Too many cells = Left click anwhere for next Left click anywhere to find out

What is this called? Proliferative glomerulonephritis Too many cells = Thickening of basement membranes = Membranous glomerulonephritis Left click anwhere for next Left click anywhere to find out

What is this called? Proliferative glomerulonephritis Too many cells = Thickening of basement membranes = Membranous glomerulonephritis Increase number of cells and thickening of basement membranes = Membrano-proliferative glomerulonephritis Have a guess. It’s easier than you think Left click anwhere for next Left click anywhere to find out

What is this called? Proliferative glomerulonephritis Too many cells = Thickening of basement membranes = Membranous glomerulonephritis Increase number of cells and thickening of basement membranes = Membrano-proliferative glomerulonephritis Nephrotic syndrome but thickening of basement membranes = Minimal Change glomerulonephritis Left click anwhere for next Left click anywhere to find out

What is this called? Proliferative glomerulonephritis Too many cells = Thickening of basement membranes = Membranous glomerulonephritis Increase number of cells and thickening of basement membranes = Membrano-proliferative glomerulonephritis Nephrotic syndrome but thickening of basement membranes = Minimal Change glomerulonephritis Collagen scars in some glomeruli = Focal Glomerulosclerosis Left click to proceed Left click anywhere to find out

Click in each box in turn to explore each type in turn
HISTOLOGICAL NAMES USED IN PRIMARY GLOMERULONEPHRITIS Click in each box in turn to explore each type in turn Proliferative glomerulonephritis Too many cells = Thickening of basement membranes = Membranous glomerulonephritis Increase number of cells and thickening of basement membranes = Membrano-proliferative glomerulonephritis Nephrotic syndrome but thickening of basement membranes = Minimal Change glomerulonephritis Collagen scars in some glomeruli = Focal Glomerulosclerosis left click in here to return to “Pathology” page. SECONDARY GLOMERULONEPHRITIS

Left click anywhere to learn more
HISTOLOGICAL CLASSIFICATION OF GLOMERULAR DISEASE Proliferative glomerulonephritis (too many cells) Endothelial cells Diffuse Proliferative g/n Inflammatory cells Mesangio-proliferative g/n typical of Berger’s disease Mesangial cells Epithelial cells (as “Cresents” in Bowman’s space) Rapidly Progressive g/n Left click anywhere to learn more

HISTOLOGICAL CLASSIFICATION OF GLOMERULAR DISEASE
Proliferative glomerulonephritis (too many cells) Endothelial cells Diffuse Proliferative g/n Inflammatory cells Left click anywhere to see a picture and to read about the clinical correlations of each Mesangio-proliferative g/n typical of Berger’s disease Mesangial cells Epithelial cells (as “Cresents” in Bowman’s space) Rapidly Progressive g/n

Left click anywhere for next
Diffuse proliferative g/n Too many cells (endothelial and mesangial) Swelling of cells but Normal basement membranes (not visible in this section) Clinical Correlations Presents as acute nephritic syndrome. When associated with an acute onset and a recent history of sore throat, this would be characteristic of post-streptoccocal immune complex glomerulonephritis. Can occur in other types of glomerulonephritis, both primary and secondary. When post-strep. - excellent prognosis especially in children. Left click anywhere for next Left click anywhere for clinical correlations Left click a nywhere for clinical correlations

Left click anywhere for next
Mesangio proliferative g/n Too many mesangial cells but Normal basement membranes Clinical Correlations Berger’s disease. (hint > Frenchman and so pronounced “Bearjey”.) Children and adults. Presents with recurrent painless haematuria =/- proteinuria and hypertension. Characteristically has IgA deposition in mesangium. Prognosis good. Left click anywhere for next Left click anywhere for clinical correlations Left click a nywhere for clinical correlations

nywhere for clinical correlations
Cresentic g/n (different stain) Bowman’s space expanded and filled with proliferating epithelial cells to form a cresent. Collapsed tufts of damaged glomeruli Clinical Correlations If 80% of the glomeruli show epithelial cell cresents, this is bad new. Because of this - The diseases that show this change are usually grouped together under the collective label of Rapidly Progressive Glomerulonephritis (including Goodpasture’s disease). They present with devastating haematuria and proteinuria and renal failure. And have a very poor prognosis. Left click a nywhere for clinical correlations Left click anywhere for clinical correlations That finished this section -left click anywhere to proceed

HISTOLOGICAL NAMES USED IN PRIMARY GLOMERULONEPHRITIS Click in each box in turn to explore each type in turn Proliferative glomerulonephritis Too many cells = Thickening of basement membranes = Membranous glomerulonephritis Increase number of cells and thickening of basement membranes = Membrano-proliferative glomerulonephritis Neohrotic syndrome but thickening of basement membranes = Minimal Change glomerulonephritis Collagen scars in some glomeruli = Focal Glomerulosclerosis left click in here to return to “Pathology” page. SECONDARY GLOMERULONEPHRITIS

nywhere for clinical correlations Left click anywhere to return
Membranous g/n No increase in numbers of cells but Increased thickness of basement membranes Clinical Correlations Presents with proteinuria. Commonest cause of nephrotic syndrome in adults in UK. Usually due to chronic immune complex disease. What are the likely antigens? In UK: most - don’t know but can be malignancy or drugs (penicillamine) In Japan: Most likely to be Hepatitis B In some parts of Africa: Most likely to be Malaria Left click a nywhere for clinical correlations Left click anywhere to return Left click anywhere for clinical correlations

If you want to explore these click in this box
Membrano-proliferative g/n Too many cells and Thickening of all the basement membranes Clinical Correlations Presentation Proteinuria or Nephrotic syndrome There are in fact three types of Membrano-proliferative g/n Otherwise If you want to explore these click in this box Left click anywhere for clinical correlations Left click anywhere else to return Left click a nywhere for clinical correlations Left click anywhere for more Left click a nywhere for clinical correlations

Three types of Membrano-proliferative g/n
Type 1 = Mesangiocapillary g/n Immune complex mediated Causes mostly unknown Some associated with infections, drugs, tumours, etc. Many associated with persistent C3 hypocomplementaemia Course = progressive deterioration Type 2 = Dense deposit disease Related to activation of the alternate complement pathway Dense deposits in basement membrane are not immune complexes Type 3 Rare Left click anywhere to return

nywhere for clinical correlations
Minimal change glomerulonephritis Light microscopy (histology) - essentially normal Electron microscopy - fusion of epithelial cell foot processes. (this is not specific for any one type of glomerulonephritis. It correlates with heavy proteinuria.) Clinical Correlations Cause unknown Presents with steroid responsive nephrotic syndrome. Commonest (90%) cause of nephrotic syndrome in children aged 1-5 in UK. These children are not usually biopsied. Rapid response to steroids. Prognosis Children - excellent. Adults - variable. Left click a nywhere for clinical correlations Left click anywhere for clinical correlations Left click anywhere to return

Focal glomerular sclerosis
Collagen scar tissue (stained red) in some glomeruli but not others and in one part of the glomerulus Clinical Correlations Presents with proteinuria. In UK. Cause of 10%-15% of nephrotic syndrome. Also associated with other diseases (secondary g/n) Prognosis Most patients eventually develop end stage renal failure. Left click a nywhere for clinical correlations Left click anywhere for clinical correlations Left click anywhere to return

Otherwise left click anywhere else to return
SECONDARY GLOMERULONEPHRITIS It is convenient to group these under three headings Autoimmune diseases with immune complexes as the mechanism of glomerular damage for more on each left click in here Metabolic diseases various mechanisms of glomerular damage Vascular diseases various mechanisms of glomerular damage Otherwise left click anywhere else to return

SECONDARY GLOMERULONEPHRITIS
Autoimmune diseases with immune complexes as the mechanism of glomerular damage Examples include Systemic lupus erythematosus variety of pathological patterns variety of clinical presentations Henoch-Schonlein purpura clinical patterns include nephrotic syndrome and rapidly progressive g/n left click anywhere for next

Metabolic diseases various mechanisms of glomerular damage Examples include Diabetes mellitus Whole range of patterns of damage to kidneys Whole range of patterns of damage in glomeruli. Cinically glomerular damage causes proteinuria nephrotic syndrome and renal failure. Renal amyloid In virtually all patients with systemic amyloid. Presents as proteinuria/nephrotic syndrome - often presenting feature. Inevitable renal failure left click anywhere for next

Diabetic nodular glomerulopathy
There is a variety of different ways in which diabetes mellitus affects the glomeruli This is the pattern that is usually illustrated in books - not because it is the commonest, but because it is the most specific for DM. and because it has a long eponymous name = Kimmelsteil-Wilson lesion. (you only need to remember it if you hare going for the gold medal. It’s more important to know thisfact: half of patients with childhood onset DM die in renal failure left click anywhere for next

Vascular diseases various mechanisms of glomerular damage Examples include Microscopic Polyarteritis nodosa Different disease than classical PAN. Prognosis untreated very poor but very good response to immuno-suppression. Haemolytic-uraemic syndrome Clinically - acute nephropathy, haemolysis and thrombocytopaenia. Prognosis depends on type: Childhood (better prognosis) Adult (poorer prognosis) Secondary (poorer prognosis) left click anywhere to return

Biopsy Pathology of Glomerular Disease
That ends the mini-unit on Light microscopy left click in here to return to “Pathology” page

ELECTRON MICROSCOPY

Welcome to a mini-unit on Electron microscopy Left click anywhere to enter

Click anywhere to proceed
ELECTRON MICROSCOPY Electron microscopy makes some important contributions to the understanding of the glomerulus in health to the understanding of mechanisms of disease in diagnosis Click anywhere to proceed

Click within a box to find out more about each in turn
ELECTRON MICROSCOPY Here I have selected for you the three topics that I think are most relevant. Of these the first section is by far the most important. Normal Appearances Changes with Proteinuria Immune Complex Disease Click within a box to find out more about each in turn Otherwise click in here to return to Pathology page

Left click anywhere to proceed Left click anywhere to proceed
NORMAL APPEARANCES Here is our standard histological light microscope picture of a normal human glomerulus Now let’s imagine that we could peer at great magnification into Bowman’s space and look at the external (downstream) side of one of these capillaries. Left click anywhere to proceed Left click anywhere to proceed

The next slide will be a scanning electron microscope picture of exactly this - at great magnification Tufts of capillaries Left click anywhere to proceed Left click anywhere to proceed

And here we are Bowman’s space We are now in Bowman’s space and here are all the capillaries. Left click anywhere to proceed

Now let’s wind up the magnification even further and look at the outside (downstream) side of one single calillary Bowman’s space Tufts of capillaries Left click anywhere to proceed Left click anywhere to proceed

And this is what we would see
The downstream side of all the capillaries are clothed in epithelial cells that have complicated interdigitating patterns that are traditionally called foot processes. Bowman’s space Left click anywhere to proceed

Left click anywhere to do this and see inside the capillary
Now let’s break open this capillary and look inside to see the upstream side of the filter which is the endothelial lining of the blood capillary. Bowman’s space Left click anywhere to do this and see inside the capillary Left click anywhere to proceed

Left click anywhere to proceed Left click anywhere to see labels
Here again is the downstream side of the filter with the interlacing foot processes of the epithelial cells. Bowman’s space And here is the endothelial cell lining of the blood capillary. Look at the 3.5nm pores in the endothelial cell lining. These hold back the blood cell but allow plasma access to the basement membrane filter underneath. Left click anywhere to proceed Left click anywhere to see labels

which is a very thin section in two dimensions only
Now let’s see what this would look like in a conventional electron transmission microscope which is a very thin section in two dimensions only Left click anywhere to proceed

which is a very thin section in two dimensions only
Now let’s see what this would look like in a conventional electron transmission microscope which is a very thin section in two dimensions only Here are the foot processes of the epithelial cells. Red cells And here is the endothelial cell lining of the blood capillary. We can hardly see the pores in the endothelial cell lining. Left click anywhere to proceed Left click anywhere to see labels Left click anywhere to proceed

Left click anywhere to return
In diagnostic pathology transmission electron microscopy is usually used, rather than scanning electron microscopy Red cells Left click anywhere to return

CHANGES WITH PROTEINURIA
Page one of one Proteinuria is associated with a change in the configuration of the interlacing pattern of the epithelial cell foot processes. On scanning electron microscopy the processes become simplified so that the outer surface of the basement membranes is covered in sheets rather than processes. This configuration can be seen on the more usual transmission electron microscopy., where it is historically known as “fusion of the foot processes” Comments: 1. Correlates with heavy proteinuria. 2. ? cause ? effect ? 3. Not specific to any particular type of glomerulonephritis. Left click anywhere to proceed

IMMUNE COMPLEX DISEASE
(Page one of three) Although immune complexes can be identified by immunofluoresence, it is sometimes helpful to know exactly where these deposits are in relation to the basement membranes. Click anywhere to see examples

Immune complex disease
(Page two of three) Sub-epithelial deposits in post-streptococcal g/n Click anywhere to see another example

Immune complex disease
(Page three of three) Deposits within thickened basement membranes in membranous g/n Click anywhere to return

That ends the mini-unit on Electron microscopy left click in here to return to “Pathology” page

IMMUNOLOGY

Pathology of Glomerular Disease Immunological investigation of a
Welcome to a mini-unit on Immunological investigation of a renal biopsy. Left click anywhere to enter

IMMUNOLOGY Antibodies are prepared, specific for abnormal things that might be present in the diseased glomerulus. A fluorescent molecule is attached to the back end of the antibody molecule so that the molecule will be visible down the light microscope under ultra-violet light. Thin sections are cut from the frozen fresh material. These are then “stained” using specific antibodies prepared in the laboratory. The “stained” sections are viewed under ultra-violet light. Positive “staining” appears as green fluorescence on a black background Left click anywhere to proceed

IMMUNOLOGY Fluorescent molecule Target material Antibody molecule Antigen-specific terminal Tissue section Glass slide Left click anywhere to proceed

Left click anywhere to see three examples
IMMUNOLOGY Usually three variables are scored. 1. Identity of abnormal materials in glomerulus. Usually patient’s own immune reactants eg IgG IgM IgA C3 2. Where is it? eg In capillary loops In mesangium 3. What is it like? eg lumpy-bumpy granular linear Left click anywhere to see three examples

Left click anywhere for next example
Which immune reactants? IgG +/- IgM Complement C3 Where? in walls of glomerular capillaries Pattern ? Lumpy-bumpy granular Interpretation ? Immune complex deposition Left click anywhere for next example

Left click anywhere last example
Which immune reactants? IgG +/- IgM Complement C3 Where? in walls of glomerular capillaries Pattern? Linear Interpretation ? Anti-basement membrane disease (Goodpasture’s) Left click anywhere last example

Left click anywhere to return
Which immune reactants? IgA Complement C3 Where? In mesangial stalks Pattern ? Granular Interpretation ? Berger’s IgA disease Left click anywhere to return

There are several things to explore under this heading. You can choose from this list. 1. Patterns of damage 2. Light microscopy = histology 3. Electron microscopy 4. Immunological 5. Clinical indications for a renal biopsy 6. How a renal biopsy is handled in the laboratory 7. Exit tutorial Use the arrow/hand to click on your choice

That ends the mini-unit on Immunological investigation of a renal biopsy left click in here to return to “Pathology” page

CLINICAL INDICATIONS FOR A RENAL BIOPSY

Welcome to a mini-unit on Clinical indications for a renal biopsy (three slides only) Left click anywhere to enter

General principles Making a diagnosis Planning treatment Deciding when not to treat Assessing prognosis Left click anywhere to proceed

Proteinuria with impairment of renal function Symptomless isolated proteinuria if more than 2g/day Nephrotic syndrome in adults In children it is most likely to be due to steroid sensitive minimal change g/n so trial of steroids is less risky than biopsy. Persistent haematuria with proteinuria especially if there is renal impairment. Acute renal failure if likely to be renal on origin, as opposed to pre-renal (hypovolaemic shock) or post-renal (obstructive) in origin. Chronic renal failure with normal sized kidneys Renal transplant dysfunction Systemic disorders with features that include haematuria, proteinuria and renal failure. Left click anywhere to enter

SOMECONTRA-INDICATIONS FOR A RENAL BIOPSY
Asymmetric kidneys Tiny shrunken kidneys Obstructive renal disease Coagulation defects Acute infections Left click anywhere to proceed

That ends the mini-unit on Clinical indications for a renal biopsy left click in here to return to “Pathology” page

BIOPSY

Welcome to a mini-unit on How a renal biopsy is handled in the laboratory One slide only Left click anywhere to enter

HOW A RENAL BIOPSY IS HANDLED IN THE LABORATORY
Core of fresh tissue Dissected into three parts ensuring some glomeruli in each For histology (light microscopy) For electron microscopy For immuno-fluorescence Left click anywhere to proceed

That ends the one page mini-unit on How a renal biopsy is handled in the laboratory They don’t come any more “mini” than that. left click in here to return to “Pathology” page

left click mouse to proceed.
Try this short test to find out whether you need to revise some basic things about the human glomerulus. left click mouse to proceed.

Revision Test: The structures of the nephron.
1. 2. 5. 3. 8. 7. 4. 6. Glomerulus Tubules 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. Glomerulus Tubules Don’t cheat. There’s no point. You are only cheating yourself. Left click to proceed

1. 2. 5. 3. 8. 7. 4. 6. Glomerulus Tubules Have you written down all 8? Don’t proceed until you have. The next slide gives the answers. Then left click to see all the answers.

1. Afferent arteriole 7. Distal convoluted tubule 2. Glomerular capillaries 3. Efferent arteriole 4. Capsule of glomerular sac 8. Collecting Duct 5. Proximal convoluted tubule 6. Loop of Henle left click to continue the short test

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

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

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

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

Previous knowledge requirements
How did you get on? If you struggled with the quiz - I suggest that you Work through a tutorial on Bristol Biomed entitled “Understanding the Glomerulus”. It will take you about 15 minutes, and has some excellent animations. When you get back you will then be equipped to conquer the subject of GLOMERULONEPHRITIS. To exit and return to Bristol Biomed for a background tutorial on the Glomerulus left click on this button To return to the main tutorial on Pathology of Glomerulonephritis left click on this button

Left click anywhere to find the exit
I hope that this tutorial has been useful. If you liked it, or didn’t, or have any suggestions: Then please let me know on: Left click anywhere to find the exit

How to EXIT THE TUTORIAL There is no need to “save” this program
To return to first page of this tutorial - left click within this button To return to Bristol BioMed - left click within this button To shut down if you are in Outlook Express or Netscape - right click the mouse and select “End Show” then close the browser in the usual way. To shut down if you are in Powerpoint - right click the mouse and select “End Show” then close Powerpoint in the usual way.

Then - left click mouse anywhere to proceed.

Similar presentations

Presentation on theme: "Then - left click mouse anywhere to proceed."— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Then - left click mouse anywhere to proceed.

Similar presentations

Presentation on theme: "Then - left click mouse anywhere to proceed."— Presentation transcript:

Similar presentations

About project

Feedback