Pathology of Glomerular disease

Question 1

What molecules are not able to pass through the glomerular membrane?

Answer 1

All proteins equal to or larger than albumin (including immunoglobulins) will not be filtered - they will stay in plasma

Question 2

describe the arrangement of podocytes around glomerular capillaries?

Answer 2

podocytes have interdigitating ‘fingers’ or foot processes - that surround the capillaries

Question 3

What are the 3 layers of the glomerular membrane (ie the filter barrier)

Answer 3

endothelial cell cytoplasm, basal lamina and podocyte

Question 4

What are mesangial cells?

Answer 4

‘tree-like’ group of cells which support capillaries in the glomerulus

Question 5

In the image below - identify a mesangial cell

Answer 5

Question 6

What is Glomerulonephritis?

Answer 6

Disease of the glomerulus

Can be inflammatory or non-inflammatory

Question 7

Describe the aetiology of glomerulonephritis

Answer 7

Some are due to Immunoglobulin deposition

Some are not - for example diabetic glomerular disease

Question 8

What are the 4 common presentations of glomerulonephritis?

Answer 8

Haematuria _{- blood in urine}

Heavy proteinuria _{- nephrotic syndrome}

Slowly increasing proteinuria

Acute renal failure

Question 9

What are the main causes of Haematuria?

Is glomerulonephritis an important cause?

Answer 9

Main causes are:

• Urinary tract infection
• Urinary tract stone
• Urinary tract tumour

Glomerulonephritis is a relatively rare cause of Haematuria

Question 10

What investigation is best for identifying Immunoglobulin deposits in glomerulonephritis?

Answer 10

Renal biopsy i think

Question 11

Whats wrong with this bois glomerulus

Answer 11

This patient has glomerulonephritis (IgA nephropathy)

Too many mesangial cells

Accumulation of mesangial matrix which stains nice flat pink

These changes occur with the deposition of immunoglobulins in the mesangial area

Question 12

How does immunoglobulin deposition affect the mesangium of the glomerulus?

Answer 12

IgA – ‘irritates’ mesangial cells and causes them to proliferate and produce more matrix

Question 13

What is the prognosis for IgA nephropathy ?

Answer 13

Usually self limiting

Can rarely cause chronic renal failure (via continued deposition of matrix)

Question 14

What causes ‘membrane glomerulonephritis’?

Answer 14

Thickening of the glomerular basement membrane

Question 15

Is there immunoglobulin deposition in membranous glomerulonephritis?

Answer 15

Yes - there are deposits of IgG

This takes place between the basal membrane and the podocytes

Question 16

Describe how the IgG deposits seen in membranous glomerulonephritis cause albumin to leak into the blood

Answer 16

IgG is too big to be filtered into urine, but IgG activates complement (C3), which punches holes in filter

This allows albumin to leak through and be filtered into the urine - hence membranous glomerulonephritis leads to nephrotic syndrome

Question 17

What is the prognosis of membranous glomerulonephritis?

Answer 17

25% of patients progress to chronic renal failure within 10 years

Question 18

What is the underlying cause of membranous glomerulonephritis?

(ie what causes the IgG production and accumulation in membranous glomerulonephrits)

Answer 18

Unknown but can be related to:

autoimmunity against phospholipase A2 receptor

malignancy

amongst other things

Question 19

What are the main features of diabetic damage to the glomerulus?

Answer 19

Glycated molecules lead to matrix deposition in:

• basal lamina - underneath endothelial cells
• mesangial matrix

The effects of this are:

• Thickened but leaky basement membranes
• Compression of capillaries

Question 20

What histological feature of diabetic nephropathy is different from the previous types of glomerulonephritis discussed?

Answer 20

There are NO IMMUNE COMPLEXES DEPOSITED

Question 21

Summarise the histological features of glomeruli in diabetic nephropathy

Answer 21

Increased mesangial matrix +/- Kimmelsteil-Wilson lesions

Compressed capillaries w/ thickened walls (due to^)

Adhesions to Bowmans capsule

Thickened, narrowed arterioles reduce blood flow to glomerulus

Question 22

What are Kimmelsteil-Wilson lesions?

Answer 22

Feature of diabetic nephropathy - in which there is gross excess of mesangial matrix forming nodules

Question 23

What is the prognosis for diabetic nephropathy?

Answer 23

Poor if already established and evener poorerer if poor diabetic control

Question 24

What is the significance of Creatinine in all this stuff?

Answer 24

Rapidly rising creatinine = acute renal failure

Question 25

The image below came from a patient with acute renal failure

What type of glomerulonephritis is shown?

Answer 25

Crescentic glomerulonephritis

pattern/cause of acute kidney injury/failure seen with:

• Granulomatosis with Polyangiitis (aka Wegeners)
• Microscopic polyarteritis
• Goodpasture syndrome (Antiglomerular basement membrane disease)
• Other types of glomerulonephritis

Question 26

What features of Crescentic glomerulonephritis allow you to distinguish it?

Answer 26

Presentation - acute renal failure

Investigations - raised creatinine

Histology:

• Crescent shape - due to macrophages in Bowman’s space
• Crushed glomerular tuft

Question 27

What is Granulomatosis with polyangiitis?

Answer 27

A form of vasculitis - which affects vessels in kidneys, nose and lungs

Question 28

What further tests are available for Granulomatosis with polyangiitis?

Answer 28

Serum test shows presence of anti-neutrophil cytoplasmic antibodies (ANCA)

These are not deposited in the kidney - but are found attacking neutrophils

this is because they attack 2 enzymes in the primary granules of neutrophils

Question 29

Anti-neutrophil cytoplasmic antibodies (ANCA) important in the pathology of glomerulonephritis?

Answer 29

ANC Antibodies produce tissue damage in the glomerulus via interactions with primed neutrophils and endothelial cells

Question 30

Note - there are many types of glomerulonephritis which can cause varying and overlapping presentations

Answer 30

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