Pathology of Glomerular disease Flashcards
What molecules are not able to pass through the glomerular membrane?
All proteins equal to or larger than albumin (including immunoglobulins) will not be filtered - they will stay in plasma
describe the arrangement of podocytes around glomerular capillaries?
podocytes have interdigitating ‘fingers’ or foot processes - that surround the capillaries
What are the 3 layers of the glomerular membrane (ie the filter barrier)
endothelial cell cytoplasm, basal lamina and podocyte
What are mesangial cells?
‘tree-like’ group of cells which support capillaries in the glomerulus
In the image below - identify a mesangial cell
What is Glomerulonephritis?
Disease of the glomerulus
Can be inflammatory or non-inflammatory
Describe the aetiology of glomerulonephritis
Some are due to Immunoglobulin deposition
Some are not - for example diabetic glomerular disease
What are the 4 common presentations of glomerulonephritis?
Haematuria - blood in urine
Heavy proteinuria - nephrotic syndrome
Slowly increasing proteinuria
Acute renal failure
What are the main causes of Haematuria?
Is glomerulonephritis an important cause?
Main causes are:
- Urinary tract infection
- Urinary tract stone
- Urinary tract tumour
Glomerulonephritis is a relatively rare cause of Haematuria
What investigation is best for identifying Immunoglobulin deposits in glomerulonephritis?
Renal biopsy i think
Whats wrong with this bois glomerulus
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
How does immunoglobulin deposition affect the mesangium of the glomerulus?
IgA – ‘irritates’ mesangial cells and causes them to proliferate and produce more matrix
What is the prognosis for IgA nephropathy ?
Usually self limiting
Can rarely cause chronic renal failure (via continued deposition of matrix)
What causes ‘membrane glomerulonephritis’?
Thickening of the glomerular basement membrane
Is there immunoglobulin deposition in membranous glomerulonephritis?
Yes - there are deposits of IgG
This takes place between the basal membrane and the podocytes
Describe how the IgG deposits seen in membranous glomerulonephritis cause albumin to leak into the blood
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
What is the prognosis of membranous glomerulonephritis?
25% of patients progress to chronic renal failure within 10 years
What is the underlying cause of membranous glomerulonephritis?
(ie what causes the IgG production and accumulation in membranous glomerulonephrits)
Unknown but can be related to:
autoimmunity against phospholipase A2 receptor
malignancy
amongst other things
What are the main features of diabetic damage to the glomerulus?
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
What histological feature of diabetic nephropathy is different from the previous types of glomerulonephritis discussed?
There are NO IMMUNE COMPLEXES DEPOSITED
Summarise the histological features of glomeruli in diabetic nephropathy
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
What are Kimmelsteil-Wilson lesions?
Feature of diabetic nephropathy - in which there is gross excess of mesangial matrix forming nodules
What is the prognosis for diabetic nephropathy?
Poor if already established and evener poorerer if poor diabetic control
What is the significance of Creatinine in all this stuff?
Rapidly rising creatinine = acute renal failure
The image below came from a patient with acute renal failure
What type of glomerulonephritis is shown?
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
What features of Crescentic glomerulonephritis allow you to distinguish it?
Presentation - acute renal failure
Investigations - raised creatinine
Histology:
- Crescent shape - due to macrophages in Bowman’s space
- Crushed glomerular tuft
What is Granulomatosis with polyangiitis?
A form of vasculitis - which affects vessels in kidneys, nose and lungs
What further tests are available for Granulomatosis with polyangiitis?
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
Anti-neutrophil cytoplasmic antibodies (ANCA) important in the pathology of glomerulonephritis?
ANC Antibodies produce tissue damage in the glomerulus via interactions with primed neutrophils and endothelial cells
Note - there are many types of glomerulonephritis which can cause varying and overlapping presentations
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