Glomerular Disease Flashcards
How does a normal glomerulus function?
- Blood enters via afferent arteriole
- Blood is filtered across glomerular membrane
- All proteins equal to or larger than albumin (including immunoglobulins) will not be filtered- they will stay in the plasma)
- Filtrate goes into Bowman’s space then into proximal tubule
- Blood cells, some fluid and albumin and larger proteins exit via efferent arteriole
What cells wrap around the capillaries present in the glomerulus?
Podocytes
How are podocytes able to wrap around capillaries?
They have interdigitating fingers or foot processes
What are the 3 components of the filter barrier (membrane)?
- Endothelial cell cytoplasm
- Basal lamina
- Podocyte
What are mesangial cells?
Tree-like group of cells which support capillaries
What is present in the efferent arteriole of the glomerulus?
Contains plasma including unfiltered proteins such as albumin and antibodies
What is glomerulonephritis?
- Diseases of the glomerulus which can be inflammatory or non inflammatory
- Large range of conditions
What does primary glomerulonephritis affect?
Only affects the glomerulus
What does secondary glomerulonephritis affect?
Glomerulus and other parts of the body e.g. in SLE or Wegener’s
What is the aetiology of glomerulonephritis?
- Some are due to immunoglobulin deposition
- Some are diseases with no immunoglobulin deposition - for example- diabetic glomerular disease
What are 4 common presentations of glomerulonephritis?
- Haematuria (blood in the urine)
- Heavy proteinuria (nephrotic syndrome)
- Slowly increasing proteinuria
- Acute renal failure (rapidly rising creatinine)
What are the main causes of glomerulonephritis?
- UTI
- Urinary tract stone
- Urinary tract tumour
- Glomerulonephritis
What must be done before a renal biopsy can be carried out?
Check clotting
What may the initial presentation of IgA proliferative nephropathy?
Discoloured urine (due to presence of blood)
What investigations may be carried out for IgA proliferative nephropathy?
- Dipstick urine
- Urine culture
- Ultrasound of abdomen
- Renal biopsy
What may be found on histology of IgA proliferative nephropathy?
- Accumulation of pink mesangial matrix
- Too many mesangial cells
- Deposits of IgA with prominent of mesangial cells
What may be seen on immunofluorescence of IgA proliferative nephropathy?
Immunoglobulin (of IgA type) and complement component C3 in mesangial area of all glomeruli
Why is there increased mesangial cells in IgA proliferative nephropathy?
IgA deposits cause increased proliferation of mesangial cells
What is the aetiology of IgA glomerulonephritis?
-Unknown
-May be due to excess antibody production as excess antibody (IgA) sometimes present in serum, but this is also true of some people who do not have IgA glomerulonephritis
n
Why is IgA not removed by the glomerulus?
It is not known why but it is probable very important to the cause of the disease
Does IgA get filtered into the urine?
No, the IgA is stuck within the mesangium
What part of the glomerulus becomes clogged with IgA?
The filter NOT the mesangium
Why does IgA blocking the filter of the glomerulus lead to red cells escaping into the urine?
This is not known
Why do mesangial cells produce more matrix in IgA proliferative nephropathy?
IgA irritates mesangial cells and causes them to proliferate and produce more matrix
What is the prognosis of IgA nephropathy?
- Usually self limiting
- Small % go onto develop chronic renal failure (via continued deposition of matrix)
How may nephrotic syndrome present?
Oedema, particularly of the legs
What investigations should be carried out for nephrotic syndrome?
- Blood biochemistry and haematology tests
- Urine dipstick
- Renal biopsy
What may be found on blood tests of nephrotic syndrome??
Serum albumin low
What may be found on urine dipstick of nephrotic syndrome?
Proteinuria
What may found in the urine in nephrotic syndrome?
Protein (albumin) -very heavy loss
What must be true for a clinical diagnosis of nephrotic syndrome?
Must be abnormality of glomerular filter
What may be seen on histology of membranous glomerulonephritis?
- Thickened glomerular basement membrane
- Spikes of new basement membrane matrix material underneath podocytes
- Deposits of IgG
What happens to antibody and albumin with a normal basement membrane?
They stay in the plasma. They are NOT filtered
How does IgG become stuck in the membrane?
IgG deposits itself between basal lamina and podocyte but cannot go further and is not filtered into urine
How does albumin get filtered into the urine in membranous glomerulonephritis?
- IgG is too big to be filtered into urine, but IgG activates complement (C3), which punches holes in filter
- Leaky filter now allows albumin to be filtered into urine causing nephrotic syndrome
What is the prognosis of membranous glomerulonephritis?
-1/4 in chronic renal failure within 10 years
What is the underlying cause of IgG production and accumulation in membranous glomerulonephritis?
- Unknown but can sometimes have underlying malignancy
- In many patients antigen is phospholipase A2 receptor but it is unknown why
What is the pathology behind diabetic nephropathy?
- Glycated molecules
- Matrix deposition in basal lamina underlying endothelium and In mesangial matrix
- Thickened but leaky basement membranes and mesangial matrix compresses capillaries (no immune complexes)
What may be seen on histology of diabetic nephropathy?
- Small compressed capillary lumen
- Thickened capillary wall
- Increased mesangial matrix
- Thickened narrowed arterioles
- Adhesions to Bowman’s capsule
What are Kimmelsteil Wilson lesions?
Gross excess of mesangial matrix forming nodules that is characteristic of diabetic nephropathy
What is the prognosis of diabetic nephropathy?
- Inevitable decline if established diabetic nephropathy and if continued poor diabetic control
- Damage can be arrested but not reversed
What will be evident on serum biochemistry of AKI?
Rapidly rising creatinine
What may be seen on histology of crescentic glomerulonephritis?
- Early endothelial damage with fibrin deposition
- Cellular proliferation and influx of macrophage (=crescent) around glomerular tuft, within Bowman’s space
What can cause a crescentic glomerulonephritis pattern of injury?
- Granulomatosis with polyangiitis (also known as Wegener’s granulomatosis)
- Microscopic polyarteritis (a disease very much like Wegeners)
- Antiglomerular basement membrane disease
- Many other forms of glomerulonephritis
What is granulomatosis with polyangiitis?
A form of vasculitis (= inflammation in vessels) which affects vessels in kidneys, nose and lungs
What test should be done with Wegener’s granulomatosis?
Serum test will show presence of anti-neutrophil cytoplasmic antibodies (ANCA)
Where are ANCA not deposited?
Not deposited in the kidneys
What is ANCA directed against?
Antibodies directed against proteinase 3 and myeloperoxidase, 2 enzymes in primary granules of neutrophils
What does ANCA produce?
Antibodies produce tissue damage via interactions with primed neutrophils and endothelial cells.
Why do ANCA form?
Unknown at present. Perhaps a form of autoimmunity
What is the prognosis of Wegener’s?
- Fatal (mean survival 6 months) if left untreated
- Cyclophosphamide (treatment) – 75% complete remission
