Glomerular Disease Pathology Flashcards
Where does blood enter a normal glomerulus?
Via an afferent arterial
What proteins will not be filtered through the glomerulus?
All proteins equal to or larger than albumin will not be filtered so will stay in the plasma
What are mesangial cells?
‘Tree-like’ groups of cells which support the capillaries
Where does the filtrate go?
Into Bowman’s space and then into the proximal tubule
How do blood cells, some fluid and albumin and larger proteins exit?
Via an efferent arteriole
What are the types of glomerulonephritis?
Disease of the glomerulus - can be inflammatory or non-inflammatory
What parts of the body are affected by primary glomerulonephritis?
Only the glomerulus
What is affected by secondary glomerulonephritis?
Other parts of the body e.g. SLE, granulomatosis with polyangiitis
What is the aetiology of glomerulonephritis?
Some are due to immunoglobulin deposition
Some are diseases with no immunoglobulin deposition e.g. diabetic glomerular disease
What are the four most common presentations of glomerulonephritis?
Haematuria
Heavy proteinuria
Slowly increasing proteinuria
Acute renal failure
What are the main causes of haematuria?
Urinary tract infection
Urinary tract stone
Urinary tract tumour
These 3 should be excluded before a diagnosis of glomerulonephritis is reached
CASE
40 year old male
Discoloured urine
Dipstick urine positive for blood
Frank haematuria
What investigations would you do/organise?
Urine culture
Ultrasound - pelvic/abdomen
Clotting screen
Renal biopsy
What is seen in a renal biopsy of IgA glomerulonephritis?
Immunofluorescence
Immunoglobulin (IgA) and complement component C3 in mesangial area of all glomeruli
What effect do IgA deposits have on mesangial cells?
IgA deposits cause increased proliferation of mesangial cells
In IgA glomerulonephritis, IgA is not removed by the glomerulus, what does this mean?
IgA does not get filtered into the urine and is stuck within the mesangium
The mesangium becomes clogged with the antibody, this causes RBCs to escape into the urine
IgA irritates the mesangial cells and causes them to proliferate and produce more matrix
What is the outcome of IgA nephropathy?
Usually self-limiting, patient will return to normal
A small percentage will go on to develop chronic renal failure via continued deposition of the matrix
CASE 2
50 year old male
3 week history of feeling unwell and swollen legs
What investigations would you do/organise?
Blood biochemistry and haematology tests
Dipstick
Clotting screen
Renal biopsy
CASE 2
Blood biochemistry and haematology tests show that serum albumin is low
Urine dipstick shows proteinuria
Referred to nephrologist who identifies very heavy protein loss in urine
Biopsy shows thickened glomerular basement membrane
Spikes of new basement membrane matrix material is present underneath podocytes
What is the most likely diagnosis?
Membranous glomerulonephritis
What is the pathological process of membranous glomerulonephritis?
IgG stuck in the membrane
IgG deposits itself between the basal lamina and podocyte but cannot go further and is not filtered into the urine
IgG is too big to be filtered but activates complement (C3) which punches holes in the filter
Leaky filter now allows albumin to wbefiltered into the urine, resulting in nephrotic syndrome
What is the prognosis of membranous glomerulonephritis?
1/4 will be in chronic renal failure within 10 years
What is the underlying cause of IgG production and accumulation in membranous glomerulonephritis?
Unknown but sometimes associated with underlying malignancy
In many patients, the antigen is phospholipase A2 receptor but it is unknown why
CASE 3
31 year old woman
Type 1 diabetes since childhood
Long periods of poor glycaemic control
Developed retinopathy
Albumin in urine slowly increasing over last few years, now heavy proteinuria
Glycated molecules seen on biopsy, matrix deposition in the basal lamina underlying the endothelium and mesangial matrix
Thickened but leaky basement membranes and mesangial matrix compressing the capillaries
What is the most likely diagnosis?
Diabetic nephropathy
What is a Kimmelsteil-Wilson lesion?
Gross excess of mesangial matrix forming nodules
What is the prognosis of diabetic nephropathy?
Inevitable decline if established diabetic nephropathy and if poor glycaemic control continues
