Lecture 8: Glomerular Disease (Pathology) Flashcards
what is the glomerular membrane filter barrier composed of?
three things:
- endothelial cell cytoplasma
- basal lamina
- podocyte
what is the name given to a ‘tree-like’ group of cells which support capillaries in the glomerulus?
mesangial cells
which substances leave the efferent arteriole of the glomerulus, having not been filtered?
blood cells
some fluid
albumin and larger proteins, antibodies
what is glomerulonephritis?
disease of glomerulus
inflammatory or non-inflammatory
what is the aetiology of glomerulonephritis?
- some due to immunoglobulin deposition
- some are diseases with no immunoglobulin deposition - for example - diabetic glomerular disease.
list 4 common presentations of glomerulonephritis
- haematuria (blood in urine)
- heavy proteinuria (nephrotic syndrome)
- slowly increasing proteinuria
- acute renal failure
list the main causes of haematuria
- UTI
- urinary tract stone
- urinary tract tumour
- glomerulonephritis
how is haematuria investigated?
- dipstick urine - positive for blood
- urine culture
- arrange ultrasound examination
- if normal, check his clotting factors are normal, then proceed to renal biopsy.
how can excess immunoglobulin deposition cause glomerulonephritis?
- IgA is not filtered into urine > gets ‘stuck’ within the mesangial cells
- mesangium, not the filter membrane, becomes clogged with antibodies
- IgA ‘irritates’ mesangial cells and causes them to proliferate and produce more matrix > mesangial cella and matrix expansion
IgA nephropathy prognosis
- usually self-limiting, i.e. return to normal
- small % go onto chronic renal failure (via continues deposition of matrix)
how would you investigate a low serum albumin?
- dipstick proteinuria
- refer to nephrologist to measure protein (albumin) in urine
- if there is heavy loss > clinical diagnosis of nephrotic syndrome > must be abnormality of glomerular filter
- check clotting screen then do renal biopsy
pathology of membranous glomerulonephritis
- IgG is stuck in membrane: deposits itself between basal lamina and podocyte but cannot go further and is not filtered into urine.
- IgG activates complement (C3), which punches holes in filter
- leaky filter now allows albumin to be filtered into urine > nephrotic syndrome
membranous glomerulonephritis prognosis
1/4 in chronic renal failure within 10 years
pathophysiology of diabetic glomerulonephritis
- glycated molecules > matrix deposition in basal lamina underlying endothelium and in mesangial matrix > thickened but leaky basement membranes + mesangial matrix compresses capillaries (no immune complexes)
in diabetic nephropathy, what are the nodules of meangial matrix called?
Kimmelsteil-Wilson lesion = gross excess of mesangial matrix forming nodules
- glomerulus attempt to prevent massive leaking of albumin into urine
diabetic nephropathy prognosis
- inevitable decline if, established diabetic nephropathy and if continued poor diabetic control
what does a rapidly rising serum creatinine level indicate?
acute renal failure
what is the appearance of cresentic glomerulonephritis in a biopsy?
list causes of crescentic glomerulonephritis
- granulomatosis with polyangiitis (previously known as Wegener’s granulomatosis)
- microscopic polyarteritis (very similar to above)
- antiglomerular basement membrane disease
- other - many other forms of glomerulonephritis
what are further tests for granulomatosis with polyangitis?
- biopsy
- serum tests show presence of anti-neutrophil cytoplasmic antibodies (ANCA)
how do ANCA cause tissue damage in granulomatosis with polyangitis?
- produce tissue damage via interactions with primed neutrophils and endothelial cells.
granulomatosis with polyangitis (Wegener’s) prognosis?
- fatal (mean survival 6 months) if left untreated
- cyclophosphamide > 75
% complete remission
