Glomerular Disease (Pathology) Flashcards
What are podocytes?
Podocytes are cells in the Bowman’s capsule in the kidneys that wrap around capillaries of the glomerulus
What proteins are filtered by the glomerulus?
All that are smaller than albumin
What structual feature do podocytes have?
From outside they have interdigitating ‘fingers’ or foot processes (‘podo’) which clamp on to the capillary loop and stop massive fluxes of proteins
What are the 3 layers of the filter barrier membrane?
Endothelial cell cytoplasm
Basal lamina (connective tissue)
Podocyte (foot process)
What are mesangial cells?
‘tree-like’ group of cells which support capillaries
How does filtrate travel after being filtered from the glomerulus?
Goes into Bowman’s space then into proximal tubule
What 3 substances exit the glomerulus via the efferent arteriole?
Blood cells, some fluid and albumin + larger proteins
What is glomerulonephritis? Is it inflammatory or non-inflammatory?
Disease of the glomerulus
What is affected in primary glomerulonephritis?
Only affects glomerulus
What is affected in secondary glomerulonephritis?
Other parts of body affected e.g. SLE (lupus) or Wegner’s
Glomerulonephritis is sometimes cause by immunoglobulin deposition, but sometimes it isnt, e.g. in…
diabetic glomerular disease
What are 4 common presentations of glomerulonephritis? (IMPORTANT)
- Haematuria (blood in urine)
- Heavy proteinuria (nephrotic syndrome)
- Slowly increasing proteinuria
- Acute renal failure
How is haematuria diagnosed in a lab test?
Dipstick urine - positive for blood
4 causes of haematuria? (IMPORTANT)
- UTI
- Urinary tract stone
- Urinary tract tumour
- Glomerulonephritis (uncommon compared to first three)
What should be done after haematuria is diagnosed?
- Send off urine culture
- Arrange hosp appointment for USS (to find calculi/tumours)
What to do if urine culture and USS are both normal?
Renal biopsy
What is important to do before performing biopsy?
Clotting screen (risk of bleeding to death)
What could be found in a renal biopsy of glomerular pathology in a patient with haematuria (Case 1)? What would the light microscopy show? What would electron microscopy show?
Immunoglobulin (of IgA type) and complement component C3 in mesangial area of all glomeruli
LM - Accumulation of pink mesangial matrix; profileration of mesangial cells
EM - deposits of IgA with prominent mesangial cells (and profileration of mesangial cells)
Aetiology of IgA glomerulonephritis is not entirely known, what could cause it?
Execess antibody (IgA) sometimes present in serum (but this also true of ppl who dont have IgA glomerulonephritis) IgA is for some reason not removed by the glomerulus and is 'stuck' within the mesangium
Mesangium (not the filter membrane), becomes clogged with antibody
What effect does IgA have on the mesangial cells?
‘irritates’ mesangial cells and causes them to proliferate and produce more matrix
Is it known why IgA nephropathy causes haematuria (RBCs in urine)?
Nope
What is the usual prognosis of IgA nephropathy?
Usually self-limiting i.e. return to normal
What happens in a small % of people with IgA nephropathy?
Go into chronic renal failure (via continued deposition of matrix) - histology shows completely sclerosed glomerulus
(can be up to 25% - particularly high in Japan)
A 50 yr old male presents with 3 weeks of feeling unwell and swollen legs - what to do?
Send off biochemistry and haematology tests
The man’s serum albumin is low, what next?
Dipstick proteinuria
Send into hosp to see nephrologist
The nephrologist measures the protein (albumin) in the man’s urine, it shows a v heavy loss, what then is th diagnosis?
Nephrotic syndrome (showed that it must be an abnormality of glomerular filter)
Check clotting screen of man and then do renal biopsy - what features be seen in this mans histology? (hint - ‘membranous glomerulonephritis’)
- thickened glomerular basement membrane
- deposits of IgG
- spikes of new basement membrane matrix material under podocytes - ‘basal lamina spikes’ (to try and surround and remove the deposit)
-
In membranous glomerulonephritis (one of most common causes of nephrotic syndrome), IgG deposits itself in the glomerular membrane, is it stuck there?
Yep; deposits itself between basal lamina and podocyte but cannot go further and is not filtered into urine as it is too big
What does IgG stuck in the membrane activate? How does this cause nephrotic syndrome?
Complement (C3) which punches holes in the filter and this now leaky filter allows albumin to be filtered into urine, causing nephrotic syndrome
What is the prognosis for membranous glomerulonephritis?
1/4 in chronic renal failure within 10 yrs; then progressively more after that
Treatment is not v good at moment
Is the underlying cause of IgG production and accumulation in membranous glomerulonephritis known?
No, but can sometimes have underlying malignancy
In many patients antigen is phospholipase A2 receptor - unknown why this protein specifically as it is on podocytes which are a v immunologically isolated part of the body - almost never meed inflammatory cells
(case 3 - type 1 DM; poor glycaemic control; retinopathy; albumin in urine slowly inreasing over last few yrs, not has heavy protein leakage in urine; renal biopsy done)
Where does matrix deposition in diabetic nephropathy occur?
In basal lamina underlying endothelium and in mesangial matrix
In diabetic nephropathy, what effect does matrix deposition have on basement membranes?
Makes them thickened but leaky
What effect does mesangial matrix have on capillaries in diabetic nephropathy?
Compresses them
Are there any immune complexes in diabetic nephropathy?
Nope
Describe some histological features of diabetic nephropathy
- thickened capillary wall which is leaking albumin
- increased mesangial matrix - leading to small, compressed capillary lumens
- thickened, narrowed arterioles reducing BF to glomerulus
- adhesions to Bowman’s capsule (glomerulus’ trying to stop massive leakage of albumin into urine)
What is a Kimmelsteil-Wilson lesion (‘in established diabetic nephropathy’)?
Nodule of mesangial matrix (gross excess of matrix forming nodules)
Prognosis for diabetic nephropathy?
Inevitable decline if established diabetic nephropathy and continued poor diabetic control
Case 4 - female, 50 yr old; unwell 3 wks; cough; serum biochem - creatinine 500)
What is rapidly rising creatinine associated with?
Acute renal failure
What else should be done in this case?
USS to see if renal tract lesion
Check clotting then do renal biopsy
What type of glomerulonephritis has cellular proliferation and influx of macrophages (crescent) within Bowmans space?
Crescentic glomerulonephritis
GIve 4 causes of the crescentic glomerulonephritis pattern of injury
- Granulomatosis with polyangitis (aka Wegners granulomatosis)
- Microscopic polyarteritis (similar to Wegners)
- Antiglomerular basement membrane disease
- Many other forms of glomerulonephritis
What is granulomatosis with polyangitis?
A form of vasculitis which affects vessels in kidneys, nose and lungs (which is why woman presented with cough)
Further test in Wegners is serum test, which might show what?
Presence of anti-neutrophil cytoplasmic antibodies (ANCA)
What are ANCAs directed against? Are they deposited in the kidney?
- Proteinase 3 and myeloperoxidase, 2 enzymes + primary granules of neutrophils
- NO
How do ANCAs produce damage?
Via interactions with primed neutrophils and endothelial cells
(not sure why they form - possibly a form of autoimmunity)
Prognosis for Wegner’s?
Fatal - mean survival is 6 months if left untreated
Must be treated v quickly with cycophosphamide chemo - 75% complete remission
