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 from te glomerulus?
All that are smaller than albumin
Immunoglobulins do not get filtered - they stay in the plasma
What structural feature do podocytes contain?
They have interdigitating 'fingers' or foot processes
What are the three layers of the filter barrier?
What are mesangial cells?
Tree like group of cells which support capilalries
Where does filtrate travel after the glomerulus?
Goes into bowmans space and then into the proximal tubule
What substances leave the efferent arteriole?
Blood cells someme fluid
abumin and larger proteins
What is glomerulonephritis?
It is disease of the glomerulus
Either inflammatory or non-inflammatory
Primary - only affects the glomerulus or secondary other body parts are affected - SLE or Wegners
What are the 4 comon presentations of glomerulonephritis?
1. Haematuria (blood in urine)
2. Heavy proteinuria (nephrotic syndrome)
3. Slowly increasing proteinuria
4. Acute renal failure
What are the main causes of haematuria?
Urinary tract infection
Urinary tract stone
Urinary tract tumour
What is the necessary test before taking a renal biopsy?
Clotting screen - risk of bleeding to death
What is the pathogenesis of IgA nephropathy?
Excess IgA sometimes present in the serum (but this is true in some people who do not have glomerulonephritis)
IgA deposits are stuck in the mesangium and are not filtered in the urine - IgA – ‘irritates’ mesangial cells and causes them to proliferate and produce more matrix
Unknown why this causes RBC's to escape
What is the prognosis of IgA nephropathy?
Usually self-limiting - ie returns to normal
SMall % go onto chronic renal failure (via continued deposition of matrix)
How is the clinical diagnosis of nephrotic syndrome made?
Must be abnormality of the glomerular filter - renal biopsy
What is the hallmark feature of membranous glomerulonephritis?
Thickened glomerular basement membrane
Spikes of new basement membrane matrix material underneath podocytes - spikes try to surround and remove deposits of IgG
Deposits of IgG in the subendothelial site - between basal lamina and podocyte - cannot go further and is not filtered in the urine
What is the issue associated with IgG in the subendothelial layer?
IgG is too big to be filtered into the urine, but IgG activates compliment (C3) which punches holes in the filter
What is the consequence of complement punching holes in the filter?
Leaky filter allows albumin to be filtered into urine - nephrotic syndrome
What is the prognosis of glomerulonephritis?
•1/4 in chronic renal failure within 10 years
This is not associated with inflamamtion– on wrong side of the basal lamina – inflammatory cells cannot reach
What is the underlying cause of IgG production and accumulation in membranous glomerulonephritis?
Unknown but can have underlying malignancy
IN many patients antigen is phospholipase A2 receptor
Phospholipase A2 is present on podocytes – IgG is against this receptor
Where does matrix deposition occur in diabetic nephropathy?
Matrix deposition in basal lamina underlying endothelium and in mesangial matrix
Kimmelsteil Wilson lesio - gross excess of mesangial matrix forming nodules
Describe the basement membrane in diabetic nephropathy
Thickened and leaky
Describe the messangial matrix in diabetic nephropathy
What are the histological features of diabetic nephropathy?
Small compressed capillary lumen (by messangial matrix)
Thickened capillary wall - leaks albumin
Thickened and narrowed arterioles reduce blood flow to glomerulus
Adhesions to bowmans capsule (glomerulus's attempt to stop massive leakage of albumin into urine)
What is the prognosis of diabetic nephropathy?
Inevitable decline if 1. established diabetic nephropathy and if 2. continued poor diabetic control
What is rapidly rising creatinine associated with?
Acute renal failure
What type of glomerulonephritis has cellular proliferation and influx of macrophages (crescent) within bowmans space?
What are the main patterns of crescentic glomerulonephritis?
•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 does granulomatosis with polyangitis affect?
It is a form of vasculitis
Causes: Inflammation in the vessels which affects the vessels in the kidneys, nose and lungs
What are further tests for granulomatosis with polyangitis?
Serum tests show presence of anti-neutrophil cytoplasmic antibodies
What are anti-neutrophil cytoplasmic antibodies?
•Antibodies directed against proteinase 3 and myeloperoxidase, 2 enzymes in primary granules of neutrophils
They are not deposited in the kidney
How do ANCA produce tissue damage?
•Antibodies produce tissue damage via interactions with primed neutrophils and endothelial cells.
What is the prognosis of wegners?
6 months if left untreated
Cyclophosphamide - 75% complete remission