Glomerular Disease Pathology Flashcards
What is glomerulonephritis?
Inflammation of the tinu filters in your kidney (glomeruli)
How does blood enter the glomerulus?
Via afferent arteriole
What happens once blood enters the glomerulus?
Some of it is filtered across glomerular membrane
When blood enters the glomerulus, what happens to large and charge substances?
They are not filtered and will stay in plasma
What are the cells called in the Bowman’s capsule that wrap around the capillaries of the glomerulus?
Podocytes
What are podocytes observed to have?
Interdigitating fingers or foot processes
What can be seen if you took a secrtion through a capillary loop?
Filter barrier, which is a membrane composed of endothelial cell cytoplasm, basal lamina and podocyte
What are the 3 parts of the filter barrier?
Endothelial cell cytoplasm
Basal lamina
Podocyte
What are mesangial cells?
‘Tree like’ group of cells which support capillaries
What happens to filtrate after glomerulus?
Goes into Bowman’s space, then into proximal tubule
After the glomerulus, what do blood cells, some fluid and albumin and larger proteins exit via?
Efferent arteriole
What are the different kinds of glomerulonephritis?
Inflammatory or non-inflammatory
Primary
Secondary
What is primary glomerulus?
Only affects glomerulus
What is secondary glomerulus?
Affects other parts of the body
What are examples of diseases causing secondary glomerulus?
SLE or Wegener’s
What is the aetiology of glomerulonephritis?
- immunoglobulin deposition
- no immunoglobulin deposition
What are the 4 common presentations of glomerulonephritis?
- Haematuria (blood in urine)
- Heavy proteinuria (nephrotic syndrome)
- Slowly increasing proteinuria
- Acute renal failure
What are different conditions that cause glomerulonephritis?
IgA glomerlonephritis
Membranous glomerulonephritis
Diabetic nephropathy
Crescentic glomerulonephritis
What does IgA glomerulonephritis often present with?
Often presents with discoloured urine, investigation would be dipstick urine which is positive for blood
What are the main causes of IgA glomerulonephritis?
- Urinary tract infection
- Urinary tract stone
- Urinary tract tumour
- Glomerulonephritis
What investigations are done for IgA glomerulonephritis?
Dipstick urine
Urine culture
Ultrasound scan
If all normal, renal biopsy
If all typical investigations are normal for IgA glomerulonephritis, what investigation would be done?
Renal biopsy
What is immunofluorescence?
Method in biology that relies on the use of antibodies chemically labeled with fluorescent dyes to visualize molecules under a light microscope
What can be done with urinary biopsy in IgA glomerulonephritis?
What is seen in a renal biopsy and immunofluorscence for IgA glomerulonephritis?
- Reveals immunoglobulin (of IgA type) and complement component of C3 in mesangial area of all glomeruli
What is the aetiology of IgA glomerulonephritis?
Aetiology of IgA glomerulonephritis is unknown:
- Excess antibody (IgA) sometimes present in serum, but this is also true of some people who do not have IgA glomerulonephritis
What is the pathogenesis of IgA glomerulonephritis?
IgA also does not get filtered into urine, it is “stuck” within the mesangium
This causes mesangium, not the filter membrane to become clogged with antibody – causing red blood cells to escape into urine:
- IgA irritates mesangial cells and causes them to proliferate and produce more matrix
What is the prognosis of IgA glomerulonephritis?
- Usually self-limiting, ie return to normal
- Small percentage go onto chronic renal failure (via continued deposition of matrix)
What is the typical presentation of membranous glomerulonephritis?
Could present with feeling unwell and swollen legs
What investigations are done for membranous glomerulonephritis?
- Check clotting screen then do renal biopsy
What is seen in a dipstick of urine for membranous glomerulonephritis?
Proteinuria
What is seen in blood biochemistry for membranous glomerulonephritis?
Serum albumin low
What is the pathogenesis of membranous glomerulonephritis?
In membranous glomerulonephritis IgG is stuck in the membrane:
- IgG deposits itself between basal lamina and podocyte but cannot go further and is not filtered into urine
- IgG is too big to be filtered into urine, but activates complement (C3) which punches holes in filter
- This leaky filter now allows albumin to be filtered into urine, causing nephrotic syndrome
What does renal biopsy reveal for membranous glomerulonephritis?
Thickened glomerular basement membrane
Deposits of IgG
Basal lamina spikes (matrix which tries to surround the deposit)
What is deposited on the membrane in membranous glomerulonephritis?
IgG
What is the prognosis of membranous glomerulonephritis?
- 1/4 will get chronic renal failure within 10 years
What is the aetiology of membranous glomerulonephritis?
- Unknown but ca sometimes have underlying malignancy
- In many patients antigen is phospholipase A2 receptor
What investigations are done for diabetic nephropathy?
Dipstick urine
Clotting screen
Renal biopsy
What can be seen in the biopsy for diabetic nephropathy?
What is the pathogenesis of diabetic nephropathy?
What kind of lesion does diabetic nephropathy cause?
Diabetic nephropathy causes nodules of mesangial matrix to form, known as Kimmelsteil-Wilson lesion:
- Is gross excess of mesangial matrix forming nodules
What is the prognosis of diabetic nephropathy?
- Inevitable decline if established diabetic nephropathy ad if continued poor diabetic control
What is a sign of acute renal failure?
Rapidly rising creatinine
What are the typical investigations for renal disease?
Urine dipstick
Clotting screen
Renal biopsy
What is seen in the biopsy for crescentic glomerulonephritis?
Early endothelial damage with fibrin deposition
Crush glomerular tuft
Cellular proliferation and influx of macrophages (is the crescent) around glomerular tuft, within Bowman’s space
What are some causes for the crescentic glomerulonephritis pattern of injury?
- Granulomatosis with polyangiitis (also known as Wegener’s granulomatosis)
- Form of vasculitis (inflammation in vessels) which affects vessels in kidneys, nose and lungs
- Microscopic polyarteritis (a disease very like Wegener)
- Antiglomerular basement membrane disease
- Many other forms of glomerulonephritis
What is granulomatosis with polyangitis also known as?
Wegener’s granulomatosis
What is Wegener’s granulomatotis?
- Form of vasculitis (inflammation in vessels) which affects vessels in kidneys, nose and lungs
What further tests can be done for Wegener’s?
- Serum test shows presence of anti-neutrophil cytoplasmic antibodies (ANCA)
- These are not deposited in the kidneys
- Antibodies directed against proteinase 3 and myeloperoxidase, 2 enzymes in primary granules of neutrophils
- Antibodies produce tissue damaged via interactions with primed neutrophils and endothelial cells
What do serum tests reveal in Wegener’s?
Presence of anti-neutrophil cytoplasmic antibodies (ANCA)
What does ANCA stand for?
Anti-neutrophil cytoplasmic antibodies
What is ACNA a form of?
Autoimmunity
What is the prognosis of Wegener’s?
- Fatal (mean survival time is 6 months) if left untreated
- Cyclophosphamide
- 75% complete remission
