Glomerular disease Flashcards
where does blood enter into the glomerulus and where does it go after
through the afferent arteriole - filtered across the glomerular membrane
what proteins do not get filtered across the membrane
all proteins equal to or large than albumin (including immunoglobulin) will not be filtered - stay in plasma
what comprises the filter barrier
it a membrane made up of three things (as plasma would be filtered)
- endothelial cell cytoplasm
- basal lamina (connective tissue)
- podocytes (with interdigitating foot processes
what are mesangial cells
tree-like groups of cells found inside the capillaries that support the capillaries
after the glomerulus, where does filtrate go
the bowmans space and then into the proximal tubule
what exits via the efferent arteriole
plasma containing blood cells, unfiltered proteins (e.g. albumin) and antibodies
define glomerulonephritis
disease of the glomerulus - can be inflammatory or non-inflammatory
what is the difference between primary and secondary GN
primary - only affects the glomerulus
secondary - affects other parts of the body too e.g. SLE or Wegeners)
what is the aetiology of GN
some due to immunoglobulin deposition - immunoglobulin gets stuck in the filter (large sticky molecule)
some are diseases with NO immunoglobulin deposition (e.g. diabetic glomerular disease)
what are the 4 common presentations of GN
- Haematuria (blood in urine)
- Heavy proteinuria* (nephrotic syndrome)
- Slowly increasing proteinuria (can take years)
- Acute renal failure (rapid rising creatinine)
* usually albumin
what are the main causes of haematuria
UTI
urinary tract stone
urinary tact tumour
Glomerulonephritis
what is the most common cause of mesangial proliferative glomerulonephritis and how does this come about
IgA nephropathy
- IgA (and complement component C3) deposits in mesangium “irritate” mesangial cells and cause them to proliferate and produce more matrix
what is the prognosis for IgA nephropathy
usually self limiting
BUT
small % go into chronic renal failure (via continued deposition of matrix - leads to sclerosis)
CASE 1: 40 yr old man, discoloured urine (said to be straw coloured/translucent – now darker despite drinking enough fluid)
dipstick urine positive for blood BUT NOT proteins
urine culture normal
US abdomen normal
check clothing and renal biopsy - shows increased mesangium
differential diagnosis
mesangial proliferative GN
what causes membranous glomerulonephritis
thickened glomerular basement membrane with spikes from deposition of IgG
spikes form when basal lamina matrix tried to surround and remove deposit
why does the IgG get stuck in the basal lamina
deposits between basal lamina and podocyte but cannot go further along as it is too big - therefore initially not cleared and filtered into the urine - leads to build up
what does IgI activate and what does this cause
activates complement (C3) which punches holed in the filter
how would the usual complement (C3) cascade work
Complement – system in blood – like clotting cascade – function is to punch holes in bacteria – IgG binds to bacteria – cascade of complement goes on beside it
Good system for against bacteria – bad agaisnt own tissues
what happens once C3 ha punched holes into the filter
leaky filter now allows albumin to filtered into urine - leads to nephrotic syndrome
what is the underlying cause of IgG production and accumulation in membranous GN
unknown but sometimes have underlying malignancy
in many patients antigen is phospholipase A2 receptor - an antigen on podocytes
how does diabetic nephropathy occur
long term diabetes leads to glycated molecules - deposited in matrix of basal lamina under endothelium and in mesangial matrix - thickened but leaky membranes +mesangial matrix compresses capillaries - reduced blood flow
also glomerulus adheres to bowmans capsule to try stop massive leakage of albumin into urine - causes podocytes to fall off
NO IMMUNE COMPLEXES
what is formed when there is a build up of mesangial matrix due to glycation
nodules
= KIMMELSTEIL-WILSON LESIONS
**very characteristic of diabetic nephropathy
what is the prognosis for diabetic nephropathy
inevitable decline if
- established diabetic nephropathy
- continued poor diabetic control
if changes made to lifestyle - won’t reverse state of glomerulus BUT will halt digression
what are the 3 main causes of crescentic glomerulonephritis
- granulomatotsis with polyangiitis (Wegeners granulomatosis)
- microscopic polyarteritis
- antiglomerular basement membrane
what is granulomatosis with polyangiitis
a form of vasculitis (inflammation in vessels) that affects the vessels in the kidneys, nose and lungs
explains why patient may have a cough
what would serum tests show for granulomatosis with polyangiitis
presence of anti-neutrophil cytoplasmic antibodies (ANCA)
how does the presence of ANCA cause disease
NOT DEPOSITED IN KIDNEYS
Antibodies directed against proteinase 3 and myeloperoxidase, 2 enzymes in primary granules of neutrophils
antibodies produce tissue damage via interactions with primed neutrophils and endothelial cells
what is the treatment for granulomatosis with polyangiitis
can treat with chemotherapy - cyclophosphamide = 75% complete remission
BUT fatal if left untreated
CASE:
Female, 50 years old
Unwell for 3 weeks
Cough
Serum biochemistry – creatinine 500 (was 60 one year before)
does this women have acute or chronic renal failure
acute as creatinine rapidly rising
CASE:
Ultrasound: no renal tract lesion
Check clotting then renal biopsy - early endothelial damage with fibrin deposition
- huge bowmans space filled with cells (mostly macrophages) in a crescent shape
diagnosis =
crescent glomerulonephritis
CASE: looking at her symptoms as well as renal biopsy result - what type of crescent glomerulonephritis does this lady have
cough = lungs affected
= granulomatosis with polyangiitis
