Glomerulonephritis Flashcards
What is glomerulonephritis?
immune-mediated disease of the kidneys affecting the glomeruli with secondary tubulointerstital amage
What mediates GN?
humoral- antibody mediated- intrinsic or planted antigent or deposition of circulating immune complexes
What happens in GN to the glomerular membrane?
disruption of the barrier leads to haematuria and/or proteinuria
What happens if there is damage to enothelial or mesangial cells?
proliferative lesion and RBCs in the urin
What happens if there is damage to the podocytes?
non-proliferative lesion and protein in the urine
Why does damage to different cells at the glomerulus cause different responses?
cells of the nephron respond to injury in different ways
What happens to the podocytes when they are injured?
atrophy- loss of size/charge specific barrier
What happens if there is injury to the mesangium?
mesangial cells proliferate and release ATII and chemokines; attracts inflammatory cells
What happens if there is injury to the endothelial cells?
vasculitis
What is the difference between endothelial and mesnagial injury if they are both prolferative lesions?
endothelial injury is a much more aggressive process and has lots of inflammation
What is done if there is haematuria seen on urinalysis?
RBC (dysmrophic; granular casts and lipiduria
What is done is there is protein seen on UA?
PCR
What is the typical presentation of haematuria with GN?
asymptomatic microscopic or painless macroscopic
What is microalbuminuria?
30-300mg albuminuria/day
What is heavy proteinuria?
1-3g/day
What is nephrotic syndrome efined as in proteinuria?
> 3g/day
What is the appearance of RBCs on microscopy if they have come from the glomerulus? why?
dysmorphic- have been squeezed through the tubule
What are RBC casts?
protein that tubules produce gathers roudn the blood cells and they end up in a tubular shaped clump
What is nephritic syndrome?
ARF; oliguria; oedema/fluid retention; HT; active urinary sediment
What is active urinary sediment?
RBCs; RBC and granular casts
What is nephritic syndrome indicative of?
a proliferative process affeting endothelial cells
What is nephrotic syndrome?
proteinuria >3g/day; hypoalbuminaemia; oedema; hypercholeseterolaemia
What is nephrotic syndrome indicative of?
a non-proliferative process affecting podocytes
What are the complications of nephrotic syndrome?
infections; renal vein thrombosis; PE; volume depletion
Why do patients with nephrotic syndrome get infections?
loss of opsonising antibodies
What should be suspected with AKI in nephrotic syndrome?
renal vein thrombosis
What causes volume depletion with nephrotic syndrome?
overagressive use of diuretics
What may volume depletion lead to?
pre-renal ARF
What is the difference between interstital nephritis and GN on urinemicroscopy?
interstital nephritis doesn’t have dysmorphic RBCs
How are renal biopsies analysed?
light microscopy; immunofluorescence; EM
What does diffuse GN indicate?
> 50% glomeruli affeced
What does global/segmental GN indicate?
whether all or parts of the glomeruli are affected
What is crescenteric GN?
presence of crescents- epithelial cell extrancapillary (Bowman’s space) proliferation
What are the principles of treatmnet of GN?
reduce proteinuria; induce remission of nephrotic syndrome; presence longterm renal function
What is the target BP for renal patients?
<130/80
What is the target BP for patients with proteinuria?
<120/75
What are the non-immunosuppressive treatments for GN?
anti-HTs; ACEi; diuretics; statins; anticoag- if albumin <20
When is plasmapharesis considered with GN?
if very agressive disease due to circulatin antibodies
What is the prupose of giving IV immunoglobulin with GN?
will attach autoantibodies
What is the prupose of monoclonal T or B cell antibodies in GN
directed at B cells which produce the autoantibodies
What is the treatmnet of nphrotic patients?
fluid and salt restrict; diuretics; ACEi; anticoag; IV albumin- only if volume deplete; immunosuppression
What is the definition of complete remission of nephrotic syndrome?
proteinuria <300mg/day
What is the definition of partial remission of nephrotic syndrome?
proteinuria <3G/day
What are the riks of immunosuppressing a patient who is nephrotic?
increased risk of infeciton- do very badly so offload them vefore start immunosuppressives
What is the target in minimal change GN?
podocyte but specific antigen and antibody unkown
What is the commonest cause of nephrotic syndrome in chidlren?
minimal change
What is seen on EM with minimal change?
foot process fusion
What is the first line for minimal change?
steroids
What is second line for minimal change GN?
cyclophosphamide
What is the prognosis for minimal change?
does not cause progressive renal failure
What is the commonest cause of nephrotic syndrome in adults?
focal segmental glomerulosclerosis
What are the secondary causes of FSGS?
HIV; heroin use; obesity; reflux nephropathy
What is the treatmnet for FSGS?
steroids
What is the prognosis for FSGS?
50% progress to ESRF after 10 years
What happens in FSGS?
podocyte injury- parietal epithelial cells try to transfer over to atrophied pododcytes to fill hole creating scar tissue
What is the second commonest cause of nephrotic syndrome in adults?
membranous nephrotpathy
What are the important secondary causes of membranous nephropathy?
infections- hep B; SLE; malignancies; drugs- gold; pencillamine
What is seen on renal biospy with membranous nephropathy?
subepithelial immune complex deposition in the BM- thickened basmement membrane
What is the prognosis for membranous nephropathy?
30% progress to ESRF in 10 years
What is the antigen in membranous nephropathy?
within podocyte- phosopholipase A2 receptor
what is the antibody in membranous nephropathy?
anti-PLA2r AB
What is the treatment for MN
steroids; alkylating agents (cyclophosphamide)
What is the presentation of IgA nephropathy?
asymptomatic microhaematuria +/- non-nephrotic range proteinuria; or macroscopic haematuria after resp/GI infection; AKI/CKD
What vasculitis is IgA nephropathy associated with?
Henoch-Schonlein Purpura
What are the symtpoms of HSP?
arthritis; colitis; purpuric skin rash
What is seen on renal biopsy with IgA nephropathy?
mesangial cell prliferation and expansion with IgA deposits in mesangium
What is the prognosis for IgA nephropathy?
25% progress to ESRF in 10-30 years
What is the treatment for IgA nephropathy?
BP control; ACEi; fish oil
What causes IgA nephropathy?
antigen is not within kidne- abnormal IgA, IgG is produced against the abnormal IgA whcih get stuck in the mesangium
Why is there an exacerbation of IgA nephropathy with infection?
infection of mucosal surfaces eg GI or resp- increase in IgA
What happens with rapidly progressive glomerulonephritis?
rapid deterioration in renal function over days/ weeks
What is rapidly progressive glomerulonephritis associated with on biopsy?
glomerular crescents
What are the 2 main categroeis of RPGN?
ANCA positive nad ANCA negative
What are the types of ANCA positive RPGN?
GPA nad microscopic polyangiitis
What are the types of ANCA negative RPGN?
Goodpasture’s; HSP; SLE
How does ANCA cause a vasculitis?
attacks neutrophil cytoplasms which become sticky and bind to vascular walls which begins the inflam cascae and proteolytic enzymes are produces which destroy the vascular wall
What happens in RPGN when the BM is interrupted?
inflammatory cells and RBCs gather in Bowman’s space in the shape of a crescent which compresses the glomerular tuft and closes the cpiallry lumens leading to glomerular death
What is the antigen in Goodpasture’s?
type 4 collagen in GBM
What are the treatments for RPGN?
immunosuppression and plasmapharesis
