glomerulonephritis Flashcards
what are mesangial cell and what is their function
smooth muscle–like cells that contain actin and myosin -> they connect to each other via gap junctions and to the Glomerular Basement Membrane via cell processes;
Contraction of mesangial cells regulates the size of the capillary lumen and thus the amount of glomerular blood flow
what is a focal glomerulonephritis
affecting only some glomeruli
what is a diffuse glomerulonephritis
affecting all glomeruli
what is a segmental glomerulonephritis
affecting only one part of the glomerulus
what is a global glomerulonephritis
affecting the whole glomerulus
what is proliferation
increase in number of cells
what is cell expansion
increase in intracellular matrix
what is crescent proliferation
proliferation of cells within the bowman’s space
2 mechanisms underlying glomerulonephritides
- immunological
- vascular
types of immunological glomerulonephritides + examples !!! (4)
- antibody binding to INTRINSIC glomerular antigens (i.e. the body happens to have auto-antibodies to glomerular antigens) e.g. goodpastures;
- antibody binding to PLANTED glomerular antigens e.g. post strep glomerulonephritis;
- deposition of circulating antigen-antibody complexes -> in active autoimmine disease, complexes can deposit nonspecifically in the BM e.g. lupus nephritis
- NON-SPECIFIC DEPOSITION of circulating antibodies -> binds through the heavy chain (constant region) resulting in more sticky antibodies that can bind randomly e.g. IgA nephropathy
brief pathophys of goodpasture’s disease
antibodies against T4 collagen -> T4 collagen is used to form the basement membrane => destruction of glomerular basement membrane
what is “pauci-immune” crescentic glomerulonephritis
an idiopathic form of crescentic glomerulonephritis that typically lacks significant deposits within glomeruli and most often is associated with ANCA -> systemic vasculitis
indications for renal biopsy (6)
- nephrotic syndrome
- renal dysfunction of unknown cause (e.g. AKI with unknown cause)
- to guide treatment of assess prognosis where diagnosis is known
- dysfucntion of kidney transplant (sus of rejection)
- haematuria
- proteinuria
might not biopsy in last 2
complications of renal biospy (2)
- pain
- bleeding -> may need embolisation/nephrectomy, blood transfusion and may result in death
contraindications to renal biopsy
- abnormal clotting/thrombocytopenia -> take a drug history!!
- drugs (e.g. aspirin, clopi, warfarin)
- uncontrolled hypertension
- single kidney (risk of damaging only working kidney, can still biopsy but only if absolutely necessary)
- hydronephrosis
- urinary tract infection
what imaging guidance is used in renal biopsies
ultrasound
what does the EM of minimal change disease biopsy show
fusion of podocyte foot processes -> biopsy looks normal on light microscopy so EM must be done
what drug class is often implicated in minimal change disease
NSAIDs
what malignancy is often implicated in minimal change disease
lymphoma; leukemia
how does focal segmental glomerulosclerosis present
with nephrotic syndrome and renal impairment
what is seen on biopsy of focal segmental glomerulosclerosis (if correct area taken)
segmental sclerotic lesions with C3 and IgM deposition
if nephrotic syndrome doesn’t improve with steroids, what underlying cause should be suspected
- focal segmental glomerulosclerosis !
- membranous nephropathy
what can FSGS and membranous nephrapthy progress to
CKD
secondary causes of focal segmental glomerulosclerosis (4)
- obesity (hyperfiltration causes damage)
- IV heroin use
- HIV
- drugs (e.g.pamidronate)
what is the commonest cause of nephrotic syndrome in adults
membranous nephropathy
pathophys of membranous nephropathy
an autoimmune disorder in which immune complexes deposit along the subepithelial region of the glomerular basement membrane (IgG)
what is membranous nephropathy associated with (3)
- solid organ malignancy
- drugs (e.g. gold, penicillamine, captopril)
- infections (e.g. hepaitis, malaria)
what is the rule of 1/3s if membranous nephropathy is untreated
1/3 improve spontaneously
1/3 remain the same
1/3 develop progressive disease
how can mesangiocpillary glomerulonephritis (aka membranoproliferative GN) present
nephrotic or nephritic syndrome
mesangiocpillary glomerulonephritis biopsy findings
- mesangial proliferation (often lobular)
- thickened capillary walls -> “double contouring” of basement membrane
- +ve immunoflouresence
what other conditions is mesangiocapillary glomerulonephritis associated with (3)
- infections eg. hepatitis, malaria, endocarditis, shunt nephritis
- cryoglobinaemia (abnormal antibodies that precipitate in the cold)
- malignancy
what is shunt nephritis
a rare disease of the kidney that can occur in patients being treated for hydrocephalus with a cerebral shunt (infection of shunts being used to drain)
what glomerulonephritis may recurr post transplant
mesangiocapillary glomerulonephritis
what is the earliest clinical feature of diabetic nephropathy
microalbuminuria -> low level proteinuria (too low for dipstick detection)
how does diabetic nephropathy progress
- microalbuminuria
- protienuria becomes heavier (+/- nephrotic syndrome)
- progressive decline in GFR (goes up before it comes down due to hyperfiltration and then damage)
what does a diabetic nephropathy renal biopsy often show
kimmelstiel-wilson lesions -> Nodules of pink hyaline material form in regions of glomerular capillary loops in the glomerulus
what are the 2 types of amyloidosis
AL - primary amyloidosis, light chain deposition e.g. myeloma
AA - chronic inflammation e.g. infection, connective tissue disorders
what is amyloidosis
deposition of amyloid within multiple organs, including kidneys
causes of nephrotic syndrome (9)
- minimal change (children)
- FSGS
- membranous nephropathy (single commonest cause in adults)
- mesangiocapillary glomerulonephritis
- other proliferative
- diabetes
- amyloid
- lupus
what is the commonest glomerulonephritis in the world
IgA nephropathy (berger’s disease)
buerger’s disease presentation (5)
- painful blue fingertips
- rest pain
- Hx of smoking (and being a young man)
- microscopic haematuria/episodic macroscopic haematuria
- nephrotic syndrome
IgA vasculitis (henoch-schonlein purpura) presentation (5)
- symmetrical rashes usually located in the lower extremities
- palpable purpura
- migratory arthritis in the lower large joints
- nausea/ vomiting
- abdominal pain
IgA nephropathy (berger’s disease) presentation (3)
- nephritic syndrome
- dark urine
- oedema
what is buerger’s disease
a non-atherosclerotic vasculitis resulting in segmental occlusions of small and medium-sized arteries, commonly affecting the lower limbs of young men who smoke
what is IgA nephroapthy (berger’s disease)
a disease in which IgA protein builds up in and damages the filtering part of the kidney (glomerulus)
what other conditons is IgA nephropathy associated with
- henoch-schonlein purpura aka IgA vasculitis (abdo pain, joint pain, skin rash)
- liver disease
what is the triad of nephritic syndrome
- hypertension
- haematuria
- renal impairment
what are causes for nephritic syndrome (5)
- post-infectious glomerulonephritis
- systemic vasculitis
- goodpasture’s disease (Anti-GBM disease)
- cresentic nephritis
- lupus nephritis
when does post-infectious glomerulonephritis usually present
2-3 weeks after group A strep infection
post-infectious glomerulonephritis brief pathophsy
immune-complex to strep A results in damage to glomerulus
why are C3 levels usually low in post-infectious glomerulonephritis
alternate complement pathway is activated -> C3 consumed in complement cascade (C4 will be normal as not consumed)
what will the renal biopsy of post-infectious glomerulonephritis show (4)
- neutrophil infiltration
- mesangial and epithelial cell proliferation
- IgG and C3 deposition
- subepithelial deposits
what is a red cell cast
clear cylinders containing red blood cells and may have an orange-red tinge seen in the urine -> indicates microscopic bleeding in the kidneys i.e. glomerulonephritis
what condition are red cell casts seen in
nephritic syndrome
3 examples of systemic vasculitises that cause glomerulonephropathy
- GPA (wergener’s granulomatosis)
- microscopic polyangiitis (MPA)
- eosinophilic granulomatosis with polyangiitis (churg-strauss)
what are the other names for cANCA and pANCA
cANCA= PR3
pANCA = MPO
what does ANCA stand for
Antineutrophilic cytoplasmic antibody
what ANCA is seen in GPA
cANCA
what ANCA is seen in MPA
pANCA
what is seen on renal biopsy in systemic vasculitis
crescents, pauci-immune
pauci etymology
latin for small/few
systemic vasculitis mgx
immunosuppression +/- plasma exchange
how does goodpasture’s disease present
- nephritic syndrome
- AKI
- pulmonary haemorrhage
goodpasture’s disease biopsy
crescents with linear antibody deposition
why must goodpasture’s disease be treated early and how
treat with immunosuppression +/- plasma exchange - organ damage happens very quickly so must be treated early
crescentic nephritis presentation
nephritic illness with rapidly deteriorating renal function
what conditions can preceed crescentic nephritis
many incl. goodpasture’s disease and systemic vasculitis
what does the cresentic nephritis renal biopsy show
acute inflammatory process with crescent formation (cellular proliferation in bowman’s spacce)
what is lupus nephritis
occurs when lupus autoantibodies affect parts of the kidneys that filter out waste
what test is vital in lupus nephritis
renal biopsy
lupus nephritis biopsy findings (6)
- endocapillary hypercellularity
- neutrophil infiltration/karyorrhexys
- fibrinoid necrosis
- hyaline deposits
- cellular/fibrocellular crescents
- interstitial inflammation
key inveStigations to consider in glomerular disease pt
- urine
- bloods
- imagine
- renal biopsy
what are “renal screen” blood test components
- autoantibodies (ANA, ANCA etc.)
- serum immunoglobulin and electrophoesis
- serum free light chains
- cryoglobulin levels
- blood cultures
- serology
