Histo path - kidneys Flashcards
Immune complex deposition in glomerulus - what sites are there?
Mesangial - mild disease - mild haematuria and proteinuria
Sub-epithelial : meaning between podocyte and BM. Severe proteinuria, nephrotic syndrome
Sub-endothelial - Meaning between endothelium and BM. In contact with circulation and inflammatory cells, causing glomerular inflammation and structural damage. - More likely to be nephritic syndrome
What are the signs of direct tubular cell injury?
Necrosis, apoptosis, swelling
Clinical - nephrotoxic drugs and toxins or ischaemic
Why does acute tubular necrosis cause AKI?
Blocking of tubule by casts
Leakage into interstitium
Flow reduced
Presents with oliguria, with urine casts containing red and white blood cells. Due to inflammation of glomeruli
Glomerulonephritis
Mild-moderate necrosis of glomerular segments adjacent to crescents.
Immunofluorescense - lumpy bumpy IgG
Electron mic - Immune complex deposits as subepithelial humps or mesangial deposits, fibrin at glomerular basement membrane breaks.
Crescentic Glomerulonephritis (type 2) - 35%
immune complex mediated
E.g. SLE, IgA nephropathy, post-strep GN
Can see complexes with immunohistochemistry or electron microscopy - granular staining
Treat underlying disease, plasmapheresis of no use
Hypercellular glomeruli, crescents in > 50% glomeruli at time of biopsy, variable neutrophils, no / rare intracapillary cell proliferation and earliest lesion is focal segmental fibrinoid necrosis
Immunofluorescense - linear IgG
Electron mic - no deposits
Crescentic Glomerulonephritis (type 1) - 15%
Anti-GBM disease
Targeted at Type IV collagen in the GBM
Characteristic linear IgG deposition
Same antibodies may affect alveolar basement membrane and cause lung haemorrhage a.k.a. Goodpasture's Disease
Hypercellular glomeruli, crescents in > 50% glomeruli at time of biopsy, variable neutrophils, no / rare intracapillary cell proliferation and earliest lesion is focal segmental fibrinoid necrosis
Immunofluorescence - Ig negative
Electron mic - No deposits
Crescentic Glomerulonephritis (type 3) - 50%
Pauci-immune (i.e. very minimal immune component).
Associated with ANCA
Commonest cause of crescentic GN.
Antibodies cause neutrophil activation leading to glomerular necrosis.
Patients also have vasculitis in other organs e.g. skin rash, lung haemorrhage (Wegener's [GPA])
Had diarrhoea a few days ago, now in AKI
Haemolytic uraemic syndrome
e.coli toxin causes endothelial damage in the arterioles, which leads to a Thrombotic microangiopathy. Cause renal failure, haemolytic anaemia, fever and possibly neuro signs.
Shiga toxin
Histo: will see fibrin depositis
What the causes of nephrotic syndrome?
Systemic
Diabetes
SLE
Amyloid
Primary membranous disease
Minimal change disease Focal/Segmental glomerulosclerosis Membranous glomerulonephritis
Hyperfiltration, then kidney problems, Kimmelsteil-Wilson Nodules, thick BM
Diabetic Glomerulonephrosis
- Hyaline arterosclerosis in glomerular capillaries - causes efferent arteriole dilation, ↑flow - hyperfiltration
- Causes mesangial matrix expansion which is diffuse - may have Kimmelsteil-Wilson nodules in mesangium
- Causes thickening of BM, which stretches it and makes it more permeable, as podocytes are damanged.
Progressively gets worse
Deposition of protein that looks green with stained with congo red
Amyloidosis
AA
Derived from Serum Amyloid Associated protein (SAA)
SAA is an acute phase protein which is increased in chronic inflammatory conditions e.g. rheumatoid arthritis, chronic infections
AL
Amyloid Light: derived from immunoglobulin light chains
80% of these patients have Multiple Myeloma
Child, post infection, nephrotic syndrome.
Normal glomeruli, tubules have lipid droplets due to reabsorption of lipoproteins that leak from glomeruli (“lipoid nephrosis”)
Immunofluorescence - nothing
Electron mic - foot process effacement (retraction) in podocytes
Minimal change disease
Glomeruli look normal apart from podocyte damage to foot processes ("effacement of foot processes") - thought to be cytokine mediated
Commonest cause of nephrotic syndrome in children
Generally responds to immunosuppression i.e. prednisolone
Nephrotic syndrome
Fibrosis of mesangium and glomerulus
Immunofluorescence - nothing
Electron mic - Severe podocyte foot process effacement, occlusion of capillaries by endocapillary hypercellularity including foam cells, and hyaline deposits
Focal and segmental glomerulosclerosis
Again, only abnormality is sick podocytes Glomeruli develop progressive segmental scars Less likely to respond to immunosuppression
Adult, Nephrotic syndrome
Basement membrane ‘spikes’
Immuno - Granular diffuse peripheral deposits, usually IgG and C3, also C5b-C9 and occasionally IgM or IgA
Electron mic - Subepithelial deposition
Membranous Glomerulonephritis
ONLY affects the podocytes on the basement membrane, not the whole glomerulus, hence why we only see proteinuria, not urine casts etc. as in acute GN.
Primary:
Associated with antibodies to phospholipase A2 receptor
PLA2 receptor found on podocytes - important discovery
Secondary:
SLE
Infection (particularly hepatitis)
Drugs
Malignancy (against tumour antigens deposited in the kidney)
What is chronic renal failure?
Progressive, irreversible loss of renal function characterized by prolonged symptoms and
signs of uraemia (fatigue, itching, anorexia and if severe eventually confusion).
Commonest causes in the UK;
● Diabetes (19.5%)
● Glomerulonephritis (15.3%)
● Hypertension & Vascular disease (15%)
● Reflux nephropathy (chronic pyelonephritis) (9.5%)
● Polycystic kidney disease (9.4%)
