Renal pathology Flashcards
What are the different terminologies for glomerular lesions?
FOCAL - less than 50% all gloms involved
DIFFUSE - more than all 50%
SEGMENTAL - less than 50% of individual glom involved
GLOBAL - more than 50% of individual glom involved
What are the different presentations of glomerular lesions?
acute renal failure/impairment chronic renal failure/impairment asymptomatic haematuria asymptomatic proteinuria nephrotic syndrome
What are the different types of glomerular diseases?
primary secondary to systemic disorder - hypertension - DM - SLE - Vasculitis - Amyloidosis (abnormal protein deposited)
What is the pathogenesis of glomerular disorders?
usually immune mediated
- 1) antibody against a constituent of the glom e.g. antiGBM disease - goodpastures
- 2) antibody against something that has been deposited in the glom
- 3) deposition of a circulating Ag-Ab immune complex
Glomerular disorders produce an inflammatory response. What does this result in?
1) complement activation
2) neutrophil accumulation
3) other inflammatory cells e.g. macrophages and lymphocytes
4) activation of mesangial cells
5) platelet thrombi
6) activation of coagulation cascade
OVERALL
- accumulation of cells and release of substances which promote further accumulation and proliferation of cells
- tissue damage caused by these cells and complement
decreased GFR=> tubular injury
production of ECM=> sclerosis / obliteration of glom
What histological changes occur in glomerular disorders?
hypercellularity
- proliferation of mesangial, endothelial +/- epithelial cells
- leucocyte infiltration
- formation of crescents = accumulation of cells in bowman’s space
basement membrane thickening
- accumulation of immune complexes - usual
- other things = amyloid, fibrin and cryoglobulins
hyalinisation and sclerosis
What are the clinical features of acute glomerulonephritis?
haematuria, increased Cr and urea, oligouria +/- proteinuria
inflammatory alteration in glomeruli
What are the causes of acute glomerulonephritis?
1) postinfectious GN
- children most often following streptococcal infection
- anti-streptococcal antibodies
- 95% children recover (adults worse prognosis)
2) necrotising/crescentic GN
- 1) anti-GBM
- 2) immune complex mediated
- 3) ANCA associated often associated with a systemic vasculitis
- poor prognosis: most patients eventually require dialysis
What are the clinical features and causes of nephrotic syndrome?
massive proteinuria =>oedema hyperlipidaemia causes: - membranous nephropathy - minimal change disease - FSGS
What is membranous nephropathy?
most common cause of nephrotic syndrome in adults
diffuse thickening of GBMs
subepithelial immune complex deposition
85% idiopathic - majority = autoimmune
- anti-PLA2R antibodies
secondary - drugs, malignancy, infections, metabolic disorders
What is minimal change disease?
most common in children 2-6 yrs old
normal glomeruli on light microscopy
EM fusion of epithelial foot processes=> proteinuria
follows respiratory tract infection
responds to steroids
occurs in adults related to lymphomas and leukaemias and NSAIDs
What is FSGS?
Focal segmental glomerular sclerosis - less common
- occurs in 10-15% adults and children
poor response to steroids
many progress to chronic renal failure
most common primary glomerular disease =>ESRF
caused by podocyte depletion
- loss of 20-40%=> mild proteinuria
- loss of >40% => full blown FSGS
What is podocytopathy?
abnormalities in podocytes
- caused by abnormalities in:
- podocyte transcription factors
- actin cytoskeleton
- slit diaphragm
- adhesion molecules by podocyte and GBM
Which ethnicity is FSGS more common in?
Africans - have the APOL1 gene - protects them against trypanosomiasis (worm infection)
What circulating factor can damage podocytes?
suPAR = soluble urokinase plasminogen activator receptor
