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
What happens in IgA nephropathy?
causes haematuria
- deposits IgA into mesangium
What happens in Alports syndrome?
familial accompanied by nerve deafness and eye disorders
haematuria
defective GBM synthesis - mutation in genes for collagen
EM - variable thickening and thinning of GBM with splits
often goes onto renal failure
What happens in thin glomerular basement membrane disease?
causes haematuria
- histologically normal glomeruli
- EM - marked thinning of GBM
What are the main features of chronic glomerulonephritis?
end stage of acute glomerulonephritis
chronic renal failure
small symmetrical kidneys - fairly uniform abnormality in glomeruli throughout
diffuse granular surface
What happens in diabetic nephropathy?
leading cause of chronic renal failure
thickening of GBMs
mesangial increase +/- nodule(kimmelstiel-wilson nodules)
What are the features of amyloidosis?
abnormal proteinaceous material deposited in tissues
congo red positive + birefringence under polarised light
primary = light chains=> multiple myeloma
secondary = chronic disease e.g. TB, CD (secondary to chronic disease)- less common
What is systemic lupus erythematosus?
autoimmune disease
many different histological patterns of glomerular involvement
mesangial increase
necrosis segmental or global, diffuse or focal
membranous protein => can give nephrotic syndrome
involves deposition of all immunoproteins (IgG,M,A and complement)
What does hypertension cause in relation to the kidneys?
affects arteries and arterioles
intimal thickening with narrowing of the lumen
hyalinosis of arterioles
leads to ischaemic changes in the kidney
- glomerular sclerosis
- tubular atrophy
- intersitial fibrosis
What are some diseases of the tubules and interstitium?
acute pyelonephritis chronic pyelonephritis reflux nephropathy acute interstitial nephritis acute tubular necrosis myeloma kidney
