Introduction to renal pathology Flashcards
What structure should you want to include in a renal biopsy?
Glomeruli
What is the gold standard for diagnosis of glomerular disease?
Renal biopsy
What bedside investigations are done for suspected glomerulonephritis?
Urine dip
Urine albumin: creatinine ratio
Obs -> esp BP (high)
What bloods should be done in a suspected glomerulonephritis?
FBCs, U&Es, LFTs, bone panel, CRP
Lipid profile, Coagulation, HbA1c
What imagging should be done for suspected glomerulonephritis?
Ultrasound - size and morphology
CXR - fibrosis, pulmonary haemorrhage
What specialised investigations may be done for suspected glomerulonephritis?
Hep B, Hep C, HIV
ANCAs
Anti-GBM antibodies
ANAs
Anti-dsDNA antibodies
Complement screen
Immunoglobulins
Anti-PLA2R antibodies
Myeloma screen (serum free light chains, serum/urine electrophoresis)
What are the key histological features of this healthy glomerulus?
Mesangial cells
Capillary loop
Afferent arteriole
Bowmans capsule
What are the three layers of the glomerular filtration barrier?
Fenestrated endothelium
Basement membrane
Visceral epithelial cells (podocytes) - foot processes
What does the glomerular filtration barrier look like under an electron microscope?
What is the difference between a focal and diffuse disease of the glomeruli?
Focal - only some glomeruli
Diffuse - all glomeruli
What is the difference between a segmental vs a global disease of the glomeruli?
Segment - only fraction of the glomerulus
Global - the whole of the glomerus
Does not relate to the number of glomeruli affected
What is the key clinical syndrome of nephrotic syndrome?
Proteinuria 3-3.5g or more per day
Hypoalbuminemia - plasma albumin less than 35g/L
Generalized oedema
Hyperlipidemia and lipiduria
What are the key presentation features of nephrotic syndrome?
Periorbital/facial oedema
Hypertension
Proteinuria
Peripheral pitting oedema
Genital/sacral oedema
Ascites
Pleural effusion
What are the key features of nephrotic syndrome on urine dip?
Protein 2-3+
usually no blood
What are the key features of nephritic syndrome on urine dip?
Blood +
Protein +
What is the most common cause of nephrotic syndrome in children?
Minimal change disease
What are the difference causes of nephrotic syndrome in children?
Minimal change disease - 75%
Focal segmental glomerulosclerosis - 10%
Membranous nephropathy - 3%
IgA nephropathy - 2%
What is the most common cause of nephrotic syndrome in adults?
Focal segmental glomerulosclerosis - 35%
Membranous nephropathy - 30%
What are the key secondary causes of nephrotic syndrome?
Diabetes mellitus
Amyloidosis
What are all potential secondary causes of nephrotic syndrome?
DM
Amyloidosis
SLE
Drugs - NSAIDS, penicillamine, heroin
Infections - malaria, syphilis, hep B/C, HIV
Malignant disease -carcioma, lymphoma
Miscellaneous (bee-sting, herediatry)
What are the key pathological features of minimal change disease?
Primary disorder of the podocytes
Normal under-light microscopy
Immunofluorescence negative
Electron microscopy - effacement (dec height and wider width) fusion of the podocyte foot processes
Patient presents with neprhotic syndrome, this is the change in electron microscopy - what pathology is shown on the right?
Flattened and effacement of podocyte foot processes - looks more like a grey blob surrounding
Shows minimal change disease
What is the key treatment and prognosis for minimal change disease?
Corticosteroid therapy
>90% respond rapidly to treatment
What is the key pathology of Focal segmental glomerulosclerosis?
Podocytopathy
Sclerosis of some glomeruli - affecting only portion of capillary tuft
Immunofluorescent negative
Light micscrope - picks up collagenous sclerosis.
What type of biospy (where in the kidney) is needed to ensure Focal glomerulosclerosis is not missed?
Cortico-medullary junction sampling
What are the different causes of focal segmental glomerulosclerosis?
Primary/idiopathic
Secondary to HIV or adpative (compensatory hypertrophy of remaining tissue due to loss of renal tissue)
What is the typical management of FSGS?
Variable response to corticosteroids
Children better prognosis that adults
50% will develop end stage renal disease within 10yrs
20% within 2years
May recur in renal transplant
What are the key pathology of membranous nephropathy?
Immune mediated - antigen antibody complexes - typically subepithelial
Diffuse process
Complement C5b-C9 membrane attack complex injures glomeruli epithelial and mesangial cells
Release proteases and oxidants
Capillary wall injury
Increased protein leakage
What is the key antigen inovled in primary membranous nephropathy?
This causes 75% of cases
M type phospholipase A2 receptor (PLA2R) on epithelial/podocyte cells
What are the causes of secondary membranous nephropathy?
Drugs - penicillamin, captopril, NSAIDs
Underlying malignancy - lung, colon, melanoma
SLE
Infections - chronic Hep B, hep C, syphilis, schistosomiasis malaria
What does membranous nephropathy look like on light microscopy?
Capillary loops are diffusely thickened and prominent
Cellularity is not changed
Silver stain - spikes - BM deposition between immune complexes
What does membranous nephropathy look like on immunofluorescence?
Immunofluorescence positive
Granular IgG deposition - along glomerular capillary loops.
What does membranous glomerulopathy look like on electron microscopy?
Thickened basement membrane due to interleaved immune complex deposition
Looks like snake
How does the location of immune complex deposition relate to the disease?
Subepithelial -> acute glomerulonephritis
Membranous deposits -? membranous
Subendothelial -> Lupus nephritis
What is the typical treatment for membranous nephrotic syndrome?
Low risk - conservative (watch and wait)
High risk - in heavy proteinuria/declining renal function - immunosuppression such as steroids, cyclophosphamide, rituximab
What are the key pathological features of DM causing nephrotic syndrome?
Microvascular injury -> of the glomerular capillaries
If marked proteinuria and retinopathy -> most likely diabetic nephropathy
Significantly increased morbidity associated with cardiovascular complications
What are the key features of diabetic nephropathy on biopsy?
Initial diffuse glomerulosclerosis - increased mesangial matrix
Later nodule formation -> called Kimmelstiel-Wilson lesions (N) -> these are dense deposits with rim of cells around nodules
Thickened capillaries
What is the treatment for diabetic nephropathy?
SGLT2 inhibitors - dapagliflozin
ACEi
Supportive - statins
What are the key features of nephrotic syndrome secondary to amyloidosis on a light microscopy?
Pink deposits of amyloid in/around artieres, interstitium or glomeruli
Note - unlike DM are NOT rimmed by cells
What is the pathology of nephrotic syndrome secondary to amyloidosis?
Extracellular deposition of protein fibrils with a characteristic Beta -pleated sheet confirmation
primary - light chains - plasma cell
secondary -AA - due to systemic chronic inflammatory conditions
What special stain can be used to identify amyloidosis in the glomeruli?
What does this look like?
Congo red stain - deep red colour
Can also be viewed under polarised light showing apple green refringence
What are the clinical features of nephritic syndrome?
Microscopic hematuria (rbcs and casts)
Subnephrotic proteinuria with or without oedema
Decline in kidney function
Hypertension
What are the three main categories of nephritic syndrome?
Immune mediated GN (proliferative)
Pauci-immune GN
Anti-GBM
What are the different types of immune mediated nephritic syndrome?
IgA nephropathy
SLE
Post-infectious
Membranoproliferative glomerulonephritis (MPGN)
What are the difference types of Pauci-immune glomerulonephritis?
ANCA associated microscopic vasculitis (wegners, Churg-strauss)
How does lupus relate to nephrotic and nephritis syndrome?
Stage 5 lupus = cause nephrotic syndrome
All other stages are nephritis
What are the key features of rapidly progressive glomerulonephritis as a cause of nephritic syndrome?
Rapid deterioation in renal function
Oliguria and nephritic -> death from renal failure within weeks to months
Severe glomerular injury
What is the appearance of rapidly progressive glomerulonephritis on light microscopy?
Crescentic
What are the different causes of cresenteric glomerulonephritis?
SLE
IgA nephropathy
Post infectious
ANCA associated microscopic vasculitis
Anti-GBM disease
What are the key pathological features of anti_GBM disease?
Anti-body mediated nephritis against fixed glomerular antigens
Most common in males 20-40yrs
Presents with rapidly progressive glomerulonephritis and pulmonary haemorrhage (good pasture syndrome)
What glomerular antigens are targeted in Anti-GBM disease?
alpha 3 chain of type 4 collagen in GBM
Also found in the lungs
What are the features of anti-GBM on light microscopy?
Segmental necrotizing lesions with capillary rupture
Crescents
What does anti-GBM disease look like on fluorescence?
Crushed ribbon - linear fluorescence along the glomerular basement membrane
