Renal pathology Flashcards
Renal pathology classification
According to part of nephron affected
Glomerulus - Nephritic, Nephrotic
Tubules + Interstitium - ATN, Tubulointerstitial, Pyelonephritis
Blood vessels - Thrombotic microangiopathy (TTP, HUS)
Whole kidney - AKI, CKD
Layers of glomerulus
Fenestrated endothelium
GBM
Podocyte foot processes (epithelial)
(Sub-epithelial = between GBM and podocytes)
Nephrotic syndrome
Damage to glomerulus = more permeable to large molecules (e.g. albumin)
1. Proteinuria (>3.5g/24h)
2. Hypoalbuminaemia
3. Oedema
4. Hyperlipidaemia
Swelling (adults peripheral, children face), frothy urine
3 primary causes of nephrotic syndrome
Minimal change
Membranous glomerular
Focal segmental
Most common cause of nephrotic syndrome in children
Minimal change disease
90% respond to steroids, 5% progress to RF
Childhood nephrotic syndrome
T cells destroy podocytes
EM: Loss of foot processes
90% respond to steroids, 5% develop RF
Minimal change disease
White people Ig deposition + complement activation destroys podocytes + GBM Entire length of GBM 'granular' Spike and dome GBM thickening Poor steroid response, 40% get RF
Membranous glomerular
Black people
Ig deposition and complement activation destroys podocytes + GBM
Focal scarring of GBM (glassy hyalinolysis)
50% get RF
Focal segmental
Spike and dome GBM proliferation
Membranous glomerular
Glassy hyalinolysis
Focal segmental
Causes of membranous glomerular
Primary (85%) - anti-phospholipid antibodies
Secondary - AI (SLE), drugs, infections
Nephritic vs. nephrotic
Both glomerular inflammation
Nephrotic - pores let protein through
Nephritic - pores let red cells through (+ a little protein but not as much)
2 secondary causes of nephrotic syndrome
Diabetes (glucose injures - diabetic nephropathy)
Amyloidosis (amyloid deposits)
Mesangial matrix ‘Kimmelstiel Wilson’ nodules
Asian
Diabetic nephropathy
Congo red stain - polarised light - apple green birefringence
Amyloidosis
What are the 6 features of nephritic syndrome?
PHAROH
- Proteinuria (less than nephrotic)
- Haemoglobinuria (coke-coloured urine)
- Azootemia (raised urine and creatinine on U+Es ~RF)
- Red cell casts (in urine)
- Oliguria
- HTN
Coke coloured urine
Haemoglobinuria due to nephritic syndrome
Azootemia
Raised urea and creatinine
Red cell casts
Glomerulonephritis
What is the pathogogenesis of nephritic syndrome?
Damage to glomerulus
Red cells pass + a little protein pass through
Body compensates by slowing GFR (causing oliguria and HTN)
Tamm-Horsefell secreted in DCT +CD stick RBCs together to form casts
Protein that forms red cell casts
Tamm-Horsefell protein
What are the 5 main causes of nephritic syndrome?
- Post-strep GN
- IgA nephropathy + HSP
- Rapidly progressive GN (crescentic)
- Hereditary (Alport’s)
- Thin basement membrane disease
1-3w post-strep throat (/6w post impetigo)
Group A haemolytic strep
Subepithelial IgG deposition + C3 activation
- LM: Hypercellular enlarged glomerulus
- EM: IgG deposit humps
- IF: Granular starry sky appearance along entire GBM
Raised ASOT titre + C3
Usually self-limiting, 25% progress to RPGN
Post-strep GN
Prognosis post-strep GN
Usually self limiting
25% adults progress to RPGN
1-2d after URTI
Mutated IgA (I) not cleared - accumulates in mesangium - alternative complement activation
Frank haematuria
Tx: Steroids stop IgA(I) mutation. Treat HTN
IgA nephropathy (aka Berger’s disease)
Treatment IgA nephropathy
Steroids stop IgA(I) mutation
What is the difference between IgA nephropathy and HSP?
Both involve IgA deposition in kidney, but IgA nephropathy is kidney specific, HSP is system wide
What is the difference in onset of post-strep GN and IgA nephropathy?
Post-strep appears 1-2w after strep throat
IgA appears 1-2d after URTI
What complement pathway is stimulated in IgA nephropathy?
Alternative
Really rapid glomerular damage due to many other causes (progressive from other causes)
Oliguria + azootemia (RENAL FAILURE basically)
Very aggressive
Crescents (crescent shaped scars)
3 types - IgG, complex or Pauci immune (ANCA) mediated (all cause inflammation)
Rapidly progressive GN
aka Crescentic GN
What are the three types of RPGN?
- IgG (Goodpasture’s)
- Complex (SLE, IgA nephropathy, post-strep)
- Pauci-immune (ANCA)
Crescents
Linear IgG along GBM
Pulmonary haemorrhage
Goodpasture’s
Crescents
Granular lumpy complexes along GBM
Complex RPGN (SLE, IgA nephropathy, post-strep)
Crescents
Vasculitis (cANCA / pANCA)
Scanty / no deposition along GBM
Pauci-immune RPGN (cANCA Wegeners, pANCA MPA
X-linked
Ineffective GBM due to alpha5 Type IV collagen mutation
Sensorineural deafness + eye problems
Hereditary nephritis
Aka Alport’s
TRIAD
Nephritic syndrome + eye problems + sensorineural deafness
Alport’s syndrome
AD
Diffuse GBM thinning due to alpha4 Type IV collagen mutation
Incidental microscopic haematuria
Quite common - ~5%
Thin basement membrane disease
aka benign familial haematuria
Incidental microscopic haematuria
Thin basement membrane disease
aka benign familial haematuria
What is the difference between Alport’s and thin basement membrane disease?
Alport’s is X linked, thin basement is AD
Alpha5 chain vs. alpha4 chain of type IV collagen
Incidental microscopic haematuria
Thin basement membrane disease
What are the 3 main causes of asymptomatic haematuria?
- Thin basement membrane disease
- IgA nephropathy ‘frank’
- Alport syndrome
Note that with these conditions asymptomatic haematuria is actually more common than nephritic syndrome features
What is ATN?
Damage to epithelial cells of renal tubule
Dead epithelial cells are shed to form muddy brown cell casts that clog up the nephron, raising nephron pressure
Reduces pressure gradient across glomerulus starting vicious cycle of reduced renal perfusion and kidney failure
Most common renal cause of AKI
Red cell casts
Nephritic syndrome
White cell casts
Pyelonephritis
Muddy brown casts
ATN
What are the two main causes of ATN?
Ischaemia - sepsis, burns (look for RF despite recovery)
Toxins - NSAIDs, gentamicin, contrast agents, heavy metals, myoglobin, rhabdomyolysis
Ischaemia or toxin injury
Muddy brown cell casts
Necrosis of short tubule
ATN
What is tubulointerstitial nephritis?
Inflammation of tubule lining epithelial cells or cells of interstitium between tubules
Renal failure days after drug exposure
Skin rash + EOSINOPHILS
Tubulointerstitial nephritis
Acute vs chronic pyelonephritis
Acute = inflammation resolves Chronic = inflammation can lead to scarring; infection superimposed on obstruction (e.g. stones) / reflux
What are the two renal thrombotic microangiopathies?
HUS
TTP
What are the 3 features of thrombotic microangiopathies?
MAHA
Thrombocytopenia
Renal failure
Mechanism of MAHA
Non-AI HA (DAAT negative)
Schistocytes
Fibrin mesh with platelet aggregation in small vessels, shears RBCs
Child
Renal specific
Classically diarrhoea associated (0157) - child petting zoo
Renal failure most common
HUS
Adult
Systemic
Not associated with diarrhoea
Neuro symptoms > renal symptoms
TTP
What are the 5 main functions of the kidneys?
Excrete waste
Regulate fluids, electrolytes, acid/base balance
Regulate BP (renin)
Regulate RBC production (EPO)
Regulate calcium and vitamin D (1alpha-hydroxylase)
Causes of AKI
Pre-renal (most common overall) - Renal hypoperfusion (burns, sepsis, RAS, acute pancreatitis)
Renal - ATN, GN, thrombotic microangiopathy
Post-renal - Obstruction (stones, tumours, BPH)
Most common renal cause of AKI
ATN
Causes of CKD
Diabetes GN HTN + vascular disease Chronic pyelonephritis Polycystic kidney disease
GFR values for kidney failure stages (1-5)
Stage 1: Damage normal function >90 Stage 2: Mildly impaired 60-89 Stage 3: Moderately impaired 30-59 Stage 4: Severely impaired 15-29 Stage 5: Complete (RRT needed) <15
Cysts + End stage renal failure
Berry aneurysms
Polycystic kidney disease
85% PKD1 mutation, 15% PKD2 mutation
Cysts replace renal tissue
Polygonal cells with very clear cytoplasm
Male smoker, used to work in chemical factory
Palpable mass in flank
Haematuria
Paraneoplastic syndrome
Varicocele (compressed left renal vein)
(Clear cell) renal carcinoma
Histology of RCC:
- Clear (75%)
- Papillary (15%)
- Chromophobic (5%)
- Polygonal cells with very clear cytoplasm
- Dialysis pts with cysts
- Pale eosinophilic cells
What are the 2 main causes of RCC?
Mutated VHL gene on chromosome 3 (RCC has 3 letters). This may be:
SPORADIC (male, chemical exposure, smoker - solitary upper kidney tumour) or SYNDROME (VHL disease - multiple tumours + eye, CNS tumours)
Mutated VHL gene chromosome
RCC
Paraneoplastic syndromes RCC
EPO (polycythaemia), renin (HTN), PTHrP (hypercalcaemia), ACTH (Cushings)
Poor prognostic factor in RCC
Invasion into renal vein (-> IVC spread)
6 stages of SLE nephritis
- Minimal mesangial (deposition, no change in structure)
- Mesangial proliferation (deposition AND increased cellularity + inflammation)
- Focal (active swelling of <50% glomeruli)
- > 50% glomeruli
- Membranous (sub-epithelial deposition)
- Advanced sclerosing (scarring of >90%)
