Renal pathology Flashcards by Beth T

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

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Layers of glomerulus

Fenestrated endothelium
GBM
Podocyte foot processes (epithelial)

(Sub-epithelial = between GBM and podocytes)

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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

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3 primary causes of nephrotic syndrome

Minimal change
Membranous glomerular
Focal segmental

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Most common cause of nephrotic syndrome in children

Minimal change disease

90% respond to steroids, 5% progress to RF

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Childhood nephrotic syndrome
T cells destroy podocytes
EM: Loss of foot processes
90% respond to steroids, 5% develop RF

Minimal change disease

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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

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Black people
Ig deposition and complement activation destroys podocytes + GBM
Focal scarring of GBM (glassy hyalinolysis)
50% get RF

Focal segmental

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Spike and dome GBM proliferation

Membranous glomerular

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Glassy hyalinolysis

Focal segmental

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Causes of membranous glomerular

Primary (85%) - anti-phospholipid antibodies

Secondary - AI (SLE), drugs, infections

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Nephritic vs. nephrotic

Both glomerular inflammation
Nephrotic - pores let protein through
Nephritic - pores let red cells through (+ a little protein but not as much)

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2 secondary causes of nephrotic syndrome

Diabetes (glucose injures - diabetic nephropathy)

Amyloidosis (amyloid deposits)

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Mesangial matrix ‘Kimmelstiel Wilson’ nodules

Asian

Diabetic nephropathy

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Congo red stain - polarised light - apple green birefringence

Amyloidosis

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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

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Coke coloured urine

Haemoglobinuria due to nephritic syndrome

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Azootemia

Raised urea and creatinine

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Red cell casts

Glomerulonephritis

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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

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Protein that forms red cell casts

Tamm-Horsefell protein

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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

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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

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Prognosis post-strep GN

Usually self limiting

25% adults progress to RPGN

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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?

1. IgG (Goodpasture's) 2. Complex (SLE, IgA nephropathy, post-strep) 3. 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?

1. Thin basement membrane disease 2. IgA nephropathy 'frank' 3. 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

1. Minimal mesangial (deposition, no change in structure) 2. Mesangial proliferation (deposition AND increased cellularity + inflammation) 3. Focal (active swelling of <50% glomeruli) 4. >50% glomeruli 5. Membranous (sub-epithelial deposition) 5. Advanced sclerosing (scarring of >90%)