Histopathology 8 - Renal disease Flashcards
Which part of the nephron is impermeable to water?
Distal convuluted tubule
What is a “horse shoe kidney”?
Congenital renal fusion
What is the inheritance pattern of adult polycystic kidney disease?
Dominant
What is the triad of symptoms/signs associated with adult PCKD?
Hypertension
Flank pain
Haematuria
What are the genetic associations of PCKD?
PDK1 PDK2
implicated protein: polycystin 1 and polycystin 2
What is the most strongly associated aneurysm with PCKD?
Berry aneurysm
In which patients are kidney cysts most likely to form?
End stage renal failure and on dialysis
How can the causes of acute renal failure be classified?
Pre-renal/renal/post-renal
What is the most common cause of acute renal failure?
Acute tubular injury
How does acute tubular injury affect glomerular filtration?
Blockage of tubules by casts –> leakage into interstitial space –> secondary haemodynamic changes that affect GFR
What is acute tubulo-interstitial nephritis, and what causes it?
Injury to tubules and interstitium that is usually immune but can also be caused by infection/drugs
these drugs can include NSAIDS and antibiotics
What is the most common cause of acute tubulo-interstitial nephritis?
Drugs (especially NSAIDs)
How does acute glomerulonephritis present?
Oligouria
Urine casts containing erthrocytes and leucocytes
Crescents present when it is bad enough to cause acute renal failure
What is acute crescentic glomerulonephritis?
Immune mediated inflammation of glomerulonephritis with crescents as main histopathological finding
Includes:
Anti-GBM disease
Pauci-immune disease
Which aetiologies might cause immune complex associated crescentic glomerulonephritis?
SLE
IgA nephropathy
Post-infectious glomerulonephritis
What is anti-GBM disease?
Rare and severe disease caused by Ig directed against the GBM
How can anti-GBM disease affect the lung?
Cross-reaction with alveolar basement membrane leading to pulmonary haemorrhage
What are the features of Pauci-immune crescentic glomerulonephritis?
Only scanty glomerular Ig deposits
Usually ANCA associated
Vasculitis everywhere
What on earth is thrombotic microangiopathy? (no seriously if someone works this out pls pm me)
Damage to endothelium in glomeruli, arterioles and arteries leading to thrombosis??
*HUS, TTP, DIC
What is nephrotic syndrome, and what are is its four diagnostic requirements?
Breakdown in selectivity of glomerular filtration barrier leading to protein leak
Proteinuria (>3.5g/day)
Hypoalbuminaemia
Oedema
Hyperlipidaemia
Recall a pre-renal cause of acute renal failure
Failure of perfusion of kidney
Recall 3 renal causes of acute renal failure
Acute tubular injury
Acute glomerulonephritis
Thrombotic microangiopathy
How can acute renal failure be caused post-renally?
Obstruction
How can trauma cause acute renal failure?
Release of myoglobin damages tubular epithelial cells, causing acute tubular injury (rhabodmyolysis)
Which antibodies are present in pauci-immune acute crescentic glomerulonephritis?
Anti-neutrophil cytoplasm Ig
How can immune complexes in the glomerulus be identified?
Immunohistochemistry
Electron microscopy
Which syndromes are associated with Pauci-immune Crescentic Glomerulonephritis?
Wegener’s
Churg Strauss
Microscopic polyangiopathy
Which kidney disease is associated with E coli diarrhoea?
Thrombotic microangiopathy
Recall 2 examples of non-immune complex related, primary nephrotic syndrome
Minimal change disease
Focal segmental glomerulosclerosis
Recall an example of a primary cause of nephrotic syndrome that is immune mediated?
Membranous glomerulonephritis
Recall 3 systemic diseases that can cause nephrotic syndrome
Diabetes mellitus
Amyloidosis
SLE
In minimal change glomerulonephritis, how do glomeruli appear under electron microscopy?
Effacement of foot processes
What is a common cause of the nephrotic syndrome in children?
Minimal change disease
What treatment does minimal change glomerulonephritis usually respond to?
Immunosuppression
Does focal segmental glomerulonephritis produce the nephrotic or nephritic syndrome?
Nephrotic
What is the broad pathophysiology of primary membranous glomerulonephritis?
Description of membraneous glomerulonephritis?
Immune complex related
Immune deposits are subepithelial, outside GBM
Description: spikey subepithelial deposits
What age group does membranous glomerulonephritis usually affect?
Adults
What is the most common cause of membranous glomerulonephritis?
75% are immune
Antipody against phospholipase A2 receptor
Does diabetic nephropathy cause nephrotic or nephritic syndrome?
Nephrotic
What is amyloidosis?
Deposition of extracellular proteinaceous material exhibiting β-sheet structure
What is the inheritance pattern of Alport’s syndrome?
X-linked dominant
Affects alpha 5 subunit
What are the symptoms of Alport’s syndrome?
Renal failure in middle age
Deafness
Ocular disease
What is the most common form of glomerulonephritis worldwide?
IgA nephropathy
What eGFR is indicative of end-stage renal failure?
<15
What is the most common cause of chronic renal failure?
Diabetes
What are anti-GBM antibodies directed against?
The C terminal domain of type IV collagen
What kidney disease is characterised by shrunken kidneys with granular cortices?
Hypertensive nephropathy
What stain is used to detect amyloidosis?
Congo red (–> apple green birefringeance)
What socring system is used to score IgA renal disease?
Oxford classification
What might histopathology show in hypertensive nephropathy?
Nephrosclerosis
What is the commonest cause of kidney failure requiring renal replacement therapy?
Diabetes
How does SLE affect the kidney?
Anti-nuclear anti-dsDNA Ig directed against a broad range of intracellular and extracellular antigens
What would be the histological appearance of acute tubulo-interstitial nephritis?
Eosinophils and granulomas
also white cell casts
What is the usual cause of non-diarrhoea-associated thrombotic microangiopathy?
ADAMTS13 deficiency (eg scleroderma and anti-phospholipid syndrome)
Describe each stage of diabetic nephropathy
Stage 1: Basement Membrane thickening
Stage 2: Mesangial matrix expansion
Stage 3: Nodular lesions (Kimmelstiel-Wilson)
Stage 4: Advanced glomerulosclerosis
How is IgA nephropathy graded?
Oxford classification (MEST-C)
What two properties does the filtration barrier created by the podocytes depend on?
Charge dependent and size dependent
Role of the PCT
Actively resorbs sodium
Carries out hydrogen exchange to allow carbonate resorption
Co-transport of amino acids, PO4 and glucose
Reabsorption of potassium
Role of the LoH
- The descending and thin ascending limb is permeable to water
- but NOT ions or urea
- The ascending limb actively reabsorbs sodium and chloride
- This creates a counter-current multiplier that is aligned with the vasa recta
- vasa recta= straight arterioles, and the straight venules of the kidney
**basc point is to concentrate the urine
Role of DCT
- Impermeable to water
- Regulates pH by active transport of proteins and bicarbonate
- Regulates sodium and potassium by active transport (aldosterone regulated)
- Regulates calcium (PTH, 1,25-dihydroxy vitamin D)
Role of the collecting duct
Aldosterone acts on these cells → Na retention and K excretion
Reabsorbs water (principle cells, ADH)
Regulates pH (intercalated cells, proton excretion)
What is the renal corpuscle?
Consists of the glomerulus and bowman’s capsule
Membranous glomerulonephritis histology
Treatment of membranous glomerulonephritis?
- IgG deposits with C3
- In sub-epithelial area
**NB- this is immune complex mediated unlike minimal change disease and focal segmental glomerulosclerosis
Treatment: canot be treated with steroids unlike minimal change disease; treated with antihypertensives
What protein is deficient in adult polycystic kidney disease?
polycystin-1
Complications of adult PKD
- subarachnoid haemorrhage (berry aneurysms)
- 10% mortality from renal failure
Which cancer do renal cysts increase the risk of?
Papillary renal cell cancer
Definition of AKI
Increase in SCr by ≥0.3mg/dL w/in 48h
Increase in SCr ≥ 1.5 x baseline w/in last week
Urine volume < 0.5 ml/kg/h for 6h
Drugs that affect glomerular blood flow (and therefore predispose to pre-renal AKI)

ATN histology
necrosis of short segments of tubules
Epithelial cell casts
(epithelial cells lining the tubules die and then block off the actual lumen of the tubule
What intrinsic renal failure can pre-renal AKI lead to?
Can eventually lead to ATN if damage is sufficient
Most common cause of AKI
Acute tubular necrosis
**intrinsic renal failure**
Histology of HUS
Fibrinoid necrosis
*because you get fibrin strand deposition which leads to MAHA*
Which form of glomeruloneprhitis is a medical emergency?
Crescentic
Causes of crescentic glomerulonephritis
- Immune complex associated
- SLE
- IgA nephropathy
- post-infectious glomerulonephritis
- Anti-GBM disease
- Pauci-immune (pauci = not much)
- ANCA mediated eg Wegener’s (c-ANCA) (WC)

What cells are seen on biopsy in goodpasture’s disease?
Crescent cells
Histology of acute tubulointerstitial nephritis
heavy interstitial inflammatory infiltrate with tubular injury:
Eosinophils
Granulomas
How does rhabdomyololysis cause AKI? Tx
Myoglobin causes acute tubular necrosis
Treatment: fluids to wash out the myoglobin
3 common causes of nephrotic syndrome
Primary glomerular causes (non-immune complex mediated)
- Miminal change disease
- focal segmental glomerulosclerosis - same changes on electron microscopy as minimal change disease (loss of podocyte foot processes) but on light microscopy you see FOCAL AND SEGMENTAL SCARRING
Primary (immune complex mediated)
Membranous glomeurlonephritis
Systemic diseases
- diabetic nephropathy
- Amyloidosis
- SLE

Minimal change disease: light and electron microscopy
Light microscopy: no change
Electron microscopy: effacement of podocytes
IgA nephropathy findings
main clinical feature: frank haematuria

PSGN
histology findings
- Light microscope (LM): ↑cellularity of glomeruli
- Fluorescence Microscope (FM):
- granular deposits of IgG and C3 in GBM
- Electron Microscope (EM):
- Subendothelial humps

Membranoproliferative glomerulonephritis hsitology
- mesangial cell proliferation
- and capillary thickening
What are two hereditary causes of microscopic haematuria?
Alport’s syndrome
Thin basement membrane disease - usually get microscopuc haematuria unlike frank haematuria in IgA nephropathy

Classification+ description of lupus nephritis
Renal Histology: immune complex deposition in capillaries à ‘wire loop capillaries’, deposition of immune complexes & complement I the GBM in a lumpy-bumpy granular fashion

Histology of diabetes causing nephrotic sydnrome
Diffuse glomerular basmenet membrane thickening
Mesangial matrix nodules- aka Kimmelstiel Wilson nodules
Histology of acute pyelonephritis
leucocytic casts
Histology of acute interstitial nephritis
Histology: inflammatory infiltrate with tubular injury, eosinophils & granulomas
HUS vs TTP

Commonest causes of chronic renal failure in the UK
Diabetes (19.5%) ● Glomerulonephritis (15.3%) ● Hypertension & Vascular disease (15%) ● Reflux nephropathy (chronic pyelonephritis) (9.5%) ● Polycystic kidney disease (9.4%)
3 types of renal cell carcinoma
Clear cell carcinoma – well differentiated
● Papillary carcinoma – commonest in dialysis-associated cystic disease
● Chromophobe renal carcinoma – pale, eosinophilic cells
What is alport syndrome?
Inheritance pattern?
nephritic syndrome, cataracts and sensorineural deafness suggests what underyling diagnosis?
x linked dominant
Classification of nephritic and nephrotic syndromes

Which protein is responsible for dark urine in rhabdomyololysis?
myoglobin