Histopathology 8 - Renal disease

Question 1

Which part of the nephron is impermeable to water?

Answer 1

Distal convuluted tubule

Question 2

What is a “horse shoe kidney”?

Answer 2

Congenital renal fusion

Question 3

What is the inheritance pattern of adult polycystic kidney disease?

Answer 3

Dominant

Question 4

What is the triad of symptoms/signs associated with adult PCKD?

Answer 4

Hypertension
Flank pain
Haematuria

Question 5

What are the genetic associations of PCKD?

Answer 5

PDK1 PDK2

Question 6

What is the most strongly associated aneurysm with PCKD?

Answer 6

Berry aneurysm → SAH

Question 7

In which patients are kidney cysts most likely to form?

Answer 7

End stage renal failure and on dialysis

Question 8

Which cancer does adult polycystic kidney disease increase the risk of ?

Answer 8

↑risk of cancer - papillary renal cell carcinoma (most common neoplasm)

Question 9

How can the causes of acute renal failure be classified?

Answer 9

Pre-renal/renal/post-renal

Question 10

What is the most common cause of acute renal failure?

Answer 10

Acute tubular injury

Question 11

How does acute tubular injury affect glomerular filtration?

Answer 11

Blockage of tubules by casts –> leakage into interstitial space –> secondary haemodynamic changes that affect GFR

Question 12

What is acute tubulo-interstitial nephritis, and what causes it?

Answer 12

Injury to tubules and interstitium that is usually immune but can also be caused by infection/drugs

Question 13

What is the most common cause of acute tubulo-interstitial nephritis?

Answer 13

Drugs

NSAIDs - inhibit vasodilatory prostaglandins

Antibiotics

Diuretics

Allopurinol

PPIs

Question 14

How does acute glomerulonephritis present?

Answer 14

Oligouria

Urine casts containing erthrocytes and leucocytes

Crescents present when it is bad enough to cause acute renal failure

Question 15

What is acute crescentic glomerulonephritis?

Answer 15

Immune mediated inflammation of glomerulonephritis with crescents as main histopathological finding

Includes:
Anti-GBM disease
Pauci-immune disease

Question 16

Which aetiologies might cause immune complex associated crescentic glomerulonephritis?

Answer 16

SLE
IgA nephropathy (adult HSP)
Post-infectious glomerulonephritis

Question 17

What is anti-GBM disease?

Answer 17

Rare and severe disease caused by Ig directed against the GBM - C-terminal domain of Type IV collagen

Question 18

What are anti-GBM antibodies directed against?

Answer 18

The C terminal domain of type IV collagen

Question 19

How can anti-GBM disease affect the lung?

Answer 19

Cross-reaction with alveolar basement membrane leading to pulmonary haemorrhage

Question 20

What are the features of Pauci-immune crescentic glomerulonephritis?

Answer 20

Only scanty glomerular Ig deposits

Usually ANCA (anti neutrophil cytoplasmic) associated

Vasculitis everywhere

Question 21

What on earth is thrombotic microangiopathy? (no seriously if someone works this out pls pm me)

Answer 21

Damage to endothelium in glomeruli, arterioles, arteries → thrombosis

Red cells may be damaged by fibrin (MAHA/HUS)

Question 22

What can thrombotic microangiopathy be caused by?

Answer 22

Diarrhoea associated -

Bacterial gut infection (E. coli) - Gastroenteritis

Toxins released target renal endothelium

Non diarrhoea associated -

Defects in regulation of complement

Deficiency in ADAMTS13

Drugs (calcineurin inhibitors; i.e. tacrolimus)

Radiation

Hypertension

Scleroderma

Antiphospholipid Antibody Syndrome (+/- SLE)

Question 23

What is nephrotic syndrome, and what are is its four diagnostic requirements?

Answer 23

Breakdown in selectivity of glomerular filtration barrier leading to protein leak

Proteinuria (>3.5g/day)

Hypoalbuminaemia

Oedema

Hyperlipidaemia

Question 24

Recall a pre-renal cause of acute renal failure

Answer 24

Failure of perfusion of kidney

Question 25

Recall 3 renal causes of acute renal failure

Answer 25

Acute tubular injury Acute glomerulonephritis Thrombotic microangiopathy

Question 26

How can acute renal failure be caused post-renally?

Answer 26

Obstruction

Question 27

How can trauma cause acute renal failure?

Answer 27

Release of myoglobin damages tubular epithelial cells, causing acute tubular injury (rhabodmyolysis)

Question 28

Which antibodies are present in pauci-immune acute crescentic glomerulonephritis?

Answer 28

Anti-neutrophil cytoplasm Ig

Question 29

How can immune complexes in the glomerulus be identified?

Answer 29

Immunohistochemistry Electron microscopy

Question 30

Which syndromes are associated with Pauci-immune Crescentic Glomerulonephritis?

Answer 30

Wegener's Churg Strauss Microscopic polyangiopathy

Question 31

Which kidney disease is associated with E coli diarrhoea?

Answer 31

Thrombotic microangiopathy

Question 32

Recall 2 examples of non-immune complex related, primary nephrotic syndrome

Answer 32

Minimal change disease Focal segmental glomerulosclerosis

Question 33

Recall an example of a primary cause of nephrotic syndrome that is immune mediated?

Answer 33

Membranous glomerulonephritis

Question 34

Recall 3 systemic diseases that can cause nephrotic syndrome

Answer 34

Diabetes mellitus Amyloidosis SLE

Question 35

In minimal change glomerulonephritis, how do glomeruli appear under electron microscopy?

Answer 35

Effacement of foot processes

Question 36

What is a common cause of the nephrotic syndrome in children?

Answer 36

Minimal change disease

Question 37

What treatment does minimal change glomerulonephritis usually respond to?

Answer 37

Immunosuppression

Question 38

Does focal segmental glomerulonephritis produce the nephrotic or nephritic syndrome?

Answer 38

Nephrotic

Question 39

Does focal segmental glomerulosclerosis respond to immunosuppression?

Answer 39

Some glomeruli are partially scarred + thickened GBM Less likely to respond to immunosuppression

Question 40

What is the broad pathophysiology of primary membranous glomerulonephritis?

Answer 40

immune deposits on outside of GBM + thickening of BM (subepithelial)

Question 41

What age group does membranous glomerulonephritis usually affect?

Answer 41

Adults

Question 42

What are some secondary causes of membranous glomerulonephritis?

Answer 42

Epithelial malignancy Drugs Infections SLE

Question 43

What is the most common cause of membranous glomerulonephritis?

Answer 43

75% are immune Antipody against phospholipase A2 receptor

Question 44

Does diabetic nephropathy cause nephrotic or nephritic syndrome?

Answer 44

Nephrotic causes nodular glomerular sclerosis

Question 45

What is amyloidosis?

Answer 45

Deposition of extracellular proteinaceous material exhibiting β-sheet structure

Question 46

What stain is used to detect amyloidosis?

Answer 46

salmon pink WO staining Congo red (--\> apple green birefringeance under polarised light)

Question 47

What are the two forms of amyloidosis and which proteins are they derived from?

Answer 47

**AA Amyloidosis** Derived from serum amyloid associated protein (SAA) – acute phase protein **AL Amyloidosis** Derived from Ig light chains (MM)

Question 48

What are the causes of microscopic haematuria

Answer 48

thin basement membrane IgA nephropathy

Question 49

What is the inheritance pattern of Alport's syndrome?

Answer 49

X-linked dominant Affects alpha 5 subunit

Question 50

What are the symptoms of Alport's syndrome?

Answer 50

Renal failure in middle age Deafness Ocular disease

Question 51

What is the most common form of glomerulonephritis?

Answer 51

IgA nephropathy Secondary forms observed in liver, bowel and skin disease small-vessel vasculitis (HSP)

Question 52

What socring system is used to score IgA renal disease?

Answer 52

Oxford classification

Question 53

What eGFR is indicative of end-stage renal failure?

Answer 53

\<15

Question 54

What is the most common cause of chronic renal failure?

Answer 54

Diabetes

Question 55

What kidney disease is characterised by shrunken kidneys with granular cortices?

Answer 55

Hypertensive nephropathy

Question 56

What might histopathology show in hypertensive nephropathy?

Answer 56

Nephrosclerosis/fibrinoid necrosis: Arteriolar hyalinosis Arterial intimal thickening Ischaemic glomerular changes Segmental glomerulosclerosis Global glomerulosclerosis

Question 57

What is the commonest cause of kidney failure requiring renal replacement therapy?

Answer 57

Diabetes

Question 58

How does SLE affect the kidney?

Answer 58

Anti-nuclear anti-dsDNA Ig directed against a broad range of intracellular and extracellular antigens

Question 59

Does SLE cause the nephrotic or nephritic syndrome?

Answer 59

Nephrotic

Question 60

What would be the histological appearance of acute tubulo-interstitial nephritis?

Answer 60

Eosinophils and granulomas

Question 61

What is the usual cause of non-diarrhoea-associated thrombotic microangiopathy?

Answer 61

ADAMT313 deficiency (eg scleroderma and anti-phospholipid syndrome)

Question 62

Describe each stage of diabetic nephropathy

Answer 62

Stage 1: Basement Membrane thickening Stage 2: Mesangial matrix expansion Stage 3: Nodular lesions (Kimmelstiel-Wilson) Stage 4: Advanced glomerulosclerosis

Question 63

How is IgA nephropathy graded?

Answer 63

Oxford classification (MEST-C)

Question 64

What is reabsorbed at the proximal convoluted tubule?

Answer 64

actively resorbs sodium ## Footnote H+ exchange to allow carbonate resorption (acid-base control) Co-transport of amino acids, phosphate, glucose Potassium also reabsorbed

Question 65

What is reabsorbed at the loop of Henle?

Answer 65

Descending / thin ascending limb permeable to H20 - not ions or urea Ascending - actively resorbs sodium and chloride Countercurrent Multiplier (aligned with vasa recta)

Question 66

What is the role of the distal convoluted tubule?

Answer 66

* Regulates pH via active transport (proton / bicarbonate) * Regulates Na+, K+ via active transport (aldosterone) * Aldosterone = MR agonist * Creates ENaC + K excretion through ROMK * Regulates Ca (PTH, 1,25 dihydroxycholecalciferol)

Question 67

What is the role of the collecting duct ?

Answer 67

Resorbs water (principal cells, antidiuretic hormone) Regulates pH (intercalated cells, proton excretion)

Question 68

What stain can be used in Goodpasture's disease?

Answer 68

Silver stain: crescent morphology

Question 69

Recall the triad of nephrotic syndrome

Answer 69

Proteinuria (\>3.5g/day) Hypoalbuminemia (\<25g/L) Oedema + Hyperlipidaemia

Question 70

What is the classification pattern of SLE?

Answer 70

ISN/RPS Classification (Simplified)