Week 17 Pathology - Renal

Question 1

How can you broadly classify glomerular disease?

Answer 1

Primary vs secondary

Question 2

What are the primary causes of glomerular disease?

Answer 2

1. Minimal change
2. Focal segmental glomerulosclerosis
3. Membranous nephropathy
4. Acute post infective GN
5. Membranoproliferative GN
6. IgA Nephropathy

Question 3

Which of the primary causes of glomerular disorders are nephritic syndromes?

Answer 3

Acute post infective GN
IgA Nephropathy

Question 4

What are some secondary causes of GN?

Answer 4

SLE
Diabetic nephropathy
Amyloidosis
Goodpasture/Anti-GBM
Henoch-Schonlein Purpura
Endocarditis mediated GN

Question 5

Define nephrotic syndrome:

Answer 5

1. Massive proteinuria: >3.5g/day
2. Hypoalbuminaemia
3. Generalised oedema
4. Hyperlipidaemia and lipiduria

Question 6

What is the pathophysiology of nephrotic syndrome?

Answer 6

Derangement in capillary walls of the glomeruli via podocyte damage, leading to increased permeability to plasma protein

Question 7

Define nephritic syndrome:

Answer 7

1. Haematuria (dysmorphic red cells and casts in urine)
2. Oliguria + azotaemia
3. Hypertension
4. Proteinuria and oedema (to a lesser extent than nephrotic syndrome

Question 8

With intrinsic renal disease, what are the two major types?

Answer 8

Glomerular
Tubular

Question 9

How can the pattern of antibody deposition help distinguish the likely source of glomerular injury?

Answer 9

Granular deposition = formed by immune complexes either in situ or from circulation

Linear deposition = likely basement membrane auto-antibodies

Question 10

What does the umbrella term ‘Acute tubular injury’ refer to?

Answer 10

Morphologically damaged tubular epithelial cells and biochemically acute decline of renal function, with granular casts and tubular cells in the urine

Question 11

What are the causes of ATI?

Answer 11

RPGN
Acute drug induced allergic interstitial nephritis
Ischaemia secondary to shock
Nephrotoxic ATI: heavy metals, drugs

Question 12

What is the pathophysiology of ATI?

Answer 12

Damage (either ischaemic or nephrotoxic) to renal tubules, intra-renal vasoconstriction resulting in reduced GFR and and diminished O2 and nutrient delivery to tubular cells. Damage to tubular cells can cause backleak to interstitium and oedema, compressing/collasping tubules.

Question 13

What are the key morphological features of ATI?

Answer 13

Proteinaceous casts
Vacuolisation of cells
Detachment from BM

Question 14

What are proteinaceous casts made of?

Answer 14

Tamm-Horsfall protein, Hb, plasma proteins

Question 15

Describe the clinical course of ATN?

Answer 15

Initiation: initial insult leading to acute reduction in GFR

Extension: sustained hypoxia –> ischaemic injury and inflammatory cascade, leading to further reduction in GFR

Maintenance: maintained reduction in GFR leading to increased BUN, but end of the extension phase of injury. Lasts 1-2 weeks, initiation of tissue repair

Recovery: tubular function returns, leading to decreasing BUN levels

Question 16

What is the characteristic histological finding of rapidly progressive GN?

Answer 16

Crescents (deposition of fibrin and plasma proteins within Bowman’s capsule)

Question 17

What is the pathophysiology of PSGN?

Answer 17

Glomerular deposition of immune complexes resulting in proliferation of and damage to glomerular cells and infiltration of leukocytes

Question 18

When does PSGN develop?

Answer 18

1-4 weeks post recovery from GAS infection

Question 19

What type of complement activation occurs in PSGN?

Answer 19

Classical pathway

Question 20

What is the clinical course of PSGN?

Answer 20

Abrupt onset malaise, fever, nausea, nephritic syndrome.

Question 21

What biochemically indicates PSGN?

Answer 21

Renal injury + low serum complement and ASOT titres raised

Question 22

What are the clinical features of adult PCKD?

Answer 22

Autosomal dominant inheritance
Mutations in Polycystin 1 or 2 gene
Accounts 10% of all CKD requiring dialysis
10-30% associated berry aneurysms
25% mitral valve prolapse