Glomerular pathology

Question 1

Define focal vs diffuse.

Answer 1

Focal: less that 50% of the glomeruli on light microscopy.
Diffuse: involving more that 50% of glomeruli on light microscopy.

Question 2

Define segmental vs global.

Answer 2

Segmental: part of the glomerular tuft.
Global: all of the glomerular tuft.

Question 3

Define crescent pathology.

Answer 3

Accumulation of cells within the Bowman’s capsule that compress the glomerulus.

Question 4

Define glomerulosclerosis.

Answer 4

Segmental or global capillary collapse resulting in no filtration.

Question 5

Define Glomerulonephritis.

Answer 5

Inflammation of the glormerular tuft.

Question 6

Describe the damagable structures in Glomerulonephritis. (4)

Answer 6

Capillary endothelium - lumen narrows.
Glomerular basement membrane.
Mesangial cells - increase in number or matrix amount - can’t support the other things that exist.
Podocytes - fusion - can’t allow stuff through.

Question 7

Define nephrotic syndrome. (8)

Answer 7

Basement membrane or pOdocytes damage leading to glomerular charge barrier disruption and Oedema. Normal holes get bigger - triad of hypoalbuminaemia, proteinuria >350mg/mmol and oedema. Often accompanied with high cholesterol, normal BP and normal GFR (indicated with a normal creatinine). - normal holes get bigger leading to proteinuria only.

Question 8

Describe and explain primary causes of nephrotic syndrome. (9).

Answer 8

Minimal change Glomerulonephritis - idiopathic podocyte only damage that occurs in childhood. May recur, but responds to steroids, and will not normally progress to renal failure.
Focal segmental Glomerulosclerosis (FSGS) - adults have that doesn’t respond to steroids due to a circulating factor damaging podocytes. Does progress to renal failure due to scarring, which reduces GFR.
Membranous Glomerulonephritis - commonest cause of nephrotic syndrome in adults. Autoantibodies formed against podocytes which inflames the basement membrane. The damage is visible.

Question 9

Describe secondary causes of nephrotic syndrome. (3)

Answer 9

Diabetes, lupus (see later), amyloidosis (bone marrow dysfunction).

Question 10

Describe the management of nephrotic syndrome. (4)

Answer 10

Hypercholesterolanemia - statins stop atherogenesis but can’t give to kids.
Oedema - diuretics and salt/fluid restriction.
ACE-inhibitor - anti-proteinuric.
Treat underlying condition - steroids for MCD.

Question 11

Describe nephritic syndrome.

Answer 11

Inflammation damages endothelium and podocytes. Blasts holes in sieve leaving to: haematuria (and proteinuria), hypertension and reduced GFR. Can sometimes lead to crescents.

Question 12

Describe and explain causes of nephritic syndrome. (12)

Answer 12

Post-infectious - following rheumatic fever.
IgA nephropathy - commonest, prevents at any age with haematuria. Relationship with mucosal infections because IgA for these infections attack the glomerulus. Most progress to renal failure.
ANCA-associated vasculitis - antibodies formed against neutrophils causing inflammation of blood vessels in the kidney and lungs.
AntiGBM disease / Goodpasture’s disease - autoantibodies to collagen IV found in basement membrane causing basement membrane inflammation and glormerular crisis - will also attack alveolar basement membrane if predamaged. Treated with severe immunosuppresion.
Lupus - many patterns of renal disease which can be nephrotic or nephritic.

Question 13

Describe the treatment of nephritic syndrome. (5)

Answer 13

Blood pressure control - ACEi
Oedema - diuretics
Disease specific treatment - generally immunosuppressants.
CVS risk management - stop smoking, statins.
Dialysis - often short term.

Question 14

Describe heredity nephropathies. (6)

Answer 14

Benign - thin GBM nephropathy, benign familial nephropathy, isolated haematuria.
Alport Syndrome - X linked, abnormal collagen IV meaning GBM is defective. Associated with deafness, and progresses to renal failure.

Question 15

Describe the pathological changes in diabetic nephropathy. (10)

Answer 15

The commenest cause of end stage renal disease. Pathological not inflammatory.
1. Hyperfiltration and capillary hypertension - hyperglycaemia increases GFR.
2. Glomerular basement membrane thickening.
3. Meningial expansion.
4. Podocyte injury.
5. Glomerular sclerosis / arteriosclerosis.
High glormerular pressure means more NaCl and glucose reabsorption. This means less NaCl delivered to the macula densa so the kidney thinks something is wrong, so it releases renin. Constriction efferent, dilation afferent raises BP.

Question 16

Describe the signs and symptoms of diabetic nephropathy. (5)

Answer 16

1. Hyperfiltration and hypertrophy with increased GFR.
2. Latent stage - normal albuminuria, GMB thickening and mesangial expansion.
3. Microalbuminuria - more of everything - reversible.
4. Overt proteinuria - diffuse glomerular histopathological changes, systemic hypertension, falling GFR - cannot be reversed.
5. End stage renal disease.

Question 17

Describe diabetic nephropathy risk factors. (5)

Answer 17

Genetics, race (black = higher risk), hypertension, increasing age, duration of diabetes, smoking.

Question 18

Describe primary prevention of diabetic nephropathy. (2)

Answer 18

Tight blood glucose control can reverse hyperfiltration. Tight blood pressure control.

Question 19

Describe management of microalbuminuria and proteinuria. (3)

Answer 19

RAAS inhibition to reduce hyperfiltration - reduces proteinuria.
Statin therapy and CVS risk management.
Moderate protein intake.