Lecture 8: Glomerular Disease (Pathology)

Question 1

what is the glomerular membrane filter barrier composed of?

Answer 1

three things:
- endothelial cell cytoplasma
- basal lamina
- podocyte

Question 2

what is the name given to a ‘tree-like’ group of cells which support capillaries in the glomerulus?

Answer 2

mesangial cells

Question 3

which substances leave the efferent arteriole of the glomerulus, having not been filtered?

Answer 3

blood cells
some fluid
albumin and larger proteins, antibodies

Question 4

what is glomerulonephritis?

Answer 4

disease of glomerulus
inflammatory or non-inflammatory

Question 5

what is the aetiology of glomerulonephritis?

Answer 5

• some due to immunoglobulin deposition
• some are diseases with no immunoglobulin deposition - for example - diabetic glomerular disease.

Question 6

list 4 common presentations of glomerulonephritis

Answer 6

• haematuria (blood in urine)
• heavy proteinuria (nephrotic syndrome)
• slowly increasing proteinuria
• acute renal failure

Question 7

list the main causes of haematuria

Answer 7

• UTI
• urinary tract stone
• urinary tract tumour
• glomerulonephritis

Question 8

how is haematuria investigated?

Answer 8

• dipstick urine - positive for blood
• urine culture
• arrange ultrasound examination
• if normal, check his clotting factors are normal, then proceed to renal biopsy.

Question 9

how can excess immunoglobulin deposition cause glomerulonephritis?

Answer 9

• IgA is not filtered into urine > gets ‘stuck’ within the mesangial cells
• mesangium, not the filter membrane, becomes clogged with antibodies
• IgA ‘irritates’ mesangial cells and causes them to proliferate and produce more matrix > mesangial cella and matrix expansion

Question 10

IgA nephropathy prognosis

Answer 10

• usually self-limiting, i.e. return to normal
• small % go onto chronic renal failure (via continues deposition of matrix)

Question 11

how would you investigate a low serum albumin?

Answer 11

• dipstick proteinuria
• refer to nephrologist to measure protein (albumin) in urine
• if there is heavy loss > clinical diagnosis of nephrotic syndrome > must be abnormality of glomerular filter
• check clotting screen then do renal biopsy

Question 12

pathology of membranous glomerulonephritis

Answer 12

• IgG is stuck in membrane: deposits itself between basal lamina and podocyte but cannot go further and is not filtered into urine.
• IgG activates complement (C3), which punches holes in filter
• leaky filter now allows albumin to be filtered into urine > nephrotic syndrome

Question 13

membranous glomerulonephritis prognosis

Answer 13

1/4 in chronic renal failure within 10 years

Question 14

pathophysiology of diabetic glomerulonephritis

Answer 14

• glycated molecules > matrix deposition in basal lamina underlying endothelium and in mesangial matrix > thickened but leaky basement membranes + mesangial matrix compresses capillaries (no immune complexes)

Question 15

in diabetic nephropathy, what are the nodules of meangial matrix called?

Answer 15

Kimmelsteil-Wilson lesion = gross excess of mesangial matrix forming nodules
- glomerulus attempt to prevent massive leaking of albumin into urine

Question 16

diabetic nephropathy prognosis

Answer 16

• inevitable decline if, established diabetic nephropathy and if continued poor diabetic control

Question 17

what does a rapidly rising serum creatinine level indicate?

Answer 17

acute renal failure

Question 18

what is the appearance of cresentic glomerulonephritis in a biopsy?

Answer 18

Question 19

list causes of crescentic glomerulonephritis

Answer 19

1. granulomatosis with polyangiitis (previously known as Wegener’s granulomatosis)
2. microscopic polyarteritis (very similar to above)
3. antiglomerular basement membrane disease
4. other - many other forms of glomerulonephritis

Question 20

what are further tests for granulomatosis with polyangitis?

Answer 20

• biopsy
• serum tests show presence of anti-neutrophil cytoplasmic antibodies (ANCA)

Question 21

how do ANCA cause tissue damage in granulomatosis with polyangitis?

Answer 21

• produce tissue damage via interactions with primed neutrophils and endothelial cells.

Question 22

granulomatosis with polyangitis (Wegener’s) prognosis?

Answer 22

• fatal (mean survival 6 months) if left untreated
• cyclophosphamide > 75
  % complete remission