Glomerular Disease (Pathology)

Question 1

What molecules are not filtered at the glomerulus?

Answer 1

All proteins equal to or larger than albumin

• Including Immunoglobulins (antibodies)

Question 2

What are the layers of the glomerular membrane?

Answer 2

1. Endothelium (w fenestrations)
2. Basal lamina
3. Podocyte foot processes (pedicels)

Question 3

What is the mesangium?

Answer 3

• ‘tree-like’ group of cells which support capillaries at the glomerulus
• It is continuous with the smooth muscles of the arterioles. It’s outside the capillary lumen, but surrounded by capillaries

Question 4

Describe the flow of blood at the glomerulus

Answer 4

• Blood enters via the afferent arteriole
• 20% of plasma is filtered into Bowmans capsule along with smaller molecules
• Blood containing larger proteins and immunoglobulins leave via the efferent arteriole

Question 5

What is Glomerulonephritis?

Answer 5

Disease of the glomerulus

• According to slides: can be inflammatory or non-inflammatory

Question 6

What are the 4 common presentations of glomerulonephritis?

Answer 6

1. Haematuria
2. Heavy proteinuria (nephrotic syndrome)
3. Slowly increasing proteinuria
4. Acute renal failure

Question 7

What are the main causes of haematuria?

Answer 7

• UTI
• Urinary tract stone
• Urinary tract tumour
• Glomerulonephritis

Question 8

How does IgA cause nephropathies?

Answer 8

Deposition of IgA at the glomerulus causes the proliferation of mesangial cells and increased mesangial matrix deposition

• This causes RBCs to leak into the urine (mechanism unknown)

Question 9

What is the prognosis for IgA mediated nephropathy?

Answer 9

• Usually self limiting, return to normal
• Small percentage go to chronic renal failure due to continued deposition of matrix and cell proliferation within the mesangium, which obstructs normal blood flow at the glomerulus

Question 10

If a patient presents with swollen legs and feeling unwell, what is a possible renal ddx?

Answer 10

Glomerulonephritis

• need to test urine protein and serum albumin
• Most likely albumin is being filtered and excreted in the urine

Question 11

How does IgG lead to membranous glomerulonephritis?

Answer 11

• IgG becomes deposited between podocyte and basal lamina, too big to be filtered into urine
• Basal lamina thickens in attempt to surround and remove the deposit
• IgG activates compliment C3 which punches holes in the glomerular filter
• Leaky filter allows albumin through

Question 12

What is the prognosis for membranous glomerulonephritis?

Answer 12

25% develop chronic renal failure within 10 years

Question 13

How does prolonged hyperglycaemia lead to diabetic nephropathy?

Answer 13

• Glycated molecules become deposited in basal lamina and mesangial matrix
• Increased mesangial matrix compresses arterioles and blood flow to glomerulus
• Basement membrane becomes thickened but leaky due to deposits of glycated molecules
• Albumin leaks into urine, membrane may even adhere to Bowmans capsule to prevent mass leakage

Question 14

What is a Kimmelsteil-Wilson lesion?

Answer 14

Gross excess of mesangial matrix due to diabetic nephropathy, leads to formation of nodules

Question 15

What is Crescentic glomerulonephritis?

Answer 15

• Cellular proliferation and influx of macrophages (inflammation) into the Bowmans space, around the glomerulus. Crushes the glomerulus

Question 16

What are some possible causes of crescentic glomerulonephritis?

Answer 16

Granulomatosis with polyangiitis

Microscopic polyarteritis

Antiglomerular basement membrane disease

Other - Many other forms of glomerulonephritis

Question 17

What is granulomatosis with polyangiitis? (Wegener’s granulomatosis)

Answer 17

A disorder that causes inflammation of the blood vessels (vasculitis) in your nose, sinuses, throat, lungs and kidneys

• Can lead to crescentic glomerulonephritis

Question 18

What is an investigation that can be done to test for granulomatosis with polyangiitis? (Wegener’s granulomatosis)

Answer 18

• Serum anti-neutrophil cytoplasmic antibodies (ANCA)

Question 19

How do anti-neutrophil cytoplasmic antibodies (ANCA) cause the inflammation in crescentic glomerulonephritis?

Answer 19

• They are antibodies against enzymes in the primary granules of neutrophils
• Antibodies produce tissue damage via interactions with primed neutrophils and endothelial cells
• Causes inflammation at glomerulus

Question 20

What is the prognosis for granulomatosis with polyangiitis? (Wegener’s granulomatosis) Are there any treatments?

Answer 20

• Fatal if left untreated

- Cyclophosphamide – 75% complete remission