Glomerular Disease

Question 1

What are podocytes?

Answer 1

Podocytes are cells in the Bowman’s capsule in the kidneys that wrap around capillaries of the glomerulus

Question 2

What proteins are filtered from the glomerulus?

Answer 2

All that are smaller than albumin

Immunoglobulins do not get filtered - they stay in the plasma

Question 3

What structural feature do podocytes contain?

Answer 3

They have interdigitating ‘fingers’ or foot processes

Question 4

What are the three layers of the filter barrier?

Answer 4

Endothelial cell

Basal lamina

Podocyte

Question 5

What are mesangial cells?

Answer 5

Tree like group of cells which support capilalries

Question 6

Where does filtrate travel after the glomerulus?

Answer 6

Goes into bowmans space and then into the proximal tubule

Question 7

What substances leave the efferent arteriole?

Answer 7

Blood cells someme fluid

abumin and larger proteins

Antibodies

Question 8

What is glomerulonephritis?

Answer 8

It is disease of the glomerulus

Either inflammatory or non-inflammatory

Primary - only affects the glomerulus or secondary other body parts are affected - SLE or Wegners

Question 9

What are the 4 comon presentations of glomerulonephritis?

Answer 9

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

Question 10

What are the main causes of haematuria?

Answer 10

Urinary tract infection

Urinary tract stone

Urinary tract tumour

Glomerulonephritis

Question 11

What is the necessary test before taking a renal biopsy?

Answer 11

Clotting screen - risk of bleeding to death

Question 12

What is the pathogenesis of IgA nephropathy?

Answer 12

Excess IgA sometimes present in the serum (but this is true in some people who do not have glomerulonephritis)

IgA deposits are stuck in the mesangium and are not filtered in the urine - IgA – ‘irritates’ mesangial cells and causes them to proliferate and produce more matrix

Unknown why this causes RBC’s to escape

Question 13

What is the prognosis of IgA nephropathy?

Answer 13

Usually self-limiting - ie returns to normal

SMall % go onto chronic renal failure (via continued deposition of matrix)

Question 14

How is the clinical diagnosis of nephrotic syndrome made?

Answer 14

Must be abnormality of the glomerular filter - renal biopsy

Question 15

What is the hallmark feature of membranous glomerulonephritis?

Answer 15

Thickened glomerular basement membrane

Spikes of new basement membrane matrix material underneath podocytes - spikes try to surround and remove deposits of IgG

Deposits of IgG in the subendothelial site - between basal lamina and podocyte - cannot go further and is not filtered in the urine

Question 16

What is the issue associated with IgG in the subendothelial layer?

Answer 16

IgG is too big to be filtered into the urine, but IgG activates compliment (C3) which punches holes in the filter

Question 17

What is the consequence of complement punching holes in the filter?

Answer 17

Leaky filter allows albumin to be filtered into urine - nephrotic syndrome

Question 18

What is the prognosis of glomerulonephritis?

Answer 18

•1/4 in chronic renal failure within 10 years

This is not associated with inflamamtion– on wrong side of the basal lamina – inflammatory cells cannot reach

Question 19

What is the underlying cause of IgG production and accumulation in membranous glomerulonephritis?

Answer 19

Unknown but can have underlying malignancy

IN many patients antigen is phospholipase A2 receptor

Phospholipase A2 is present on podocytes – IgG is against this receptor

Question 20

Where does matrix deposition occur in diabetic nephropathy?

Answer 20

Matrix deposition in basal lamina underlying endothelium and in mesangial matrix

Kimmelsteil Wilson lesio - gross excess of mesangial matrix forming nodules

Question 21

Describe the basement membrane in diabetic nephropathy

Answer 21

Thickened and leaky

Question 22

Describe the messangial matrix in diabetic nephropathy

Answer 22

Compresses capillaries

Question 23

What are the histological features of diabetic nephropathy?

Answer 23

Small compressed capillary lumen (by messangial matrix)

Thickened capillary wall - leaks albumin

Thickened and narrowed arterioles reduce blood flow to glomerulus

Adhesions to bowmans capsule (glomerulus’s attempt to stop massive leakage of albumin into urine)

Question 24

What is the prognosis of diabetic nephropathy?

Answer 24

Inevitable decline if 1. established diabetic nephropathy and if 2. continued poor diabetic control

Question 25

What is rapidly rising creatinine associated with?

Answer 25

Acute renal failure

Question 26

What type of glomerulonephritis has cellular proliferation and influx of macrophages (crescent) within bowmans space?

Answer 26

Crescentic glomerulonephritis

Question 27

What are the main patterns of crescentic glomerulonephritis?

Answer 27

• Granulomatosis with polyangiitis (also known as Wegener’s granulomatosis)
• Microscopic polyarteritis (a disease very much like Wegeners)
• Antiglomerular basement membrane disease
• Many other forms of glomerulonephritis

Question 28

What does granulomatosis with polyangitis affect?

Answer 28

It is a form of vasculitis

Causes: Inflammation in the vessels which affects the vessels in the kidneys, nose and lungs

Question 29

What are further tests for granulomatosis with polyangitis?

Answer 29

Serum tests show presence of anti-neutrophil cytoplasmic antibodies

(ANCA)

Question 30

What are anti-neutrophil cytoplasmic antibodies?

Answer 30

•Antibodies directed against proteinase 3 and myeloperoxidase, 2 enzymes in primary granules of neutrophils

They are not deposited in the kidney

Question 31

How do ANCA produce tissue damage?

Answer 31

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

Question 32

What is the prognosis of wegners?

Answer 32

6 months if left untreated

Cyclophosphamide - 75% complete remission