Glomerular Disease Pathology

Question 1

Where does blood enter a normal glomerulus?

Answer 1

Via an afferent arterial

Question 2

What proteins will not be filtered through the glomerulus?

Answer 2

All proteins equal to or larger than albumin will not be filtered so will stay in the plasma

Question 3

What are mesangial cells?

Answer 3

‘Tree-like’ groups of cells which support the capillaries

Question 4

Where does the filtrate go?

Answer 4

Into Bowman’s space and then into the proximal tubule

Question 5

How do blood cells, some fluid and albumin and larger proteins exit?

Answer 5

Via an efferent arteriole

Question 6

What are the types of glomerulonephritis?

Answer 6

Disease of the glomerulus - can be inflammatory or non-inflammatory

Question 7

What parts of the body are affected by primary glomerulonephritis?

Answer 7

Only the glomerulus

Question 8

What is affected by secondary glomerulonephritis?

Answer 8

Other parts of the body e.g. SLE, granulomatosis with polyangiitis

Question 9

What is the aetiology of glomerulonephritis?

Answer 9

Some are due to immunoglobulin deposition

Some are diseases with no immunoglobulin deposition e.g. diabetic glomerular disease

Question 10

What are the four most common presentations of glomerulonephritis?

Answer 10

Haematuria
Heavy proteinuria
Slowly increasing proteinuria
Acute renal failure

Question 11

What are the main causes of haematuria?

Answer 11

Urinary tract infection
Urinary tract stone
Urinary tract tumour

These 3 should be excluded before a diagnosis of glomerulonephritis is reached

Question 12

CASE

40 year old male
Discoloured urine
Dipstick urine positive for blood
Frank haematuria

What investigations would you do/organise?

Answer 12

Urine culture
Ultrasound - pelvic/abdomen
Clotting screen
Renal biopsy

Question 13

What is seen in a renal biopsy of IgA glomerulonephritis?

Answer 13

Immunofluorescence

Immunoglobulin (IgA) and complement component C3 in mesangial area of all glomeruli

Question 14

What effect do IgA deposits have on mesangial cells?

Answer 14

IgA deposits cause increased proliferation of mesangial cells

Question 15

In IgA glomerulonephritis, IgA is not removed by the glomerulus, what does this mean?

Answer 15

IgA does not get filtered into the urine and is stuck within the mesangium
The mesangium becomes clogged with the antibody, this causes RBCs to escape into the urine
IgA irritates the mesangial cells and causes them to proliferate and produce more matrix

Question 16

What is the outcome of IgA nephropathy?

Answer 16

Usually self-limiting, patient will return to normal

A small percentage will go on to develop chronic renal failure via continued deposition of the matrix

Question 17

CASE 2

50 year old male
3 week history of feeling unwell and swollen legs

What investigations would you do/organise?

Answer 17

Blood biochemistry and haematology tests
Dipstick
Clotting screen
Renal biopsy

Question 18

CASE 2

Blood biochemistry and haematology tests show that serum albumin is low
Urine dipstick shows proteinuria
Referred to nephrologist who identifies very heavy protein loss in urine
Biopsy shows thickened glomerular basement membrane
Spikes of new basement membrane matrix material is present underneath podocytes

What is the most likely diagnosis?

Answer 18

Membranous glomerulonephritis

Question 19

What is the pathological process of membranous glomerulonephritis?

Answer 19

IgG stuck in the membrane
IgG deposits itself between the basal lamina and podocyte but cannot go further and is not filtered into the urine
IgG is too big to be filtered but activates complement (C3) which punches holes in the filter
Leaky filter now allows albumin to wbefiltered into the urine, resulting in nephrotic syndrome

Question 20

What is the prognosis of membranous glomerulonephritis?

Answer 20

1/4 will be in chronic renal failure within 10 years

Question 21

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

Answer 21

Unknown but sometimes associated with underlying malignancy

In many patients, the antigen is phospholipase A2 receptor but it is unknown why

Question 22

CASE 3

31 year old woman
Type 1 diabetes since childhood
Long periods of poor glycaemic control
Developed retinopathy
Albumin in urine slowly increasing over last few years, now heavy proteinuria
Glycated molecules seen on biopsy, matrix deposition in the basal lamina underlying the endothelium and mesangial matrix
Thickened but leaky basement membranes and mesangial matrix compressing the capillaries

What is the most likely diagnosis?

Answer 22

Diabetic nephropathy

Question 23

What is a Kimmelsteil-Wilson lesion?

Answer 23

Gross excess of mesangial matrix forming nodules

Question 24

What is the prognosis of diabetic nephropathy?

Answer 24

Inevitable decline if established diabetic nephropathy and if poor glycaemic control continues

Question 25

CASE 4

50 year old female
Unwell for 3 weeks
Cough
Serum biochemistry done, creatinine is 500 (was 60 one year before) - indicates acute renal failure
Ultrasound shows no renal tract lesion
Glomerular crescent formation seen on renal biopsy

What is the most likely diagnosis?

Answer 25

Crescentic glomerulonephritis

Question 26

What are the possible causes of crescentic glomerulonephritis?

Answer 26

Many causes, including:

Granulomatosis with polyangiitis
Microscopic polyarteritis
Anti-glomerular basement membrane disease
Other forms of glomerulonephritis

Question 27

What is granulomatosis with polyangiitis?

Answer 27

Form of vasculitis which affects the vessels in the kidneys, nose and lungs

Question 28

What is seen in serum tests of patients with granulomatosis with polyangiitis?

Answer 28

Presence of anti-neutrophil cytoplasmic antibodies (ANCA)

Question 29

What are anti-neutrophil cytoplasmic antibodies (ANCA)?

Answer 29

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

Question 30

How do ANCA produce tissue damage?

Answer 30

Via interactions with primed neutrophils and endothelial cells

Question 31

What is the prognosis of granulomatosis with polyangiitis?

Answer 31

Fatal if left untreated, mean survival of 6 months

75% complete remission with cyclophosphamide therapy