Glomerular disease pathology

Question 1

what does a normal glomerulus look like?

Answer 1

Question 2

label glomerulus histology

Answer 2

Question 3

how does blood enter the glomerulus?

Answer 3

via the afferent arteriole

Question 4

where is blood filtered?

Answer 4

across glomerular membrane

All proteins equal to or larger than albumin (including immunoglobulins) will not be filtered - they will stay in plasma)

Question 5

from the outside wht do podocytes have?

Answer 5

Question 6

what are the three components of the filter barrier?

Answer 6

endothelial cell cytoplasm, basal lamina and podocyte

Question 7

what are mesangial cells?

Answer 7

‘tree-like’ group of cells which support capillaries

Question 8

where does filtrate from glomerulus go?

Answer 8

into Bowman’s space then into proximal tubule

Question 9

what exists via efferent arteriole?

Answer 9

Blood cells, some fluid and albumin and larger proteins exit via efferent arteriole

Efferent arteriole (contains plasma, including unfiltered proteins such as albumin and antibodies)

Question 10

wh

Question 11

at is glomerulonephritis?

Answer 11

= Disease of glomerulus
Inflammatory or non-inflammatory

Question 12

what is the aetiology of glomerulonephritis?

Answer 12

Some are due to immunoglobulin deposition

Some are diseases with no immunoglobulin deposition – for example - diabetic glomerular disease

Question 13

what is glomerulonephritis?

Answer 13

Large range of conditions
Difficult to cover all variants

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

Question 14

what are the three main causes of haematuria?

Answer 14

Urinary tract infection
Urinary tract stone
Urinary tract tumour

Question 15

what is immonoflourecence done for?

Answer 15

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

IgA deposits (yellow arrow) cause increased proliferation of mesangial cells

Excess antibody (IgA) sometimes present in serum, but this is also true of some people who do not have IgA glomerulonephritis

Question 16

Does IgA get filtered into urine?

Answer 16

No, the IgA is ‘stuck’ within the mesangium

Question 17

what effect does IgA have on mesangial cells?

Answer 17

IgA – ‘irritates’ mesangial cells and causes them to proliferate and produce more matrix

Question 18

50 year old male
3 weeks of feeling unwell and swollen legs

Answer 18

Send of blood biochemistry and haematology tests 🡪 Serum albumin is low

Question 19

what do you do if serum albumin is showed to be low?

Answer 19

Dipstick proteinuria
Send into hospital to see nephrologist
Nephrologist measures protein (albumin) in urine – very heavy loss

Clinical diagnosis of nephrotic syndrome – must be abnormality of glomerular filter
Check clotting screen then do renal biopsy:

Question 20

why do you do clotting screen before renal biopsy?

Answer 20

risk of bleeding

Question 21

what happens in membranous glomerulonephritis?

Answer 21

IgG is stuck in membrane
IgG deposits itself between basal lamina and podocyte but cannot go further and is not filtered into urine

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

Leaky filter now allows albumin to be filtered into urine 🡪 nephrotic syndrome

Membranous glomerulonephritis - Prognosis
1/4 in chronic renal failure within 10 years

Question 22

Underlying cause of IgG production and accumulation in membranous glomerulonephrits?

Answer 22

Unknown but can sometimes have underlying malignancy
In many patients antigen is phospholipase A2 receptor – why this protein? – as yet unknown.

Question 23

Case 3

31 year old woman
Type 1 diabetes since 7 years of age
Long periods of poor glycaemic control
Developed retinopathy
Albumin in urine slowly increasing over last few years. Now has heavy protein leakage into urine
Check clotting screen then do renal biopsy

Answer 23

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 24

diabetic nephropathy?

Answer 24

Question 25

Female, 50 years old
Unwell for 3 weeks
Cough
Serum biochemistry – creatinine 500 (was 60 one year before)

Answer 25

Rapidly rising creatinine = acute renal failure
Ultrasound: no renal tract lesion
Check clotting then renal biopsy:

Crescentic glomerulonephritis Many causes of this pattern of injury, for example:A form of vasculitis (= inflammation in vessels) which affects vessels in kidneys, nose and lungs

Question 26

causes of crescentic glomerulonephritis of injury?

Answer 26

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

Question 27

wegners further tests?

Answer 27

Serum test shows presence of anti-neutrophil cytoplasmic antibodies (ANCA)

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