Glomerular Disease (Pathology)

Question 1

what is this showing?

Answer 1

a normal glomerulus

Question 2

what can be seen either side of the glomerulus?

Answer 2

Need 2 small arterioles on either side to regulate blood pressure other wise the capillaries will burst

Question 3

a

Answer 3

Podocyte

Question 4

b

Answer 4

Red blood cell in capillary loop

Question 5

c

Answer 5

Endothelial cell lining capillary loop

Question 6

what is a Podocyte?

Answer 6

Podocytes are cells in the Bowman’s capsule in the kidneys that wrap around capillaries of the glomerulus. Podocyte cells make up the epithelial lining of Bowman’s capsule, the third layer through which filtration of blood takes place

Question 7

where does blood enter the glomerulus?

Answer 7

Question 8

Blood is filtered across glomerular membrane, what is not?

Answer 8

Question 9

From outside podocytes have what?

Answer 9

From outside podocytes have interdigitating ‘fingers’ or foot processes

Question 10

Filter barrier = membrane = 3 things, what are they?

Answer 10

endothelial cell cytoplasm, basal lamina and podocyte

Question 11

what is the Mesangium?

Answer 11

The mesangium is a space which is continuous with the smooth muscles of the arterioles. It is outside the capillary lumen, but surrounded by capillaries. It is in the middle (meso) between the capillaries (angis)

Mesangial cells = ‘tree-like’ group of cells which support capillaries

Question 12

where does filtrate flow?

Answer 12

Question 13

where do the things that cannot be filtered into bowmens space go?

Answer 13

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

Question 14

what is Glomerulonephritis?

Answer 14

= Disease of glomerulus

Can be inflammatory or non-inflammatory

Glomerulonephritis is inflammation of the tiny filters in your kidneys (glomeruli). Glomeruli remove excess fluid, electrolytes and waste from your bloodstream and pass them into your urine. Glomerulonephritis can come on suddenly (acute) or gradually (chronic)

Question 15

what is the aetiology of Glomerulonephritis?

Answer 15

Some are due to immunoglobulin deposition

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

Question 16

Is Glomerulonephritis just one disease?

Answer 16

• Large range of conditions
• Difficult to cover all variants

Question 17

what are 4 common presentations of Glomerulonephritis?

Answer 17

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

Question 18

Case 1:

• 40 year old male
• Discoloured urine
• Dipstick urine – positive for blood

what are the main causes of Haematuria?

Answer 18

• Urinary tract infection
• Urinary tract stone
• Urinary tract tumour
• Glomerulonephritis - not as common of a cause as the ones above

Question 19

case 1 continued:

• Send off urine culture
• Arrange hospital appointment for ultrasound examination
• Urine culture normal
• Ultrasound of abdomen – normal
• Check his clotting then proceed to renal biopsy: what is seen on biopsy?

Answer 19

Question 20

Case 1 biopsy - what is seen on immunoflourescence?

(a method in biology that relies on the use of antibodies chemically labeled with fluorescent dyes to visualize molecules under a light microscope)

Answer 20

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

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

Question 21

what is the aetiology of IgA glomerulonephritis?

Answer 21

unknown – Is excess antibody produced?

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

Question 22

Why is IgA not removed by glomerulus?

Answer 22

Unknown, but probably very important part of cause of disease

Question 23

Does IgA get filtered into urine?

Answer 23

No, the IgA is ‘stuck’ within the mesangium

Question 24

Mesangium, not the filter membrane, becomes clogged with antibody

How does this cause red blood cells to escape into urine?

Answer 24

unknown

Question 25

what does IgA cause to mesangial cells?

Answer 25

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

Question 26

what is the prognosis of a IgA nephropathy?

Answer 26

* Usually self-limiting, ie return to normal (haematuria goes away) * Small % go onto chronic renal failure (via continued deposition of matrix)

Question 27

case 2: * 50 year old male * 3 weeks of feeling unwell and swollen legs * Send of blood biochemistry and haematology tests - Serum albumin is low * Dipstick proteinuria * Send into hospital to see nephrologist * Nephrologist measures protein (albumin) in urine – very heavy loss what is this and what is it due to?

Answer 27

• Clinical diagnosis of nephrotic syndrome – must be abnormality of glomerular filter

Question 28

Case 2: • Check clotting screen then do renal biopsy: what would be see?

Answer 28

Question 29

Membranous glomerulonephritis: electron microscopy

Answer 29

Question 30

In Membranous glomerulonephritis, what happens to IgG?

Answer 30

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

Question 31

IgG is too big to be filtered into urine, but IgG activates what?

Answer 31

complement (C3), which punches holes in filter

Question 32

IgG is too big to be filtered into urine, but IgG activates complement (C3), which punches holes in filter what does this now cause?

Answer 32

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

Question 33

What is the prognosis of Membranous glomerulonephritis?

Answer 33

1/4 in chronic renal failure within 10 years

Question 34

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

Answer 34

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

Question 35

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 what would be seen?

Answer 35

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 36

what does diabetic nephropathy look like on histology?

Answer 36

Question 37

in diabetic nephropathy, nodules of mesangial matrix can be seen, what are they?

Answer 37

Kimmelsteil-Wilson lesion = gross excess of mesangial matrix forming nodules

Question 38

what is the prognosis of diabetic nephropathy?

Answer 38

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

Question 39

Case 4: * Female, 50 years old * Unwell for 3 weeks * Cough * Serum biochemistry – creatinine 500 (was 60 one year before) what is her diagnosis?

Answer 39

Rapidly rising creatinine = acute renal failure

Question 40

case 4: * Ultrasound: no renal tract lesion * Check clotting then renal biopsy: what is seen?

Answer 40

Early endothelial damage with fibrin deposition Cellular proliferation and influx of macrophages (= crescent) around glomerular tuft, within Bowman’s space

Question 41

another picture showing crescent

Answer 41

Question 42

what is the cause of Crescentic glomerulonephritis?

Answer 42

Many causes of this pattern of injury, for example: 1. Granulomatosis with polyangiitis (previously known as Wegener’s granulomatosis) 2. Microscopic polyarteritis (a disease very much like granulomatosis with polyangiitis) 3. Antiglomerular basement membrane disease 4. Other - Many other forms of glomerulonephritis

Question 43

Our example = Granulomatosis with polyangiitis (previously known as Wegener’s granulomatosis) what is it?

Answer 43

A form of vasculitis (= inflammation in vessels) which affects vessels in kidneys, nose and lungs

Question 44

What are further tests for Wegeners?

Answer 44

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

Question 45

what are Anti-neutrophil cytoplasmic antibodies (ANCA)?

Answer 45

autoantibodies directed against antigens found in the cytoplasmic granules of neutrophils and monocytes. ANCA testing is usually performed to help diagnose or exclude Wegener's granulomatosis and microscopic polyangiitis Not deposited in kidney Antibodies directed against proteinase 3 and myeloperoxidase, 2 enzymes in primary granules of neutrophils

Question 46

How does Anti-neutrophil cytoplasmic antibodies (ANCA) cause tissue damage?

Answer 46

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

Question 47

Anti-neutrophil cytoplasmic antibodies (ANCA) – why do they form?

Answer 47

Unknown at present - ? A form of autoimmunity

Question 48

what is the prognosis of Wegener's?

Answer 48

* Fatal (mean survival 6 months) if left untreated * Cyclophosphamide – 75% complete remission