Glomerular Disease Pathology

Question 1

What is glomerulonephritis?

Answer 1

Inflammation of the tinu filters in your kidney (glomeruli)

Question 2

How does blood enter the glomerulus?

Answer 2

Via afferent arteriole

Question 3

What happens once blood enters the glomerulus?

Answer 3

Some of it is filtered across glomerular membrane

Question 4

When blood enters the glomerulus, what happens to large and charge substances?

Answer 4

They are not filtered and will stay in plasma

Question 5

What are the cells called in the Bowman’s capsule that wrap around the capillaries of the glomerulus?

Answer 5

Podocytes

Question 6

What are podocytes observed to have?

Answer 6

Interdigitating fingers or foot processes

Question 7

What can be seen if you took a secrtion through a capillary loop?

Answer 7

Filter barrier, which is a membrane composed of endothelial cell cytoplasm, basal lamina and podocyte

Question 8

What are the 3 parts of the filter barrier?

Answer 8

Endothelial cell cytoplasm

Basal lamina

Podocyte

Question 9

What are mesangial cells?

Answer 9

‘Tree like’ group of cells which support capillaries

Question 10

What happens to filtrate after glomerulus?

Answer 10

Goes into Bowman’s space, then into proximal tubule

Question 11

After the glomerulus, what do blood cells, some fluid and albumin and larger proteins exit via?

Answer 11

Efferent arteriole

Question 12

What are the different kinds of glomerulonephritis?

Answer 12

Inflammatory or non-inflammatory

Primary

Secondary

Question 13

What is primary glomerulus?

Answer 13

Only affects glomerulus

Question 14

What is secondary glomerulus?

Answer 14

Affects other parts of the body

Question 15

What are examples of diseases causing secondary glomerulus?

Answer 15

SLE or Wegener’s

Question 16

What is the aetiology of glomerulonephritis?

Answer 16

• immunoglobulin deposition
• no immunoglobulin deposition

Question 17

What are the 4 common presentations of glomerulonephritis?

Answer 17

• Haematuria (blood in urine)
• Heavy proteinuria (nephrotic syndrome)
• Slowly increasing proteinuria
• Acute renal failure

Question 18

What are different conditions that cause glomerulonephritis?

Answer 18

IgA glomerlonephritis

Membranous glomerulonephritis

Diabetic nephropathy

Crescentic glomerulonephritis

Question 19

What does IgA glomerulonephritis often present with?

Answer 19

Often presents with discoloured urine, investigation would be dipstick urine which is positive for blood

Question 20

What are the main causes of IgA glomerulonephritis?

Answer 20

• Urinary tract infection
• Urinary tract stone
• Urinary tract tumour
• Glomerulonephritis

Question 21

What investigations are done for IgA glomerulonephritis?

Answer 21

Dipstick urine

Urine culture

Ultrasound scan

If all normal, renal biopsy

Question 22

If all typical investigations are normal for IgA glomerulonephritis, what investigation would be done?

Answer 22

Renal biopsy

Question 23

What is immunofluorescence?

Answer 23

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

Question 24

What can be done with urinary biopsy in IgA glomerulonephritis?

Question 25

What is seen in a renal biopsy and immunofluorscence for IgA glomerulonephritis?

Answer 25

* Reveals immunoglobulin (of IgA type) and complement component of C3 in mesangial area of all glomeruli

Question 26

What is the aetiology of IgA glomerulonephritis?

Answer 26

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

Question 27

What is the pathogenesis of IgA glomerulonephritis?

Answer 27

IgA also does not get filtered into urine, it is “stuck” within the mesangium This causes mesangium, not the filter membrane to become clogged with antibody – causing red blood cells to escape into urine: * IgA irritates mesangial cells and causes them to proliferate and produce more matrix

Question 28

What is the prognosis of IgA glomerulonephritis?

Answer 28

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

Question 29

What is the typical presentation of membranous glomerulonephritis?

Answer 29

Could present with feeling unwell and swollen legs

Question 30

What investigations are done for membranous glomerulonephritis?

Answer 30

* Check clotting screen then do renal biopsy

Question 31

What is seen in a dipstick of urine for membranous glomerulonephritis?

Answer 31

Proteinuria

Question 32

What is seen in blood biochemistry for membranous glomerulonephritis?

Answer 32

Serum albumin low

Question 33

What is the pathogenesis of membranous glomerulonephritis?

Answer 33

In membranous glomerulonephritis IgG is stuck in the 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 activates complement (C3) which punches holes in filter * This leaky filter now allows albumin to be filtered into urine, causing nephrotic syndrome

Question 34

What does renal biopsy reveal for membranous glomerulonephritis?

Answer 34

Thickened glomerular basement membrane Deposits of IgG Basal lamina spikes (matrix which tries to surround the deposit)

Question 35

What is deposited on the membrane in membranous glomerulonephritis?

Answer 35

IgG

Question 36

What is the prognosis of membranous glomerulonephritis?

Answer 36

* 1/4 will get chronic renal failure within 10 years

Question 37

What is the aetiology of membranous glomerulonephritis?

Answer 37

* Unknown but ca sometimes have underlying malignancy * In many patients antigen is phospholipase A2 receptor

Question 38

What investigations are done for diabetic nephropathy?

Answer 38

Dipstick urine Clotting screen Renal biopsy

Question 39

What can be seen in the biopsy for diabetic nephropathy?

Answer 39

Question 40

What is the pathogenesis of diabetic nephropathy?

Answer 40

Question 41

What kind of lesion does diabetic nephropathy cause?

Answer 41

Diabetic nephropathy causes nodules of mesangial matrix to form, known as Kimmelsteil-Wilson lesion: * Is gross excess of mesangial matrix forming nodules

Question 42

What is the prognosis of diabetic nephropathy?

Answer 42

* Inevitable decline if established diabetic nephropathy ad if continued poor diabetic control

Question 43

What is a sign of acute renal failure?

Answer 43

Rapidly rising creatinine

Question 44

What are the typical investigations for renal disease?

Answer 44

Urine dipstick Clotting screen Renal biopsy

Question 45

What is seen in the biopsy for crescentic glomerulonephritis?

Answer 45

Early endothelial damage with fibrin deposition Crush glomerular tuft Cellular proliferation and influx of macrophages (is the crescent) around glomerular tuft, within Bowman's space

Question 46

What are some causes for the crescentic glomerulonephritis pattern of injury?

Answer 46

* Granulomatosis with polyangiitis (also known as Wegener’s granulomatosis) * Form of vasculitis (inflammation in vessels) which affects vessels in kidneys, nose and lungs * Microscopic polyarteritis (a disease very like Wegener) * Antiglomerular basement membrane disease * Many other forms of glomerulonephritis

Question 47

What is granulomatosis with polyangitis also known as?

Answer 47

Wegener's granulomatosis

Question 48

What is Wegener's granulomatotis?

Answer 48

* Form of vasculitis (inflammation in vessels) which affects vessels in kidneys, nose and lungs

Question 49

What further tests can be done for Wegener's?

Answer 49

* Serum test shows presence of anti-neutrophil cytoplasmic antibodies (ANCA) * These are not deposited in the kidneys * Antibodies directed against proteinase 3 and myeloperoxidase, 2 enzymes in primary granules of neutrophils * Antibodies produce tissue damaged via interactions with primed neutrophils and endothelial cells

Question 50

What do serum tests reveal in Wegener's?

Answer 50

Presence of anti-neutrophil cytoplasmic antibodies (ANCA)

Question 51

What does ANCA stand for?

Answer 51

Anti-neutrophil cytoplasmic antibodies

Question 52

What is ACNA a form of?

Answer 52

Autoimmunity

Question 53

What is the prognosis of Wegener's?

Answer 53

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