150 - Glomerular Diseases

Question 1

Aspects of epithelium of glomerulus

Answer 1

Specialised basement membrane forming the wall of the capillary loop

Internal capillary lining of endothelium with large pores (‘fenestrated endothelium’)

Covering on the urinary surface of specialised epithelial cells that are continuous with the epithelium lining the tubules

Question 2

Three cell types of glomeruli

Answer 2

Endothelial (lining the internal surface of the capillaries)

Mesangial in the stalk that supports the capillaries

Epithlelial (covering the outside or urinary surface of the basement membrane)

Question 3

Basement membrane of glomerului

Answer 3

Basement membrane has specalized structure; includes Type IV collagen and negatively charged proteoglycans

Question 4

Major area of medicine where electron microscopy is still used

Answer 4

Renal imaging

Question 5

Blood effects of severe proteinuria/nephrotic syndrome 
1
2
3
4

Answer 5

1) Oedema, typically affecting the whole body
2) Proteinuria (generally more than 3 or 4 g/day)
3) Hypoalbuminaemia
4) Hyperlipidaemia

Question 6

Basic problem underlying nephrotic syndrome

Answer 6

Basic defect is in the permeability of the filter, such that proteins (particularly albumin) escape into the urine. The other components of the syndrome follow on from the proteinuria.

Question 7

Why does hyperlipidaemia result from nephrotic syndrome?

Answer 7

Liver responds to hypoalbuminaemia by producing more lipids

Question 8

What keeps proteins from being filtered?
1
2
3

Answer 8

i) The negative charge on circulating proteins and negatively charged proteoglycans in the basement membrane
ii) Physical structure of the membrane
iii) Several vital proteins in the very fine space between adjacent epithelial cells (also called ‘podocytes’)

Question 9

Example of abnormal physical structure of filtration membrane of glomerulus

Answer 9

Some people inherit an abnormal gene coding for the collagen subtype in the glomerular basement membrane (Alport syndrome)

Question 10

Example of a defect in podocyte function

Answer 10

Inherited nephrotic syndrome (Finnish type) with mutation in the gene for Nephrin

Question 11

Common causes of proteinuria or nephrotic syndrome 
1
2 a, b, c
3
4

Answer 11

1) Diabetes mellitus

2) Some forms of glomerulonephritis
a. Minimal change disease
b. Membranous glomerulonephritis
c. Others

3) Amyloid deposition
4) Inherited abnormalities in those proteins between adjacent podocytes

Question 12

Diabetic nephropathy

Answer 12

Hyperglycaemic for years leads to deposition of carbohydrates on glomerular wall, thickening it and increasing permeability.

Question 13

What does acute renal injury refer to?

Answer 13

It specifically refers to an acute reduction in glomerular filtration rate (GFR) reflected as reduced creatinine clearance – the result is increasing serum urea and creatinine.

Question 14

Different causes of acute renal failure
1
2
3

Answer 14

Pre-renal causes – not enough blood perfusing the kidney for it to do its job

Renal causes – some problem with the machinery itself, whether glomerular, tubular etc. (what this lecture is about)

Post-renal causes – problems downstream of the kidney, like prostatic obstruction

Question 15

Example of renal causes of ARF
1
2
3
4

Answer 15

1) Acute tubular necrosis or ATN (the commonest renal cause of acute renal failure)
2) Acute glomerulonephritis
3) Acute interstitial nephritis
4) Others e.g. vascular disease

Question 16

Glomerulonephritis

Answer 16

Acute glomerular injury, often immune mediated.

Most are associated with deposition of immune complexes in the tuft (followed by complement activation, formation of membrane attack complex etc.).

Some (very few) show no immune complexes (described as ‘pauci-immune’)

Question 17

Acute glomerulonephritis

Answer 17

May be acute, reversible injury (e.g. Post Streptococcal GN)
May be rapidly progressive
May be slowly progressive to chronic renal failure (e.g. some cases of IgA nephropathy)

if severe and associated with necrosis of part of the capillary tuft, acute GN may be associated with clumps of monocytes and epithelial cells, called ‘crescents’

Question 18

Most common glomerulonephritis in Australia

Answer 18

IgA nephropathy (leads often to haematuria, often without acute renal failure)

Question 19

Common form of glomerulonephritis leading to proteinuria

Answer 19

Membraneous nephropathy

Question 20

How do Glomeruli react to immune-complex-mediated injury? 
1 a, b, c
2) a, b, c
3)
4)

Answer 20

1) The glomerular cells proliferate
a. Mesangial
b. Endothelial
c. Epithelial / podocytes

2) Inflammatory cells may arrive
a. Neutrophils
b. Lymphocytes and monocytes
c. The basement membrane may proliferate

3. New layers of b.m.
4. Spikes or protrusions on the epithelial surface

Question 21

Histological appearance of post-infectious glomerulonephropathy

Answer 21

Hypercellular.

Cells are mostly netrophils, packing the capillary loops

Question 22

Diffuse (in the kidney)

Answer 22

Process affects all glomeruli

Question 23

Focal (in the kidney)

Answer 23

Affects some glomeruli

Question 24

Global (in the kidney)

Answer 24

Affects the entire glomerulus

Question 25

Opposite of global (in the kidney)

Answer 25

Segmental

Question 26

Things that can distinguish different types of immune-complex-mediated glomerulonephritises from one another

Answer 26

Different immunoglobulins in the deposited complexes
Different sites of deposition in the glomerulus
Different reactions by basement membrane, cells, mesangial matrix

Question 27

What does IgA nephropathy often lead to?

Answer 27

Haematuria

Question 28

Crescents
1
2
3

Answer 28

1) Necrosis of an area of glomerulus.
2) Segment consists of exuded fibrin, monocytes and podocytes.
3) Not specific for one kind of glomerulonephritis, but a response to severe injury with necrosis of a segment of the glomerular tuft.

Question 29

Aftereffects of crescents of the glomerulus
1
2
3

Answer 29

1) Segments of the glomerulus may be destroyed (‘necrotizing lesions’)
2) With time, segments of the glomerulus may scar and contract (‘sclerosing lesions’)
3) And later the entire glomerulus may become a sclerotic ball without patent capillaries.

Question 30

Examples of causes of glomerular injury
1
2
3
4

Answer 30

1) Inherited abnormalities
a. Podocytes
b. Basement membrane collagen
c. Mesangial sclerosis

2) Acute endothelial injury
a. HUS / TTP
b. severe hypertension
c. scleroderma

3) Diabetes mellitus
4) Deposits of protein (amyloid, cryoglobulins)