150 - Glomerular Diseases Flashcards
Aspects of epithelium of glomerulus
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
Three cell types of glomeruli
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)
Basement membrane of glomerului
Basement membrane has specalized structure; includes Type IV collagen and negatively charged proteoglycans
Major area of medicine where electron microscopy is still used
Renal imaging
Blood effects of severe proteinuria/nephrotic syndrome 1 2 3 4
1) Oedema, typically affecting the whole body
2) Proteinuria (generally more than 3 or 4 g/day)
3) Hypoalbuminaemia
4) Hyperlipidaemia
Basic problem underlying nephrotic syndrome
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.
Why does hyperlipidaemia result from nephrotic syndrome?
Liver responds to hypoalbuminaemia by producing more lipids
What keeps proteins from being filtered?
1
2
3
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’)
Example of abnormal physical structure of filtration membrane of glomerulus
Some people inherit an abnormal gene coding for the collagen subtype in the glomerular basement membrane (Alport syndrome)
Example of a defect in podocyte function
Inherited nephrotic syndrome (Finnish type) with mutation in the gene for Nephrin
Common causes of proteinuria or nephrotic syndrome 1 2 a, b, c 3 4
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
Diabetic nephropathy
Hyperglycaemic for years leads to deposition of carbohydrates on glomerular wall, thickening it and increasing permeability.
What does acute renal injury refer to?
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.
Different causes of acute renal failure
1
2
3
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
Example of renal causes of ARF 1 2 3 4
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
Glomerulonephritis
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’)
Acute glomerulonephritis
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’
Most common glomerulonephritis in Australia
IgA nephropathy (leads often to haematuria, often without acute renal failure)
Common form of glomerulonephritis leading to proteinuria
Membraneous nephropathy
How do Glomeruli react to immune-complex-mediated injury? 1 a, b, c 2) a, b, c 3) 4)
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
- New layers of b.m.
- Spikes or protrusions on the epithelial surface
Histological appearance of post-infectious glomerulonephropathy
Hypercellular.
Cells are mostly netrophils, packing the capillary loops
Diffuse (in the kidney)
Process affects all glomeruli
Focal (in the kidney)
Affects some glomeruli
Global (in the kidney)
Affects the entire glomerulus
Opposite of global (in the kidney)
Segmental
Things that can distinguish different types of immune-complex-mediated glomerulonephritises from one another
Different immunoglobulins in the deposited complexes
Different sites of deposition in the glomerulus
Different reactions by basement membrane, cells, mesangial matrix
What does IgA nephropathy often lead to?
Haematuria
Crescents
1
2
3
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.
Aftereffects of crescents of the glomerulus
1
2
3
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.
Examples of causes of glomerular injury 1 2 3 4
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)
