Glomerular Pathology Flashcards
1
Q
Define nephrotic syndrome
A
- Nephrotic syndrome - when glomerulus leaks proteins into the nephron
- Greater than 3.5g of protein loss in 24 hours
2
Q
Where is the likely site of injury for nephrotic syndrome
A
Podocytes
3
Q
What are features of nephrotic syndrome
A
- Most of the protein lost is albumin - proteinuria
- Leads to decreased oncotic pressure causing oedema
- Also present with high cholesterol levels - as protein acts as a carrier of cholesterol
- Non-proliferative - number of cells generally unchanged in inflammation
- Hallmarks - proteinuria, hypoalbuminaemia, oedema, hyperlipidaemia, lipiduria
4
Q
What are some primary and secondary causes of nephrotic syndrome
A
- Common primary causes - disease of the kidney
- Minimal change glomerulonephritis
- Focal segmental glomerulosclerosis (FSGS)
- Membranous glomerulonephritis
- Common secondary causes
- Diabetes mellitus
5
Q
State the age groups common for each nephrotic syndrome
A
- Minimal change GN - common in children and adolescence
- Focal segmental glomerulosclerosis - common in adults
- Membranous GN - common in adults
6
Q
Describe the pathogenesis of minimal change glomerulonephritis
A
- Type IV collagen in the basement membrane seen as normal
- Problem with the podocytes, where foot processes are lost
- Loss of negative charge repelling proteins, allowing albumin to pass
- No immune complex deposition
7
Q
Describe the pathogenesis of focal segmental glomerulosclerosis
A
- Circulating factor damaging podocytes
- Can be due to infection, drugs, disease such as diabetes, HIV, lupus
- Proteins not only travel into the nephron, but also become trapped between the glomerulus and capsule
- Build up leads to development of sclerosis
- Progressive to renal failure
8
Q
Describe the pathogenesis of membranous glomerulonephritis
A
- Since immune complex cannot be directly filtered, either antigens are presented on the GBM that causes antibodies to bind (autoimmune)
- Or antigens in blood is filtered by glomerulus to GBM and antibodies follow leading to autoimmune attack
- Immune complexes consist of an antigen and an antibody
- Immune complex activated releases substances that damage the endothelial layer of the glomerulus
- Activate complement system and recruits inflammatory cells
- Basement membrane becomes leaky, leading to protein filtering through
9
Q
Describe the features of nephritic syndrome
A
- Blood in urine - haematuria
- Proteinuria may also be present causing oedema
- Disruption of the endothelium results in inflammatory response and damage to glomerulus
- Commonly leads to acute renal failure and patients are hypertensive
- Proliferative - increased number of cells in the glomerulus
- Presentation triad - haematuria, reduced urine production, hypertensive
10
Q
Describe the management of nephrotic syndrome
A
- Oedema - diuretics given IV
- Salt and fluid restriction
- ACE-inhibitor - antiproteinuric
- Hypercholesterolaemia - reduce levels to prevent atheroma
- Treat underlying condition - eg. Steroids for minimal change glomerulonephritis
- Focal segmental glomerulosclerosis does not respond to steroids - fibroids irreversible
11
Q
Describe the features of IgA nephropathy
A
- Commonest type of glomerulonephritis
- Classically present with visible/invisible (picked up in urine dipstick) haematuria
- Becomes more symptomatic after mucosal infections
- Body produces more IgA to fight infection
- IgA deposits in urine and increases haematuria
- Proteinuria may or may not be present
- Likely to progress to renal failure
- No effective treatment
12
Q
Describe the pathogenesis of IgA nephropathy
A
- Auto-antibodies bind to abnormal IgA1
- Deposition of circulating IgA containing immune complexes in the glomerulus
- No semi-permeable membrane in mesangium allows immune complexes to freely deposit
- Inflammation occurs where cytokines and macrophages are recruited
- Causes proliferation of cells or high matrix quantity in mesangium
- Damage to blood vessels causes blood vessels to escape into the nephron
13
Q
Describe the pathogenesis of rapidly progressive GN
A
- Cell-mediated immunity and macrophage inflammation cause GBM to break
- Allows red blood cells to escape into the nephron and further inflammation to occur
- Epithelial cell proliferation leads to thick crescent moon shape of epithelial cells, which can undergo sclerosis (scarring)
14
Q
Describe Alport’s syndrome and its pathogenesis
A
- X-linked inherited condition
- Abnormal type IV collagen which forms the glomerular basement membrane
- Associated with deafness - collagen IV important in the ear
- Pathogenesis
- Abnormal type IV collagen overtime causes GBM to become thin and porous
- Allows red blood cells to pass into filtrate
- Excessive protein loss leading to proteinuria and sclerosis
- Progresses to renal failure
15
Q
Describe the features of Goodpasture syndrome
A
- Affects lungs and kidneys
- Relatively uncommon but rapidly progressive glomerulonephritis
- Acute onset of severe nephritic syndrome - haematuria, hypertension as well as haemoptysis
- Classically describe association with pulmonary haemorrhage (smokers)
- IgG antibodies directed against the glomerular basement membrane and triggering an inflammatory reaction
- Treatable by immunosuppression and plasmaphoresis (filter out immune complexes) if caught early
