Lecture 15 - Glomerular pathology

Question 1

Focal

Answer 1

Less than 50% of the glomeruli affected

Question 2

Segmental

Answer 2

Part of the glomerular tuft affected

Question 3

Membranous

Answer 3

Thickening of the glomerular capillary wall

Question 4

Crescent

Answer 4

Accumulation of cells within the Bowman’s capsule

Compress glomerulus

Question 5

Specialised structures of the glomerulus

Answer 5

Mesangial cells
Juxtaglomerular apparatus
Podocytes
-vely charged basement membrane 
Fenestrated endothelium

Question 6

Nephrotic syndrome cardinal signs

Answer 6

Proteinurea - frothy urine
Hypoablumineamia
Oedema

Question 7

Hypercholesteraemia and hyperlipidaemia

Answer 7

Seen in nephrotic syndrome due to decreased production of apolipoproteins due to proetinuria

Liver makes albumin to compensate and also produces lipids

Question 8

Nephrotic syndrome location

Answer 8

Podocytes
Subepithelial damage
GBM - decreased filtration allowing proteins to be filtered

Question 9

Primary causes of nephrotic syndrome

Answer 9

Minimal change glomerulonephritis
Focal segmental glomerulosclerosis
Membranous glomerulonephritis

Question 10

Secondary causes of nephrotic syndrome

Answer 10

Diabetic nephropathy

Systemic lupus erythromatous

Question 11

Minimal change glomerulonephritis

Answer 11

Seen in children

Does not progress to renal failure

Unknown circulating factor that causes acute podocyte damage - nephrotic syndrome

• intact GBM (use silver stain)

Treatment: steroids
Relapse if treatment is stopped

Question 12

Focal segmental glomerulosclerosis

Answer 12

• Seen in adults
• Can progress to renal failure
• Unknown circulating factor damaging podocytes causing scarring and decreased GFR due to glomerulosclerosis
• Less responsive to steroids
• Cannot give renal transplant because circulating factor still circulating

Question 13

Membranous glomerulonephritis

Answer 13

Most common
Affects individuals of any age

1. IgG antibody is produced against podocytes
2. The antibody forms immune complexes with the podocyte antigen
3. Immune complexes deposited in glomerulus as not filtered
4. Activates compliment cascade causing inflammation

Question 14

Prognosis of Membranous glomerulonephritis

Answer 14

1/3rd get better
1/3rd no change
1/3rd progress to renal failure

Question 15

Membranous glomerulonephritis histology

Answer 15

Immune deposits

GBM spikes

Question 16

Diabetic nephropathy

Answer 16

1 - Hyperglycaemia
2 - Glycation of proteins in the GBM 
3 - Thickened GBM wall 
4 - hyaline arteriosclerosis
5 - glomerular hypertension 
6 - Increased GFR
7 - Hyperfiltration

Question 17

Kimmel wilson nodules

Answer 17

1. Glycation of proteins
2. Increases cytokines
3. Mesangial expansion
4. Kimmel Wilson nodules - deposits of proteins
5. Vessels expand further with bigger filtration slits so more leaky

Question 18

Diabetic nephropathy stages

Answer 18

Hyperfiltration
Microalbuminuria
Overt proteinuria - decreased GFR irreversible
ESRD

Question 19

How does diabetic nephropathy cause glomerular hypertension ?

Answer 19

1. Glycation of proteins
2. SGLT2 upregulated
3. Reduced Na+ to macula densa stimulating the afferent arteriole to dilate and RAAS
4. Efferent arteriole constricts

Question 20

Nephritic syndrome cardinal features

Answer 20

Haematuria
Hypertension
Oliguria

Question 21

Causes of nephritic syndrome

Answer 21

Goodpasture’s syndrome
ANCA vasculitis
SLE

Hameaturia:
IgA nephropathy
Alport’s syndrome

Question 22

Pathphysiology of nephritic syndrome

Answer 22

1. Inflammation of glomerulus
2. Infiltration of GBM by immune cells may form platelet plug in endothelial cells
3. Renal plasma flow drops
4. Reduced GFR

Question 23

What does reduced GFR cause in nephritic syndrome?

Answer 23

Oliguria - less urine filtered
Azotemia - nitrous containing waste products are not properly filtered
Hypertension - RAAS activated

Question 24

How is nephritic syndrome managed?

Answer 24

Treat underlying cause
Treat oedema - diuretics
BP control - ACE inhibitors, angiotensin receptor blockers and salt restriction

Question 25

Goodpasture's syndrome

Answer 25

Anti - GBM disease - Body produces antibodies against the GBM where collagen IV affected. - Large holes are created which causes hyperfiltration - Rapidly progresses to acute severe nephritic syndrome - Type 3 sensitivity reaction Treatment: - Immunosuppression - Plasmapheresis (filter blood of the antibody)

Question 26

ANCA vasculitis

Answer 26

Caused by anti-neutrophilic cytoplasmic autoantibody (ANCA) - binds to and activates neutrophils - Activated neutrophils attack small blood vessels which can include the glomerulus - Develops into nephritic syndrome Treatments: - Immunosuppression - Plasmapheresis (filter blood of the antibody) Histologically: crescent segmental necrosis of glomerulus

Question 27

IgA nephropathy

Answer 27

Occurs at any age Occurs in mesangial cells MOST COMMON cause of glomerulonephritis and most progresses to renal failure Immune complexes formed with galactose deficient IgA deposits in the glomerulus mesangial cells as it cannot be filtered. Stimulates compliment pathway and inflammation

Question 28

Alports syndrome

Answer 28

X linked autosomal recessive Hereditary defective collagen IV Associated with deafness GBM already has holes

Question 29

What is damaged in glomerulonephritis?

Answer 29

1. Capillary endothelium 2. GBM 3. Mesangial cells 4. Podocytes