Glomerulonephritis and histology of the glomerulus

Question 1

What is glomerulonephritis?

Answer 1

• Inflammation of glomeruli
• Often involves immune system

Question 2

What 4 structures of the glomerulus can be damaged in glomerulonephritis?

Answer 2

• Capillary endothelium
• Glomerular basement membrane
• Mesangial cells
• Podocytes

Question 3

What is nephrotic syndrome?

Answer 3

• Podocyte damage
• Leading to glomerular charge barrier disruption
• Massive proteinuria
• Causes oedema (to the point that the face swells like in an allergic reaction)

Question 4

How does proteinuria lead to oedema?

Answer 4

• Loss of albumin
• Oncotic pressure of blood is reduced
• Hydrostatic pressure remains the same
• Reduction in osmotic pressure in capillaries
• Can’t move fluid out of interstitium back into circulation
• Fluid pools in extremities

Question 5

Which triad of signs/symptoms is associated with nephrotic syndrome?

Answer 5

• Proteinuria >350 mg/mmol
• Hypoalbuminaemia
• Oedema
• (usually accompanied by high cholesterol)

Question 6

What are other features of nephrotic syndrome?

Answer 6

• BP often normal (though can be low or high)
• Creatinine may be normal

Question 7

What are the primary causes of nephrotic syndrome?

Answer 7

• Minimal change disease
• Membranous glomerulonephritis
• Focal segmental glomerulosclerosis (FSGS)

Question 8

What are the secondary causes of nephrotic syndrome?

Answer 8

• Diabetes

Question 9

How does diabetes damage the kidneys?

Answer 9

• Excess glucose binds to proteins
• Especially at efferent arteriole
• Hyaline atherosclerosis obstructs blood flow
• Initially GFR increases
• Over time mesangial cells secrete more structural matrix
• Basement membrane thickens
• GFR decreases

Question 10

How is diabetic nephropathy treated so that it does not lead to renal damage?

Answer 10

• Treat hypertension
• Good glycaemic control
• ACE inhibitors
• Angiotensin receptor blockers

Question 11

What is minimal change disease?

Answer 11

• Most common cause of nephrotic syndrome in children under 6
• No significant renal changes are seen under light microscope
• Prognosis good in children, variable in adults
• Glomerular capillaries fuse with foot processes of podocytes
• Filtration barrier not formed
• Patients loose lots of proteins
• Swollen in eyes and face due to oedema

Question 12

What is membranous glomerulonephritis?

Answer 12

• Subepithelial deposition of immune complexes
• Thickening of basement membrane
• 40% adult nephrotic syndrome

Question 13

How is membranous glomerulonephritis treated?

Answer 13

• Immunosuppressants
• Treatment of underlying cause

Question 14

What is FSGS?

Answer 14

• Occurs in some glomeruli but not all
• Only affects some segments of affected glomeruli
• Podocytes damaged
• Proteins build up in glomerulus (hyalinosis) leading to sclerosis

Question 15

What are the causes of FSGS?

Answer 15

• Primary: idiopathic
• Secondary: sickle cell disease, HIV, heroin abuse, kidney hyperperfusion

Question 16

How is FSGS treated?

Answer 16

• Treatment with steroids
• Inconsistent results can lead to chronic renal failure

Question 17

How is nephrotic syndrome managed?

Answer 17

• Oedema is treated with diuretics (may need IV) and salt and fluid restriction
• ACE-Inhibitors - anti-proteinuric
• Treat underlying condition

Question 18

What is the triad of nephritic syndrome?

Answer 18

• Haematuria
• Reduction in GFR (renal impairment/oliguria)
• Hypertension (due to activation of RAAS caused by decreased GFR)

Question 19

What are the other features of nephritic syndrome?

Answer 19

• Often some proteinuria but less than nephrotic syndrome
• Disruption of endothelium results in inflammatory response and damage to glomerulus
• Onset may be acute or rapidly progressive

Question 20

What are some common causes of nephritic syndrome?

Answer 20

• IgA nephropathy (Berger’s disease)
• Rapidly progressive glomerulonephritis
• Goodpasture’s (Anti GMB)
• Post-streptococcal GN

Question 21

Outline IgA nephropathy

Answer 21

• Most common primary glomerular disease worldwide, causing recurrent haematuria
• Hypertension and IgA levels raised
• Deposited in mesangium
• Sclerosis of damaged segment
• 20% will develop advanced CKD

Question 22

How is IgA nephropathy treated?

Answer 22

• Control BP with antihypertensives
• Steroids

Question 23

What is rapidly progressive glomerulonephritis?

Answer 23

• Severe glomerular injury
• Leakage of fibrin
• Macrophages and epithelial cells proliferate
• Crescent shaped masses form and reduce glomerular blood supply
• Loss of renal function within days to weeks

Question 24

How is rapidly progressive glomerulonephritis treated?

Answer 24

• High dose steroids
• Immunosuppressants
• Plasma exchange

Question 25

What is Goodpasture’s Syndrome?

Answer 25

• Antibodies to type IV collagen in glomerular basement membrane develop
• Inflammation
• Results in rapidly progressive glomerulonephritis, acute renal failure, lung haemorrhage

Question 26

How is Goodpasture’s Syndrome treated?

Answer 26

• Plasma exchange (remove antibodies)
• Corticosteroids (remove inflammation)
• Prognosis poor without treatment

Question 27

What is post-streptococcal glomerulonephritis?

Answer 27

• Presents 1-3 weeks following group A beta-haemolytic streptococcal infection of tonsils, pharynx or skin

Question 28

How is post-streptococcal glomerulonephritis treated?

Answer 28

• Antibiotics to treat remaining infection
• Prognosis excellent in children
• ~60% adults recover completely (rest develop hypertension or renal impairment)

Question 29

How is nephritic syndrome managed?

Answer 29

• ACE-I or AIIR and salt restriction control BP and reduce proteinuria
• Treat oedema with diuretics and salt and fluid restriction
• Disease specific treatment (immunosuppressants)
• Stop smoking, statins etc to manage cardiovascular risk
• Dialysis (often short-term)