Pathology + clinical of glomerular disease

Question 1

Define glomerulonephritis

Answer 1

Umbrella term for diseases of the glomerulus (can be inflammatory OR non-inflammatory)

Question 2

Function of podocytes

Answer 2

Line and wrap the outside of the glomerular capillaries with their foot like processes
-help prevent proteins/other large molecules from being filtered out of blood into bowman’s space

Question 3

Function of mesangial cells

Answer 3

Lie between the loops of glomerular capillaries and hold them together, supporting them

Question 4

What things don’t get filtered into bowman’s space from the afferent arteriole

Answer 4

Blood cells

Albumin/ immunoglobulins (antibodies)/ other large proteins

Question 5

Common aetiology of glomerulonephritis

Answer 5

Leukocyte infiltration, antibody deposition, and complement activation

Question 6

Glomerulonephritis commonly presents in the following 4 ways (separate presentations)

Answer 6

Haematuria - usually microscopic

Heavy proteinuria - leg oedema

Slowly increasing proteinuria

Acute renal failure

Question 7

Main causes of haematuria (4 - 3 common, 1 less common)

Answer 7

Urinary tract

• infection
• stone
• tumour

Glomerulonephritis (LESS COMMON CAUSE)

Question 8

Pathophysiology of IgA nephropathy (a type of glomerulonephritis)

Answer 8

Idiopathic but associated with formation of circulating IgA immune complexes that are prone to depositing in the mesangium of the glomerulus –> irritates the mesangial cells and causes them to proliferate which produces a bigger mesangial matrix –> disrupts filtering ability –> blood and proteins leak into urine

Question 9

IgA nephropathy (a type of glomerulonephirits) appears within 48 hours of what

Answer 9

URTI or gastroenteritis

Question 10

IgA nephropathy presents as nephritic syndrome which means they present with what urine findings (2)

Answer 10

VISIBLE haematuria

Proteinuria - less significant than the haematuria

Question 11

Prognosis of IgA nephropathy

Answer 11

Only self limiting, usually return to normal

Question 12

Investigations of IgA nephropathy + findings (3)

Answer 12

Urinalysis - urine dipstick +ve for blood

Urine microscopy - shows RBCs, RBC casts

RENAL BIOPSY (DEFINITIVE)

• light microscopy - shows enlarged mesangial matrix
• immunofluoroscence - lights up IgA deposits

Question 13

3 types of haematuria

Answer 13

Invisible

• microscopic
• dipstick

Visible (macroscopic)

Question 14

Presentation of membranous nephropathy (think: it’s a non-proliferative form of GN)

Answer 14

Nephrotic syndrome

• oedema
• proteinuria –> FOAMY urine
• hypoalbuminaemia
• hyperlipidaemia –> xanthelasma

Question 15

Pathophysiology of PRIMARY membranous nephropathy/glomerulonephritis (commonest cause of nephrotic syndrome in ADULTS)
-what happens to GBM

Answer 15

Idiopathic/autoimmune mechanism
-IgG immune complex deposits in the glomeruli –> activates complement system which recruits inflammatory cells to the area which promote inflammation and THICKENING OF GBM –> podocytes become effaced (erased) allowing things to leak into urine

Question 16

Membranous nephropathy where the glomerular basement membrane becomes very leaky because podocytes are lost, large weight molecules like albumin are easily lost so it’s one of the biggest causes of what syndrome

Answer 16

Nephrotic syndrome

Question 17

2/3 cases of membranous nephropathy are primary (idiopathic), 1/3 are secondary to (4)

Answer 17

Autoantibodies in response to underlying conditions
Autoimmune diseases- SLE
Hepatitis
Lung/colon cancer

Question 18

Primary membranous nephropathy is IDIOPATHIC

but has been found to be associated with circulating auto-antibodies to what receptor to form immune complexes

Answer 18

Phospholipase A2 receptor (PLA2R) on podocytes

Question 19

What test must you do first before renal biopsy

Answer 19

Clotting screen - to determine risk of bleeding from the biopsy

Question 20

Pathophysiology of diabetic nephropathy* (3)

*Defined by characteristic mesangial expansion, GBM thickening, and glomerular sclerosis leading to the development of Kimmelstiel-Wilson nodules

Answer 20

Due to excess blood glucose OVER-RIDING renal threshold for glucose –> glycosuria

High BG from untreated DM causes high BP which puts strain on the tiny glomerular capillaries as it causes mesangium to expand through stretch

High BG also causes glycation of proteins which stimulate expansion and THICKENING OF GBM –> hyaline arteriosclerosis –> becomes LEAKY

Question 21

Glomerular filtration barrier consist of 3 layers

Answer 21

fenestrated endothelium, the glomerular basement membrane, and the epithelial podocytes

Question 22

In diabetic nephropathy, what happens to the mesangium

Answer 22

expands and proliferates which compresses the glomerular capillaries

Question 23

In diabetic nephropathy, mesangial matrix expansion starts to invade the glomerular capillaries and produces nodules of excess mesangial matrix called

Answer 23

Kimmelstiel-Wilson nodules,

Question 24

What is crescentic glomerulonephritis (aka rapidly progressive GN)

Answer 24

Just a name used to describe forms of glomerulonephritis that are characterised by CRESCENT SHAPED PROLIFERATION OF CELLS in bowman’s space

usually are RAPIDLY PROGRESSIVE forms of GN and associated with a poor prognosis

Question 25

Crescentic glomerulonephritis (a name used to describe forms of glomerulonephritis that are characterised by CRESCENT SHAPED PROLIFERATION OF CELLS in bowman's space) What composes the crescents

Answer 25

Cellular proliferation and macrophages

Question 26

What is granulomatosis with polyangiitis (aka Wegener's granulomatosis)

Answer 26

A form of crescentic glomerulonephritis | -is a systemic vasculitis that involves inflamed vessels in the kidneys, lungs

Question 27

Autoantibody tested for in granulomatosis with polyangiitis (aka Wegener's granulomatosis)

Answer 27

anti-neutrophil cytoplasmic antibodies (ANCA)

Question 28

Sources of haematuria

Answer 28

``` Kidney Ureter Bladder Prostate Urethra ```

Question 29

Haematuria seen in nephritic or nephrotic syndrome more

Answer 29

nephritic

Question 30

Nephrotic syndrome involves the loss of a lot of ..., whereas nephritic syndrome involves the loss of a lot of ...

Answer 30

protein blood

Question 31

Nephrotic syndrome (just describes a collection of symptoms) is characterised by (4)

Answer 31

Proteinuria - LOTS Hypoalbuminaemia - albumin lost in urine Severe oedema (--> weight gain) - albumin lost in urine so decreased oncotic pressure so moves out blood vessels Hyperlipidaemia

Question 32

Nephritic syndrome (just describes a collection of symptoms) characterised by (4) presence of acute kidney injury (renal dysfunction), hypertension, and an active urinary sediment (red cells and red cell casts).

Answer 32

Haematuria - LOTS Proteinuria - MUCH LESS THAN NEPHROTIC SYNDROME Hypertension Low urine volume - renal impairment

Question 33

Hypertension is associated more with nephritic or nephrotic syndrome

Answer 33

nephritic (lots of haematuria)

Question 34

Proliferative glomerulonephritis vs non-proliferative glomerulonephritis

Answer 34

Proliferative - excessive numbers of cells in the glomeruli, e.g. infiltrating leukocytes Non-proliferative - glomeruli look normal/may have scarring but normal numbers of cells

Question 35

Nephrotic syndrome primary* (3) and secondary causes (2) These are NON-PROLIFERATIVE forms of GN

Answer 35

Primary - Minimal change disease - Focal segmental glomerulosclerosis (FSGS) - Membranous nephropathy Secondary - DM (diabetic nephropathy) - SLE

Question 36

Nephritic syndrome causes* (4) *These are PROLIFERATIVE forms of GN

Answer 36

Post-streptococcal glomerulonephritis - is a diffuse proliferative GN IgA nephropathy - is a focal proliferative GN Crescentic glomerulonephritis (or rapidly progressive) Membranoproliferative glomerulonephritis

Question 37

Post-streptococcal GN (a form of proliferative GN) is preceded by an infection with what

Answer 37

usually group A streptococci - strep pyogenes

Question 38

Investigations of glomerulonephritis in general (4)

Answer 38

Urinalysis - urine dipstick, urine microscopy U+Es FBC Renal biopsy - light microscopy with H&E stain - electron microscopy - immunofluorescence

Question 39

Diagnosis of post-streptococcal GN

Answer 39

Symptoms/signs of GN -proteinuria, haematuria, fever History of recent throat strep infection

Question 40

Treatment of post-streptococcal GN

Answer 40

Gets better on its own so just SUPPORTIVE measures - limit salt and fluid intake - MAIN (may just need this) - diuretic - to reduce oedema - BP control - ACE/ARB +/- antibiotics - to treat any remaining streptococcus

Question 41

Crescentic glomerulonephritis (aka rapidly progressive GN) is the most severe form of proliferative GN Name 2 examples of crescentic glomerulonephritis

Answer 41

Granulomatosis with polyangiitis (Wegner's granulomatosis) - vasculitic Anti-glomerular basement membrane disease (goodpasture's syndrome)

Question 42

Goodpasture's syndrome (anti-glomerular basement membrane disease) is associated with what autoantibody

Answer 42

Anti-glomerular basement membrane antibody -attacking proteins in the GBM Affects LUNGS before kidneys

Question 43

Symptoms/signs of granulomatosis with polyangiitis (a type of crescentic glomerunephritis) - constitutional - resp - cutaneous

Answer 43

Constitutional symptoms - fever, malaise, anorexia, weight loss Resp symptoms/signs - e.g. SOB, crackles Cutaneous - rash/lesions

Question 44

Treatment of granulomatosis with polyangiitis (a type of crescentic glomerunephritis) (2)

Answer 44

Immunosuppression - high dose steroids - Cyclophosphamide - chemo drug; cytotoxic

Question 45

Treatment of Goodpasture's syndrome (anti-glomerular basement membrane disease) (3)

Answer 45

Immunosuppression - high dose steroid - Cyclophosphamide - Plasmapheresis (plasma exchange)

Question 46

Principle of crescentic glomerulonephritis (e.g. granulomatosis with polyangiitis, anti-GBM disease) treatment is IMMUNOSUPPRESSION What immunosuppressants may be given (3)

Answer 46

IV high dose steroids Cyclophosphamide - chemo drug Plasma exchange

Question 47

Principles of management of nephrotic syndrome due to glomerulonephritis (2 principles; 1st principle has 3 things)

Answer 47

General measures - treat oedema - with loop diuretic - treat hypertension - with ACEI/ARB - treat high cholesterol - with statin Specific therapy towards the underlying non-proliferative GN -usually STEROID

Question 48

Minimal change disease is the commonest type of non-proliferative GN in (this type accounts for 90% nephrotic syndrome cases in these people)

Answer 48

children

Question 49

Minimal change disease (a form of non-proliferative GN) symptoms/signs

Answer 49

Nephrotic syndrome - oedema - SUDDEN ONSET - proteinuria - hypoalbuminaemia - hyperlipidaemia

Question 50

Pathological finding of minimal change disease

Answer 50

Loss of podocyte foot processes

Question 51

Treatment of minimal change disease (2) - medical - RESPONDS VERY WELL TO THIS - lifestyle

Answer 51

Oral prednisolone - repsonds very well to this Reduce oedema - with low salt diet and fluid restriction

Question 52

What is focal segmental glomerulosclerosis + initiating factor

Answer 52

A chronic form of non-proliferative GN that affects PARTS (SEGMENTAL) of SOME (FOCAL) glomeruli --> damage, scarring Initiating factor - chronic damage to foot processes of podocytes --> EFFACEMENT

Question 53

Primary/secondary causes of focal segmental glomerulosclerosis

Answer 53

Primary - idiopathic Secondary - HIV, reflux nephropathy

Question 54

If there's lots of protein in urine like in severe nephrotic syndrome, what is the appearance of the urine

Answer 54

foamy

Question 55

Which types of glomerulonephritis have high chance of progression to end stage kidney disease

Answer 55

Proliferative -crescentic glomerulonephritis Non-proliferative -focal and segmental glomerusclerosis

Question 56

Histological findings in focal segmental glomerulosclerosis

Answer 56

segmental areas of mesangial collapse and sclerosis

Question 57

Symptoms/signs of focal segmental glomerulosclerosis

Answer 57

Non-proliferative form so presents as nephrotic syndrome (the 4 characteristics) Foamy urine

Question 58

Treatment of focal segmental glomerusclerosis (5)

Answer 58

Supportive measures - salt + fluid restriction diet - loop diuretic - ACEI/ARB - statin Prednisolone - but often resistant to steroids

Question 59

Steroid treatment is often resistant in focal segmental glomerusclerosis so what alternative immunosuppressants may be given

Answer 59

Ciclosporin | Cyclophosphamide

Question 60

Definitive investigation of focal segmental glomerulosclerosis

Answer 60

Renal biopsy

Question 61

Commonest cause of nephrotic syndrome in adults v children

Answer 61

Adults - membranous nephropathy Children - minimal change disease

Question 62

Treatment of membranous nephropathy in -low risk (3) -moderate-high (above + 2) of end stage renal failure

Answer 62

Supportive measures for at least 6 months - reduce oedema - loop diuretic - BP control - ACEI/ARB - cholesterol control - statin If moderate/high risk then PLUS -steroid + cyclophosphamide

Question 63

In membranous nephropathy - light microscopy shows what - immunofluorescence shows what

Answer 63

THICKENED GBM - electron dense deposits in the subepithelial space - IgG deposits throughout capillary walls

Question 64

Management principles of any form of glomerulonephritis - supportive (4) - specific

Answer 64

Supportive measures - restrict salt and fluid intake - reduce oedema - loop diuretic - BP control - ACEI/ARB - cholesterol control - statin +/- Immunosuppression - usually prednisolone

Question 65

Post streptococcal GN occurs how long after the URTI compared to IgA nephropathy

Answer 65

post streptococcal - about 2 weeks after URTI IgA - about 2 days after