Pathology + clinical of glomerular disease Flashcards
Define glomerulonephritis
Umbrella term for diseases of the glomerulus (can be inflammatory OR non-inflammatory)
Function of podocytes
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
Function of mesangial cells
Lie between the loops of glomerular capillaries and hold them together, supporting them
What things don’t get filtered into bowman’s space from the afferent arteriole
Blood cells
Albumin/ immunoglobulins (antibodies)/ other large proteins
Common aetiology of glomerulonephritis
Leukocyte infiltration, antibody deposition, and complement activation
Glomerulonephritis commonly presents in the following 4 ways (separate presentations)
Haematuria - usually microscopic
Heavy proteinuria - leg oedema
Slowly increasing proteinuria
Acute renal failure
Main causes of haematuria (4 - 3 common, 1 less common)
Urinary tract
- infection
- stone
- tumour
Glomerulonephritis (LESS COMMON CAUSE)
Pathophysiology of IgA nephropathy (a type of glomerulonephritis)
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
IgA nephropathy (a type of glomerulonephirits) appears within 48 hours of what
URTI or gastroenteritis
IgA nephropathy presents as nephritic syndrome which means they present with what urine findings (2)
VISIBLE haematuria
Proteinuria - less significant than the haematuria
Prognosis of IgA nephropathy
Only self limiting, usually return to normal
Investigations of IgA nephropathy + findings (3)
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
3 types of haematuria
Invisible
- microscopic
- dipstick
Visible (macroscopic)
Presentation of membranous nephropathy (think: it’s a non-proliferative form of GN)
Nephrotic syndrome
- oedema
- proteinuria –> FOAMY urine
- hypoalbuminaemia
- hyperlipidaemia –> xanthelasma
Pathophysiology of PRIMARY membranous nephropathy/glomerulonephritis (commonest cause of nephrotic syndrome in ADULTS)
-what happens to GBM
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
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
Nephrotic syndrome
2/3 cases of membranous nephropathy are primary (idiopathic), 1/3 are secondary to (4)
Autoantibodies in response to underlying conditions
Autoimmune diseases- SLE
Hepatitis
Lung/colon cancer
Primary membranous nephropathy is IDIOPATHIC
but has been found to be associated with circulating auto-antibodies to what receptor to form immune complexes
Phospholipase A2 receptor (PLA2R) on podocytes
What test must you do first before renal biopsy
Clotting screen - to determine risk of bleeding from the biopsy
Pathophysiology of diabetic nephropathy* (3)
*Defined by characteristic mesangial expansion, GBM thickening, and glomerular sclerosis leading to the development of Kimmelstiel-Wilson nodules
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
Glomerular filtration barrier consist of 3 layers
fenestrated endothelium, the glomerular basement membrane, and the epithelial podocytes
In diabetic nephropathy, what happens to the mesangium
expands and proliferates which compresses the glomerular capillaries
In diabetic nephropathy, mesangial matrix expansion starts to invade the glomerular capillaries and produces nodules of excess mesangial matrix called
Kimmelstiel-Wilson nodules,
What is crescentic glomerulonephritis (aka rapidly progressive GN)
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
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
Cellular proliferation and macrophages
What is granulomatosis with polyangiitis (aka Wegener’s granulomatosis)
A form of crescentic glomerulonephritis
-is a systemic vasculitis that involves inflamed vessels in the kidneys, lungs
Autoantibody tested for in granulomatosis with polyangiitis (aka Wegener’s granulomatosis)
anti-neutrophil cytoplasmic antibodies (ANCA)
Sources of haematuria
Kidney Ureter Bladder Prostate Urethra
Haematuria seen in nephritic or nephrotic syndrome more
nephritic
Nephrotic syndrome involves the loss of a lot of …, whereas nephritic syndrome involves the loss of a lot of …
protein
blood
Nephrotic syndrome (just describes a collection of symptoms) is characterised by (4)
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
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).
Haematuria - LOTS
Proteinuria - MUCH LESS THAN NEPHROTIC SYNDROME
Hypertension
Low urine volume - renal impairment
Hypertension is associated more with nephritic or nephrotic syndrome
nephritic (lots of haematuria)
Proliferative glomerulonephritis vs non-proliferative glomerulonephritis
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
Nephrotic syndrome primary* (3) and secondary causes (2)
These are NON-PROLIFERATIVE forms of GN
Primary
- Minimal change disease
- Focal segmental glomerulosclerosis (FSGS)
- Membranous nephropathy
Secondary
- DM (diabetic nephropathy)
- SLE
Nephritic syndrome causes* (4)
*These are PROLIFERATIVE forms of GN
Post-streptococcal glomerulonephritis - is a diffuse proliferative GN
IgA nephropathy - is a focal proliferative GN
Crescentic glomerulonephritis (or rapidly progressive)
Membranoproliferative glomerulonephritis
Post-streptococcal GN (a form of proliferative GN) is preceded by an infection with what
usually group A streptococci - strep pyogenes
Investigations of glomerulonephritis in general (4)
Urinalysis - urine dipstick, urine microscopy
U+Es
FBC
Renal biopsy
- light microscopy with H&E stain
- electron microscopy
- immunofluorescence
Diagnosis of post-streptococcal GN
Symptoms/signs of GN -proteinuria, haematuria, fever
History of recent throat strep infection
Treatment of post-streptococcal GN
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
Crescentic glomerulonephritis (aka rapidly progressive GN) is the most severe form of proliferative GN
Name 2 examples of crescentic glomerulonephritis
Granulomatosis with polyangiitis (Wegner’s granulomatosis) - vasculitic
Anti-glomerular basement membrane disease (goodpasture’s syndrome)
Goodpasture’s syndrome (anti-glomerular basement membrane disease) is associated with what autoantibody
Anti-glomerular basement membrane antibody
-attacking proteins in the GBM
Affects LUNGS before kidneys
Symptoms/signs of granulomatosis with polyangiitis (a type of crescentic glomerunephritis)
- constitutional
- resp
- cutaneous
Constitutional symptoms - fever, malaise, anorexia, weight loss
Resp symptoms/signs - e.g. SOB, crackles
Cutaneous - rash/lesions
Treatment of granulomatosis with polyangiitis (a type of crescentic glomerunephritis) (2)
Immunosuppression
- high dose steroids
- Cyclophosphamide - chemo drug; cytotoxic
Treatment of Goodpasture’s syndrome (anti-glomerular basement membrane disease) (3)
Immunosuppression
- high dose steroid
- Cyclophosphamide
- Plasmapheresis (plasma exchange)
Principle of crescentic glomerulonephritis (e.g. granulomatosis with polyangiitis, anti-GBM disease) treatment is IMMUNOSUPPRESSION
What immunosuppressants may be given (3)
IV high dose steroids
Cyclophosphamide - chemo drug
Plasma exchange
Principles of management of nephrotic syndrome due to glomerulonephritis (2 principles; 1st principle has 3 things)
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
Minimal change disease is the commonest type of non-proliferative GN in
(this type accounts for 90% nephrotic syndrome cases in these people)
children
Minimal change disease (a form of non-proliferative GN) symptoms/signs
Nephrotic syndrome
- oedema - SUDDEN ONSET
- proteinuria
- hypoalbuminaemia
- hyperlipidaemia
Pathological finding of minimal change disease
Loss of podocyte foot processes
Treatment of minimal change disease (2)
- medical - RESPONDS VERY WELL TO THIS
- lifestyle
Oral prednisolone - repsonds very well to this
Reduce oedema - with low salt diet and fluid restriction
What is focal segmental glomerulosclerosis + initiating factor
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
Primary/secondary causes of focal segmental glomerulosclerosis
Primary - idiopathic
Secondary - HIV, reflux nephropathy
If there’s lots of protein in urine like in severe nephrotic syndrome, what is the appearance of the urine
foamy
Which types of glomerulonephritis have high chance of progression to end stage kidney disease
Proliferative
-crescentic glomerulonephritis
Non-proliferative
-focal and segmental glomerusclerosis
Histological findings in focal segmental glomerulosclerosis
segmental areas of mesangial collapse and sclerosis
Symptoms/signs of focal segmental glomerulosclerosis
Non-proliferative form so presents as nephrotic syndrome (the 4 characteristics)
Foamy urine
Treatment of focal segmental glomerusclerosis (5)
Supportive measures
- salt + fluid restriction diet
- loop diuretic
- ACEI/ARB
- statin
Prednisolone - but often resistant to steroids
Steroid treatment is often resistant in focal segmental glomerusclerosis so what alternative immunosuppressants may be given
Ciclosporin
Cyclophosphamide
Definitive investigation of focal segmental glomerulosclerosis
Renal biopsy
Commonest cause of nephrotic syndrome in adults v children
Adults - membranous nephropathy
Children - minimal change disease
Treatment of membranous nephropathy in
-low risk (3)
-moderate-high (above + 2)
of end stage renal failure
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
In membranous nephropathy
- light microscopy shows what
- immunofluorescence shows what
THICKENED GBM
- electron dense deposits in the subepithelial space
- IgG deposits throughout capillary walls
Management principles of any form of glomerulonephritis
- supportive (4)
- specific
Supportive measures
- restrict salt and fluid intake
- reduce oedema - loop diuretic
- BP control - ACEI/ARB
- cholesterol control - statin
+/- Immunosuppression - usually prednisolone
Post streptococcal GN occurs how long after the URTI compared to IgA nephropathy
post streptococcal - about 2 weeks after URTI
IgA - about 2 days after