Glomerular Diseases Flashcards
What sturctures could be damaged in glomerulonephritis?
Capillary endothelium
Glomerular basement membrane
Mesangial cells
Podocytes
What changes can occur in glomerulonephritis?
Narrowed capillary lumen
Fusion of foot processes (podocytes)
Increased number of mesangial cells
Subepithelial immune complexes (“humps”)
What are the 5 different clinical presentations of GN?
- Asymptomatic proteinurea / haematuria
- Chronic glomerulonephritis
- Acute glomerulonephritis
- Rapidly progressive glomerulonephritis
- Nephrotic syndrome
Most of the diseases can present in more than one of these ways.
What is the difference between nephrotic and nephritic syndromes?
Nephrotic - podocytes damage leading to glomerulus charge -barrier disruption + massive proteinurea and oedema
Nephritic - Inflammation disrupting the glomerular basement membrane. It presents with haematuria (coco-cola coloured urine).
How do you define nephrotic syndrome?
Triad of:
Proteinuria
Hypoalbuminaemia
Oedema
Usually accompanied by high cholesterol
BP often normal (but can be high or low)
Creatinine may be normal
Proteinuria > 350mg/mmol alone.
What are common causes of nephrotic syndrome?
Primary:
Minimal change disease
Membranous nephropathy
Focal segmental glomerulosclerosis (FSGS)
Secondary:
Diabetes
SLE
Amyloidosis
How do you manage nephrotic syndrome?
Oedema:
- Diuretics, need large dose and may need to be i.v. if gut oedema
- Salt and fluid restriction
ACE-inhibitor
-anti-proteinuric
Hypercholestrolaemia
- Statin if need be but not always
Treat underlying condition / cause of disease
How do you define nephritic syndrome?
Triad of:
Haematuria
Reduction on GFR
Hypertension
Other features
- Proteinuria - less than nephrotic
- Disruption of the endothelium results in inflammatory response and damage to the glomerulus
- Onset may be acute or rapidly progressive
- Rapidly progressive GN is a severe nephritic syndrome
What are some common causes of nephritic syndrome?
Anti-GBM disease (goodpasture’s) ANCA-associated vasculitis IgA / Henoch-Schonlein purpura Post-infectious Lupus
How do you manage nephritic syndrome?
BP control / reduction of proteinuria
- ACE
- Salt
Treatment of oedema
Disease specific treatments
-Generally immunosuppressants
CVS risk management
-Stop smoking, statin ect..
Dialysis (short-term)
What is ANCA-associated vasculitis?
Granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis
Affect small arterioles
Often kidneys and lungs
‘Pulmonary-renal syndrome’
Often systemic symptoms - fatigue, arthralgia, myalgia, weight loss
No immune deposits in kidney - circulating antibodies to white cells. Endothelial damage.
What is anti-GBM disease (Goodpasture’s)?
Caused by antibodies to a3 chain of Collage IV in GBM or (but less likely as heard to reach) alveolar basement membrane.
Pulmonary haemorrhage likely- especially if pre existing damage to endothelium (smokers, infection..)
Always cases rapidly progressing glomerulonephritis
What is systemic lupus erythematosus (SLE)?
Auto-immune systemic disease that can affect multiple systems.
Has many different patterns of renal disease
so it can cause nephritic and nephrotic syndrome
Prognosis depends on type of lesion, activity n amount fo kidney involves.
Treatment varies according to pattern of lupus nephritis.
What is diabetic Nephropathy?
Commonest cause of end stage renal disease.
30-40% of all types of diabetes eventually get ESRD
What pathological changes occur in diabetic nephropathy?
- Hyperfiltration / capillary hypertension - early, related by hyperglycaemia, glomerular hypertension and increase GFR.
- Glomerular basement membrane thickening
- Mesangial expansion
- Podocyte injury
- Glomerular sclerosis / arteriosclerosis
How nephron change in DM?
Afferent vasodilation and efferent vasoconstriction.
Afferent vasoconstriction:
- Hyperglycaemia
- High blood amino acid levels
- Low NaCl delivery to the macula dense
Also:
Increased NaCl and glucose filtration and reabsorption. (So decreased distal delivery of NaCl)
Efferent vasodilation:
-High local angiotensin II levels.
How doe GBM change in DN?
Damage to podocytes
Thickened GBM increases pore size
High intraglomerular pressure
Mesangial expansion
More Wilson nodules
What are the clinical signs of diabetic nephropathy in the 1st stage (hyper filtration and hypertrophy)?
Increased GFR
Normal histology.
What are the clinical signs of diabetic nephropathy in the latent stage?
Normal albuminurea
GBM thickening and mesangial expansion
What are the clinical signs of diabetic nephropathy in the 3rd stage (Microalbuminuria)?
Variable mesangial expansion / sclerosis
Increased GBM thickening
Podocyte changes
GFR normal
What are the clinical signs of diabetic nephropathy in the 4th stage (Overt proteinuria)?
Diffuse glomerular histopathological changes
Systemic hypertension
Falling GFR
Then end stage renal disease
How long does it take to develop ESRD?
About 20yrs - but not decreasing and less people get to the end.
What is microalbuminuria?
First clinical sign
GBM thickening and mesangial expansion
Albuminuria
30-300mg/day
‘Albustix’ -used to measure albumin.
At this stage, it is potentially reversible.
What is overt proteinuria?
Proteinuria over 30mg/mmol Cr detectable on a dipstick.
It was previously associated with ESRD in 3-7years but prognosis is improving lots.
GFR normal then gradually drops.
Mesangial expansion and sclerosis means there is reduced surface area for filtration
Worsening systemic hypertension
Microvascular changes (hyalinosis of arterioles) causes tissue ichaemia.
