8. Glomerular pathology Flashcards
label this diagram
name the 4 sites of possible glomerular injury - which is most commonly affected in nephortic and nephritic syndrome
- subepithelial - affects podocytes (nephrotic syndrome)
- glomerular basement membrane
- subendothelial - affects arteriolar endothelium (nephritic syndrome)
- mesangium
name the 4 clinical features of nephrotic syndrome - why do these occur
Nephrotic syndrome:
- Proteinuria (>3.5g/day) - due to loss of glomerular filtration barrier (gaps between podocytes)
- Hypoalbuminaemia - due to loss in urine
- Oedema - due to decreased capillary oncotic pressure from albmin loss
- Hyperlipidaemia - due to hepatic lipoprotein overproduction (side effect of attempting to increase protein synthesis)
name the 5 clinical features of nephritic syndrome - explain why these occur
- Haematuria (coca-cola coloured urine) - due to glomerular capillary inflammation
- Proteinuria (<3.5g/day) - due to glomerular capillary inflammation
- Oligouria (decreased UO) - due to progressive glomerular damage causing decreased overall GFR
- Hypertension - due to disruption of normal renal BP regulation
- Red cell casts (in urine) - form in nephron tube due to glomerular damage
name 3 common primary and 2 secondary causes of nephrotic syndrome
which is the most common primary cause in children and adults
Primary:
- minimal change glomerulonephritis (most common cause in children)
- focal segmental glomerulosclerosis
- membranous glomerulonephritis (most common cause in adults)
Secondary:
- diabetes mellitus
- amyloidosis
what is the pathophysiology and prognosis in minimal change glomerulonephritis
- pathogenesis unclear - likely immune-mediated: unknown circulating factor damages podocytes (only visible on electron microscopy, i.e. minimal change)… decreased selectivity of glomerular filtration… significant albuminuria
- good prognosis: incidence reduces with age, responds to steroid treatment (although may recur), usually no progression to renal failure
what is the pathophysiology and prognosis in focal segmental glomerulosclerosis
- on a spectrum with MCG, but also affects adults
- pathogenesis unclear (likely immune-mediated): unknown circulating factor damages podocytes in subset of glomeruli… localised deposition of plasma proteins… initiates a “segment” of sclerosis in those glomeruli… decreased selectivity of glomerular filtration… non-selective proteinuria
- poor prognosis: typically progressive towards chronic renal failure, less responsive to steroid therapy. Requires dialysis/other renal support.
what is the pathophysiology and prognosis in membranous glomerulonephritis
- Pathogenesis:
i. auto-antibodies (IgG) generated against antigen in glomerular barrier…
ii. form ‘in-situ’ immune complexes on subepithelial basement membrane… activate complement…
iii. thickened basement membrane and podocyte damage…
iv. decreased selectivity of glomerular filtration… non-selective proteinuria - Prognosis: 1/3 improve with treatment, 1/3 no change, 1/3 progress to renal failure
describe the management of nephrotic syndrome
- oedema treatment:
- large doses of diuretics
- salt and fluid restriction - ACE-inhibitors: anti-proteinuric (not if intravascularly depleted or if renal function deteriorating acutely)
- Statins: hypercholesterolaemia treatment
- Treat underlying condition, e.g. steroids for MCD
name 3 common causes for nepritic syndrome
name 2 common immune causes for haematuria
Nephritic syndrome:
- Goodpasture syndrome (anti-GBM disease)
- Vasculitis, e.g. ANCA-associated vascultitis
- Lupus
Haematuria:
- IgA nephropathy
- Thin GBM disease/hereditary nephropathy (Alport’s syndrome)
what is the pathophysiology and prognosis in IgA nephropathy
- pathophysiology: deposition of IgA immune complexes in mesangium… mesangial damage and glomerulus inflammation… nephritic syndrome (episodic manifestation often associated with mucosal infections)
- prognosis: variable histological features and course, with some progressing to renal failure, with no effective treatment
describe the pathogenesis of ANCA-associated vasculitis - how will P present
- Pathogenesis: dev. of auto-antibodies that activate neutrophils to damage endothelium of small blood vessels, e.g. renal arterioles (but also other parts of body, e.g. lungs)… inflammation.
- Often systemic symptoms (inflammatory condition): fatigue, arthralgia, myalgia, weight loss, rash (inflammation of skin BVs)
describe the management of nephritic syndrome
- BP control/reduction of proteinuria:
- ACEi or AngIIRi 1st line (if renal function allows)
- salt restriction - oedema treatment:
- large doses of diuretics
- salt and fluid restriction - cardiovascular risk management: stop smoking, statins, etc.
- diseases-specific treatments, generally immunosuppressants, e.g. prednisolone
which condition can cause nephrotic or nephritic syndrome
systemic lupus erythematosus
