Haematuria & nephritic syndrome Flashcards
Common causes of nephritic syndromes
- *Post streptococcal GN**
- Most common in children
- 2-4 weeks post GAS infection (strep pharyngitis, impetigo)
Pathophysiology
- M-protein virulence factor form type 3 hypersensitivity reaction
- IgG & IgM immune complexes deposit b/w podocytes and basement membrane
- lead to activation of inflammatory processes- C3 activation, cytokines, proteases → damage podocytes
Investigations/diagnosis
- decreased C3, elevated strep titres/serology (ASOT), kidney bx not diagnostic but can support dx
- IgG,M & C3 deposits along BM/mesangium ‘starry sky appearence’
- usually resolves, can lead to ESRD → age affects prognosis
- *IgA nephropathy (Berger’s)**
- Often following respiratory or GI infection (IgA present in these tissues)
Pathophysiology
- Abnormal IgA formed in body → IgG targets and forms immune complexes which deposit in kidney (mesangium)
- Activate alternative complement pathway → proinflammatory cytokines & macrophage activation → glomerular injury
Investigations/treatment
- Mesangial proliferation on light microscopy, immune complexes on immunofluorescence
- *IgA vasculitis (HSP)**
- Seperate disorder
- Systemic disease
- Purpuric rash, abdominal pain, arthritis
- Can cause nephritic or nephrotic syndrome
- *Diffuse proliferative GN/SLE nephritis**
- Type 3 hypersensitivity reaction
- Classified by site of immune complex deposition
- >50% of glomeruli in both kidneys affected
Pathophysiology
- SLE leads to autoimmune complex formation → deposition in multiple parts of the body → deposits in subendothelial space of kidney
Investigations
- light microscopy: wire loop appearence/subendothelial immune complexes
- immunofluroescence: granular immune complexes
Membranoproliferative GN (MPGN)
3x types:
Type 1: most common → idiopathic or Hep B/C
- type 3 hypersensitivity
- immune complexes from hep B/C → activate classical complement pathway → complement/immune complex deposition between GBM/endothelium
- *Type 2:** Inappropriate activation of alternative complement pathway (genetic mutation or IgG autoantibody- C3NEF)
- C3→ C3a/b by C3 convertase (stabilised by C3NEF)
- Low C3 levels
- Complement deposits in subendothelium of kidney
Type 3 poorly understood
Pathophysiology
- Complex/complement deposition in subendothelium → activation of inflammatory cytokines → inflammation damages GBM, thickening of GBM & mesangial proliferation → mesangial interposition
Light microscopy: tram track appearence
Immunofluorescence: granular immune complexes
- *Rapidly progressive GN (RPGN)**
- Type 2 or 3 hypersensitivity, or no immune complexes
- Inflammation so severe → breaks BM → decline in renal function in weeks
- *Type 1: Goodpasture disease**
- Type 2 hypersensitivity
- AntiGBM antibodies → activate complement and damage BM & collagen
- Also occurs in lungs → haemoptysis
Type 2
- Type 3 hypersensitivity
- Can be caused by PSGN/diffuse proliferative (SLE)
- *Type 3: granulomatosis polyangitis (GPA) + microscopic polyangitis**
- Pauci-immune vasculitis
- GPA: sinusitis, otitis media, haemoptysus, cANCA present- non caseating granulomas on histology (DDx goodpastures but no URT sx)
- MPA: haemoptysus, no URT sx, pANCA positive, no granulomas
Pathophysiology
- Rapid and severe injury leading GBM to break → loss of blood, plasma proteins, immunoglobulins → inflammatory markers, macrophages, fibrin → GBM thickening and cresent moon shape in bowman’s space
Investigations
- Light microscopy: crescent moon fibrin deposits
- immunofluorescence: linear deposits (goodpastures), granular deposits (type 2), pauci immune → will not show deposits
Nephritic syndrome overview
Caused by inflammation that damages GBM
Macroscopic/microscopic haematuria
RBC casts in urine
Progresses to renal failure:
- HTN
- Oliguria
- Oedema
Investigations
- Urinalysis: haematuria, RBC casts in urine proteinuria (<3.5g/d, more elevated in severe cases)
- Elevated BUN
- Kidney Bx for diagnosis
Common causes
- Type 3 hypersensitivity
- Post strep GN (PSGN)
- IgA nephropathy
- Diffuse proliferative GN - Multiple causes
- Membranoproliferative/mesangiocapillary GN
- Rapidly progressive GN - Alport syndrome
Alport syndrome
Alport syndrome genetic cause of glomerular dysfunction is caused by mutations in genes encoding the alpha-3, alpha-4, and alpha-5 chains of type IV collagen.
This leads to abnormalities of the basement membranes of the kidney (glomerular disease), cochlea (sensorineural hearing loss), and eye (anterior lenticonus is pathognomonic).
Autosomal dominant: 5% (mutations in COL4A3 or COL4A4).
Autosomal recessive: 15% (mutations in COL4A3 or COL4A4).
Most cases are X linked (mutations in COL4A5 gene).
Light microscopy: thin GBM in areas, ‘basket weave appearance’ → occasional thickening
