Nephrotic, nephritic & glomerulonephropathies Flashcards
Define nephrotic syndrome
Nephrotic syndrome is a triad of;
- Proteinuria (>3g/24hr)
- Hypoalbuminaemia (<25g/L)
- Oedema
Hyperlipidaemia
What causes the oedema in nephrotic syndrome?
Hypoalbuminaemia? (although oncotic pressure is unchanged)
It is due to;
- Na+ retention in ECM
- Inc permeability in capillary barrier
Exacerbation of oedema:
- Oedema causes ↓plasma volume
→ Detected by baroreceptors
→ Nucleus tractus solitarius → Ventrolateral medulla → ↑sympathetic outflow & via hypothalamus & post. pituirty ↑ADH release - Oedema causes ↑plasma osmolarity
→ Detected by osmoreceptors in hypothalamus
→ post. pituirty ↑ADH release
ADH: ↑water permeability in collecting duct
What causes the hypoalbuminaemia in nephrotic syndrome?
- Heavy proteinuria
- Inc renal catabolism of filtered protein
More than 3g protein exits the blood, most is reabsorbed and catabolised in the nephron, the rest is excreted with urine.
What causes the hyperlipidaemia in nephrotic syndrome?
Increased synthesis (by the liver along side its compensation for the loss of protein) and impaired catabolism
What are the clinical features of Nephrotic syndrome?
Signs;
- Oedema: typically pitting and dependent (↑ with gravity), periorbitally and peripherally
- Genital oedema, ascites & anasarca
- Normal BP (or ↑)
- Proteinuria (3g/24hrs)
- Hypoproteinaemia (hypoalbuminaemia) <25g/L
Define nephritic syndrome and its pathophysiology
- Haematuria (with dysmorphic RBCs and RBC casts proving its from the glomerulus)
- ↑BP (hypertension)
- Progressive oligouria & renal impairment
Also proteinuria, hypoproteinaemia & oedema present (nephrotic); although less.
Inflammation causes ↓renal perfusion (and hence progressive oligouria)
→ Activation of renin-angiotensin-aldosterone system
→ Angiotensin 2: ↑Na+/water resorption proximal CT & vasoconstriction & ↑sympatheitc & aldosterone/ADH release)
→ Aldosterone: ↑Na+/water resorption distal CT
→ ADH (post. pituitary): ↑water permeability in collecting duct
→ ↑blood volume and_ ****↑BP_
What causes the oligouria in nephritic syndrome?
Inflammation causes ↓renal perfusion (and hence progressive oligouria)
What causes the hypertension in nephritic syndrome?
Inflammation causes ↓renal perfusion (and hence progressive oligouria)
→ Activation of renin-angiotensin-aldosterone system
→ Angiotensin 2: ↑Na+/water resorption proximal CT & vasoconstriction & ↑sympatheitc & aldosterone/ADH release)
→ Aldosterone: ↑Na+/water resorption distal CT
→ ADH (post. pituitary): ↑water permeability in collecting duct
→ ↑blood volume and ↑BP
How do you determine if haematouria originated in the glomeruli?
- Dysmorphic RBCs
- RBC casts
What are the 8 glomerulonephropathies?
- Minimal Change GN
- Membranous Nephropathy (GN)
- Focal Segmental Glomerulosclerosis
- Mesangiocapillary GN
- IgA Nephropathy
- Thin Basement Membrane Nephropathy
- Proliferative (Post-Streptococcal) GN
- Rapidly Progressive GN
LOADS!
What GNs are most common in children and adults?
Children;
- Minimal-change nephropathy
Adults;
- Membranous nephropathy
- Focal segmental glomerulosclerosis
- IgA nephropathy in developed world!
Outline Minimal Change Glomerulonephritis
- Histological findings and cause
- Aetiology & associations
- Tests
- Treatment
- Prognosis
Histological findings and cause;
- T-cell medited → Cytokines → Effaced podocyte foot processes (EM)
- Normal on LM
- No immune complexes seen on immunofluorescence
Aetiology;
- 76%+ of children, 20% of adults
- Predominantly boys
Associations
- Hodgekin’s lymphoma
- Drugs (NSAIDs)
Tests
- Selective proteinuria (albumin) often
- Biopsy → EM → Effaced podocyte foot processes
Treatment
- Steroids!
- Cyclophosphamide/ ciclosporin
Prognosis
- ~1% → ESRF
Outline Membranous Nephropathy (GN)
- Histological findings
- Associations
- Presentation & Prognosis
- Treatment
Histological findings
- Thickened GBM → IgG & C3 deposits resorbed! Spike & dome!
Associations
- Drugs (penicillamine, gold, NSAIDs, captopril [ACE inhibitor])
- Autoimmune disease (SLE, thyroiditis)
- Neoplasia (carcinoma of lung, colon, stomach, breast & lymphoma)
- Infections (hepatitis B & C, schistosomiasis & Plasmodium malariae
- Others (Sarcoidosis, sickle cell)
Presentation
- Mainly nephrotic
- Common in adults
Prognosis
- 1/3 remit, 1/3 same, 1/3 ESRF
Treatment
- Steroids → Cyclophosphamide/ Ciclosporin/ Chlorambucil
Outline Focal Segmental Glomerulosclerosis
- Meaning of the name
- Histological findings
- Causes
- Treatment
- Prognosis
Focal Segmental Glomerulosclerosis
- Focal = Not ALL of the kidneys glomeruli (opposite is global)
- Segmental = Not ALL of a particular glomeruli (opposite is diffuse)
- Glomerulosclerosis = Hardening of the glomeruli
Histological findings
- IgM & C3 deposits → focal segmental sclerosis
- Similar findings in HIV infection
Causes
- Primary (unknown/ idiopathic)
- Secondary
- Vesicoureteric reflux (urine backflow from bladder)
- IgA nephropathy
- Alport’s syndrome (type 4 collagen issue)
- Vasculitis
- Sickle cell
- Heroin use
- HIV is associated with a subtype
Treatment
- Corticosteroids → Cyclophosphamide/ Ciclosporin
Prognosis
- 3050% → ESRF
- Recurs in 20/50% of transplanted kidneys
Outline Mesangiocapillary GN
- Common presentation
- Histological changes & causes
- Types
- Prognosis
Typical presentation
- Nephrotic (30% nephritic)
Histological changes & causes
- Large glomeruli
- Mesangial proliferation
- Thickened capiliary wall → ‘tramline’ BM
- Due to deposits in;
Types
- Subendothelial immune deposits
- Classical complement (↓C4)
- Idiopathic or seen with HCV, endocarditis, visceral abscess, infected arteriovenous shunts & HBV
- Intramembranous deposits
- Alternative complement ( ↓C3 & +ve C3 Nephritic factor)
- Sometimes partial lopodystopy (gaunt face appearance)
Prognosis
- 50% → ESRF
Outline IgA nephropathy (Berger’s disease)
- Common presentation
- Histological changes and cause
- Treatment
- Prognosis
Common presentation
- Macro/ microhaematouria (sometimes nephritic syndrome)
- Young male after URTI (eg pharyngitis)
- Normally self resolving
Histological changes and cause
- ↑IgA IF(possibly due to infection, which forms immune complexes and deposits in mesangeal cells)
- Mesangeal proliferation
- ↑C3 IF
Treatment
- Steroids
- Cyclophosphamide
Prognosis
- Worse if ↑BP, male, proteinuria, renal failure
- 20% of
Outline Thin Basement Membrane Nephropathy
- Genetic component
- Main presentation
- Histological findings
- Prognosis
Genetic component
- Autosomal dominant
Main presentation
- Persistent microscoptic haematuria
Histological findings
- Thin GBM on EM
Prognosis
- Usually benign
Outline Proliferative GN
- Presentation
- Histological change & cause
- Tests for diagnosis
aka Post-Streptococcal GN
Presentation
- Usually nephritic
Histological change & cause
- Streptococcal infection (sore throat/ skin infection)
- Streptococcal deposits on glomerulus
- Immune complex formation & IgG & C3 deposits (IF)
Tests for diagnosis
- Sirology
- ↑Anti-streptolysin O (ASOT)
- ↓C3
- Biopsy..
Outline Rapidly Progressive GN
- Histological findings & cause
- Classifications
- Clinical pesentation
- Treatment
Histological findings & cause
- Fibrin enters causing proliferation of epithelial cells (podocytes) & macrophages in Bowman’s capsule
- Cause of damage to GBM allowing fibrin through depends on classifications
Classifications
- Anti-GBM antibod disease (5%)
- Goodpasture syndrome when affecting lungs also
- Immune complex disease (45%)
- Post infections (endocarditis, shunt nephritis)
- SLE
- IgA nephropathy (inc. Henoch-Schonlein purpura)
- Pauci-immune disease (50%) [Vacular inflammation]
- Wegener’s granulomatosis
- Microscopic polyangiitis
- Churg-Strauss
- Many ANCA positive
Clinical presentation
- Signs of renal failure
- Signs of individual systemic diseassae
- Massive pulmonary haemorrhage is most common cause of death if ANCA+ve patients
Treatment
- Aggressive immunosuppresion
- High dose corticosteroids & cyclophosphamide
- Plasma exchange to remove existing antibodies
