Nephrotic syndrome Flashcards
Nephrotic syndrome : definition
Glomeruli are damaged therefore become more permeable and allow for plasma proteins from the blood to enter the urine resulting in proteinuria.
Triad of;
* Proteinuria >3g/24 hours
* Hypoalbuminaemia < 30g/L
* Oedema
Nephrotic syndrome : Causative diseases
- Minimal change disease
- Diabetic nephropathy
- Amyloidosis
- Membraneous Glomerulonephritis
- Membranoproliferative Glomerularnephritis
- Focal segmental glomerularnephritis
Nephrotic syndrome : Minimal change disease - Pathophysiology
- T cells in the blood release cytokines
- Damage the foot processes of the podocytes
- This causes effacement (flattening out of the podocytes)
- These foot processes are normally negatively charged thereby would normally repel large proteins like albumin
- Effacement means there is less of a charge barrier resulting in proteinuria.
Nephrotic syndrome : Minimal change disease - Clinical features
1.** Proteinuria >3.5g per day**
2. Hypoalbuinaemia : secondary to loss of albumin protein from the blood due to proteinuria
3. Oedema : reduced oncotic pressure from protein loss in the blood leads to reduced osmotic pressure, driving water out of the blood vessels and into the tissues.
4. Hyperlipidaemia and lipiduria - loss of protein from the blood inhibit synthesis of lipids leading to increased lipid levels in the blood and more lipid entering the urine.
Nephrotic syndrome : Minimal change disease - Incidence
- Most common nephrotic syndrome seen in children
Nephrotic syndrome : Minimal change disease - Investigation
Light microscopy and H&E stain - doesn’t allow for foot process effacement to be seen, thus seems as though there is no change to the glomerulus, hence the name ‘minimal change;
Nephrotic syndrome : Minimal change disease - Mx
Corticosteroid therapy - 90% of children respond very well
Nephrotic syndrome : Focal segmental glomerulosclerosis (NORD) - Definition
- continuation of minimal change disease also characterised by podocyte injury.
Nephrotic syndrome : Focal segmental glomerulosclerosis (NORD) - Pathophysiology
- Kidney disease which affects the kidney’s glomeruli and causes scarring, mainly only segments of some glomeruli are affected.
- Damage to foot processes of podocytes allows for plasma proteins and lipids to enter the urine.
- Over time - proteins and lipids get trapped and build up in the glomeruli resulting in hyalinosis - over time this results in scarring
Nephrotic syndrome : Focal segmental glomerulosclerosis (NORD) - Causes
- Primary FSGS : idiopathic
- Secondary FSGS : sickle cell disease, HIV, Heroin abuse
Has high recurrence rate in renal transplants
Nephrotic syndrome : Focal segmental glomerulosclerosis (NORD) - Investigations
- Light microscopy: Focal and segmental sclerosis and hyalinosis
- Electron microscopy - Effacement of foot processes of podocytes
Nephrotic syndrome : Membranous Glomerulonephritis - Definition
Glomerular basement membrane which lines the glomeruli in the kidneys becomes inflamed and damages - secondary to binding of immune complexes to the GMB
Nephrotic syndrome : Membranous Glomerulonephritis - Incidence
- Common type of glomerulonephritis in adults
- Third common cause of end-stage renal failure
Nephrotic syndrome : Membranous Glomerulonephritis - Pathophysiology
- Damage and inflammation is caused by binding of immune complexes (antibody-antigen complex) to the Glomerular basement membrane
- Subendothelial deposits - Immune complexes become sandwiched between epithelial cells of podocyts and GBM
- Auto antibodies may directly target the GBM : antibodies may form against two antigens expressed on the surface of podocytes - M- type phospholipase A2 receptor and neutral endopeptidase
Nephrotic syndrome : Membranous Glomerulonephritis - Causes
- Idiopathic : anti-phospholipase A2 antibodies
- Infections : Malaria, Syphillis, Hepatitis B
- Malignancy : prostate, lung, lymphoma and leukaemia
- Drugs : NSAIDs, Gold, pencillamine
- Autoimmune disease : SLE, Thyroiditis, Rheumatoid arthritis
Nephrotic syndrome : Membranous Glomerulonephritis - Incidence
Patients with end stage renal disease
Nephrotic syndrome : Membranous Glomerulonephritis - Investigation
Light microscopy
1. Thickening of the GBM - GBM matrix is deposited between the immune complex,
Electron microscopy
1. Pattern of GBM Matrix on the sub epithelial deposits creates a characteristic ‘spike and dome pattern’
* Effacement of the podocytes is also present.
Nephrotic syndrome : Membranous Glomerulonephritis - Management
- Ace inhibitor or ARB : reduce proteinuria and improve prognosis
- Immunosupression : normally in severe progressive disease, combination of corticosteroids and cyclophosphamide.
Nephrotic syndrome : Membranous Glomerulonephritis - Prognosis
Prognosis - rule of thirds
One third - Spontaneous remission
One third - Remain proteinic
One third - Develop End stage renal failure
Nephrotic syndrome : Membranoproliferative Glomerulonephritis - definition
- Chronic infection - Antigens released -> Bind antibodies in the blood -> Immune complexes deposit in the GBM
- immune complex deposits which end up in the walls of the glomerulus
- Trigger immune reactions - causing inflammation and result in structural changes to the glomerulus.
- Cause mesangial proliferation
- This leads to nephrotic syndrome - proetienuria, hypoalbumnaemia, oedema, hyperlipidaemia and lipiduria.
Nephrotic syndrome : Membranoproliferative Glomerulonephritis - T1 MPGN - causes
Causes :
Chronic infection - Hepatitis C, Hepatitis B
Antigens released -> Bind antibodies in the blood -> Immune complexes deposit in the GBM
Nephrotic syndrome : Membranoproliferative Glomerulonephritis - Investigations
- Electron microscopy : Subenthothelial and mesangium immune deposits resulting in ‘Tram-track appearance’
