Nephrotic Syndrome Flashcards
clinical clues for glomerular disease
PROTEINURIA and/or HEMATURIA (dysmorphic RBC, RBC cast)
+/- drop in GFR
+/- electrolyte/acid abnormalities
+/- change in urine output
nephrotic vs. nephritic syndromes - detailed
*nephritic syndrome:
-location of immune complex deposition = SUBENDOTHELIAL (b/w fenestrated endothelium and GBM - BAD)
-damage = INFLAMMATION of glomerular barrier
-classic clinical finding = mostly HEMATURIA
*nephrotic syndrome:
-location of immune complex deposition = SUBEPITHELIAL (b/w GBM and foot processes)
-damage = LEAKY glomerular barrier
-classic clinical finding = mostly PROTEINURIA
*mixed:
-location of immune complex deposition = mesangial
-damage = both inflammation & leakage
-finding = blend of hematuria and low-level proteinuria
subendothelial deposits - location
*between endothelial cells and basement membrane
*endothelial cells face the capillary side
*more commonly seen in nephritic syndrome
*glomerular inflammation → GBM damage → loss of RBCs into urine → dysmorphic RBCs, hematuria
naming is counterintuitive: subENDOthelial is NEPHRITIC syndrome (even though it has an “O” in it)
subepithelial deposits - location
*between the podocytes and the basement membrane
*podocytes face the urinary space/lumen
*more commonly seen in NEPHROTIC syndrome
naming is counterintuitive: subEPIthelial is nephrotic (even though it has the letter “I” in it)
immune complex deposition → glomerular damage
*type 3 hypersensitivity reaction (antigen:antibody immune complexes) → damage of the glomerular barrier
*location of immune complex deposition results in the associated syndromes:
-subendothelial deposits → nephritic syndrome
-subepithelial deposits → nephrotic syndrome
nephrotic syndrome - classic findings
*nephrotic syndrome:
1. large proteinuria (>3.5 grams/day)
2. hypoalbuminemia
3. edema
4. hypercholesterolemia
nephritic syndrome - classic findings
*nephritic syndrome:
1. hematuria
2. azotemia
3. oliguria
4. hypertension
nephrotic syndrome - overview
*clinical syndrome caused by pathological glomerular protein losses
*hallmarks:
1. proteinuria ( > 3.5 grams/24 hours)
2. hypoalbuminemia
3. edema
4. hyperlipidemia
how much protein must be in the urine to define nephrotic syndrome
> 3.5 grams per day of protein in the urine
edema in nephrotic syndrome
edema can manifest in various ways with nephrotic syndrome, including:
*periorbital edema
*puffy pale face
*lips may be swollen
*moderate to severe edema in the legs
nephrotic syndrome - urine casts
*oval fat bodies (“fatty casts”) - lipid-laden cells, associated with “Maltese cross” sign
complications of nephrotic syndrome
-
hyperlipidemia
-due to elevated production, abnormal transport, and decreased catabolism of lipids -
hypercoagulability (DVT, renal vein thrombosis)
-due to loss of anticoagulation proteins - relative increased risk of infection (staph, pneumococcus)
-due to loss of IgG, complement factors -
hypovitaminosis D
-due to proximal tubular dysfunction and vitamin D binding protein losses
quantifying proteinuria
*pathologic amounts of proteinuria: > 150 mg
150 mg - 3.5 grams/day = sub-nephrotic proteinuria
> 3.5 grams/day = nephrotic range proteinuria
albuminuria:
< 30 mg/day = normal
30-300 mg/day = “microalbuminuria” (moderately increased)
> 300 mg/day = “macroalbuminuria” (severely increased)
classifying proteinuria
- transient vs. isolated:
-occurs INTERMITTENTLY due to stress which alter renal hemodynamics (fever, vigorous exercise, exposure to extreme cold) - orthostatic vs. postural:
-occurs in chidren
-proteinuria when upright > supine - PERSISTENT:
-glomerular source: increased movement of protein across GBM
-tubular source: decreased reabsorption of protein in PCT (Fanconi)
-overflow: increased production of plasma proteins overwhelms GBM filtering capacity and tubular reabsorption (multiple myeloma)
diseases that cause nephrotic syndrome
- minimal change disease (most common in children)
- membranous nephropathy
- focal segmental glomerulosclerosis (FSGS)
- amyloidosis
- diabetic glomerulonephropathy (MOST COMMON CAUSE)
note - each disorder can be primary or secondary
information obtained from kidney biopsy
- light microscopy: allows for identification of structural changes
-thickening of the GBM, nephrosclerosis, tubular atrophy, intra-capillary proliferation - immunofluorescence: allows for identification and location of antibody deposition
- electron microscopy: allows for identification of ultrastructural changes
-location and appearance of immune complexes
-podocyte effacement
-deposited protein fibril size/orientation
minimal change disease - overview
*most common cause of nephrotic syndrome in children
*hallmark pathology: visceral epithelial cell (podocyte) damage
minimal change disease - mechanism/etiology
*primary (idiopathic)
*secondary:
-NSAIDs
-lymphoma
-triggered by recent infection, immunization, or immune stimulus
minimal change disease - light microscopy findings
normal glomeruli
proximal tubule cells may be laden with lipids (lipid necrosis)
minimal change disease - immunofluorescence findings
negative (not an immune-complex disease)
minimal change disease - electron microscopy
effacement of podocyte foot processes
this is the ONLY biopsy finding associated with minimal change disease
minimal change disease - epidemiology
*most common cause of nephrotic syndrome in CHILDREN
*can occur in adults too
minimal change disease - clinical presentation
*sudden onset of massive proteinuria and nephrotic syndrome (proteinuria, hypoalbuminemia, edema, hyperlipidemia)
*usually triggered by recent infection, immunization, or immune stimulus
minimal change disease - treatment
*primary: corticosteroids & other immunosuppression
*secondary: treat underlying cause (stop NSAIDs, treat lymphoma, etc)
