nephrotic syndrome Flashcards
Three cell populations in the glomerulus and their functions
The glomerular endothelial cell lines the inner side of the GBM (fenestrations), glomerular mesagnial cell (centrall located cell that secretes basement membrane like matrix, can contract like smooth muscle, and has macrophage like properties such as secreting cytokines, growth factors, proteases and oxidants), and epithelial cells (aka podocytes with foot processes separated by slit-like diaphragms)
glomerulus charge barrier
the basement membrane is highly negatively charged (due to the presence of heparan sulfates) and the endothelium and podocyte are also coated in negatively charged proteins (consisting primarily of sialoproteins). This prevents most negatively charged molecules from being filtered (such as proteins)
glomerulus size barrier
the critical site is the slit pore diaphragm that extends between the podocyte foot processes. The primary protein in the slit diaphragm is termed nephrin. Nephrin molecules interlock and prevent proteins from being filtered
congenital nephrotic syndrome is due to a mutation in _________
nephrin
Normal protein excretion
500mg of albumin escapes into Bowmans capsule, but most is reabsorbed in proximal tubule so only 20mg/day is excreted. Tamm-Horsfall protein from thick ascending limb and IgA are also normally excreted
Abnormal protein excretion
Albumin >30mg/day is abnormal. 30-300mg/day albumin is not detectable by UA (microalbuminuria) and is suggestive of early glomerular damage. Albumin >300mg/day is identified in UA (300-2mg/day is glomerular or tubular disease, >3mg/day is defect in glomerular permeability and can result in decreased serum albumin)
Define nephrotic syndrome
excessive leak of protein through the glomerular capillary wall into the urinary space
Define nephritic syndrome
active inflammation within the glomerulus leads to damage to the glomerulus with subsequent loss of filtration and a reduction in the GFR
Clinical definition of nephrotic syndrome
• Proteinuria (>3.5 gm/day or >40 mg/hr/M2 in children) • Hypoalbuminemia (<3.0 gms/dl) • Edema • Hyperlipidemia (elevated serum cholesterol) • Lipiduria (fat globules in the urine
Clinical definition of nephritic syndrome
Decreased renal function, hypertension, RBC and RBC casts, edema, proteinuria
What causes proteinuria in nephrotic syndrome?
Disruption of the slit diaphragm. This may result from a specific defect of the diaphragm (such as a mutation of nephrin) or if the podocyte is injured
What causes hypoalbuminemia in nephrotic syndrome?
results from the proteinuria and increased catabolism of reabsorbed protein in the renal tubules. Protein synthesis by the liver is increased but can not compensate completely for the urinary losses.
What causes edema in nephrotic syndrome?
1) Decreased serum albumin decreases plasma oncotic pressure, resulting in filtration of fluid into the interstitial space. This decreases intravascular volume with stimulation of renin-angjotensin-aldosterone and vasopressin leading to additional salt and water retention. 2) primary renal defect in sodium excretion, resulting in volume expansion, and fluid movement into the interstitium due to both the low oncotic pressure and high hydrostatic pressure
What causes hyperlipidemia in nephrotic syndrome?
Decreased plasma oncotic pressure stimulates lipoprotein synthesis in liver (VLDL and LDL) and decreases peripheral removal of VLDL.
What causes lipiduria in nephrotic syndrome?
Increased capillary wall permeability and hyperlipidemia leads to lipids in the urine that appear like Maltese crosses under polarized light
What other conditions are common in nephrotic syndrome?
Increased risk for infections (urinary loss of IgG and complement), increased risk for thrombosis (increase in synthesis of coagulation factors by the liver, urinary loss of anti-thrombin III, increased platelet aggregability, and impairment of the fibrinolytic system), poor growth and osteomalacia (loss of Vitamin D) and protein malnutrition
Classifications of glomerular disease
nephrotic syndrome, nephritic syndrome, asymptomatic proteinuria, or asymptomatic hematuria
Causes of nephrotic syndrome
Renal only: Hereditary Nephrotic Syndromes, Minimal Change Disease, Focal Glomerular Sclerosis, Membranous Nephropathy, Membranoproliferative GN (MPGN). Systemic: Diabetes, amyloid, light chain deposition disease, lupus membranous type
Renal only: Hereditary Nephrotic Syndromes, Minimal Change Disease, Focal Glomerular Sclerosis, Membranous Nephropathy, Membranoproliferative GN (MPGN). Systemic: Diabetes, amyloid, light chain deposition disease, lupus membranous type
Causes of nephritis
renal only: Post Infectious (post strep), IgA Nephropathy
Rapidly Progressive GN (RPGN) such as Anti-GBM Nephritis or Idiopathic RPGN. Systemic disease: vasculitis, lupus, Henoch-Schonlein Purpura, Cryoglobulinemia, Wegener’s Granulomatosisrenal only: Post Infectious (post strep), IgA Nephropathy
Rapidly Progressive GN (RPGN) such as Anti-GBM Nephritis or Idiopathic RPGN. Systemic disease: vasculitis, lupus, Henoch-Schonlein Purpura, Cryoglobulinemia, Wegener’s Granulomatosis
Minimal change disease definition, epidemiology, pathology
Common cause of nephrotic syndrome with normal appearing glomeruli. Mainly affects young children (2:1 M:F) or 50-60yrs. Light microscopy is normal and electron microscopy shows foot process fusion (seen in all nephrotic syndromes)
Minimal change disease cause, presentation, treatment and prognosis
Caused by a T cell derived circulating permeability factor that acts on the glomerulus to damage podocyte and permeability barrier. Presents with edema, severe hypoalbuminemia and associations with Hodgkins disease, NSAID use or allergic disease. Treatment with steroids and long term prognosis is good
FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) definition, epidemiology, pathology
Type of nephrotic syndrome common in young adults and african americans, characterized by segmental scarring in some glomeruli and diffuse defect involving the entire capillary wall. Can develop from minimal change disease. EM shows diffuse foot process fusion and light microscopy shows scarring
Focal segmental glomerulosclerosis (FSGS) cause, associations, presentation, treatment and prognosis
Cuased by circulating factor (such as suPAR). May be idiopathic or associated with minimal change disease, heroin use, HIV, and rarely sickle cell, parvo virus and obesity. Presents with idiopathic nephrotic syndrome but may be hypertensive or have microhematuria. Treated with steroids (less responsive),cyclosporine. Renal failure is common
Membranous nephropathy definition, epidemiology and pathology
immune mediated glomerular disease associated with immune complex deposits in the subepithelial space (between the podocyte and GBM). GBM appears thickened by light microscopy. Most common in older adults. Silver stains show spikes in BM representing extensions of new BM btw immune complex deposits. Immunofluorescence shos granular deposits of Ig and C3/C5b-9 in GBM.
Membranous nephropathy causes, associations, presentation, treatment, prognosis
Autoimmune- Abs against phospholipase A2 receptor on podocytes. Idiopathic or associated with chronic infection, drugs, lupus or cancer. Presents as nephrotic syndrome with edema, HTN and renal failure develop over time. Treated with steroids and cytotoxic drugs. 50% end stage renal failure
Membranoproliferative Glomerulonephritis definitions and epidemiology
MPGN refers to a histologic pattern in which there is both proliferation (usually mesangial and in a lobular pattern) as well as thickening of the GBM. Type I associated with immune complex deposits, type 2 associated with complement activation in capillary wall. affects children and adolescents
Membranoproliferative Glomerulonephritis pathology, pathogenesis,
type I light microscopy shows thickend basement membrane, mesagnial cell proliferation, lobulated glomerulus, C3 deposits on capillary walls/ mesangium and IgG deposits. Type II only has C3 deposits, no IgG. Type I is due to passive trapping of circulating immune complexes in the subendothelial and mesangial areas, followed by complement activation and leukocyte recruitment. Type II is due to circulating nephritic factor that activates the alternative pathway of complement.
Membranoproliferative Glomerulonephritis presentation, treatment and prognosis
Most present with nephrotic syndrome, some with acute nephritis. Early HTN. Associated with Hep C, cryoglobulins and RF. Prognosis is poor (many develop end stage renal disease). Treated with steroids, anti-platelet drugs
Diabetic nephropathy
Presents with nephrotic proteinuria, microhemature is common, nodular glomerulosclerosis with thickening of BM is renal biopsy. Treated with glucose control, BP control and ACEI
SLE and nephrotic syndrome
Membranous histological pattern in which renal function is normal or slightly depressed and proteinuria/nephrotic syndrome occur. Treated with prednisone and mycophenolate
Amyloidosis and plasma cell dyscrasias
Usually in older people. Workup includes free plasma light chains, and serum and urine protein electrorphoresis to look for monoclonal light chains. Renal biopsy shows amyloid deposits (in amyloidosis) or nodular glomerulosclerosis (in light chain disease).
General management of nephrotic syndrome
low salt diet, diuretics, BP control, cholesterol lowering meds, ACEI to decrease proteinuria, Vit D replacement, low protein diet
