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74 Cards in this Set
- Front
- Back
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What are the 4 manifestations of Nephrotic syndrome?
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-Massive proteinuria w/ loss of 3.5 g/day or more
-Hypoalbuminemia -Generalized Edema -Hyperlipidemia/lipiduria |
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What is the initial event in nephrotic syndrome?
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Injury to the glomerular capillary walls resulting in increased permeability to plasma proteins
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What change in serum protein levels is seen due to the massive proteinuria in Nephrotic syndrome?
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An inverted Albumin:Immunoglob ratio
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What does the massive loss of albumin lead to?
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Decreased colloid osmotic pressure and accumulation of water in interstitial spaces - generalized EDEMA.
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What aggrevates the edema seen in nephrotic syndrome and what causes it?
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Na/Water retention - caused by activation of ADH and the RAS.
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What types of protein are lost in the urine in nephrotic syndrome?
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Both albumin and immunoglobulins
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What type of proteinuria will be less or more likely to contain immunoglobulins?
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-Highly selective proteinuria will likely only be albumin
-Poorly selective proteinuria will have both albumin and High MW globulins |
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How does excess lipid in the urine appear?
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As free fat or oval fat bodies
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What are patients with nephrotic syndrome particularly vulnerable to?
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-Infections with staph/pneumo
-Thrombosis/thromboembolism |
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Why are nephrotic syndrome patients susceptible to thrombosis?
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Because of loss of anticoagulant factors through the leaky glomerulus
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What is the etiology of nephrotic syndrome in US pts
-under 17 -adults |
Under 17 - primary kidney lesion
Adults - secondary to a systemic disease |
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What are the top 3 systemic diseases associated with nephrotic syndrome in adults?
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-Diabetes
-Amyloidosis -SLE |
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What are the top 3 primary kidney lesions associated with nephrotic syndrome?
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-Minimal change disease
-Membranous glomerulopathy -Focal segmental glomerulosclerosis |
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At what age do patients get
-Minimal change disease -Membranous glomerulopathy -Focal segmental glomerulosclerosis |
MCD = children
MG = older adults FSGS = any age |
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So what is the most common cause of nephrotic syndrome in adults?
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Membranous glomerulopathy
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What are the hallmark morphologic characteristics of membranous glomerulopathy?
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-Diffuse thickening of capillary wall
-Accumulation of e-dense Ig containing subepithelial deposits |
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What % of membranous glomerulopathies are idiopathic?
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85%
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What are 5 causes of secondary membranous glomerulopathies?
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-Drugs
-Underlying malignant tumors -SLE -Infections -Autoimmune diseases ie thyroiditis |
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So what is the mechanism of glomerular damage in membranous glomerulopathy?
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Chronic Immune complex deposition
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What is the animal model that mimics Membranous glomerulopathy?
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Heymann nephritis
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How does the glomerular capillary wall become so leaky in membranous glomerulopathy?
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By the paucity of immune cells resulting in Complement activity that injures the capillary walls.
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What is the general course of disease in membranous glomerulopathy?
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Indolent with nonselective proteinuria that does not respond well to steroids.
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What does progression of membranous glomerulopathy consist of?
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Sclerosis of glomeruli
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How does glomerular sclerosis in membranous glomerulopathy correlate with clinical progression?
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The degree of it already present at diagnosis predicts worse prognosis
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What is the predominant morphologic finding in membranous glomerulopathy?
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Uniform, diffuse thickening of the glomerular capillary walls
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Where are the dense deposits seen on EM in membranous glomerulopathy?
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Subepithelial
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What effect do the subepithelial deposits have on overlying podocyte foot processes?
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They become effaced and basement membrane material is laid down between them.
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What stain shows these irregular spikes of protruding GBM material in the subepithelial space in membranous glomerulopathy?
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Silver stain
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What do the immune complexes contain as shown by FM?
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Immunoglobulins and complement
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What happens to the glomeruli over the course of time as the membrane becomes progressively thicker in membranous glomerulopathy?
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They become totally sclerossed
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What is the most important component in approaching cases of membranous glomerulopathy?
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Determine whether it is primary or secondary, so that proper treatment can ensue.
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What is the most frequent cause of nephrotic syndrome in CHILDREN?
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Minimal change disease
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What is MCD aka?
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Lipoid nephrosis
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What is the only morphologic change seen in MCD?
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Diffuse effacement of foot processes on EM
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What age is the peak incidence of MCD?
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2-6 yrs old
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What is the most characteristic feature of MCD?
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Its dramatic response to steroid therapy
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What are 2 things that often precede MCD in children?
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Respiratory infections
Prophylactic immunizations |
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What do the facts that infections/immunizations often precede MCD, and it responds well to steroids, point to?
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An immunologic basis for etiology
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So what is the principal lesion and in what cells is it seen in MCD?
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-Visceral epithelial cells
-Uniform, diffuse effacement of foot processes |
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What 3 subsequent changes are seen in the visceral epithelial cells dt foot process effacemnt?
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-Vacuolization
-Swelling -Villous hyperplasia |
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Since foot process effacement is seen in other conditions ie Membranous glomerulopathy, how is MCD diagnosed?
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By seeing ONLY foot process effacement, but otherwise normal glomeruli.
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What happens to the visceral epithelial cell changes when corticosteroids are given?
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The changes are completely reversible and the proteinuria stops.
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Why has MCD been historically termed Lipoid Nephrosis?
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Because lipoproteins filtered by damaged glomeruli accumulate in the proximal tubules.
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What does IF show in Minimal change disease?
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Nothing
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What is basically the only clinical manifestation of MCD?
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Massive proteinuria that is highly selective for albumin
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What is FSGS?
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Focal segmental glomerulosclerosis
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What is FSGS characterized by?
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Focal Sclerosis of some but not all glomeruli
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How much of individual glomeruli are affected by the sclerosis in FSGS?
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Only portions of the capillary tufts - hence it is segmental
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What is the clinical syndrome that often accompanies FSGS?
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Nephrotic syndrome w/ heavy proteinuria.
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How much nephrotic syndrome is due to idiopathic FSGS in
-children -adults |
Kids = 10%
Adults = 35% |
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In what ethnic groups is FSGS particularly a cause of nephrotic syndrome?
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African Americans and Hispanics
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What clinical features are seen in FSGS that are not present in MCD?
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-Hematuria
-Reduced GFR -Hypertension |
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How does the proteinuria in FSGS compare to that in MCD?
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Less selective
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How does the response to steroids in FSGS compare to that in MCD?
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Poor response in FSGS
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How does the progression and outcome of FSGS compare to that of MCD in general?
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-Progresses to chronic glomerulosclerosis
-50% develop ESRD in 10 yrs |
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How does IF in FSGS compare to that in MCD?
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-FSGS IF may show nonspecific trapping of IgM and C3 in affected segments
-MCD shows no deposits |
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What are the 3 main morphologic findings in FSGS that terminates in ESRD?
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-Total sclerosis of glomeruli
-Pronounced tubular atrophy -Interstitial fibrosis |
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What additional morphologic findings are seen in sclerotic areas of glomeruli in FSGS?
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-Lipid vacuoles
-Hyalinization |
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What is hyalinization again?
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Laying down of plasma proteins along the capillary wall
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What happens to the foot processes in FSGS?
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They become effaced
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What may be seen on FM in FSGS?
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Immune deposits of IgM and C3
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What variant of FSGS is the most characteristic lesion of HIV-associated nephropathy and has a particularly poor prognosis?
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Collapsing glomerulopathy
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What is the current argument regarding FSGS?
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Whether it is a distinct disease or a phase in the evolution of MCD
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What feature of FSGS suggests that the epithelial damage is caused by a circulating factor?
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The rapid recurrence of FSGS even when the kidneys are transplanted
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And what is the hallmark of FSGS?
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Degeneration and focal disruption of visceral epithelial cells
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What are 2 genes and their proteins have recently been discovered and may serve as a genetic basis of some cases of FSGS?
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NPHS1 - Nephrin
NPHS2 - Podocin |
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What are Nephrin and Podocin proteins components of?
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The slit diaphragm between podocyte foot process
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What is the function of the slit diaphragm?
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Glomerular permeability control
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What do mutations in NPHS1 give rise to?
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Congenital nephrotic syndrome of the Finnish type
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What do mutations in NPHS2 give rise to?
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Steroid-resistant nephrotic syndrome of childhood onset
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What is the tendency for spontaneous remission in idiopathic focal segmental glomerulosclerosis like?
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Not likely
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What patients with FSGS have better prognosis?
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Children > adults
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What % of FSGS cases recur even with allografts?
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25-50%
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What is the most common renal complication of HIV infection?
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Collapsing variant of FSGS
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