Small Group 4 Kidney Disease with Proteinuria Flashcards
- Know the basic approach to pathologic interpretation of glomerular diseases.
unexplained proteinuria that is not responsive to corticosteroids should be biopsyed and examined with the triple method of LM, IMF and EM to establish a diagnosis
- Define the nephrotic syndrome.
edema (peripheral, pulmonary, ascites- water and salt end up in the interstitial space)
nephrotic range proteinuria (>3.5 g per day due to intrinsic kidney disease), lipduria also possible
hypoalbuminemia: due to losses and abnormal synthesis
hypercholesterolemia- increased synthesis of lipoproteins, abnormal transport and decreased catabolism (secondary to hypoproteinemia)
- State which renal pathologic conditions commonly lead to the nephrotic syndrome and how this occurs mechanistically (pathophysiologically)- minimal change
minimal change nephropathy
most common in childhood; signs: periorbital edema, heavy proteinuria (albumin and LMW proteins), hypoalbuminemia, and hyperlipidemia
BUN, creatinine, complement levels, autoimmune serology are usually normal
unclear mechanism, possible immune disease associated with T cell cytokines (IL and INF-g) or circulating permeabilities (VEGF, heparanse and hemopexin)
tx. with croticosteroids, usually resolves w/in 3mo, relapses are much more common with presentation in teens
- State which renal pathologic conditions commonly lead to the nephrotic syndrome and how this occurs mechanistically (pathophysiologically)-membranous nephropathy.
membranous nephropathy- most common cause in the world for nephrotic syndrome
at risk populations: Hep B, malaria, syphilis, Drugs (NSAIDs), metals, tumors, ANA/Lupus; benign urine sediment (bland)
immune complex mediated disease- antigen-antibody complexes can develop by the production of immune complexes in situ or by deposition from serum (primary- PLA2R as antigen); complement membrane attack complex (C5b-9) triggers liberation of proteases and production of oxidants leading to injury of glomerular epithelial and mesangial cells
- State which renal pathologic conditions commonly lead to the nephrotic syndrome and how this occurs mechanistically (pathophysiologically)- diabetic nephropathy.
diabetic nephropathy- most common cause of nephrotic syndrome in US, requires 15-20 years to develop, unlikely to be present without retinopathy
Non-enzymatic reaction with amino groups of proteins (e.g. basement membrane components) => Advanced glycation end products (AGEs)
Increases fluid filtration; Binding of plasma proteins (albumin)
- State which renal pathologic conditions commonly lead to the nephrotic syndrome and how this occurs mechanistically (pathophysiologically)- FSGS.
focal segmental glomerulosclerosis
at risk population for secondary disease: HIV, sickle cell disease, obesity, vesico-ureteral reflux, reduction in renal mass
primary etiology is unknown, theories re: circulating permeability factor; can progress to ESRD
- Describe the effects of the nephrotic syndrome on the rest of the body.
hyper coagulability (DVTs, PEs, renal vein thrombosis) due to loss of protein C, S and antithrombin 3; increased hepatic clotting factors and impaired fibrinolysis
- Recognize histologic and electron microscopic features in minimal change disease.
minimal change disease
LM: little or no morphological change, PCT contain lipid
IMF: negative for immunoglobin or complement
EM: diffuse effacement of foot processes, absence of abnormalities in the glomerular basement membranes
- Recognize histologic and electron microscopic features in membranous nephropathy.
LM: thickening of glomerular BM, subeptihelial spikes (silver stains), normal glomerular cellularity
IMF: diffuse granular staining for IgG and often C3 (IgM, IgA and C1q deposits are uncommon; albumin and IgG possible in tubular epithelial cells
EM- granular electron-dense deposits on sub epithelial side of GBM, uniformly distributed and may be surrounded by glomerular basement membrane projections; podocytes often effaced
- Recognize histologic and electron microscopic features in FSGS.
LM: focal segmental glomerular sclerosis (duh.)
EM: foot process effacement
- Recognize histologic and electron microscopic features amyloidosis.
LM: apple green birefringence with congo red stain
EM: fibrillar structure of the amyloid
- Recognize histologic and electron microscopic features in diabetic nephropathy.
most characteristic pathological lesion is acellular nodule (Kimmmestiel-Wilson) lesion
hyaline in afferent and efferent arterioles in prominent
- Explain the clinical implications (relationship to severity of disease and prognosis) of theses histologic and electron microscopic features, and how this may affect choices of therapy.
matched with each disease
Describe conditions of hypoalbuminemic states.
nephrotic syndrome and cirrhosis- both result in decreased ‘effective’ arterial blood volume, due to lack of oncotic pressure; these conditions can also present with edema although ECV is low
- State which renal pathologic conditions commonly lead to the nephrotic syndrome and how this occurs mechanistically (pathophysiologically)- amylodosis.
amyloidosis- much more likely with myeloma, test with serum and protein electrophoresis
plasma cell neoplasia is a primary cause and chronic inflammation is a secondary cause of the abnormal deposition of fibrillar organization
