nephrotic and nephritic syndromes Flashcards
nephrotic syndromes: what is the problem? complications/symptoms? what are the nephrotic diseases?
glomerular disorders characterized by proteinuria > 3.5 g/day. proteinurea results in hypoalbuminemia (pitting edema), hypogammaglobulinemia (infections), hypercoagulable state (loss of antithrombin III, which is supposed to inactivate thrombin and coagulation factors and is augmented by heparin), hyperlipidemia and hypercholesterolemia (fatty casts in urine).
nephrotic diseases: minimal change disease, membranous nephropathy, focal segmental glomerulosclerosis, diabetic glomerulonephropathy, systemic amyloidosis. diffuse proliferative glomerulonephritis and membranoprliferative glomerulonephritis may be either a nephritic or a nephrotic disease
nephritic syndromes: what is the problem? complications/symptoms, what are the nephritic syndromes?
glomerular disorders characterized by glomerular inflammation and bleeding. limited proteinuria (less than 3.5 mg/day), oliguria and azotemia, salt retention with periorbital edema and HTN, RBC casts and dysmorphic RBCs in the urine.
biopsy will show hypercellular, inflammed glomeruli. immune complex deposition activates complement and C5a attracts neutrophils. neutrophils mediated the damage.
diseases: acute post-strep glomerulonephritis, rapidly progressive glomerulonephritis, berger disease, alport syndrome
post-strep glomerulonephritis: causes, pathophysiology, presentation, microscopy
nephritic syndrome that arises after beta hemolytic strep infection of the skin (impetigo) or pharynx
occurs with nephritogenic strains (M protein virulence factor). may occur after infection with non-strep organisms as well.
presents 2-3 wks after infection as hematuria (cola colored urine), oliguria, HTN, and periorbital edema. usually in kids, possible in adults.
hypercellular, inflamed glomeruli on H&E.
mediated by immune complex deposition (granular immunofluorescence); subepithelial humps on EM.
treatment is supportive. about 1% of kids and 25% of adults develop rapidly progressive glomerulonephritis
rapidly progressive glomeulonephritis
nephritic syndrome that progresses to renal failure in weeks to months. characterized by crescents in Bowman’s space on H&E. crescents are made of FIBRIN AND MACROPHAGES, and PLASMA PROTEINS (C3b)
clinical picture and immunofluorescence help determine etiology:
1. linear antibasement membrane immunofluorescence: goodpastures syndrome. Ab against collagen in glomerular and alveolar BM.
2. granular: post-strep glomerulonephritis, or diffuse proliferative glomerulonephritis (most common renal disease in SLE; subendothelial immune complex deposition. may be nephritic or nephrotic).
3. Negative immunofluorescence: Wegeners’s picroscopic polyangitis, Churg-Strauss. c-ANCA for Wegeners, p-ANCA for PAN and Churg-strauss. Churg strauss also has eosinophilia, granulomatous inflammation, and asthma.
Berger disease
IgA nephropathy. IgA immune complex deposition in the MESANGIUM of the glomeruli. most common nephropathy worldwide. presents during childhood as episodic gross or microscopic hematuria with RBC casts, usually following mucosal infections. may slowly progress to renal failure.
seen with Henoch-Schonlein purpura
Alport syndrome
inherited defect in type IV collagen. most commonly X linked. results in thinning and splitting of the glomerular basement membrane. presents as isolated hematuria, sensory hearing loss, and ocular disturbances.
focal segmental glomerulosclerosis
most common cause of nephrotic syndrome in Hispanics and African americans. usually idiopathic but may be associated with HIV, heroin use, and sickle cell diseae. focal and segmental on H&E. effacement of the foot processes on EM. no immune complex deposits. porr response to steroids and frequent progression to renal failure
membranous nephropathy
most cmmon cause of nephrotic syndrome in caucasian adults. usually idiopathic, but may be associated with hepatitis B or C, solid tumors, SLE, or drugs like NSAIDs or penicillamine. thick glomerula basement membrane on H&E. due to immune complex deposition (granular immunofluorescence). subendothelial depositis with a spike and dome appearance on EM.
poor response to steroids. progresses to chronic renal failure.
diabetes mellitus and kidney failure
high serum glucose leads to nonenzymatic glycosylation of the vascular basement membrane, resulting in hyaline atherosclerosis. the glomerular efferent arteriole is more affected than the afferent arteriole, laeding to a high glomerular filtration pressure. hyperfiltration leads to microalbuminuria. eventually, this progresses to nephrotic syndrome characterized by scelrosis of the mesangium with formation of Kimmelsteil-Wilson nodules. ACE inhibitors slow the progression of hyperfiltration-induced damage.
systemic amyloidosis
kidney is the most commonly involved organ in systemic amyloidosis. amyloid deposits in the mesangiu, resulting in nephrotic syndrome. characterized by apple-green birefringence under polarizd light after staining with congo red.
membranoproliferative glomerulonephritis
thick glomerular BM on H&E, often with a tram-track apperance. due to immune complex deposition. 2 types, based on location of deposits.
type I: subendothelial: associated wtih HBV and HCV.
type II: dense deposit disease: intramembranous. associated with C3 nephritic factor. autoantibody stabilizes C3 converase, leading to overactivation of complement, inflammation, and low levels of circulating C3.
both: poor response to steroids. prgoresses to chronic renal failure.
may be nephritic or nephrotic
minimal change disease
most common cause of nephrotic syndrome in kids. usually idiopathic but may be associated with Hodgkin lymphoma. Normal glomeruli on H&E but effacement of the foot processes on EM. no immune complex deposits. selective proteinuira (loss of albumin but not immunoglobulin). excellent response to steroids because the damage is mediated by cytokines from T cells.
