Nephrotic Syndrome And Its Particular Pathogenesis In Glomerulonephritis
A General Overview
Nephrotic syndrome is characterized by massive proteinuria (3.5g in 24 hours in adults and more than 2g/m2 body surface in children). It is often associated with edema, hypoalbuminemia, hyperlipidemia and lipiduria. This results from diverse causes.
- Idiopathic nephrotic syndrome: Minimal change glomerulonephritis (GN), membranous glomerulopathy, membranoproliferative GN, focal and segmental glomerulosclerosis, miscellaneous.
- Systemic illnesses: Diabetic nephropathy, collagen disorders with renal involvement, especially systemic lupus erythematosus; and renal amyloidosis.
- Drugs and allergens: Gold salts, mercurials, penicillamine, tridione (troxidone), and bee-stings.
- Infections: Secondary syphilis, leprosy, infective endocarditis, quartan Malaria (Plasmodium malariae); and hepatitis B virus.
- Neoplastic illnesses: Hodgkin’s disease, multiple myeloma, lymphatic leukemia, bronchogenic carcinoma.
- Miscellaneous conditions: Pregnancy, hereditary nephritis, sickle cell anemia and familial nephrotic syndrome.
Pathogenesis of glomerulonephritis
An immunological basis has been postulated in the pathogenesis of some types of GN producing nephrotic syndrome. The antigen may be exogenous, e.g. bacterial or viral, or endogenous e.g. nuclei, nucleoprotein, smooth muscle, glomerular basement membrane, etc. The antigen and the antibody produced against it combine to form the immune complex. When the immune complex gets deposited in any part of the body, in this case, the glomeruli, it activates the complement system. This results in inflammation, increase in the permeability of the filtering mechanism, polymorphonuclear infiltration and other changes. This inflammatory reaction leads to the development of glomerulonephritis of various types and severity.
The kidneys are usually normal in size or enlarged and the section is pale. Based on the light microscopic and electron microscopic appearances of the renal tissue, primary or idiopathic nephrotic syndrome has been classified into the various subtypes. Assignment of any case of nephrotic syndrome to the particular subtype is important to plan the management and assess the prognosis. Light microscopy helps in distinguishing the endothelial, mesangial and epithelial cells, the capillary loops and the basement membrane inside the Bowman’s Capsule. The rest of the area is constituted by the glomerular mesangium.
Nephrotic Syndrome In Glomerulonephritis
In minimal change GN, light microscopy of the glomerulus is normal. The foot processes of the epithelial cells appear to be blunted or effaced under electron microscope. The tubules, interstitium and blood vessels are grossly normal.
In membranous glomerulopathy, the basement membrane shows variable degrees of uniform thickening. There are abnormalities in the epithelial cells, visible under electron microscope. There is no cellular proliferation and the tubule, interstitium and blood vessels are within normal limits.
In membranoproliferative GN (also known as mesangiocapillary GN), there is evidence of proliferation of endothelial and mesangial cells. There is also apparent thickening of the basement membrane. The glomerulus has a lobular appearance. Under electron microscope, in addition to proliferation of the cells, interposition of the mesangium between gives the appearance of apparent thickening and splitting of the basement membrane. In focal and segmental glomerulosclerosis, the lesions are focal (involving only some of the glomeruli) and segmental (involving only part of the glomerular capillary tuft). There is no proliferation of cellular elements. The lesions are more common in the juxtamedullary glomeruli. Areas of tubular atrophy, thickening of tubular basement membrane and interstitial foam cells may be seen.
The profound proteinuria due to increase in the glomerular capillary permeability is responsible for most of the clinical manifestations of nephrotic syndrome. If the glomerular damage is severe, albumin and immunoglobulins appear in the urine, whereas with mild damage, only albumin escapes in urine. The former is called noselective proteinuria and the latter, selective proteinuria. Thus, assessing the selectivity of proteinuria helps in assessing the degree of damage to the glomerula filtering mechanism.
The loss of protein in the urine results in hypoalbuminemia. However, poor intake, defective synthesis and abnormal catabolism can exaggerate this phenomenon. Reduction in the intravascular to the extravascular compartment to produce edema. In addition, the levels of serum cholesterol and lipids increase on account of associated defects in lipid metabolism.
© 2014 Funom Theophilus Makama