Certain glomerular disease virtually always produce the nephrotic syndrome. Before the major disease associated with nephrotic syndrome are presented the pathophysiology of this clinical complex is briefly discussed and the causes are listed.
The menifestations of the nephrotic syndrome include
Massive proteinuria, with the daily loss of 3.5 gm or more of protein (less in children);
Hypoalbuminemia, with plasma albumin levels less than 3 gm/dl
Generalized edema; and hyperlipidemia and lipiduria.
The various components of nephrotic syndrome bear a logical relationship to one another. The initial event is a derangement in glomerular capillary walls resulting in increased permeability to the plasma proteins. It will be remembered that the glomerular capillary wall with its endothelium. GBM and visceral epithelial cells, acts as a size and charge barrier through which the glomerular filtrate must pass. Increased permeability resulting from either structural or physicochemical alterations allow protein to escape from the plasma into the glomerular filtrate. Massive proteinuria results.
The heavy proteinuria leads to depletion of serum albumin levels below the compensatory synthetic abilities of the liver, with consequent hypoalbuminemia and reversed albumin globulin ratio. Increased renal catabolism of filtered albumin also contributes to the hypoalbuminemia. The generalized edema is in turn the consequence of the loss of colloid osmotic pressure of the blood and the accumulation of fluid in the interstitial tissues. There is also sodium and water retention, which aggravates the edema. This appears to be due to several factors, including compensatory secretion of aldosterone, mediated by the hypovolemia enhanced antidiuretic hormone secretion; stimulation of the sympathetic system; and a reduction in the secretion of natriuretic factors, such as atrial peptides, Edema is characteristically soft and pitting, most peptides. Edema is characteristically soft and pitting, most marked in the periorbital regions and dependent portions of the body. It may be massive with pleural effusions and ascites.
The largest proportion of protein lost in the urine is albumin, but globulins are also excreted in some diseases, The ratio of low to high molecular weight proteins in the urine in various cases of nephrotic syndrome determines the so called selectivity of proteinuria. A highly selective proteinuria consists mostly of low molecular weight proteins (albumin 70,000; transferrin 76,000) whereas a poorly selective proteinuria consists of higher molecular weight globulins in addition to albumin.
The genesis of the hyperlipidemia is complex. Most patients have increased cholesterol, triglyceride, very low density lipoprotein, lo density lipoprotein, Lp(a)lipoprotein and apoprotein concentrations, and there is a decrease in high density lipoprotein concentration in some patients. These defects seem to be due, in part to increased synthesis of lipoproteins in the liver, abnormal transport of circulating lipid particles, and decreased catabolism. Lipiduria follows the hyperlipidemia, because not only albumin molecules but also lipoproteins leak across the glomerular capillary wall. The lipid appears in the urine either as free fat or as oval fat bodies, representing lipoprotein resorbed by tubular epithelial cells and then shed along with the degenerated cells.
These patients are particularly vulnerable to infection especially with staphylococci and pneumococci. The basis for this vulnerability could be related to loss of immuno globulins or low molecular weight complement components (e.g., factor B) in the urine. Thrombotic and thromboembolic complications are also common in nephrotic syndrome owing in part to loss of anticoagulant factors (e.g.,) antithrombin III) and antiplasmin activity through the leaky glomerulus. Renal vein thrombosis, once thought to be a cause of nephrotic syndrome is most often a consequence of this hypercoagulable state.
Causes
The relative frequencies of the several causes of the nephrotic syndrome vary according to age. In children younger than 15 years, for example the nephrotic syndrome is almost always caused by a lesion primary to the kidney. The most frequent systemic causes of the nephrotic syndrome are SLE, diabetes , and amyloidosis. The most important of the primary glomerular lesions are lipoid nephrosis (minimal change disease) membranaous glomerulonephritis and focal segmental glomerulosclerosis. The first is most common in children the second in elder and focal segmental glomerulosclerosis occurs at all ages.
These three lesions, as well as a fourth less common disorder, membranoproliferative glomerulonephritis, are discussed individually in the following sections. The fifth possible primary cause, diffuse proliferative glomerulonephritis, frequently presents with the nephritic syndrome.
By: sanjoea