Ans. b. Sodium and water retention Sodium and water retention is the pathology of edema in nephrotic syndrome. The nephrotic syndrome is characterized by proteinuria, edema, and hypoalbuminemia. Renal sodium retention and changes in variables of the Starling equation are fundamental to the pathophysiology of nephrotic edema. There is evidence for both intravascular volume expansion (overfilling) and intravascular volume depletion (under filling) in patients with nephrosis. Microvascular fluid exchange is described using a formulation of the Starling driving forces (DP and Dp) and it is through this equation that nephrotic edema is conceptualized. Previous theories have focused on abnormalities in DP and Dp to explain nephrotic edema. Studies have shown that hypoalbuminemia (and thus Dp) is not a likely cause of edema formation in most nephrotic patients owing to a parallel decrease in interstitial fluid albumin and an increase in interstitial fluid pressure, both of which serve to maintain edema driving forces constant. There is limited evidence suggesting that abnormalities in vascular permeability (Kf and s) may contribute to edema formation. A major advance in our understanding of the pathophysiologic basis of edema formation in the nephrotic syndrome is the discovery that proteinuria can cause primary renal sodium retention through ENaC activation. This mechanism is likely active in all patients with nephrotic syndrome, regardless of their intravascular volume status. Other causes of primary renal sodium retention include increased renal efferent sympathetic nerve activity, ANPase, and in the expression and activity of the Ne--le in the collecting duct in animal models. Fuhermore, excess serum vasopressin levels have been found to contribute to free water retention in some patients with the nephrotic syndrome."- Eric Siddall and Jai Radhakrishnan. The pathophysiology of edema formation in the nephrotic syndrome Nephrotic Syndrome Manifestations of Nephrotic Syndrome 1. Massive proteinuria, with the daily loss of 3.5 gm or more of proteinQ 2. Hypoalbuminemia, with plasma albumin levelsQ 3. Generalized edemaQ 4. Hyperlipidemia and lipiduriaQ Pathophysiology: Renal sodium retention and changes in variables of the Starling equation are fundamental to the pathophysiology of nephrotic edema. There is evidence for both intravascular volume expansion (overfilling) and intravascular volume depletion (under filling) in patients with nephrosis. Nephrotic Syndrome Mechanisms of Sodium Retention in the Nephrotic Syndrome Increased angiotensin 11-independent afferent and efferent aeriolar tone because of increased efferent sympathetic nerve activity. Tubular resistance to atrial natriuretic peptide (ANP). Increased number of open epithelial sodium channel (ENaC) channels in the coical collecting duct due to proteolytic activation of ENaC by plasmin. Increased number and activity of coical collecting duct Na/K ATPase channels Most impoant facts about Nephrotic syndrome 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. Most proteins are decreased in nephrotic syndrome except Fibrinogen and lipoproteins, due to increased synthesis. Proteins decreased Consequence Albumin Edema due to hypoalbuminemiaQ Transferrin Iron resistant microcytic anemiaQ Cholecalciferol binding proteins HypocalcemiaQ Thyroxin binding globulin Decreased thyroxin (Hypothyroid state)Q IgG Increased susceptibility of infectionsQ Renal vein thrombosis is paicularly common (up to 40%) in patients with nephrotic syndrome due to membranous glomerulopathy, memranoproliferative glomerulonephritis, and AmyloidosisQ. As a consequence of hypercoagulability and changes in proteins, patients can develop spontaneous peripheral aerial or venous thrombosis, renal vein thrombosis, and pulmonary embolismQ