Hypoalbuminemia, nephrotic syndrome

Nephrotic syndrome is a clinical and laboratory syndrome defined by heavy proteinuria (exceeding 3.5 g/1.73 m2 of body surface area in adults, or 40 mg/hr/m2 in children), accompanied by hypoproteinemia (mainly hypoalbuminemia), hypercholesterolemia (in severe cases also hypertriacylglycerolemia), lipiduria, and edema. 

Decreased cardiac output Hypoalbuminemia Liver disease Nephrotic syndrome Anaphylaxis Sepsis... 

Hypotransferrinemiacan result from protein malnutrition and accompanies hypoalbuminemia. Since transferrin has a much shorter half-life (8 days) than albumin (19 days), measurement of the transferrin level may be a more sensitive indicator of protein malnutrition than albumin measurement (see also chapter 17). Hypotransfer-rinemia also results from excessive renal loss of plasma proteins (e.g., in nephrotic syndrome). 

The extreme hypoalbuminemia of the nephrotic syndrome can be attributed to the sustained urinary loss of albumin (S39), but it is doubtful whether albumin deficiency plays a causal role in the hyperlipemia and hypercholesterolemia found in this condition. Low-density lipoprotein (LDL) (90% lipids) is converted by lipoprotein lipase in vivo to high-density lipoprotein (HDL) (70% lipids), and the liberated fatty acid anions are bound and transported by plasma albumin. In normal nonlipemic serum the mean nonesterifled fatty acid/albumin molar ratio is 0.95 0.04, while in nephrotic sera—lipemic because of accumulation of LDL-triglycerides —the corresponding ratio is about 3 (C4). The plasma hyperlipemia which is observed in the nephrotic syndrome, and can be induced in rats by injections of antikidney serum, has been considered to result from albumin deficiency (R26). However this suggestion is not borne out by more recent studies (R25) and is contradicted by the failure of LDL to accumulate in the blood of analbuminic subjects (03). Plasma lipemia in the nephrotic syndrome apparently is due to loss or inhibition of lipoprotein lipase activity. 

Most patients present initially with edema, frequently acute in onset, following a nonspecific upper respiratory tract infection, allergic reaction, or vaccinations, which might have activated the T lymphocytes. Nephrotic syndrome with massive proteinuria (substantially more than 40 mg/m per hour for children and 3 g/day for adults), edema, hypoalbuminemia, and hyperlipidemia is common. The patient s weight may be increased dramatically because of sodium and fluid retention. Nephrotic features such as gross hematuria are uncommon. However, microscopic hematuria may be seen in up to 20% to 25% of patients. Hypertension and decreased renal function are uncommon in children but are more common in older adults. In some patients, volume depletion may result in mild to moderate azotemia. 

Taken together, these data indicate that left ventricular dysfunction and elevated cardiac filling pressures, hypothyroidism, and nephrotic syndrome/ hypoalbuminemia may all contribute but are not sufficient for the formation and maintenance of large persistent pleural effusion in AL amyloidosis. The incidence of exudative chemistries and the presence of amyloid deposits on pleural biopsies suggest that amyloid infiltrates and disrupts pleural mechanics, inducing fluid secretion and impairing parietal membrane drainage from the pleural space. 

The nephrotic syndrome, which occurs most frequently in the course of chronic glomerulonephritis, is characterized by marked albuminuria, edema, hypoalbuminemia, and hypercholesterolemia (191). Extensive studies of the serum and urinary proteins in this disorder have proved fruitful in clarifying some of the disease mechanisms involved although the basic metabolic disturbance underlying the syndrome remains unknown. 

Albumin formation is generally stated to take place solely in the liver. The available evidence, reviewed by Madden and Whipple (219), favors this view, but is not compelling, does not exclude other possibilities, and leaves unexplained a number of discrepancies which are noted in certain disease states, for example, the marked hypoalbuminemia observed in some instances of the nephrotic syndrome associated with relatively little albuminuria, and in so-called idiopathic hypoproteinemia. In both these conditions, the serum albumin may reach extremely low levels yet there is no impairment of hepatic function that can be demonstrated by available methods (which does not, to be sure, exclude the possibility of a specific hepatic defect such as occurs in connection with prothrombin formation and other hepatic functions). 

The very marked hypoalbuminemia in the nephrotic syndrome is usually attributed chiefly to protein loss through the kidneys. A similar... 

An important consequence of marked hypoalbuminemia is reduction of the osmotic pressure in the intravascular compartment and the formation of edema due to accumulation of fluid in the intercellular spaces, the osmotic pressure exerted by albumin constituting by far the largest counterforce to the hydrostatic pressure. There is no critical level of plasma albumin predisposing to edema formation, earlier views to the contrary. As indicated in the discussion of the nephrotic syndrome, the factors regulating water balance are too complex for any such simple relation. Further evidence of this is afforded by the observations of Keys et al. (140, 184) on production of starvation edema without significant hypoalbuminemia. 

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