By itself, hypoalbuminemia can cause hypovolemia and circulatory collapse secondary to decreased oncotic pressure within the vascular system. Due to its metal-binding properties, hypoalbuminemia may lead to nutritional deficits including zinc deficiency. Hypoalbuminemia associated with the nephrotic syndrome can lead to the development of hyperlipidemia, although this is usually in the absence of atherosclerosis. Further, in patients on dialysis, hypoalbuminemia is associated with more advanced fluid overload. Hypoalbuminemia can be caused through a number of different mechanisms, each with the end result of decreasing albumin levels. These include: 1) impaired synthesis within the liver, 2) increased utilization by tissue, 3) distributional issues, and 4) increased excretion or loss. Often, the cause is multifactorial as in liver cirrhosis, where reduced hepatic synthesis and increased capillary leakage combine to further decrease albumin levels. Albumin is considered a negative acute phase reactant, which means that as inflammation and other acute physiologic processes occur, its levels decrease. This is in contrast to acute phase reactants like C-reactive protein (CRP), whose levels increase with inflammatory processes. With respect to mechanism, inflammation leads to decreased production of albumin as a result of increased levels of cytokines, specifically IL-1, IL-6, and TNF-α. In patients with the overwhelming infections common in sepsis and septic shock, hypoalbuminemia occurs as a result of the combinatorial effects of decreased synthesis as above, increased utilization by tissues, and increased transcapillary leakage from blood vessels due to increased vascular permeability. Albumin is synthesized in the liver, and low serum albumin can be indicative of liver failure or diseases such as cirrhosis and chronic hepatitis. If present, hypoalbuminemia is generally considered to be a sign of advanced hepatic cirrhosis, or irreversible damage to the liver. Production of albumin can be one 60–80% lower in advanced cirrhosis than in healthy liver, an effect amplified by dilution (salt and water retention), fluid shifts (following the accumulation of albumin in extracellular space and ascitic fluid), and even post-transcriptional changes to albumin itself. Hypoalbuminemia can also present as part of the nephrotic syndrome, in which significant quantities of protein are lost in the urine due to kidney damage.