TABLE 1
Pathophysiological effects of albumin 1
• Maintenance of colloid osmotic pressure
• Regulation of acid – base balance ( plasma buffering )
• Binding and transport of endogenous ligands and drugs
• Integrity of the microcirculation and capillary permeability
• Antioxidant and free radical scavenging effects
• Anticoagulant and antithrombotic effects
• Anti-apoptotic effects
in reverse , by promoting its reabsorption from the interstitial space . 1 , 3 Owing to the flexible shape conferred by its movable domains , the protein binds to multiple endogenous ligands . 1 Albumin is also capable of interacting with a multitude of exogenous substances , including antibiotics and other drugs , thus contributing to their metabolism , inactivation , or stabilization . 1 In addition , interactions with drugs can be modified by small molecules such as fatty acid chains , and the protein is known to have seven long-chain fatty acid binding sites across its three domains . 4
Albumin also plays a role in the transport of substances derived from cell catabolism that are targeted for excretion by the liver and the kidneys , and in the transport of hormones and drugs to their target cells . In addition , it is known to be involved in the elimination of toxic substances that accumulate under abnormal physiological conditions , inhibition of the production of oxygen free radicals by polymorphonuclear leukocytes , and the prevention of oxidative events through direct binding to reactive oxygen and nitrogen species . 1 , 3 In the physiological range of blood pH , albumin behaves as a weak acid , and the presence of many charged amino acid residues makes it an effective plasma buffer . Decreased albumin production in liver disease or malnutrition or increased loss in nephrotic syndrome , chronic wounds , or protein losing enteropathy , may result in mild metabolic alkalosis . In contrast , metabolic acidosis may develop in patients who are critically ill due to liver decompensation . Although exogenous albumin infusions to correct low levels in patients with hepatorenal syndrome may lead to net metabolic acidemia , this effect is very small with buffered drug formulations administered to patients with normal liver function . 6
In vitro , albumin has shown apoptosis inhibitory activity in cultured endothelial cells and anticoagulant and anti-thrombotic properties through the neutralization of coagulation factor Xa and inhibition of platelet function . 1 Moreover , in a small study of nine patients undergoing coronary bypass , albumin was capable of preventing erythrocyte crenation induced by free fatty acids , which is thought to cause impaired microcirculatory flow and tissue oxygenation in the intra and post-operatory periods . 7 In another study using endothelial and renal cell models , albumin prevented increased endothelial cell permeability induced by heparinbinding protein . In addition , patients with septic shock who developed or suffered a worsening of acute kidney injury showed a higher ratio of heparin-binding protein to albumin , as well as increased heparin-binding protein levels , than those patients without kidney injury . 8
Albumin can potentially prevent the degradation of the layer of glycoproteins present on the surface of vascular endothelial cells ( the glycocalyx ) that occurs during sepsis . This structure controls vascular permeability and microvascular tone and regulates leukocyte adhesion , and its integrity may be compromised by the conventional fluids used in resuscitation . However , albumin has been shown to be more protective of the glycocalyx than hydroxyethyl starch and normal saline solution in animal heart models , as reflected by an improved vascular filtration . 9 Other non-oncotic features of albumin include anti-inflammatory properties through binding to pro-inflammatory substances such as bacterial lipopolysaccharide and peptidoglycans . 10 , 11 Systemic inflammation in sepsis is mediated by cytokines and reactive oxygen and nitrogen species generated by neutrophils , macrophages , and endothelial cells , and albumin constitutes the main contributor in the response against oxidative stress . Albumin can also counteract , via reversible binding , the immunosuppressive effects of prostaglandin E2 in acutely decompensated liver cirrhosis , which is associated with systemic inflammation . 5 Albumin appears to have an important role in immunomodulation as well , through regulation of nuclear factor-k B activation , induction of gene expression of tumor necrosis factor-a , and induction of T-cell activation , which may potentially influence the inflammatory and immune
12 , 13 response during critical illness .
Clinical uses related to biological properties One of the first reports of clinical use of albumin was as a plasma expander during World War II . 14 Albumin infusion increases cardiac output and peripheral vascular resistance by expanding plasma volume and increasing cardiac preload while inducing arterial vasoconstriction . 3 It is , therefore , used to prevent circulatory dysfunction following therapeutic paracentesis or spontaneous bacterial peritonitis in patients with decompensated liver cirrhosis . Volume expansion with albumin solution , together with administration of vasopressors , is currently the standard of care for patients with acute kidney injury due to hepatorenal syndrome . 3 However , judicious use is recommended in the elderly and patients with borderline cardiopulmonary function or severely impaired renal function with anuria , to avoid fluid overload . 15 , 16 Providers should also be cautious in patients with an allergy to albumin , severe anemia , and those with coagulopathy who are actively bleeding . 16 Further , the high cost should be considered in optimized use of this drug in clinical practice .
Conclusion Human albumin is the main determinant of plasma oncotic pressure and plays a pivotal role in modulating the distribution of fluids between compartments . Several clinical and experimental studies support the assumption that part of its therapeutic activity is also dependent on its nononcotic properties . As an important biological product used in clinical treatment , albumin has several evidence-based indications and shows potential in the improvement of drug delivery . There is a need for a stable functional molecule with a long half-life and which is easy to store . Data are emerging on the use of a ‘ super albumin ’ molecule with the potential for transnasal delivery , which has improved FcRn binding , a higher transport across the cell membranes , and an extended plasma half-life . 17
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