Albumin

ALBUMIN

1. ALBUMIN MRIMS-2021

2. ALBUMIN The name albumin (L. albus = white) originated from the white precipitate formed during the boiling of acidic urine from patients with proteinuria . albumin is the most abundant plasma protein from the fetal period onward, accounting for about half of the plasma protein mass. It is a major component of most body fluids, including interstitial fluid , CSF, urine, and amniotic fluid . More than half of the total pool of albumin is in the extravascular space.

3. Biochemistry of Albumin Albumin has a nonglycosylated polypeptide chain of 585 amino acids and molecular weight of 66,438 Da . It has a heart-shaped threedimensional structure stabilized by 17 intrachain S-S bonds. It is a relatively stable protein, resisting denaturation up to higher temperatures than most plasma proteins. Albumin has a high abundance of charged amino acids that contribute to high solubility, and it has a net negative charge of about − 12 at neutral pH. Albumin therefore contributes about 6 to 10 mmol /L to the anion gap at normal albumin concentrations of 0.5 to 0.8 mmol /L, and lesser amounts at lower albumin concentrations.

4. Biochemistry of Albumin At a pH of 8.6 for alkaline electrophoresis, albumin has a net charge of about −25, resulting in high mobility toward the anode . One unpaired cysteine at position 34 occurs partially in reduced form and partially in exchangeable disulfide bonds with small compounds such as cysteine and homocysteine . The unpaired cysteine has an unusually low pK of <6 and high rates of disulfide exchange. Consequently, it serves as a major plasma carrier of compounds with free sulfhydryls .

5. Biochemistry of Albumin Albumin is synthesized by hepatocytes . in nephrotic syndrome, albumin synthesis can increase threefold above normal . The synthetic rate is controlled primarily by colloidal osmotic pressure (COP) and secondarily by protein intake. albumin is a negative acute-phase reactant. Catabolism occurs mainly by pinocytosis by multiple tissues, with lysosomal degradation of protein to amino acids . only small amounts (10 to 20% of the total catabolized ) are lost into the gastrointestinal tract and the glomerular filtrate.

6. Biochemistry of Albumin In protein-losing enteropathies and glomerular disorders , resulting in nephrotic states. Burn injuries also result in major losses of albumin. The normal plasma half-life of albumin is 15 to 19 days. Albumin and IgG have severalfold longer plasma half-lives than most proteins because of the action of a recycling receptor, the neonatal IgG receptor.

7. Biochemistry of Albumin At high concentrations of albumin, the receptor may be saturated and the half-life of albumin decreased . At low concentrations of albumin, such as in analbuminemia ,the half-life of albumin is markedly extended.

8. Function of Albumin Albumin may serve as a storage form of amino acids that can be delivered to tissues in catabolic states and as an antioxidant, particularly through the action of its free sulfhydryl group . The two most clearly defined functions of albumin are ( 1) serving as the major component of colloid osmotic pressure ( patients in hypoalbuminemic states, such as nephrotic syndromes , are prone to develop edema. albumin solutions sometimes are administered as a replacement fluid to try to acutely maintain intravascular volume ). (2) serving as a transporter- fatty acids and other lipids, bilirubin , drugs , thiol -containing amino acids, tryptophan, calcium, and metals.

9. Function of Albumin fatty acids and unconjugated bilirubin , have very low solubility in water carrier for a variety of hydrophobic metabolic substrates and drugs, assisting with transport to the liver or other sites of metabolism . Albumin has up to six binding sites for free fatty acids. The reference interval of 0.28 to 0.89 mmol / L for free fatty acids corresponds to a stoichiometry of about one fatty acid per albumin molecule, and this ratio increases in obesity and other states with increased free fatty acids . Purified albumin usually contains bound fatty acids.

10. Clinical Significance of Albumin Increased Plasma Concentrations. Increased concentrations : Dehydration , prolonged tourniquet time or specimen evaporation prior to analysis.

11. Clinical Significance of Albumin Decreased Plasma Concentrations. Low concentrations of Result from decreased synthesis, increased metabolic turnover, increased distribution to extravascular fluids , or losses from glomerular and gastrointestinal disorders , burns, or other wounds . Decreased synthesis occurs with rare genetic variants, acute-phase responses, and liver dysfunction. Hypoalbuminemia leads to decreases in the anion gap . Albumin usually binds half the calcium in the circulation.

12. Analbuminemia . plasma albumin concentrations <0.5 g/L ( ≤1% of normal), symptoms often are absent or consist of mild edema, lipodystrophy , and dyslipidemia . The plasma half-life of infused albumin in affected individuals is prolonged to 50 to 60 days.

13. Inflammation. Inflammatory disorders lower albumin by increasing capillary permeability, allowing increased distribution of albumin into the extravascular space ; (2) decreasing synthesis in response to inflammatory cytokines such as IL-6; ( 3) responding to increased quantities of positive acute-phase reactants that contribute to oncotic pressure; (4) increasing the catabolism of albumin by cells.

14. Hepatic Disease. The liver has synthetic capacity to maintain albumin concentrations until parenchymal damage or loss is severe, with loss of more than 50% of function. Nutritional deficiencies , direct inhibition of synthesis by toxins such as alcohol, and increased distribution of albumin in extravascular spaces.

15. Urinary Loss/Kidney Disease Normally , the glomerular filtration barrier efficiently prevents entry into the urinary ultrafiltrate by proteins the size of albumin or larger. Usually, only 1 to 2 g/d of albumin passes through the glomerular barrier , and 99.9% of albumin in the glomerular ultrafiltrate is taken up by proximal tubules of the kidney and degraded. Only about 10 mg/d of albumin is normally excreted in urine. Small increases and urine albumin excretion to >30 mg/d are indicators of early stages of glomerular or tubular injury ( microalbuminuria )

16. Urinary Loss/Kidney Disease Nonpathologic increases in albumin excretion are observed in some individuals with postural changes, strenuous exercise, and fever. First or second voided specimens in the morning may decrease postural effects . Severe glomerular injury and nephrotic syndromes are characterized by excretion of >3.5 g/d. In nephrotic syndrome, the glomerular leakage of proteins is increased but some size selectivity is retained ; therefore, very large proteins are still retained. Even though the liver compensates through increased protein synthesis, concentrations of proteins up to about 200 kDa , including albumin, decrease substantially . Concentrations of very large proteins, such as α2-macroglobulin (AMG), larger isotypes of Hp (genotypes 2-1 and 2-2), cholinesterase, and apolipoprotein B are increased.

17. Gastrointestinal Loss Protein-losing enteropathy may result in losses as great as those seen in the nephrotic syndrome . If protein-losing enteropathy occurs secondary to lymphangiectasis , larger proteins—especially the immunoglobulins — may be lost in large quantities. Patients with Ménétrier’s disease who have gastric protein losses or inflammatory bowel disease of the intestinal tract, such as Crohn’s disease with intestinal losses, can develop hypoalbuminemia .

18. Protein -Calorie Malnutrition The response of albumin to increased or decreased protein ingestion is relatively slow, in part because of its relatively long half-life. Also , effects of acute or chronic inflammation may decrease the correlation of albumin concentration with nutrition .

19. Burn Injury. Patients with burn injury can experience severe losses of albumin from wounds. (Combined effects of epithelial losses, accelerated catabolism, and stimulation of the acute-phase response).

20. Edema and Ascites decreased plasma albumin concentrations . secondary to increased vascular permeability, which permits the loss of albumin into these spaces . Albumin concentrations in these fluids vary from very low to higher than those in plasma, the latter in particular with certain forms of ascites . Increased volumes of extravascular fluid may be large enough to contain a substantial portion of total body albumin . In patients with edema or ascites associated with low plasma albumin, effects of albumin infusion are transient because of rapid equilibration with extravascular fluid. In acute hypovolemic shock, albumin infusion may help to maintain vascular volume, but rapid infusion may result in symptoms of hypocalcemia due to calcium binding by albumin .

21. Genetic Aspects of Albumin The albumin gene is on chromosome 4, linked to homologous genes for α-fetoprotein (AFP ) and vitamin D–binding protein ( Gc -globulin). Inherited analbuminemia has been reported in a few families. Inheritance is autosomal recessive, with heterozygotes having low normal to moderately reduced concentrations. More than 80 different inherited structural variants of albumin have been described, most with normal concentrations of albumin .

22. Genetic Aspects of Albumin All variants have a population frequency of <1 : 1000. Variants may have altered electrophoretic migration, leading to two bands for albumin or bisalbuminemia for heterozygotes . Variants with abnormal intramolecular disulfide bonding, such as Alb Hawkes Bay, may form homodimers or heterodimers with other proteins such as α1-antitrypsin AAT

23. Genetic Aspects of Albumin Electrophoretic variants of albumin and bisalbuminemia may be acquired as effects of bound drugs or metabolites. Most albumin isoforms have normal function; an exception consists of increased or decreased binding affinities for T4 of certain albumin variants . Variants with increased affinity for T4 yield familial dysalbuminemic hyperthyroxinemia , where total serum T4 is elevated, although individuals are euthyroid and have normal thyrotropin concentrations .

24. Laboratory Considerations for Albumin Plasma and Serum: Most clinical laboratories assay albumin in plasma or serum samples by dye-binding methods, which rely on a shift in the absorption spectrum of dyes such as bromcresol green (BCG) or purple (BCP) upon albumin binding . The affinity of these dyes is higher for albumin than for other proteins, providing some specificity for albumin. BCP generally is slightly more specific for albumin and yields

25. Laboratory Considerations for Albumin lower values than BCG, particularly for patients with kidney failure. Heparin in collection tubes is reported to affect some dye-binding methods. Dye-binding assays also tend to be less accurate when the serum or plasma protein composition is abnormal. Dye-binding methods have decreased accuracy for patients with cirrhosis, possibly related to oxidized or other modified forms of albumin. Unfortunately, disorders with abnormal plasma protein compositions, such as kidney and liver disease, often present situations in which accurate analysis is most desired.

26. Laboratory Considerations for Albumin Albumin concentrations are considered an important indicator of adequate nutrition in patients with kidney failure, total calcium. kidney failure- to maintain serum albumin concentrations of at least 40 g/L by the BCG method . Low albumin concentrations-unfavorable outcomes on chronic hemodialysis .

27. Laboratory Considerations for Albumin staging of patients with multiple myeloma, with albumin ≥3.5 g/ dL necessary for patients to be in stage I with best prognosis. serum protein electrophoresis yields discordant values with immunonephelometry and BCG methods for some patients with high paraprotein concentrations.

28. Laboratory Considerations for Albumin In assessment of albumin in ascitic fluid, dye-binding methods have been noted to give spuriously high results. Densitometric scans of electrophoretic patterns can determine the percentage of protein made up of albumin. Along with a measure of total protein concentration, albumin concentration can be calculated.

29. Laboratory Considerations for Albumin Immunoturbidimetry and immunonephelometry offer greater specificity and accuracy, higher sensitivity needed for specimens with low albumin concentrations such as urine and CSF.

30. Reference Intervals of Albumin In serum of adults 20 to 60 years of age is 35 to 52 g/L (3.5 to 5.2 g/ dL ). Albumin concentrations reach adult concentrations around 20 to 30 weeks ’ gestation and remain relatively constant until at least 20 years of age. Concentrations then slowly decrease with age in both sexes . Concentrations are lower in individuals living in the subtropics and tropics, probably because of higher immunoglobulin concentrations secondary to infection.

31. Reference Intervals of Albumin Concentrations are posture dependent, increasing by up to 10 to 15% if an individual is standing versus recumbent. This reflects a shift of fluid between intravascular and extravascular spaces. Albumin is preferentially retained in the intravascular space. A similar increase in albumin results from prolonged tourniquet time before blood collection.