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
ofmild 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
(1) 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.