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Albumin
Albumin is a carbohydrate-free protein and comprises 60% of the total serum protein and 60 to
80% of colloid osmotic pressure. Serum albumin is synthesized solely by the liver.
Synthesis
In humans the liver manufactures albumin at a massive rate and decreases production in times of
environmental, nutritional, toxic and trauma stress.
Albumin is not stored by the liver but is secreted into the portal circulation as soon as it is
manufactured. The rate of synthesis rate varies with nutritional and disease states. The liver can
increase albumin synthesis to only 2–2.7 times normal. Albumin will be synthesized only in a
suitable nutritional, hormonal and osmotic environment. The colloid osmotic pressure (COP) of
the interstitial fluid bathing the hepatocyte is the most important regulator of albumin synthesis.
The rate of synthesis depends on nutritional intake, more so than for other hepatic
proteins. Fasting reduces albumin production, but specifically omitting protein from the diet
causes a greater reduction in synthesis.
Factors that modify albumin metabolism
Reduced albumin synthesis
 Decreased gene transcription
 Trauma,
 sepsis (cytokines)
 Hepatic disease
 Diabetes
 Decreased growth hormone
 Decreased corticosteroids (in vitro)
Ribosome disaggregation
 Fasting, especially protein depletion
Degradation
Total daily albumin degradation in a 70 kg adult is around 14 g day–1 or 5% of daily whole‐body
protein turnover. Albumin is broken down in most organs of the body. Muscle and skin break
down 40–60%. The liver, despite its high rate of protein metabolism, degrades 15% or less of the
total. The kidneys are responsible for about 10%, while another 10% leaks through the stomach
wall into the gastrointestinal tract.
Albumin Metabolism
The serum albumin concentration depends on its rates of synthesis and degradation and its
distribution between the intravascular and extravascular compartments.
 The total body albumin pool measures about 3.5–5.0 g kg–1 body weight (250–300 g for a
healthy 70 kg adult).
 The plasma compartment holds about 42% of this pool, the rest being in extravascular
compartments. Some of this is tissue‐bound and is therefore unavailable to the
circulation.
 Daily 120–145 g of albumin is lost into the extravascular space. Most of this is recovered
back into the circulation by lymphatic drainage.
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Albumin is also lost into the intestinal tract (about 1 g each day), where digestion
releases amino acids and peptides, which are reabsorbed.
There is minimal urinary loss of albumin in healthy subjects. Urinary loss is usually not more than
10–20 mg day–1.
Normally, about 4% of the total body albumin is replenished each day and 120 mg/kg/dl of
albumin is synthesised per day. The rate of production is dependent on the supply of amino
acids, plasma oncotic pressure, inhibitory cytokine (especially IL-6) concentration, and the
number of functioning hepatocytes. The liver is the primary site of albumin synthesis. Circulating
half-life of plasma albumin is 19 to 21 days.
Functions of albumin
Albumin has extensively studied and well‐established physiological functions in health. There are,
however, few studies on the function of albumin in the critically ill.
Physiologic Roles of albumin
 Maintenance of the colloid osmotic pressure (COP).
 Binding and transport, particularly of drugs.
 Free radical scavenging.
 Acid base balance
 Pro and anti-coagulatory effects (inhibits platelet aggregation, enhances the inhibition of
factor Xa by antithrombin III).
 Effects on vascular permeability.
Binding and transport
Albumin binds drugs and ligands, and therefore reduces the serum concentration of these
compounds. The drugs that are important for albumin binding are: warfarin (coumadin), digoxin,
NSAIDS, midazolam, thiopental.
Osmotic pressure
Albumin is responsible for 75 - 80 % of osmotic pressure. Albumin is the main protein both in the
plasma and in the interstitium. It is the Colloidal Osmotic Pressure gradient rather than the
absolute plasma value that is important: this is what distinguishes hypoalbuminaemia derived
from redistribution (capillary leak) from that of pure full body deficiency.
Free Radicals
Albumin is a major source of sulphydryl groups, these "thiols" scavenge free radicals (nitrogen
and oxygen species).Albumin may be an important free radical scavenger in sepsis.
Acid Base Balance
Albumin is a negatively charged protein in high concentration in the plasma. It contributes
heavily to what we call the “anion gap”: the concentration of anions and cations in plasma should
be equal, classically the anion gap is calculated as (Na + K)- (Cl) = AG (mEq/l). The remaining
anions come predominantly from albumin, inorganic phosphate and hemoglobin. Thus, in
hypoalbuminemic states, the anion gap should be narrowed.
Vascular Permeability
It is possible that albumin has a role in limiting the leakage from capillary beds during stress
induced increases in capillary permeability. This is related to the ability of endothelial cells to
control the permeability of their walls, and the spaces between them. Albumin may plug this gap
or may have a deflecting effect, owing to its negative charge. This has led to the hypotheis that
colloids are effective at maintaining vascular architecture.
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Falsely low values of albumin
Plasma albumin levels are low in neonates, between 2.8 and 4.4 g/dL. Adult levels are
reached after the first week of life. Levels are slightly higher in children (4.5 - 5.5 g/dL)
between the age of 6 years and young adulthood. Thereafter, levels decline to adult
levels.
Albumin levels show a downward trend throughout pregnancy and with aging, especially
after age 70.
Serum albumin levels are normally lower in hospitalized than ambulatory patients.
Albumin levels can decrease as much as 1 g/dL after a patient becomes recumbent.
Albumin concentration may decrease after crystalloid infusion or in patients with fluid
retention.
Falsely low values will be obtained if a blood sample is drawn above an IV site.
Hypoalbuminemia
Serum albumin concentration falls due to decreased synthesis, increased catabolism, increased
loss and redistribution.
Causes of decreased plasma albumin:
1. Decreased synthesis.
2. Increased catabolism [very slow]
3. Increased loss:
 Nephrotic syndrome
 Exudative loss in burns
 Haemorrhage
 Gut loss
4. Redistribution:
 Haemodilution
 Increased capillary permeability (leakage into the interstitium)
 Decreased lymph clearance.
“Capillary leak syndrome” occurs in systemic inflammatory response syndrome. Due to
widespread damage to the capillary endothelium, there is increased loss of medium to high
molecular weight compounds, particularly albumin, into the extravascular space and therefore
loss of the normal Starling relationship.
Diseases associated with hypoalbuminaemia
Hypoalbuminemia is associated with liver and renal disease, PET, SIRS / including burns, trauma.
Low preoperative albumin is an indicator of poor outcome from surgery.
Liver Dysfunction
Plasma albumin is seldom decreased in acute hepatitis, because of its long circulating half-life.
Decreased serum albumin usually indicates liver disease of more than 3 weeks duration. Albumin
is a good indicator of decompensation and prognosis in cirrhosis.
Albumin is a poor marker of liver dysfunction; prothrombin time is more reliable.
Renal disease
Albumin loss occurs in nephropathies (nephrotic syndrome).
There is a small loss of albumin in dialysis circuits.
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Pre-Eclampsia (PET)
In normal pregnancy there is an increase in plasma volume. In PET there is a paradoxical decrease
in plasma volume, widespread capillary leak and albuminuria.
Stress response
Interleukins cause a marked decrease in synthesis of plasma proteins other than albumin.
In fact Albumin and Transferrins decrease in the stress response, a process often termed
"negative acute phase proteins".
IL6 directly decreases the expression of albumin messenger RNA.
Overall, the picture in the stress response is:
1. Initial decrease in albumin associated with increase in acute phase proteins.
2. Subsequent global increase in hepatic protein synthesis; including albumin.
Burns
There is massive protein loss from the burn site & increased vascular permeability & decreased
albumin synthesis & protein losing nephropathy. The use of albumin in patients with >15% burns
after 24 hours has been recommended.
Trauma
In trauma there is increased redistribution and transcapillary escape of albumin.
Surgery
Decreased serum albumin preoperatively is an independent indicator of poor outcome.
Sepsis
SIRS - associated with increased capillary permeability, due to the effects of bacterial endotoxin
and cytotoxic T cells. In sepsis there is a profound reduction in plasma albumin associated with
marked fluid shifts. .
Postoperative patients and patients with severe infection inevitably have low plasma albumin.
The more severe the disease is, the lower the albumin, and therefore the lower the albumin, the
worse the prognosis.
Plasma albumin is of virtually no value in assessment or monitoring of nutritional status.
Hypo-albuminemia is associated with poor surgical outcome and increased length of stay. Serum
albumin levels less than 2 g/dL are associated with a 60% thirty-day mortality rate.
Hypoalbuminemia in Critical Illness
Hypoalbuminemia in critical illness is caused by:
1. Decreased hepatic production.
2. Redistribution into the extravascular space.
3. Dilution due to fluid administration.
Low serum albumin is a non specific marker of disease. A fall in the albumin concentration
appears to reflect deterioration, and a rise, recovery. Very low levels of albumin appear to reflect
a poor outcome. The relevance of low albumin on ligand binding is unknown.
The serum albumin falls when patients become sick, and comes back up when patients get
better.
Increased serum albumin levels are seen only with dehydration or after excessive albumin
infusion.Artefactual causes of high levels include specimen evaporation and prolonged use of a
tourniquet during venipuncture.
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Specimen Type: Serum
Specimen Required Container/Tube: Plain, red-top tube(s) or serum gel tube(s)
Reject Due To
Specimens other than
Hemolysis
Serum
Mild OK; Gross reject
Reference range is 3.5 - 5.0 gm/dL.
Referance

Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Burtis CA, Ashwood ER
and Bruns DE, eds. 4th ed. St. Louis, Missouri: Elsevier Saunders; 2006, Pp 543-546.

Nicholson JP, Wolmarans MR, Park GR. The role of albumin in critical illness. Br J Anaesth
2000; 85: 599-610.

Doweiko JP, Nompleggi DJ. Role of albumin in human physiology and pathophysiology. J
Parent Enteral Nutr 1991; 15: 207–11
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